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The best path for becoming a school administrator, is to gain experience as a teacher or and earn a master’s degree in education, educational leadership, or educational administration.
Being a school administrator would involve planning and developing instructional methods and content, setting school performance goals and objectives, and recruiting, developing and supervising teachers and support staff.
This career offers excellent pay, as well as social environment, challenging and rewarding work, and no two days that are ever the same. So, if becoming a school administrator sounds like it might suit you, then read on below; we’ll tell you what you'll need to make it in this field!
To become a school administrator, you typically need a master’s degree in education administration or education leadership. The specific requirements however, are determined at the discretion of the school division or employment authority.
Such programs will train you to lead teachers, manage budgets, set and reach educational goals for your school(s), and to work with students' families and the community.
Some school administrators go right into the job out when they have completed a master’s program. Most employers however, will require that you have some experience teaching, or experience in some kind of educational administration capacity, before taking on an administrative job of higher responsibility.
For example, it’s not uncommon for working teachers to pursue a master’s degree in education administration, and move into a low-level or even high-level administrative role during their course of study, or upon completion of their studies.
Who Creates Jobs for School Administrators?
As a school administrator, you would be responsible for planning and coordinating the academic and clerical activities of a public or private elementary, middle or secondary school.
Working Hours: As a school administrator, you could expect to work normal, weekday working hours. However, because of the heavy workload, overtime would often be required, which could involve going in early, on weekends, or staying late.
Working Conditions: Working as a school administrator would be ideal if you like diversity in your work, a fast pace, large and demanding workloads, and you can work through continuous interruptions. As you would be in a position of responsibility, much of your day would involve communicating with teachers, students, parents, community members and other stakeholders.
• “Education Administrators, Elementary and Secondary School.” Occupational Employment and Wages, May 2015 edition. U.S. Government - Department of Labor Statistics; accessed July 14, 2016.
• “What Do You Need to Be a School Administrator?” Jennifer Alyson, Houston Chronicle; accessed July 14, 2016.
• “School Business Manager.” Job Profiles. British Government - Department for Business, Innovation and Skills. National Careers Service; accessed July 14, 2016.
The Applicable Majors section below shows fields of study relevant to a career as a school administrator. You can search for scholarships matched to that/those fields of study on our All Scholarships by Major page.
Studying one of the college/university majors listed below can be helpful (or necessary) for becoming a school administrator. Click on the links to find out what else you can do with these majors! | https://www.academicinvest.com/business-careers/business-administration-careers/how-to-become-a-school-administrator |
This Community of Practice supports the educational components of Vanuatu's Universal Access Program, including a training workshop for over 60 teachers and zone curriculum advisers, to be held in Port Vila between August 24th and 28th, 2015. This website serves both as the learning management system for the training, and the hub for ongoing community support.
Background
Vanuatu has liberalised its telecommunications market in 2008. One of the policies of the Government is the Universal Access Policy (UAP). This policy aims to provide telecommunications internet services into rural and unserved areas that are not commercially viable for operators to provide telecommunications services. As a means of expanding demand for the furtherance of Vanuatu’s development goals, TRR has embarked on three pilot programs. One of them, Tablets for Students (TFS), will make 7 inch Android tablets available to students in 7 schools located throughout Vanuatu. Another, the Computer Lab/Internet Community Centre programme, is designed to assist with the installation of computer labs in 15 schools across the country. Integral to the success of these programmes is the ability of teachers and other key stakeholders to understand the technical capabilities, requirements, strengths and limitations of the computing resources they have at hand, of the internet in general and most importantly of the professional community of practice which they collectively comprise.
Vanuatu UAP Training News
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One of the core components of the UAP Network is the UAP Gateway and Server. The UAP Gateway and Server was designed to address several challenges and needs of people making use of these technologies in rural schools. For example, it should be able to filter inappropriate Internet content and protect users from outside attackers as much as possible. These sites often operate in low and unreliable Internet connection environments, pre-loading the servers with many educational resources locally accessible will significantly improve the learning experience for users. The UAP Gateway and Server also comes with a collection of useful tools to build local content and share files among other things. All of these features are packaged and presented to the users into a easy to use Community and School Portal website. This session introduces the participants to this UAP Gateway and Server and a brief overview of its user features through the Community and School Portal.
Teachers and students in Vanuatu need relevant and up to date digital resources to support teaching and learning with ICTs. In addition to resources authored specifically for Vanuatu, we can look to the wider world of Open Educational Resources (OERs). OERs are any type of educational materials that are in the public domain or introduced with an open license. The UAP is making available to participating schools a large large library of digital OERs called Rachel, resources from regional organisations complied by the Secretariat of the Pacific Community (SPC) and from other sources such as UNESCO. In addition, TRR has provided Vanuatu teaching resources and curriculum materials. Vanuatu teachers also need to be aware of online resources including open distance learning courses. This session will provide a basic introduction to all of the above.
Tablets for Students (TFS) is a component of Vanuatu's Universal Access Program (UAP) that will make class sets of 7 inch Android tablets, charging trolleys and (where applicable) solar power supplies available to students in 7 schools located throughout Vanuatu. The tablets are delivered pre-configured with almost 50 educational apps in both English and French, covering a variety of content areas. This training module teaches participants how to make use of the Android platform for education. The participants will be introduced to Android and how to administer this platform. They will then review and become familiarised with the various educational applications. First steps are taken towards integrating the use of tablets into the teaching and learning environment, including ICT pedagogy, classroom and resource management including care, handling and power management.
There are many rationales pointing to the need for more locally produced and/or relevant digital resources for Pacific Islands education systems. A joint ISOC/UNESCO/OECD survey has demonstrated that the development of local content improves the value of communication networks, and contributes to increased uptake and lower prices. Teacher champions and administrators will need to understand the integral role they play in this equation, and must be provided with the skills and resources necessary to ensure the creation of content that is relevant, unique and of value to themselves and to others. With the infusion of ICTs and media culture into all aspects of modern life, young people need to acquire digital and media skills as an intrinsic part of their learning in all content areas and in literacy education. With ICT tools as powerful enablers of authentic learning experiences, school teachers, students and communities can become co-producers of local content in important curriculum areas. For instance, to ensure that indigenous knowledge and cultural values are transferred between the generations. Such local content collaborations can bring a sense of pride and achievement. In this training module participants are introduced to local content development. Participants will learn how to build their own school website, a local knowledge base using a wiki and several multimedia tools such as image, sound and video editing.
Participants are tasked with one or more evening projects they can do in small groups of 3-4. The projects should encompass knowledge acquired throughout the workshop. It can contain elements of one or more of the sessions covered throughout the week.
Vanuatu's Universal Access Program (UAP) aims to increase demand for ICTs and ICT services with the understanding that schools, especially in rural areas, are hubs for their communities in many ways. The UAP provides connectivity, equipment and capacity building for school-based facilities that will be shared with communities in mutually beneficial ways. Such synergy has been observed in studies of similar community-access and telecentre programmes around the world. Furthermore, sustainability can be regarded from several perspectives including social and organisational as well as financial. It is the facilities that are most useful and utilised that will evolve supporting ecosystems and the financial flows to keep the facilities going over time. In this session, participants will gain insights into administrative techniques and strategies for sustainable school and community shared access arrangements.
Achieving the goal of ICT integration into a country's education system cannot be achieved overnight, and has many determinants. For instance connectivity, availability of ICT equipment and digital resources, teachers' user skills and ICT pedagogy skills, the matter of infusing ICTs into the curriculum and the learning environment, teacher education and policy development at different levels. As recommended by organisations such as UNESCO, it is best achieved through a system-wide approach. At the school level, teacher champions and administrators and local education officials such as zone advisers need to nurture the evolving ICT culture and be aware of the changes it brings. For instance, ICT can enable new teaching methods, change the relations between the teacher and the student, the student and their learning, and the schools and the education authorities. This workshop is only the beginning for an ongoing process of ICT learning and appropriation by the teachers, who will all be at different stages in the process. In this session the participants will explore and begin to unpack these challenges and so gain understanding of the change management processes that will be needed.
ICT are simply tools and they come in many forms. Information systems are common tools which were for a long time mostly available to organisations with more resources. These days are mostly over due to the proliferation of free software, software developed in an open manner often collaboratively by groups of people and even commercial organisations. It is almost always possible to find some good quality free software for any task at hand and effectively improving the processes within a school administration is no exception. SchoolTool is a freely available student information system and database which can help in organising and more effectively managing student information, teacher grading of students, parent information and more. This session introduces SchoolTool which is also made available for free on the UAP Gateway and Server.
Log in to view Refresher Training programme, August 28th- Sept 8th, 2017
Demonstration of a course with TELMOOC videos. You will see how it works with full length uploaded videos and with videos added as embedded Youtube links. Test how you can download to the app. Note that you must go to the app settings and in Synchronisation allow syncing with mobile (default is Wi-Fi only).
Course used by MEHA TEST to experiment with.
This course was designed for the Moodle School demonstration site as an example of a course optimised for the mobile app.
Demonstration course. Click to proceed. | https://community.nuzusys.com/ |
The present study revealed the contributions of support and training courses to the stakeholders in addition to the problems experienced by different stakeholders during the course procedure and their solution offers based on the opinions of school administrators. The qualitative research methodology was used in the study and phenomenology was determined to be the research design. The study group consisted of 40 school administrators employed at support and training courses in Nizip district of Gaziantep province in the academic year of 2018-2019 and determined through criterion sampling. Content analysis was conducted for the in-depth analysis of research data. According to the obtained findings, it was concluded that support and training courses contributed to the students in terms of promoting school lessons and increasing school success, to the teachers in terms of financial support and professional development, to the parents in terms of freeing from financial burden, and to the administrators in terms of financial support and teaching skills development. It was found that support and training courses had several problems such as absenteeism, tiredness, intervention in course selection, indifference, increased workload, arranging teaching schedule, lack of resources, and lack of supervision. Based on the views of school administrators and relevant literature, it was recommended to maintain discipline about absenteeism by reducing the number of lessons, to establish a course employment system for teachers, to request a fair amount of money from the parents, to increase the income of administrators, to produce materials and resources by establishing course centres and to improve supervision for support and training courses to be more effective.
Support training, Support and training courses, School administrator
From the month of January 2020, the articles which will be sent to the journal have to be uploaded to the system in English and Turkish. The articles which do not comply with the format will not be taken under review.
Our journal has been indexed in H. W. Wilson (Educatin Full Text) since June 2019. | http://ijetsar.com/DergiDetay.aspx?ID=207&Detay=Ozet |
A Middle School Tutor is hired to provide non-classroom, academic instruction to students on an individual or small-group basis. A well-written Middle School Tutor Resume mentions the following duties and responsibilities – creating lesson plans to teach students subjects, assessing students to evaluate their abilities, strengths, and weakness, teaching lessons they have planned to an entire class, grading students assignments and examination, communicating with parents or guardians about the child’s progress, working with students individually and helping them overcome specific learning challenges, preparing students for standardized tests required by the state, developing and enforcing classroom rules, supervising students outside of the classroom.
Those seeking this job role must mention on the resume the following skills – strong communication skills, the ability to discuss student’s needs with parents and administrators, patience, and knowledge of using the latest teaching technologies and methodologies. A relevant subject degree and an education degree are commonplace among job applicants.
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Summary : Looking for an opportunity where I can utilize my bachelor's degree to further my passion in the field of economics. Providing basic technical support with online course set up and access. Determining from student notes and discussions the concepts that need to be taught or re-taught. Evaluating student binders, including calendars, class and text notes, book notes, etc.
Skills : CPR certified, 60 wpm typing , Familiar with most commonly used computer programs such as excel, and word.
Description :
Summary : Highly qualified Middle School Tutor with experience in the industry. Enjoy creative problem solving and getting exposure on multiple projects, and I would excel in the collaborative environment on which your company prides itself. Conducting mini lessons in the process of writing in all subject areas, study skills, and other aspects of course preparation.
Skills : Microsoft Office, Reflection Workspace, Customer Service, Telephone Troubleshooting, Writing.
Description :
Summary : To gain employment with a company where I am able to use both technical skills learned through past employment as well as the professional skills I have gained through my undergraduate and graduate experience. Establishing and maintaining control in the learning environments and to administer discipline in accordance with board policies, administrative regulations, and site policies and rules.
Skills : Bilingual in Spanish and English Understanding of ethnic diversity and cultural compassion Communication Filing and organizing Proficient in Word, Excel, Microsoft and PowerPoint Knowledge in office administration.
Description :
Summary : As a Middle School Tutor is Conducting brainstorming and clustering sessions with students, as needed. Becoming familiar with the educational materials and resources available to teachers and students. Facilitating peer critique groups in the subject area labs, as needed. Contacting teachers regarding course outlines and assignment schedules in preparation for intervention sessions.
Skills : Planning, Teaching.
Description :
Headline : Middle School Tutor with 6 years of experience in Contacting students and parents using company technologies for school program, outreach, and retention. Communicating frequently and honestly with teachers regarding student progress and areas of concern. Determining from teacher directions and evaluation of student work, the concepts that need to be the focus of tutorial sessions.
Skills : Planning, Evaluational Skills.
Description :
Objective : Middle School Tutor with 5 years of experience in Maintaining a cooperative, professional relationship with all administrators, teachers, colleagues, students, parents, and community members. Utilizing of Socratic questioning and writing techniques, as needed. Reviewing student course schedules for accuracy and support.
Skills : Scheduling, Review Planner.
Description :
Objective : As a Middle School Tutor is Periodically assisting in testing and assessments. Assisting professionals in the instructional program in maintaining discipline and encouraging acceptable behavior from students, exhibiting a positive role model for students that support the organization mission.
Skills : Testing Assistant, Instructional Skills.
Description :
Objective : Middle School Tutor is Taking all necessary and reasonable precautions to protect students, equipment, materials, and facilities. Keeping informed of and comply with district and school regulations and policies. Maintaining prompt and regular attendance for each assignment. Attending all required tutoring training and adhere to attendance policies.
Skills : Policy Assistant, Tutoring.
Description :
Objective : Middle School Tutor is Working with both middle and high school students through all aspects of the college admissions process. Managing time to accommodate a pre-determined caseload of students. Caseloading may vary year-to-year based on company need and counselor availability.
Skills : Case loader, Managing.
Description :
Objective : As a Middle School Tutor is Collaborating as part of a two-part team that includes college admissions coaches and other counselors, Delivering college admissions focused webinars, social media events, and assist with other marketing endeavors, as needed and time allows, Assisting with the delivery of institutional programming, as needed and time allows.
Skills : Directing, Programming Assistant.
Description : | https://www.qwikresume.com/resume-samples/middle-school-tutor/ |
DESCRIPTION:
The Oak Park School District is committed to a culture of high expectations and continuous improvement through aligned and meaningful professional development, a partnership with Oakland ISD services, data teams to drive instructional decisions and best practices and a relentless focus on the whole child. OPSD is hiring one full-time (1.0 FTE) general education social worker at Oak Park Preparatory Academy. OPSD is looking for a social worker who is intrinsically motivated; who has a deep desire to grow professionally; who believes children deserve to learn in an environment with the highest level of cultural competence; who is committed to providing children with boundless opportunities; and who understands that initiative, rigor and grit are essential to be a great school social worker in the 21st Century.
QUALIFICATIONS:
Required Education/Certification
- Master’s Degree in Social Work from a Council of Social Work Education (CSWE) accredited program
- Completion of an MDE-approved School Preparation Program
- Valid Social Work License (LLMSW or LMSW)
Preferred Experience
- Demonstrated ability to work with elementary students who experience a variety of social, emotional needs.
- Skilled in conducting and analyzing assessments used for differential diagnosis of emotional trauma, as well as clinical skills which include the ability to provide personalized interventions, based on sound clinical judgment, in individual or group situations.
- Skilled in a variety of flexible behavior management strategies appropriate for elementary students.
- Demonstrated leadership in functional behavior assessment and the development of Individual Behavior Plans (BIP).
- Proven ability to work with families and facilitate partnerships with community agencies/resources in order to meet the needs of student in the educational setting.
- Experienced serving as an advocate for the unique needs of students while working collaboratively with the principal, teachers, school psychologist and parents/guardians.
- Proven leadership skills in the area of compliance, MTSS, BIP and 504.
- Experience with a diverse student and parent population.
- Strong organizational skills, flexibility and exceptional at prioritizing the completion of work.
- Outstanding written and verbal communication skills.
GENERAL DUTIES AND RESPONSIBILITIES:
- Provide leadership to colleagues when identifying and implementing a variety of flexible behavior management strategies appropriate for elementary students.
- Work with families and facilitate a partnership with community agencies and resources in order to meet the needs of student in the educational setting.
- Serve as an advocate for the unique needs of students while working collaboratively with the classroom principal, teachers, school psychologist, parents/guardians and other ancillary staff.
- Counsel students individually and in small groups to provide social, emotional and behavioral support.
- Communicate and assist families to promote a positive home and school partnership.
- Provide classroom presentations for students on various subjects related to character education and building a healthy school culture.
- Participate as leader and viable member of the Traumatic Event Crisis Plan (TECIP) team.
- Provide professional development for teachers on subjects related to the role of a social worker and topics that will help support students who have faced trauma, loss and or emotional challenges.
- Create an inviting and nurturing office and meeting space that meets the needs of all learners academically, culturally, socially and emotionally.
- Provide leadership in the areas of 504’s, MTSS Tier II interventions and crisis management with the highest level of integrity and fidelity.
- Use multiple assessments develop, implement and continuously monitor Behavior Intervention Plans (BIP) that will best support student in the classroom and learning community.
- Participate in professional development opportunities that are aligned with the district and school’s mission, vision and goals.
- Be an active member of the school community through, Professional Learning Communities, various building and district committee work, the School Improvement Team and other leadership opportunities as presented.
- Engage with student activities outside of the school day that supports the programming and traditions of the building and district.
- Perform other duties assigned by the Specialized Student Services Director and building principal.
ESSENTIAL DUTIES
- Provide an educational program that meets the educational needs of each student.
- Provide emotional and social guidance which is consistent with District expectations and which meets the educational needs of all students.
- Communicate with students, parents, administrators and other staff members in a professional manner which is consistent with District and school expectations.
- Plan, implement, record data and create reports consistent with District, State and Federal mandates.
- Provide supervision which ensures a safe and nurturing work environment.
- Manage of time, equipment, and materials efficiently and maintain a physical and emotional environment that is well-organized and student centered.
APPLICATION METHOD
EXTERNAL CANDIDATES:
All interested and qualified external applicants must complete an application and upload all necessary documents on the Oakland Schools Consortium Website (please visit our HR web page at: https://www.oakparkschools.org/departments/human-resources/ to access the Oakland Schools Consortium website). All letters of interest, resumes and applications must be received no later than the deadline listed or until the position has been filled. | https://socialwork.wayne.edu/career-resources/postings/96908 |
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CHAPTER ONE
INTRODUCTION
Background of the Study
The importance of effective budgetary practices at all levels of economy has for long been the major concern of many educationists, economists and politicians. This is because effective budgetary practices reflect the focus of administrators’ expenditure and revenue for major development in any financial year. Aguba (2009) believed that a budget is a financial blue print for the operation of organization, including the school system, for the fiscal year. In consonance with this, Ogbonnaya (2005) defined a budget as the financial statement of the proposed expenditure and expected revenue of the government, public corporations, or educational institutions for a particular period of time.
Budget, therefore is an itemized summary of estimated or intended expenditures for a given period along with proposals for financing organizational programmes necessary for the attainment of pre-determined objectives. Budget is expected to control wastage and extravagant spending in grant-aided secondary schools.
School budget is an established financial standard needed to consciously guide the activities of a school administrator towards the attainment of the aims and objectives of the school in a given fiscal year (Ayodele, 2006). This position is in line with the United States General Accounting office report in 1998 when it asserted that school budgeting had historically been the process of balancing expenditure with revenue to effect changes in spending, a process policy makers view as constrictive. Constrictive in this context has to do with strict control of budget administration in schools.
According to Roe cited in Ogbonnaya (2005), education budget is the method through which the translation of educational needs into a financial plan which is interpreted to the public in such a way that when formally adopted, it expresses the kind of educational programme in focus. Educational budget can be described as the proposed income and expenditure of educational institutions within a particular period of time, usually in an academic session.
In general, Bala (2011) defined educational budget as an out line of plan for financing the school system for a particular period of time. Bala believed that the school budget should have timeframe to allow effective appraisal or evaluation of budget to take place. Educational budget therefore, is a financial plan that sets forth the resources necessary to meet a set of goals in an academic institution for a certain period of time. Budget is recorded in monetary terms, it sets realistic goals for programmes, staffing and operations. The revenue side of the budget identifies the means for financing the plan, while the expenditure side of the budget estimates the cost of the plan.
In any case the budget is the key instrument for the expression and execution of the school administration’s financial policy. Educational budget has a wide range of implications for the achievement of educational objectives because staff members have to be paid their salaries and wages, equipment need to be provided for use, infrastructural facilities need to be provided and existing ones need to be maintained for effective performance.
UNESCO’S blue print for effective budget administration as stated by Mckinnon, Walker and Davis (2002), include procedures for budget preparation, budget forecast/estimates, adequate budget provision, implementation strategies, supervision or monitoring of budgetary practices, assessment and evaluation of results. In the light of these principles of budgetary practices set out by UNESCO, the concern of this study is to appraise the following key factors as they relate to grant-aided secondary schools; procedures used for budget preparation by principals and bursars, budget estimates by principals, budgetary provisions by principals, use of formalized monitoring strategies by principals, and factors that inhibit principals’ compliance with budget guidelines in grant-aided secondary schools.
Budget procedure is the manner in which principals in grant-aided secondary schools prepare the school budget, process it, based on guidelines issued to them for revenue collection and expenditures to be incurred. Budget estimate is a preliminary assessment either of funds projected to be available to the school or funds required to complete a project. It also involves translating programmes and projects to monetary terms. In the same vein, budgetary provision is the outlines of areas necessary for revenue or completion of project, such as recurrent and capital projects. Budget provision is used for planning purpose.
Budget monitoring requires the examination of laid down principles to be used by school administrators and verification of documents kept by them for proper budgetary practices. The essence of this is to ensure orderliness in budget process and to offer suggestions for improvement in budget administration. Also budget implementation is the distribution of resources and funds from the central pool to the departments and units of a school for the execution of various projects and programmes as contained in the budget document therein.
The researcher intends to examine the budget variables to find out whether principals adhere to or comply with budget guidelines entrenched for them. It is perceived by many people that budgeting is a simple process of financial accounting, however based on the researcher’s experience many people are concerned with the weightings of money in budget estimations at the expense of laid down guidelines for budgetary practices.
Budgetary practices are the concerted efforts made by government, corporations, educational institutions or individuals to realize their organizational pre-determined goals through effective planning of budget components. Budgetary practices in schools reflect the way principals carry out processing, estimates, planning, implementing, monitoring and administration of school budgets. Budgetary practices of principals in secondary schools can be broken down into various parts forming a cycle that repeats itself on a yearly basis. Accordingly, budgetary practices require the preparedness to allocate the available resources in such a manner as to avoid discrepancies, duplication and wastage, and also communicating the approved plans of budget to the various executives who are responsible for ensuring that the plans are implemented.
Budgetary practices also involve allocation of funds and authorization of expenditure in each school year. Nzekwe (2007) believes that schools’ financial operations are measured, developed, adopted and executed through budgetary practices. Budget is one of the tools used to provide the bases for controlling the financial affairs of principals and also used to measure their efficiency. In line with Nzekwe’s believe, Omede (2010) opined that, the number of educational needs have grown so much that, there is need to operate an effective budget in order to cope with the current educational challenges in Nigeria. It becomes imperative to appraise budgetary practices in secondary school because an effective budgetary practice is believed to be a necessary condition for the improvement of secondary school administration.
Appraisal is defined by Camenon (2000) as the process of making value judgments or taking decisions about events, or their characteristics. Camenon further affirmed that the judgment is based on empirical data or information made available through review which is quantitatively measured. Appraisal in this context therefore aims at obtaining information from principals and bursars of grant-aided secondary schools to enable the researcher make value judgments about their compliance with budget guidelines. On the other hand budget appraisal is an assessment of results at the end as related to the original objectives set for the programme.
The process of appraisal takes into consideration the estimates at the initial stage of planning. The officer who operates the budget is expected to issue financial reports to the Teaching Service Board on a regular basis, indicating the total expenditures to date, balance in the account and anticipated problems in keeping within the main budget item limitation. The review of the guidelines necessitates that a recommendation could be made for better educational operations (Burup and Brimley cited in Nzekwe, 2007). Budget guidelines obtained from Teaching Service Commission of each of the six states in North Central, Nigeria is the yardstick for the appraisal of budgetary practices of principals in grant-aided secondary schools. Appraisal of budgetary practices in grant-aided secondary schools is expected to improve financial managements in these schools.
Grant-aided secondary schools are part of educational institutions which their principals ought to improve their budgetary practices in order to attain the predetermined goals of secondary schools. Principals are expected to effectively mobilize available resources and to develop good strategies for carrying out expenditure in schools. Grant-aided secondary schools are educational institutions set up for the purpose of training middle manpower, inspire students with a desire for self-improvement and achievement of excellence, to provide opportunity for education of higher level (FRN, 2009).
Oguche (2005) Also noted that grant-aided secondary schools (GASS) are post primary schools established by missions, communities, or individuals that were taken over by the government to fund and control for the purpose of preparing students for tertiary education and middle level employment. Although these institutions are taken over by the government, the proprietors who established the schools are stakeholders in managing the schools. State governments recognize the fact that grant-aided secondary schools are viable tools and capable of inducing changes into national growth and development by producing high quality students who will on the long- run become components for the cultural, socio-economic and environmental sustainable development of individuals, communities and nations (U.N.E.S.C.O., 2003).
Grant-aided secondary schools are governed by Board of Governors. The Board of Governors determines the programmes of the schools, receives budget estimates and considers it before forwarding it to the Ministry of Education/Teaching Service Board. The membership of Board of Governors in all grant-aided secondary schools in North Central, Nigeria is made up of both state government and proprietor representatives respectively.
Okpanachi (2005), observed that most of the secondary schools in the North Central, Nigeria lack basic facilities like electricity, toilet facilities and other supporting facilities that will enhance teaching and learning. In addition, if members of staff are not properly remunerated it could in turn affect teachers’ level of productivity with all the negative implications on the students. The need to maintain good budgetary practices by principals of secondary schools could be to ensure good working condition for all members of staff and to make the school environment conducive for learning and teaching in order to attain the goals of education.
Principals are the administrative heads of secondary schools. In grant-aided secondary schools, proprietors nominate three persons and the Teaching Service Commission approves one person out of the three. The principal of a secondary school is regarded as the chief executive, the mentor, the leader and the welfare officer of the school. Accordingly, Orji (2001) observed that principals are financial managers who perform financial functions. The principal also take very important decisions to ensure that funds are available and utilized in the most efficient way. Principals prepare and operate the budget of their schools with the bursars/finance clerks who over see the finance department. The bursars/finance clerks are employees of the Teaching Service Board. They are career civil servants and occupy the position by promotion. Furthermore, the bursars/finance clerks are involved in one way or the other in the financial management activities of the schools. Bursars are the custodians of school account books, make necessary entries as prescribed by financial guidelines, collect and collate budget items, effect payments on behalf of the principals, prepare and pay salaries to all categories of workers among other duties.
In the view of Ogbonnaya (2012), the success of the budget should be judged by the extent to which its estimates and expenditures agree with the actual amounts received and expended. This success can not be realized without effective monitoring of budget at all the stages of budget processes. Budget monitoring ensures proper records of revenue and expenditure made according to the estimates. Bala (2011) noted that predictive budget monitoring helps to detect corruptive tendencies of school administrators and other members of staff. Also budget monitoring forces all persons involved in budgetary practices to adhere to laid down guidelines.
The State Ministry of Education /Teaching Service Board, is expected to control the finances of the schools through the budget prepared by the principals of grant-aided secondary schools. School budget could be used to determine the compliance of principals to financial regulations in the schools. The budget guidelines as a management control system is expected to provide grant-aided secondary schools with uniform standard procedures by which principals can control and maintain up-to-date records of financial operations in their schools. It is important that budget blue prints be followed strictly to ensure that satisfactory authorization is observed before revenue collection, and before expenditure is incurred.
Attempts have been made by the government to ameliorate the problems affecting poor budgetary practices in government establishments, including grant-aided secondary schools. These efforts include: formulation of budget guidelines, setting up of budget implementation committees at the state level, setting a time frame for budget submission, issuing financial regulations to institutions, among others. These efforts are aimed at helping administrators to operate effective and reliable budget for their organizations. However there seem to be contending issues arising from budget administration in grant-aided secondary schools. Where are we getting the budgetary practices wrong? We need to find out and make it right.
There are many criticisms against budget preparation in grant-aided secondary schools as observed by the former executive secretary of Kogi State Teaching Service Commission (Adewumi, 2003). Some of the criticisms include the fact that most principals do not involve their sub-ordinates in budget preparation and that their budget administration does not follow financial guidelines. Principals are expected to disburse funds to various units and subunits in the school based on the estimates submitted earlier by the heads of departments. If funds are not disbursed appropriately some important items like instructional materials, science chemicals, chalk, etc may not be purchased for the teachers’ use. Nzekwe (2007) observed that in the school system, many principals have been accused of poor budgeting practices by the supervisors, teachers and parents. For example, it has been observed by some school officers that the principals do not follow budget guidelines in preparing estimates nor keep and use the necessary budget documents in their schools. Other problems such as failure of principals and bursars to attend training and workshops, seminars and conferences regularly to update their knowledge on how to carry out budget estimates, procedures for budget preparation and ability to monitor funds disbursed for the execution of various school projects can affect compliance with budget guidelines. Inability to delimitate support and active involvement of all cadre of management and failure to develop reasonable forecasts and realistic plans, may pose hindrances to effective budgetary practices of principals in secondary schools. Also where prejudice and personal biases are allowed, budgeting suffers. Budgetary practices are about improvement of the school system. It is not to be conceived as personal gain or benefit. The players in the school must consider the interest of the organization above personal or individual interest.
To buttress the above observation, Onyike (2009) expressed regret that poor budgetary practices had accounted for the seeming neglect and dilapidation of buildings and infrastructure in greater percentage of schools over a decade particularly at secondary school level. If school budgets are poorly estimated, not properly planned, poorly processed, not effectively implemented and not properly monitored, it could translate into poor infrastructure and inadequate provision of instructional materials which could also lead to series of agitations, crises, strikes, protests and demonstrations by teachers and students. In contrast, Okpanachi (2005) and Onojah (2008) contended that principals and bursars were knowledgeable enough to handle budget making practices in secondary schools based on their track records of experiences. In view of the conflicting opinions of various educationists and the problems observable in budgetary practices in grant-aided secondary schools, this study looked at the planning stages of school budget holistically and made some recommendations for improvement. Particularly the extent principals and bursars in grant-aided secondary schools in North Central, Nigeria comply with budget guidelines.
Statement of the Problem
The inability of principals to prepare budget components in grant-aided secondary schools has severally disrupted school programmes, leading to a threat in the achievement of educational objectives. The effectiveness of budgetary practices in grant-aided secondary schools towards school improvement seems to be in doubt because of many criticisms labeled against principals and bursars. Most of these allegations bother on principals’ budgetary practices that appear to be shady with no regard to budget guidelines, neglect of the contributions of subordinates during budget preparation, refusal to set up budget committees at the school level to collate and harmonize budget items, prepare budget hurriedly thereby missing out some items that are important for the running of their schools, lack of seriousness on the part of the principals in monitoring budget operations in their schools among others. These scenarios have often led to some aggrieved vice principals and teachers writing petitions against principals and bursars accusing them of shady deals and not showing transparency in the operation of the budget preparation in their schools. As a result of this, crises of various dimensions such as strike actions, work to rule actions, brain-drain among teachers, mistrust of administrators among others, are of regular occurrences in grant-aided secondary schools in North Central, Nigeria. For the past six years or so there has not been any academic session that teachers in grant-aided secondary schools in North Central, Nigeria do not go on strike. Sometimes the strike lasts for four or five months. Our worry is that their students must write external examinations with other students who have un-interrupted school programmes, they must graduate with them, and they must be certificated. Can one at this point say that educational objectives are being achieved at this level or unit of secondary school? The problem of this study put in question form is; to what extent do principals in grant-aided secondary schools comply with budget guidelines?
Purpose of the Study
The purpose of the study was to appraise the budgetary practices in grant-aided secondary schools in order to ascertain the extent Principals of grant-aided secondary schools comply with budget guidelines in North Central, Nigeria. Specifically, the study sought to:
1. Find out the extent procedures used for budget preparation by principals and bursars in grant-aided secondary schools comply with budget guidelines
2. Determine the extent budget estimates of principals in grant-aided secondary schools are prepared in accordance with laid down budget guidelines.
3. Ascertain the extent budgetary provisions by principals in grant-aided secondary schools are in accordance with laid down budget guidelines.
4. Determine the extent principals in grant-aided secondary schools use formalized monitoring strategies to ensure heads of departments’ compliance with budget guidelines.
5. Find out factors that inhibit principals’ compliance with the school budget guidelines.
Significance of the Study
The significance of this study emanates from both theoretical and practical bases of budgetary practices in schools. Theoretically, the study is hinged on the Wiseman–Peacock hypothesis and Roseman’s theory of appraisal. The findings of this study would ginger a strong desire to appreciate credible data used and the reviews of empirical studies as it relates to the purpose of this study. The findings would also create rooms for assumptions that can be tested empirically. It would serve as a reservoir of knowledge for budget experts.
Practically, the findings of this study would be beneficial to the followings:
Principals and bursars of grant-aided secondary schools, Secondary School Boards, Ministry of Education, proprietors, teachers, students, education system and future researchers.
The findings of the study would create a general awareness on how principals and bursars in grant-aided secondary schools will comply with budget guidelines to stimulate improvement in school administration. The study is hoped to control the financial behaviour of school administrators and bursars. It is hoped that the results of this study would assist principals and bursars in grant-aided secondary schools to improve on areas of budget components they are defective.
The findings of the study would be of immense benefit to the Teaching Service Commission. It would induce the State School Boards to assess their budget guidelines and call circulars to ascertain their strengths, weaknesses, opportunities and threats (SWOT) and effect improvements where necessary. This is critical for the realization of educational objectives in grant-aided secondary schools.
State Ministries of Education and other educational agencies saddled with the responsibilities of formulating policies and ensuring compliance with such policies would avail themselves the opportunity from the findings of the study to formulate effective school budget and financial management policy for grant-aided secondary schools. The Ministries and her agencies would find the result useful for decision-making. The result would create a major impact on the operations of school programmes which will definitely improve the process of administration of grant-aided secondary schools and in general develop the society. The findings will also help to provide feedback to the State Ministries of Education and educational agencies most especially as regards principals’ adherence to budget guidelines.
The findings of the study would also be beneficial to the proprietors of grant-aided secondary schools. The proprietors would have idea of budget operations by the principals especially the restrictions placed on them by the school budget guidelines. This awareness will help them minimize interferences on financial management in grant-aided secondary schools and would greatly support the principals to realize educational objectives. The findings also offer solution and ensure greater participation of proprietors in the financial plan of their schools.
The findings from the study would be of importance to the teachers who support the principals to achieve compliance with laid down budget guidelines in grant-aided secondary schools. When their needs are met they will collaborate in a greater measure to achieve educational objectives of the schools.
The findings of the study would be of immense benefit to the students who stand to gain if the problems occasioned by poor budgetary practices by principals and bursars are handled. The society would benefit immensely from the findings of this study because if there is conducive environment for learning in grant-aided secondary schools, the objectives of the school to train middleman power will be greatly achieved. | https://codemint.net/guidance-counseling/appraisal-of-budgetary-practices-in-grant-aided-secondary-schools-in-north-central-nigeria-implication-for-counselling/index.html |
This course examines the relationship between form and meaning in human language. We consider the rules for combining word meanings to derive sentence meanings in a predictable way, and we explore the principles which allow speakers to communicate more by uttering a sentence than is contained in the sentence meaning itself. We apply these concepts not only to content words but also to grammatical morphemes such as tense, aspect, and modality markers. This course is required for the MA in Applied Linguistics and satisfies the prerequisite for AL5316 Theory and Practice of Translation.
Course DetailsLevel: Master's Level
Credit hours: 3
Term(s) course is offered: Spring
Prerequisites: AL4410b Principles of Grammatical Analysis (b).
Back to course list
To view more details for this course (instructor, session, time, textbooks, etc.), login to Campus Cafe or view the course schedule. | https://www.diu.edu/course/al5315-sl/ |
Technical Writing. Tense–aspect–mood - Wikipedia. Tense–aspect–mood, commonly abbreviated tam and also called tense–modality–aspect or tma, is the grammatical system of a language that covers the expression of tense (location in time), aspect (fabric of time – a single block of time, continuous flow of time, or repetitive occurrence), and mood or modality (degree of necessity, obligation, probability, ability). In some languages, evidentiality (whether evidence exists for the statement, and if so what kind) and mirativity (surprise) may also be included.
The term is convenient because it is often difficult to untangle these features of a language. On-line Chinese Tools.
IPA symbols. Learn Words in Any Language. Quiz Yourself: Lights, (Camera Emoji), Action! Glossary of grammatical terms – Oxford Dictionaries. Oxford Dictionaries. Some grammatical terms may be familiar to you, but others can be confusing or hard to remember.
Clicking on any term below will give you a quick and clear definition. Below the categorized section you’ll find all the terms listed from A–Z, so you can browse that way if you prefer. abstract noun A noun which refers to an idea, quality, or state (e.g. warmth, liberty, happiness), rather than a physical thing that can be seen or touched. Compare with concrete noun. active An active verb has a subject which is performing the action of the verb, for example: John ate the apple. The opposite of passive. Adjective A word, such as heavy, red, or sweet, that is used to describe (or modify) a noun. Adjunct A type of optional adverbial that adds extra information to a sentence, for instance: I can’t sleep at night. Read more about adverbials and adjuncts. adverb.
Computer-assisted translation. This article has multiple issues.
Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (January 2011) (Learn how and when to remove this template message) This article needs additional citations for verification. Computer-assisted translation, computer-aided translation or CAT is a form of language translation in which a human translator uses computer software to support and facilitate the translation process. Content and language integrated learning. Content and language integrated learning (CLIL) is a term created in 1994 by David Marsh as a methodology similar to but distinct from language immersion and content-based instruction.
It is an approach for learning content through an additional language (foreign or second), thus teaching both the subject and the language. The idea of its proponents was to create an "umbrella term" which encompasses different forms of using language as the medium of instruction. CLIL is fundamentally based on methodological principles established by research on "language immersion". This kind of approach has been identified as very important by the European Commission because: "It can provide effective opportunities for pupils to use their new language skills now, rather than learn them now for use later.
Ubc VISIBLE SPEECH. Introduction to Articulatory Phonetics (Consonants) British English Pronunciation and the Importance of Phonetics. A Latin Dictionary - Wikipedia. History The division of labour between the two editors was remarkably unequal.
Short, a very thorough but slow worker, produced material for the letters A through C, but B and C were lost by Harpers, meaning that his work now only appears in the letter A (216 pages), while Lewis was solely responsible for the entries beginning with the letters B through Z (1803 pages), who worked on his spare time from his law practice. In 1890 Lewis published a heavily abridged version the dictionary, entitled An Elementary Latin Dictionary, for the use of students. Sometimes called the Elementary Lewis, it is still in print today. Deep Grammar. Learn Spanish, French, English and other languages for free. BBC Languages – Free online lessons to learn and study with.
Learning, made joyful - Memrise. Lerne kostenlos Spanisch, Französisch, Deutsch, Portugiesisch, Italienisch und Englisch. German Flash Cards. Quick Directions 1) Load flash cards into the Main Deck by choosing one of the following: Load cards from the database...
[e.g. German 101, Vorsprung Kapitel 4] Create your own custom cards... [individually or using a Word List] Load cards from saved session... 2) Now go through the cards in the Main Deck one at a time using the arrow keys: Use the Up Arrow Key to flip the card over, and decide whether or not you are familiar with the vocab on the card.If the card is immediately familiar, use the Left Arrow Key to move it to the "Easy Deck" (top left).If you decide that you need to keep studying this card, use the Right Arrow Key to move it to the "Hard Deck" (top right).Use the Down Arrow Key once or repeatedly as an "Undo" button to if you accidentally send one or more cards to the wrong deck 3) When you get to the end of the Main Deck, the Easy Deck should contain all the cards that you already know, and the Hard Deck should contain all the cards that you still need to review.
Center for Open Educational Resources and Language Learning. Quotations and Proverbs Search. Livemocha - Free Online Language Learning - Free Lessons Online. English-Zone.Com. Boardreader - Forum Search Engine. English. Livemocha - Free Online Language Learning - Free Lessons Online. Learn French Online : Learn French for Free. Listening comprehension. Level B2.
Dictionaries. Free French lessons. Digcit. English. Learn German podcast: German phrases, slang words, sayings and idioms. German grammar. German grammar is the grammar of the German language.
Although some features of German grammar, such as the formation of some of the verb forms, resemble those of English, German grammar differs from that of English in that it has, among other things, cases and gender in nouns and a strict verb-second word order in main clauses. German has retained many of the grammatical distinctions that other Germanic languages have lost in whole or in part. There are three genders and four cases, and verbs are conjugated for person and number. | http://www.pearltrees.com/topicalsearch/languages/id5494492 |
Findings from a new report have laid the automotive industry’s cybersecurity practices bare after highlighting critical cybersecurity challenges and deficiencies affecting many organisations in the industry.
Synopsys and SAE International Release released the report (Securing the Modern Vehicle: A Study of Automotive Industry Cybersecurity Practices) that is based on a global survey conducted by Ponemon Institute.
The report surveyed 593 professionals from global automotive manufacturers, suppliers, and service providers. To ensure knowledgeable responses, all respondents are involved in assessing or contributing to the security of automotive technologies, including infotainment systems, telematics, steering systems, cameras, SoC-based components, driverless and autonomous vehicles, and RF technologies such as Wi-Fi and Bluetooth, among others.
According to the survey, a staggering 84 percent of automotive professionals have concerns that their organisations’ cybersecurity practices are not keeping pace with evolving technoligies. Furthermore, 30 percent of organisations don’t have an established cybersecurity programme or team, while 63 percent test less than half of the automotive technology they develop for security vulnerabilities.
Further key findings from the report include:
-
More than half of respondents say their organisation doesn't allocate enough budget and human capital to cybersecurity, while 62 percent say they don't possess the necessary cybersecurity skills in product development.
-
Less than half of organisations test their products for security vulnerabilities. Meanwhile, 71 percent believe that pressure to meet product deadlines is the primary factor leading to security vulnerabilities.
-
Only 33 percent of respondents reported that their organisations educate developers on secure coding methods. Additionally, 60 percent say a lack of understanding or training on secure coding practices is a primary factor that leads to vulnerabilities.
-
Seventy-three percent of respondents expressed concern about the cybersecurity of automotive technologies supplied by third parties. Meanwhile, only 44 percent say their organisation imposes cybersecurity requirements for products provided by upstream suppliers.
SAE International Ground Vehicle Standards director Jack Pokrzywa says the real-world data validates the concerns of cybersecurity professionals across the industry - and highlights a way forward.
"SAE members have sought to address cybersecurity challenges in the automotive systems development lifecycle for the last decade and worked together to publish SAE J3061, the world's first automotive cybersecurity standard,” says Pokrzywa.
“Armed with the findings of the study, SAE stands ready to convene the industry and lead development of targeted security controls, technical training, standards, and best practices to improve the security, and thus the safety, of modern vehicles."
Synopsys Software Integrity Group co-general manager Andreas Kuehlmann says in trying to stay on the pulse of innovation, the industry has fallen behind on cybersecurity.
"The proliferation of software, connectivity, and other emerging technologies in the automotive industry has introduced a critical vector of risk that didn't exist before: cybersecurity," says Kuehlmann.
"This study underscores the need for a fundamental shift—one that addresses cybersecurity holistically across the systems development lifecycle and throughout the automotive supply chain. Fortunately, the technology and best practices required to address these challenges already exists, and Synopsys is poised to help the industry embrace them." | https://securitybrief.asia/story/report-finds-automotive-industry-seriously-wanting-in-cybersecurity |
As attackers evolve their techniques to infiltrate systems and networks, cyber-attacks against critical infrastructure continue to bring risk to the air transport network. Aviation presents unique challenges due to the interconnected components within its ecosystem of airlines, airports, air traffic control, flight operations, air navigation services, maintenance, the supply chain, vendors, manufacturers, etc. Additionally, the aviation sector has become increasingly dependent on various technological advancements to ensure the safety and efficiency of its operations. The adoption of new technologies and increased connectivity presents several challenges that increase the risk of cyber-attacks.
Although hackers and other external parties can initiate cyber-attacks to exploit vulnerabilities within these systems, there are also insider threats and hazards posed by untrained employees, disgruntled personnel, and third-party access throughout the aviation supply chain. Consequently, various points of entry can make these systems vulnerable. Cyberattacks affect all connected systems and third parties. Any incident could have severe consequences that may result in the disruption of businesses, financial losses, reputational damage, compromised flight safety, and/or decreased trust in the aviation sector.
Aviation practitioners need to understand the risks and manage the challenges associated with a mix of legacy and new technologies, inefficient processes, and untrained personnel. Cybersecurity includes information technology (IT) and operational technology (OT) systems that can impact flight safety and routine operations. Cybersecurity affects all areas of an enterprise it is important that all employees understand and contribute to best practices. This includes board members, executives, and all management levels.
To address the importance and urgency of protecting civil aviation’s critical infrastructure against cyber threats, Embry-Riddle Aeronautical University, in collaboration with ICAO, designed a new 40-hour foundational course to introduce aviation practitioners to the domain of cybersecurity — focusing on the aviation field. During the first 16 hours, students will receive an introduction to core concepts and principles. Then the course will divide into two tracks 1) Leadership and 2) Technical Management. The leadership track focuses on governance and risk management, organizational resilience and incident response. The Technical Management track focuses on securing various organizational assets and systems and building resilient systems. Participants are encouraged to select the path that aligns with their respective roles and responsibilities. Both tracks are taught for another 16 hours, and then all attendees come together for the remaining eight hours to focus on various exercises that put their knowledge into practice.
Register now for the new Foundations of Aviation Cybersecurity Leadership and Technical Management course. The first session begins on 2 August 2021 with additional sessions taking place throughout 2021. | https://unitingaviation.com/news/capacity-efficiency/the-launch-of-our-new-foundations-of-aviation-cybersecurity-course/ |
What is mole in chemistry?
Mole is defined as the quantity of a substance that contains 6.022 X 1023 particles ( atoms, molecules ,formula units or ions).
Mole is represented by ” mol”.
It’s unit is mol-1
Chemical equation Representation:
A chemical equation is a way to represent chemical reaction by using symbols, chemical formulae and notations.
A balance equation represents molecular, molar, mass and volume ratio. However volume ratio is for gases only.
N2(g) + 3H2(g) —-> 2NH3(g)
Molecular ratio
1 molecule 3 molecules 2 molecules
Molar ratio
1 mole 3 moles 2 moles
Mass ratio
(14×2)=28g 3(1×2)=6g 2(14+1×3)=34g
Volume ratio (for gases only)
1 volume 3 volumes 2 volumes
Check out free notes !! | https://mydigitalkemistry.com/mole-and-chemical-equation/ |
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dja01
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Lab Question
«
on:
March 12, 2023, 06:41:00 PM »
I'm following a procedure and was wondering if anyone had some insight.
Two mole equivalents of NaX are meant to be dissolved, with X being Br, I, etc. When calculating the amount of grams I actually need, do I just convert 2 moles of NaX to grams? Or do I have to look at reaction stoichiometry?
Thanks.
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DrCMS
Chemist
Sr. Member
Posts: 1290
Mole Snacks: +209/-81
Gender:
Re: Lab Question
«
Reply #1 on:
March 13, 2023, 06:16:18 AM »
Two mole equivalents of NaX (X being Br, I, etc.) are not the same as 2 moles of NaX so yes you need to look at reaction stoichiometry.
If for example you need 2 moles of NaX for every 1 moles of reactant you need to work out how many moles of reactant you have and then scale the weight of NaBr or NaI to give twice as many moles as you calculate for the reactant.
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As usual, Winfuture has been the first to post all the specs and details for Samsung’s upcoming flagships, on this occasion the Samsung Galaxy S21 and S21 Plus.
The two devices are nearly identical except for screen size, with one having 6.2 inches and the other 6.7-inch screen. The resolution is however identical at 2400 x 1080 pixel (lower than the S20’s 3200×1440 pixel previously) which means the larger screen is less sharp.
Both can, however, deliver an impressive 1300 candela and support 60 and 120 Hz refresh rates.
They have identical camera units and phase detection auto-focus. The Samsung Galaxy S21 Plus has a 4800 mAh battery vs 4000 for the S21, both can fast-charge at 25 mAh, and the S21 Plus supports UWB, which should find use with future accessories. Neither, of course, supports the S-Pen.
Samsung Galaxy S21
Samsung Galaxy S21 Plus
See the full spec sheet below: | https://www.proftec.com/tech/corporations/samsung/spec-sheet-of-the-samsung-galaxy-s21-and-s21-plus-posted.php |
The successor to the Samsung Galaxy S4 (above) is expected to arrive in early 2014. PHOTO: AFP/ DON EMMERT
The next high-end smartphone from Samsung, the Galaxy S5, could come with an iris scanner capable of recognizing any user based on their eye, according to ZDNet Korea.
Expected to arrive in the first quarter of 2014, the phone could also be equipped with an ultra high-definition (Quad HD) display screen.
While Apple opted to use a fingerprint reader for unlocking the screen of its iPhone 5S, Samsung is reportedly using a slightly different method of user identification based on an iris scanner.
The Samsung Galaxy S5 will also reportedly have a Quad HD screen with a resolution of 2560 x 1440 pixels, a record for a smartphone.
ZDNet Korea suggests that the Samsung Galaxy S5 could be presented at the Mobile World Congress in Barcelona, taking place February 24-27, 2014. | https://www.herworld.com/life/samsung-galaxy-s5-rumoured-feature-iris-scanner/ |
Samsung Galaxy S21 series has three models, just like last year, but this time the South-Korean giant isn’t particularly keen on maintaining feature parity between them. The upside is that these distinctions are also reflected in prices and the Galaxy S21 and Galaxy S21+ cost significantly lesser than the Galaxy S21 Ultra (review) while staying true to the expected tier-1 flagship experience. (Samsung Galaxy S21+ Review हिंदी में पढ़िए)
We were indeed curious to check how much is Samsung actually cutting back in practical terms. In our Samsung Galaxy S21+ review, we will discuss how it compares against the other two Galaxy S21 siblings, what we liked about the phone, and where it fell short. Let’s get started.
Contents:
- Samsung Galaxy S21+ review: Price and Specs
- Samsung Galaxy S21+ review: Unboxing
- Samsung Galaxy S21+ review: Design and Build
- Samsung Galaxy S21+ review: Display
- Samsung Galaxy S21+ review: Performance and Software
- Samsung Galaxy S21+ review: Camera
- Samsung Galaxy S21+ review: Battery and Audio
- Samsung Galaxy S21+ review: Verdict, Pros & Cons
Samsung Galaxy S21+ review: Price and Specs
|Model||Samsung Galaxy S21 Plus|
|Display||6.7-inches AMOLED, 1080 x 2400 pixels, Gorilla Glass Victus|
|Dimensions||161.5 x 75.6 x 7.8 mm; 200 g|
|Chipset||5nm Exynos 2100 octa-core (2.9 GHz Cortex-X1 + 3x 2.80 GHz Cortex-A78 + 4x 2.2 GHz Cortex-A55)|
|RAM and Memory||8GB; 128GB/ 256GB not expandable|
|Rear camera||12 MP (f/1.8) primary, OIS64 MP (f/2.0), 1.1x optical zoom, 3x hybrid zoom, OIS12 MP ( f/2.2) ultra-wide|
|Front camera||10 MP, f/2.2|
|Battery||4800mAh, 25W fast charging|
|Software||OneUI 3.1 (Android 11)|
|Others||In-display fingerprint sensor, Samsung Dex, Samsung Pay, UWB connectivity, AKG Tuned stereo speakers|
|Price||Galaxy S21+ 8GB +128GB: Rs. 81,999
|
Galaxy S21+ 8GB +256GB: Rs. 85,999
Samsung Galaxy S21+ Unboxing
As most of you must know by now, Samsung has heavily cut down on the box contents to reduce wastage and carbon footprint – gone are the adaptors and those comfy AKG tuned wired earphones. Whatever the motivations may be behind this radical change, we are willing to take one for planet earth.
Box contents include:
- Samsung Galaxy S21+ handset with pre-applied screen protector
- USB Type-C to Type-C cable
- SIM ejector tool and documentation
That’s it.
Samsung Galaxy S21+ Review: Design and Build
- 161.5 x 75.6 x 7.8 mm; 200 g
- Handling comfort: Galaxy S21>> Galaxy S21+ >> Galaxy S21 Ultra
The first thing we noticed was that the Samsung Galaxy S21+ is lighter and so much more manageable than the Galaxy S21 Ultra (Review). The distinctive camera module remains the veritable highlight of Samsung’s design this year.
The triple camera setup has a slice of metal layered on top, which from a distance feels like an extension of the side aluminum frame. With one less sensor to accommodate, as compared to the bigger and bolder Ultra sibling, this metal leaf is slimmer and less broad – and feels a tad more appealing to us.
Samsung retains the smudge-resistant frosted glass back for the Galaxy S21+. But honestly, for someone who’s all too familiar with the agony of shattered glass backs, I wouldn’t mind a good quality polycarbonate back half bit – the kind we experienced on the Galaxy S20 FE last year. And probably the kind that’s on the base Galaxy S21.
On the front, Samsung has further shaved off the chin and bezels are resultantly more uniform. The major omission is the display curves. I, for one, like those curves and firmly opine that they make a phone feel more premium. At the same time, many people detest them and consider them a classic case of form over function – and they’d probably be more welcoming to the Galaxy S21+.
The bigger and faster ultrasonic fingerprint sensor has made the cut and so have the excellent AKG tuned stereo speakers. There’s no expandable storage or audio jack this year.
All said and done, we quite adore the Galaxy S21+. It looks amazing and feels remarkably solid. It’s more comfortable to handle as compared to Ultra, but if it’s this comfort that you are after, you may also consider the yet slimmer, lighter, and more compact Galaxy S21.
Samsung Galaxy S21+ Display
- 6.7-inches AMOLED, Full HD+; 48Hz to 120Hz variable refresh rate
- LTPS backplane (unlike faster, less power consuming LTPO on the Ultra)
There is no justification for why Samsung couldn’t have delivered both 2K and 120Hz for a plus size S-series flagship, but the display on the Galaxy S21+ still feels amazing. This is an HDR10+ compliant AMOLED screen that goes up to 1300 Nits bright!
We played a lot of HDR content side-by-side on the Galaxy S21 Ultra and Galaxy S21+. Yes, the Ultra is sharper but the difference isn’t worth splitting hairs over.
It’s also worth pointing out that a full HD+ display is sharper than a 2K display scaled down to Full HD+, because then the remaining of the 2K pixels are judged and filled by the software. The point being, that a full HD+ display at 120Hz (adaptive) is any day better than a 2K screen dialed down to Full HD+ for higher refresh rate support (as was the case with last year’s Galaxy Note 20 and Galaxy S20 series).
The refresh rate is adaptive, which is to say that it can vary from 48 to 120Hz based on the content being displayed and a few other parameters like brightness. For the Galaxy S21 and Galaxy S21+, Samsung is using an LTPS backplane instead of LTPO (or HoP) display backplane used on S21 Ultra that allows the latter to switch in a wider range between 10 and 120Hz, resulting in lesser battery consumption. That’s perhaps also why the battery backup while running the display at maximum settings fell a tad short of what we had on the Ultra.
Also Read: Best phones with true VRR displays in 2021
From settings, you can choose between DCI-P3 (Vivid) and sRGB (Natural) color profiles, of which we prefer the latter.
We are quite fastidious about our phone displays, and the difference while switching from sharper 2K to Full HD screen was less impactful than what we had expected. This is an awesome display to consume content on – one of the very best available options!
Samsung Galaxy S21+ Review: Performance and Software
- Exynos 2100 performance is a significant bump over Exynos 990
- Software is intuitive
- Fingerprint reader is exceptionally fast
All Galaxy S21 series phones are powered by Exynos 2100 chipset which is a significant improvement when compared to Exynos 990 from last year. This one is restricted to a relatively lesser 8GB LPDDR5 RAM, but should it really matter if we don’t feel a difference?
Samsung Galaxy S21+ Benchmark scores
- Geekbench Single Core – 1070, 1102
- Geekbench Multicore – 3206,3599
- PCMark work 2.0 – 13107
- 3DMark Wildlife – 5779
- Androbench Random Read – 302.25 MB/s
- Androbench Random Write – 281.6 MB/s
As is also indicated by benchmark scores, the phone runs exceptionally fast and smooth. The difference is very noticeable compared to Exynos 990 phones. No complaints here. The Ultra scored better and has faster sequential reads and write speeds (UFS 3.1 vs UFS 3.0), but the difference isn’t reflected in day-to-day usage or gaming.
We’d be remiss to not highlight how impressive the fingerprint reader performance is on Samsung’s 2021 flagships! Samsung has included cutting-edge connectivity options including 5G, Ultra wide-band connectivity, Wi-Fi 6E, and Bluetooth 5.2. Call quality is also excellent.
There is no MST this year, which could be used to store credit/ debit cards and make secure payments across almost all sale terminals. Personally, MST has been very helpful as it ensured we had all our credit cards with us at all times. I am hoping most PoS terminals now have NFC support and Galaxy S21 owners won’t miss out on this convenience.
Also Read: 5 Cool Multitasking Tricks for Samsung Phones with OneUI
As for the software, we are by now quite familiar with Samsung’s OneUI 3.1 (Android 11). It’s extremely intuitive, well designed and one of our personal favourite interfaces. On the downside, Samsung is still a bit pushy about its own services. We’d have preferred Google’s Smart Home dashboard over Samsung’s ‘Devices’. Samsung Dex, Samsung Pay, and Knox security are welcome additions.
Also Check: Best Samsung Phones To Buy In 2021
Samsung Galaxy S21+ Review: Camera Performance
Talking about the camera, the Galaxy S21 Plus shows iterative refinements over the last-gen S20+. It’s missing the 108MP sensor and zoom chops of the Ultra, but there are new software tricks like 8K snaps, Portrait mode filters, and director’s view to look forward to.
The primary camera is a 1/7.6-inch 12MP sensor, and it’s paired with a 64MP 3x hybrid zoom camera – both of which have OIS. The third 12MP wide-angle camera doesn’t have AF as on the Ultra.
The camera performance is simply fantastic. In daylight, Samsung Galaxy S21+ captures stunning details with a wide-dynamic range and properly exposed highlights and shadows. The end result is quite close to what we have on the Galaxy S21 Ultra.
The good thing about flagships is that the wide-angle camera is not just an afterthought. The one on the Galaxy S21+ proved genuinely useful when we had to capture a wider canvas. There is a zoom camera too (3x hybrid zoom) but the performance doesn’t come anywhere close to what we have with the Galaxy S21 Ultra.
The live focus mode is now portrait mode and it sees a ton of improvement this generation – for both front and rear cameras.
In dark scenes, once again we were surprised to find out that the Galaxy S21 Ultra and Galaxy S21+ were quite close. The phone also has a night mode but if the scene optimizer is on, it detects night and fine-tunes capture settings accordingly in the auto mode.
Samsung Galaxy S21+ is also one of the best Android phones for videos. Director’s View can be used to shoot reaction videos from different cameras and there’s also the ‘8K video snap’ which allows you to snap a still image from an 8K video. We are not sure how frequently we’d be using these, though.
So, overall, the S21+ has an impressive flagship-grade camera that’s among the best you can get for the price.
Samsung Galaxy S21+ review: Battery and Audio
- 4800mAh battery with 25W fast charging
- Powerful stereo speakers
There is a 4800mAh battery onboard and we could stretch the battery to a little more than a day with moderate to heavy usage. It’s quite likely that you will need to resort to late evening charging on days you actively use your phone.
Fast charging maxes at 25 watts and you will need to buy a USB PD fast charger, separately. This definitely feels lackluster by 2021 standards.
As for audio, the S21+ has excellent stereo speakers. We didn’t face any issues with wireless audio either.
Also Read: Samsung Galaxy S21 Ultra Review
Samsung Galaxy S21+ Review: Verdict
The Samsung Galaxy S21+ is an extremely premium flagship with a mesmerizing display and bold, distinctive looks. It’s backed by a powerful chipset, has a very assuring battery, and runs delightful software.
The camera performance is surprisingly close to what you get with the pricier Ultra (save for the zoom prowess, of course).
This is surely a phone we can recommend. The Galaxy S21 Ultra is clearly superior but, if you ask us, the choice between the three variants should primarily be based on the size you are most comfortable with. | https://www.smartprix.com/bytes/samsung-galaxy-s21-review-pros-cons/ |
FYI: The screen of Samsung's Galaxy Note 8 has a default resolution of 1080 x 2220 pixels
Officially announced by Samsung earlier this week, the Galaxy Note 8 sports a dual-curve 6.3-inch screen - the largest ever on a Note smartphone. While this is definitely a Quad HD+ (1440 x 2960 pixels) display, you won't be seeing that resolution out of the box.
Of course, users will be able to easily change the screen resolution to Quad HD+ (1440 x 2960) at any time from the Settings menu of the Note 8. But maybe you won't want to do that too often, as 1080 x 2220 pixels is still sharp enough, and, in everyday scenarios, you'll probably find it hard to notice differences between that and 1440 x 2960 pixels. Plus, with Full HD+, battery life will likely be better.
If you're planning to buy a Samsung Galaxy Note 8, does not having a Quad HD+ resolution by default bother you in any way? | https://www.phonearena.com/news/Samsung-Galaxy-Note-8-screen-resolution-default_id97430 |
Samsung Galaxy S8 vs S8+: what's the difference?
Samsung has finally introduced the Galaxy S8 and the S8+. But what are the differences between the two new Samsung smartphones?
The Galaxy S8 and S8+ have more in common than S7 and S7 Edge did. In the eighth generation of the S series of Samsung phones, Edge displays have become standard. In addition, the camera, display resolution and the arrangement of buttons are the same on both devices.
The differences between both smartphones are therefore minimal yet simultaneously huge. From a technical perspective, the main differences are between the display and the battery. The Galaxy S8 has a display of 5.8 inches. The S8+, on the other hand, is 6.2 inches. So the Galaxy S8+ is considerably larger than the S8, as can be seen in the picture below.
This "small" difference in size leads to quite a significant difference when you hold each device in your hand. The hands-on review shows that the fingerprint sensor on the S8+ is not as good as on the S8: aside from its strange placement beside the rear camera, on the S8, the sensor is much easier to reach. At best, the sensor is difficult to reach if you use the device single-handed on the S8+. And on top of all that, the notification bar is far away.
Regarding the battery, the Galaxy S8+ has a slightly larger battery, by 500 mAh, so it should last a bit longer in a direct comparison.
Galaxy S8 vs Galaxy S8+: comparison of technical specs
Samsung Galaxy S8 vs. Samsung Galaxy S8+ technical specifications
|Samsung Galaxy S8||Samsung Galaxy S8+|
|Dimensions:||148.9 x 68.1 x 8 mm||159.5 x 73.4 x 8.1 mm|
|Weight:||152 g||173 g|
|Battery size:||3000 mAh||3500 mAh|
|Screen size:||5.8 in||6.2 in|
|Display technology:||AMOLED||AMOLED|
|Screen:||2960 x 1440 pixels (568 ppi)||2960 x 1440 pixels (531 ppi)|
|Front camera:||8 megapixels||8 megapixels|
|Rear camera:||12 megapixels||12 megapixels|
|Flashlight:||Dual-LED||Dual-LED|
|Android version:||7.0 - Nougat||7.0 - Nougat|
|User interface:||TouchWiz||TouchWiz|
|RAM:||4 GB||4 GB|
|Internal storage:||64 GB||64 GB|
|Removable storage:||microSD||microSD|
|Chipset:||Samsung Exynos 8895||Samsung Exynos 8895|
|Number of cores:||8||8|
|Max. clock speed:||2.3 GHz||2.3 GHz|
|Connectivity:||HSPA, LTE, NFC, Bluetooth||HSPA, LTE, NFC, Bluetooth|
Which will it be - Galaxy S8 or Galaxy S8+?
The S8 and the S8+ both offer high-end performance. If you want a big smartphone, you might be more interested in the S8+. The 5.8-inch display of the S8 should not drive away those who prefer compact smartphones: the S8 remains pleasantly compact, even if it is again a little bit bigger than the Galaxy S7 from last year.
Overall, Samsung has gone the same way as others have already gone - like Google: a generation with two different sized smartphones, for which the main differences lie in size and battery. As such, the S8 and S8+ are not noticeably different. The choice between the two is, therefore, mainly a question of size preference. | https://www.androidpit.com/samsung-galaxy-s8-vs-s8-plus |
Two hours after the publication of the first renders of the flagship Samsung Galaxy S21 , insider Steve Hemmerstofer (OnLeaks) released the first details about the Galaxy S21 Ultra (or Galaxy S30).
Unlike the Galaxy S21, where the display will be flat, the Galaxy S21 Ultra will have branded curves on the sides. The diagonal will be between 6.7 and 6.9 inches, in the center of the screen, there is a hole for the front camera. Dimensions: 65.1 x 75.6 x 8.9mm (10.8mm including protruding chamber).
Behind a dedicated huge block of cameras, which will house four sensors at once (in the younger version there are three of them). There is no information about the cameras, but there are rumors that there will be two telephoto lenses (or periscopes), an ultra-wide-angle and a wide-angle main one.
According to the source, the release of the Galaxy S21 line is expected earlier than usual – in January 2021. Typically, the presentation of the flagship series took place from February to April. | https://www.gadgetsfarms.com/samsung-galaxy-s21-ultra-first-redners-and-spefications/ |
South Korean electronics company Samsung has released another update for the Samsung Galaxy S21 series this week with various upgrades. With this update, Samsung has improved the performance of the camera and the overall performance of the device. This includes security updates for Google’s February 2021 and bug fixes and performance improvements for the new Samsung Galaxy S21 5G, S21 + 5G and S21 Ultra 5G with each update. It is recommended to back up the data before the update so that it is protected during the update. The built-in number for the Samsung Galaxy S21 series is G991BXXU1AUB3, with G996BXXU1AUB3 and G998BXXU1AUB3. To download the latest security updates to your device, the device must have the latest available Android version installed. More information about this update can be found below or from Samsung.
February 2021 -> Samsung Galaxy S21 series update for specs
The update contains the following build number, which can now be downloaded and installed using the update function via ⚙ Menu Settings → Software Update → Download.
- Device: Galaxy S21 5G (SM-G991B) – Build Number: G991BXXU1AUB3
- Device: Galaxy S21 + 5G (SM-G996b) – Build Number: G996BXXU1AUB3
- Device: Galaxy S21 Ultra 5G (SM-G998b) – Build Number: G998 PXX11 AUP3
- Release Date: 2021-02-05 – Security Link Status: 2021-02-01
New Features and Improvements for the Samsung Galaxy S21 Series:
- Camera performance has been improved.
- The overall consistency of operations was improved.
- The security of your device has been improved.
Software updates for Samsung Galaxy models
If you get a new smartphone or tablet, you will receive software updates from Samsung even after you purchase it. These may be new functions, but they are also security updates that are available for download. We recommend installing these updates as soon as they are released. It is very easy to be notified about the availability of new updates for your smartphone or tablet: Once the automatic update is enabled, you will automatically receive a notification on your mobile device when an update is available for download and installation. | https://nintendo-power.com/samsung-galaxy-s21-gets-security-update-for-february-2021-it-blogger-net/ |
Samsung Galaxy S21 Ultra discontinued, sales already stop in certain markets
Samsung has discontinued the Galaxy S21 Ulta in anticipation of the Galaxy S22 Ultra that’s coming tomorrow, February 9.
Samsung has stopped selling the S21 Ultra on its official websites in France, Germany, the UK and the US, among others. However, you can still buy the Galaxy S21 and S21+ alongside the new S21 FE.
The Galaxy S21 Ultra is still available for purchase from third-party retailers that have the phone in stock, in many cases at a lower price. Getting your own flagship phone at a serious discount is the reasonable thing to do on the eve of the Galaxy S22 series’ launch. | https://phonewale.com/samsung-galaxy-s21-ultra-discontinued-sales-already-stop-in-certain-markets/ |
his item includes the following components:
- LCD Screen;
- Digitizer Touch Screen;
- Front Housing;
- Ear Speaker;
- Side Button.
Notes: Please test the functionality of this item before installation.
Specifications
Screen Size: 5.6 inches
Resolution: 1440 x 2960 pixels, 570 ppi pixel density
Material: AMOLED capacitive touchscreen, 16M colors
Protective Material: Corning Gorilla Glass 4
Compatibility: Samsung Galaxy S8
Features:
- This Galaxy S8 LCD assembly does include the frame.
- This Galaxy S8 LCD and digitizer assembly is a brand new original replacement.
- This screen replacement is compatible with all Samsung Galaxy S8 models.
How to Install / Tips:
- Special repairing tools are required for assembling or disassembling, as the Galaxy S8 LCD display and digitizer are hermetically attached.
- Handle the vulnerable and fragile flex cable ribbon carefully.
- Please try to handle the repair or replacement work in a dry and dust free environment without direct sunlight.
- The installation of any new part should be done by a qualified person. We are not responsible for any damage caused during installation. | https://shop.repairpartners.com.au/products/sam-gs8-950-lcd-scp |
The Samsung Galaxy S11 Mobile phone features a 6.4 inches display with a screen resolution of 1440 x 3040 pixels and runs on Android 9.0 operating system. The Mobile Phone is powered by Octa-core processor and Exynos chipset. It has 256GB Built-in storage and 8GB RAM. The Samsung Galaxy S11 runs Android 9.0 and is powered by a 3700 mAH non-removable Li-Po battery.
Samsung Galaxy S11 Specs
Display 6.4 Inches Dynamic AMOLED display System
Storage: 256GB, 8GB RAM, microSD card slot
Processor: Octa-core
Chipset: Exynos 9 Octa 9820
SIM: SIM1: Nano SIM2: Nano (Hybrid) (Nano SIM, GSM+GSM)
Rear Camera: 13MP + 13MP + 16MP + 5MP
Selfie Camera: 10MP + 8MP
OS: Android 9.0 Operating System
RAM: 8GB RAM, Internal Memory 256GB expandable up to 512GB via MicroSD card slot
Battery: 3700 mAh Li-ion battery. | https://www.electrorates.com/samsung-galaxy-s11-446.php |
New alleged details emerge on Samsung's “Project Zero”, or about the processor, display and camera of the future Samsung Galaxy S6!
For a long time Samsung has been the leading mobile company, but its position has begun to falter in recent times. Most likely also for this reason, the company decided to design its next terminal, the Galaxy S6, "starting from scratch" (hence the name of the current project).
According to rumors, the new smartphone should be released in two different models, one with a 810-bit Snapdragon 64 chip and the other with a 7420-bit octa-core Samsung Exynos 64 processor.
Exact display measurements remain unknown, however Quad HD resolution (1440 x 2560 pixels) is expected. As for the camera, there is talk of a 16MP or 21MP Sony Exmor RS IMX240 rear sensor (with optical stabilizer) and a 5MP front sensor. The internal memory, on the other hand, is believed to be available in three different versions, respectively 32GB, 64GB and 128GB. | https://en.gizchina.it/2014/11/new-alleged-details-samsung-galaxy-s6-zero-project/ |
Here’s how Samsung’s S Pen works with the new Galaxy S21 Ultra
Samsung’s new Galaxy S21 Ultra supports the company’s S Pen stylus. Support for the accessory has been a staple of Samsung’s Galaxy Note smartphones for years, but this is the first time it’s been supported in the company’s Galaxy S-series. The stylus will be available as an optional $39.99 accessory, and Samsung says the S21 Ultra will also work with S Pens from other Galaxy Note or Galaxy Tab devices.
As for what you can use the stylus to do on the S21 Ultra, Samsung has outlined a range of familiar use cases. These include drawing, note-taking, photo editing, and signing documents. Physically, the new stylus is a little bigger than previous Galaxy Note S Pens, but it retains the side button.
Source: | https://mamizi.com/heres-how-samsungs-s-pen-works-with-the-new-galaxy-s21-ultra/ |
The Google Pixel 6 has already been announced by Google, and many of its features have been shared by the company itself. For now, yes, we are not clear on the date of presentation of the new Google smartphones, although all the rumors point to the end of October.
Google Pixel 6 Pro Full Features Leaked
Therefore, we are still separated by several weeks until the day of the presentation event of this new series of phones. And that can only mean that, most likely, the leaks will not give up until the last minute.
On this occasion, the people of XDA have had access to a good part of the technical specifications of the Google Pixel 6 Pro, thanks to an anonymous source. Thus, today we know a good handful of more details about the new devices.
Google Pixel 6 Specifications & Features
The leak begins by denying some recent rumors, such as the inclusion of pressure-sensitive edges, “Active Edge” in the Pixel 6 Pro. Actually, this function will not be included in the new device, in the same way, that it will not be included either. it was on the previous Pixel 5.
On the other hand, it will have the possibility of sharing battery wirelessly thanks to a reverse charging system, enabled through the Qi wireless charging system integrated into the terminal.
It has also been possible to confirm the inclusion of a screen with a resolution of 3120 x 1440 pixels in the Pixel 6 Pro, which will also be able to refresh at a frequency of 120 Hz. In addition, Google will allow combining the maximum screen resolution with the highest refresh rate supported by the panel.
The panel is capable of reducing its refresh rate to 10 Hz when necessary, for example, in those cases where static content is displayed and it is not necessary to refresh the screen content so frequently.
Samsung Exynos 5123 Chepset
Other features that are confirmed are the inclusion of technology Ultra Wide Band -UWB-, which among other things will serve to unlock our car without using the key. Also, the device will have 5G connectivity thanks to a modem signed by Samsung, specifically the Exynos 5123.
The data of the new Tensor processor designed by Google has also been revealed, and it is indicated that the SoC will consist of a configuration of 2 x 2 x 4 cores, with two of them running at 2.8 GHz, another two at 2, 25 GHz, and four at 1.80 GHz.
12 GB LPDDR5 RAM, 5,000 mAh battery
All this will be supported by a 12 GB capacity LPDDR5 RAM module, a 5,000 mAh battery, and a Mali-G78 GPU. Its base storage would be 128 GB, and the device would have an on-screen fingerprint reader, Wi-Fi 6E, and software based on the Linux kernel version 5.10. This last data makes the rumors about the five years of assured updates stronger since it is a version of the kernel that will be officially supported until the end of the year 2026.
Google Pixel 6 Camera
The details of the photographic system have also been revealed, indicating that the main camera of the Pixel 6 Pro will use a Samsung GN1 50 megapixel sensor. The ultra-wide-angle camera will use a 12-megapixel Sony IMX386, and the four-magnification optical zoom telephoto will use a 48-megapixel Sony IMX 586. As for the front sensor, it will be a 12-megapixel Sony IMX663. | https://ismartprice.com/google-pixel-6-pro-full-features-leaked-12gb-ram-design-camera-more/ |
At today’s pre-IFA 2014 Samsung Unpacked 2014 Episode 2 Event (Episode 1 was in February when Samsung unveiled the Galaxy S5) in Berlin, the company unveiled not one, but two new Galaxy Note devices. They are the Galaxy Note 4 and Galaxy Note Edge.
Having created the phablet category three years ago, the pressure is on Samsung to bring this category to the next level, especially when Apple is highly expected to unveil two larger iPhones on September 9. So how did the two Galaxy Note devices fare in our initial round of usage? Let’s find out in this hands-on article.
But first. here’s a quick overview of their specs in comparison to the Galaxy Note 3:
|Samsung Galaxy Note 4||Samsung Galaxy Note Edge||Samsung Galaxy Note 3|
|Screen||5.7-inch, 2,560 x 1,440 pixels,
|
Super AMOLED
|5.6-inch, 2,560 x 1,440 pixels, Super AMOLED||5.7-inch,1,920 x 1,080 pixels, Super AMOLED|
|CPU||Quad-core 2.7GHz
|
or
1.9GHz Quad-Core (1.9GHz Quad + 1.3GHz Quad-core) processor
|Quad-core 2.7GHz||Qualcomm Snapdragon 800 quad-core 2.3GHz|
|RAM||3GB||3GB||3GB|
|Battery||3,220mAh||3,000mAh||3,200mAh|
|Rear Camera||16MP with Smart OIS||16MP with Smart OIS||13MP|
|Internal Storage||32GB||32GB / 64GB||32GB|
|Dimensions||153.5 x 78.6 x 8.5mm||151.3 x 82.4 x 8.3mm||151.2 x 79.2 x 8.3mm|
|Weight||176g||174g||168g|
Samsung Galaxy Note 4: Design & Hardware
Ironically, Samsung chose not to increase the display size on the Galaxy Note 4. For the past three years, we saw it increase in 0.2-inch increments from the 5.3-inch Galaxy Note to the 5.5-inch Galaxy Note II to the 5.7-inch Galaxy Note 3.
This year, Samsung chose to maintain the screen size at 5.7-inches and bumped up the resolution to Quad-HD - 2,560 x 1,440 pixels. This is an expected move since it recently released an updated Galaxy S5 model with an equally high resolution display albeit smaller at 5.1-inches. As expected, colors were really bright, vibrant and vivid thanks to the Super AMOLED display.
The next major but visible hardware change is the use of a metallic frame, a strategy that Samsung recently adopted with the 4.7-inch Galaxy Alpha to fend off criticisms of its plastic based design over the years. It’s great to see Samsung stepping up its game on the design for the Galaxy Note 4; it definitely looks more premium and elegant than its predecessors.
If you are hoping to see water and dust resistance features on the Galaxy Note 4, you may have to wait for another variant or the next generation. For now, this feature remains exclusive to the Galaxy S5/S5 4G+.
Over on the back, Samsung still uses the soft-textured material for its rear cover. While it looks slightly different from the Galaxy Note 3, the back cover of the Galaxy Note 4 still offers a good grip, handling and some resistance against fingerprints and smudges.
Despite all the new hardware changes in the Galaxy Note 4, it is only marginally thicker than the Galaxy Note 3. It is also 8g heavier due to a slightly higher capacity 3,220mAh battery. Overall, we still find the Galaxy Note 4 easy to handle for its form factor.
Other notable hardware additions include a fingerprint sensor on the home button, a UV sensor (a first in a mobile device) and heart rate sensor at the rear and Smart Optical Image Stabilization for its 16-megapixel rear camera. As the unit handled was a prototype, we were unable to test out these other features.
Software Features: Enhanced S Pen, S Note and Air Command
Three new software features made their debut on the Galaxy Note 4; they are Smart Select, Snap Note and using the S Pen like a PC mouse. As mentioned earlier in our news piece, Smart Select lets you crop or choose a particular segment/section from different sources such as a website, a photo and a text message, and share the content easily. Below is a short video demonstrating Smart Select on the Galaxy Note 4:
Although the Galaxy Note devices are popular among consumers who like to type and write on the large screens, Samsung understands that there are scenarios in our daily lives that require a faster and more efficient way of inputting data. Using Snap Note, the Galaxy Note 4 can take a picture of notes on a paper or on a white board and digitizes the information into a S Note. During our hands-on session, we were told that Snap Note requires a pair of steady hands to function properly. We also realized that Snap Note required a few seconds to read and convert the information.
Another interesting feature is how Samsung modified the S Pen to function like a PC mouse. Akin to how we scroll and highlight a wall of text in a document or on a website to copy and paste, you can do the same on the S Pen by tapping on the side button and highlighting the particular portion. Below is a snappy video showing how this feature actually works:
Availability and Pricing
At press time, there is no information on its pricing. Samsung states that the Galaxy Note 4 will be available in global markets from October although we were told by our sources that it will be launched in Singapore on September 26.
Over on the next page, we continue our Galaxy Note coverage with the Edge edition! | https://www.hardwarezone.com.sg/feature-hands-samsung-galaxy-note-4-and-galaxy-note-edge |
New leaks from reliable source evlkeaks confirm that the LG G5 will feature a dual display, which we saw in the LG V10 or the recently announced X Screen, where the company joined a secondary screen for adding shortcuts to the applications.
Finally saw the G5; secondary screen confirmed.
— Evan Blass (@evleaks) February 16, 2016
In the specific case LG V10 we have a main panel of Quad HD 2560 x 1440 pixel 5.7 inch accompanied by a second panel of 2.1 inches with a resolution of 1040 x 160 pixels which occupies part of the upper frame forcing the camera roll one side, so the G5 LG shots could go the same way. LG’s announcement event for the handset at MWC 2016 is officially set for February 21, which just so happens to coincide with Samsung’s unveiling of the Galaxy S7 line, so, it is definitely shaping up as an interesting day. | https://tech4gamers.com/the-lg-g5-offers-a-dual-screen-design/ |
How To Take A Screenshot on The Samsung Galaxy M20
It is very easy to take a screenshot on the Samsung Galaxy M20. Even You do not need to use or install any additional application on your Samsung phone. You can capture a screenshot on the Galaxy M20 using its Hardware keys.
How To Take A Screenshot on Samsung Galaxy M20 using its Hardware Keys:
1- Get the content you want to capture ready on your phone’s screen (webpage, Game score, WhatsApp chat…etc).
2- Press and hold the Power and Volume Down keys at the same time for about 2 seconds. You’ll hear the camera shutter sound and see a short flashing animation on the phone’s screen.
3- The Galaxy M20 operating system will save the captured screenshot in the Screenshots folder. To see the screenshot photo go to Gallery App > Screenshots. Or you can use My Files app to open the Screenshots folder.
4- Once you find the screenshot photo, You can share it with your friends and family via any Social application, Email, Or send it to another device via a Bluetooth or WiFi connection. Or any sharing options available on your Samsung Galaxy M20.
Notices:
- The resolution of the captured screenshots is the same as your Samsung device screen resolution (Samsung Galaxy M20 has 1080 x 2340 pixels of Display Resolution).
- You can edit the screenshot photos the same way you do with any other photos and images. | https://tsar3000.com/take-screenshot-on-samsung-galaxy-m20/ |
The South Korean tech giant recently launched its new S-series after a lot of speculation, Samsung unveiled its new device, the Galaxy S21 Plus on January 14, along with the standard Galaxy S21, top...
Category - Galaxy S21
South Korea’s tech giant Samsung unveiled its latest Samsung Galaxy S21 series on Friday and the company also revealed the price of the phone for the...
The biggest annoyance is that this Samsung Galaxy s21 lineup will be launched in mid January 2021 and before that we are supported by the leaked information of...
Samsung is going to launch its new flagship smartphone Galaxy S21 on January 14, the top-end phone of this series will be Galaxy S21 Ultra, Recently this...
The Samsung Galaxy S20 series was announced on 11 February, but several reports suggest that the samsung S21 may have landed a while ago and it is now almost 9... | https://www.androidleo.com/category/galaxy-s21/ |
I ordered the active adapter and it worked for my LG Ultrawide: go to display settings on macbook air first, select best for LG Ultrawide then plug in cable with active adapter, then in display settings select the 2560×1080 resolution.
In the same way How do I increase screen resolution on Mac?
To change the display resolution on your Mac, click the Apple menu → click System Preferences → click Display → click the Scaled option → select the resolution or display scaling you want to use.
Subsequently, How do I use SwitchResX on Mac? Step 1: Download and install SwitchResX. Step 2: Open System Preferences → SwitchResX → Applications. Step 3: Check Monitor Applications, click the + sign in the bottom left-hand corner and choose an application. Step 4: Click Create new Display Set.
Where is SwitchResX installed?
SwitchResX lives in the Preference Pane folder of your System Library. To access it, simply go to System Preferences and click its icon in the bottom section. Here you can check what version of SwitchResX you are running and if you have installed the assisting modules.
Does macbook pro support 3440×1440?
1 Answer. Your Mac can easily handle a 3440×1440 monitor (in terms of resolution), using Thunderbolt-C to DisplayPort as linked in your question.
Is 1080p full HD?
Full HD, also known as FHD, is the resolution that’s currently most common among televisions, Blu-ray players, and video content. The image is 1920 pixels wide and 1080 pixels high: a total of 2.07 megapixels. Full HD is also referred to as 1080i and 1080p.
How do I fix my Mac screen resolution?
On your Mac, choose Apple menu > System Preferences, click Displays, then click Display. Press and hold the Option key while you click Scaled to see additional resolutions for the second display. Select a scaled resolution option for the second display.
How do I find out my Mac screen resolution?
PS–If all you want is the size in pixels you go to About This Mac in the Apple menu, click the More Info button, then the Displays tab. Click on Apple icon on left top. You should see the resolution there. If you switch to “scaled” it will list the selected resolution.
How many pixels is a 1080p monitor?
In the case of a monitor with an industry-standard Full HD 1080p resolution, this display has a resolution of 1920 x 1080. This means that the screen will have a width of 1,920 pixels while the height of the screen will be 1,080 pixels. This results in a grand total of 2,073,600 pixels on-screen.
How do I enable custom resolution SwitchResX?
- After launching SwitchResX, select the external monitor from the list on the left.
- Select the ‘Custom Resolutions’ tab.
- Add a new custom resolution be clicking the + symbol at the bottom of the window.
- Adjust the settings to match the appropriate PNG provided in this gist.
- Press ‘Ok’
How do you mimic a 2K monitor as retina display on Mac using Hidpi?
Setup
- Download and install SwitchResX.
- (For macOS Sierra only) Disable SIP under recovery mode. …
- Open SwitchResX from system preference menu, go to your 2K monitor, open the tab Custom Resolutions, press “+” . …
- After reboot, open SwitchResX again, go to your 2K monitor. …
- Done! …
- (
How do I set custom resolution in SwitchResX?
Creating a new resolution
Go to System Preferences->SwitchResX. Select your display in the left pane and click the Custom Resolutions tab. Here, I have two external displays connected to my laptop (whose internal display is turned off and is not showing). Click the + sign below the list of resolutions.
What is 1440p resolution size?
About 1440p Resolution: 1440p is a progressive resolution containing 2560 x 1440 pixels.
How do I remove SwitchResX from my Mac?
Open up Finder, and access to the /Applications folder from the sidebar or Go menu. Locate SwitchResX, drag its icon to the Trash in Dock, and drop it inside the Trash icon (alternatively, right click on SwitchResX and choose Move to Trash option)
What resolution is 3440×1440?
3440×1440 is considered to be 2K. 4K resolution starts at 3840×2160. That said, for games that support 3440×1440 the end results are amazing. Since it is an ultra wide monitor you see more of what is to the left and right of even a monitor with 4K resolution.
What is DisplayPort vs HDMI?
DisplayPort is often video-only, while HDMI delivers video and audio in a single cable. But the differences don’t stop there. There are four different versions of DisplayPort that may be found on monitors and graphics cards, each offering a slightly different mix of support for different resolutions and frame rates.
Is HD or 720p better?
You’ll sometimes see displays with a resolution of 1920 x 1080 resolution also called HD, but this is more officially referred to as 1080p or Full HD (FHD).
720p compares favorably
to the old Standard Definition (SD), which is usually around 640 x 480.
…
Common Display Resolutions.
|5K||5120 x 2880|
|HD aka 720p||1280 x 720|
•
20 janv. 2020
Which is better 1080p or 1920×1080?
The 1080P has better quality as the entire screen is updated at 60HZ. The 1080i is updated at half the rate. 1920×1080 defines the pixel matrix of the screen (i.e. 1920 vertical pixels and 1080 horizontal pixels).
Is 4K 4 times 1080p?
In television and consumer media, 3840 × 2160 is the 4K standard, whereas the movie projection industry uses 4096 × 2160 due to the larger projection size. 4K is four times the pixel resolution of 1080p (1920 x 1080 pixels). With 4 times the pixels, the image will be 4x as detailed.
What resolution is 1080p?
A High Definition TV with 1080p resolution is composed of two million pixels (1920 x 1080), while a 4K TV (aka Ultra High Definition) has over eight million pixels (3840 x 2160).
Is 2560×1600 a 4K?
Many enthusiasts today run 27-inch or 30-inch monitors at much higher resolutions of 2560×1440 or 2560×1600, respectively. … For 2014 and beyond, though, 4K is the new aspirational resolution for every hardcore PC gamer.
How do I change the resolution on my Macbook Pro?
To change the resolution:
- Choose Apple menu > System Preferences.
- Click Displays.
- Select Scaled, then select any of the four or five scaled resolutions, depending on your Mac model. With scaled resolutions, text and objects can appear larger and more visible, or smaller to provide more space for windows and apps.
What resolution is 1920×1080?
1080p = 1920 x 1080 – is usually known as FHD or “Full HD” resolution. 1440p = 2560 x 1440 – is commonly known as QHD or Quad HD resolution, and it is typically seen on gaming monitors and on high-end smartphones.
Is 2560×1440 better than 1080P?
2560×1440 has 78% more pixels than 1920×1080, but is it always better? … In comparison to 1920×1080, 2560×1440 provides you with more vivid details and more screen real estate (just how much more depends on the screen size and pixel per inch ratio), but it’s also more power-hungry when it comes to gaming.
Is 2560×1600 better than 1080P?
2560×1600 will require the high end card to get its full potential. Couple with the high end card (i.e. 5970, single or CF) you definitely get a better gaming quality than 1080P. Yes 2560×1600 will be better if you have the right video card to drive it.
Don’t forget to share this post with your friends ! | https://big-photography.com/guides/how-do-i-get-2560x1080-resolution-on-mac/ |
Samsung Galaxy S21 Ultra came out recently, and it seems to remain the only classic flagship of the manufacturer until next year, as there will be no Galaxy Note devices this year.
But already now, many would like to know how the Galaxy S22 Ultra will look like. The author of the Technizo Concept channel has created a concept for this smartphone, which is based on the current design and rumors on the web.
As you can see, according to the author, the Galaxy S22 Ultra can retain the style of the camera module. The camera itself, thanks to the not yet presented, but preparing for release, 200-megapixel sensor, will look quite unusual.
The author also believes that this smartphone will retain the periscope camera, which is quite logical. From the rest, we can note the visually absent frames around the screen and the subscreen front camera.
Again, this is just a concept, but quite worthy of attention and created on the basis of the available data. | https://hunchmag.com/this-is-what-the-samsung-galaxy-s22-ultra-might-look-like-we-look-at-the-original-concept/ |
Welcome to a new feature on Flashback Friday where we’re going to occasionally look back at the beginning of a smartphone line and compare it to its newest iteration. Up this week, the Galaxy Note says hello to the Galaxy Note 4.
The original Galaxy Note was introduced at IFA 2011 and released on Oct. 29, 2011. The Galaxy Note 4 debuted at IFA 2014 this year, but has no official release date yet. So how has the line changed in three years? Quite a bit actually. As you look through the specs below, you’ll see what was once a top of the line phone would now be considered pretty basic. And remember, there are probably still some people holding on to the original Galaxy Note as they simply can’t afford their upgrade, or they bought late in the product cycle.
The Galaxy Note did receive OS updates, but there is no getting around that dual-core in today’s world, or the maximum microSD size of 32GB. It’s scary to think that the phone that pretty much launched the phablet category of phones such a short time ago feels like it belongs in an antique shop already.
Enjoy the pictures and specs and let us know your thoughts in the comments below.
Galaxy Note Gallery
Galaxy Note 4 Gallery
|Samsung - Galaxy Note||Samsung - Galaxy Note 4|
|Display Size||5.3-inch, 800 x 1280 pixel display (285 ppi)||5.7-inch, 1440 x 2560 pixel display (515 ppi)|
|Resolution X||800||1440|
|Resolution Y||1280||2560|
|Display Type||WXGA Display Super AMOLED||Quad HD Super AMOLED|
|Operating System||Android 2.3 (at launch)||Android 4.4 (at launch)|
|Processor||1.4 GHz dual-core ARM Cortex-A9||2.7 GHz Quad-Core Processor or 1.9 GHz Octa-Core (1.9GHz Quad + 1.3GHz Quad-Core) Processor (varies by country/carrier)|
|RAM||1GB||3GB|
|Storage||
||
|
|External Storage||Yes||Yes|
|External Storage Specs||
||
|
|Main Camera (Back)||8MP||16MP|
|Secondary Camera (Front)||2MP||3.7MP|
|Networks||
||
|
|Bluetooth||Bluetooth 3.0||Bluetooth 4.1|
|Battery||2500 mAh||3220 mAh|
|NFC||Yes (vary by carriers)||Yes|
|Connectivity||
||
|
|Sensors||
||
|
|GPS||
||
|
|Height||146.85 mm (5.78 inches)||153.5 mm (6.04 inches)|
|Width||82.95 mm (3.27 inches)||78.6 mm (3.09 inches)|
|Depth||9.65 mm (0.38 inches)||8.5 mm (0.33 inches)|
|Weight||178 g (6.28 oz)||176 g (6.21 oz)|
|Colors||Black, Pink, White||Black, Gold, Pink, White|
|Supported Audio Formats||MP3, AAC, AMR, WMA, WAV, FLAC, OGG||MP3, AAC/AAC+/eAAC+, WMA, AMR-NB/WB, Vorbis, FLAC|
|Supported Video Formats||MPEG4, H.264, H.263, WMV, DivX, Xvid, VC-1||H.264, MPEG-4, H.263, VC-1, WMV7, WMV8, Sorenson Spark, MP43, VP8|
|Other Features||
||
|
|In The Box||N/A||N/A|
Add magic to your living space with these string lights
String lights add personality and soft light to your living space. Here are some of the best.
Disguise your little one with the help of a themed costume
From roaring lions to hoppy bunnies, costumes speak to every child's unique spirit. And we've collected our favorite options.
The Galaxy S20 Ultra's Space Zoom camera is amazing and a bit creepy
The Galaxy S20 Ultra supports up to 100X zoom, which Samsung calls Space Zoom, but is it any good? Can a phone really product usable photos at 100x zoom? We've got our Galaxy S20 Ultra already so join us to find out!
Find the right wall charger for your new iPhone 12
The new iPhone will not come with a wall charger in the box. If you are looking to buy the phone you will need to buy a charger as well. We've got you covered. | https://www.technobuffalo.com/galaxy-note-vs-galaxy-note-4-spec-shootout |
After Samsung announced its Galaxy Unpacked event 2021. We got some more leaks on the Samsung Galaxy S21 ultra S Pen support. Thanks to WinFuture, the Samsung Galaxy S21 Ultra case shows a spot to store S Pen in it.
Although the Image shows a book cover for the S21 Ultra. But with time we will also see back covers for S21 ultra to store the S Pen. There will be no spot for storing S Pen in the S21 Ultra itself.
Also, it is reported that the S Pen will be sold separately for 40 Euros ($50). There is no official news for this right now.
Like all other Galaxy Note line S Pens. It will also support gestures and actions like playing/pausing videos and capturing photos.
Samsung is bringing the Support of the S Pen on their more foldable and flippable devices. Because Samsung will end the production of the note Series this year. | https://getthetechnow.com/2021/01/s-pen-support-for-galaxy-s21-ultra.html |
Last month Samsung Display announced that it has designed a new OLED stack (its M11 stack) that is 16% more efficient compared to its currently OLED stack. The first phone to adopt the new OLED materials will be the Galaxy S21 Ultra.
Anandtech posted an interesting and what seems to be comprehensive review of the Galaxy S21 Ultra display, comparing it to Samsung's previous generation panels. As you can see in the chart above, the results show that the new OLED stack is actually 26% to 31% more efficient when showing a full white screen. The brighter the display, the more efficient the new stack is compared to SDC's previous M10 OLED stack.
SDC did not reveal much about the new materials beyond saying that the new architecture "speeds up electron flows in the display’s organic layers". | https://www.oled-info.com/just-how-much-more-efficient-samsungs-latest-m11-oled-stack |
Ada Lovelace published a translation from of an article on the Analytical Engine by an Italian engineer, Luigi Menabrea, to which Ada added extensive notes of her own. The Notes included the first published description of a stepwise sequence of operations for solving certain mathematical problems and Ada is often referred to as ‘the first programmer’.
Ada Lovelace also speculated that the Engine ‘might act upon other things besides number… the Engine might compose elaborate and scientific pieces of music of any degree of complexity or extent’. This idea that a machine could manipulate symbols in accordance with rules and that number could represent entities other than quantity mark the fundamental transition from calculation to computation.
An engraving of Ada Lovelace, the first computer programmer.WIKI
“The Analytical Engine weaves algebraic patterns just as the Jacquard loom weaves flowers and leaves.”
Ada Lovelace
Kathleen Booth with the ARC.CENTER FOR COMPUTING HISTORY
During 1947–1953
Kathleen Booth wrote the first assembly language and designed the assembler and autocode for the first computer systems at Birkbeck College, University of London..
She also helped design three different machines including the ARC (Automatic Relay Calculator), SEC (Simple Electronic Computer), and APE(X)C.
During 1945–1946
Kay McNulty, Betty Snyder, Marlyn Wescoff,
Ruth Lichterman, Betty Jennings and Fran Bilas programmed the world’s first all-electronic digital computer–the ENIAC. With zero programming manuals or courses, these women had to figure out how the make the ENIAC work only with the help of logical diagrams.
Computer operators with an Eniac — the world’s first programmable general-purpose computer.CREDIT
Kay McNulty, Alyse Snyder, and Sis Stump operate the differential analyser in the basement of the Moore School of Electrical Engineering, University of Pennsylvania, Philadelphia, Pennsylvania
“They had no books or anything to teach us how to program it.”
Marlyn Wescoff
During 1947–1953
Erna Schneider Hoover computerized telephone switching method which “revolutionized modern communication”.It prevented system overloads by monitoring call center traffic and prioritizing tasks on phone switching systems to enable more robust service during peak calling times.
Potrait of Erna Schneider Hoover
Grace Hopper in a computer room in Washington,D.C.LYNN GILBERT
In the 1950s
Grace Hopper popularized the idea of machine-independent programming languages, which led to the development of COBOL, an early high-level programming language still in use today.
During 1961–1970
Katherine Johnson, Dorothy Vaughan and
Mary Jackson formed part of the country’s space work force and helped provide NASA with the raw computing power it needed to dominate space.
Katherine Johnson calculated the trajectory for Alan Shepard. She continued to work at NASA until 1986 combining her math talent with electronic computer skills. Her calculations proved as critical to the success of the Apollo Moon landing program and the start of the Space Shuttle program, as they did to those first steps on the country’s journey into space.
Dorothy Vaughn was the head of the National Advisory Committee for Aeronautics’ (NACA’s) segregated West Area Computing Unit from 1949 until 1958, Vaughan was both a respected mathematician and NASA’s first African-American manager.
Mary Jackson started as a computer at the segregated West Area Computing division. She took advanced engineering classes and, in 1958, became NASA’s first black female engineer.
Mary Jackson working at the Langley Research Center.NASA
Portrait of Dorothy Vaughan
Katherine Johnson at Work.NASA
Margaret Hamilton standing next to listings of the software she and her MIT team produced for the Apollo project.MIT MUSEUM
In the 1960s
Margaret Hamilton led a team credited with developing the on-board flight software for the Apollo space program. Another part of her team designed and developed the systems software which included the error detection and recovery software which Hamilton designed and developed. She worked to gain hands-on experience during a time when computer science courses were uncommon and software engineering courses did not exist.
Margaret Hamilton was also known as the first person to invent the term software engineer.
““There was no choice but to be pioneers.”
Margaret Hamilton
Margaret Hamilton standing next to listings of the software she and her MIT team produced for the Apollo project.MIT MUSEUM
In the 1960s
Mary Allen Wilkes designed the interactive operating system LAP6 for the LINC, one of the earliest such systems for a personal computer.
Mary Allen Wilkes was the first person ever to have a computer in their living room
The LINC, in the home of Mary Allen Wilkes.MARY ALLEN WILKES & DIGIBARN
Through 1968-1981
Lynn Conway led the Mead & Conway revolution, which was a very-large-scale integration (VLSI) design revolution which resulted in a worldwide restructuring of academic education, and was paramount for the development of industries based on the application of microelectronics.
Lynn Conway
Sophie Wilson
Through 1978-1985
Sophie Wilson designed the instruction set of ARM processor, the processor which was at the core of mobile device revolution.
Through 1973-1974
Frances Allen contributed to the theory and practice of optimizing compiler techniques that laid the foundation for modern optimizing compilers and automatic parallel execution.
Frances Allen is also the first female IBM fellow and in 2006 won the Turing Award, making her the first woman to do so.
Frances Allen
Radia Perlman
In 1985
Radia Perlman invented the Spanning Tree Protocol (STP), which allows each switch in the network to figure out its place in the scheme of things.
ALGORHYME
by Radia Perlman
I think that I shall never see
a graph more lovely than a tree.
A tree whose crucial property
is loop-free connectivity.
A tree that must be sure to span
so packet can reach every LAN.
First, the root must be selected.
By ID, it is elected.
Least-cost paths from root are traced.
In the tree, these paths are placed.
A mesh is made by folks like me,
then bridges find a spanning tree.
In 1994
Barbara Liskov defined a particular definition of sub typing, the Liskov Substitution Principle for OOP.
Barbara Liskov
Lisa Gelobter
in the 1990s
Lisa Gelobter worked on several pioneering Internet technologies, including Shockwave, Hulu, and the ascent of online video. | https://read.wearedevelopers.com/great-women-in-tech/ |
The IT world is studded with notable scientists, inventors, researchers, and outstanding personalities. As far as the stereotype goes, it's a man's world. But that's not entirely true. Women aren’t always on the scientific sidelines, despite the challenges associated with gender imbalance in IT. In fact, a lot of essential inventions came into existence thanks to women.
In the spirit of International Women's Day, we want to highlight the most prominent women in the tech industry who continue to inspire thousands of women to choose technology and sciences as a career path. Let's dive in.
Famous women in technology: Past
Ada Lovelace
(1815-1852)
Contribution: Created first computer algorithm
Ada Lovelace is often referred to as the founder of computer science, creator of the first software program, and prophet of the computing age.
Considered the first famous woman in technology, Ada indeed was ahead of her time. Born in the family of famous English poet Lord Byron, she had a knack for sciences and maths, which was unusual for a girl at that time. At the age of 17, she met Charles Babbage, the creator of Analytical Engine, which is considered the first computing machine on Earth whose principles laid the foundation for modern сomputers. Long story short, Charles hired Ada as an assistant and tasked her with translating his works into French. Ada did an amazing job. Not only did she translate the description of Analytical Engine but also supplemented it with copious notes that contained equations and formulas she came up with for calculating Bernoulli numbers. To this day, this formula is known as the first computer program ever written.
Ada is often referred to as a prophet because she had an idea that the machine could produce music on its own, given that pitches and composition theory can be broken into formulas and fed to the machine.
Hedy Lamarr
(1914-2000)
Contribution: Created transmission technology behind modern Wi-Fi, GPS, and Bluetooth
Hedy Lamarr is an Austrian-American actress and inventor. No one could imagine that one of the highest paying actresses would abandon her acting career to break into the science field (and even make a splash there), given that she didn't even have relevant education.
It began in 1940 when Germany sank an American evacuation ship with 77 children aboard. Hedy was so moved by the tragedy that she couldn't stay aside. Together with George Antheil, an American composer and her close friend, she set about working on a novel, remotely controlled signal transmission system for a torpedo that could not be intercepted by enemies. In a nutshell, the idea behind it was using a random code on the transmitter that would change the transmission channel so that it couldn't be intercepted. The technology was named "Hopping Frequencies." Although it was skeptically received by the government, mainly because non-specialists developed it, Lamarr and Antheil received a patent two years later. The technology received the credit it deserved during the Caribbean crisis in 1962.
Besides the military field, "Hopping Frequencies" principles are under the hood of modern communication technologies, such as Bluetooth, COFDM (Wi-Fi), GSM, and CDMA (wireless phones). In 2004, Hedy Lamarr's name was included in the National Inventors Hall of Fame in the USA.
Karen Spärck Jones
(1935-2007)
Contribution: Created language processing technology underlying modern search engines
Karen's innovative idea is that instead of interacting with computers using numbers and equations, they can be taught to understand human language. Google can understand the words we type them up, and this is what Karen Spärck Jones can take full credit for.
Karen Spärck Jones was born in Yorkshire, England, and went to Grinton College in Cambridge, where she majored in history and philosophy. After graduation, she briefly worked as a school teacher before joining the language research department at Cambridge University, focusing on machine speech processing. In her line of work, she found synonyms to words and put them into punched cards, the early data carriers. The purpose of Karen's work was to train a machine to recognize the words' contextual meanings. For example, in the sentence "a farmer works in the field," the polysemantic word "field" has many meanings. By adding a context, like "agriculture," the machine would choose the correct meaning of the word "field," such as "land."
Spärck Jones published a breakthrough paper that laid the foundation for the technology behind modern search engines based on her work at Cambridge. The main idea she elaborated in her paper was to combine statistics with linguistics, a novel approach that allowed computers to interpret relations between words using formulas. By 2007, most search engines were running on the principles described in her paper, making Karen Spärck Jones one of the most famous women in technology whose contribution is often overlooked.
Female technology leaders: Present
Radia Joy Perlman
(1951–)
Contribution: developed the algorithm behind the Spanning Tree Protocol (STP)
Although Radia Perlman owns many patents for Internet-related technology, her main invention remains the STP channel protocol used for routing the Internet traffic. Back in the 80s, it was a novelty that has transformed the Ethernet from a technology limited by a hundred nodes to a technology that can serve a massive network. For all we know, it wouldn't be the Internet as we know it today if it wasn't for Radia's work.
Radia was born on January 1, 1951, in Portsmouth, Virginia, in a family of American government workers. Science ran in the family, given that her father worked as a radar engineer and her mother was a programmer.
Radia Perlman made her first significant contribution to IT when she was a student at the Massachusetts Institute of Technology. She developed a children's version of LOGO education robotic language, which she named TORTIS. Thus, Radia is considered a pioneer in teaching computer programming to young children.
Radia designed the STP working at Digital Equipment Corporation, where she also invented several other important protocols. For example, the routing protocol called "link-state routing" and the IS-IS protocol, which is now the preferred routing protocol for most modern Internet service providers. She has also contributed largely to the security of the Internet.
Perelman is often referred to as "Mother of the Internet," thanks to her fruitful work in the field. Yet, she brushes off this stigma modestly, emphasizing that although her invention mattered, she wasn't the only one contributing to Internet development. Hence, she isn't in a position to take full credit for the creation of the Internet.
Sophie Wilson
(1957–)
Contribution: developed an ARM processor, which is widely used in modern mobile devices
Sophie Wilson is a British scientist and the pioneer of the first commercially viable personal computers. She was born in 1957 in Leeds, England, and studied Informatics at the University of Cambridge. Inspired by MK-14, a microcomputer kit, she developed her own microcomputer with a 6502 processor with 64 Mb operation memory. After graduation, Sophie joined Acorn Computers, a famous computer company.
Her contribution elevated the company to new heights. In the early 80s, Sophie Wilson worked on the expansion of the BASIC language for the Acorn Atom computer. She aimed to transform Atom into an improved version, Proton. In under a week, Wilson developed everything, from the system board to components and software. It ended in resounding success, given that British Broadcasting Corporation signed up Acorn Computers and started using this invention.
The invention of her lifetime, the ARM (Acorn RISC Machine) chip, began in 1983, when she was working on manuals for the first RISC (Reduced Instruction Set Computing) processors. She managed to decrease the number of instructions required for the microprocessor's proper functioning and reduced the number of transistors to a bare minimum, even less than in Intel's microprocessors. The simplified architecture of ARM microprocessors allowed them to be faster and use less energy than their rivals. This way, she laid the path for modern lightweight but robust mobile devices.
In 1999, Wilson started her own company, Element 14, where she developed a new processor called FirePath used in today’s broadband networks.
Influential women in tech: Future
Jewel Burkes
Contribution: A cutting-edge computer vision app called Partpic she designed herself
Jewel Burkes Solomon lived the modern dream of many. She worked for Google, came up with an idea for software, started her own company, and sold it to a giant, such as Amazon. Her cutting-edge startup, Partpick, makes it easier to identify industrial parts and order them instantly using computer vision technology.
She's an inspiration for many girls out there because she's a self-made woman who taught herself how to build a computer-vision app without a background in computer vision.
Jewel was named as one of Forbes 30 Under 30 in 2016, one of Ebony Magazine's Power 100 in 2018, and one of Atlanta's 100 Most Influential People in 2020. Moreover, at her current position at Amazon, she works every day to bring technology closer to people, no matter race, gender, and nationality.
Ayah Bdeir
Contribution: making technological knowledge closer to everyone
An engineer by calling and education, Ayah Bdeir founded littleBits, a startup that produces open-source modular electronic components that fit together with magnets. littleBits is an engaging way for kids (and not only kids) to learn electronics, robotics, and programming.
At an early age, Ayah was fascinated by how things held together and loved to dismantle electronic devices to see what's inside. Her parents were extremely supportive of her career choice, despite gender-based stereotypes. She graduated from the American University of Beirut with an engineering degree and interned at MIT Media Lab.
Not only did Ayah's company sell millions of products in more than 150 countries but the company also launched an initiative that aims to bring electronics closer to everyone. It's called the littleBits Inventor Clubs, a place where people of all ages, backgrounds, and abilities can feel supported and empowered to create. There are currently 300 littleBits Inventor Clubs worldwide. Besides, thanks to Bdier's initiative, more girls are coming into tech as part of Disney's Snap The Gap project that provides 10-year-old girls in California with littleBits kits to ignite and nurture their interest in technology.
From past to present and into the future, these examples of women in the tech industry prove once again that technology is gender-agnostic. Inventions and scientific discoveries are often down to having a passion for technologies and an inquisitive mind. Hopefully, we will see more and more women in tech in the years to come. | https://ncube.com/blog/most-inspiring-women-in-tech-past-present-and-future |
Ada Lovelace (1815-1852) – The first computer programmer
Ada Lovelace, née Augusta Ada Byron, revealed a talent for numbers and language at an early age. The daughter of Lord Byron and Anne Isabella Milbanke, Baroness of Wentworth, she was brought up by her mother – Byron left them a few weeks after Ada’s birth, never to return – and received a very unconventional education for an aristocratic girl of that era. Her tutors taught her mathematics and science because her mother thought that the rigor and discipline would keep her away from the moody and unpredictable temperament shown by her father.
At 17, she met and became friends with Charles Babbage, a mathematician and inventor who served as her mentor. Through him, she began studying advanced mathematics at London University. Babbage had invented the difference machine – an ancestor of the computer that could perform mathematical calculations – and had made plans for the analytical engine, designed for more complex calculations. Asked to translate an article on the latter from French into English, Lovelace not only did what was required but also added her own thoughts and ideas on the invention. Her notes were three times as long as the original paper and her work was published in an English science journal in 1843.
Her notes described how codes could be created for the device to handle letters and symbols along with numbers. She also devised a method for the machine to repeat a series of instructions, the looping process used by computer programmes today.
Her husband, William King, Earl of Lovelace, whom she married in 1835, was always very supportive of her scientific endeavour.
Lovelace’s contributions to computer science remained a well-kept secret for more than 100 years. In 1953, her notes were republished in a book by B.V. Bowden, Faster than Thought: A Symposium on Digital Computing Machines. In 1980, the US Department of Defense honoured Lovelace, giving the name Ada to a new computer language.
ENIAC (1946) – The refrigerator ladies
In 1943, two men, John Mauchly and J. Presper Eckert, along with the United States Army, began designing and engineering a system called the Electronic Numerical Integrator and Computer (ENIAC), part of a secret World War II project. They explored the possibility of an electronic calculator made from wiring and vacuum tubes and detailed their plans in a paper entitled The Use of High-Speed Vacuum Tube Devices for Calculation. To complete their project, they needed people, math majors, to programme the machine.
Six mathematicians, all women, were chosen. They learned to program without programming languages or tools, because none existed. They used only logical diagrams and the work they did calculating ballistic trajectories was extremely complex. When the project was completed, ENIAC could run missile trajectories in seconds.
When ENIAC was unveiled to the press and the public in 1946, the six women – Kay McNulty, Betty Jennings, Betty Snyder, Marlyn Wescoff, Frances Bilas and Ruth Lichterman – remained invisible. What’s more, most of them didn’t receive recognition for their work during their lifetime. They appeared in photos documenting the project but were, for many years, mistaken for models posing next to the machines. Some called them the "refrigerator ladies"!
Grace Hopper (1906-1992) – First Lady of software
"Amazing Grace" for some, the "First Lady of Software" for others, US Navy Rear Admiral Grace Murray Hopper was a leading figure in computer science and programming from the 1940s to the 1980s.
Born in New York, she graduated from Vassar College in 1928 with a bachelor in mathematics and physics. She then went to Yale where she earned a master’s degree in mathematics in 1930 and a PhD in 1934. Née Grace Murray, she married New York University Professor Vincent Foster Hopper in 1930 and retained his name after their divorce in 1945.
From 1931 to 1943, Hopper occupied various positions, from mathematics assistant to associate professor, at Vassar. In 1940 she applied to the US Navy but was refused. She persisted and in 1943 joined the US Navy Reserve, enlisting in the Women Accepted for Volunteer Emergency Service (WAVES). A year later she was assigned to the Bureau of Ordnance Computation Project at Harvard where she was part of the Mark I computer programing staff headed by Howard Aiken. The Harvard Mark I, or IBM Automatic Sequence Controlled Calculator (ASCC) was a huge electromechanical computer (16 meters long, 2,4 meters high weighing 4 500 kg), that was used to compute data for the scientists working on the Manhattan Project, the R&D undertaking that produced the first nuclear weapons. The Mark I also computed and printed mathematical tables, as inspired by Charles Babbage’s analytical engine.
Programmers can thank Hopper for making their life and work easier. When she began her career, all computer programmes were written in numerical codes by people with a mathematical background. To make computer coding more accessible, she devised a human-friendly programming language that used English words that were then translated into machine codes. She met with much resistance but persisted in her endeavor, and in 1952, the first "compiler" was born.
In the late 1950s, Hopper was part of the team that developed COBOL, the Common Business-Oriented Language used by businesses and governments. In the following years, many computer companies had developed their own – not always compatible – version of COBOL. In the late 1960s, Hopper was Director of the Navy Programing Languages Group and as such, developed validation software for COBOL and its compiler in an effort to standardize COBOL for the entire Navy. In the 1970s, she was responsible for the implementation of standards for testing computer systems and components, including COBOL. Since the 1980s, the National Institute of Standards and Technology (NIST) has taken over this role.
On a more anecdotal note, Hopper is said to have coined and helped popularize the terms "bug" and "de-bugging", after a moth was removed from inside her computer.
Hopper has received a great number of awards, including the first "Computer Science Man of the Year Award" in 1969. She retired in 1986, at 79, with the rank of US Navy Rear Admiral. In 1997, the US Navy named a new guided-missile destroyer in her honour: USS Hopper.
Lovelace, Hopper and the ENIAC women all contributed greatly to the development of today’s computer programming languages. Hopper’s efforts to standardize COBOL in particular, have shown the need for interoperable languages. In 1987, the IEC and ISO established ISO/IEC JTC 1: Information technology, a Joint Technical Committee that has brought about a number of very successful and relevant information and communication technologies (ICT) International Standards in many fields: IC cards (smart cards), automatic identification and data capture (AIDC) technologies, information security, biometrics, cloud computing, multimedia (MPEG), database query and programming languages as well as character sets, to name just a few. In particular, its Subcommittee ISO/IEC JTC 1/SC 22 deals with programming languages, their environments and system software interfaces.
Hedy Lamarr (1914-2000) – Hollywood star and inventor
MGM studios called her "the most beautiful woman in the world". After leaving her native Austria - and a first husband – in 1938, when Germany invaded her country, Hedy Lamarr – née Hedwig Eva Maria Kiesler in Vienna – met MGM studio head Louis B. Mayer who offered her a movie contract in Hollywood.
Beauty and acting weren’t her only gifts. She was an inventor in her own rights, although the press took little interest in this aspect of her personality at the time. Long after her acting career went into decline at the end of the 1950s, Lamarr’s inventions and love of science came to light, culminating in prestigious awards. In 1997, together with her friend and co-inventor, composer and pianist George Antheil, she received the Electronic Frontier Foundation (EFF) Pioneer Award and the BULBIE™ Gnass Spirit of Achievement Award, a prestigious lifetime accomplishment prize for inventors, dubbed "The Oscar™ of Inventing". And in 2014 Lamarr and Antheil were posthumously inducted into the National Inventors Hall of Fame.
During World War II, not wanting to limit her contribution to the war effort to what was demanded of Hollywood actors, i.e. troop entertainment, Lamarr who had gained previous knowledge about torpedoes from her first husband, military arms merchant and munitions manufacturer Friedrich Mandl, asked Antheil to help her develop a communication system using frequency-hopping signals to guide radio-controlled missiles underwater so that they would be undetectable, and therefore could not be jammed, by the enemy. To create the device, Antheil synchronized a miniaturized player-piano mechanism with radio signals. In 1942, they were granted a patent for their invention.
At the time, the US Navy seldom considered inventions made outside of the military and didn’t use the "secret communications system". Twenty years later, the importance of their work was finally recognized when an updated version of their design was used by the Navy during the Cuban missile crisis.
Last but not least, Lamarr and Antheil’s work with spread spectrum technology contributed to the development of Bluetooth and Wi-Fi, technologies that are essential to the work of ISO/IEC JTC 1 and its subcommittees.
Mária Telkes (1900-1995) – The Sun Queen
Hungarian-born Mária Telkes moved to the US in 1925 after obtaining her PhD in physical chemistry from the University of Budapest. In 1939, she joined the Massachusetts Institute of Technology (MIT) Solar Energy Research Project where she worked until 1953. At MIT, she developed the first thermoelectric power generator in 1947 and the first refrigerator using the principles of semiconductor thermoelectricity in 1953.
During World War II, Telkes worked for the US Office of Scientific Research and Development, where she developed a solar distiller capable of vaporizing seawater and recondensing it into drinkable water. Army life rafts carried the distiller during the war and a rescaled version of it was deployed to supplement the water demands of the Virgin Islands.
Telkes is also remembered as the woman who, together with American architect Eleanor Raymond, designed and built the first modern residence heated by solar energy. The system used a chemical process that crystalized and retained the heat and then radiated it back to keep a constant temperature.
Telkes is considered one of the founders of solar thermal storage systems, earning her the nickname "the Sun Queen". She received many prestigious awards during her lifetime.
Telkes is one of the inventors and scientists whose research led to major advances in solar photovoltaic (PV) and solar thermal technologies in the second half of the 20th century, as well as to the creation of two IEC TCs whose standardization work addresses solar energy, IEC TC 82: Solar photovoltaic energy systems, and IEC TC 117: Solar thermal electric plants.
Marie Van Brittan Brown (1922-1999) - The first CCTV
In the 1960s, Marie Van Brittan Brown lived in the New York borough of Queens with her husband and two children. She was a nurse and her husband an electronics technician; both had irregular work schedules and she often didn’t feel safe when alone at home. Crime rate was high and police response time often too long. Because she resented opening her door not knowing who was calling, she came up with a homemade solution that she devised with her husband’s help: four peepholes and a camera that slid up and down to film what could be seen through each hole. What the camera picked up was transmitted to a monitor inside and a two-way microphone permitted conversation with anybody outside the door. In addition, buttons could sound an alarm or remotely unlock the door.
In 1969, the Browns received a patent for their invention, the groundwork for CCTV and all modern home security systems.
In 1979, the IEC set up IEC TC 79: Alarm and electronic security systems, which prepares Standards for the protection of buildings, persons, areas and properties against fraudulent actions. The equipment and systems include access control, alarm transmission, video surveillance, building intercom, digital door locks, fire detection and fire alarm, intruder and hold-up alarm to name but a few. | https://iecetech.org/Technology-Focus/2018-03/Women-in-a-man-s-world |
Suzanne believes women throughout history have made a difference. Her goal is to discover and celebrate women's contributions to history.
Computers as we know them now are a relatively new technology. Yet the history of computer innovation goes as far back as the 1800's. Many women were pioneers in the development of computers through the years and played an important role in the overall advancement of technology. To this day they blaze a trail to new ideas and science in the field of computer engineering.
Ada Byron was the daughter of poet Lord Byron. Soon after she was born in 1815, her mother left her poet husband determined that Ada would study science and mathematics rather than poetry. But Ada never lost her creative side and approached her mathematical pursuits with imagination and poetic metaphors.
In 1834, Ada became aware of Henry Babbage who was working on a new calculating engine which he called an Analytical Engine. He imagined inventing a machine that had not only foresight but the ability to act on it. Ada was fascinated by Babbage's theories and began corresponding with him. He encouraged her interest and ideas. Ada suggested a plan to Babbage on how the engine could calculate using Bernoulli numbers. This plan is considered now the very first "computer program". In 1979, a software language was developed and named "Ada" in her honor by the U.S. Department of Defense.
You might have thought Hedy Lamarr was just another pretty face on the Silver Screen but the Austrian actress was brainy too. Though not recognized for her accomplishments until years later, Hedy and partner George Anthiel were responsible for the development of a "Secret Communications System". It was designed to manipulate radio frequencies between transmission and reception at irregular intervals. The goal of the invention was to help combat Nazis during World War II by creating an unbreakable code preventing the enemy from intercepting classified information.
Lamarr and Anthiel received a patent for their device in 1941 but it was only first used aboard naval ships during the Cuban Missile Crisis. Since then the system has been implemented in various military applications. The inventor's "spread spectrum" technology went on to form the backbone of digital communications as we know it now. Hedy Lamarr is recognized as one of the 20th century's most important women inventors and was honored with the Electronic Frontier Foundation Pioneer award in 1997.
Grace Murray Hopper earned her B.A. in mathematics from Vassar in 1928 and went on to get her Ph.D from Yale in 1934. She joined the Navy in 1943 and was quickly commissioned to work on Howard H. Aiken's electromechanical Mark I computing machine. By the end of World War II, the diminutive Hopper was working on the Mark II version of the machine and writing complicated operating manuals on the subject. Always full of energy, Hopper divided her time between military, business and academic pursuits.
She is credited with inventing the compiler, a program that translates English language instructions into the computer's language. In 1983, Hopper was promoted to rear admiral in a ceremony at the White House. She is considered one of the most important futurists in the computing world and is thought of as one of the first software engineers. On January 7, 1992, Admiral Hopper was buried at Arlington National Cemetery with full Naval honors.
Sister Mary Kenneth Keller is thought to be the first woman to earn a Ph.D. degree in computer science. From Cleveland, Ohio, Sister Keller entered the Catholic religious order, Sisters of Charity in 1932. Her Ph.D. degree work included the study of constructing algorithms used for algebreic analytic differentiation. She was allowed into a previously "men only" computer center at Dartmouth where she had a hand in the development of BASIC.
Sister Keller was a passionate advocate of encouraging women to enter the field of computer science. She accepted a faculty position at Clarke College in Dubuque, Iowa where she went on to found the Computer Science Department and act as its chair for the next 20 years. Her vision included the concept of artificial intelligence. Sister Keller died at the age of 71 leaving behind a legacy of advanced computer studies at Clarke College.
As one of the most important women in computer science, Karen Sparck Jones pioneered automatic language and information processing since the early days of computers. Her work in information retrieval is among the most cited and influential in the field. Born in Huddersfield, Yorkshire, England she held the position of Professor of Computers and Information at Cambridge's computer laboratory until 2002.
One of Prof. Sparck Jones most significant contributions to the field was the concept of inverse document frequency (IDF) which is still used in most search engines today. She never took her retirement seriously and continued to work at Cambridge until her death in 2007. She was recognized with several awards including the prestigious ACL Lifetime Achievement Award in 2004.
Sometimes referred to as the "Mother of the Internet", Radia Perlman is most well known for her invention of the spanning-tree protocol which is fundamental to the functioning of network bridges. She was born in Portsmouth, Virginia in 1951 and earned her Ph.D. in Computer Science from MIT. While in college she developed a small version of LOGO, an educational robotics language. She called it TORTIS. Radia is known as an innovative advocate for teaching very young children computer programming.
Perlman was named one of the most influential people in the computer field by Data Communications magazine. She is a software designer and network engineer at Sun Microsystems and specializes in network security. She holds over 50 patents and has published textbooks and academic papers on a variety of technological subjects.
That is an eye-opening hub. I had no idea there were so many influential women involved in the early stages of IT.
Love the hub, partly because it makes me think of how interesting technology will be when our photos look as ancient to a new generation as some of these look to us! Voted up.
You are all welcome. These women certainly deserve recognition for their accomplishments.
Hi suziecat7. Very informative and enjoyable to read. I have enjoyed your excellent hub exceptionally, and I am proud of all these talented women.
And all this time I thought we women just didn't exist, well maybe we didn't exist up until a certain time in history, or at least got no credit anyway at least Not in great literature. I like this hub. Great hub.
Thanks, everyone - it is always wonderful to hear from you all. Love ya.
Science sure is getting popular and more women are now studying for it. This is a great tribute to ladies who have proven that we are just as accomplished as guys! Cheers!
What a great subject, Suziecat - very inspirational and I think I see myself in one of those photos! Great job as always....love all the pictures, too - couple of these brainiacs were beautiful!
Darlene - you were on the cutting edge. Thank you for your kind words.
Thanks, suziecat7 for writing this. I learn much from you. Those women are great women and inspiring us in doing the best. Well done, my friend. Vote up!
This is really awesome. I learned a lot I didn't know about key roles in history. I bet if you expanded this with longer bio's and a few more women, you could make a nice ebook you could sell.
Dahoglund ans WillStarr - Thank you both so much for commenting.
What a fantastic hub! Steve Jobs and Bill Gates are the only names that appear to fill this hall of fame. Time for them to move aside and share some of the limelight, perhaps?
How wonderful to read all about these gifted women. Thank you, suzie, for sharing this fascinating information. Was especially interested to learn about Ada Byron and Hedy Lamarr - way, way ahead of their time.
Just shows how women can be as intelligent and innovative as men.Really learned some things for the first time. Thanks suziecat7.
Fascinating stuff. I really enjoyed the Admiral Hopper video. And who knew that about Hedy Lamarr?
Mentalist - Not yet but women are getting there. Always nice to see you - thanks for the comment.
Interesting history of women in computer science. | https://hubpages.com/education/Women-of-Computer-Science |
While you say expertise, IT or innovations, the gender to which you relate these phrases is routinely masculine. And never with out cause. Now, though these first associations are justified, that doesn’t imply that in our lengthy historical past some feminine inventors who’ve revolutionized the world of expertise haven’t participated equally. To have fun the Worldwide Girls’s Day, we’ve got determined to pay tribute to among the most fascinating girls in historical past that we’ve got had the privilege of studying and learning all through historical past.
1. Hedy Lamarr and wi-fi expertise
Whereas she started her life journey as a famed actress within the early 1940s, it turned out that this girl boasted numerous skills. Hedy Lamarr, particularly, was one of many primary inventors of the so-called unfold spectrum, which later performed an necessary function within the growth of WiFi, Bluetooth and CDMA (code division multiplexing). The expertise was primarily developed for different functions (the torpedoes of the US Navy) however was later utilized in excessive safety army communication.
2. Ada Lovelace – The World’s First Pc Programmer
The one reliable daughter of Lord Byron and Anne Isabella Milbanke, Miss Augusta Ada King was the one who translated the doc written by Luigi Menabrea on Charles Babbage’s Analytical Engine in 1843. However she not solely did the interpretation: she additionally added her personal notes which in reality they characterize an algorithm for a pc that was not but invented. In keeping with many, Lovelace is taken into account the world’s first programmer.
3. Grace Hopper popularizes the phrases Bug and Debugging
Admiral (sure, you learn that proper, Admiral!) Grace Hopper was not solely the primary girl to graduate from Yale and earn a doctorate in arithmetic, she was additionally the primary admiral within the US Navy. What’s your contribution to expertise? She developed the primary compiler in 1952 and COBOL (an acronym from English that stands for Widespread Enterprise Oriented Language). As well as, it popularized the phrases which can be used at this time every day: bug and debugging.
4. Marissa Mayer: The Grasp of Search
Earlier than turning into the CEO of Yahoo in 2012, Marissa had spent about 13 years at Google the place she was accountable for growing the corporate’s most profitable merchandise akin to Google Maps, Google Earth, Road View, Google Information and Gmail. She was additionally Google’s first engineer and certainly one of solely 20 girls accountable for an organization belonging to the world’s most prolific firms. Whereas at Google, Marissa was the one who handed each Google Doodle we’re already acquainted with.
5. Radia Perlman – The mom of the web
Though he’s not captivated with his nickname, it’s true that Radia Perlman was liable for the event of Ethernet. She created STP, the Layer 2 community protocol of the OSI (Knowledge Hyperlink Layer) mannequin, in accordance with Wikipedia, the idea of community bridging. This innovation had a huge effect on switches – gadgets that join different gadgets with a pc community. Perlman graduated from MIT and has a grasp’s diploma in arithmetic and a doctorate in laptop science.
What different inspiring lady would you add to this checklist? Share it with us!
Blissful Worldwide Girls’s Day! | https://techno-logy.com/5-crucial-women-for-technological-development/ |
26 October, 2020
Women in STEM have saved countless lives with their calculations and discoveries, have facilitated momentous events like the moon landing and the cracking of the Enigma Code, and have helped invent the malaria vaccine and GPS. But we rarely hear their stories.
Even when women have defied all the obstacles and embarked on a successful career in STEM, their achievements have often been questioned or credited to their male colleagues. And as the gender imbalance in STEM remains a glaring issue today, it is important for women and girls to have role models who represent them. So, who are some famous women in STEM who have changed our world?
Ada Lovelace is considered to be the world’s first computer programmer. In the 1840s, she struck up a friendship with mathematician Charles Babbage, who had designed a computing machine known as the Analytical Engine. Despite the fact that the Analytical Engine existed only on paper until the 1980s, Lovelace explained in a 20,000 word paper exactly how it would operate and devised an algorithm for generating numbers on the machine. What’s more, Lovelace predicted with astounding foresight that such machines could be used not just for mathematical and scientific purposes, but even to produce graphics and compose music.
Did you know? Ada Lovelace Day is celebrated on 15th October each year to honour the achievements of women in STEM.
Joan Clarke was a British mathematician best known for her role in cracking the Enigma Code during WWII. The Enigma Machine was used by the German military to communicate, and intercepting the Naval Enigma – strategic messages regarding German submarines in the Atlantic – was particularly crucial. Clarke was recruited to work alongside Alan Turing at Bletchley Park, the British codebreaking HQ, after winning a Double First in Mathematics from Cambridge. Her contribution to cracking the Enigma Code saved countless lives and is said to have shortened the war by at least two years. Despite her genius, Clarke’s work was overshadowed by her brief relationship with Turing, and the roles of male cryptanalysts at Bletchley has dominated the history books.
Did you know? You can learn about Joan Clarke’s work at Bletchley Park in the 2016 film The Imitation Game, where she is played by Keira Knightley.
If you’ve used Google Maps, ordered an Uber, or checked the local weather, then you have Gladys West to thank for that. After achieving her Master’s in Mathematics at Virginia State University, West began working at the US Naval Surface Warfare Centre, where she was the second African-American woman ever hired there. West developed the Global Positioning System – GPS – by working with the most powerful computers of the time and using satellites to measure the surface elevations of the Earth, creating an accurate mathematical model of our planet (a geoid). Though her efforts in developing such vital technology went unrecognised for decades, West was inducted into the US Air Force Hall of Fame in 2018.
Margaret Hamilton helped put the first man on the moon. She was a young mother and computer scientist working on the SAGE air defence system when she was recruited to join the MIT Instrumentation Laboratory. Over the next years, Hamilton was responsible for designing the on-board flight software for the Apollo missions. To comprehend the scale of the work done by Hamilton’s team, there is a famous photograph of Hamilton standing next to the printed source code of the Apollo Guidance Computer. She is credited with coining the term ‘software engineering’, when explaining that her work was just as much a discipline of engineering as hardware engineering. In 2016, Hamilton was awarded the Presidential Medal of Freedom by Barack Obama.
http://www.tech-heroines.org/2017/09/margaret-heafield-hamilton.html (photograph)
Katherine Johnson is one of the most famous female mathematicians, who made calculations for NASA’s first space missions. She studied mathematics at university before starting work at NACA, where she performed calculations as part of the ‘coloured computers’ – a segregated group of African American women. After NASA took over in 1958, Johnson was relocated to an all-male team, where she thrived despite the sexism she faced. Johnson calculated trajectories, launch windows, and emergency return paths for the first manned flight into space and the Apollo 11 moon landing. Her mathematical abilities were so respected that astronaut John Glenn refused to fly unless Johnson personally calculated his trajectory. Katherine Johnson was awarded the Presidential Medal of Freedom in 2015.
Did you know? The story of Katherine Johnson, Mary Jackson, and Dorothy Vaughn (two other inspirational African American women working at NASA) is told in the 2017 film Hidden Figures.
Grace Hopper is known as the ‘Queen of Code’ thanks to her instrumental role in developing computer technology. She earnt a PhD in Mathematics from Yale in 1934 before working on Mark I, a prototype of the electronic computer, at Harvard during the War. She later helped to create the world’s first all-digital computer, UNIVAC, developed the world’s first computer language compiler, and co-developed one of the world’s earliest standardised computer languages written in English, COBOL. Not only this, but Hopper was a member of the navy from 1943 until her retirement in 1986 – at which point she was the oldest serving officer in the US Navy. Hopper posthumously received the Presidential Medal of Freedom in 2016.
Did you know? Grace Hopper coined the term ‘bug’, meaning a computer failure, after a moth got into the circuitry of the computer she was working on!
A university degree is not the only way to make a difference in the world. Tu Youyou helped find a cure for malaria, for which she became the first Chinese scientist to win a Nobel Prize in a scientific category – and she achieved all this without a medical degree. After studying medicinal plants at Beijing Medical College, Youyou began working at the Academy of Traditional Chinese Medicine in 1955. She headed a project to find a cure for malaria, reviewing ancient Chinese medical texts and testing 240,000 different compounds. Her team finally isolated a compound found in sweet wormwood – artemisinin – which had been used in Chinese medicine for 2 millennia. Youyou’s discovery was adopted by the WHO as the world’s chief method of fighting malaria. She was awarded the Nobel Prize for Medicine in 2015.
Aspiring game designers will be inspired by the life of Carol Shaw, the first female video game developer. After receiving a Master’s in Computer Science from UC Berkeley, Shaw began working at Atari. She programmed classic games for the Atari 2600 console such 3-D Tic-Tac-Toe, which was the first commercially released game designed by a woman. Later, Shaw moved to Activision and wrote the award-winning game River Raid. In the end, Shaw was such a successful video game designer that she was able to retire at 35 years old!
Thanks for reading this article and if you have any questions or comments on this topic or coding and STEM in general, please feel free to contact us. | https://www.codeadvantage.org/coding-for-kids-blog/famous-women-in-stem |
March is Women in History month and TDS is remembering three women who were visionaries in their field of technology. Necessity may be the mother of invention, but these women were innovators due to their passion to help others.
Katherine Johnson (Aug. 26, 1918 to Feb. 24, 2020)
One of the women featured in the film, Hidden Figures, Katherine Johnson was a physicist and mathematician who contributed to America’s aeronautics and space program. She calculated the trajectory for Project Mercury and the Apollo 11 flight to the moon. In 1970, she worked on Apollo 13’s mission to the moon. The mission was aborted and Johnson’s work on backup procedures and charts helped the crew safely return to earth.
Hedy Lamarr (Nov. 9, 1914 to Jan. 19, 2000)
In between her film career and during World War II, Lamarr and composer George Antheil presented the U.S. Navy with a radio guidance system technology for Allied torpedoes. The intent was to use frequency-hopping spread spectrum designed to guide torpedoes and avoid the interference that was threatened by the Axis powers. Although the U.S. Navy did not adopt the technology until the 1960s, the technology developed by Lamarr and Antheil has been incorporated into Wi-Fi, Bluetooth, and CDMA (a type of radio tech).
For their work, the pair was posthumously inducted into the National Inventors Hall of Fame in 2014. If looking for a good read about the life of Hedy Lamarr, check out the book, The Only Woman in the Room by Marie Benedict.
Grace Murray Hopper (Dec. 9, 1906 to Jan. 1, 1992)
Grace Murray Hopper was a pioneer in the world of computer programming. She popularized the idea of machine-independent programming languages, which led to the development of COBOL. She was a U.S. Navy Rear Admiral, and in 1973 she became the first person from the United States to be named a Distinguished Fellow of the British Computer Society. She’s also an IEEE Fellow, the 1964 winner of the Society of Women Engineers Achievement Award, a National Medal of Technology winner, and was posthumously awarded the Presidential Medal of Freedom.
Also celebrating women’s achievements this month are Telecom’s Women in Technology Employee Resource Group, TDS ACE, and U.S. Cellular Women In Action in their 2020 Partnership Series. The groups are honoring six women who in 2019 “made history, shattered glass ceilings, and became ‘firsts'” in their field. The six women include:
Gita Gopinath: First woman to become chief economist for the International Monetary Fund
Yalitza Aparicio: First indigenous woman (and second Mexican actress) to be nominated for a Best Actress Oscar
Karen Uhlenbeck: First woman to win the Abel Prize (the top award in mathematics)
Laura Yeager: First woman to lead an Army Infantry Division
Jessica Meir and Christina Koch: First astronauts to complete an all-female spacewalk. | https://blog.hellotds.com/women-in-technology-that-changed-history/ |
Contrary to modern gender stereotypes, female innovators have been at the forefront of technological advances throughout history. This year’s Women’s History Month offers an ideal opportunity to trace the history of women in tech.
On 8 March 2021, the world held another year of (mostly virtual) gatherings to advance the cause of economic, social, and political empowerment for women around the world.
The theme of this year’s International Women’s Day, #ChooseToChallenge, encouraged individuals and organizations to renew our commitment to challenging the status quo when it comes to gender bias, inequality, and injustice.
It was a bold call, steeped in the true history of International Women’s Day – which arose out of the very political fights for women’s suffrage and workers’ rights in the early 20th century. The global response to the #ChooseToChallenge theme was a reminder that IWD is far more than just a day of recognition, and that the fight for a more equal and just world continues into our time.
One of the ways that we in the tech industry can challenge outdated elements of the status quo is by exposing the persistent biases in our own professional world. In few places is this bias more persistent, foolish, and historically inaccurate as in society’s collective perceptions of ‘women in tech’.
The gender gap is persistent, and it is real. According to the World Economic Forum, gender parity will not be realized until the 20s…. the 2120s, that is.
The tech industry remains one of the gender gap’s worst offenders, and as a result many people are simply unaware of the influential role women have played in the development of modern technology since the beginning of the Industrial Revolution.
Despite facing social, political, and economic barriers their male counterparts did not have to endure, many of history’s tech pioneers have been women. Their achievements are recognizable throughout modern technology and areas of scientific knowledge which continue to make their mark today.
Here’s a snippet of just a few female difference-makers who challenged the established conventions and expectations of their world – and inspire us to do the same in ours.
During much of the 18th and 19th centuries, women did not have the right to participate in the political process across most of the world, and were closed off from serving in many key professions. It’s enough to make you wonder how much further society would have advanced if over half of the population had not been largely excluded from scientific and technological fields.
Yet despite these structural barriers, women contributed in important ways to the technological advances of that time. In 1762, Nicole Reine Lepautre, a French mathematician and astronomer, accurately predicted the return of Halley’s Comet by calculating the timing of a solar eclipse and constructing a group of catalogs for the stars.
Halley’s Comet, which has been observed and recorded by humans since 240 BC, is the only known comet that can appear twice in a human lifetime. Nicole Reine Lepautre’s research contributed significantly to our understanding of the comet and its regular reappearance. Hopefully, by the next time Halley’s Comet comes around in 2061, the last outdated relics of gender bias – in both the tech world as well as society as a whole – will have been fully dismantled.
Although women started being offered the possibility not only to study, but also to teach in colleges during the 19th century, female faculty members were forced to quit if they decided to get married. It’s no wonder that balancing career and family is still such a central topic when it comes to modern day discussions of gender equality.
But neither formal obstacles, nor the sole responsibility for caring for the home, could hold back women like Ada Lovelace – who is recognized today as one of the first computer programmers. Lovelace is best known for her work on the Analytical Engine, the mechanical computer proposed by Charles Babbage which calculated algebraic functions over 100 years before the first general purpose computer.
Lovelace’s impact on our world of tech should be quite familiar – having discovered that her colleague’s machine could have applications beyond basic mathematical calculation, she is credited with publishing the very first algorithm.
The second Industrial Revolution in the late 1800s intensified women’s interaction with technology. Later, women played in integral role working in factories, as telephone operators, and even as snipers during both world wars. Amelia Earhart, meanwhile, is famous for being one of the early pioneers of aviation.
Behind these more visible contributions, there is also a rich history of women making an impact in highly technical fields. Building on the legacy of Ada Lovelace, the German mathematician and philosopher Grete Hermann was instrumental in establishing algorithms for abstract algebra, which served as a steppingstone for modern-day computer algebra.
Hermann also made important contributions to the theory of quantum mechanics.
Few people today may have heard of Hedy Lamarr, the Austrian-born film actress and inventor, but she has some impressive accolades to her name. Born in 1914, Lamarr starred opposite actors like Clark Gable and James Stewart in several early Hollywood films, and probably would have achieved fame as a movie star alone. Yet she also made breakthrough contributions to the defeat of fascism in World War II, as the co-inventor of a radio guidance system for Allied torpedoes. Based on an early version of spread spectrum technology, Lamarr’s innovation would later form the basis for many other wireless communications, including long-range naval communication and eventually even Bluetooth.
Although Rosie the Riveter might have captured the popular imagination, women in the United States made highly visible contributions to many other aspects of the Allied war effort. In 1942 a group of women were hired by the U.S. Army to program the ENIAC, one of the first computers. The work of Kathleen McNulty, Betty Jean Jennings, Frances Bilas, Elizabeth Snyder Holberton, Marlyn Wescoff and Ruth Lichterman, collectively known as “the ENIAC girls”, would go on to revolutionize computer programming.
In the commercial space, we cannot fail to mention Evelyn Berezin, who both created the world’s first word processor and developed the first airline ticket reservation system during the 1960s and 70s; Mary Kenneth Keller, developer of the BASIC programming language, who in addition to being a Roman Catholic nun was one of the first two people to earn a PhD in computer science in the United States; and Grace Hopper, inventor of the first natural language processor as well as the COBOL programming language, which is still used in business, finance, and administrative applications to this day.
In the early 1970s Hopper was instrumental in encouraging the United States Department of Defense to switch from large, centralized computer systems to networks of small, distributed computers connected via a common database – an innovation that would pave the way for the emergence of the consumer internet 20 years later.
It’s stories like those of Hedy Lamarr, Mary Kenneth Keller, Evelyn Berezin, and Grace Hopper which show how foolish today’s tech gender gap really is. Perhaps instead of fighting an ongoing battle for more representation, women should be in the position of being recognized for enabling our tech-driven world in the first place.
This is especially true when considering that the fight for gender equality in the tech space increasingly also has a strategic component, with companies in constant need of fresh tech talent. And talent has no gender.
Still, while significant overall efforts have been made to reduce the gender gap in the workplace, many companies still indicate only a small percentage of female tech employees. In addition to WEF’s Gender Gap Report, another worthy read on this topic is the Women in Technology Survey 2019. The survey’s key findings pinpoint important areas that individuals as well as companies can look toward when trying to make a difference.
Here an overview of some of the WiT Survey 2019 key stats:
With the support of our D&I council, we at PayU we are doing our best to motivate and support female employees wanting to grow in tech.
As a company we recognize the need for supporting and encouraging female leadership within the tech space, while demonstrating the importance of active participation.
As another Women’s History Month comes to a close, our responsibility to push for a more just and equal world continues. And while the tech space still has a lot of work to do in terms of equal opportunities and gender representation, the history of women at the forefront of technological change and development provides an inspiring example of how increasing the scope for diversity and inclusion benefits everybody.
At the same time, we know that challenging outdated perceptions of ‘women in tech’ isn’t only a matter of coming up with new strategies and initiatives for the 21st century. We can also learn from becoming more aware of the history that is already with us.
With the world changing fast, the contributions of women to the tech field isn’t just a niche topic for discussion in panel sessions during one month each year. Women helped invent the modern day tech industry, and will be fundamental to the future of a world increasingly dependent on it. | https://corporate.payu.com/blog/the-history-of-women-in-tech/ |
Amongst many others, these five women have made / are continuing to make huge waves in STEM. May we continue to be inspired by them!
Grace Hopper
New York City, USA
1906-1992
Studied: Computer Science, Mathematics
"A ship in port is safe, but that is not what ships are for. Sail out to sea and do new things."
Photo credit: https://www.britannica.com/biography/Grace-Hopper
Grace received a master's degree and a PhD in Mathematics from Yale University, and was a mathematics professor at Vassar College. She joined the Navy Reserves in 1943. Grace was one of the first three modern 'programmers' and is well known for her contributions to the development of computer languages. She is also recognized as the person most responsible for the success of COBOL, the first standardized general business computer language.
Hopper was originally rejected from the Navy because of her age (34) and size. Instead, she joined the U.S. Naval Reserve where she worked on the Mark I, one of the earliest computers. At her retirement, Hopper was the oldest (79) serving officer in the U.S. Armed Forces.
She was posthumously given the Presidential Medal of Freedom in recognition for her great contributions to computer science.
Fun fact - Hopper was the first to refer to a computer problem as a "bug" when she found a large moth in a Mark II computer.
Find out more - Book: Grace Hopper and the Invention of the Information Age by Beyer, Improbable Warriors: Mathematicians Grace Hopper and Mina Rees in World War II by Kathleen Williams.
Katherine Johnson
White Sulphur Springs, West Virginia, USA
1918-2020
Studied: Mathematics, Science, Physics
"Like what you do, and then you will do your best."
Photo credit:
https://www.nasa.gov/content/katherine-johnson-biography
Katherine graduated with a bachelor's degrees in mathematics and french. She was the first African-American woman to attend graduate school at West Virginia University. She pursued a career as a research mathematician, and worked for the National Advisory Committee for Aeronautics (NACA) and NASA.
Katherine calculated the trajectory for the space flight of Alan Shepard, the first American in space. She verified NASA's computer calculations for John Glenn's orbit around Earth. She also helped calculate the trajectory for the 1969 Apollo 11 flight to the Moon. Johnson spent her later years encouraging students to enter STEM fields.
She was awarded the Presidential Medal of Freedom in 2015 for her work as a pioneering physicist, mathematician, and space scientist.
Fun fact - Katherine graduated from high school at the age of 14 and finished college at 18.
Find out more - Book: Reaching for the Moon by Johnson; Movie: Hidden Figures.
Radia Perlman
Portsmouth, Virginia, USA
1951-
Studied: Computer Science, Mathematics
"But the world would be a better place if more engineers, like me, hated technology. The stuff I design, if I'm successful, nobody will ever notice. Things will just work, and be self-managing."
Photo credit:
https://www.invent.org/inductees/radia-perlman
Radia enjoyed math and science from a young age and took her first programming class in high school. She attended MIT where she received bachelor's and master's degrees in mathematics. She received her PhD in computer science from MIT in 1988.
Radia is often referred to as the "Mother of the Internet." She invented the spanning tree protocol (STP), which is fundamental to the operation of network bridges. She later improved STP by designing TRILL (TRansparent Interconnection of Lots of Links), which allows Ethernet to make optimal use of bandwidth. Today, the majority of Internet Service Providers (ISPs) use this routing protocol, which has been standardized by the International Organization for Standardization (ISO). She was also one of the major designers behind DECnet.
Radia currently holds over 100 patents, and she was named 2004 Inventor of the Year by the Silicon Valley Intellectual Property Law Association.
Fun fact - Radia attended MIT at a time where the number of women in her class was limited by the number that could fit into a single female dorm. She was one of 50 women in her class of 1000 students.
Find out more - Book: Interconnections: Bridges and Routers by Perlman, Network Security by Perlman
Rosalind Franklin
Notting Hill, London, England, UK
1920-1958
Studied: Chemistry
"Science and everyday life cannot and should not be separated."
Photo credit:
https://www.invent.org/inductees/radia-perlman
Rosalind studied physics and chemistry at Newnham College in Cambridge and earned a PhD in physical chemistry from Cambridge University. She worked for the British Coal Utilisation Research Association and the King's College London biophysics unit. Rosalind's work was critical to the understanding of the molecular structures of DNA, RNA, viruses, coal, and graphite. She used X-ray diffraction and crystallography to photograph elements, and her photographs provided key insights into the structure of DNA.
Franklin and her student Raymond Gosling discovered that there were two forms of DNA: a dry "A" form and a wet "B" form. A picture they took of the "B" form of DNA became famous (known as Photograph 51) as it was used by Watson and Crick as the basis for their famous model of DNA. Watson and Crick received a Nobel Prize for the discovery in 1962 but did not credit Franklin for her role in the discovery.
After she left King's College, Franklin published 17 papers on viruses in five years. Her research laid the foundation for structural virology.
Fun fact - Rosalind was diagnosed with ovarian cancer in 1956. She published seven scientific papers that year, and published six more in 1957, all while she was undergoing chemotherapy.
Find out more - Book: Rosalind Franklin: The Dark Lady of DNA by Maddox
Jane Goodall
Hampstead, London, England, UK
1934-
Studied: Primatology, Anthropology
“What you do makes a difference, and you have to decide what kind of difference you want to make.”
Photo credit: https://www.britannica.com/biography/Jane-Goodall
Jane began studying chimpanzees in Gombe Stream National Park in Tanzania in 1960. In 1962, Goodall attended the University of Cambridge. She then studied at Newnham College, Cambridge, where she earned a PhD in Ethology. At that point in time, she was only the eighth person allowed to study for a PhD without a bachelor's degree. | https://www.1mwis.com/post/women-making-waves-1 |
Me, thinking to myself last week: “Whoa…March is coming to an end soon – which means Women’s History Month is coming to an end soon! We’ve got to bring some awesome #womenshistory to Ask Trish!”
As I’m sure many of you know, March is Women’s History Month. Women’s History Month is about recognizing, celebrating, and sharing the stories of women that have made incredible contributions – big and small – to our society and world. It’s not just an opportunity to shed light on those stories we know well, but to remember women who have been forgotten by history, or are rarely discussed in their fields. With the end of March near, I thought that for Ask Trish’s last post of the month, I’d shine a light on 3 women who helped build the internet (the very thing we talk so much about on Ask Trish!). These women’s stories are uplifting, inspiring, and deeply powerful – and through their stories, I hope to share that energy with all of you, especially women-identifying readers.
Up first is Ada Lovelace, an English mathematician that is well known for claiming the title of the world’s first computer programmer. (Yes, that’s right – the world’s first computer programmer was a woman! #Queen) As a girl, her mother insisted that she receive an education in mathematics (unusual at the time for women). Then, at 17, she met Charles Babbage, known to many as the father of the computer – he invented the first mechanical computer. Over the years, they collaborated extensively. Her best-known work, completed in collaboration with Babbage, was the translation of an article on “the Analytical Engine,” which Ada annotated heavily, adding extraordinary and visionary ideas. Among them was a description of how the engine could be used to solve mathematical problems – in other words, a description of an algorithm, making her the world’s first computer programmer. Today, she is remembered by women in STEM fields around the world as a pioneer in her work.
Next up is Grace Hopper, an American computer scientist who actually coined the term “computer bug.” (Did you know that?! So cool.) Grace graduated from Vassar College in 1928 with degrees in mathematics and physics; she then received her masters degree at Yale and a doctorate at Vassar (all in mathematics). Talk about all of school! She put it all to work when, following the bombing of Pearl Harbor/the US’s entrance into World War II, she joined the war effort. (She was initially rejected for being small, but persisted.) As part of her work, she joined a team at Harvard working to develop MARK I, the first electromechanical computer; using MARK I, Grace and her colleagues computed calculations critical to the war effort. From there, Grace continued to work with computers, from building compilers that translated mathematical code into machine-readable code (a key step toward modern computer programming languages) and building the first programming language to use word commands (rather than symbols). The latter was considered a huge advance in making computer science more accessible. She is remembered as a true visionary and “Amazing Grace.”
Last, but certainly not least is Radia Perlman, whose work was crucial to the creation of ethernet technology. In high school, she took her first computer programming class – as the only woman in the class – an experience that spurred her interest in computers. She then attended MIT to pursue her undergraduate studies, as just one of a few women (out of 1,000 students in her class). During her undergraduate studies, she did work to develop a child-friendly version of an educational robotics language, making computer programming education more accessible to youth. It was during her graduate studies (also at MIT) that Radia first got involved in network protocols. And indeed, she is most well-known for building the “Spanning Tree Protocol,” or STP, that, to put it very simply, builds communication infrastructure for Ethernet networks. (This was a huge contribution!) Today, Radia is an author, has received over 100 issued patents, and received numerous Lifetime achievements awards. In other words, she’s a #girlboss.
I hope you enjoyed this post – and found these incredible women as inspiring and empowering as I do. Before we part ways, one last thing: whether you’re an #AskTrish regular, or you’ve just started recently tuning in to #AskTrish, don’t hesitate to share any of your thoughts, musings, or questions about the internet here. Your topic just might be featured in next week’s TikTok/blog post! Remember, any time you share a thought or question, you benefit our entire community – there’s a good chance there are other youth wondering the same thing. So take a chance – and just 2 minutes – to fill out that form. And as always: anything goes. No matter what’s on your mind, I’m so excited to hear from you.
Thank you all! Until next Tuesday, | https://www.connectsafely.org/ask-trish-womens-history-month/ |
From ancient times, a woman was considered the guardian of the hearth, so science and other social activities have been the prerogative of men. However, there were well-known women in the history, who have come up with a truly fundamental inventions and have broken down stereotypes about women's logic and that the engine of progress can only be a man.
A huge contribution to the development of the astrolabe - one of the oldest astronomical instruments, instrument for measuring the coordinates of celestial bodies - has been made by the world's first woman scientist Hypatia Aleksandriyska. Also Hypatia – an ancient philosopher, mathematician and astronomer - credited with the invention (improvement) of the device to both produce distilled water and measure its density.
English mathematician Ada Lovelace (Ada Lovelace) is known for the creation of the first description of a computer, a draft of which was designed by Charles Babbage (Charles Babbage), and the writing of the first program for it in 1840.
Program became an algorithm for calculating Bernoulli numbers, thanks to him the girl is considered the first programmer in history. Furthermore, it is Ada who coined the term "cycle" and "work cell".
Thanks to Nicole Clicquot Barbier (Barbe Nicole Clicquot) in 1816, technology "remuage" came into use of winemakers thanks to which the champagne becomes crystal clear and got rid of sediment after three months. This was landmark event in the wine business, because previously champagne was cloudy (through the pellet containing the dead yeast) and did not have the status of elite wines.
French physicist of Polish origin, chemist, teacher Maria Sklodowska-Curie and her husband opened the chemical elements radium and polonium. She became the first woman to receive the Nobel Prize, and the first double winner of the award (in Physics - 1903, in Chemistry - 1911). She is the only researcher in the history to get this distinguished award in two different fields of natural sciences.
American military computer scientist Grace Hopper, who participated in the creation of the first computer in the United States, "Mark I", in 1950 developed the first compiler in the history. It was intended for the programming language COBOL.
In 1845, Sarah Mather has patented periscope - an optical instrument for observation from the shelter, which is used in submarines.
In 1873 at the World Exhibition in Vienna Russian woman Nadejda Kozhina has demonstrated a method for preparing canned meat, for which she won a gold medal.
Inventions Dennis Olive completely changed the nature of the trip by rail in the early XX century. Among them - the folding shelves, dirt-repellent upholstery, free towels, liquid soap. Moreover, Olive designed ventilation system for trains when clean fresh air is supplied to each passenger individually, as well as the lights that are turned off at night.
American inventor Josephine Cochrane has designed and built in 1886, the first in the history mechanized dishwasher. According to legend, frustrated that the items from the family porcelain service split during washing, she said: "If no one is going to invent a dishwashing machine, then I'll do it myself." By the way, the device Cochrane was deemed necessary thing only 40 years later.
Bette Nesmith Graham, who is known as the inventor of the "liquid paper", was a simple corrector, correcting mistakes of typists. After reviewing the basics of chemistry and long time experimenting in his garage with different mixtures of white color, she got at last one that glosses over the error, quickly dried up and allowed reprinting.
Ellen Eglui invented the washing machine drum, and in 1888 she sold the patent for $ 18, because "no one would buy a washing machine, if he knew that the patent for it is owned by some kind of" black woman ".
American refrigeration engineer Mary Engle Pennington in 1907 introduced into the use mobile refrigeration plants, which are extensively used for food supply during the First World War.
Inventor Jesse Cartwright has made a lot of innovation of home appliances, including the creation in the late 1940s the first model of microwave oven Radarange.
In 1942, the actress Hedy Lamarr has patented a secret communication device, with a help of which broadcasting frequency was dynamically changed to make it more difficult to intercept communications by enemy. Since 1962, this device was used in the American torpedoes, and now - in the mobile and Wi-Fi.
First car wipers were invented by Mary Anderson in 1903 - she felt sorry for the driver, who was forced during a blizzard constantly stopping the machine and shovel snow from the windshield.
Car exhaust silencer also was invented by a woman - an acoustic filter in 1917 was designed by Elle Dolores Jones.
Ann Moore, who visited as part of the Peace Corps in Africa and saw the delight with which African children were placed behind their mothers in the 1960s, has designed a very good backpack for carrying children, which is called Snugli. | https://kpi.ua/en/inventor |
Steve Jobs, Bill Gates, Tim Cook, Meg Whitman, our very own Satya Nadella. All these names sound familiar, don’t they?
They are not just famous personalities. They are creators, inventors, revolutionaries and visionaries with strong business acumen. Their names are synonymous with the brands and products they have created or helped sustain, without which most the twenty first century would probably be unimaginable.
However, have you ever wondered about the names that you perhaps never heard of? The names that have changed your lives in one way or another. The unsung heroes, who perhaps by no fault of their own, have their names on the last pages of history textbooks, or not there at all?
If you have, this is the story you need to read. Here are a few people whose contributions have perhaps shaped our lives in more ways that we can imagine, and even allowed our technology gurus and innovators to be who they are today. These are people who laid the founding stones upon which today’s technological empires have been built.
1. Ada Lovelace
Ada Lovelace was unique, in that she developed an algorithm for a computer that didn’t yet exist — an accomplishment that some say qualifies her to be called as the world’s first computer programmer.
Born to English nobility in 1815, Lovelace was made to work by Charles Babbage in 1843, documenting his otherworldly (at that time) idea of what could be known as a ‘computer,’ - The Analytical Engine. Starting with a document written in French by Luigi Menabrea, an Italian mathematician, Lovelace added extensive notes to the English translation, including the world’s first computer algorithm. The Analytical Engine was intended to count Bernoulli numbers, but Babbage was unsuccessful in getting funding for an idea that seemed ludicrous at the time. But Lovelace saw deep potential, recognizing the capacity of a machine like that.
“Many persons who are not conversant with mathematical studies imagine that because the business of Babbage’s Analytical Engine is to give its results in numerical notation, the nature of its processes must consequently be arithmetical and numerical, rather than algebraic and analytical. This is an error. The engine can arrange and combine its numerical quantities exactly as if they were letters or any other general symbols; and in fact it might bring out its results in algebraic notation, were provisions made accordingly,” Lovelace wrote in the Sketch of the Analytical Engine Invented by Charles Babbage
Ada Lovelace died at the age of 36 in 1852 because of uterine cancer and for many years, her work was not only ignored but thought to be of no substance. Today, she is celebrated each year on Ada Lovelace Day, a practice that only began many years after her death. She never received her due recognition while she was alive. Four generations and many technological revolutions later, her descendant, Honora Smith is now aspiring to make her own mark in the world of mathematics and computer science.
2. Hedy Lamarr
Largely known as a screen star of the 1920s, Hedy Lamarr proved to be more than just a pretty face. She played a key role in the invention of spread-spectrum technology; specifically, by conceptualizing the idea of frequency hopping, which itself is a method of sending radio signals from different frequency channels.
Lamarr, along with co-inventor George Antheil, created the technology that was originally intended to help the Navy control torpedoes. However, little did they or the world know that this small scale innocent work of the two would lead to the creation of the basis upon which present day wireless technologies such as Bluetooth, Wi-Fi and Code Division Multiple Access (CDMA) would function.
The two received a patent for their idea on August 11, 1942, according to the American Heritage of Invention & Technology. But despite lobbying and fundraising efforts on their part, the Navy ultimately passed on the technology.
This only goes to show how ahead of their time the two were with their ideas and work.
But all was not lost. It was reborn in the late 1950's when engineers at Sylvania Electronics Systems Division recognized the potential behind the gold mine the world was sitting on. And it was then that their work was used to secure military communications.
After initially receiving very little recognition for her work on spread-spectrum technology, Lamarr was honored with a special award: the Pioneer Award by the Electronic Frontier Foundation in 1997. This long overdue recognition for her scientific endeavors came just three years before her death in 2000.
3. Alan Turing
Alan Mathison Turing (23 June 1912 – 7 June 1954) was a pioneering English computer scientist, mathematician, logician, cryptanalyst and theoretical biologist. He was highly influential in the development of theoretical computer science, providing a formalization of the concepts of algorithms and computation with the Turing machine, which can be considered a model of a general purpose computer. Turing is considered to be the father of theoretical computer science and artificial intelligence.
He came up with many techniques for breaking German ciphers. Turing played a pivotal role in cracking intercepted coded messages that enabled allies to defeat the Nazis in many crucial times, saving uncountable lives and reducing the war time in Europe by an estimated four years.
Turing was the tortured and wronged genius behind the decoding the Enigma machine and the development of computing. From the iPad to Facebook, much of the technology we use today was coded, created and worked on by him.
Turing was prosecuted in 1952 for homosexual acts, when such behavior was still a criminal act in the UK. He accepted treatment with DES (chemical castration) as an alternative to prison. Turing died in 1954, 16 days before his 42nd birthday. A post-mortem examination established that the cause of death was cyanide poisoning. When his body was discovered, an apple lay half-eaten beside his bed, and although the apple was not tested for cyanide, it was speculated that this was the means by which the fatal dose was consumed.
Some even believe that the tech giant Apple got its name and logo as an inspiration from Turing's end.
The historical 2014 drama film, 'The Imitation Game,' starring Benedict Cumberbatch as Alan Turing was a huge success.
Queen Elizabeth II granted him a posthumous pardon in 2013, almost 6 decades after his unjust treatment and death.
4. Barbara Liskov
Born November 7, 1939 as Barbara Jane Huberman, Barbara Liskov is an American computer scientist who is an institute professor at the Massachusetts Institute of Technology and Ford Professor of Engineering in its school of engineering's electrical engineering and computer science department. As one of the first women to earn a Ph.D. in computer science, Barbara Liskov has always been an IT trailblazer
Liskov has several notable achievements to her name, including the invention of CLU, a programming language that helped lay the foundation of object-oriented programming; Argus, a programming language (largely an extension of CLU), that supports distributed programs; and Thor, an object-oriented database system.
These advances in object-oriented programming have contributed to the wealth of many modern OOP-based languages and operating systems, including Mac OS X, Objective-C, Visual Basic.NET and Java. Computers as we know them would not be able to coherently integrate language use without this woman.
At 76 years of age, Professor Liskov continues her research at the Massachusetts Institute of Technology. In 2008, she was honored with the A.M. Turing Award, an annual recognition given by the Association for Computing Machinery that many consider to be ‘the Nobel Prize of computing’. In 2012, she was inducted into the National Inventors Hall of Fame for her contributions to programming languages and system design.
5. Anthony Michael "Tony" Fadell
Born March 22, 1969, Tony Fadell is a Lebanese-American inventor, designer, entrepreneur and angel investor. He served as the senior vice president of the iPod Division at Apple Inc., from March 2006 to November 2008, and is known as ‘one of the fathers of the iPod’ for his work on the first generations of Apple's popular music player. In May 2010, he founded Nest Labs, which announced its first product - the Nest Learning Thermostat, in October 2011. Nest was acquired by Google in January 2014 for $3.2 billion. Since early 2015, he has been leading the Google Glass.
Tony created both the concept and the initial design of the world famous iPod. Starting as a lowly contractor, Fadell's work on the project eventually found him in a senior vice president position, with a host of popular devices to his name and his work reaching more than 350 million people.
Although he does not work with Apple any more, he was never truly given the credit for the revolutionary way in which he has affected tech and music industries. At one point, when the American auto industry had almost collapsed, he also revealed that he and Steve Jobs once discussed an Apple car. Fadell pointed out that phones and cars aren't that different: 'A car has batteries; it has a computer; it has a motor; and it has mechanical structure,’ he was quoted as saying.
'If you look at an iPhone, it has all the same things. It even has a motor in it.
6. Ajay Bhatt
This list would be severely incomplete without acknowledging the man of our own soil, who created the ubiquitous standard widely known as the USB. Yes, the standard without which our smartphones won’t charge, data won’t transfer, and a lot of gadgets just won’t work. The USB port (and largely, the standard) is a commonplace device on video game consoles and smartphones alike, and has even replaced many old technologies such as charging devices and portable chargers. Bhatt is an Indian-American computer architect who helped define and develop several widely used technologies, including USB (Universal Serial Bus), AGP (Accelerated Graphics Port), PCI Express, Platform Power management architecture and various chipset improvements.
Ajay Bhatt rose to global celebrity status as the co-inventor of USB through an Intel 2009 TV advertisement, where he was portrayed by actor Sunil Narkar. After having spent his formative and youthful years in India and upon completing his graduation in Vadodara, India, Bhatt completed his master's degree in New York and joined Intel in 1990. He currently holds 31 US patents.
7. Shiva Ayyadurai
Facebook, Twitter, YouTube, even Tumblr. So what exactly is it that these platforms have in common, except for trying to outdo each other in terms of market value and working together for symbiotic growth and prominence? What they have in common is the last genius on our list.
Without Shiva Ayyadurai’s creation, neither of the above websites would be able to properly function.
The Email. They all need require an email address to sign up and log in, the first step to being a part of the online world on any of these platforms. Not just that, we all use email for just about everything, professional and personal communication included. It is one such creation that almost single- handedly made the ancient art and requirement of letter writing nearly obsolete in a record time of less than a decade.
Shiva Ayyadurai is the man behind the creation of the email. It is worth a mention that Ayyadurai missed on the fame for some reason, even though he was just a 14 year old teenager when he invented email in 1978. He developed a full-scale emulation of the interoffice mail system, which he called ‘EMAIL’ and copyrighted in 1982. The name's resemblance to the generic term ‘email’ and the claims he later made for the program have led to controversy over Ayyadurai's place in the history of computer technology. | https://cio.economictimes.indiatimes.com/news/strategy-and-management/7-unsung-heroes-of-technology/52724912 |
Radia Perlman, also know as the mother of the internet is a network engineer who developed a computer protocol known as Spanning Tree Protocol (STP). STP made it possible to build extensive networks over Ethernet connections. Because of this network, we can surf the internet and its seemingly infinite sources of information from the comfort of our home. She has had a profound impact on how networks self-organize and move data. More impressively, Perlman is currently working at Intel and recently developed the Transparent Interconnection of Lots of Links (TRILL), which is a new standard for data center connectivity that could very well replace STP.
Susan Kare
If you’re reading this on a computer, you owe a debt to Susan Kare. Kare is the pioneering designer behind the original Mac icons and the first digital typefaces like Chicago. She led the Apple team into the redesigning process of Mac computers in the 1980s and proved that computers could have great fonts. Kare continued creating graphics we all recognize today like the card deck for Microsoft’s Solitaire game, Paypal, Facebook, and Digg among others.
Marissa Mayer
Marissa Mayer is Google’s first female engineer who started with the tech giant back when it was a startup in 1999. Not only was Marissa Mayer, Google’s first female engineer, her work on Google Maps, Google Books, Google Images, and Gmail helped catapult the company to become the No.1 search company. Mayer currently still works with Google as vice president of location and local services, and leads project management.
Hedy Lemarr
Hedy Lamarr was known for her talents on screen, often referred to by many critics and fans alike as the most beautiful woman to ever appear in films. However, it was during World War II that she proved to be more than just a pretty face. She was responsible for creating what is known as frequency hopping, a process which sends radio signals from different frequency channels. Frequency hopping was originally created as a communication system to fight against the Nazis back in WWII. Her invention, along with co-inventor, George Antheil, became a key component to the development in our modern wireless technology. In other words, we are able to use Wi-Fi and Bluetooth because of Lemarr’s idea that oringinated over 70 years ago. | http://heragenda.com/how-5-remarkable-women-changed-technology/ |
In celebration of Women’s History Month, we wanted to take the opportunity to recognize the women who have impacted the technology industry. The following women have impacted this industry over the years and this list is only a fraction of the influential female leaders in technology.
Ada Lovelace, First Computer Programmer
Elizabeth Feinler, Pioneer of the Internet
Donna Dubinsky, Creator of Digital Assistants
Hedy Lamar, The Mind Behind Secure Wi-fi, GPS and Bluetooth
Grace Hopper, Esteemed Computer Scientist
Radia Perlman, The Mother of the Internet
“If your actions create a legacy that inspires others to dream more, learn more, do more and become more, then, you are an excellent leader.” -Dolly Parton
As we celebrate and acknowledge these women, we want to assure women that they will always have a seat in the world of technology. A huge thank you to these women for their contributions and their impact in today’s world!
Want to join some of the amazing women here at The 20? Apply now! | https://www.the20.com/blog/celebrating-women-in-technology/ |
There is no future without a past… - Siri Hustvedt
As this quote rightly states, we cannot see a future without honoring our past. This holds true in every domain, including the world of technology and innovation. And, with International Women’s Day right around the corner, it is a good time to take a look at some of the women trailblazers of the coding industry who have paved the way for fellow women to make their mark in this field.
These women trailblazers fearlessly shattered the glass ceiling and broke the conventional barriers of gender inequality.
This article aims to celebrate the achievements of these great achievers and how their contribution has impacted the world of coding today.
No list of the popular women trailblazers in the world of coding could be complete without mentioning the first computer programmer, Ada Lovelace.
Ada Lovelace was a mathematician and writer known for her work on Charles Babbage’s proposed mechanical general-purpose computer, the Analytical Engine. She was the first to discover that a computer could follow a series of sequences (a program). In 1843, she drew an outline of the world’s first program that could perform all computations, and not just mathematics as Babbage was originally aiming for.
Two centuries later, even as the science of computers has taken quantum leaps, Lady Ada’s name continues to live on. She helped usher in the idea of what modern computers would become.
To honor her legacy, a team led by Dr. Jean Ichbiah at CII-Honeywell-Bull in France, created the Ada programming language in the early 1980s. This version, today, is known as Ada 83.
Sister Mary Kenneth Keller, the first person in the US to earn a Ph.D. in Computer Science, was a trailblazer in higher education. She worked tirelessly to expand the reach of computer science and truly paved the way for women wanting to learn programming.
After graduating from the University of Wisconsin-Madison, she collaborated with John G. Kemeny and Thomas E. Kurtz to create BASIC, a simple computer code that allows people without intermediate mathematical skills to develop computer software.
She also founded the Association of Small Computer Users in Education (ASCUE). This organization, which is still active today, works towards promoting the use of technology in education. She also founded the Computer Science department at Clarke University in Iowa. She taught and then directed the department for 18 years.
She worked throughout her life to make it possible for women to learn computer sciences and advocated for women in coding. The Keller Computer Center and Information Services and Mary Kenneth Keller Computer Science Scholarship, both honor her remarkable legacy at Clarke University.
Grace Hopper was an American computer scientist who also served as a rear admiral in the United States Navy.
Known for her involvement as one of the earliest developers in the creation of the Harvard Mark I computer while he served in the United States Navy during World War II. She is also a pioneer in the field of computer programming who invented one of the first linkers.
She is also accoladed for developing the COBOL language that is still in use today. Throughout her career, Grace Hopper advocated for making the field of computer science, coding, and research more accessible for women.
Fun trivia! Grace Hopper was the first person to use the word bug when she found a moth in her computer hardware that was causing the computer to malfunction.
Joan Ball is a computer pioneer. She was the first to create a computer dating service in England in 1964, known as the St. James Computer Dating Service; this pre-dated even the earliest American dating services, such as Operation Match at Harvard.
After conducting a survey about what people look for in their prospective match, she created a program that helped match people with eligible partners. The first match made by this program was in 1964, a year before Operation Match at Harvard was created!
In 1965, Joan Ball merged her computer dating service with another marriage bureau and renamed St. James Computer Dating Service to Com-Pat, which was short for Computerized Compatibility.
In 1955, Annie Easley was a computer scientist. She was initially given the task of handling computations for researchers by analyzing and calculating problems by hand.
Soon she adapted herself to computer languages and became a programmer after which she developed the code which is used in researching energy-conversion systems.
It is interesting to note that Easly did all of this before she got any formal education. Throughout her life, Easly took up many schools tutoring programs to inspire women and other students from minority sections to take up careers in technology and coding.
It can be said that today, the world of coding for women is much more accessible. However, it is thanks to the efforts of these women, and many more, that women have made their place in the technology field and are creating wonders today.
A global survey—conducted in 2021 to determine the gender distribution among software developers—found that only 5% of the 82,000+ respondents were women.
It is interesting to note that coding, which today is a male-dominated field, began as an ideal career option for women. During the Second World War, women performed computer-related tasks as they could not be drafted to fight in the fields.
Ada Lovelace is regarded as the first computer programmer. She is also considered to be the mother of programming.
One of the main reasons for the fewer number of women in the world of coding is the masculine stereotypes created in society for choosing STEM majors in early school and college education.
Margaret Hamilton, born in 1936, is regarded as the first woman software engineer.
Margaret Hamilton, born in 1936, is regarded as the first woman software engineer. | https://vivacoder.com/women-in-coding |
In the week that Halloween is celebrated, few things scare me as much as the stereotypes generated around women who choose tech professions. I share 5 myths that contribute to a skewed sociocultural narrative and discourage women from taking an interest in these professions – leading to only one in four IT jobs being held by female professionals, Pew Research Center and Gartner reveal.
Myth #1 – “Women are not interested in technology.”
Women do not have an “aversion” to technology. Instead, they have an “aversion” to this area’s sociocultural barriers (prejudice, salary inequality, etc.). Also, from an early age, children are still misled into thinking that there are “feminine” and “masculine” professions, in which rockets, video games, science kits, and technological gadgets are often more part of the boys’ imagination. It is urgent to change this narrative and encourage girls to get to know the technological universe and the inspiring female figures that history has: Ada Lovelace, considered the first woman programmer; Grace Hopper, the creator of COBOL – COmmon Business Oriented Language; Hedy Lamarr, the woman who 80 years ago patented the technology for Wi-Fi; Katherine Johnson, known as the “human computer” at NASA for her extraordinary contributions; or Radia Joy Perlman, responsible for the creation of Spanning Tree Protocol (STP), fundamental to operate in networks.
Myth #2 – “You need to know math and code to have a tech career.”
Sure, many women have academic backgrounds and bright careers in fields like Computer Science, Computer Engineering, Information Systems, and others. But the possibilities outside of math and hand-coding are immense – I, for example, have a BS in Biology and an MS in Computer Science. Today, I’m a Software Developer working at a technology company pioneering intelligent automatic software modeling and generation! Talking about technology and digitalization-driven innovation is today talking about many professions in fields such as People Management, Project and Product Management, UX/UI Design, Marketing and Sales, Customer Experience, and Data Science. Professions need not only technical hard skills but also behavioral and human soft skills, such as creativity, abstract thinking, adaptability, and agility in ever-changing contexts. In short: a technology career comprises a very wide range of skills.
Myth #3 – “Women like to leave the more technical and complex issues to men.”
The truth is that women still feel insecure in primarily male environments. And they often choose silence during a discussion or team meeting. But they still have something to add or say on the subject, be it more or less technical. It may mean they have much to contribute but are afraid of being interrupted, criticized, corrected, or belittled by their male peers. Studies such as Yoctoo’s point to situations of maintaining (interruptions by men), mansplaining (obvious explanations from a man to a woman), bioprinting (when a man takes credit for a woman’s ideas), and psychological and moral harassment as the main prejudices suffered by women in the technology workplace. On the other hand, when women speak out openly, boldly, or achieve leadership positions, they are often called ambitious, arrogant, or “bossy” by their colleagues. Therefore, finding a balance where everyone can ask for, give and receive feedback with empathy and true team spirit is crucial.
Myth #4 – “Younger people are the ones with a future in technology.”
There is always time to (re)start anything. How many professionals today have professions that did not exist when they chose their path in higher education? How many have decided to embrace other challenges and completely change their career by discovering new possibilities enabled by technological developments? How many women choose to take a career break to dedicate themselves to their families and then return, later and in force, to the labor market to work in a completely different field? The truth is that not all of us need to start liking IT at a young age and do our first experiments in the garage of our parents’ house like Steve Jobs and Steve Wozniak. The passion for technology is only sometimes portrayed in the movies. It can come in many forms… and at any age.
Myth #5 – “Motherhood hurts women’s work performance.”
In my ideal world, mother and father should take care of their children and take advantage of the flexibility brought by the Work-Life Balance trends and the new hybrid/remote work models to ensure more quality family time. But supposing that one of the parents has more significant work constraints and the other has more availability, and this other parent happens to be the woman, the question that arises is: how does being a mother affect the professional contribution of women? The values, qualities, and skills applied in raising a child (or two, as is my case) are assets to any organization, regardless of its area of activity – conflict resolution skills, storytelling, critical thinking, negotiation, empathy, creativity, resilience, multi-tasking… Just think that many of these “requirements” appear in the job ads we see every day. Being a mother is one of the most significant tests of overcoming and high performance that I know of, and organizations that still need to understand this are losing talent.
Promoting women’s training and technological empowerment cannot be merely a matter of filling quotas in educational institutions or the labor market. Instead, it is about fostering the different interests and vocations of young people, regardless of their gender, whether through extracurricular activities and training, museum visits, robotics competitions, or computer clubs. With the support of teachers, mentors, and other allies who are aware that it is by adding various points of view, different talents, experiences, and male and female perspectives (and not excluding unfounded prejudices) that value, productivity, creativity, agility, and innovation are generated.
By demolishing these and other myths one by one, we will continue to move towards that increasingly inclusive future in schools, universities, and organizations. That future where a woman can choose any technological career without being an exception or a minority in the statistics.
*This article was originally published in Mais Superior. | https://quidgest.com/en/blog-en/5-myths-that-keep-women-away-from-technology/ |
First General-Purpose Automated Digital Computer Charles Babbage 1791-1871 Charles Babbage Analytical Engine Charles Babbage, its father. • Analytical Engine • It was never completed by Babbage, due to a lack of standardized parts. • English mathematician • Frustrated genius • One of the most interesting characters in the history of computers.
Analytical Engine CPU Central Processing Unit Primary Storage 1,000 50 –digit numbers ALU < > = + - Control Unit Analytical Engine Input Cards Output Cards Secondary Storage Data on Cards
Ada Lovelace • Augusta Ada Byron, Lady of Lovelace, Dec 15, 1815 • Born to Anna Isabella Milbanke and George Gordon Noel Byron • Ada was privately home schooled in mathematics and science • Died November 27, 1852at the age of 36 in London, England • She was bled to death by her physicians, who were trying to treat her uterine cancer https://computersciencepre-ap1.wikispaces.com/file/view/Augusta+Ada+Byron,+Lady+of+Lovelace.ppt
What’s their invention? • She is known as the first programmer, because she wrote a description of Charles Babbage’s early mechanical general-purpose computer, the analytical engine • Ada’s Bernoulli calculation program for specialized calculus operations achieves correct values in today’s computers
What technological Advances/Developments came about because of their invention? • The computer language Ada, created by the U.S. Defense Department, was named after Lovelace. The reference manual for the language was approved on December 10, 1980, Ada's birthday, and the Department of Defense Military Standard for the language, "MIL-STD-1815" was given the number of the year of her birth
Did someone help with the invention or who used the innovation process to enhance this development? • Ada wrote a program for the Analytical Engine on her own, but she heard a lecture about the difference engine designed by Charles Babbage • Ada was inspired her to write her own program based on his lecture
ComputationalLinguistics INTroduction Lecture 1 Computers and Language http://staff.um.edu.mt/mros1/lin2160/
Noam Chomsky • Noam Chomsky’s work in the 1950s radically changed linguistics, making syntax central. • Chomsky has been the dominant figure in linguistics ever since. • Chomsky invented the generative approach to grammar. • Basis of context-free grammars can you study in CS CLINT - Lecture 1
By: Joyce Blasingame Teacher Mathematician Computer Scientist Inventor Systems Designer Software Programmer Marketing Whiz Military Leader Grace Hopper http://www.slideshare.net/Elaine1975/grace-hopper-14275961
Grace Brewster Murray Hopper • December 9, 1906 – January 1, 1992 • Married in 1930 • Husband died in 1945 • 1928 BA from Vassar College • 1930 MA from Yale University • 1934 PhD from Yale University
Admiral Hopper • 1943 United States Naval Reserve • 1946 Harvard’s Computation Laboratory • 1949 Senior Mathematician at Eckert-Mauchly Computer Corporation • 1955 Sperry Corporation • 1967 Leader in the NDAC • 1986 Retired from Navy with rank Rear Admiral, Senior Consultant to DEC
Compiler • Grace’s biggest contribution to computing was the invention of the compiler. • In 1952 the A-0 Compiler was completed.
Alonzo Church • June 14, 1903 – August 11, 1995 • American mathematician and logician • Made major contributions to: • Mathematical logic and the • Foundations of theoretical computer science web.eng.fiu.edu/~arellano/1002/Computers/Presentation1.ppt
Alonzo Church • He is best known for the lambda calculus, • is a formal system for function definition, function application and recursion • smallest universal programming language of the World • It is equivalent to Turing machines. However, it emphasizes the use of transformation rules and does not care about the actual machine implementing them • Underlies LISP, ML, etc. • Church–Turing thesis, • Frege–Church ontology, and the • Church–Rosser theorem.
Alonzo Church: Mathematician. Philosopher. Computer Scientist? Alonzo Church is a mathematician and philosopher who developed the very first computer programming language known as Lambda Calculus. Church also worked with Alan Turing in the Church-Turing Thesis, which also was another huge impact on the world of computer science. “He was a pioneer in the field of mathematical logic and the theory of computation” -Alan Turing • LAMBDA CALCULUS • Lambda (λ) Calculus is a system that is in the world of math logic and computer science for creating a computation by way of combining variables using abstraction. Today, λ Calculus has applications in several different areas: mathematics, philosophy, linguistics, and computer science. λ Calculus, along with Alan Turing’s Turing machine are important models in computation. • EX: Start with the function: 2x • Rewritten in Lambda as λx[2x] • Now solve this when x=3. • λx[2x](3) • [2x](3) • [2(3)] • = 6 ACCOMPLISHMENTS Church died in 1995 being a well decorated man in the math and computer science world. He earned a Ph.D. from Princeton University. His contributions to number theory and the theories of algorithms and computation laid a solid foundation to computer science. CHURCH TURING THESIS The Church-Turing thesis states that any real-world computation can be written into an equivalent computation involving a Turing Machine. wiki.western.edu/mcis/images/3/3f/Alonzo_Church_draft1.ppt
Tim Berners Lee By Jack Neus socialstudiesorange.pbworks.com/f/Tim+Berners+Lee.ppt
What did he do? • He invented the World Wide Web, which linked hypertext with TCP and DNS. • He invented W3 while working in CERN, a physics lab in Switzerland. • Hypertext is the idea of jumping from one document to another. A web page is a document too. • TCP and DNS were the early versions of WWW. That was what was used to create the first email.
Who was he? • Tim Berners Lee was born on June 8, 1955. • Tim Berners Lee graduated from Oxford University. • Tim Berners Lee was 35 in 1989, when he first created the world wide web. • Tim Berners Lee lives in London, England. • Tim Berners Lee is now the president of W3C.
Company Statistics • Tim Berners Lee founded W3C, otherwise known as the WWW Consortium. • The company is private. You cannot buy shares of it. • The company was founded in 1994. • The business was a first of its kind, finally introducing things like web pages.
http://www.cs.armstrong.edu/greenlaw/presentations/TenScientists.ppthttp://www.cs.armstrong.edu/greenlaw/presentations/TenScientists.ppt Ten Interesting Computer Scientists Dr. Raymond Greenlaw Armstrong Atlantic State University School of Computing
History of Computer Science • 1673 – Gottfried Wilhelm von Leibniz invents a machine to do multiplication • 1821 – Charles Babbage builds a machine to calculate exponential functions, begins designing Analytical Engine • 1832 – Ada Lovelace begins writing programs (on punch cards) for the nonexistent Analytical Engine, inventing such concepts as loops and subroutines • 1935 – Alan Turing defines a model for computation
History of Computer Science • 1937 – Claude Shannon links Boolean logic to digital circuit design • 1939 – Turing’s work plays a key role in breaking the Germans’ Enigma code machine • 1943 – Small computers are being built in multiple countries • 1950 – Turing proposes a test of machine intelligence, the Turing test • 1956 – John McCarthy coins the term “artificial intelligence”
History of Computer Science • 1957 – FORTRAN is released by John Backus and the IBM team • 1958 – John McCarthy invents Lisp • 1959 – John Backus and Peter Naur propose the use of context-free grammars to describe programming languages • 1961 – Edsger Dijkstra applies the semaphore principle used in train signaling systems to mutual exclusion in computer operations
History of Computer Science • 1962 – Donald Knuth begins work on The Art of Computer Programming • 1971 – Alan Kay develops the first object-oriented programming language, Smalltalk • 1971 – Stephen Cook publishes a paper on non-deterministic polynomial completeness (NP-completeness), defining a new family of problems that is not computable in a practical sense
History of Computer Science • 1973 – Leonid Levin publishes a paper identifying the class of NP-complete problems independently of Cook (research was conducted in 1971) • 1977 – Leslie Lamport defines a model of time for distributed systems based on a partial order of events • 1980 – Microsoft is founded, helping to push PCs into widespread use with the public
John Backus “We simply made up the language as we went along. We did not regard language design as a difficult problem, merely a simple prelude to the real problem: designing a compiler which could produce efficient programs...”
Biography - John Backus • 1949 – Graduated from Columbia University with a B.S. in Mathematics • 1950 – Joined IBM and worked on the SSEC (Selective Sequence Electronic Calculator) for three years • Collaborated with Peter Naur to create Backus-Naur Form • Developed FP which helped push functional programming • Retired in 1991
Achievements - John Backus • Designer of FORTRAN • Backus-Naur Form • Designed FP, a functional programming language • 1977 – Turing Award winner • 1987 – named an IBM Fellow • 1993 – awarded a Draper Prize
Trivia - John Backus • Has a plate in his head of his own design after having a bone tumor • Roughly half the work of designing FORTRAN went into generating efficient machine code • After retiring in 1991, has completely withdrawn from computer science • Practices meditation
Edsger Dijkstra "Computer Science is no more about computers than astronomy is about telescopes." | https://fr.slideserve.com/mcelligott/history-of-computing-founders-re-pls-powerpoint-ppt-presentation |
The birthplace of legendary composer Wolfgang Amadeus Mozart, the beautiful and enchanting city of Salzburg is a treasure-trove of architectural delights — not least the fortress of Hohensalzburg, one of the largest medieval fortresses in Europe. With stunning Baroque architecture throughout the city, Salzburg has so much to offer guests and Bus2alps has paired it with other great European cities, such as Florence, Budapest, and Vienna.
Budapest, Vienna & Salzburg
Florence 2 Budapest, Vienna & Salzburg
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Get off the beaten path and check out the Eastern European hotspot of Budapest, moving onto Vienna before ending in Salzburg.
Budapest, Vienna & Salzburg
Budapest, Vienna & Salzburg – Meet Us There
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These three cities are a winter wonderland, perfect to explore at the beginning of your semester abroad. | https://bus2alps.com/tour-destination/salzburg/ |
Salzburg is the fourth-largest city in Austria and is also the name of the regional capital of the province of Salzburg. The town was re-established as Bishopric city on the ruins of the old Roman town of Iuvavum. It came into wealth by mining and trading salt, and much of its architectural splendour as a home of regents is accredited to the work of Wolf Dietrich and his successors. The regency of Salzburg's Prince-Archbishops lasted more than a thousand years. Salzburg's old town is now protected by its status as a UNESCO world heritage site and boasts a long history of cultural tradition. Today the city is home to over 150,000 inhabitants. Wolfgang Amadeus Mozart, the Salzburg Festival and ?The Sound of Music' are just 3 reasons for Salzburg's world fame as a city of music and culture. The baroque city exudes a special kind of magic that even makes working here and attending meetings an enchanting experience.
Salzburg is much more than the City of Mozart and home of the Salzburg Festival. At the most important tourist attractions, not only are you able to experience Salzburg's rich history, but there are also countless fascinating insights and surprising moments around practically every corner. Hohensalzburg Fortress, the Mozart museums, the Getreidegasse and Hellbrunn Palace are among Salzburg's most popular attractions. A visit to the Top 10 provides an ideal overview of this UNESCO World Heritage-listed city.
Hohensalzburg Fortress: Hohensalzburg Fortress is enthroned on the Festungsberg, high above the rooftops of the Baroque historical district. The biggest fully preserved castle in Central Europe, this emblem of Salzburg draws millions of tourists every year.
Mozart's Birthplace: W.A. Mozart was born in 1756 in the "Hagenauer Haus” at No. 9 Getreidegasse in Salzburg. Today, Mozart's Birthplace is one of the most visited museums in Austria and is an absolute highlight, above all for Mozart fans.
Mirabell Palace and Gardens: Mirabell Palace was built in 1606 by prince-archbishop Wolf Dietrich for his beloved Salome Alt. Today, it serves as the backdrop for the most romantic weddings you could possibly imagine.
Getreidegasse: The Getreidegasse is the bustling heart of Salzburg's Old City, its unmistakable charm as well as Mozart's Birthplace making it an irresistible destination for countless visitors from around the world. Aside from an array of international fashion chains, the Getreidegasse also charms passers-by with its traditional inns and unique businesses steeped in history.
Hellbrunn Palace & Trick Fountains: For more than 400 years, Hellbrunn Palace has enchanted and amazed its visitors with its trick fountains. A unique experience with all kinds of surprises in store!
Museum of Natural History and Technology: Giant dinosaurs from prehistoric times come together at the Haus der Natur with milestones of space travel, diverse underwater worlds and reptiles from the most distant corners of the globe. The journey into the human body is guaranteed to astonish you, as will the interactive experiments in the Science Center.
Museum of Modern Art Salzburg Mönchsberg: The Museum der Moderne is located on the Mönchsberg, high above the rooftops of Salzburg's Old City. On a total of four levels, international art treasures from the 20th and 21st centuries are presented in a stylish setting.
DomQuartier Salzburg: The DomQuartier is a unique cultural highlight in the heart of Salzburg City. In the magnificent state rooms, history comes alive, while a museum tour also allows you to enjoy imposing views of the city itself.
Salzburg Museum | Neue Residenz: The Salzburg Museum has garnered numerous awards, an institution with its own unique character housed within the magnificently restored Neue Residenz. Aside from aesthetic presentations and valuable art objects, a number of multimedia installations also invite visitors to marvel and learn.
Salzburg Zoo: From exotic lions to the domestic lynx: Salzburg Zoo captivates visitors, big and small, with its wealth of animal species. An ideal excursion destination in the south of Salzburg City. | https://eca2019.com/en/ABOUT-SALZBURG.html |
Austrian writer Hugo von Hofmannsthal once called Salzburg the heart of the heart of Europe. Centrally located in mainland Europe, Salzburg is easily accessible by air, train or car – Salzburg lies at the heart of Austria and is always easy to reach.
Once you have arrived in this enchanting convention city, you will find that everything you need is within easy reach you need walking: Salzburg Congress is situated right in the centre of the city of Mozart, you will find shopping, entertainment and world class hotels right on your doorstep.
Arriving by Air
Salzburg’s W. A. Mozart Airport is located only four kilometers from the city center, a fifteen minute journey by taxi or bus. Used by many international airlines and low-cost carriers, Salzburg is directly accessible from cities such as Berlin, Düsseldorf, Hannover, Hamburg, Cologne/Bonn, Frankfurt, Leipzig-Halle, Amsterdam, Vienna, Paris, London, Manchester, Stockholm, and Zurich.
As well as its own airport, Salzburg is also connected to Munich Airport by shuttle bus.
Regular ÖBB railjet train service straight from Vienna Airport to Salzburg main station.
Since December 2015 ÖBB Intercity and railjet trains have been providing a direct daytime service twice an hour from Vienna International Airport via Vienna main station - straight to Salzburg main station.
The scheduled journey time form Vienna International Airport to Salzburg main station is 2 hours and 49 minutes.
In total, Austrian Federal Railways (ÖBB) offers 26 ÖBB railjet services and 25 ÖBB Intercity train connections between Vienna International Airport and Salzburg main station.
Links
ÖBB journey planning & Ticketing
Air to rail 2016
Arrivals / Departures at Vienna International Airport
Airport map
For a complete information service for rail travel to, from and within Austria, and to view the current service schedules click here.
More info about arrival to Strasbourg by plane available here
Arriving by Train
Salzburg Train Station is a 5 minutes' walk from Salzburg Congress. Being close to the German border means that, Salzburg has outstanding Eurocity, Intercity and ICE connections to cities across Europe. You can also catch a local or suburban train to Salzburg from most towns in the region.
More info available here.
Car and Public Transport
Salzburg is at the centre of the European highway network: the A1 Vienna-Salzburg, the A8 Munich–Salzburg and the A10 Villach–Salzburg all converge in Salzburg. Please remember to purchase a toll sticker if you are driving to Salzburg.
From nearby Salzburg Train Station, you can catch a local train or suburban train to most towns in the region, or a trolley or regional bus to more local destinations.
Click here for more info about car arrivals.
Click here for more info about public transportation. | http://www.esdr2017.org/esdr-2017/transportation |
Hello everyone, welcome to my new post. I hope that you have found some good way to refresh yourself because these heat can be sometimes very hard for health. Last week, I promised you that I will write you my impressions of a city of good music and even better chocolate! Of course, it’s a joke as you know Salzburg is the city where the music virtuoso Mozart was born. Music genius who learned the music notes first than letters, the person who was known in the world because of his great talent… If you looking for the right description, this is for you: “Salzburg is a city of open heart and good music!”
When I received a invitation from the Salzburg Tourism Board, I couldn’t believe that I had the opportunity to show on my blog one of the most famous cities of culture in Europe such as Salzburg. It was a great honour to me and with great pleasure I accepted the invitation and headed immediately to explore all beauties of this charming city in Austria.
Salzburg is the fourth largest city in Austria, located in the central part of the country. Salzburg is the administrative, economic, cultural and social centre of the Salzburg region of the same name, which makes it a special city district. It is the most famous city in Europe that still has a preserved Baroque style in the very heart of the city. Therefore, only the heart of the city centre is listed on the UNESCO cultural heritage list.
Due to the proximity of the Alps and the famous winter centres, Salzburg got a special second name – “The Gate of the Alps”. All of this together makes Salzburg an important tourist destination not only in Austria, but also in Europe and world as well.
How was Salzburg got it’s name? There is an interesting legend dating from the Middle Ages when the salt was transported via Salzach River. Since at that time salt represented a very valuable good, it was necessary to pass custom control and customs stations was built on the place of today’s city of Salzburg. Thanks to this, the castle was first built after which a city settlement was finally built. Salzburg means “City of Salt”. Very interesting, isn’t it?
I enjoyed this interesting story of guide while we walked the streets of this beautiful city. What do you think by your estimation, how many people live in the heart of the city? Have you imagined a number? To help you, about 3,000 people live in the centre of Salzburg. I have to admit that I envy on them, Salzburg is a very beautiful city and it’s comfortable, if you want to enjoy walking on foot or with bicycle around the city.
At the end of the first day we pass by the most famous building in Salzburg – Mozart’s Birthplace.
A yellow color building with beautiful white windows, a place where the 18th century music genius was born – Volfgang Amadeus Mozart. The man who conquered the world with his music, he was loved and with his wife Constance he had two sons. Mozart also had a sister Maria Anna who was also very talented and gifted, but she remained in the shadow of her brother. Mozart was a golden child, a miracle which they all expected to happen.
Their father who left his violinist career to teach his two children and practicing musical compositions, until Mozart wrote his first composition when he had only 5 years. Sister Anna was there to support him and follow him on his tours. Mozart died very young, under unclear circumstances in his 35th year in Vienna. The people of Salzburg are very proud that the world recognize Salzburg for such a genius as Mozart.
After this interesting story which was about musical genius, it’s time to know more about a man, who is something similar but in another different world of art and fashion – yes, about me! Of course, it’s a joke and I’m far from it, but who knows maybe I succeed as Mozart with a lot of work and effort, my name will be mentioned at least in a booklet how to start your blog! ?
The first day in Salzburg was come to an end, it was time for dinner, so my photographer and I decided to make a well-deserved break and we go to grab something nice to eat.
Salzburg is perhaps a small town, but believe me nothing is behind the bigger capitals in Europe. In the main street you will find all the most famous world fashion brands. Nice restaurant, wonderful view it will be enough to enjoy in the beauties of the city like Salzburg. You can buy one pack of original Mozart chocolates and you will be very happy, it’s much better than buying of expensive shoes but you will feel much better! I will write you in the next post about famous Austrian Folkwear, I’m sure you will love it!
The sun slowly descended behind the mountains, the lights of the shops were the new light of the city, the young couples in love decided to take over the city! ? In addition to the epithet of good music and even better candies, I will add another one – THE CITY OF LOVE.
Oh yes, Salzburg is a city where you can find everything you need and is not far away, if you are living in Europe, Austria is quite near and you must visit this wonderful city.
I wish Salzburg a good night and scheduled a meeting for tomorrow. Meeting with the city in which you are currently located may be quite interesting, irrespective of whether it is a well-known capital or city in which you live, something interesting can happen to you. Try it, you will not make a mistake! I’m currently negotiating with Belgrade where we will hang out a little tomorrow. ?
New Day, New Challenges! I went out of the hotel and I remembered that I did not take a photo of beautiful corner of the street in the centre of the city and immediately I went there to get the best photo, for the good picture the best light is a natural light of the morning sun.
Yes, I think that’s it! The perfect shot! A married couple (we see the wedding rings after! :D) and another tourist who wants to take a piece of this architectural paradise in their online library. Yes, it’s the 21st century where phones have taken their place, who knows why that is good…
My dear ones we have come to the end of this post, time just flies so fast when you are having a good time! Don’t worry in a couple of days I will publish a new post where we will continue together to enjoy the charms of beautiful Salzburg. I will try to leave you now for a moment just because you maybe would like more to enjoy in the beautiful view on the last photo of the post!
How do you like this story about Salzburg? I would like to hear your opinion! If you have a question, comment, suggestion or message for me, you can write me down in the comments. Of course, as always you can contact me via mail or social networks, you can find on the CONTACT page.
As I promised we’ll see again in a couple of days, so if something new and interesting happens to me, I promise, I will write to you!
Best,
Mr.M
The post is sponsored by the Salzburg Tourism Board. For these beautiful photos I used the Sony Alpha 7r camera. | https://mrm-style.com/en/i-love-salzburg-because/ |
Impressions from a Semester at the University of Salzburg2 min read
Two graduate students of the American University of Armenia (AUA) Political Science and International Affairs (PSIA) program spent their Fall semester at the Paris Lodron University of Salzburg, Austria, as Erasmus+ exchange students. Liana Simonyan (PSIA ’20) and Alvina Saakyan (PSIA ’20) returned to Armenia full of enthusiasm and determination to achieve their educational goals.
Comparing their experience at AUA and the Paris Lodron University of Salzburg, the students have observed no major differences between the educational systems of the two universities. However, as Simonyan noted, the teaching methodology of many courses differed in several aspects: “At the Paris Lodron University of Salzburg, the classes concentrated more on reading materials, while at AUA our professors encourage us to think more broadly and explore concepts and themes beyond those related to specific readings. Also, in Salzburg, more emphasis was put on the methodology and the research design of the articles that we examined, which helped me to improve my research skills a great deal.”
Simonyan and Saakyan were impressed by the enchanting city of Salzburg and its friendly and hospitable people. The students had the opportunity to explore the local culture, compare the worldviews of individuals from different places, and get a better insight into international relations. They also made new friends from other countries and established new connections. Their Erasmus+ mobility experience fully met their expectations.
“I obtained a number of useful skills, such as planning, organizational, and time management skills. I also improved my communication skills, self-confidence, and most importantly, my proficiency in English leveled up. These mobility programs are important, as you go out of your comfort zone and become a more confident individual, who comes back being more certain of what he or she wants and ready to accept different challenges,” remarked Simonyan.
Founded in 1991, the American University of Armenia (AUA) is a private, independent university located in Yerevan, Armenia, affiliated with the University of California, and accredited by the WASC Senior College and University Commission in the United States. AUA provides local and international students with Western-style education through top-quality undergraduate, graduate, and certificate programs, promotes research and innovation, encourages civic engagement and community service, and fosters democratic values. | https://newsroom.aua.am/2020/02/21/semester-university-salzburg/ |
Amid the flickering candles and ornate ceiling of the Baroque Hall at St Peter’s Abbey, the programme implores us to ‘be a guest of Wolfgang Amadeus Mozart’.
A high note in kitsch? Absolutely – but when you’re being poured a glass of riesling before a three-course dinner interspersed with hits from Don Giovanni, The Magic Flute and The Marriage Of Figaro, all sung by up-and-coming opera stars, it’s hard not to be seduced.
Especially when you’ve spent most of the day on the Mozart trail: hearing about his early life in an apartment above Salzburg’s main shopping street and visiting his residence on the other side of the River Salzach.
Wolf pack: Salzburg is one of the prettiest cities in Austria – and the whole of Europe
It’s fair to say that if you don’t care for Mozart, the Austrian city of Salzburg might be of little interest. He is everywhere — outside shops as a cardboard cut-out, on posters advertising piano recitals and, of course, staring imperiously out of the massive statue erected in his honour in Mozart Square.
The big ticket here is the annual summer festival that reaches a crescendo at the end of August.
We arrive shortly after this jamboree, which means we practically have St Peter’s to ourselves and don’t have to queue for the funicular that whisks tourists up to the castle above the city.
We could walk, but our excuse is that my 87-year-old father-in-law is with us and he might find it a stretch. But this city is wonderful for someone of his age. One square leads into the next, and everything but the castle is on the flat.
Salzburg is organised, clean and a lot more manageable than I’d thought.
Only 150,000 people live here, but more than 7 million look in for a few days, many of them (my wife Joanna included) because The Sound Of Music, shot here, is their favourite film.
As we reach Mirabell Palace, Joanna breaks into Do-Re-Mi; when we cross Residenz Square, she hums I Have Confidence; outside the riding school from where the von Trapp family escape, she sings Edelweiss.
Hear the music: Salzburg was the birthplace of Wolfgang Amadeus Mozart in 1756
It gets tricky when we have dinner at Gasthof Goldgasse, a minute’s walk from the cathedral and Joanna sees a man in lederhosen and one of those jackets with trimmed lapels that look pretentious worn anywhere outside Austria or Germany.
‘Christopher Plummer was my ideal man,’ she says. ‘I wish you would dress more like that.’ Thankfully, our menus arrive and the subject is dropped.
This is a charming restaurant, packed with locals.
Austrian cuisine is not over elaborate. My wienerschnitzel comes with just boiled potatoes and creamy cucumber, but I wolf it down with gusto.
We opt to stay just out of town, at a hotel called Schloss Fuschl, perched above Lake Fuschl. The castle dates back to the 15th century and the view from the restaurant, across the lake, is so enchanting that I expect Joanna to break into Climb Every Mountain at breakfast.
The hotel has a deck with steps down to the lake. And my father in law has his first experience of a whirlpool bath in the spa but doesn’t quite see the point of simmering in bubbles.
But we do all agree that Salzburg is ideal for a short break and, for those with even the slightest ear for music, it’s close to perfect. | https://expressdigest.com/on-the-trail-of-mozart-in-splendid-salzburg/ |
To most Americans who grew up in the 1960s, the city of Salzburg in Austria will always be etched in their minds as the place where the beloved movie The Sound of Music, from 1965, starring Julie Andrews and Christopher Plummer, took place and was filmed. Who can forget the beautiful travelogue of Salzburg splashed on the screen as Maria, the governess, and the six children tour the city when singing “Do-Re-Mi” wearing costumes Maria made by hand from drapes?
Even with that great reputation, there are so many other things to see and do in the enchanting, compact city of Salzburg.
Salzburg’s historic city center was added to the UNESCO World Heritage list in 1996, and it has beautifully preserved baroque architecture. The city boasts 23 churches and three universities. It is the birthplace of composer Wolfgang Mozart, and the city celebrates his talents and history in many ways.
Things To Do In Salzburg
Salzburg has an abundance of culture, art, music, and history to pack into a weekend.
Mirabell Palace And Gardens
Long known as one of the most spectacular formal gardens in Austria, the Mirabell Palace and Gardens should be on the top of your must-visit list. The palace was built in 1606 and borders the Salzach River near the medieval city walls. The Salzburg Palace Concerts are scheduled in the opulent Marble Hall. The symmetrically designed gardens created in 1687 have four groups of mythology-themed statues sculpted by an Italian artist. Scenes from The Sound of Music were shot in the gardens.
Mozart’s Residence
Mozart spent his formative years in this house. Unfortunately, it was destroyed during WWII, but it was faithfully reconstructed and is now a museum. The museum relates how the family lived and reflects their daily routines.
Salzburg Cathedral
The Salzburg Cathedral is a baroque-style wonder on a square alongside St Peter’s Abbey and the Salzburg Residenz. Founded in 774, the Salzburg Cathedral has been destroyed and rebuilt a number of times. The latest structure was constructed in 1811 in the distinctive baroque style. Inside the cathedral are illustrious frescoes and a grand organ.
Toy Museum
Definitely not for kids only, the Toy Museum is a fun and fascinating look into antique toys. Divided into two sections, the museum part displays old and vintage toys and games, and the “play” part lets you unleash your inner child by participating in interactive games. There’s also a children’s library and screening room with films for the youngsters. The museum has special themed and seasonal activities and games.
DomQuartier Museum
The DomQuartier Museum combines five small museums that explore the baroque roots of Salzburg. The museums include the St. Peters Museum, the Cathedral Museum, the Residenz, and Residenzgalerie, which, together, display and tell the rich history of the city.
Hangar 7
If you want to advance to the Salzburg of the 21st century, Hangar 7 will get you caught up. Located near the Salzburg airport, the enormous, glass-enclosed space features exhibitions of motorcycles and Formula 1 cars and displays of spaceships and planes. Since it’s next to the airport, Hangar 7 presents air shows. The Ikarus Concept Restaurant invites chefs from around the globe for a month at a time for guest stints during which they get to cook their most creative dishes. Hangar 7 also has a casual cafe and restaurant, their Mayday and Threesixty Bars — which have glorious views and a wide selection of Champagnes, sparkling wines, and ciders — temporary photo exhibits, and a souvenir boutique.
Sound Of Music Tours
A visit to Salzburg wouldn’t be complete without a Sound of Music Tour. There are a number of ways to experience the magic of the film and the von Trapp family, either in a big tour bus, in a van, by bicycle (just like the film!), or while walking. The tours include the many locations in the film, such as the Schloss Leopoldskron, the family home; Hellbrunn Palace, where many of the singing scenes took place; St. Gilgen on Wolfgangsee Lake (roughly 40 minutes outside the city), where the opening scene was filmed; and finally, Mondsee Basilica, where Maria and the captain get married. There are other Sound of Music-inspired of tours available, and there’s even a Salzburg tour guide who sings songs from the film.
Music, Concerts, And Theater
The city that musicians and composers — from Mozart to Bach to Strauss — thrived in and where they composed their most iconic musical works, Salzburg is truly the capital for classical music. Concert halls and venues are abundant and offer an incredible range of musical performances.
The Mozart Dinner Concert comprises a three-course, candlelit dinner, using historical recipes of the time and updating them, and two opera singers and five musicians dressed in period costumes who perform excerpts from Mozart’s best operas including “The Magic Flute,” “Don Giovanni,” and “The Marriage of Figaro.” The setting is the Baroque Hall at St. Peter Stiftskulinarium, a former monastery.
The Philharmonie Salzburg orchestra features the new generation of musicians fresh from the Mozarteum University. Not only do the promising musicians play treasured classical music; they also perform pieces of contemporary music including the crossover compositions featured in Mozart Goes Jazz. The Philharmonie is also home to the premieres of modern composers.
The Salzburg Festival, now celebrating its centennial year, is the biggest music, opera, and theater festival in Austria and is internationally known. Slated usually for almost a two-week period from mid to the end of July, the festival involves performances at dozens of venues including churches, palaces, cathedrals, concert halls, and universities, plus outdoor venues such as city squares and arenas.
Best Places To Eat In Salzburg
Salzburg is considered the culinary capital of Austria, with a high concentration of sophisticated, Michelin star restaurants, but there are still many casual and homey places plus authentic coffee houses.
Cafe Tomaselli
A true, old world-style cafe that dates back to 1700, Cafe Tomaselli is a Salzburg institution. The cafe serves rich, classic Viennese pastries and strong coffee on silver trays in an interior of rich wood walls and floors, authentic caned chairs, and crystal chandeliers. You may even spot the ghost of Mozart, who frequently visited the cafe.
Restaurant s’Herzl
A traditional style restaurant with the look of an old-fashioned inn, Restaurant s’Herzl serves Austrian specialties such as wiener schnitzel, sausages with sauerkraut, and, for dessert, Kaiserschmarren, pancakes with stewed plums.
Die Weisse
Since 1901, Die Weisse beer garden and restaurant has been a hometown favorite. It’s the oldest brewery in Salzburg for wheat beer, and today they still adhere to the original brewing methods. At the restaurant, they serve hearty dishes such as bratwurst, spinach and cheese dumplings, roasted pork, and apple strudel with whipped cream.
Restaurant Esszimmer
Modern Viennese cuisine at Restaurant Esszimmer takes on the qualities of French haute cuisine along with a Michelin star. Since 2004, chef Andreas Kaiblinger has been bringing his creative flair to Salzburg in a dining room with a sophisticated ambiance.
Cafe Konditorei Furst
Famous for inventing the Mozartkugel, a delicious, chocolate sphere filled with pistachio marzipan and nougat candy, Cafe Konditorei Furst is the quintessential Austrian cafe. The original owner of the cafe and the inventor of the Mozartkugel, which is wrapped in silver foil and named after Mozart, won the gold medal at a Paris food fair. Other specialties include the Furst truffle, made with dark chocolate, vanilla, and coffee; the Salzburger Schilling, with layers of nougat; and the Doppler Kon(Ef)fekt, a chocolate treat made with Champagne, named after Viennese physicist Christian A. Doppler.
Best Hotels In Salzburg
Hotel Sacher
The home of the first Sacher torte, the rich, sinful chocolate cake, is also one of the finest hotels in Salzburg. Hotel Sacher has elegantly decorated suites and rooms range from a spacious 300 square feet for the smallest room to the over-2,000-square-foot presidential suite. All rooms are furnished with antiques and tasteful artworks to match, along with marble bathrooms. Three dining establishments include Zirbelzimmer Restaurant, which dates back to 1866, overlooks the Salzach River, and serves updated classic Austrian dishes; the more informal Sacher Grill, serving their famous Salzburger and a winning wiener schnitzel; and the Cafe Sacher, with incomparable pastries and desserts. The full-service spa includes massages and treatments, a fitness center, and a steam bath and sauna.
Hotel Goldgasse
The award-winning boutique Hotel Goldgasse offers individually decorated rooms at reasonable prices, starting at a little over 100 euros per night. The four-star hotel has a cozy dining room serving fresh, mostly organic products, and guests can enjoy relaxing in their garden. Hotel Goldgasse is a member of the prestigious Small Luxury Hotels of the World.
The Little Guesthouse
In a calm residential area away from the bustling center of Salzburg is The Little Guesthouse. The 11-room guesthouse has en-suite bathrooms in every room, plus a delightful garden with chaise lounges and chairs. The Little Guesthouse has received a 9.5 rating on Booking.com and was awarded the Certificate of Excellence 2019 from TripAdvisor. | https://www.travelawaits.com/2555761/how-to-spend-a-weekend-in-salzburg/ |
Salzburg, the capital of the Austrian province of the same name, is located only a few kilometers from the German border. The city is located on the northern edge of the Alps in the middle of the Salzburg Basin at an altitude of about 420 to 430 meters above sea level. Characteristic for Salzburg are the river Salzach and the city mountains. To the left of the Salzach rise the Festungsberg, Mönchsberg and Rainberg, while on the right bank of the river are the Kapuzinerberg and the somewhat smaller Bürglstein. Also in the Salzburg basin are the Morzger Hügel, the Hellbrunner Berg and the small Grafenhügel. The climate in Salzburg is temperate: summers are relatively mild, winters cold. Characteristic are the high amounts of precipitation compared to other Austrian cities. Strong winds also occur frequently. The location in the Salzburg basin often leads to fog.
Salzburg is the birthplace of composer Wolfgang Amadeus Mozart. The inhabitants are proud of their most famous son, which is why Salzburg bears the epithet "Mozartstadt" and the official name of the airport is "Salzburg Airport W. A. Mozart". Salzburg also has much to offer culture lovers. Every summer, the Salzburg Festival takes place. The old town of Salzburg with its numerous ecclesiastical and secular buildings was designated a UNESCO World Heritage Site in 1996. The Hohensalzburg Fortress is the largest completely preserved castle in Central Europe. Just like Hellbrunn Palace, Mirabell Palace and other castles, it attracts numerous visitors every year. The diverse shopping opportunities leave nothing to be desired. If you visit Salzburg in the winter months, you should visit the Christmas markets. Winter sports enthusiasts will find a variety of opportunities in the surrounding area.
Already in October, winter is ushered in in Salzburg. Temperatures drop to just above freezing. In November, but no later than December, they fall below freezing for the first time. January is considered the coldest month in Salzburg. The cold period continues in February and can extend into March. However, the sub-zero temperatures in the winter months are sometimes interrupted by foehn weather. This causes relatively mild temperatures and long-distance visibility. In the spring months of April and May, the mercury column of the thermometer also climbs in Salzburg: the temperatures in this season are often in the double digits. The summer months of June, July and August are the warmest in Salzburg. In the past, several heat records have been set there. September is still quite mild in Salzburg, while in October you should dress warmer again.
The amount of precipitation in Salzburg is relatively high compared to the rest of Austria, with about 1350 millimeters per year. The prolonged rainfall, which hits the city mainly in the summer months, is notorious among locals and tourists as the "Salzburger Schnürlregen". Its cause lies in Salzburg's location on the northern edge of the Alps: the moist air masses from Central Europe get stuck on the mountains and form rain clouds. This has definite advantages, especially in summer, because a warm morning, a hot afternoon and a sultry eve are often followed by a refreshing thunderstorm in the evening hours. | https://www.travelclimate.net/Climate/Salzburg |
The city and province of Salzburg were ruled by rich (though reasonably powerful) Prince Archbishops independently of Austria. Baroque art was introduced by Prince Archbishop Wolf Dietrich von Raitenau in the early 17th century - therefore, many of Salzburg′s most important Baroque buildings precede those of Vienna for decades (if not a century).
At a time when the Habsburgs in Vienna struggled with Protestants, Turks and Hungarians all at once, Salzburg re-invented itself in Baroque glory still visible in every corner of the city. Note the difference to Vienna: The early Baroque buildings of Salzburg are smaller and often less elaborate; plus, they are usually rather sacral, as Salzburg was essentially a church-state.
It is hard to find anything that is not Baroque in Salzburg - nonetheless, here is a short list of the most important buildings and sites: The Salzburger Dom Cathedral; the gardens of Schloss Mirabell Castle as well as the castle′s marble hall; the Church of the Holy Trinity, the Erhardskirche Church, the church of the Stift St. Peter; the Collegiate Church, the Kajetanerkirche Church, Mülln Parish Church, Markuskirche Church, Schloss Hellbrunn Castle; the Zoo Hellbrunn; the trick fountains of Hellbrunn; the Getreidegasse Lane and the many burgher houses; the Residenz and the Neue Residenz with the Glockenspiel; the Pferdeschwemme horse wells and Schloß Leopoldskron as well as Schloss Klessheim (both are late Baroque/Rococo); the Basilica of Maria Plain. A hidden gem is the Johanneskirchlein just underneath the Capuchin′s monastery, one of my favourite churches in Salzburg.
The noble families that built their fancy "Palais" palaces in Vienna often had even more impressive palaces in the area where they normally lived - where they were the local landlords. Often the main castles are "Baroquinised" versions of previously existing, Medieval buildings. Seriously rich nobility could also afford to build summer palaces or countryside retreats for hunting and other rural leisure. Altogether, Austria is blessed with a rather large number of Baroque palaces and castles all over the place - regardless of where you are, it is always worth to ask for the closest castle.
There are only two that I would like to name here, because both of them are within easy reach from Vienna and particularly impressive: Schlosshof in the Marchfeld area is Austria′s biggest castle on the countryside and was build for - surprise - Prince Eugene of Savoy, a gay Frenchman who turned into a national-hero for being efficient in killing Turks. The castle′s gardens were recently reconstructed to their original Baroque glory. Unfortunately, I haven′t seen them after the reconstruction, I remember Schlosshof only as a slightly run-down, yet extremely charming palace. These days, it is said to be a firework of Baroque art and architecture.
The second site I would like to point out is Laxenburg: Here you can find the Habsburg′s "other" summer retreat (the primary one being Schönbrunn) with a huge, huge garden, three palaces (of which only one is Baroque) and summer palaces of other Austrian top-notch nobility nearby. The palaces are not open to the public (they are usually private property or rented by an educational/research institution), but it is the parks that attract the crowds and will provide deep insights into the joys and delights of being rich in the 18th century: Hunting, ambling, gambling. The parks of Laxenburg must have been a joyful place. | http://tourmycountry.com/austria/baroque3.htm |
Okay, I have to admit we discussed more than what I have written above in our group chat. But it doesn’t matter, we still ended up in Salzburg, Mozart’s birthplace.
I don’t even know why I mentioned it twice.
Anyway, with our A-levels and some freedom it was time to travel!
I went to Austria twice, once to Vienna- the capital.
And this time with Luisa and Sara, two of my closest friends and I would never break the friendship with these guys. Why? – Just because they know already too much about me.
Here is Salzburg in pictures, which marks also unofficially the start of my world travel.
5 days in Salzburg was wonderful, we highly recommend you to visit the fourth largest city in Austria.
There aren’t many pictures, but this lovely city deserves an introduction of mine. This post doesn’t contain important or useful information.
But it does have an immense meaning to me, therefore it can’t be omitted. | https://www.surf-theglobe.com/salzburg/ |
To help policymakers navigate the impact of digitalisation and understand their potential to influence it, Readie has launched a series of explainers, aimed at clarifying important issues in digitalisation. This one focuses on artificial intelligence, the attempt to create machines that can act independently.
Artificial intelligence (AI) describes when computers act independently, in a way that resembles human reasoning.
Most, if not all, current AI systems employ machine learning. Fundamentally, machine learning algorithms are computerised techniques for recognising patterns in data. Unlike basic computer algorithms, machine learning algorithms do not need a person to directly code the decisions they will follow. Instead these systems are able to ‘learn’ from examples, data and experience to create their own set of decisions.
Once the stuff of futuristic films, artificial intelligence is a real life proposition and an area of importance to digital policymaking.
AI is used in business for routine tasks in manufacturing, data processing, and even calculating credit scores. Long term, this will result in fundamental shifts in business, affecting productivity, employment and living standards. AI has the potential to change industries as diverse as translation, customer service, medical diagnosis, and manufacturing.
AI is being employed in government to save time spent on monitoring, documenting and other paperwork, freeing people for the key tasks which uniquely require human reasoning. For example, AI already detects benefit fraud.
As a House of Lords Committee heard, Europe is in a good position to become a leader in research and applications of AI, but competing with players in the US and China. Commentators disagree on whether foreign approaches are a threat or an example to follow, but it is clear that action is necessary to shape the future of this important technology.
The impact of AI is hard to estimate, partially because its applications are so far limited to specific domains, such as playing Go, maintaining aircraft, patient care, or analysing medical images. But the technology is moving fast and it is difficult to predict where it will lead. Overview of the applications within government, by Nesta and Deloitte, hint at the potential for saving time and effort of civil servants, allowing them to focus on creative problem solving.
How AI should be regulated is a contested area not least because the legal definitions are still unclear. Geoff Mulgan, CEO of Nesta, has called for a Machine Intelligence Commission to create wider public trust, understanding and informed decisions as opposed to paranoia.
Because AI research is carried out by many private parties; individual companies or labs might prioritise getting their system to work over ethical concerns. In absence of regulation, AI might be deployed first, with crucial questions being asked later, much like sharing economy applications were, but with potentially more severe consequences.
Even if policymakers decide not to limit AI legally, as some experts demand, this should still be a conscious decision.
Closely linked to regulation, is that AI systems are likely to assume unconscious biases from their creators or the data they are trained on. See Readie's forthcoming explainer on algorithmic accountability and bias.
A debate in expert circles is whether or when AI will surpass human intelligence and what the consequences of this might be with positions ranging from confidence in humanity's ability to control technology to warnings on how AI is uniquely predisposed to escape such control. | https://www.nesta.org.uk/blog/readie-explainer-artificial-intelligence/ |
by Daniel Webster, dWeb.News Publisher
SINGAPORE, Oct. 9, 2021 /PRNewswire/ — The Singapore Tourism Board announced today that vaccinated U.S. and Canadian tourists are now able to visit the island destination once again. With Singapore’s high vaccination rate, the destination is moving to the next step of the safe reopening of the tourism sector by implementing local measures to keep travelers and residents safe, abiding by the requirements on COVID-19 prevention and Singapore public health regulations.
With visitor’s safety being a top priority, Singapore has implemented Safe Travel Lanes to facilitate travel, providing details on testing protocols, vaccination requirements, and other distancing and social regulations. To raise hygiene standards and transform the cleanliness levels of public spaces, the SG Clean campaign was launched in February 2020, which requires tourism establishments to adhere to stringent levels of the SG Clean Quality mark reflecting their commitment and ownership of maintaining high standards of environmental public hygiene at their premises.
“We look forward to safely welcoming back U.S. and Canadian tourists to Singapore, providing the opportunity for travelers to fully explore all that our destination has to offer,” said Rachel Loh, Senior Vice President America, Singapore Tourism Board Americas. “Our enhanced cleaning protocols, contactless amenities, and social distancing measures have been designed to mitigate the risk of spreading COVID-19. “
As part of Singapore’s efforts to reopen borders safely, fully vaccinated U.S. and Canadian travelers looking to make future travel plans can safely enter and depart Singapore via the Vaccinated Travel Lane (VTL) that require:
- For travelers vaccinated in the U.S. or Canada, we currently accept vaccination certificates issued in the SMART Health Card (SHC) format, by issuers in Canada or the U.S. on the Common Trust Network.
- Vaccinated travelers will be required to undergo two COVID-19 PCR tests, including a pre-departure PCR test within 48 hours of their scheduled departure and obtain a negative test result. They must also take a Changi Airport arrival test and remain isolated until the test results are confirmed negative.
- Travelers who are traveling to Singapore under the VTL must travel into Singapore on designated VTL flights.
- Short-term visitors must purchase travel insurance for the entire duration of their stay in Singapore, with a minimum coverage of S$30,000 for COVID-19-related medical treatment and hospitalization costs, prior to travel to Singapore.
- Prior to travel to Singapore, visitors who wish to travel under the VTL will need to apply for a Vaccinated Travel Pass (VTP) seven to 30 days prior to the intended date of entry into Singapore. Applications for the VTP will open on October 12, 2021 for entry into Singapore on or after October 19, 2021.
- More details on the VTL requirements into Singapore can be found at https://safetravel.ica.gov.sg/
For the latest travel updates on Singapore, please visit www.visitsingapore.com and https://safetravel.ica.gov.sg/.
About the Singapore Tourism Board
The Singapore Tourism Board (STB) is the lead development agency for tourism, one of Singapore’s key economic sectors. Together with industry partners and the community, we shape a dynamic Singapore tourism landscape. We bring the Passion Made Possible brand to life by differentiating Singapore as a vibrant destination that inspires people to share and deepen their passions.
www.stb.gov.sg | www.visitsingapore.com
Media Contacts:
Bullfrog + Baum
Andrea Holden + Kate Pressman
[email protected]
Singapore Tourism Board, Americas
Krisna Bharvani
Manager, Marketing, Americas, International Group
Tel: +1 212-302-4861
Email: [email protected]
SOURCE Singapore Tourism Board
For more dWeb.News Business News: https://dweb.news/news-sections/business-news/
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Recruitment process for this position and onboarding trainings are conducted online.
What do you need to start?
5-10 years of outsourcing experience preferably in client facing role;
Experience in one of the areas:
- delivery of customer services to develop, maintain and improve the relationship with the client;
- project and program management;
- Service Management including GxP Compliance
Experience in a wide variety of information technology fields to fully understand the details of the services that can be provided;
Good understanding of the various service level agreements and the performance measures required to manage the agreements and the relationship with the clients;
Excellent customer relations skills to understand client concerns and requirements;
Working with different teams and legal entities
Experience of managing a team onshore and offshore
Understanding of financial management in an outsourcing environment.
Willingness to travel and to work at customer site.
What duties will help you grow?
- Having total overview of all services, spotting risks and adjusting plans and execution in cooperation with the Operations Leads (OPS Lead);
- SDM is accountable for contract revenue, CM% and OTACE on the account, reporting to the overall Delivery Executive of the Global account;
- Identifies further service/project opportunities to grow business & revenue;
- Understands, anticipates and influences customer demand for services and ensures that service delivery organizations are capable to fulfill the demand;
- Client Intimacy;
- Assists with developing solutions that meet client needs and can be delivered in a fashion that allows firm financial targets to be achieved;
- Know where to go within the delivery organization to get issues addressed and resolved;
- Maintains compliance to regulatory obligations and ensures that operations are delivered securely.
General:
- Proactively manages the day-to-day relationship with the client(s)/client representatives to ensure a high levelof satisfaction;
- Becomes a point of escalation for customer issues and for service towers regarding client issues / opportunities/ contractual obligations;
- Works closely with Capgemini legal team on contract items, issues and change requests;
- Works closely with the Ops lead to track project status, issues and issue resolution.
- Sales and Solution knowledge would be preferable as SDM may be asked to participate in customer orals sessions, solution development or governance review stage gates.
- Monitors SLA achievement and CSIP performance to identify negative trends and agree with OPS Lead get-well plans implementation;
- Assess quality of work produced by the teams providing services (reports, project deliverables, etc.) to ensure consistency and accuracy of information;
- Focus is on delivering projects and services according to contract/SLA and target CM%;
- Controls SLA measurement and analysis management to ensure all commitments are met;
- Ensure timely delivery and accuracy of regular (monthly) management reports for client and attends review meetings (if applicable);
- Review’s summary reports on trends, root cause analysis and other reports before they are provided to the client for completeness, contractual requirements, SLA impact and service impacts;
- Provides service performance reporting to Client and Capgemini Management (as required).
- Has a substantial input in the development of contractual schedules and Service Level Agreements in line with the current service line aspirations;
- Develops and maintains close working relationships with representatives of Capgemini in the world and Client;
- Identifies and assists in the perusal of business opportunities within the existing contract with the Client;
- Recognizes commercial opportunities and engages in Commercial negotiation;
For the Global account we are expanding the Infrastructure Services SDM team. The Service Delivery Manager(SDM) is accountable for the contract obligations, delivery, financial agreements (revenue, billing), organic sales opportunities and overall client satisfaction. It is also responsible for cost control, add on project sales at firm contribution margins, customer reference ability, customer satisfaction & managing our services to the terms &conditions of the contract. Acts as single point of contact for the client with regards to Service delivery issues and challenges. Works closely with the assigned OPS Leads and assists with customer escalation.
What have we prepared for you?
Space where you can develop yourself:
- Development programs, external courses, education & certificates co-funding, NEXT platform with free access to Pluralsight, TED talks, Coursera materials, and virtual trainings: e.g. Excel, VBA, RPA or customer care.
- You will have a possibility to join various technical communities.
- Flexible working hours thanks to a variety of projects. Ask your recruiter about possible options.
Our legendary atmosphere:
- We don’t have a rigid dress code, but what we do have are awesome communities and world– changing initiatives like Grant Program. We are a big company with unique atmosphere – we make friendships, share important moments, and simply… like each other!
A lot of benefits:
- Private medical care which can be extended by a package of dental services purchased on preferential terms.
- Private life insurance which can be extended by oncology package purchased on preferential terms.
- Referral bonuses for recommending your friends to Capgemini.
- Access to Inspiro Audiobooks & MyBenefit (cinema tickets, Multisport and more).
- Offices in great locations, car leasing program, carpooling options and bicycle parking.
Who are we?
Capgemini is a global leader in consulting, technology services and digital transformation. Our scope is wide. One of the teams is Data Services – part of business unit called Cloud Infrastructure Services.
Do you want to get to know us better? Watch a video: https://www.youtube.com/watch?v=L49dIpnS3lE
Do you have any additional questions about our job offers? Check our Instagram (@capgeminipl) or visit our Facebook profile (Capgemini Polska). | https://www.capgemini.com/jobs/service-delivery-manager-12/ |
Healing and the Client and Practitioner Relationship
All healing of the human structure begins with a commitment from the client to change – as well as a practitioner who functions as both a facilitator and a teacher. Whether you want to create a healthier lifestyle for yourself, kick a bad habit, or overcome a persistent physical issue, your commitment to change behavior is where successful change begins.
The Behavior Changing Elements
Changing behavior is rarely easy. To begin, it is important to understand the three most essential elements in changing behavior:
- Readiness to change behavior- Engaging a practitioner to guide a lasting change successfully
- Barriers to changing behavior- Identify what is preventing you from changing
- Likelihood of relapse- Recognizing the triggers that will return the former behavior
The US Institute of Medicine’s landmark report, Crossing the Quality Chasm, emphasized healthcare providers should be “respectful of and responsive to individual patient preferences, needs, and values,” and ensure “patient values guide all healthcare decisions.
The Role of the Practitioner Partner
A Healing Practitioner who facilitates patient engagement represents a significant shift from paternalistic models of care in the past in which practitioners tell patients what they should do, to one in which they partner with patients to meet the desired goal. The collaborative partnership is intended to help make better medical decisions, educate patients about how to get healthy and manage conditions, and sustain patient interest in their ongoing care.
Accomplishing a health behavior change must start with the patient. Without a complete commitment and understanding of the care and needed changes, a patient will not be able to effectively improve their health. The practitioner’s role is to inform, educate and recommend an action plan to achieve a positive outcome.
Patients that are not ready to make a health behavior change should consult a Healing Practitioner to:
- Discuss the importance of the change for you
- Discuss the risks of continuing the unhealthy behavior
- Discuss the rewards of adopting healthy behavior
- Identify roadblocks they will encounter to change their behavior
Common examples of health decisions include whether and how to make health behavior changes, when to start and how to get preventive screening, management for acute or chronic conditions, how to prioritize competing health needs, and even when to change or stop treatment.
Countless research studies have shown that incorporating a patient’s goals and motivations into planned behavior change increases the likelihood that a patient will be successful with behavior change. If you are ready to change your behavior and improve your health, engage a Healing Practitioner to help inform, educate and recommend the appropriate action plan.
To learn more about how Healing and the Importance of the Client and Practitioner Relationship visit:
https://bobalonzi-advanced-rolfer.com. | https://bobalonzi-advanced-rolfer.com/healing-and-the-client-and-practitioner-relationship/ |
Meeting areas are simultaneously one of the most desired areas in an office and one of the most unused (something interestingly highlighted in an article by Andrew Mawson in OfficeInsight). This could be in part because conference rooms are mis-designed for their actual use. One interesting consideration for conference rooms is an understanding of how the space affects the posture of the people in it – and how that can influence their behavior.
Andrew Yap, a business researcher with Columbia, has done two significant studies on how posture and body position impacts behavior. Basically, there are two types of positions: open and closed. In an open position, a person is loose, possible even stretched out (such as reaching for objects), while in a close positions, the person’s limbs are kept close to the torso. An open position is clearly a dominant position, and there were measurable and direct effects to the body chemistry of a person (male or female) in that position:
- Increased testosterone levels
- Decreased cortisol levels (a hormone related to stress)
That change in chemistry impacts behavior and attitude, especially for actions that increase risk tolerance. An openness to risk had some negatives (like experiments showing an increased likelihood to cheat and to drive recklessly), but it also had significant positives, such as increasing creative and original ideas, improving mood and productivity, and inspiring a willingness to change.
That actually does have an impact on the design of conference rooms. Yap’s study revealed two things. First, the effects of body position occurred naturally, when the subject was not even aware of the posture, such as creating a task where the person had to reach for objects or where the person was confined. Second, the affects were invisible to the subjects themselves, who rated their own mental state as being unchanged even when both chemical levels and other people’s assessments observed a difference.
So creating a certain environment has a direct and measurable influence even if your employees are never consciously aware of it.
When looking at conference or meeting rooms, it is imperative to realize that the purposes of meetings are different. That means that the design should be different. This impacts everything: the shape of the table, the sizes and numbers of chairs, the open space in the room.
There are three ways of viewing meeting types, depending on the desired interactions: collaborative, persuasive, or adversarial. Each of these has different requirements for designing an ideal conference room.
Collaborative
These are project meetings, brainstorming sessions, types of meetings where people are working together toward a creative goal. These are the situations where everyone should feel equal within the group and powerful. The structure should enforce open postures, to maximize the surge of productivity, creativity, and risk.
- Incorporate white whiteboards, colorful Post-It notes, and brainstorming tools to encourage everyone to lengthen their movements and open their posture.
- Use round tables to enforce a sense of equality.
- Limit tables or chairs to create sufficient working space to allow people to stretch out.
- Use natural lighting and windows to give a sense of space.
- Use comfortable, adjustable chairs.
- Avoid smaller rooms with limited clearance around furniture.
Persuasive
This is a more structured environment where two groups are working toward a common goal, but for different reasons. Think of a consulting firm, where a consultant and client are working jointly on a project. The idea here is to extend a feeling of graciousness and comfort so that the atmosphere is constructive and positive.
It’s not specifically related to conference room design, but Roger Dawson, a business negotiator, tells how a British admiral invited an Argentine admiral aboard ship after the Argentinian loss in the Falklands War. The British admiral hosted a luxurious dinner and thanked the Argentine leader for a “splendid campaign.” A show of graciousness helped the peace negotiations.
That attitude is a mindfulness of the other party that is beneficial in many business situations.
- Have a coffee service or other snacks available to be welcoming and comfortable.
- If possible, use round tables to foster a sense of equality. Otherwise, arrange the seats in a circular way to prevent a hierarchical structure.
- Have an adequate number of power outlets for laptops and other devices so everyone can participate.
- Use larger chairs that encourage open postures while sitting. Make sure that the chairs are adjustable to minimize any disparities in height.
The balance of seating and space is crucial – plan it carefully, using more than the minimum requirements.
Adversarial
It’s an old trope of imperial bosses to have a big chair while employees sit in a much shorter chair or for the boss to have a massive, looming desk. Having a disparity in furniture size creates a perception of power and can be very psychologically effective. However, adversarial conference room arrangements lead to very negative associations, and there are few instances where it is truly appropriate. Most of these elements are really things to be avoided:
- Using oversized furniture in a small room.
- Having too many chairs or too little clearance around chairs.
- Using bold colors in a small space, creating a sense of being confined.
- Using smaller chairs in a conference room, creating a sense of being confined – which can be compounded if participants have different sized chairs.
- Using chairs of a fixed size, rather than adjustable, emphasizing a lack of control.
- Using large, rectangular tables, establishing a strong power structure. | https://www.noobpreneur.com/2014/02/14/positions-power-conference-rooms-revisited/ |
DRAWING ROOM T15
This drawing room design on the transitional design style which is the most common design style preference as far as drawing room is concern. The color is chose to be kept on off white with some black and neutral colors.
Client wants a luxurious and classical design style with finely tufted sofas and seats in it, two ottoman to add more simpler and low space consuming seating in the room.
Further detailing is incorporated through walls and ceiling details, the touch of brass through sleek lines in tables adding the luxurious and desired look to the room.
The detailed and minimal molding on wall and wall scones enhancing the mood of space and making it lavish. | http://interiochic.com/drawing-room-t15/ |
Sleep Deprivation & Cognitive-Function. Alertness Is Only The Beginning:
One of the typical habits many people have is operating based on assumptions.
It’s not always a bad idea, because we each come from a context we’re born into, that teaches us a worldview.
And life is already too complex, so we often need a type of shorthand.
Especially for stored-knowledge that gets handed down over time.
But those ideas can often be wrong at the start, or become obsolete with time.
And some researchers from Michigan State are finding out anyone interested in both Health & Productivity is making a huge mistake in their assumptions about sleep…
Good Sleep Pooh-Poohed By Workaholics, Bosses, Elons:
So for many of us, we just assume that Sleep is an intermittent inconvenience.
It’s something we have to do that gets in the way of the rest of our lives.
This is especially-true for anyone who has an obsessive-attitude about their job.
Honestly, I have no idea how Elon Musk does any of it, especially 80+ hour work-weeks.
Because of this assumption, we often treat sleep with less respect than it deserves and end up with some kind of debt or deficit.
But The Short Answer for the current study is that sleep-debt and deprivation are actually much more serious than we thought,
And can lead to significant, measurable declines in productivity and accuracy in any task that has more than 1 step, or relies on very-short-term memory, often with serious consequences.
Read on to find out the Details…
The Cognitive-Performance Tests You’re Actually Taking Every Day:
So not all of us will volunteer to take a standardized cognitive-aptitude or processing test each day of our lives.
On the other side of that, our key assumption about sleep-debt is that it’s only component is a lack of alertness.
But what if that assumption were wrong?
And what if our daily lives, our daily commutes, and especially our jobs,
However much they consist of memorized-routines,
Are all actually a repeated set of various cognitive performance-tests we all take every day without thinking of them as such?
Wait. Where Was I Going With That Again?:
And that’s where the current-research picks up.
Because several dimensions of your cognitive ability are being impacted by your sleep quality & quantity; -or lack of it.
And they Are being tested on a daily-basis; just ask the passengers on a commuter-train where the engineer fell asleep a mile before the station.
So Kimberly Fenn’s team as MSU got together about 140 subjects.
They participated in an overnight sleep experiment where almost 80 of them stayed up all night,
And about 60 went home and got their normal amount & quality of sleep.
Early at night, several hours before they would have gone to sleep, they all took 2 baseline tests to determine their cognitive abilities.
One was for Reaction-Time. And another was for the ability to complete a multi-step task and whether they could complete it without omitting or repeating any steps.
This test also included interruptions as a way to test the subjects’ short-term working-memory.
Disruption-Junction What Was That Function?:
And the results are pretty-telling.
For the initial-baseline, the place-keeping Error-Rate for subjects on the multi-step task with interruptions was 15%.
The next morning after 1 night of sleep-deprivation, that error-rate doubled to 30% on average.
And since it’s been previously-studied to show that even 1/2 night of sleep-loss can reduce a person’s cognitive-function down to the level of someone with a 0.1% Blood-Alcohol-Level,
It won’t surprise you to find that the Alertness scores got even worse than the place-keeping ones.
Lapses in attention to the test went up by 300% after the MSU subjects lost 1 full night of sleep.
Be Careful! Even Regular Tasks Can Still Have Consequences:
Now even though we all have memorized-things we do throughout the day,
The key takeaway that Dr. Fenn wants people to get is they should not underestimate how impaired their Function is,
Not just their Attention.
If you have a simple-procedure you’ve memorized to do that’s one thing.
But it’s another issue entirely if you have a complex, multi-step procedure to complete where each successive step depends on the previous ones,
And any mistakes could have serious-consequences.
Like a truck-driver trying to navigate bad road-conditions, a doctor completing a medical procedure, or an iron-worker doing very tricky and dangerous engineering assemblies.
There are probably Many systems in the brain running at 1/2 speed, 1/3 speed, or less.
But the assumption we make that sleepiness only means lack of Alertness is wrong and could have serious consequences.
So this means you have to be honest with yourself about how indebted you are to your 8-hour/night obligation,
And be seriously-careful about every single thing you do; especially the important stuff.
But Wait, Sleep Deprivation’s Dangers Get Even More Serious:
Other studies in the past suggest that sleep-debt actually hurts your brain.
For example, one study found that after 3 nights of only 25% of normal sleep,
One quarter of the cells in the brains of test-animals’ alertness-region died and didn’t grow back.
-Even with recovery-sleep allowed afterwards.
This may not be the case with humans, but it’s a sobering stat.
Especially since, the average adult in the western world is estimated to be in at least 12-15% of some kind of sleep-debt.
So you too may be a Zombie!
Even though being allergic to sleep is seen as a badge-of-honor in the business world,
It’s really doing no good for your Brain.
And that study just looked at One region; who knows what it’s doing to all the others, including your memory-center, the Hippocampus.
A Short List Of Sleep-Debt Related Health Problems:
So not only do all-nighters wreck your metabolism,
There are a set of health-problems that come along with chronic sleep-debt.
A short list of them is as follows:
1) Obesity and Reduced Insulin Sensitivity
2) Slower Metabolism
3) Immune Problems
4) Increased Inflammation
5) Higher Chance of Getting Colds & Flu
6) Lower Productivity
7) Increased Stress
8) Lower Work & Education Achievement
9) Impaired Creativity, Cognitive Function, Decision-Making, and Memory
10) Increased Correlation With Anxiety & Depression
11) Increased Correlation With Alzheimer’s & Dementia
and the worst of all:
12) Increased Correlation With Having A Shorter Lifespan
SCIENCE To The Rescue! There Is Something You Can Do About It!:
Sleeping in on weekends has been shown to reduce #12 to the same rate as people who get normal amounts of sleep.
So that’s one more tool at your disposal.
But there’s one that’s even better.
Naps.
In a series of exhaustive tests, Dr. Sara Mednick examined all kinds of cognitive-performance similar to what the MSU team measured.
And what she found is that the best were 90-minute naps, but even shorter ones helped.
They significantly-restored at-least Productivity and Creativity back to the high-level they were at both:
The beginning of the work-day, and also the beginning of the work-week.
As those two metrics tail-off as time passes throughout both frames of reference.
Just Ask Sara Mednick; Naps Have A Fantastic List Of Benefits:
Furthermore, contrary to all the awful stuff chronic-sleep-debt is supposed to wreck about your body and your life,
Check out the awesomeness of all the things Naps improve (that Caffeine only tricks you into thinking it has):
1) Alertness
2) Creativity
3) Stress Levels & Management
4) Productivity
5) Job Satisfaction
6) Stamina
7) Decision-Making Abilities
8) Longevity
9) Weight Loss
10) General Cardiovascular Health
11) Mental Health
12) Memory Of All Types
Social Jet Lag Be Damned! Power Naps Rescue Night-Owls, Productivity:
So there you go!
Another set of assumptions we all work-on, either subconsciously, or begrudgingly,
Busted; when it comes to Sleep.
But as more than one study has shown, there Are things you can do to claw-back at the chronic loss of sleep.
Even something as lowly as a 30 or 60 minute Power-Nap has been shown to be effective!
Just think what would happen if you followed the NSF’s list of healthy sleep recommendations,
Even if you were a Socially-Jetlagged, office-working, early-bird-boss-plagued Night-Owl!
Sleep-deprivation may be terrible for your attention, memory, procedural place-keeping and all kinds of other things, but you can still fight back!
Links: | https://healthtrekker.net/sleep-deprivation-dangers-worse-alertness |
THE BUILDING BLOCKS FOR A GOOD QUALITY OF LIFE
Education, financial stability and health are the building blocks for a good life. Education is essential to getting and keeping a job with a livable wage and health benefits. An income adequate to pay for today’s necessities and save for the future provides families some sense of financial stability. Access to quality health care keeps children on track in school and adults productive at work. Remove any one of these building blocks and the other two topple.
HEALTH
Activating and inspiring our community to get healthy and stay healthy.
Priorities
- Individuals are supported, connected, and engaged to lead healthy lives
- Individuals will have access to needed mental health services
- Unfunded Priority: United Way will advocate on behalf of health issues aligned with selected priorities/strategies
United Way of Central Illinois advances the common good by focusing on protecting services vital to the immediate basic needs of the most vulnerable members of our community; while making long term investments in education, financial stability and health, because these are the building blocks for a good quality of life.
We bring together people and organizations from all across the community who bring the passion, expertise and resources needed to get things done. UWCIL accomplishes this goal by targeting resources to a determined set of priorities that were selected and are continuously reviewed by Vision Councils with the help of the community, requiring consistency in outcome measurement and striving towards community wide shared metrics, and gradually increasing the proportion of funding directed toward BIG community change.
Below is information regarding United Way’s Strategic Investment Plan and Community Priorities for health. The Strategic Investment Plan and related information outline a multi-year funding plan that was developed in partnership with community leaders and service providers which will track community level indicators and the effectiveness of United Way funded programs.
United Way and its partners identified priorities, strategies and aligned outcomes to direct our work. Together, we identified and are working toward key indicators of success. We hold ourselves and our partners accountable to achieving success by using concrete metrics, based on local, state and federal data to measure our progress. We will adjust our programs and approaches as needed to ensure that we are making the most effective use of available resources.
You can learn more about Health priorities and strategies here.
Coming soon... | https://www.uwcil.org/issue-area-health |
The Greater Tampa Chamber of Commerce is reflective of the industries and businesses it serves. As such, we are called to evolve, transform, and innovate to ensure that our priorities and organizational structure are aligned with the evolving needs for our members.
Vision 2026 is the 10-year vision plan, which is comprised of three pillars – Catalyst, Inclusive Organization and HUB for Business – all supported by a foundation of Organizational Excellence. Review the entire 10-year vision plan here.
See our strategic goals for 2017-2019 here. | https://www.tampachamber.com/Your-Chamber/Vision-2026.aspx |
Amendment C94gpla to the Golden Plains Planning Scheme
Amendment C94gpla introduced the Bannockburn Growth Plan into the Golden Plains Planning Scheme. The Amendment was approved by the Minister for Planning and gazetted on 17 September 2021.
To view a copy of the approved amendment documentation, including the Bannockburn Growth Plan, refer to:
- Bannockburn Growth Plan – May 2021 (PDF) (Approved and Gazetted)
- Amendment C94gpla
About the Bannockburn Growth Plan
The Bannockburn Growth Plan (Growth Plan) guides the sustainable growth of Bannockburn to the year 2050. The Growth Plan identifies where and when future housing will be developed. It also identifies what infrastructure is needed to support the growing community, such as roads and community facilities, and land for employment and retail.
VPA Fast Track Program
The Bannockburn Growth Plan and subsequent priority Precinct Structure Plan were identified as a project on the VPA’s Fast Track Program here.
The project used the VPA Projects Standing Advisory Committee (SAC) to consider unresolved matters from public consultation and provide advice to the Minister and the Victorian Planning Authority (VPA) prior to the VPA finalising the a draft amendment for the Minister for Planning’s consideration.
VPA Projects Standing Advisory Committee (SAC) Roundtable
The SAC held a roundtable hearing in March 2021 to consider submissions referred to it by the Minister. The SAC submitted its report on the outcomes and recommendations of the roundtable to the Minister and the VPA on 6 April 2021. For a copy of the report, refer to:
Background information
A growth plan identifies locations for new housing, jobs, infrastructure and services for an urban area. A growth plan:
- guides sustainable growth and development over the long term
- identifies the steps needed to manage growth
- defines key projects and infrastructure required to support growth
- provides a more certain environment for making both public and private investment decisions.
A growth plan is used to guide more detailed local planning work.
Bannockburn is one of the fastest growing towns in regional Victoria. The population is expected to reach more than 13,000 people by 2036, but there’s a shortage of land available to develop for new houses. The growth plan will identify the most appropriate land for houses and ensure the infrastructure is provided to support these new homes.
Bannockburn is the largest town in Golden Plains Shire. The Victorian Government and Council see it as an ideal place to support Golden Plains’ growing population, thanks to its existing infrastructure and amenity.
In addition to identifying land that is suitable for new homes, the Bannockburn Growth Plan will identify land for jobs and ensure land with environmental values is protected. This will ensure that Bannockburn develops in a sustainable way.
The Victorian Planning Authority (VPA) is preparing the Bannockburn Growth Plan with Golden Plains Shire Council (Council). The VPA is a Victorian government body that undertakes strategic planning and coordinates infrastructure for the future growth and transformation of Victoria’s cities and regions. The VPA and Council will work closely with other state government agencies and the community to plan for Bannockburn’s vibrant future.
The Victorian Planning Authority (VPA) is a State Government statutory authority that reports to the Victorian Minister for Planning and acts as the state’s strategic planner.
The VPA’s main task is to make sure Melbourne and Victoria’s regions remain a great places to work and live. This requires vision and long-term planning, to ensure Victorians have equitable access to employment, public transport, attractive public space and affordable housing for our growing population.
The Minister for Planning has appointed the Victorian Planning Authority (VPA) to lead this project from conception through to finalisation. Throughout all steps of the project we will be working in partnership with the council, state government agencies and local community members to ensure the growth plan considers and reflects their input.
The Victorian Planning Authority (VPA) is working in partnership with Golden Plains Shire Council to consider the infrastructure and service needs of areas that might accommodate new homes and jobs. Once the growth plan is finalised and in the planning scheme, council will take over the project and be responsible for putting the plan into action.
Growth Plan
No. The growth plan will identify the location and timing of areas for housing. More detailed planning work will take place to rezone the land once the growth plan has been finished. This more detailed planning work may take two to three years. We will also welcome community input into this detailed planning work as it happens.
The growth plan seeks to guide growth in a sustainable manner so that Bannockburn remains a great place to live. This will involve creating a high-level plan that identifies the best areas to locate new housing, jobs, retail and other uses.
Yes. The growth plan aims to identify a new growth boundary to accommodate the projected population growth to the year 2050.
Development will be directed away from areas:
- with high environmental values
- with an unmanageable bushfire risk
- that are highly productive for agricultural purpose
- that can’t be easily serviced by infrastructure
- that are too steep.
These decisions will be informed by technical reports and by working with agencies such as the Country Fire Authority and Barwon Water. Community engagement will be undertaken throughout the project to give community members a chance to voice their opinions.
There is some land within the current town boundary that is yet to be developed. The growth plan will identify when this land might develop and what infrastructure is required to service it.
Not all of the land in the Growth Plan Investigation Area will be suited for development. We expect approximately 5,500 new homes will be needed to accommodate the population growth to the year 2050. The growth plan will not only identify what land should be developed, but when it should be developed in stages. By staging development in the short, medium and long term, infrastructure can be funded and delivered so it’s built at the time it’s needed.
Yes. Community engagement forms a key part of the process for developing the growth plan.
The first phase of community engagement was completed in March 2020. The Victorian Planning Authority (VPA) and Golden Plains Shire Council asked the Bannockburn community what their priorities were for the future of their town. The community outlined their priorities, including improvements to shopping facilities, transport, recreational facilities and green spaces. You can see the full results in the Bannockburn Key Issues & Opportunities Community Engagement Summary Report (PDF)
The second phase of community engagements was completed in late November 2020. The outcomes of these engagement are to be posted on the webpage. | https://vpa.vic.gov.au/project/bannockburn-growth-plan/ |
In October 2016, the Regional Committee for the Eastern Mediterranean Region granted me the great honour of being nominated to be the new Regional Director for the WHO Eastern Mediterranean Region (1). In January 2017, the WHO Executive Board endorsed the Regional Committee recommendation and confirmed my appointment for a five-year period beginning 1 February 2017 (2).
I have begun my new role by putting the commitments made to the Regional Committee into action; namely by establishing an Interdepartmental Taskforce to develop a clear roadmap for WHO’s work in the Region during the coming five years. The establishment of the Taskforce aims to facilitate a Regional Office-wide approach to addressing the health priorities of the Eastern Mediterranean Region in a systematic and comprehensive way. In addition, it ensures that the work of the Regional Office is aligned with the needs of Member States and streamlined with the Governing Bodies’ (World Health Assembly [WHA], Executive Board and Regional Committee) resolutions and decisions.
Moreover, the Taskforce has included a work plan for the preparation of this Roadmap, taking into consideration the need to involve staff at the Eastern Mediterranean Regional Office (EMRO) as well as in WHO country offices and Member States of the Region. This plan has involved a series of meetings with stakeholders, physically and virtually, to ensure active participation and fruitful contribution of staff and Member States. With this in mind, the outline framework of the Roadmap was shared with the Subcommittee of the Regional Committee during its meeting in April 2017, followed by the presentation of a draft Roadmap to Member States in the Region on 21 May 2017 in Geneva, Switzerland, just before the 70th World Health Assembly (3); and to the heads of WHO's country offices in their meeting of 13–15 June 2017. I would expect the Roadmap to be finalized in September 2017 in order to start its implementation by October 2017.
Ultimately my vision is to increase EMRO capacity in order to meet the needs of Member States, by making WHO in the Region more effective, efficient, open, accountable, and transparent over the next 5 years. It is my desire to see EMRO on the front line in providing health leadership and the necessary technical and managerial support to Member States in addressing health challenges in the Region.
The Roadmap takes into consideration the global and regional environments in which EMRO is working, including the global commitment to the 2030 Agenda for Sustainable Development (4) and WHO Reform Agenda (5). Moreover, it considers the sustainable development goals (SDGs) as the overall framework guiding the work of the Organization with Member States in the Region.
While WHO ensures the consistency of this Roadmap with SDGs, I have formulated five top priority areas in order to make tangible achievements during the next five years. In addition, the Roadmap looks to promote a productive, creative and innovative environment within EMRO, with efforts focused on further development of staff skills, effective communication, appropriate coordination mechanisms, a stronger teamwork environment and enhanced delegation of authority to staff in order to promote greater accountability and transparency.
The Roadmap has been constructed on four interrelated pillars; namely joint public health priorities; enabling factors; EMRO’s presence in Member States; and EMRO’s working environment.
“Joint public health priorities” represent the top technical priority area that EMRO will focus on from 2017 to 2021. They are called “joint” to clearly draw attention to the fact that they cannot be addressed individually, but remain interlinked both in terms of challenges as well as strategic approaches. They include:
Emergencies and health security; ensuring a coherent public health approach to an emergency response in crisis countries, preparedness and health security for the Region.
Health systems strengthening: ensuring Universal Health Coverage and for essential public health functions.
Prevention and control of communicable diseases: addressing weaknesses in vaccination coverage and implementing integrated disease surveillance.
Prevention and control of non-communicable diseases, mental health and substance abuse: strengthening efforts to reduce the burden and mortality by focusing on reducing their risk factors.
Maternal, child, and adolescent health: focusing on neonatal mortality and the remaining burden of high maternal and adolescent mortality.
“Enabling factors” will emphasize the need for EMRO to deliver better on its strategic directions in order to meet Member States’ expectations for support with national policies, strategies and plans of action. These principles include advocating for health in all policies; focusing on capacity building of public health management and leadership; expanding partnership with different stakeholders including the United Nations; Engaging with civil society organizations and academic institutions; enhancing regional capacities in resource mobilization, especially at country level; ensuring that monitoring and evaluation systems are established and strengthened for better performance and quality; increasing communications and advocacy to support various WHO priorities; and ensuring consideration of social and environmental determinants of health in all WHO approaches.
Since EMRO aims to strengthen and enhance its work at the country level to be more responsive to the needs of Member States, “WHO presence at country level” will represent action to be taken to implement the commitment I made to strengthen EMRO’s engagement and response and to improve the image of the Organization at the country level.
“Work environment” focuses on how we can make EMRO a centre of excellence by ensuring an enabling environment to strengthen the Regional Office for efficient and effective programme implementation. I wish to see EMRO as a supporting environment for future public health leaders; to develop and attract talent; and retain staff through investment in their career development, aligned with the Region’s emerging and evolving needs. Staff rotation and mobility will be utilized sensitively to ensure the needs of staff members and their families are met, while ensuring that EMRO has the right skills-set it requires.
As a results-oriented Organization, EMRO will ensure clear strategic planning in the Roadmap, including clear targets and indicators for monitoring and evaluation of all the Regional Office’s important work.
Progress in addressing all areas in the Roadmap will only be possible through the sustained commitment of EMRO, its Member States, and stakeholders. It is imperative that we all unite in a combined effort to ensure a holistic improvement of health in the Region, while drawing on our well-founded existing strengths and resources. Within EMRO, a collective approach is needed to make it possible. Every individual, unit, department and office will be responsible to work in close coordination and harmony with each other to demonstrate collective responsibility, to follow the same strategic direction and guidance, and to work towards the same goal.
References
- WHO Regional Office for the Eastern Mediterranean. Dr Fikri from United Arab Emirates nominated as WHO regional director. Cairo: WHO Regional Office for the Eastern Mediterranean; 2017 (http://www.emro.who.int/media/news/dr-fikri-from-united-arab-emirates-nominated-for-who-regional-director.html, accessed 13 June 2017).
- WHO Regional Office for the Eastern Mediterranean. Mahmoud Fikri appointed as regional director for the WHO Eastern Mediterranean Region. Cairo: WHO Regional Office for the Eastern Mediterranean; 2017 (http://www.emro.who.int/media/news/mahmoud-fikri-from-united-arab-emirates-appointed-as-who-regional-director-for-the-eastern-mediterranean.html, accessed 13 June 2017).
- 70th World Health Assembly. Geneva: World Health Organization; 22–31 May 2017 (http://www.who.int/life-course/news/events/70-wha/en/, accessed 13 June 2017).
- United Nations. Transforming our world: the 2030 agenda for sustainable development. New York: United Nations; 2015 (https://sustainabledevelopment.un.org/post2015/transformingourworld, accessed 13 June 2017).
- World Health Organization. WHO reform process. Geneva: World Health Organization; 2013 (http://www.who.int/about/who_reform/process/en/, accessed 13 June 2017). | http://www.emro.who.int/emhj-volume-23-2017/volume-23-issue-5/roadmap-20172021-stronger-organization-and-better-response-to-the-needs-of-member-states-in-the-eastern-mediterranean-region.html |
The Administration for Children and Families (ACF), Office of Community Services (OCS) will solicit applications to award approximately $12.3 million in Community Economic Development (CED) discretionary grant funds to Community Development Corporations (CDC) for well-planned, financially viable, and innovative projects to enhance job creation and business development for individuals with low income. CED grants will be made as part of a broader strategy to address objectives such as decreasing dependency on federal programs, chronic unemployment, and community deterioration in urban and rural areas. CED projects are expected to actively recruit individuals with low income to fill the positions created by CED-funded development activities, to assist those individuals in successfully maintaining employment, and to ensure that the businesses and jobs created remain viable for at least two years after the grant period. CED projects can be non-construction or construction projects, however, short-term construction jobs associated with preparing for business startup or expansion are not counted when determining the number of jobs created under the CED program as those jobs are temporary in nature. OCS encourages applicants to target rural and underserved areas in states with current projects.Furthermore, OCS encourages potential applicants to explore how proposed projects can be aligned and/or integrated with other OCS-funded programs and priorities to more comprehensively address the needs of rural and urban communities with high rates of poverty, unemployment, and substance use disorder, as well as communities experiencing persistent poverty, as identified by US Department of Agriculture's Economic Research Service.
Categories: Income Security and Social Services.
Categories: Income Security and Social Services. | https://inomics.com/scholarship/community-economic-development-projects-1530433 |
We know we have a great school, but we also know we need to keep evolving to make it even better!
We have a wonderful new building and that has taken a lot of focus and hard work over the last few years. But we need a plan to ensure it continues to deliver on the high expectations of our students, whanau and staff.
Here is our new Ohope Beach School Strategic Plan 2019-21.
This is an Interim Plan while the Government are making changes to the schools planning cycle. The Board of Trustees would love to hear what you think about this new plan (see ways to contact us below). We have developed it using the feedback from the survey undertaken in 2018 (see below). We haven't managed to capture every comment within this plan (we wanted to keep it to 1 page to keep it interesting), but as you'll see, some of our actions are to respond in more detail to the valuable feedback we've received from the community.
How did we get to this point?
You gave us your feedback
In 2018 we asked you, the school community, what your priorities were for our school. Your views are important to us, by working together we can ensure we can make OBS the best school for our children.
To help contribute towards making sure Ōhope Beach School meets the needs of all our children we needed to hear your views. You answered 3 questions for us and we used your feedback to inform our direction in our Strategic Plan.
We asked you:
KEEP
What do you love about our school?
START
What are your good ideas to make OBS even better?
STOP
What do you think needs to change?
You answered the survey:
How does the survey fit into the Strategic Review?
Current Strategic PlanInterested in learning more about our current Strategic Plan? Check out the school Charter and Annual Plan 2019
Contact Us
If you have any additional thoughts or comments you would like to share with the Board of Trustees feel free to contact us. | http://www.ohopebeach.school.nz/71/easy_pages/1-strategic-review-2018-19 |
Pandemic recovery initiatives, a local headspace centre to support mental health, investment in local sporting facilities, funding boosts for parks and waterways, and encouraging sustainable and active transport – including a Western Gateway Station at Airport West are among the priority advocacy initiatives endorsed last week by Moonee Valley City Councillors.
Council last week endorsed its Advocacy Strategy 2022-25 and will be using the upcoming State and Federal elections to call for much needed investment in the municipality. The Strategy contains more than 50 initiatives that will benefit local residents. It was developed following extensive community consultation and includes plans for greater transparency for residents with the development of an annual report card and framework. The Advocacy Strategy aligns to priorities in Council’s long-term plan, MV2040 and the Council Plan to progress the Community Vision into reality.
Moonee Valley Mayor Samantha Byrne said advocacy is an important role of local government and the Strategy was developed to outline what is needed to get the best outcomes for our community on all projects, not just the ones that Council manages.
“We have already been meeting with our local MPs to brief them about the Strategy priorities, and will seek meetings with State and Federal Ministers over the coming months to put the case forward for better and more investment in Moonee Valley,” said Mayor Byrne.
“We have worked closely with our community to identify our advocacy priorities – now clearly documented. Now it’s time for the Federal and State Government to ensure they respond quickly so our community can thrive.
“Council works hard to get the best use of ratepayer dollars to ensure Moonee Valley is a great place to live, work and play, however the Advocacy Strategy demonstrates we need major investment in infrastructure and services, and our fair share of grants and funding.”
Mayor Byrne also encouraged local residents to remain involved in advocacy promotion.
Visit our Advocacy page to view our Advocacy Strategy 2022-25. | https://mvcc.vic.gov.au/advocating-our-way-to-2025-with-a-list-of-priorities/ |
Amid the COVID-19 pandemic, the Los Angeles LGBT Center has continued to provide services to more LGBT people than any other organization in the world. Normally, the Center sees more than 42,000 clients visits each month.
However, community needs are growing and changing during the crisis, and the Center has been evolving to meet those needs — all while losing a significant amount of much-needed funding due to social distancing and economic uncertainty.
“The Center is so committed to providing these critical services that mean so much right now,” Center Board of Directors Co-Chair Susan Feniger said during a virtual town hall meeting with donors on April 7.
For assistance during these tough financial times, the Center has established theCARE (Community Action Response Effort) Fund. Contributions ensure that resources and services, such as health care and food distribution, are available to those who need them throughout the pandemic.
“Clearly we’re the first responders for the LGBT community and that is so important,” Feniger added. ”We have never, ever walked away from the community during tough times. The Center’s team—these incredible first responders—are working day and night to make sure we continue to provide these very needed services.”
Procedural adjustments have been made to the Center’s Health Services, Senior Services, Youth Services, and other areas to remain in operation. For instance, the vast majority of routine primary care, HIV care, PrEP and transgender appointments have been converted to telehealth. Other programs, such as Legal Services, Policy and Community Building, Trans* Lounge, and youth mentoring are continuing virtually.
The biggest financial hit has been cancelation of the seven-day, 545-mile AIDS/LifeCycle scheduled for May 31 – June 6, which benefits both the San Francisco AIDS Foundation and the HIV/AIDS-related services of the Center. In order to maintain the current level of HIV/AIDS services provided to the community, both organizations have still set a joint fundraising goal of $13 million—of which more than $6.5 million has already been raised by the ride’s participants through the innovative My 545 challenge.
“We’re going to take a huge loss for the AIDS/LifeCycle this year,” Center Chief of Staff Darrel Cummings explained during the town hall. “That’s not money for the future—that’s money we are spending now. To the degree that we don’t have it, we have to figure out other ways of compensating for that and (The CARE Fund) is one of those ways.”
To contribute to the CARE Fund, visit lalgbtcenter.org/care. | https://lgbtnewsnow.org/do-you-care-enough-to-help-the-los-angeles-lgbt-center-then-keep-reading/ |
Learning & Development Strategy & Communications Project Manager
Citi Learning drives business performance by connecting employees with relevant and innovative learning experiences when and where they need them.
This person will support Citi’s Chief Learning Officer (CLO) and the Citi Learning function, reporting to Citi Learning’s Chief Administrative Officer. This role will advise on and execute against multiple strategic initiatives and priorities across the Learning function. The candidate will be highly organized and motivated with demonstrated successes in managing complex organizational initiatives. He/she will implement and manage a multi-channel communication strategy to drive engagement within the function and aid in building Citi Learning’s brand externally. He/she will need to create the relevant project planning documentation associated with driving priorities and meetings forward. He/she will be responsible for delivering regular status reports, executive level dashboards and presentations to a variety of audiences across HR. He/she should have excellent interpersonal skills and work constructively with people across all businesses and regions to facilitate project deliverables.
Key responsibilities include:
- Serve as a thought partner to the CLO , driving strategy, communications, and ad-hoc special projects
- Assist with the prioritization, planning, organization and implementation of Citi Learning’s priorities and key objectives
- Manage the creation of Citi Learning executive level presentations, agendas and materials, for both internal and external uses
- Oversee agendas and materials for the CLO’s Staff and Operating Committee meetings
- Work with global and regional stakeholders to ensure alignment across key initiatives and projects across the function
- Project manage certain workstreams and special projects aligned to the function’s key priorities, monitoring progress, accountabilities, and making adjustments as necessary to ensure successful completion
- Develop, implement and drive a function-wide communication strategy, utilizing all communication channels, both internally and externally
- Oversee Citi Learning communication processes and procedures, and serve as main point of contact and partner to Global Public Affairs
Qualifications:
- Undergraduate degree required, HR preferred
- 5+ years experience in project management, communications or related field in global environment with complex stakeholder group
- Ability to collaborate and influence internal stakeholders at various levels in a matrixed environment
- Ability to create high quality executive level presentations, telling compelling stories using qualitative and quantitative data
- Excellent analytical, critical thinking and problem-solving skills with attention to detail
- Strong verbal and written communication skills
- Capable of performing effectively in complex situations with limited guidance
- Results oriented and ability to manage multiple concurrent projects
- Ability to adapt to rapidly evolving and changing priorities; resilient and flexible
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Job Family Group:Project and Program Management
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Job Family:Project Management
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Time Type:Full time
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Citi is an equal opportunity and affirmative action employer.
Qualified applicants will receive consideration without regard to their race, color, religion, sex, sexual orientation, gender identity, national origin, disability, or status as a protected veteran.
Citigroup Inc. and its subsidiaries ("Citi”) invite all qualified interested applicants to apply for career opportunities. If you are a person with a disability and need a reasonable accommodation to use our search tools and/or apply for a career opportunity review Accessibility at Citi.
View the "EEO is the Law" poster. View the EEO is the Law Supplement.
View the EEO Policy Statement.
View the Pay Transparency Posting
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Join our team
of 200,000+
strong diverse employees
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Socially minded employees volunteering in communities across 90 countries
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Meaningful career opportunities thanks to a physical presence in over 98 markets
We foster a culture that embraces all individuals and encourages diverse perspectives, where you can make an impact and grow your career. At Citi, we value colleagues that demonstrate high professional standards, a strong sense of integrity and generosity, intellectual curiosity, and rigor. We recognize the importance of owning your career, with the commitment that if you do, we promise to meet you more than half way. | https://jobs.citi.com/job/new-york/learning-and-development-strategy-and-communications-project-manager/287/8850344688 |
Thermal therapies – particularly the use of thermal ablation (including microwave, RF, cryoablation, and high-intensity-focused ultrasound), hyperthermia, and heat activated drug delivery in the treatment of cancer have been the focus of increasing laboratory and clinical research. In the various ablation methods, either significantly elevated temperatures (typically above 50 ◦ C) generated by electromagnetic waves or ultrasound, or freezing temperatures generated by cryogens are used to cause very rapid and localized tissue destruction. In the case of hyperthermia, moderately elevated temperatures (typically between 40 ◦ C and 45 ◦ C) have been shown to achieve cytotoxic effects that render cancer cells more vulnerable to radiotherapy and chemotherapy, as well as inducing both apoptotic and necrotic cell death given a sufficient thermal dose. Motivated by this knowledge, researchers have developed microwave systems capable of inducing localized hyperthermia as an adjuvant cancer treatment modality.
With these potential applications in mind, a pre-clinical prototype of a non invasive thermal therapy system has been developed by researchers within MiXIL for the targeted treatment of breast cancer cells using focused microwaves. In the system, an array of antennas operating at 915 MHz is used to focus continuous-wave microwave energy transcutaneously into the pendent breast suspended in a coupling medium (shown in Fig. 1). Prior imaging studies are used to ascertain the material properties of the breast tissue, and these data are incorporated into a multiphysics model. Time-reversal techniques are then employed to find a solution (relative amplitudes and phase) for focusing at a given location, resulting in maximal thermal dose at the tumor location. Using this system, focal spot sizes in the array plane of approximately 1.5 cm in diameter have been achieved and significant differential heating in the target region has been observed in focused heating tests within tissue-mimicking gelatin phantoms.
Based on these results, the system has the potential to offer improved targeting and delivery of focused heating over current microwave thermal therapy systems, without the need for invasive probes.
Two-dimensional microwave thermal therapy system prototype. (a) Signal generator, (b) 12-channel electronic phase control, (c) 10-W per channel amplifiers (120 W total), and (d) 12-element therapy array. | https://mixil.usc.edu/research/synergistic-microwave-and-ultrasound-cancer-treatment-systems/ |
- 1H MRI phase thermometry in vivo in canine brain, muscle, and tumor tissue.
- A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.
- A coaxial microwave applicator for transurethral hyperthermia of the prostate.
- A comparative study of the effect of arterial and venous occlusion after various periods of ischemia.
- A comparison of temperatures in canine solid tumours during local and whole-body hyperthermia administered alone and simultaneously.
- A method of MRI-based thermal modelling for a RF phased array.
- A method to convert MRI images of temperature change into images of absolute temperature in solid tumours.
- A new technique allowing prolonged temporary cerebral artery occlusion.
- A pilot study of cerebral and haemodynamic physiological changes during sedation with dexmedetomidine or propofol in patients with acute brain injury.
- A pilot study to examine maturation of body temperature control in preterm infants.
- A randomized controlled trial of the Arctic Sun Temperature Management System versus conventional methods for preventing hypothermia during off-pump cardiac surgery.
- A selective inhibitor of cyclooxygenase-2 reverses endotoxin-induced pyretic responses in non-human primates.
- A simple, inexpensive method of monitoring brain temperature in conscious rodents.
- Absence of biochemical evidence for renal and hepatic dysfunction after 8 hours of 1.25 minimum alveolar concentration sevoflurane anesthesia in volunteers.
- Absence of detectable pharmacological effects after oral administration of isoxsuprine.
- Accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas.
- Accurate temperature imaging based on intermolecular coherences in magnetic resonance.
- Action of preoptic injections of beta-endorphin on temperature regulation in rabbits.
- Admission Temperature and Associated Mortality and Morbidity among Moderately and Extremely Preterm Infants.
- Aerobic fitness, acute exercise and sleep in older men.
- Age, dose, and environmental temperature are risk factors for topiramate-related hyperthermia.
- American Clinical Neurophysiology Society Guideline 5: Minimum Technical Standards for Pediatric Electroencephalography.
- Antidepressant effects of nicotine in an animal model of depression.
- Application of new technology in clinical hyperthermia.
- Assessment of cadaveric organ viability during pulsatile perfusion using infrared imaging.
- Assessment of hand osteoarthritis: correlation between thermographic and radiographic methods.
- Attenuation of alcohol consumption by MDMA (ecstasy) in two strains of alcohol-preferring rats.
- Automated feedback control of body temperature for small animal studies with MR microscopy.
- Autonomic and behavioral responses of selectively bred hypercholinergic rats to oxotremorine and diisopropyl fluorophosphate.
- Aversive effects of ethanol in adolescent versus adult rats: potential causes and implication for future drinking.
- Behavioral thermoregulation in the rat following the oral administration of ethanol.
- Biobehavioral Responses of Preterm Infants to Conventional and Swaddled Tub Baths: A Randomized Crossover Trial.
- Biomechanics of running indicates endothermy in bipedal dinosaurs.
- Body temperature and mortality in patients with acute respiratory distress syndrome.
- Body temperature in premature infants during the first week of life: Exploration using infrared thermal imaging.
- Body temperature instability and respiratory morbidity in the very low birth weight infant: a multiple case, intensive longitudinal study.
- Body temperature is a poor predictor of malaria parasitaemia in children with acute diarrhoea.
- Body weight is not always a good predictor of longevity in mice.
- Brain temperature alters hydroxyl radical production during cerebral ischemia/reperfusion in rats.
- Brief report: The declining incidence of cerebral hyperthermia during cardiac surgery: a seven-year experience in 6,334 patients.
- CEM43°C thermal dose thresholds: a potential guide for magnetic resonance radiofrequency exposure levels?
- Cardiac cryosurgery: effects of myocardial temperature on cryolesion size.
- Cardiopulmonary bypass induces neurologic and neurocognitive dysfunction in the rat.
- Cardiopulmonary bypass reduces the minimum alveolar concentration for isoflurane.
- Cardiopulmonary bypass time does not affect cerebral blood flow.
- Cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. CNS Subgroup of McSPI.
- Cerebral physiology of cardiac surgical patients treated with the perfluorocarbon emulsion, AF0144.
- Characterization of tumour temperature distributions in hyperthermia based on assumed mathematical forms.
- Chimeric Sindbis/eastern equine encephalitis vaccine candidates are highly attenuated and immunogenic in mice.
- Circadian rhythms in rat mid-brain and caudate nucleus biogenic amine levels.
- Clinical application of thermal isoeffect dose.
- Clinical experience with a multi-element ultrasonic hyperthermia system: analysis of treatment temperatures.
- Clinical importance of polymicrobial bacteremia.
- Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants.
- Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction.
- Conduction block after cardioplegic arrest: prevention by augmented atrial hypothermia.
- Continuous jugular venous versus nasopharyngeal temperature monitoring during hypothermic cardiopulmonary bypass for cardiac surgery.
- Controlled Multifactorial Coagulopathy: Effects of Dilution, Hypothermia, and Acidosis on Thrombin Generation In Vitro.
- Day-specific probabilities of clinical pregnancy based on two studies with imperfect measures of ovulation.
- Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats.
- Deep hypothermia markedly activates the small ubiquitin-like modifier conjugation pathway; implications for the fate of cells exposed to transient deep hypothermic cardiopulmonary bypass.
- Developmental differences in the acquisition of tolerance to ethanol.
- Differential age effects of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery.
- Differential cardiopulmonary monitoring system for artifact-canceled physiological tracking of athletes, workers, and COVID-19 patients.
- Differential ventricular ischemic injury: an experimental model of right ventricular failure with a variable degree of left ventricular dysfunction.
- Discrete cerebral hypothermia in the management of traumatic brain injury: a randomized controlled trial.
- Diurnal torpidity in the California pocket mouse.
- Divergent action of verapamil perfused in two hypothalamic areas on body temperature of the cat.
- Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice.
- Effect of Laser Settings and Irrigation Rates on Ureteral Temperature During Holmium Laser Lithotripsy, an In Vitro Model.
- Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice.
- Effect of inborn vs. outborn delivery on neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy: secondary analyses of the NICHD whole-body cooling trial.
- Effect of local hypothermia on early wound repair.
- Effect of perfusion pressure on cerebral blood flow during normothermic cardiopulmonary bypass.
- Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice.
- Effect of temperature during cardiopulmonary bypass on gastric mucosal perfusion.
- Effect of temperature on kainic acid-induced seizures.
- Effects of NMDA receptor antagonists and body temperature in the gerbil carotid occlusion model of transient forebrain ischemia.
- Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat.
- Effects of aortopulmonary collaterals on cerebral cooling and cerebral metabolic recovery after circulatory arrest.
- Effects of calcium channel inhibitors on the hypothermic response to oxotremorine in normo and hypercholinergic rats.
- Effects of clenbuterol hydrochloride on pulmonary gas exchange and hemodynamics in anesthetized horses.
- Effects of continuous-wave, pulsed, and sinusoidal-amplitude-modulated microwaves on brain energy metabolism.
- Effects of epinephrine and lactate on the increase in oxygen consumption of nonexercising skeletal muscle after aerobic exercise.
- Effects of immobilization restraint on Syrian golden hamsters.
- Effects of pentobarbital anesthesia on the energy metabolism of murine tumors studied by in vivo 31P nuclear magnetic resonance spectroscopy.
- Effects of phentermine and phenformin on biomarkers of aging in rats.
- Effects of postischemic halothane administration on outcome from transient focal cerebral ischemia in the rat.
- Effects of the sazetidine-a family of compounds on the body temperature in wildtype, nicotinic receptor β2-/- and α7-/- mice.
- Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor.
- Elevated temperature after hypoxic-ischemic encephalopathy: risk factor for adverse outcomes.
- Elimination of GRK2 from cholinergic neurons reduces behavioral sensitivity to muscarinic receptor activation.
- Energy metabolism in uncoupling protein 3 gene knockout mice.
- Enhanced morphine analgesia in mice lacking beta-arrestin 2.
- Equal antipyretic effectiveness of oral and rectal acetaminophen: a randomized controlled trial [ISRCTN11886401].
- Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex.
- Experimental studies of the thermal effects associated with radiation force imaging of soft tissue.
- False increase BIS values with forced-air head warming.
- Feasibility of estimating the temperature distribution in a tumor heated by a waveguide applicator.
- Finite-element analysis of temperature rise and lesion formation from catheter ultrasound ablation transducers.
- Further selection of rat lines differing in 5-HT-1A receptor sensitivity: behavioral and functional correlates.
- Fusion of fibroblast growth factor 21 to a thermally responsive biopolymer forms an injectable depot with sustained anti-diabetic action.
- Golden Hour Protocol for Preterm Infants: A Quality Improvement Project.
- Halothane reduces focal ischemic injury in the rat when brain temperature is controlled.
- Hemodynamic and histological differences in end-to-side anastomoses.
- High-dose fentanyl does not adversely affect outcome from forebrain ischemia in the rat.
- Hyperthermic effects on behavior.
- Hyperthermic modulation of radiolabelled antibody uptake in a human glioma xenograft and normal tissues.
- Hypothermia: role of alpha 1- and alpha 2-noradrenergic receptors in the hypothalamus of the cat.
- Identification and functional characterization of a stable, centrally active derivative of the neurotensin (8-13) fragment as a potential first-in-class analgesic.
- Immunologic and hematopoietic alterations by 2,450-MHz electromagnetic radiation.
- Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.
- Improved magnetic resonance thermal imaging by combining proton resonance frequency shift (PRFS) and apparent diffusion coefficient (ADC) data.
- Incompatible bone-marrow transplantation in lymphopenic immunologic deficiency. Circumvention of fatal graft-versus-host disease by immunologic enhancement.
- Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knock-out mice.
- Infrared thermography: a rapid, portable, and accurate technique to detect experimental pneumothorax.
- Inhibition of nitric oxide synthesis attenuates alcohol consumption in two strains of alcohol-preferring rats.
- Insulin in aging and cancer: antidiabetic drug Diabenol as geroprotector and anticarcinogen.
- Interpreting properties of microbicide drug delivery gels: analyzing deployment kinetics due to squeezing.
- Inverse techniques in hyperthermia: a sensitivity study.
- Involving the male partner for interpreting the basal body temperature graph.
- Laser Doppler monitoring of replants using a small prism probe.
- Limb tourniquets and central temperature in anesthetized children.
- Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children.
- Liver genomic responses to ciguatoxin: evidence for activation of phase I and phase II detoxification pathways following an acute hypothermic response in mice.
- Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mice.
- Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions.
- Metabolic response to respiratory heat loss-induced core cooling.
- Metabolism and thermoregulation during fasting in king penguins, Aptenodytes patagonicus, in air and water.
- Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia.
- Microwave effects on energy metabolism of rat brain.
- Migratory movements, depth preferences, and thermal biology of Atlantic bluefin tuna.
- Miniature microwave applicator for murine bladder hyperthermia studies.
- Monitoring of the electrical status of the ventricle during cardioplegic arrest.
- Monitoring the jugular-venous oxyhemoglobin saturation as a decision aid for normothermic cardiopulmonary bypass.
- Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.
- Negative Temperature Differential in Preterm Infants Less Than 29 Weeks Gestational Age: Associations With Infection and Maternal Smoking.
- Neuroanatomical mapping of hypothalamic regions mediating verapamil hyper- and hypothermia in the cat.
- Neurological injury during cardiopulmonary bypass in the rat.
- Neuroprotection in cardiac surgery.
- Nicotine-alcohol interactions and cognitive function in rats.
- No association between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients undergoing temporary clipping during cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.
- Non-invasive body temperature measurement of wild chimpanzees using fecal temperature decline.
- Novel adamantyl cannabinoids as CB1 receptor probes.
- Observations on man in an oxygen-helium environment at 380 mm. Hg total pressure. 3. Heat exchange.
- On the accuracy of noninvasive thermometry using molecular diffusion magnetic resonance imaging.
- On the thermal effects associated with radiation force imaging of soft tissue.
- Opposite function of dopamine D1 and N-methyl-D-aspartate receptors in striatal cannabinoid-mediated signaling.
- Optimal body temperature in transitional extremely low birth weight infants using heart rate and temperature as indicators.
- Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.
- Oxygen affinity and amino acid sequence of myoglobins from endothermic and ectothermic fish.
- Oxygen transport by the circulatory system of the green iguana (Iguana iguana) at different body temperatures.
- Paradoxical inhibition of decreases in body temperature by use of heated and humidified gases.
- Perioperative hypothermia (33 degrees C) does not increase the occurrence of cardiovascular events in patients undergoing cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.
- Pharmacological and toxicological evaluation of 2-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-F-A-85380), a ligand for imaging cerebral nicotinic acetylcholine receptors with positron emission tomography.
- Phenobarbital and temperature profile during hypothermia for hypoxic-ischemic encephalopathy.
- Postischemic diazepam is neuroprotective in the gerbil hippocampus.
- Postoperative hyperthermia following off-pump versus on-pump coronary artery bypass surgery.
- Postoperative hyperthermia is associated with cognitive dysfunction after coronary artery bypass graft surgery.
- Pre- and postmortem diffusion coefficients in rat neural and muscle tissues.
- Predetermination of sexual fate in a turtle with temperature-dependent sex determination.
- Predictors of cognitive decline after cardiac operation.
- Prevention of cerebral hyperthermia during cardiac surgery by limiting on-bypass rewarming in combination with post-bypass body surface warming: a feasibility study.
- Prognostic usefulness of white blood cell count and temperature in acute myocardial infarction (from the CARDINAL Trial).
- Pulsatile blood flow effects on temperature distribution and heat transfer in rigid vessels.
- Putting class IIb recommendations to the test: the influence of unwitnessed and Non-VT/VF arrests on resource consumption and outcomes in therapeutic hypothermia and targeted temperature management.
- Quantitative determination of the partial oxygen pressure in the vitrectomized rabbit eye in vivo using 19F NMR.
- Rapid selection for serotonin-1A sensitivity in rats.
- Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium.
- Real-time monitoring of luminal esophageal temperature during left atrial radiofrequency catheter ablation for atrial fibrillation: observations about esophageal heating during ablation at the pulmonary vein ostia and posterior left atrium.
- Recovery from swimming-induced hypothermia in king penguins: effects of nutritional condition.
- Regional hyperthermia by magnetic induction in a beagle dog model: analysis of thermal dosimetry.
- Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil.
- Relationship between clinical evaluation of peripheral perfusion and global hemodynamics in adults after cardiac surgery.
- Relative ontogeny of opioid and catecholaminergic regulation of thyrotropin secretion in the rat.
- Repeat exposure to ciguatoxin leads to enhanced and sustained thermoregulatory, pain threshold and motor activity responses in mice: relationship to blood ciguatoxin concentrations.
- Respiratory physiology of house sparrows in relation to high-altitude flight.
- Retinal toxicity of cyanoacrylate tissue adhesive in the rabbit.
- Retinitis pigmentosa: clinical management based on current concepts.
- Risk factors for cancer of the testis.
- Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's lymphoma receiving CHOP chemotherapy.
- Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence from mice lacking the transporter.
- Serious toxicity associated with annular microwave array induction of whole-body hyperthermia in normal dogs.
- Sex differences in the neurochemical and functional effects of MDMA in Sprague-Dawley rats.
- Six-month survival of a calf with an artificial heart.
- Steady-state gas exchange in normothermic, anesthetized, liquid-ventilated dogs.
- Temperature differences during sleep between fullterm and preterm neonates at matched post-conceptional ages.
- Temperature measurement during cardiac surgery.
- Temperature measurements in normal and tumor tissue of dogs undergoing whole body hyperthermia.
- Temperature monitoring.
- The Association Between Very Premature Infant Body Temperatures Over Time and Respiratory Care.
- The Effect of patient warming during Caesarean delivery on maternal and neonatal outcomes: a meta-analysis.
- The Effects of Thermal Preconditioning on Oncogenic and Intraspinal Cord Growth Features of Human Glioma Cells.
- The effect of arthroscopic irrigation fluid warming on body temperature.
- The effect of continuous cryotherapy on glenohumeral joint and subacromial space temperatures in the postoperative shoulder.
- The effect of systemic acidosis on perfusion of replanted extremities.
- The esophageal temperature gradient in anesthetized children.
- The impact of short-term depot-medroxyprogesterone acetate treatment on resting metabolic rate.
- The influence of xenon, nitrous oxide and nitrogen on gas bubble expansion during cardiopulmonary bypass.
- The relationship between cervical secretions and the daily probabilities of pregnancy: effectiveness of the TwoDay Algorithm.
- The relationship of sleep with temperature and metabolic rate in a hibernating primate.
- The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.
- The role of irrigation in the development of hypothermia during laparoscopic surgery.
- The use of hydralazine to manipulate tumour temperatures during hyperthermia.
- The utility of thermal dose as a predictor of tumor and normal tissue responses to combined radiation and hyperthermia.
- Thermal responses in humans exposed to cold hyperbaric helium-oxygen.
- Thermal study of longitudinal and torsional ultrasound phacoemulsification: tracking the temperature of the corneal surface, incision, and handpiece.
- Thermoregulation and thermography in neonatal physiology and disease.
- Transcriptomics in the wild: Hibernation physiology in free-ranging dwarf lemurs.
- Transient effects of long-term leptin supplementation in the prevention of diet-induced obesity in mice.
- Tumor temperature distributions predict hyperthermia effect.
- Use of nitroprusside to increase tissue temperature during local hyperthermia in normal and tumor-bearing dogs.
- Validation of haemodialysis recirculation and access blood flow measured by thermodilution.
- Vancomycin pharmacokinetic parameters in patients with acute brain injury undergoing controlled normothermia, therapeutic hypothermia, or pentobarbital infusion.
- Verification of a hyperthermia model method using MR thermometry.
- Wearable sensors enable personalized predictions of clinical laboratory measurements.
- Whole body hyperthermia in dogs using a radiant heating device: effect of surface cooling on temperature uniformity.
- Whole-body hyperthermia. Rationale and potential use for cancer treatment.
- alpha-Melanocyte-stimulating hormone infused ICV fails to affect body temperature or endotoxin fever in the cat.
- ΔN-TRPV1: A Molecular Co-detector of Body Temperature and Osmotic Stress. | https://scholars.duke.edu/display/meshD001831 |
Nanoparticle research is currently an area of immense scientific interest due to a wide variety of applications in biomedical, optical, and electronic fields. This is mainly due to their properties (depending on the material they consist of) such as: (i) High electron density and strong optical absorption (e.g., metal particles, in particular Au), (ii) photoluminescence (semiconductor quantum dots, e.g., CdSe or CdTe) or phosphorescence (doped oxide materials, e.g. Y2O3), (iii) magnetic moment (e.g., iron-oxide, γFe2O3, La0.7 Sr0.3 MnO3, or cobalt nanoparticles),, and (iv) a high surface area-to-volume ratio as compared to their bulk counterparts. Moreover, it is their large surface area that makes them more amenable to functionalize with various targeting agents to deliver nanoparticles to the diseased site. Owing to their small size (1–100 nm), nanoparticles can penetrate the cell interior and even cross the blood-brain barrier when labeled with appropriate agents such as polysorbates and chitosan., Among nanoparticles, iron oxide nanoparticles (IONPs) have gained immense attention for various biomedical applications due to their biocompatibility and relatively economic and simple method of synthesis. IONPs are superparamagnetic in nature (i.e., they have high magnetic moment in the presence of an external magnetic field and zero coercivity at room temperature) as against the ferromagnetic property of their bulk counterparts at room temperature. This property makes IONPs as an excellent candidate for magnetic hyperthermia therapy (MHT) as heat generation can be controlled/modulated by an externally applied alternating current magnetic field (AMF). Moreover, IONPs formulations having high specific absorption rate value may be developed, thereby enabling the use of low concentrations of IONPs for MHT applications, and thus, minimizing the inherent toxicity of the formulations.
HT involves exposing the diseased site (here it is tumor tissue) or whole body to an elevated temperature (42–43°C), which either kills the tumor cells directly or sensitizes them to chemo-/radiation-therapy. However, conventional HT suffers from two major drawbacks: (i) Nonaccessibility of the deep-seated tumors and (ii) nonuniform heating of the tumor tissue due to the generation of a temperature gradient from the surface to the tumor core. These limitations cause insufficient killing of tumor cells and severe side effects such as skin burns, blisters, pain, and discomfort to the patients. These drawbacks can be significantly overcome by the application of MHT due to following reasons. IONPs can be specifically targeted to the tumor site and thus can heat the tumor from within and more uniformly. This feature minimizes the development of temperature gradients and thermoresistance in tumor, and thus enabling better tumor control. Although MHT alone is significantly effective, a combinatorial approach of MHT along with chemo-, radiotherapy, and other sensitization approaches may lead to a much better cancer treatment.
The tumor microenvironment characterized by leaky/disorganized vasculature, nutrient deprivation, hypoxic tumor cores, and acidosis leads to the development of radioresistance [Figure 1],,,, which can be largely overcome by the application of HT through the mechanism of vasodilation and subsequent increased blood (oxygen) supply to the hypoxic regions of the tumor. It may be noteworthy to mention that even though the combinatorial approach of chemotherapy (CT) with radiotherapy (RT) has been well practiced clinically, combining RT with HT has shown limited success in clinic. In the present review, an overview of the current status of MHT in clinics has been presented along with its emerging therapeutic potential in combination with RT [Figure 1].
In clinics, HT has been used along with RT for the treatment of various tumor types such as head and neck, breast, prostate, and other superficial lesions., The radiosensitization ability of HT is known to be mainly due to heat induced-increased oxygenation of the tumor mass. In one study, HT was used to improve the tumor oxygenation along with RT for the treatment of soft tissue sarcomas. Results showed a positive correlation between the magnitude of improved tumor oxygenation after first HT fraction and percentage necrosis in the resection tumor specimen. Song et al. demonstrated a significant rise in tumor oxygenation in R3230 Ac adenocarcinoma tumors of Fischer rats after mild hyperthermia. Measurement of the oxygenation status using a polarographic oxygen electrode system showed that the tumor pO2 measured within 10–15 min after heating (for 30 min at 42.5°C) was about three-folds greater than that in the control tumors. In another study, HT was combined with radiation for the treatment of locally advanced prostate cancer. In these patients, at a median follow-up of 70 months (range: 18–110 months), the 7-year overall survival rate was 94% and out of that, 61% of patients showed no recurrence. Thus, HT seems to be a promising approach; however, its application in clinics is not well appreciated, probably due to the conventional mode (such as water bath and infra-red) of application of hyperthermia. This limitation is overcome by MHT, and hence, it may prove to be an effective alternative mode for HT of cancer.
Compared to conventional HT, MHT has received immense attention due to several reasons such as (i) targeted, homogenous, and controlled heat generation capacity; (ii) the ability to access deep-seated tumor; and (iii) ability to specifically target the tumor vasculature/hypoxic tumor cells. In this direction, significant progress has been made to formulate IONPs for efficient targeting to tumor vasculature and hypoxic regions, however, their application for MHT needs to be established. In addition, MHT may also be employed to co-deliver drugs (such as anti-cancer agents, angiogenesis inhibitors, and radiosensitizers) for efficient combination therapy. Current targeting approaches for nanoparticles include ligands such as antibodies, peptides, and porphyrins to improve tumor uptake and specificity of the desired drug, and thus lower the amount of drugs needed for cancer treatment., Many other novel strategies have been developed to target nanoparticles to the tumor site. In one such approach, Ohta et al. recently developed nanoparticles functionalized with folic acid (FA). The presentation of FA on the surface of the nano-assembly was controlled by changing its shape using DNA as molecular keys. This in turn changes the position of FA from hidden to exposed state, thereby making it available for interaction with tumor cells over-expressing FA receptors resulting in enhanced (2.5 folds) targeted delivery of the nanoformulation to the tumor site. Most of these targeting approaches are used for the delivery of anti-cancer agents along with nanoparticles. However, utilization of these targeting strategies for IONPs would enable increased accumulation of the IONPs as well as the drug at the tumor site, thus resulting in effective heating during magnetic hyperthermia-based cancer therapy.
Several studies for preclinical applications of MHT are reported in literature. Zhao et al. (2012) reported the application of magnetic nanoparticles (MNPs) for the treatment of head and neck cancers using a mouse xenograft model. Results showed that the temperature of the tumor center was dramatically elevated from body temperature to 40°C in 5–10 min. This hyperthermia treatment resulted in necrosis in the treated tumor tissue. Similarly, Hu et al. used MHT for the treatment of murine lung carcinoma models. Results showed inhibition of the tumor growth via induction of apoptosis. Shetake et al. recently demonstrated the efficacy of oleic acid coated IONPs for MHT of murine fibrosarcoma tumor models. Results showed significant inhibition of tumors after MHT by induction of apoptosis via modulation of heat shock protein 90 (HSP 90)/AKT pathway. It may be pertinent to emphasize that in these animal studies, MNPs were injected intratumorally, a mode of injection not suitable for deep-seated and metastatic tumors. Moreover, intratumoral injections may cause tumor incongruence, invasiveness, and recurrence, especially from under-treated tumor regions. Therefore, for targeting and systemic administration of MNPs, intravenous injection is the preferred route. However, so far, it has been difficult to achieve the effective concentrations in tumors when MNPs were administered through intravenous route. Huang and Hainfeld demonstrated intravenous administration of polyethylene glycol-coated IONPs, with a well-tolerated dose, achieving a tumor concentration of 1.9 mg Fe/g of tumor tissue in a subcutaneous squamous cell carcinoma mouse model, with a tumor-to-nontumor ratio of >16. With an applied field of 38 kA/m at 980 kHz, tumors could be heated to 60°C for 2 min ablating them with millimeter range.
Route of administration of MNPs may vary depending on the type of cancer. For example, in case of lung cancer, inhalation would be the preferred route of administration. Sadhukha et al. demonstrated the administration of inhalable epidermal growth factor receptor-targeted MNPs in a murine orthotopic model of nonsmall cell lung carcinoma, which showed significant enhancement in targeting and retention of MNPs in the lung tumors. Moreover, in combination with AMF, it showed a significant growth inhibition of these tumors. This study also demonstrated that pulmonary delivery of targeted IONPs can circumvent their nonspecific distribution into organs such as liver and spleen, which commonly receive the highest concentration when NPs were administered intravenously. Thus, (i) targeting by tumor cell-specific molecules (e.g., antibodies, receptors or ligands, etc.,), (ii) an appropriate choice of route of administration of MNPs, based on cancer type, and (iii) combination with other modalities such as CT or RT may result in accomplishment of a better tumor control.
Cancer relapse and its metastatic spread is a major challenge for the clinicians. Cancer stem cells (CSCs) were found to contribute to these features of cancer in addition to the mechanism of chemo- and radio-resistance. Many molecular and cellular approaches have been developed to target and kill the CSCs. Strategies for the application of MHT to target and kill the cancer cells are quite nascent but could prove highly effective, if the challenging task of targeting the CSCs in the tumor mass with MNPs could be achieved. Recently, Burke et al. compared the effectiveness of breast CSCs killing by conventional and nanoparticle-mediated photothermal therapy. Their findings suggest that breast CSCs are resistant to conventional hyperthermia partly due to the higher basal expression of HSP 90. In contrast, when these breast CSCs were treated with multiwalled carbon nanotubes, they became sensitive to hyperthermia delivered using a low power 1064 nm near infrared laser. It has been inferred that the cell death after laser-based HT was proportional to the time of laser exposure. Further,in vivo evaluation of efficacy of nanoparticle-mediated hyperthermia showed 100% survival of the mice compared to 20% survival in control. Atkinson et al. showed that in combination therapy, i.e., radiation therapy followed by optically activated gold nanoshells-based MHT resulted in radiosensitization of breast CSCs. Forty-eight hours after treatment, cells derived from the tumors treated with ionizing radiation and hyperthermia showed a significant decrease in tumorigenicity as well as increased differentiated phenotype than individual treatments. In another study, Galanzha et al. selectively targeted the circulating breast CSCs by tagging MNPs to folate or anti-human CD44 antibodies. Cancer cells targeted with these conjugated antibodies showed higher photothermal-based ablation when treated with NIR light., Sadhukha et al. demonstrated the efficacy of IONPs-mediated MHT in human lung and breast CSCs. Results showed that MHT caused a significant decrease in the CSCs of lung (A549) and breast (MDA-MB-231) carcinoma cells. Moreover, MHT was found to be significantly effective to suppress the colony and mammosphere formation of these tumor cells inin vitro conditions, respectively. Thus, these studies suggest that nanoparticles-based MHT may be an effective modality to kill CSCs and suppression of tumor growth and recurrences, which however, need to be further validated in other tumor models and under the clinical scenario.
The first step toward the application of MHT in clinics was the development of magnetic field therapy system for treatment of human patients. Gneveckow et al. developed the first clinical 100-kHz, ferrite core-based magnetic field applicator, magnetic fluid hyperthermia (MFH ®) 300F (MagForce Nanotechnologies AG, Berlin, Germany) with a magnetic field strength of up to 18 kA/m in a cylindrical treatment area (20 cm diameter and aperture height 300 mm). Johannsen et al. showed for the first time, the clinical application of MHT for prostate cancer in a 67-year-old patient, using aminosilane-coated MNPs and the MagForce MFH 300F applicator (100 kHz radio-frequency and variable field strength (0–18 kAm −1). Hyperthermia using MNPs was feasible and well tolerated in this pilot study, in previously irradiated and locally recurrent prostate carcinoma. In another study, Matsubara et al. reported a novel MHT system for the treatment of patients with bone metastases. They used a calcium phosphate cement containing MNPs for MHT and combined the therapy with acridine orange for photodynamic therapy. MHT was applied postoperatively by inserting the limb into a cylindrical coil of the electromagnetic field generator. This MHT treatment was performed in six patients with seven bone cancer metastasis locations. Their study showed that this combination therapy for bone metastasis can preserve the limb function without local recurrence. Thus, this clinical evidence signifies the potential of MHT as a promising and emerging modality for combinatorial cancer therapy.
In addition, optimization of the treatment plans (combining MHT and RT or CT) needs to be carried out in order to acquire maximum therapeutic gain, with minimum side effects to the patients.
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Matsubara T, Kusuzaki K, Matsumine A, Asanuma K, Nakamura T, Uchida A, et al. A minimally invasive surgery for bone metastases using the combination of photodynamic therapy and hyperthermia treatment. Int J Clin Med 2013;4:357-63. | http://www.journalrcr.org/article.asp?issn=2588-9273;year=2016;volume=7;issue=1;spage=13;epage=17;aulast=Shetake |
Focused Ultrasound (FUS) has drawn much attention in recent years because of its capability of providing localized therapeutic effects non-invasively at targeted regions. Traditionally, FUS exposures have been utilized at high rates of energy deposition for thermal ablations of benign and malignant tumors. More recently, FUS exposures have also been evaluated in a pulsed mode, which reduces the rate of energy deposition (for thermal effects) and generates mechanical effects resulting in enhanced tissue permeability. These exposures can also be modified for low-level hyperthermia (39 - 44°C) as an adjuvant therapy for drug delivery applications. Due to the relatively small size of the FUS focal zone, however, this type of treatment may require clinically unrealistic procedure times. Therefore, obtaining optimal FUS exposures is of great interest to both researchers and clinicians to reduce the treatment duration. Until now, the optimal exposure parameter selection and experimental demonstration of these parameters have not been reported for FUS-induced hyperthermia applications. In this dissertation, procedures to obtain optimal FUS exposures were proposed based on theoretical simulations. Initial simulations were carried out for the commonly used FUS tissue-mimicking phantoms, while subsequent measurements with thermocouples allowed for validation (18.4% difference) of the theoretical model. Once this was accomplished, the exposure optimization protocol was demonstrated for a murine xenograft flank tumor model. The evaluated FUS parameters included total acoustic power (TAP), duty cycle (DC), pulse repetition frequency (PRF), and blood perfusion. Preliminary in vivo studies of FUS mediated anti-tumor drug delivery via heat sensitive liposomes were conducted, and qualitative results were presented. The optimal FUS exposure for this particular in vivo setup was determined to be TAP of 4 W, DC of 50% and PRF of 5 Hz. The proposed protocol was then applied to a human tumor model (retinoblastoma) to explore the feasibility of using FUS and heat sensitive liposomes to achieve targeted chemotherapy. It was concluded that FUS frequency between 2 - 3.5 MHz may be best suited for such ocular tumor treatments.In addition to hyperthermia, FUS-induced mechanical effects were evaluated for monoclonal antibody delivery via in vivo experiments. Tissue processing and image based quantitative analysis techniques were developed to examine antibody penetration from the blood vessel walls and tumor periphery. It was observed that antibody intensities were doubled with FUS treatments in the proximity of both tumor periphery and blood vessel walls. Finally, the effects of temperature dependent micro-vascular perfusion (capillary network) and the effects of macro-vascular perfusion (large blood vessels) on FUS-induced hyperthermia were discussed. Micro-vascular perfusion was found to have a greater impact at long treatment times (i.e. 5 min or longer). The effects of macro-vascular perfusion (when treatment time was 2 min or longer) were observed to be confined within 2 - 4 mm from blood vessel surfaces.In summary, both FUS-induced thermal and mechanical effects can be utilized for targeted delivery into malignant tissues. Careful selection of FUS parameters would allow researchers and clinicians to conduct treatments in a more effective manner. | https://scholarspace.library.gwu.edu/concern/gw_etds/6m311p473?locale=en |
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Dr. Mazzaferro is a staff critical care specialist that has lectured at national and international veterinary conferences on the treatment of hyperthermia and heat-induced illness. She has authored a chapter on this subject in Ettinger's Textbook of Veterinary Internal Medicine.
Exertional heat stroke or hyperthermia can occur in as little as 30 minutes if animals are exercised in hot humid weather with little shade or opportunity to cool down and rest, leading to an impaired ability to dissipate heat. The most common form of hyperthermia is when an animal has been locked inside a vehicle on a hot day. Rapid early recognition of hyperthermia and prompt aggressive appropriate treatment are of utmost importance in having a favorable outcome.
Pathophysiology
Normally, heat balance occurs through the actions of heat gaining and heat dissipating mechanisms. Heat gain occurs through oxidative metabolism of foodstuffs, exercise and increased muscle or metabolic activity, and elevated environmental temperature. Heat dissipating mechanisms to prevent excessive heat gain include behavioral changes (i.e., seek a cooler location), peripheral vasodilation and changes in circulation, evaporative cooling primarily in the form of respiratory heat exchange, radiation, and convection. As environmental temperature approaches body temperature, evaporative heat loss becomes important to maintain body temperature. Animals, who lack sweat glands, depend primarily on heat dissipation and evaporative cooling from the respiratory system by panting. When body temperature rises, signals to the thermoregulatory center initiates a relay of signals to the panting center, creating a reflex to help dissipate heat and prevent hyperthermia. As air comes in contact with the mucous membranes of the upper airways, evaporative cooling occurs. Further accumulation of heat occurs as metabolic rate increases. A second method of cooling can occur by convection, in which an overheated animal lays on a cooler surface, and the body heat is transferred to the cooler surface. Risk factors for developing hyperthermia include high ambient humidity, upper airway obstruction, laryngeal paralysis, brachiocephalic airway syndrome, collapsing trachea, obesity, and previous history of hyperthermia. Lack of shade and a lack of a cool-down period after exercise can also predispose an animal to develop exertional hyperthermia. Any animal that works or exercises in a hot humid climate must be allowed time to rest in a cool, shady place with plenty of water every ½ hour to hour. Animals that have not acclimated to warm humid climates should not be worked as hard, as they may have an increased risk of developing hyperthermia. In one study of 42 cases of hyperthermia, Weimaraners, St. Bernards, Australian Shepards, and Bulldogs were overrepresented.
Nonpyrogenic hyperthermia results from the body's inability to adequately dissipate heat. Antipyretic agents are therefore often ineffective in reducing body temperature, and are actually contraindicated due to potentially adverse side effects of decreasing renal perfusion and increased chance of gastrointestinal ulceration. Differential diagnoses in patients with rectal temperatures greater than 104.9 degrees Fahrenheit include inflammatory diseases of the central nervous system including meningitis and encephalitis, and hypothalamic mass lesions affecting the thermoregulatory center. Other potential differential diagnoses include malignant hyperthermia in affected animals, particularly Labrador Retrievers or Collie-type dogs, and unwitnessed seizure activity.
The gastrointestinal tract is also a key player in multiorgan failure associated with hyperthermia. Decreased perfusion to the mesentery and thermal injury to enterocytes often results in a disruption of the gastrointestinal mucosal barrier and subsequent bacterial translocation. Bacteremia and elevation of circulating bacterial endotoxin can lead to sepsis, systemic inflammatory response (SIRS) and multiorgan failure. Patients with severe hyperthermia often present with hematemesis and severe hematochezia, often sloughing the lining of their intestinal tract. Thermal injury to hepatocytes can also result in decreased hepatic function, with elevation of hepatocellular and cholestatic enzyme activities. Persistent hypoglycemia in affected patients may be associated with hepatocellular dysfunction and depletion of glycogen stores. Hyperthermia also induces widespread endothelial damage, one of the key factors in the development of disseminated intravascular coagulation (DIC). Massive global thrombosis can result in multiorgan failure and death. Finally, hyperthermia can cause cellular neuronal damage, neuronal death, and cerebral edema. Thrombosis or intracranial hemorrhage and seizures can also occur. Altered levels of consciousness are among the most common clinical signs of heat-induced illness.
As hyperthermia progresses, central nervous system depression, seizures, coma, and death may occur. Severe mentation abnormalities including coma is associated with a negative outcome.
Clinical Signs
Patients with heat-induced illness or hyperthermia often present with a history of excessive panting, collapse, vomiting, ataxia, hypersalivation, seizures, or diarrhea. Listlessness, muscle tremors, loss of consciousness, altered level of consciousness, hematuria, cyanosis, epistaxis, swollen tongues, head tremors, vocalizing, stridor, and dilated pupils are also less frequently described. Clinical signs may not become apparent for several days after the inciting event. Changes in mentation, oliguria, vomiting, hematemesis, diarrhea, dyspnea, icterus, and petechiation can occur almost immediately after heat-induced illness, or can occur 3–5 days after the inciting event.
Laboratory Changes
All patients with hyperthermia should have serial complete blood counts, biochemical analyses, coagulation profiles, arterial blood gases, venous lactates, and urinalyses performed. In many cases, prerenal and renal azotemia is present, with elevated BUN and creatinine concentration secondary to renal tubular necrosis. Alterations and elevations in hepatocellular enzyme function secondary to hepatocellular thermal injury or hepatic thrombosis are also demonstrated with elevated ALT, AST, and total bilirubin. Elevations in creatine kinase (CK) and AST are secondary to rhabdomyolysis. Blood glucose may be decreased, but this finding is inconsistent. Packed cell volume and total solids may be increased secondary to hypovolemia and dehydration with subsequent hemoconcentration. Thrombocytopenia, prolonged PT and APTT and elevated FDPs may be observed if DIC is present. In some cases, thrombocytopenia may not become apparent for several days after the initial insult. Arterial blood gas analyses can be variable, with a mixed respiratory alkalosis and metabolic acidosis secondary to increased lactate can be present. Urinalysis may reveal the presence of renal tubular casts or glucosuria, both indicators of renal tubular epithelial damage.
Treatment
Treatment goals are to manage the hyperthermia, provide cardiovascular support, and to treat any complications associated with the hyperthermia. Cornerstones of therapy include restoration of circulating blood volume, improving glomerular filtration and renal blood flow, stabilizing electrolyte balance, and providing broad-spectrum antibiotics to minimize complications of bacterial translocation and sepsis. In the field, the animal should be moved to a cool area in the shade or indoors, away from direct sunlight. The animal should be sprayed with cool but not cold water. Cool packs can be placed in the axillary and inguinal regions. Air conditioning or cool fans can also help dissipate heat and improve convective cooling mechanisms. It is very important to cool the patient to 103 degrees within 30 to 60 minutes of initial presentation, but to avoid overcooling. Immersion in ice baths or cold water is absolutely contraindicated because this practice causes peripheral vasoconstriction. Vasoconstriction results in further elevation of core body temperature. Other methods of cooling that have been described, but offer no real advantage or improvement of clinical outcome include administration of cool intravenous fluids, gastric lavage, cold-water enemas, and cool peritoneal lavage.
Intravenous fluids should be administered judiciously during the early stages of hyperthermia and heat-induced illness, as early in the course of disease, fluid loss is not great, and oversupplementation of crystalloids can worsen cerebral edema and cause pulmonary fluid overload. A balanced electrolyte fluid such as Normosol-R, Plasmalyte-M, or lactated Ringer's can be administered, tailoring each patient's individual fluid needs based on central venous pressure, acid-base and electrolyte status, blood pressure, thoracic auscultation, and colloid oncotic pressure. If a free water deficit is present, as evidenced by hypernatremia, the clinician should calculate the free water deficit and replace it slowly over a period of 24 hours, to prevent further cerebral edema. Oxygen should be administered in animals with signs of upper airway obstruction. If laryngeal paralysis is present, sedative and anxiolytic agents such as acepromazine should be administered. In severe cases of upper airway obstruction and laryngeal edema, glucocorticoids can also be administered to decrease airway edema. The use of empiric glucocorticoids in patients without signs of airway obstruction is controversial, as they can further impair renal perfusion and predispose to gastrointestinal ulceration. Their empiric use is not justified and is not advised at this time. Broad-spectrum antibiotics such as the Unasyn, cefoxitin, ampicillin with enrofloxacin, and sometimes metronidazole should be administered to decrease bacteriemia.
Prognosis
Severe hyperthermia can result in widespread organ failure, and must be recognized and treated promptly. In most cases, prognosis is guarded to grave, depending on the presence of underlying diseases and complications. Mortality rates are directly associated with the duration and intensity of hyperthermia. Permanent damage to kidneys, liver and brain can occur, including permanent changes in the hypothalamic thermoregulatory center that can predispose the patient to further hyperthermic episodes. The clinician must give a guarded prognosis in most cases.
If death is going to occur, it usually happens within the first 24 hours of the incident. If an animal survives past 48 hours of hospitalization, the outcome is generally good. Animals who present with coma or hypothermia after a hyperthermic event generally have a very grave prognosis, even with extremely aggressive therapy.
References
References are available upon request. | https://www.vin.com/apputil/content/defaultadv1.aspx?pId=14365&catId=73680&id=7259207&ind=91&objTypeID=17 |
1. School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, P. R. China.
2. State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China.
3. West Anhui University, Lu'an, P.R. China
4. Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources, P. R. China.
*These authors contributed equally to this work.
Drug delivery for tumor theranostics involves the extensive use of the enhanced permeability and retention (EPR) effect. Previously, various types of nanomedicines have been demonstrated to accumulate in solid tumors via the EPR effect. However, EPR is a highly variable phenomenon because of tumor heterogeneity, resulting in low drug delivery efficacy in clinical trials. Because ultrasonication using micro/nanobubbles as contrast agents can disrupt blood vessels and enhance the specific delivery of drugs, it is an effective approach to improve the EPR effect for the passive targeting of tumors. In this review, the basic thermal effect, acoustic streaming, and cavitation mechanisms of ultrasound, which are characteristics that can be utilized to enhance the EPR effect, are briefly introduced. Second, micro/nanobubble-enhanced ultrasound imaging is discussed to understand the validity and variability of the EPR effect. Third, because the tumor microenvironment is complicated owing to elevated interstitial fluid pressure and the deregulated extracellular matrix components, which may be unfavorable for the EPR effect, few new trends in smart bubble drug delivery systems, which may improve the accuracy of EPR-mediated passive drug targeting, are summarized. Finally, the challenging and major concerns that should be considered in the next generation of micro/nanobubble-contrast-enhanced ultrasound theranostics for EPR-mediated passive drug targeting are also discussed.
Keywords: EPR effect, ultrasound, micro/nanobubbles, controlled drug delivery, tumor theranostics
Solid tumors exhibit a special microenvironment featuring tortuous vascularity, angiogenesis, and hypoxia [1-3]. Abnormal tumor vasculature, high interstitial fluid pressure, growth-induced solid stresses. And solid stresses from the abnormal stromal matrix are the main limitations that prevent drugs from penetrating the solid tumor [4, 5]. Therefore, the accurate and efficient delivery of theranostic agents into tumor lesions in a controlled manner is critical and remains a significant challenge till date. However, the absence of vascular supportive tissues in tumors results in the formation of leaky vessels with pores (200 nm to 1.2 μm in diameter) and leads to poor lymphatic drainage, which is the structural basis of the enhanced permeability and retention (EPR) effect. The EPR effect is considered an effective method to achieve the passive targeting of tumor tissues [7, 8]. In preclinical studies, targeted delivery systems based on EPR have demonstrated a remarkable improvement in anticancer efficacy when compared with the efficacy of traditional chemotherapeutic drugs [7-9].
However, numerous parameters (such as vascular permeability and mutation, tumor cell density, and tumor stromal heterogeneity) prevent the successful application of EPR-based theranostics in clinical applications because of tumor heterogeneity [10-15]. Different patients with the same type of tumor, different types and sizes of tumor, and different developmental stages of the same tumor may show different EPR effects [16, 17]. For example, hepatocellular carcinoma and renal cell carcinoma both have high vascular density and exhibit a strong EPR effect, whereas pancreatic and prostate cancers are characterized by low vascular density, resulting in a lower EPR effect . Metastatic tumors have a high degree of necrosis at the central site relative to the primary tumor because of the lack of blood vessels due to the decrease in the EPR effect. Therefore, accurately monitoring and evaluating the EPR conditions of different tumors is essential to formulate personalized EPR-mediated tumor treatment .
In recent years, various nanomaterials based on the EPR effect have been used because the sizes of these nanomaterials can be modulated according to the pore sizes in tumor blood vessels. Because different types of tumors have different sized gaps in the endothelial cells, a suitable nanoparticle size must be selected according to the type of tumor. Furthermore, the interception by biological barriers when nanomaterials enter the circulation system also needs to be considered. Particularly, nanoparticles should not be destroyed by the reticuloendothelial system (increased particle size) while maintaining the ability to penetrate the tumor (reduced particle size) [20, 21]. Although the gaps and pores in the wall of tumor vessels may provide a pathway for the exudation of nanoparticles, the intermittence and disorder of the vascular structure reduce the blood flow and intravascular pressure. This may result in the reduction of macromolecular drugs or nanocarriers entering the stroma through the vascular gaps by diffusion . Without further increasing the movement of these drugs via diffusion, the efficiency of delivery will not be significantly improved.
Various diagnostic and therapeutic strategies that make the best use of the EPR effect.
In view of these challenges, to best leverage the EPR effect in nanomedicine delivery, various diagnostic and therapeutic strategies have been developed (Figure 1). To monitor and evaluate the heterogeneity of the EPR effect in a particular patient, non-invasive imaging techniques (such as ultrasound, magnetic resonance imaging (MRI), and positron emission tomography (PET)) have been applied. With the development of contrast agents such as micro/nanobubbles (MNBs) [23-25], magnetic nanoparticles [26, 27], radionuclides, and fluorophores, the EPR effect can be accurately visualized and quantified [28-31]. Nanomaterial-based EPR targeting strategies mainly focus on controlling the size of the drug or carrier and/or using ligands that bind to molecules that are related to the EPR effect. An appropriately sized material can pass through the permeable tumor vascular system and passively accumulate in the tumor tissue via passive targeting. The modification of the ligands on the surface leads to active targeting. The transport of the micro-materials and nanomaterials in tumor tissue is shown in Figure 2. Perfluorocarbon (PFC) nanodroplets can accumulate in the tumor tissue via passive targeting, and the targeted microbubbles and nanobubbles are used to realize active targeting.
Transportation of micro/nanobubbles in the tumor tissue.
Summary of ultrasound classification and acoustic vehicles for tumor theranostics.
|Payload classification||Ultrasound Classification||Therapeutic|
Substance
|Vehicle||Tumor Type||Author, Year, Publishing Periodicals, Ref.|
|Chemicals||Low-frequency Ultrasound||Paclitaxel (PTX)||poly(lactide-co-glycolic acid) nanobubbles||prostate cancer||Wu, 2017, Int J Nanomedicine, |
|Endostar||lipid microbubbles||colon cancer||Zhang, 2014, Cancer Lett, |
|High-frequency Ultrasound||Cilengitide nanoparticles (CGT-NP)||phospholipid-based microbubbles||gliomas||Zhao, 2016, J Controlled Release, |
|Focused Ultrasound||boron drug||polymer microbubbles||brain glioma||Fan , 2019, ACS Appl Mater Interfaces, |
|Doxorubicin (DOX)||phase-changeable nanodroplets||breast cancer||Cao, 2018, Theranostics, |
|Doxorubicin(DOX)||lipid microbubbles||brain tumor||Park, 2017, J Control Release, |
|Nanoparticles (NPs)||Low-frequency Ultrasound||Gold nanoparticles and Gemcitabine and miR-21 Inhibitor||Dendrimer-Entrapped Gold|
Nanoparticles
|pancreatic cancer||Lin, 2018, Theranostics, |
|High-frequency Ultrasound||superparamagnetic nanoparticles (MNPs) and Anethole dithiolethione (ADT)||magnetic nanoliposome (AML)||HepG2||Liu ,2017, ACS nano, |
|superparamagnetic iron oxide nanoparticles (SPIO) and RGD‐l‐TRAIL||magnetic microbubbles (Polymer microbubbles)|
.
|colon cancer||Duan, 2016, Adv Funct Mater, |
|Focused Ultrasound||superparamagnetic iron oxide nanoparticles (SPIO)- Doxorubicin (DOX)||lipid microbubbles||rat cerebral glioma||Fan , 2016, Theranostics , |
|Therapeutic gases||Low-frequency Ultrasound||O 2, Paclitaxel (PTX)||Lipid Microbubble||ovarian cancer||Liu, 2015 Cancer Lett, |
|NO/DOX||Ultrasound responsive|
liposome
|breast cancer/|
pancreatic cancer
|Wang, 2017, J Control Releae |
|CO2||Hollow Mesoporous Silica|
Nanoparticle
|pancreatic cancer||Zhang, 2015, Theranostics, |
|Focused Ultrasound||NO||Hollow Mesoporous Silica Nanoparticles||pancreatic cancer||Zhang, 2016, Acs Nano, |
To enhance the efficacy of delivery, three approaches based on the EPR effect have been developed. The first approach involves exerting physical exogenous factors (light [32-34], heat [35-37], ultrasound [38-41], and radiation [42, 43]) to promote the permeability of tumor blood vessels and tissues. The second is to develop tumor microenvironment-targeted smart responsive nanomaterials to improve the permeability and retention of drugs at the tumor site [44-48]. The third is to combine the internal biochemical response with external regulatory factors. Some micro-nano materials have special properties because of which they can respond to internal and external triggers. Using a series of biological effects generated during such a response, the drug delivery efficiency at the tumor site can be further improved. In this review, we summarize the EPR effects based on ultrasound and MNBs and the enhancement of these effects. First, the physical effects of ultrasound on EPR are briefly introduced. The interaction between EPR- and MNB-assisted acoustic energy is highlighted. Finally, some new trends in smart bubble drug delivery systems are summarized and speculated for future cancer theranostics.
Acoustic transducers are used to generate transverse or longitudinal waves with frequencies greater than 20 kHz. Medical ultrasound is characterized by a broad frequency range of 0.1-50 MHz and peak negative pressures of 0.01-10 MPa. It can be classified into focused and unfocused ultrasound depending on the radiation distribution of transducers. It can also be characterized into continuous and pulsed ultrasound depending on the waveform and with parameters such as pulse length and pulse repetition frequency. When used in biomedical applications, the acoustic densitometry of ultrasound can be expressed in the following manner. Sonic intensity can be defined as the time-averaged rate of sonic energy-flow through unit area . Ultrasound with a sonic intensity higher than 5 W/cm2 is generally referred to as high-intensity ultrasound, while that with an intensity between 0.5 and 1 W/cm2 is usually considered to be low-intensity ultrasound. In clinical ultrasound imaging, the output levels of the ultrasound equipment can be quantified using the mechanical index (MI) defined by the U.S. Food and Drug Administration (FDA). MI is expressed as the ratio of in situ peak negative pressure (PnP) to the square root of the center frequency (Fc), as shown in Equation (1):
(1)
In general, the maximum output levels of diagnostic devices are limited to an MI of 1.9, which is the maximum allowed value for clinical imaging applications without microbubbles . Incompressible drug carriers such as micelles and liposomes can be applied with the maximum MI of 1.9, while compressible material such as microbubbles should be applied with the maximum allowable MI of 0.8 .
When ultrasonic energy is applied for the diagnosis and treatment of tumors, acoustic waves can be used to enhance the EPR in two ways: drug release and bioeffects. During drug release, ultrasound can stimulate the carrier to release its cargo and increase the distribution concentration of drugs in the tumor. The efficiency of drug release is controlled by acoustic parameters such as ultrasound frequency, power density, and pulse duration [52, 53]. Alexander et al. compared the effects of continuous wave (CW) and pulsed ultrasound on doxorubicin (DOX) uptake by HL-60 cells. The drug uptake increased with a pulse duration in the range 0.2-2 s, and was comparable with CW ultrasound (10 s pulse) when a pulse with a duration of 2 s was applied. High-frequency ultrasound exhibits sharper focusing than low-frequency ultrasound, whereas low-frequency ultrasound penetrates the interior of the body deeper than high-frequency ultrasound. The typical penetration depth of 1-MHz ultrasound for various tissues is generally a few millimeters. In contrast, low-frequency ultrasound (20-100 kHz) can penetrate depths reaching tens of centimeters in some types of tissues. High-frequency ultrasound has, therefore, been advantageous for use in the targeted delivery of drugs to small superficial tumors, whereas low-frequency ultrasound is beneficial for treating large and deeply located tumors . For all frequencies studied , the drug release increases with increasing power density.
For bioeffects, the use of acoustic energy with EPR mainly focuses on the enhancement of cell membrane permeability . For example, Liu et al. found that compared with other treatment intensities, ultrasonic exposure at 1 MHz and 0.25 W/cm2 can promote the platelet penetration of gold nanoparticles (GNPs). The results indicated that ultrasound can enhance membrane permeability, which has been proved using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
Besides, acoustic waves interact with drug carriers, body tissues, and cell membranes via a combination of thermal and mechanical effects . The key mechanisms by which EPR interacts with acoustic waves are mechanical and thermal energy. Low-intensity ultrasound (0.51 W/cm2) is known to be non-thermal, and this may be regarded as the boundary between mechanical and thermal effects.
The mechanical effects of ultrasound and MNB-assisted ultrasound on EPR are based on both acoustic radiation forces and mechanical bioeffects.
Because of the momentum exchange between the object and the sound field, an acoustic wave can move suspended micro-objects by exerting a force known as the acoustic radiation force (ARF) .
The various forces that act on an air bubble in a sound field are often referred to as Bjerknes forces , which include two physical phenomena: primary Bjerknes forces and secondary Bjerknes forces. The force that influences the microcapsule via the ''primary'' (external) sound field is called the primary Bjerknes force and can be expressed as Equation (2). Assuming that the microcapsules are spherical and placed in an ideal plane ultrasonic wave, the force acts to propel the capsules in the direction of acoustic propagation as per the following equation:
(2)
where P is the mean energy density of the incident wave, Yp is a dimensionless factor known as the radiation force function that depends on the scattering and absorption properties of the capsule, and r is the radius of the capsule.
The force between two bubbles that is caused by the ''secondary'' sound fields emitted by other bubbles is known as the secondary Bjerknes force . The secondary Bjerknes force is given by Equation (3):
(3)
where < > denotes the time average, ρ is the density of the liquid, d is the distance between the first bubble and the second one, V1 and V2 describe the volume of the first and second bubbles, respectively, and er denotes the radial unit vector. The mutual interaction forces between two small coupled gas bubbles (R0<10 μm) in a strong low-frequency acoustic field (Pa>1 bar, f = 20 kHz) have been investigated in a previous study using the Keller-Miksis equations. The nonlinear resonance of bubbles leads to secondary Bjerknes forces between the bubbles that are stronger by a factor of 103-106 than that expected from linear approximations.
The EPR effect would be considerably increased if the agent was initially concentrated in a particular region, and if the velocity of the agent passing the potential binding site was decreased. Dayton et al. demonstrated that the radiation force of ultrasound can displace a microbubble contrast agent to the wall of a 50-mm blood vessel, significantly reduce the velocity of the flowing contrast agents, and produce reversible aggregation. Such microbubble aggregates in large vessels were observed optically under the influence of acoustic radiation force by Wang et al. . The first acoustic radiation force intravascular ultrasound transducer was designed to translate microbubbles to the vessel wall under flow velocities comparable with that in the human common carotid artery to enhance the binding efficiency of intravascular microbubbles and drug delivery .
Acoustic streaming is defined as the radiation force from reflectors and scatterers in an ultrasonic field that can cause local particle displacements and fluid currents. The movement of localized fluid currents in the direction of the propagating ultrasound radiation forces that are induced by sound waves is termed bulk streaming. Microstreaming involves localized eddies or currents that are generated next to cavitating bodies. The differences between bulk streaming and microstreaming are shown in Figure 3. The acoustic streaming effect can be used to displace particles in the blood or change the motion of blood flow . These mechanical actions generated by ultrasound may result in the release of drugs from carriers and the associated movement of the drug into the targeted tissue . Microstreaming with bubbles or particles plays an important role in in vitro low-frequency sonophoresis .
With the same acoustic-pressure amplitude, the maximum streaming velocity of ultrasound contrast agent (UCA) microbubbles is achieved under the action of resonance frequency. The velocity fields of the streaming sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model . The maximum streaming velocity was approximately 60 mm/s at a resonance frequency of 2.25 MHz, and the streaming velocity decreased to 15 mm/s at 1.0 MHz for the same amplitude of acoustic pressure.
Bulk streaming and microstreaming in the blood vessel.
Gas-filled bubbles show different oscillation performances when acoustic parameters such as the pulse length, amplitude, and frequency are varied. The stable cavitation (SC) of UCAs is usually accomplished at low sound pressures (<0.1 MPa). When exposed to sufficiently large acoustic rarefactional pressure amplitudes, UCAs undergo a violent collapse known as inertial cavitation (IC) . This phenomenon results in the generation of shock-waves, broadband acoustic emissions , jetting , and microstreaming . These effects have been identified as key mechanical triggers for various medical [40, 71] and industrial applications [72-74].
The difference between SC and IC is due to the different degrees of bubble deformation under ultrasonic irradiation. Many models have been developed to describe the deformations that can occur on the surface of a coated bubble because of oscillation. Marmottant et al. presented a model that incorporates the effect of coating on the response of a microbubble to ultrasound. Based on the US-induced SC or IC, UCAs have wide applications in medical diagnosis and treatment such as contrast harmonic imaging and ultrasound-induced gene/drug delivery [76-78].
For US-induced SC or IC of MNBs, MNBs are either excited, causing them to oscillate and mechanically massage the vascular wall, or are destroyed, generating micro-jets. These mechanical effects can lead to the creation of pores in the cell membrane. The opening of the inter-endothelial junctions contributes to an enhancement in the vessel permeability and improves the extravasation of co-administered drugs .
MNB-mediated sonoporation occurs because of the physical perturbation of cellular structures . Marmottant et al. controlled vesicle deformation and lysis by a single oscillating bubble. They found that gentle bubble oscillations are sufficient to achieve the rupture of lipid membranes.
The enhanced efficiency can be evaluated through the accurate measurement of the spatial and temporal scales of these pores. Some methods are available to measure these pores. SEM and atomic force microscopy (AFM) have both been employed to obtain information about pores [82-85]. The transmembrane current (TMC) of a single cell under a voltage clamp can also be used for monitoring sonoporation in real-time .
When a blood vessel is located near the focal spot, a part of the acoustic energy is absorbed and converted to thermal energy. Tissues may have different sensitivities to ultrasound-induced damage. This sensitivity to the effects of ultrasound-induced heating has primarily been studied by Stanley et al. . Thermal conversion efficiency is related to protein content and blood perfusion. For example, it has been reported that the absorption coefficient increases as a function of the protein content, which has a positive effect on the ultrasound-induced increase in temperature. Furthermore, biological tissue with poor blood perfusion can also be significantly heated by ultrasound because of slow heat dissipation .
Ultrasound energy can be absorbed and transformed into thermal energy in tissues as the acoustic waves propagate through the tissue and generate friction . Mild hyperthermia in a tumor (41-43 °C for 10-60 min) may improve the therapeutic efficacy of drugs by acting on tumor hemodynamics . The mild hyperthermia induced by focused ultrasound may, therefore, enhance drug or drug carrier extravasation in tumor tissue . In a previous study, a thermo-sensitive liposome was designed , and the results showed that drug release can be triggered by mild hyperthermia when the temperature is just above the normal physiological temperature.
Estimating the efficiency of the temperature rise caused by radiation of ultrasound is critical. When the distance between the surface of the blood vessel and the focal point is 2.5 mm, the temperature at the focal point was saturated after approximately 50 s of radiation, and the maximum cooling caused by the blood flow was approximately 0.5 °C when the supply of radiation was ceased . Based on the thermal wave model of bioheat transfer, Tan et al. numerically investigated the influence of blood vessels on temperature during high-intensity focused ultrasound hyperthermia . The results showed that a longer duration of thermal relaxation leads to the production of smaller thermal lesions.
MNBs comprise a gaseous core encapsulated in a shell of biocompatible materials such as lipids or proteins, typically ranging from 0.1 to 10 μm in diameter. When exposed to ultrasound, MNBs can contract and expand, which may result in backscattering of the ultrasound, cavitation, or even bursting of the shell. Because of these acoustic behaviors, MNBs have been extensively used as UCAs and have shown increasing potential for drug delivery. Under low-intensity ultrasound irradiation, MNBs can be used as contrast agents in ultrasound imaging for EPR evaluation. Through high-intensity ultrasound-mediated cavitation, EPR mediated therapy can be improved with enhanced drug delivery.
The materials of the encapsulated gas and shell together determine the physicochemical properties of a bubble. The transport properties of the encapsulated core gas mainly affect the stability of the bubbles. Air and bioinert heavy gases such as sulfur hexafluoride or perfluorocarbons are often used in commercial UCAs found in clinics. One approach to increase the stability of UCAs is to use insoluble gases. For example, perfluorocarbons have a higher resistance to water permeation than to air [92, 93]. Recently, bioactive gases that have significant therapeutic potential, including nitric oxide [94, 95] and oxygen [96, 97]; have been encapsulated in UCAs for parenteral delivery.
The performance of MNBs primarily depends on the physicochemical properties of the shell material. Proteins, polymers, and lipids are mainly used as shell materials for bubbles. The echogenicity of MBs and NBs is significantly different because of the size difference. MBs possess good echogenicity and have been widely used for ultrasound imaging. A reduction in the size reduces the acoustic response of the bubble . The microbubbles may be more useful in inducing vessel permeability than nanobubbles due to their larger volume change and higher acoustic response under the ultrasound radiation. The echogenicity of NBs can be improved via shell modification and bubble aggregation. Research has shown that NBs are more stable and exhibit a longer circulation time than MBs . However, extravasation is different in MBs and NBs. The size of MBs is usually in the order of a few microns. MBs are used as blood pool contrast agents because they are transported after intravenous injection into the bloodstream , where they either remain in circulation until taken up by the spleen or the liver or are dissolved over short periods. Typically, tumor vessels are permeable to particles smaller than 1 μm . Based on these premises, MBs cannot escape the capillaries and enter the defective tumor microcirculation via the EPR effect. Compared with MBs, NBs can penetrate the sites where tumor vascular leakage takes place via EPR and can accumulate in the tumor. The gaps between the endothelial cells in tumors, therefore, allow passive targeting with NBs. Fluorescent dye-labeled NBs have been found in the intracellular spaces of tumor cells . NBs are also more stable and exhibit longer circulation time than MBs, which leads to further accumulation in tumors. In vivo studies have confirmed the ability of NBs to passively target tumor tissues via the EPR effect . The accumulation of NBs in the tumor area can lead to higher quality imaging and more effective drug delivery. Cavalli et al. showed that amphiphilic drugs and negatively charged complexes can be simultaneously loaded into a NB, which indicates their theranostic capability .
The mechanical effects that ultrasound-mediated MNBs have on the EPR are associated with the process of cavitation, which is mainly due to the oscillation of gas-filled bubbles in an acoustic field. MNBs have different responses to external stimulation based on the features of the applied ultrasound, as shown in Section 2 in the review. Under diagnostic frequency and low sound pressure (<0.1 MPa), bubbles expand and contract with a small amplitude, and the generated energy is low enough to form an SC. This regular oscillation can echo the ultrasonic wave utilized by ultrasound imaging. The SC can create a circulating flow of fluid around the bubble, which is known as microstreaming. Under higher sound pressures (>0.1 MPa), the oscillation of the bubble becomes nonlinear and the expanded diameter is much larger, causing the microbubbles to oscillate drastically. When the sound pressure exceeds a certain threshold, the bubbles instantaneously collapse to release strong jets, shock waves, and shear force (IC). Both SC and IC lead to the creation of pores in the cell membrane and the opening of interendothelial junctions, thus enhancing vessel permeability and improving the extravasation of co-administered drugs .
Inducing cavitation via MNBs changes the vascular and cell membrane permeability of a tumor. Both SC and IC can cause mechanical disturbance to the vessel walls and cell membranes in cancer tissue, thus improving the EPR effects in the tumor. The application of ultrasound to vessels containing MNBs can change the permeability of the blood vessel wall, resulting in the extravasation of drugs into the interstitial space. The change in the permeability of the capillaries depends on various factors, including shell composition, bubble size, the ratio of capillary diameter to bubble diameter, and ultrasound parameters. In addition to changing the permeability of the blood-vessel wall, the cavitation of MNBs can enhance the permeability of a cell membrane. The collapse of a bubble and the associated production of a jet can instantly break adjacent cell membranes. Small holes are produced within a cell membrane, resulting in either repairable or non-repairable sonoporation. With different ultrasound parameters, short-lived pores are produced within the cell membrane and exogenous materials can thus be transported into the cytoplasm. The collapse of MNBs can also cause cell death in the tumor tissue, which further alleviates solid stress and can reduce the barriers to deeper penetration. Studies have shown that cavitation effects can alter vascular and cell membrane permeability through three different mechanisms: (1) During the regular mechanical disturbance of the oscillating bubbles undergoing SC, the cell membrane potential is changed to promote endocytic uptake [103, 104]. (2) The volume of the oscillating bubble changes during the transition from SC to IC. The gap between the vascular endothelial cells is temporarily increased and the integrity of the vascular endothelium is destroyed, thereby allowing enhanced diffusion of the active substances, which can then enter the tissue [71, 105, 106]. (3) Based on the sonoporation produced by IC, transient pores are generated within the vascular endothelial cells, which promote the uptake of intracellular macromolecules [86, 107-109].
Cavitation is directly affected by various factors, such as ultrasound frequency, intensity, and the length of US pulses, which in turn influence the EPR in the biological tissues or cells. Low-frequency ultrasound (20-100 kHz) can penetrate the tissues deeper than high-frequency ultrasound (1-3 MHz). Transdermal transport and cell penetration are enhanced as the US frequency decreases [110, 111]. Yang et al. experimentally demonstrated the cavitation of polymer shelled MBs mediated by ultrasound fields of different frequencies and sound pressures. MBs loaded with Fe3O4 nanoparticles ruptured and released the nanoparticles into the cells under exposure to ultrasound. The results showed that cells internalized the Fe3O4 nanoparticles released by the MBs most efficiently at 1 MHz and 0.25 MPa. The pores in the cell membrane can be simultaneously repaired by the lysosomal membrane associated protein (LAMP-1). When the sound pressure exceeded 0.25 MPa, the severe nonlinear oscillation of the microbubbles may have caused permanent damage to the cells. It has been found that high-intensity focused ultrasound combined with microbubbles can open the blood-brain barrier (BBB), which provides a means for treating brain tumors. Pulsed US causes less negative biological interactions with healthy cells and tissues not intended for treatment . For medical purposes, the use of pulsed US is, therefore, more favorable than the use of CW. High-intensity focused ultrasound (HIFU), which can focus US intensity at the target site, has been developed for ablating various types of live tissue . This treatment is known to have irreversible thermal effects, including hemostasis and blood vessel occlusion. However, the pulsed-HIFU (pHIFU) treatment can reduce these irreversible thermal effects by reducing the average intensity of US at the target tissue. This pulsed-HIFU (pHIFU) method has been developed to enhance the extravasation and tissue penetration of nanoparticles in the femoral tissue of mice .
In addition to cavitation, MNBs can also generate other biological effects, such as thermal effects, under the guidance of high-intensity ultrasonic energy. These biological effects work together to temporarily enhance the permeability of biological tissues and blood vessels, allowing the active substances carried in the MNBs to enter the tumor tissue more easily through the EPR effect, which is the theoretical basis of ultrasound-assisted MNB-enhanced EPR.
The high heterogeneity of EPR among individual patients is considered a major barrier to the clinical application of nanomedicines. In preclinical validation, drug delivery systems generally work very well, with significant improvements in both target site accumulation and therapeutic efficacy. Clinically, however, the efficacy of passive tumor-targeted nanomedicines is compromised because of the large inter- and intra-individual variability in EPR. Significant increases in tolerability but hardly any increases in efficacy have been seen in clinical therapy [10, 11, 19]. Consequently, it is necessary to develop methods to visualize and characterize the EPR effect before treatment. Based on the assessment of individual EPR, patients presenting with sufficiently high levels of EPR, pre-stratify responders, and non-responders could be pre-selected to individualize and improve nano-chemotherapeutic treatments.
Ultrasound contrast imaging is a simple, non-invasive imaging modality used to evaluate vascular conditions. However, tumors are characterized by tortuous vascularity, angiogenesis, and hypoxia. To address these problems, different strategies for MNB-enhanced ultrasound imaging based on EPR have been developed. One important factor to be considered in ultrasound imaging is the accumulation of MNBs in tumor tissue. As mentioned above, NBs of an appropriate size can penetrate the leakage sites of tumor vascular tissue. EPR-mediated passive targeting can result in the accumulation of NBs in the tumor. However, the enhancement of ultrasound imaging by nanobubbles is reduced relative to microbubbles in clinical applications. Therefore, it is important to maintain its ability to enhance ultrasound imaging while the bubble size is reduced. A sufficient aggregation of NBs within the tumor is beneficial for a high quality image and can be used for enhanced ultrasound imaging of a tumor . The shell composition of the bubbles can also be adjusted to increase the echo signals of bubbles in an ultrasonic field. Studies have shown that the incorporation of magnetic nanoparticles into bubble shells can enhance ultrasound imaging [117, 118], which could be used to improve the imaging ability of NBs.
Although MBs cannot pass through blood vessels and enter tumor tissue, efforts can be made to allow them to accumulate around the blood vessels of the tumor. Angiogenesis is a remarkable characteristic in the tumor microenvironment. Endothelial cells and receptors associated with angiogenesis are readily accessible for targeting with MBs. The conjugation of ligands onto the surface of MBs has already been proven successful for MB accumulation in tumors for imaging purposes. It has been reported that a better ultrasound signal was detected from MBs in angiogenic areas after the conjugation of arginylglycylaspartic acid (RGD) peptides onto the MB surfaces .
Another important factor in contrast ultrasound imaging for EPR characterization is to identify the correlation between the imaging parameters of tumor blood vessels and drug accumulation in tumors. A US-based assessment of tumor vascularization can potentially be used to predict the efficiency of passive tumor targeting. EPR assessment based on ultrasound imaging is simple, general, and easily transformed for clinical use. In an exemplary preclinical study , the relative blood volume (rBV) in tumors was assessed using contrast-enhanced US imaging. The rBV values were correlated with the tumor accumulation of HPMA-based polymeric drug carriers. A good positive correlation was observed, supporting the fact that imaging vascular parameters such as rBV may be useful in predicting EPR-mediated tumor targeting. Applying multi-modal imaging (MRI, μCT, US, and microscopy), Sulheim correlated the accumulation of polystyrene nanoparticles in different tumor models with parameters such as the functionality of tumor vessels measured via the inflow of MBs using US . The density of functional blood vessels measured by fluorescence microscopy was significantly correlated (p = 0.0056) with nanoparticle accumulation, and the inflow of microbubbles measured with ultrasound also showed a moderate, but significant (p = 0.041), correlation with nanoparticle accumulation, indicating that both the number of vessels and the vessel morphology and perfusion can predict nanoparticle accumulation. This indicates that blood vessel characterization using contrast-enhanced ultrasound imaging or other methods could be valuable in patient stratification for treatment with nanomedicines.
MNBs can act as carriers for therapeutic payload delivery. Therapeutic payloads including therapeutic gas, targeting ligands, drug molecules, and nanoparticles can be loaded into the bubble.
The delivery of drugs used for chemotherapy suffers from many problems including severe side effects and the resistance of tumor cells . MNBs can be developed as multifunctional carriers for drug transport and delivery. The drugs encapsulated in MNBs are protected from intracellular reactions. MNBs can mediate drug delivery in tumors through EPR effects or active targeting. Particularly, when combined with ultrasound, drug delivery can be controlled and enhanced in tumors. A fluid flow is created when MNBs undergo oscillation mediated by ultrasound . This phenomenon increases the drug convection inside the blood vessels and elevates the accumulation of a drug in the surrounding tumor tissues through the EPR effect, resulting in the increased therapeutic index of a drug [121, 122]. Local US application can further induce a transient increase in the endothelial cell membrane permeability to enhance the uptake of therapeutic agents by the target cells. Fan et al. proposed a boron-polymer/microbubble complex (B-MB)-assisted focused ultrasound (FUS) treatment for brain glioma . B-MBs can simultaneously achieve the safe opening of the blood-brain tumor barrier and enhance boron drug delivery into the tumor tissue using FUS sonication. Cao et al. reported the release of an anticancer drug (DOX) from phase-changeable nanodroplets triggered by low-intensity FUS (LIFU) . They found that the intratumoral accumulation and distribution of a drug with LIFU exposure was significantly enhanced. The combination of ultrasound, microbubbles, and gemcitabine is now under phase-II clinical trials for the treatment of pancreatic cancer .
Nanoparticles (NPs) such as gold and superparamagnetic iron oxide NPs are widely used in tumor diagnosis and treatment. The delivery of these NPs at the tumor-specific site is a challenging task. Small nanoparticles (<5 nm) can be rapidly removed from vessels by renal clearance or uptake by the liver, whereas large particles (>200 nm) are removed by the spleen or the reticuloendothelial system (RES) [126, 127]. NPs can be delivered to specific cancer tissue only by designing a proper carrier system and avoiding the delivery of the drug to normal tissues. MNBs can be used as carriers to deliver NPs to the tumor tissue site via the enhanced EPR effect. NPs are often loaded into the shell of MNBs and delivered to tumor cells in a process controlled by ultrasound. A typical example is the delivery of superparamagnetic iron oxide (SPIO) NPs through MNBs. Different types of bubble related carriers including magnetic microbubbles and magnetic nanoliposomes have been developed for in situ microbubble generation. Combined with US, SPIO NPs were locally released at the tumor and taken up by the tumor cells though EPR effects. These bubble-based magnetic carriers offer an attractive possibility for clinical MR imaging, hyperthermia, and the magnetically targeted release of therapeutic agents for cancer.
Gaseous molecules including oxygen (O2), nitric oxide (NO), hydrogen sulfide, and carbon monoxide have important physiological roles or can elicit biological responses. Therefore, they have significant therapeutic potential . These bioactive gases are much smaller than classical drugs and can easily diffuse across the barriers within vessels and cell membranes . While the therapeutic effect of a gas is concentration dependent, a major hurdle in biomedical application is the controlled and site-specific delivery of the gas. Compared with solid carriers, MNBs are good containers for gas, with effective loading and controlled release. It is estimated that at least 50-60% of advanced solid tumors contain hypoxic tissue, which is a significant factor leading to the resistance of tumors to treatment . Vaupel et al. developed O2 nanobubbles for spontaneous oxygenation in response to the tumor microenvironment . The intratumoral O2 level can be significantly increased by the O2 released from O2 nanobubbles that have been passively accumulated within the tumor because of the EPR effect. NO plays a critical role in vascular physiology and cancer biology. At low concentrations, NO promotes tumor cell growth by stimulating angiogenesis, while at high concentrations, NO is cytotoxic and may be a useful chemotherapeutic agent . MNBs can protect NO from endogenous scavengers and provide an opportunity for targeted delivery, thus providing a therapeutic potential for cancer.
MNBs can effectively enhance the ultrasound echo signals for evaluating the EPR effect of a tumor; at the same time, modifications can be made to the membrane shell structure, allowing the easy loading or coupling of other contrast agents, drugs, and targets. Mediated by an ultrasonic field, MNBs can also lead to various useful biological effects such as cavitation and hyperthermia to enhance EPR and achieve a synergistic interaction. Therefore, studies on MNB-based theranostic drug-loading systems have received extensive attention in recent years.
The EPR effect is strongly dependent on the size of nanomedicines. If the nanomedicines are too large, they will not be able to leak through the tumor blood vessels into the solid tumor. If they ate too small, they will be quickly removed by the kidneys. Even if the nanoparticles reach the tumor tissue through the blood vessels, the difference in size affects their ability to spread further. Therefore, the design of a drug carrier with adjustable size can promote the penetration and enrichment of a drug inside a tumor. The special properties by which MNBs respond to an external field can be used to change the size of MNBs under the guidance of an external field such as ultrasound and temperature. This can be achieved by devising ingenious designs of the membrane and the gas core component, thus forming an effective diagnostic and therapeutic carrier. At present, two strategies are applied for size adjustment of MNBs: one is "small to large" and the other is "large to small".
The “small to large” strategy is mainly used in EPR targeting to overcome the contradiction between particle size and the sound intensity of the contrast agent. Nanobubbles exhibit in vivo stability and can even reach the interstitial space through the vascular endothelium, providing enhanced tissue imaging and obtaining more abundant imaging information. Thus, nanobubbles are useful to evaluate the EPR effect. However, the clinical practicality of using ultrasound imaging with small-sized bubbles is considerably lower . It is, therefore, important to maintain the imaging ability when the bubble size is reduced. One typical class of “small to large” bubbles are phase-inversion UCAs, as seen in Figure 4 [134, 135]. Nanoparticles or nanodroplets containing liquid fluorocarbons have been extensively explored and designed. The nanoscale and internal liquid environment promotes prolonged stability and tissue penetration. When the external temperature changes under the trigger of ultrasonic energy, the liquid fluorocarbon inside undergoes a liquid-to-gas phase transition and the volume increases accordingly, resulting in enhanced ultrasonic imaging at the lesion site. Finally, the bubble bursts, and the drug that is released in the target region may exert a further synergistic therapeutic effect. Min et al. developed tumor-homing echogenic chitosan-based nanoparticles, in which bioinert perfluoropentane (PFP) was encapsulated into glycol chitosan nanoparticles . These particles showed prolonged echogenicity via the sustained microbubble formation process in the liquid-phase PFP at body temperature. A significant increase was found in the tumor-homing ability through the EPR effect of the nanoparticles, and this was used for cancer theranostics. Liu et al. prepared folic-acid-modified nanodroplets (FA-NDs) with phase-change ability, which undergo a liquid-gas phase transition under LIFU irradiation . FA-NDs were found to be enriched in the tumor area under LIFU, and the resulting micron-sized MBs could enhance the ultrasound imaging signals.
The “small to large” strategy. Schematic of the method used to phase-change porphyrin nanodroplets into microbubbles, and the imaging contrast provided by both agents. Porphyrin nanodroplets, which provide photoacoustic contrast because of the strong optical absorption of porphyrin, can absorb acoustic or photonic energy which causes the liquid perfluorobutane core to phase-change into a gas microbubble, thereby providing ultrasound contrast due to its hyper-echogenic and nonlinear acoustic properties .
The "big to small" strategy is mainly used to help microbubbles bypass the EPR effect and release drugs at the tumor site. Micro-sized bubbles are good angiographic contrast agents and drug carriers, but they cannot penetrate blood vessels to reach the tissues. If MBs can somehow be made smaller to become nanobubbles after reaching the tumor blood vessels and completing the imaging function, they could spread across the vascular barrier and into the tumor tissue to be used for further tissue imaging and drug release. Huynh et al. reported a method used for the conversion of microbubbles to nanoparticles using low-frequency ultrasound, as shown in Figure 5 . Porphyrin loaded microbubbles can be used as tri-modality contrast agents for ultrasound, photoacoustic, and fluorescent imaging. During exposure to ultrasound, the microbubbles burst and formed smaller nanoparticles, which maintains the imaging and therapeutic properties and allows drug delivery to the tumor. With this conversion, microbubbles can potentially be used to bypass the EPR effect when delivering drugs to tumors.
Therefore, through the delicate design of the bubble structure and the appropriate introduction of external triggers, a new size-controllable theranostic agent with ultrasound enhancement effect and tissue penetration ability can be constructed to evaluate and enhance the EPR effect.
The "big to small" strategy. Schematics of porphyrin microbubbles (pMBs) and their micro-to-nano conversion. A. The pMBs consist of a BChl-lipid shell encapsulating perfluorocarbon gas. B. Conversion of pMBs to porphyrin nanoparticles (pNPs) via sonication with low-frequency, high-duty-cycle ultrasound (conversion ultrasound) .
In vivo US imaging. A US imaging and B the corresponding average gray values of VX2 tumors on rabbit livers before and after intravenous injection of SGC (SPIO@GCS/acryl/biotin-CAT/SOD-gel) at various times. C. Schematic mechanism of responsive bubble generation for US imaging. D. Yellow arrows indicate outlines of the VX2 tumors. The bars in A correspond to 0.5 cm. The standard deviation in B is derived from a group within the region of interest (ROI) (n = 3) .
Different types of stimuli have been reported to trigger the in-situ generation of bubbles in a solid tumor. These types of stimuli are usually endogenous and are closely related to changes in the tumor microenvironment. Agents that are responsive to such stimuli are encapsulated in nanocarriers, which accumulate at the tumor site through the EPR effect. Stimuli are then applied, thus triggering the generation of gas free bubbles at the tumor tissue. The advantages of this in situ generation strategy are as follows: (1) The bubbles generated in situ at the tumor site do not need to be transported through blood. They can, therefore, avoid various biological barriers in the human body and can also bypass the requirement for EPR in changing the bubble size. (2) The generation of bubbles enhances the ultrasound imaging effect at the tumor site, which is conducive to diagnosis. If the generated gas can also be used for treatment, targeting, diagnosis, and treatment can be integrated.
For example, the production of reactive oxygen species (ROS) is much higher in cancer tissues than in normal tissues. H2O2 is an ROS and a diagnostic marker in the development of certain diseases. Studies have found that Prussian blue nanoparticles have a catalase-like function in neutral environments, catalyzing H2O2 to produce oxygen . When the oxygen generated exceeds the saturation concentration, it can form free oxygen bubbles, enhancing ultrasound imaging. Together with the MRI properties of Prussian blue nanoparticles, this could be used as an ultrasound/magnetic resonance bimodal imaging system which is triggered by the disease environment . Similarly, Wang et al. constructed a multifunctional carrier system loaded with two catalase enzymes and SPIO. The two enzymes catalyze the reaction of the ROS in the body under pathological conditions to produce oxygen that can be utilized for ultrasound imaging, as can be in Figure 6. The changes to the reaction environment also enhance the MRI capabilities of SPIO within the system.
In the above studies, the aggregation of bubbles and release of drugs in the target region were mainly dependent on various exogenous and endogenous stimuli and were not caused by specific active targeting. EPR and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and ligand-based active targeting have attracted considerable attention. Kunjachan et al. visualized and quantified passive and active tumor targeting using RGD- and NGR-modified polymeric nanomedicines . Wu et al. developed paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-co-glycolic acid) nanobubbles, which can be aimed specifically at prostate cancer cells to sustainably release the loaded PTX via the EPR effect and US-triggered drug delivery . Li et al. reported the use of neuropeptide Y Y1 receptor-mediated biodegradable photoluminescent nanobubbles as UCAs for targeted breast cancer imaging .
Rapid and efficient early binding of MNBs to the blood vessels of the tumor occurred through vascular targeting, but passive targeting was significantly more efficient over time. These results indicate that a combination of passive and active targeting is required for effective tumor imaging and therapy. Based on the above ideas, a multi-gradient targeting strategy has emerged. Multi-gradient targeting strategies refer to the further coupling of specific targeting factors on MNBs to combine active targeting with EPR-mediated passive targeting. When such MNBs are intravenously injected into the body, they become actively enriched in the tumor blood vessels under the action of specific targeting ligands, contributing to clearer ultrasound imaging. Following the application of an ultrasound field or various other internal and external sources of stimulation, the structure and/or the size of the MNBs changes. On the one hand, this change triggers various biological effects, which affect the permeability of the tumor blood vessels and enhance the EPR effect. On the other hand, the drug is released, forming a high drug concentration gradient in the microcirculation of the tumor tissue, efficiently allowing the drug to enter the tumor tissue for treatment by virtue of the EPR effect.
Several classes of ligands have been conjugated onto the surface of UCAs to achieve better targeting of tumor cells, including peptides, aptamers, and affibody molecules. These targeting ligands allow the UCAs to remain at a size at which the EPR effects can be exploited . Cell membranes are a new type of shell material that have been used in the construction of bubbles. The inherent properties of natural lipids and protein components on a membrane can be used for natural targeting. For example, platelet membranes are rich in natural vessel adhesive components such as α2β1, α5β1, α6β1, and αbβ3, and the glycoproteins, GPIb-IX-V and GPV, which can naturally target injured vasculature . Mingxi Li et al. used platelet membranes to fabricate bio-nanobubbles and demonstrated their lesion-targeting ability . The abnormal vasculature within tumors provides the possibility of using bio-shelled bubbles for the targeting of tumors.
Active targeting can be performed by modifying bubble shells using a range of targeting ligands; such bubbles can therefore be applied in different types of cancer. There are several strategies that allow the binding of ligands to the bubble shell. First, avidin or streptavidin is commonly used for non-covalent attachment of biotinylated ligands onto the shell materials . Yang et al. used the avidin-biotin method to combine NBs with biotinylated anti-ErbB2 Affibody® molecules . The resulting NB-Affibody had a specific affinity for human epidermal growth factor receptor type 2 (HER2)-over-expressing tumors. Second, the covalent binding of ligands to the shell has also been explored. One approach involves the binding of activated carboxylic groups to shells with amino-groups from the lysine residues of binding ligands . In a third approach, the ligands are coupled with the shell components (e.g., to phospholipids), followed by the formation of MBs. Chung-Hsin Wang et al. conjugated sgc8c aptamers to functional lipids and prepared DOX-loaded acoustic droplets . The fully vaporized droplets resulted in the highest DOX uptake by cancer cells.
Multi-gradient targeting can be applied to both microscale and nanoscale bubbles. Nanoscale bubbles modified with targeting ligands are good carriers. Li et al. reported that the soft biodegradable glycine/PEG/RGD-modified poly (methacrylic acid) nanobubbles can be applied as intelligent theranostic vehicles for drug delivery . Gao et al. developed the targeted ultrasound-triggered phase transition nanodroplets for Her2-overexpressing breast cancer diagnosis and gene transfection . For micron-sized bubbles, Duan et al. demonstrated a multi-gradient continuous targeting strategy based on the RGD-l-TRAIL-labeled magnetic microbubbles shown in Figure 7 for cancer therapy. The designed RGD-l-TRAIL@MMB system had a complex but elaborate multilayer structure: gas in the core for US imaging, SPIO on the shell for MRI imaging and magnetic targeting control, and RGD-l-TRAIL ligands for an enhanced combination of the tumor-targeted delivery of TRAIL. First, the RGD-l-TRAIL protein on the MMB surface enables the microbubbles to actively target angiogenesis of a tumor. The size of the micro-scaled bubbles around the tumor is beneficial for real-time US imaging and MRI to clearly delineate the tumor margin. Therefore, it is micron-scale targeting and diagnosis. Second, after US imaging, the microbubbles in situ around the tumor rupture and the nanoscale SPIOs with associated RGD-l-TRAIL molecules can travel through the blood vessels and enter the tumor tissue because of the tumor ligand induced integrin αvβ3-receptor-mediated endocytosis. At this stage, the tumor tissue can also be imaged using MRI. With the accumulation of RGD-l-TRAIL and SPIOs in the tumor tissue and cells, tumor apoptosis induced by TRAIL molecules can also be observed during this process; therefore, this process involves nanoscale targeting and diagnosis. The multi-gradient targeting drug delivery system has a reasonable structure, an adjustable drug dosage, and a clear target. It is a typical example of applying a multi-gradient targeting strategy for in vivo diagnosis and treatment.
In addition to the ultrasound field, external factors including light, magnetic fields, radiation, and microwaves affect EPR. Internal factors such as pH, high concentrations of active oxygen, and various special cytokines are provided by the special pathological environment of the lesion. The mechanism by which each factor affects the EPR is different. Combining multiple energy fields can exert the combined effects of all of the different mechanisms to obtain an optimized and enhanced EPR effect.
Schematic diagram showing multi-gradient targeting strategy of RGD-l-TRAIL@MMBs for tumor diagnostics and therapy .
Local heating of the tumor site tends to increase the accumulation of nanomedicine, resulting in more effective intratumoral drug delivery. Hyperthermia enhances the increase in nano drug delivery within tumors because of the increased blood flow to the tumor caused by vasodilation. This increased vascular permeability is due to the increased intercellular space between endothelial cells [152-154]. Through the photothermal conversion effect, the irradiation of a tumor with a laser can also change the physiological state of the tumor and enhance the penetration of the nano drug into the tumor. By constructing a versatile theranostics carrier that responds to light and other external fields, thermal effects can be combined with other effects to improve vascular permeability. Ke et al. constructed a multifunctional nanocapsule (NC) by loading perfluorooctylbromide (PFOB) and superparamagnetic iron oxide nanoparticles into poly(lactic acid) (PLA) NCs, followed by the formation of PEGylated gold nanoshells on the surface. Such a theranostic agent could efficiently kill tumor cells using NIR laser irradiation under the guidance of contrast-enhanced US/MRI to achieve great therapeutic effectiveness without systemic toxicity to the patient. Above all, the bimodal imaging guidance could display dynamic complementary information about a tumor to help alter the treatment on an individual basis with high efficiency.
The strategy of combining internal and external stimuli is also beneficial. Yang et al. [156, 157] constructed a composite microcapsule with internally encapsulated L-arginine, SPIO in the membrane shell, and glucose oxidase on the surface, which is a double-response, microcapsule transport system that reacts to both glucose and external magnetic fields, as shown in Figure 8. First, the glucose oxidase on the surface of the microcapsule specifically reacts with glucose in diabetic patients, reducing the glucose concentration and generating H2O2 and gluconic acid. The magnetic nanoparticles in the microcapsule shell then move under the action of the external magnetic field to generate gaps in the membrane, and the internally loaded L-arginine further reacts with the H2O2 to form NO. Therefore, it is apparent that through the dual response of the microcapsule structure to glucose and magnetic fields, high concentrations of glucose can be reduced and the generated NO gas can enhance the ultrasound imaging and the EPR effect, thus treating the disease. In addition to responding to external magnetic fields, the SPIO in the system also functions for MRI imaging. This system can be used as a multifunctional carrier platform for the effective regulation of blood glucose.
Schematic diagram of microvesicles encapsulated with magnetic nanoparticles and glucose oxidase for the dual-stimuli responsive programmable delivery model. The encapsulated glucose-specific enzyme catalyzes glucose into gluconic acid and H2O2. The subsequent alternating magnetic field increases the porosity of the polymer shell, leading to the reaction between L-arginine and H2O2 to produce nitric oxides .
Concepts and schematics of AMLs and their nano to micro conversion for US/MR dual modal imaging and the spatiotemporal-bombed combination tumor accurate therapy .
Liu Yang et al. designed a liposome drug delivery system, as seen in Figure 9, which is a complex structure of a therapeutic gas prodrug, anthranil trisulfide, and magnetic nanoparticles, which is efficiently concentrated at the targeted tumor site by the EPR effect under the control of an external magnetic field. Under the catalysis of biological enzymes such as CBS and CSE in the tumor, hydrogen sulfide is produced, which has antitumor properties. The liposome-loaded magnetic nanoparticles respond specifically to the external magnetic field. The intratumoral targeted aggregation of liposome can monitored and regulated by MRI; and the hydrogen sulfide microbubbles catalyzed by the enzyme enhance the intratumoral ultrasound contrast, leading to a greater intensity of ultrasound energy. The microbubble then ruptures, ultrasonic cavitation leads to physical tumor ablation, and the antitumor properties of the hydrogen sulfide itself lead to necrosis of the original dense intratumoral tissue, creating favorable conditions for the use of nanocarriers. This liposome drug system can achieve better theranostic destruction of a tumor under ultrasound/magnetic resonance bimodal image monitoring.
There are also multifunctional carrier systems with sophisticated designs that combine lasers, heat, radiation, and other external and ultrasonic fields to improve the permeability of tumor blood vessels and tissues and deliver drugs effectively.
The ideal process for tumor diagnosis and treatment based on the EPR effect is shown in Figure 10. Before starting treatment, an accurate individualized assessment of the EPR level should be performed for each individual patient, and different treatment options should be developed based on the results of the assessment. For patients with high EPR levels, an appropriate drug delivery system can be selected for treatment. For patients with low EPR levels, the EPR effect should be enhanced using various physical and pharmacological methods before treatment. Would it be possible to construct a multifunctional theranostics carrier that can play a role in all aspects of the evaluation, enhancement, and treatment, realizing the integration of EPR evaluation, enhancement, and EPR-based tumor treatments on a single platform? MNB-based drug delivery systems have become a potential choice because of their special properties such as imaging, drug release, changing structures, and production of various biological effects that can be mediated with ultrasound fields.
Around the process of tumor diagnosis and treatment and applying the four strategies mentioned, the potential of MNBs can be described in detail, as seen below in Figure 10. Firstly, MNBs can be used as contrast enhancers to visually and quantitatively evaluate the EPR levels of a patient. The accuracy of the assessment depends on two key processes: (1) Whether MNBs can efficiently reach tumor blood vessels through blood circulation, and (2) whether a strong echo signal can be generated after reaching the tumor site. The various strategies mentioned can have a positive effect on both of these processes. As described previously, the "small to large" size control strategy has been applied to construct small-sized nanodroplets that have higher stability in the blood circulation than MNBs. A multi-level targeting strategy can also be applied to couple the targeting factors on the surface of the nanodroplets to reach the tumor blood vessels more efficiently. In the latter process, through the mediation of an external energy field, the liquid droplets within the nano-droplet core can be transformed, thus increasing the volume to generate a stronger echo signal which is beneficial to ultrasound imaging. It is also possible to use the "in situ generation" strategy to generate bubbles in situ using the specific microenvironment of the tumor to create ultrasound contrast with which to evaluate the EPR.
Second, for patients with low EPR levels, MNBs can be combined with internal biochemical triggers and external energy fields to enhance the EPR effect using various strategies, as shown in Figure 10. For example, the "large to small" size control strategy facilitates the micron-sized bubbles to bypass the EPR effect and become smaller nanobubbles that can penetrate the vascular endothelial cell gap, allowing movement into the tumor tissue. The “multi-field association” strategy comprehensively uses light, heat, ultrasound, radiation, and various endogenous factors to increase vascular permeability and enhance the ability of the drug components carried by MNBs to spread out of the blood vessels. The “multi-gradient targeting” strategy allows the drug released after the rupture of a bubble to utilize molecular targeting to efficiently reach the tumor tissue through the blood vessel.
In addition, while enhancing the EPR effect, various energy fields can mediate the gradual disintegration of the structure of MNBs, releasing the various active substances the MNBs carry, including drugs, other nanoparticles, and therapeutic gases. These active substances are enriched in tumor tissues by the enhanced EPR effect and lead to further therapeutic or real-time imaging functions.
In the complex and variable micro-environment of a living organism, the key to effective treatment is drug components reaching a lesion efficiently and exerting continuous therapeutic effect. The nano carrier targeted drug delivery system, based on EPR, is one way to effectively improve the anticancer effect of drugs. In recent decades, various forms of multifunctional carrier materials such as liposomes, MNBs, micelles, nanoemulsions, magnetic nanoparticles, polymer nanoparticles, and dendrimers have been designed and developed to improve the aggregation and permeability of the drug at the tumor site. In this review, we focused on the effects of ultrasound and MNBs on EPR, discussed in detail the potential mechanisms by which their respective roles and synergies affect EPR, and illustrated new strategies that have been developed to enhance EPR. Although these new strategies do show promise, further research is needed in this area to demonstrate effective drug delivery and therapeutic effects. In this study, we discuss the advantages of MNB-assisted ultrasound to enhance the EPR effect, the current problems, and any possible countermeasures.
Ideal process for tumor diagnosis and treatment based on the EPR effect by ultrasound and its contrast agents.
MNBs are distinctly distinguished from other carrier materials in that they have multiple forms of response to the ultrasound field, and the rich biological effects of these responses have a potential role in both EPR imaging and enhancement processes. Under ultrasound energy mediation, the MNB theranostic carrier can affect the EPR in combination with various favorable conditions. First, ultrasound and MNBs can both affect the EPR. The ultrasonic streaming and hyperthermia effect from the ultrasound itself can improve the ability of a drug to diffuse into a tissue, promote the extravasation of drugs, and enhance the permeability of blood vessels. MNBs can also be used as drug carriers with certain EPR effects using various strategies such as structural design, size control, and modification of the membrane shell. Second, ultrasound can be used to further assist MNBs, which are imaged by low-intensity ultrasound energy to evaluate EPR. MNBs can also rupture under high-intensity ultrasound energy and produce biological effects such as cavitation, which leads to the more efficient transport of a drug into the tumor tissue through the vascular endothelial cells. Through sophisticated design, the internal and external source energy fields can be combined, making full use of “adjustable size modulation”, “in situ generation”, “multi-gradient targeting”, and “multi-field association” strategies, which can further improve the penetration ability and delivery efficiency of drugs at the tumor site.
The size of the MNBs is still a barrier to the EPR effect. The efficacy of a diagnostic and therapeutic agent through the EPR effect is size-dependent. Related research has shown that liposomes with a hydrodynamic particle size between 100 and 200 nm showed a 4-fold higher accumulation in tumors than liposomes with a particle size of less than 50 nm and above 300 nm . The preparation of nanobubbles with a size of less than 200 nm remains challenging. Although studies have shown that ultrasound can rupture lipid microbubbles in the body and form smaller nanoparticles with the same optical properties as the original microbubbles, meaning that micron-sized bubbles can bypass the EPR effect when delivering drugs to the tumor, there is still a need to develop small-sized nanobubbles with the ability of enhanced accumulation. Therefore, it is critical that new preparation processes are developed, and that various adverse problems such as the weak imaging effects caused by small-sized nanobubbles and the decreased drug-loading capacity are dealt with. The combination of NBs with other nanocarriers is one possible way to increase the efficiency of these bubbles in terms of drug delivery.
Multi-modal imaging, in which targeting factors are coupled with the response to various energy fields and other functions, makes the structure of MNBs complex, thus increasing the difficulty in constructing carriers. Therefore, it is necessary to further study and optimize the preparation method of MNBs theranostics carriers, improve the fineness, controllability, and repeatability, and finally to achieve standardization. It is also necessary to further study the effects of MNB carrier structures on their function, such as the material from which membrane shells are built, size, drug-loading mode, and the effects of target type on imaging and targeting. In addition, in the complex and variable microenvironment of the body, it is very challenging to simultaneously achieve a targeted system with high diagnostic sensitivity, high specificity, and good therapeutic effect. The more complex a structure is, the more risk there is, so it is difficult to anticipate the realization of a function and to achieve clinical transformation, especially when using relatively large targeting systems (hundred nanometers and above) such as MNBs. The sensitivity of different biological tissues to ultrasound is quite different, so the applied ultrasound parameters will need to be changed accordingly. The ultrasound parameters used to stimulate the MNBs would also need to be adjusted for use with the different kinds of bubbles.
More in vivo experiments are needed to clarify the toxicity, distribution, and pharmacokinetics of a carrier within the body and to provide abundant evidence for clinical application. It is foreseeable that with the continuous development of biomedical nanotechnology based on ultrasound and MNBs, more innovative and more powerful theranostics carriers will be designed and developed to further promote tumor-targeted therapy.
One of the important principles of drug delivery system development is safety. The safety issues for micro/nano-bubble-assisted ultrasound to enhance EPR effects, such as micro/nano-bubble toxicity [159-161] and damage to vessels through acoustic energy still need to be fully investigated on priority for future clinical applications [162, 163]. The safety issues related to ultrasound have been addressed in Section 2 of this review. The biodegradability and metabolites of ultrasound contrast agents should be investigated. Although some studies have investigated the short-time toxicity, safety tests for biocompatibility, acute toxicity, subacute toxicity, carcinogenicity, developmental toxicity, immunotoxicology, genotoxicity, and irritation to blood vessel should be conducted in the future, especially when MNBs are coupled with ultrasound energy.
EPR: permeability and retention; UCA: Ultrasound contrast agent; TI: thermal index; MI: mechanical index; FDA: Drug Administration; PnP: negative pressure; CW: continuous wave; DOX: Doxorubicin; GNPs: gold nanoparticles; DDS: drug delivery system; PIV: particle image velocimetry; SC: stable cavitation; IC: inertial cavitation; SEM: scanning electron microscopy; AFM: atomic force microscopy; TMC: Transmembrane current; CAD: computer-aided detection; UOM: ultrasound-modulated optical microscopy; CEUS: contrast-enhanced US; IVUS: intravascular ultrasound; BFR: blood flow resistance; MNBs: micro/ nanobubbles; UCAs: ultrasound contrast agents; PLGA: poly-(lactic-co-glycolic acid); rBV: relative blood volume; BBB: blood-brain barrier; B-MB: boron-polymer/microbubble complex; FUS: focused ultrasound; LIFU: low-intensity focused ultrasound; NPs: nanoparticles; RES: reticuloendothelial system; PFP: perfluoropentane; FA-NDs: folic-acid-modified nanodroplets; pMBs: porphyrin microbubbles; pNPs: porphyrin nanoparticles; ROS: reactive oxygen species; PFOB: perfluorooctylbromide; PLA: poly(lactic acid); NCs: nanocapsules; PSV: peak systolic velocity; SGC: SPIO@GCS/acryl/biotin-CAT/SOD-gel; PFC: perfluocarbon; AML: the anethole dithiolethiones (ADT)-loaded magnetic nanoliposomes; CBS: cystathionine-β synthase; CSE: cystathionine-γ-lyase; MMB: magnetic microbubbles
This investigation was financially funded by the National Key Research and Development Program of China (2017YFA0104302, 2018YFA0704103), the National Natural Science Foundation of China (51832001, 61821002, 81701833 and 81971750), Natural Science Foundation of Jiangsu Province (BK20191266), and the Natural Science Foundation of Anhui Province (1808085QH233). Funding also partially comes from the Six Talent Peaks Project of Jiangsu Province (2017-SWYY-006) and Zhong Ying Young Scholar of Southeast University. The authors also would like to thank the support from the Fundamental Research Funds for the Central Universities.
The authors have declared that no competing interest exists.
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The effect of tripterygium glucoside tablet on pharmacokinetics of losartan and its metabolite EXP3174 in rats.
Hu Yongsheng,Zhou Xuexue,Shi Hui,Shi Wenyu,Ye Shengjie,Zhang Hai
Biomedical chromatography : BMC
Losartan and tripterygium glucoside tablet (TGT) are often simultaneously used for reducing urine protein excretion in clinic. However, it is unknown whether there is potential herb-drug interaction between losartan and TGT. The aim of this study was to investigate their potential herb-drug interaction, and clarify the mechanism of the effect of TGT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. The plasma concentrations of losartan and EXP3174 were determined by LC-MS, and the main pharmacokinetic parameters were calculated. The C , t and AUC of losartan became larger after co-administration, while the C and AUC of EXP3174 became smaller, suggesting that TGT could influence the pharmacokinetics of losartan and EXP3174. The effects of TGT and its main components on the metabolic rate of losartan were further investigated in rat liver microsomes. Results indicated that TGT and its two main ingredients could decrease the metabolic rate of losartan. Therefore, it was speculated that TGT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 by inhibiting the metabolism of losartan. The results could provide references for clinical medication guidance of losartan and TGT to avoid the occurrence of adverse reactions.
10.1002/bmc.3973
Nanoparticle multivalency counterbalances the ligand affinity loss upon PEGylation.
Hennig Robert,Pollinger Klaus,Veser Anika,Breunig Miriam,Goepferich Achim
Journal of controlled release : official journal of the Controlled Release Society
The conjugation of receptor ligands to shielded nanoparticles is a widely used strategy to precisely control nanoparticle-cell interactions. However, it is often overlooked that a ligand's affinity can be severely impaired by its attachment to the polyethylene glycol (PEG) chains that are frequently used to protect colloids from serum protein adsorption. Using the model ligand EXP3174, a small-molecule antagonist for the angiotensin II receptor type 1 (AT1R), we investigated the ligand's affinity before and after its PEGylation and when attached to PEGylated nanoparticles. The PEGylated ligand displayed a 580-fold decreased receptor affinity compared to the native ligand. Due to their multivalency, the nanoparticles regained a low nanomolar receptor affinity, which is in the range of the affinity of the native ligand. Moreover, a four orders of magnitude higher concentration of free ligand was required to displace PEGylated nanoparticles carrying EXP3174 from the receptor. On average, one nanoparticle was decorated with 11.2 ligand molecules, which led to a multivalent enhancement factor of 22.5 compared to the monovalent PEGylated ligand. The targeted nanoparticles specifically bound the AT1R and showed no interaction to receptor negative cells. Our study shows that the attachment of a small-molecule ligand to a PEG chain can severely affect its receptor affinity. Concomitantly, when the ligand is tethered to nanoparticles, the immense avidity greatly increases the ligand-receptor interaction. Based on our results, we highly recommend the affinity testing of receptor ligands before and after PEGylation to identify potent molecules for active nanoparticle targeting.
10.1016/j.jconrel.2014.07.062
AXL Overexpression in Tumor-Derived Endothelial Cells Promotes Vessel Metastasis in Patients With Hepatocellular Carcinoma.
Chai Zong-Tao,Zhang Xiu-Ping,Ao Jian-Yang,Zhu Xiao-Dong,Wu Meng-Chao,Lau Wan Yee,Sun Hui-Chuan,Cheng Shu-Qun
Frontiers in oncology
Portal vein tumor thrombus (PVTT) is one of the most serious forms of hepatocellular carcinoma (HCC) vessel metastasis and has a poor survival rate. However, the molecular mechanism of PVTT has not yet been elucidated. In this study, the molecular mechanism of AXL expressed in tumor-derived endothelial cells (TECs) in vessel metastasis was investigated. High AXL expression was observed in TECs, but not in the tumor cells of HCC patients with PVTT and this was associated with poor overall survival (OS) and disease-free survival (DFS). AXL overexpression was positively associated with CD 31 expression both and . AXL promoted the cell proliferation, tube formation, and migration of both TECs and normal endothelial cells (NECs). High expression of AXL in TECs promoted the cell migration, but not the proliferation of HCC cells. Further studies demonstrated that AXL promoted cell migration and tube formation through activation of the PI3K/AKT/SOX2/DKK-1 axis. AXL overexpression in HUVECs promoted tumor growth and liver or vessel metastasis of HCC in xenograft nude mice, which could be counteracted by treatment with R428, an AXL inhibitor. R428 reduced tumor growth and CD 31 expression in HCC in PDX xenograft nude mice. Therefore, AXL over-expression in TECs promotes vessel metastasis of HCC, which indicates that AXL in TECs could be a potential therapeutic target in HCC patients with PVTT.
10.3389/fonc.2021.650963
Expression of caspase-3 and hypoxia inducible factor 1α in hepatocellular carcinoma complicated by hemorrhage and necrosis.
Liang Hui,Wu Jian-Guo,Wang Fei,Chen Bo-Xuan,Zou Shi-Tian,Wang Cong,Luo Shuai-Wu
World journal of clinical cases
BACKGROUND:Hepatocellular carcinoma (HCC) is a malignant tumor that occurs in the liver. Its onset is latent, and it shows high heterogeneity and can readily experience intrahepatic metastasis or systemic metastasis, which seriously affects patients' quality of life. Numerous studies have shown that hypoxia inducible factor1α (HIF-1α) plays a significant role in the occurrence and development of tumors, as it promotes the formation of intratumoral vessels and plays a key role in their metastasis and invasion. Some studies have reported that caspase-3, which is induced by various factors, is involved in the apoptosis of tumor cells. AIM:To investigate the expression of caspase-3 and HIF-1α and their relationship to the prognosis of patients with primary HCC complicated by pathological changes of hemorrhage and necrosis. METHODS:A total of 88 patients with HCC complicated by pathological changes of hemorrhage and necrosis who were treated at our hospital from January 2017 to December 2019 were selected. The expression of caspase-3 and HIF-1α in HCC and paracancerous tissues from these patients was assessed. RESULTS:The positive expression rate of caspase-3 in HCC tissues was 27.27%, which was significantly lower than that in the paracancerous tissues ( < 0.05), while the positive expression rate of HIF-1α was 72.73%, which was significantly higher than that in the paracancerous tissues ( < 0.05). The positive expression rates for caspase-3 in tumor node metastasis (TNM) stage III and lymph node metastasis tissues were 2.78% and 2.50%, respectively, which were significantly lower than those in TNM stage I-II and non-lymph node metastasis tissues ( < 0.05). The positive expression rates of HIF-1α in TNM stage III, lymph node metastasis, and portal vein tumor thrombus tissues were 86.11%, 87.50%, and 88.00%, respectively, and these values were significantly higher than those in TNM stage I-II, non-lymph node metastasis, and portal vein tumor thrombus tissues ( < 0.05). The expression of caspase-3 and HIF-1α in HCC tissues were negatively correlated ( = - 0.426, < 0.05). The median overall survival time of HCC patients was 18.90 mo (95% CI: 17.20-19.91). The results of the Cox proportional risk regression model analysis showed that TNM stage, portal vein tumor thrombus, lymph node metastasis, caspase-3 expression, and HIF-1α expression were the factors influencing patient prognosis ( < 0.05). CONCLUSION:The expression of caspase-3 decreases and HIF-1α increases in HCC tissues complicated by pathological changes of hemorrhage and necrosis, and these are related to clinicopathological features and prognosis.
10.12998/wjcc.v9.i23.6725
Immunotherapy and targeted therapy converted radical surgery in an advanced hepatocellular carcinoma with tumor emboi of portal vein and hepatic vein.
Huang Xing-Hua,Zhang Xiao-Jin,Jiang Yi,Hu Huan-Zhang
Asian journal of surgery
10.1016/j.asjsur.2021.06.044
Hepatocellular Carcinoma with Portal Vein Tumor Involvement: Best Management Strategies.
Liu Po-Hong,Huo Teh-Ia,Miksad Rebecca A
Seminars in liver disease
Portal vein tumor thrombosis (PVTT) commonly occurs in patients with hepatocellular carcinoma (HCC). Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, higher recurrence rates after treatment, and, therefore, worse overall survival. Among untreated HCC patients with PVTT, the median overall survival has been reported as low as 2 to 4 months. Historically, many aspects of PVTT have impacted the theoretical and practical safety and efficacy of treatment, for example, disordered blood flow and associated impairment of liver function, heat-sink effects of blood flow in the area of the PVTT, and risk of recurrence due to tumor location in the blood vessel. The current Barcelona Clinic Liver Cancer staging system categorizes HCC patients with PVTT as advanced stage, for which the standard of care is targeted therapy with sorafenib. However, sorafenib is associated with only marginal benefits among patients with PVTT. First-line lenvatinib, which was shown to be noninferior to sorafenib, excluded patients with main portal trunk invasion. Regorafenib and nivolumab, an immune-based therapy, were recently approved in the United States for second-line therapy after sorafenib. Preliminary results for cabozantinib suggest a benefit in the second-/third-line after sorafenib failure. In addition, rapid advances in many fields (surgery, interventional radiology, nuclear medicine, and immunotherapy) have increased the potential treatment options for the management of this complex disease entity. A large portion of the emerging evidence focuses on the broader category of advanced HCC of which PVTT is a subgroup. While many of these studies show promising results, the efficacy among PVTT patients requires validation in prospective studies. Real-world data may help fill the evidence gap for patients not eligible for clinical trials due to common hepatic function requirements. The variety of new treatment advances for the heterogeneous and complex disease entity of HCC with PVTT means that personalized, multidisciplinary management may be necessary to achieve optimal outcomes. In this narrative review, we summarize the evolving management strategies for patients with HCC and PVTT.
10.1055/s-0038-1666805
Contrast-enhanced ultrasound for the characterization of portal vein thrombosis vs tumor-in-vein in HCC patients: a systematic review and meta-analysis.
Chen Jifan,Zhu Jianing,Zhang Chao,Song Yue,Huang Pintong
European radiology
OBJECTIVES:Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. However, differentiation of thrombosis and tumor-in-vein (TIV) may be challenging. Contrast-enhanced ultrasound (CEUS) is an excellent method for detection of vascularization and could help in the distinction. We performed a systematic review and meta-analysis for evaluating the diagnostic value of CEUS in differentiating between PVT and TIV in hepatocellular carcinoma (HCC) patients. METHODS:PubMed, Embase, Cochrane Library, and Web of Science were searched up to the 5th of May 2019. The study quality was assessed by QUADAS-2 tool. Pooled sensitivity and specificity were calculated by the bivariate random effect model and hierarchical summary receiver-operating characteristic (SROC) curve was plotted. RESULTS:Seven studies including 425 participants were analyzed after screening 986 articles searched from databases. The pooled sensitivity and specificity of CEUS in diagnosing TIV were 0.94 (95%CI, 0.89-0.97) and 0.99 (95%CI, 0.80-1.00), respectively. The area under the curve (AUC) of SROC curve was 0.97 (95%CI, 0.95-0.98). The pooled sensitivity and AUC were consistent across all the subgroups of different subject numbers, country, study design, CEUS contrast agents, and diagnostic criteria. CONCLUSIONS:CEUS is highly efficient in differentiating TIV from PVT and is an alternative or a substitute for CT and/or MRI. TRIAL REGISTRATION:PROSPERO registration number: CRD42019138847 KEY POINTS: • Characterization of portal vein thrombosis (PVT) vs tumor-in-vein (TIV) is critical for HCC staging. • CEUS has an excellent safety profile, provides a real-time analysis without any loss in accuracy compared with CT and MRI. • This meta-analysis demonstrates that contrast-enhanced ultrasound (CEUS) is a suitable method for the detection of PVT and distinction with TIV.
10.1007/s00330-019-06649-z
A stable and reliable animal model for hepatocellular carcinoma with portal vein tumor thrombus.
Chai Zong-Tao,Chen Zhen-Hua,Zhang Xiu-Ping,Feng Jin-Kai,Liu Zong-Han,Cheng Shu-Qun
Hepatobiliary & pancreatic diseases international : HBPD INT
10.1016/j.hbpd.2021.03.003
S100P as a novel biomarker of microvascular invasion and portal vein tumor thrombus in hepatocellular carcinoma.
Qi Lu-Nan,Ma Liang,Wu Fei-Xiang,Chen Yuan-Yuan,Xing Wan-Ting,Jiang Zhi-Jun,Zhong Jian-Hong,Chen Zu-Shun,Gong Wen-Feng,Ye Jia-Zhou,Li Hong-Hao,Shang Jin-Jie,Xiang Bang-De,Li Le-Qun
Hepatology international
BACKGROUND:Portal vein tumor thrombus (PVTT) and microvascular invasion (MVI) are types of intrahepatic vascular metastasis of hepatocellular carcinoma (HCC) and are highly correlated with poor prognosis. However, the underlying biomarkers of PVTT and MVI are unclear. METHODS:We identified a PVTT/MVI-associated gene S100P by cDNA microarray analysis, and assess the potential value of serum S100P measurement in the differential diagnosis of HCC and prediction of MVI status with large retrospective and perspective cohort studies. RESULTS:The mRNA and protein of S100P was increased in HCCs with PVTT or MVI. High S100P immunostaining in tumors was correlated with inferior tumor-free survival. Serum S100P values discriminated patients with HCCs from those with benign liver tumors, and it showed predictive potential of MVI status in both retrospective and perspective cohorts. S100P may regulate HCC tumorigenicity and invasive ability; S100P also was associated with up-regulation of CD44, which may mediate HCC cell adhesion to form PVTT/MVI. CONCLUSIONS:Serum S100P may be a novel differential diagnostic marker for HCC and a potential predictor of MVI status pre-surgery for HCC patients. S100P overexpression in HCC is highly correlated with the formation of PVTT and MVI, which may make S100P as a potential therapeutic target for HCC metastasis.
10.1007/s12072-020-10130-1
Transcriptome sequencing-based personalized analysis of hepatocellular carcinoma patients with portal vein tumor thrombus.
Journal of gastrointestinal oncology
BACKGROUND:The mechanism of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) has been widely studied, and numerous diagnostic and prognostic biomarkers for HCC with PVTT have been identified. We aimed to evaluate the extent to which these biomarkers may aid the personalized precision therapy of HCC with PVTT. METHODS:Matched tissue specimens [primary HCC tumor (PT), adjacent normal (N) liver, and PVTT tissues] were acquired from 3 Chinese HCC patients who underwent surgery at Sun Yat-sen University Cancer Centre between 2019 and 2020. Ribonucleic acid (RNA) sequencing was performed on the 9 tissue samples. GFOLD (generalized fold change) algorithm was used to analyze the differently expressed genes (DEGs) between the PVTT, PT, and normal tissues from each patient. Genes with a P<0.01 and a |GFOLD value| >1 were identified as having significantly different expression. RESULTS:In total, 3,543, 32,472, and 12,901 tumorigenesis-associated genes, and 2,919, 17,679, and 14,825 metastasis-associated genes, were detected in Patient 1 (P1), Patient 2 (P2), and Patient 3 (P3), respectively. We analyzed the expression levels of genes associated with hypoxia, macrophage recruitment and cancer stem cells (CSCs). The results showed that hypoxia and CSCs may have contributed to tumorigenesis but not to metastasis in P1. We also found the hypoxia microenvironment played an important role in tumorigenesis and metastasis in P2, and CSCs may have contributed to metastasis. Additionally, we found that CSCs played critical roles in metastasis but not in tumorigenesis in P3. The results also showed that the long non-coding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was greatly overexpressed in the PTs and PVTT in all 3 patients, and Heart and Neural Crest Derivatives Expressed 2-antisense RNA 1 (HAND2-AS1) was downregulated in PVTT compared with PTs in all 3 patients. Thus, MALAT1 and HAND2-AS1 may be robust biomarkers for metastasis in HCC patients with PVTT. CONCLUSIONS:Tumor-associated macrophages (TAMs)-targeted immunotherapy is a promising therapy for HCC patients with PVTT. LncRNAs MALAT1, and HAND2-AS1 may be promising targets for HCC therapy.
10.21037/jgo-21-162
Identification of prognostic biomarkers associated with the occurrence of portal vein tumor thrombus in hepatocellular carcinoma.
Lin Tong,Lin Zhimei,Mai Peipei,Zhang E,Peng Lisheng
Aging
The occurrence of portal vein tumor thrombus (PVTT) is strongly correlated to the staging and poor prognosis of hepatocellular carcinoma (HCC) patients. However, the mechanisms of PVTT formation remain unclear. This study aimed to investigate differentially expressed genes (DEGs) between primary tumor (PT) and PVTT tissues and comprehensively explored the underlying mechanisms of PVTT formation. The DEGs between PT and paired PVTT tissues were analyzed using transcriptional data from the Gene Expression Omnibus (GEO) database. The expression, clinical relevance, prognostic significance, genetic alternations, DNA methylation, correlations with immune infiltration, co-expression correlations, and functional enrichment analysis of the DEGs were explored using multiple databases. As result, 12 DEGs were commonly down-expressed in PVTT compared with PT tissues among three datasets. The expression of , , , , , , and was progressively decreased from normal liver, PT, to PVTT tissues, whose up-expression associated with favorable survivals of HCC patients. The genetic alternations and DNA methylation of the DEGs frequently occurred, and several methylated CpG sites of the DEGs significantly correlated with outcomes of HCC patients. The immune infiltration in the tumor microenvironment of HCC was correlated with the expression level of the DEGs. Besides, the DEGs and their co-expressive genes participated in the biological processes of extracellular matrix (ECM) organization and focal adhesion. In summary, this study indicated the dysregulation of ECM and focal adhesion might contribute to the formation of PVTT. And the above seven genes might serve as potential biomarkers of PVTT occurrence and prognosis of HCC patients.
10.18632/aging.202876
Neoadjuvant Three-Dimensional Conformal Radiotherapy for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Randomized, Open-Label, Multicenter Controlled Study.
Wei Xubiao,Jiang Yabo,Zhang Xiuping,Feng Shuang,Zhou Bin,Ye Xiaofei,Xing Hui,Xu Ying,Shi Jie,Guo Weixing,Zhou Dong,Zhang Hui,Sun Huichuan,Huang Cheng,Lu Congde,Zheng Yaxin,Meng Yan,Huang Bin,Cong Wenming,Lau Wan Yee,Cheng Shuqun
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS:A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients' serum before RT and in surgical specimens was correlated with response to RT. RESULTS:In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group ( < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% ( < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; < .001] and 0.45 [95% CI, 0.31 to 0.64; < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT. CONCLUSION:For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.
10.1200/JCO.18.02184
Expression of the chemokine receptor CXCR4 in human hepatocellular carcinoma and its role in portal vein tumor thrombus.
Li Nan,Guo Weixing,Shi Jie,Xue Jie,Hu Huasheng,Xie Dong,Wu Mengchao,Cheng Shuqun
Journal of experimental & clinical cancer research : CR
BACKGROUND:This study was conducted to investigate the expression of CXCR4 in portal vein tumor thrombus (PVTT) tissue and its possible role in the invasiveness of tumor thrombus cells. METHODS:We detected differential expression of CXCR4 between PVTT and hepatocellular carcinoma (HCC) by an immunohistochemical assay. Lentivirus-mediated RNA interference and a migration assay were performed on human primary cells derived from PVTT to study the impact of CXCR4 on the invasiveness of HCC. RESULTS:The expression of CXCR4 in tumor thrombus tissue was higher than that in HCC tissue. The invasion ratio of PVTT cells was significantly decreased (P < 0.05) after being infected with a CXCR4-targeting siRNA lentivirus, indicating that downregulation of CXCR4 by lentivirus-mediated RNA interference significantly impaired the invasive potential of PVTT. CONCLUSIONS:These results indicate that CXCR4 is an effective curative target for hepatocellular carcinomas with PVTT.
10.1186/1756-9966-29-156
Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus (2018 Edition).
Cheng Shuqun,Chen Minshan,Cai Jianqiang,Sun Juxian,Guo Rongping,Bi Xinyu,Lau Wan Yee,Wu Mengchao
Liver cancer
Portal vein tumor thrombus (PVTT) is very common, and it plays a major role in the prognosis and clinical staging of hepatocellular carcinoma (HCC). We have published the first version of the Consensus in 2016. Over the past several years, many new evidences for the treatment of PVTT become available especially for the advent of new targeted drugs which have further improved the prognosis of PVTT. So, the Chinese Association of Liver Cancer revised the 2016 version of consensus to adapt to the development of PVTT treatment. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials.
10.1159/000503685
Challenging the Treatment Paradigm: Selecting Patients for Surgical Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.
Nevarez Nicole M,Yopp Adam C
Journal of hepatocellular carcinoma
Portal vein tumor thrombus (PVTT) remains a common presentation in patients with hepatocellular carcinoma (HCC). Approximately 30-50% of patients newly diagnosed with HCC will present with a concomitant PVTT. Current guidelines recommend systemic therapy for treatment of HCC with PVTT. Real-world application of partial hepatectomy in HCC patients with PVTT has increased over the past two decades, as perioperative complications have declined. However, it is unclear if there is an association between the extent of PVTT and overall survival and rates of recurrence and whether the perioperative morbidity outweighs these potential benefits. Partial hepatectomy with en bloc resection of PVTT in second-order branches and distal can offer significant benefits in carefully selected patients; however, once the HCC-associated PVTT extends into first-order portal venous branches or more proximal into the superior mesenteric vein, the risks of surgical resection outweigh the benefits. The aim of this review is to determine which patients with HCC presenting with PVTT benefit from surgical resection. We will discuss the classification systems of PVTT and review both outcome and perioperative measures in patients undergoing partial hepatectomy with extirpation of HCC-related PVT.
10.2147/JHC.S291530
Determination of portal vein tumor thrombus blood supply using in vivo cellular magnetic resonance imaging in a rabbit model.
Zhang Xiuming,Wu Bei,Guo Zhen,Gao Yang,Xi Wei,Yu Hui,Feng Guodong,Zhang Jingyuan,Shen Wenrong,Chen Jun
Cancer management and research
This study aimed to investigate the anatomic configuration of the blood vessels that contribute to portal vein tumor thrombus (PVTT), a common complication of hepatocellular carcinoma, in VX2 rabbits. Peripheral blood mononuclear cells (MNCs) were isolated and labeled using superparamagnetic iron oxide particles in vitro. Twenty-four rabbits were injected with the VX2 tumor via the portal vein to establish the PVTT model. The rabbits (n=6/treatment group) were randomly assigned into four groups. Rabbits of groups A, B and C received an infusion of iron-labeled MNCs via the hepatic artery, the portal vein or the auricular vein, respectively, whereas rabbits of group D received an injection of normal saline via the auricular vein 7 days after the injection of VX2 tumors. MRI was performed, and the signal intensity (SI) of the PVTTs was measured on T2-weighted images (T2WIs) 1 day after the transfusion of iron-labeled cells. The SI of PVTTs, as measured on T2WIs, in rabbits of groups A, B, C and D was 241.400 (172.350, 364.825), 221.150 (203.775, 318.225), 590.200 (363.325, 728.875) and 568.050 (474.725, 705.150), respectively. Our data showed a significant decrease in the SI of PVTTs in rabbits of groups A and B compared with rabbits of groups C and D (group A vs group C, U=4.000, =0.025; group A vs group D, U=2.000, =0.010; group B vs group C, U=4.000, =0.025; group B vs group D, U=1.000, =0.006). There was no significant difference in the SI of PVTTs in rabbits of group A and B. Our results indicated that the portal vein and the hepatic artery supplied blood flow to the PVTT in rabbits.
10.2147/CMAR.S197231
The evaluation of anti-angiogenic effects of Endostar on rabbit VX2 portal vein tumor thrombus using perfusion MSCT.
Feng Guoquan,Lei Zhen,Wang Dongqing,Xu Na,Wei Qiang,Li Dinuo,Liu Jingyi
Cancer imaging : the official publication of the International Cancer Imaging Society
BACKGROUND:There were many treatments for hepatocellular carcinoma with portal vein tumor thrombus (PVTT), in which targeted anti-angiogenic drug therapy is becoming a popular research topic. However, an objective and non-invasive method that can evaluate the treatment effects is still lacking. METHODS:Eighteen New Zealand white rabbits implanted with VX2 tumor thrombus in portal vein were randomly assigned into 3 groups: Endostar, saline, or control, six in each group. Multi-slice CT (MSCT) perfusion scanning was performed to measure the differences in blood flow (TBF), tissue blood volume (TBV), and capillary permeability time the surface (PS) before and after Endostar treatment, between Endostar and saline treatment. Two weeks after treatment, both Endostar and saline groups underwent CT perfusion scan. The rabbits then were sacrificed by air embolism, and specimens of tumor thrombosis were collected. Immunohistochemistry assay was also performed to compare the expression of vascular endothelial growth factor (VEGF) in PVTT after Endostar, saline and placebo treatment. RESULTS:In Endostar group, PVTT CT perfusion parameters (TBF, TBV, PS) significantly decreased after the treatment (p <0.05). Post-treatment PVTT CT perfusion parameters (TBF, TBV, PS) were significantly lower in Endostar group than in Saline group (p <0.05). VEGF is mainly expressed in cytoplasma. After Endostar treatment, the expression of VEGF in PVTT was markedly reduced. There was also significant difference on post-treatment VEGF protein expression measured by Immunohistochemistry assay between Endostar group and control group (p <0.05). Post-treatment PVTT CT perfusion parameters (TBF, TBV, PS) were positively correlated with VEGF protein expression in all 3 groups (rs > 0, p <0.05). CONCLUSIONS:Multi-slice CT perfusion imaging can evaluate the anti-angiogenic effects of Endostar for the VX2 tumor thrombus in portal vein, and provide quantitative functional information.
10.1186/1470-7330-14-17
Apatinib treatment of advanced hepatocellular carcinoma with portal vein and inferior vena cava tumor thrombus: A case report.
Yang XueGang,Wu Ge,Xu GuoHui
Medicine
RATIONALE:Hepatocellular carcinoma (HCC) is a highly invasive cancer associated with vascular invasion. The survival of advanced HCC is very poor. In this case study, we describe the efficacy and safety of apatinib in patient with advanced HCC as the first-line therapy. PATIENT CONCERNS:A 46-year-old male complained of abdominal distention and pain for half a month. DIAGNOSES:HCC patient with portal vein and inferior vena cava tumor thrombus. INTERVENTIONS:The apatinib alone was used as first-line therapy. OUTCOMES:Intrahepatic tumors, portal vein, and inferior vena cava tumor thrombus were diminished. The patient achieved partial response (PR) soon after the treatment, and progression-free survival (PFS) was 12.5 months. During the entire process, the alpha-fetoprotein (AFP) continued to decrease. LESSONS:Apatinib alone may be a safe and effective therapy for HCC patients with portal vein and inferior vena cava tumor thrombus. However, it is warranted further investigation in the future prospective randomized clinical studies.
10.1097/MD.0000000000014582
The multidisciplinary management of hepatocellular carcinoma with portal vein tumor thrombus.
Qiu Guoteng,Xie Kunlin,Jin Zhaoxing,Jiang Chuang,Liu Hu,Wan Haifeng,Huang Jiwei
Bioscience trends
Portal vein tumor thrombus (PVTT) is one of the most common complications of hepatocellular carcinoma (HCC), which refers to the advanced stage of HCC and indicates an extremely poor prognosis. Monotherapy cannot effectively prolong the survival benefit of patients with HCC-PVTT characterized by a high recurrence rate. With great progress in the area of immune and molecular targeted therapy, there comes a promising era of multidisciplinary management of HCC. Survival benefits can be achieved based on accurate diagnosis, staging, and multidisciplinary management. Additionally, in terms of the presence of controversy about the standard treatment algorithm and the absence of universal treatment guidelines, a multidisciplinary management program may afford the best hope for HCC-PVTT patients via appropriate implement of various treatment protocols.
10.5582/bst.2021.01173
Better surgical treatment method for hepatocellular carcinoma with portal vein tumor thrombus.
Peng Shu-You,Wang Xu-An,Huang Cong-Yun,Li Jiang-Tao,Hong De-Fei,Wang Yi-Fang,Xu Bin
World journal of gastroenterology
Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is a disease that is not uncommon, but the treatments vary drastically between Eastern and Western countries. In Europe and America, the first line of treatment is systemic therapy such as sorafenib and the surgical treatment is not a recommend option. While an increasing number of studies from China and Japan have suggested that surgical treatment results in better outcomes when compared to transcatheter arterial chemoembolization (TACE), sorafenib, or other nonsurgical treatments, and two classification systems, Japanese Vp classification and Chinese Cheng's classification, were very useful to guide the surgical treatment. We have also found that surgical treatment may be more effective, as we have performed surgical treatment for HCC-PVTT patients over a period of approximately 15 years and achieved good results with the longest surviving time being 13 years and onward. In this study, we review the efficacy and principles of current surgical treatments and introduce our new, more effective surgical technique named "thrombectomy first", which means the tumor thrombus in the main portal vein, the bifurcation or the contralateral portal vein should be removed prior to liver resection. Thus, compression and crushing of PVTT during the operation could be avoided and new intrahepatic metastases caused by tumor thrombus to the remnant liver minimized. The new technique is even beneficial to the prognosis of Cheng's classification Types III and IV PVTT. The vital tips and tricks for the surgical approach are described.
10.3748/wjg.v24.i40.4527
Spontaneous Regression of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.
Koya Yudai,Suzuki Tomohiro,Tai Mayumi,Ichii Osamu,Matsuhashi Nobuo,Ejiri Yutaka,Shibata Michihiko,Harada Masaru
Case reports in gastroenterology
An 83-year-old man underwent transcatheter arterial chemoembolization (TACE) for a 20-mm hepatocellular carcinoma (HCC) in Couinaud's segment 4. Computed tomography (CT) 4 months after TACE showed tumor thrombus in the portal vein in addition to diffuse metastases and arterioportal shunts in the left lobe. Although we performed the best supportive care, the tumor thrombus in the portal vein and tumors in the left lobe had completely disappeared on CT 16 months after the TACE. Rapidly grown portal vein tumor thrombus and arterioportal shunt might be the causes of spontaneous regression of HCC, probably associated with tumor hypoxia.
10.1159/000490661
Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?
Zuo Shiyi,Song Jiaxuan,Zhang Jingxuan,He Zhonggui,Sun Bingjun,Sun Jin
Theranostics
Immunotherapy provides a new avenue for combating cancer. Current research in anticancer immunotherapy is primary based on T cell-mediated cellular immunity, which can be divided into seven steps and is named the cancer-immunity cycle. Unfortunately, clinical applications of cancer immunotherapies are restricted by inefficient drug delivery, low response rates, and unmanageable adverse reactions. In response to these challenges, the combination of nanotechnology and immunotherapy (nano-immunotherapy) has been extensively studied in recent years. Rational design of advanced nano-immunotherapies requires in-depth consideration of "which" immune step is targeted, "why" it needs to be further enhanced, and "what" nanotechnology can do for immunotherapy. However, the applications and effects of nanotechnology in the cancer-immunity cycle have not been well reviewed. Herein, we summarize the current developments in nano-immunotherapy for each stage of cancer cellular immunity, with special attention on the which, why and what. Furthermore, we summarize the advantages of nanotechnology for combination immunotherapy in two categories: enhanced efficacy and reduced toxicity. Finally, we discuss the challenges of nano-immunotherapy in detail and provide a perspective.
10.7150/thno.59953
Synthesis of Multifunctional Nanoparticles for the Combination of Photodynamic Therapy and Immunotherapy.
Lee Mei-Hwa,Thomas James L,Li Jin-An,Chen Jyun-Ren,Wang Tzong-Liu,Lin Hung-Yin
Pharmaceuticals (Basel, Switzerland)
Programmed death-ligand 1 protein (PD-L1) has been posited to have a major role in suppressing the immune system during pregnancy, tissue allografts, autoimmune disease and other diseases, such as hepatitis. Photodynamic therapy uses light and a photosensitizer to generate singlet oxygen, which causes cell death (phototoxicity). In this work, photosensitizers (such as merocyanine) were immobilized on the surface of magnetic nanoparticles. One peptide sequence from PD-L1 was used as the template and imprinted onto poly(ethylene--vinyl alcohol) to generate magnetic composite nanoparticles for the targeting of PD-L1 on tumor cells. These nanoparticles were characterized using dynamic light scattering, high-performance liquid chromatography, Brunauer-Emmett-Teller analysis and superconducting quantum interference magnetometry. Natural killer-92 cells were added to these composite nanoparticles, which were then incubated with human hepatoma (HepG2) cells and illuminated with visible light for various periods. The viability and apoptosis pathway of HepG2 were examined using a cell counting kit-8 and quantitative real-time polymerase chain reaction. Finally, treatment with composite nanoparticles and irradiation of light was performed using an animal xenograft model.
10.3390/ph14060508
Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer.
Huang Kuan-Wei,Hsu Fu-Fei,Qiu Jiantai Timothy,Chern Guann-Jen,Lee Yi-An,Chang Chih-Chun,Huang Yu-Ting,Sung Yun-Chieh,Chiang Cheng-Chin,Huang Rui-Lin,Lin Chu-Chi,Dinh Trinh Kieu,Huang Hsi-Chien,Shih Yu-Chuan,Alson Donia,Lin Chun-Yen,Lin Yung-Chang,Chang Po-Chiao,Lin Shu-Yi,Chen Yunching
Science advances
While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8 T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
10.1126/sciadv.aax5032
NIR-absorbing Prussian blue nanoparticles for transarterial infusion photothermal therapy of VX2 tumors implanted in rabbits.
Pang Huajin,Tian Chen,He Genghan,Zhang Di,Yang Jinghong,Zhang Qianbing,Liu Ruiyuan
Nanoscale
Nanomaterial-related photothermal therapy has been intensively investigated for treatment of hepatocellular carcinoma (HCC). However, owing to the low specificity to tumors and easy excretion from the systemic circulation, the low dose of photoactive nanomaterials in solid tumors severely hinders the photothermal therapy applications for HCC. Herein, an innovative strategy for transarterial infusion photothermal therapy (TAIPPT) of VX2 tumors implanted in rabbits is reported. NIR-absorbing Prussian blue nanoparticles were prepared by microemulsion methods, which demonstrate excellent photothermal therapy capacity and satisfactory biocompatibility. Prussian blue nanoparticles are transarterially infused into VX2 tumors and irradiated for photothermal therapy. TAIPPT achieves fast and efficient delivery of nanoparticles into tumors and complete ablation by one-time transarterial infusion treatment. Furthermore, TAIPPT could activate the immune cells in rabbits and inhibit distant tumors. Our findings describe a promising strategy for tumor eradication and may benefit future clinical HCC patients.
10.1039/d1nr01394g
Homotypic Cell Membrane-Cloaked Biomimetic Nanocarrier for the Targeted Chemotherapy of Hepatocellular Carcinoma.
Liu Xiaojun,Sun Yingxue,Xu Shushen,Gao Xiaonan,Kong Fanpeng,Xu Kehua,Tang Bo
Theranostics
Hepatocellular carcinoma (HCC) has been reported to be the third most common malignant tumor and has the highest rate of mortality. To increase the chemotherapy efficacy of HCC, a drug delivery system featured with desirable active targeting ability, delivery efficiency and immune evasion is in high demand. We have developed a drug nanocarrier by utilizing a homotypic cancer cell membrane for targeted chemotherapy of HCC. Structurally, the homotypic HepG2 cell membrane was used as the cloak, and a poly (lactic--glycolic acid) (PLGA) nanoparticle as the core, resulting in the nanocarrier . The nanoparticles exhibit excellent targeting ability toward HepG2 cells. Doxorubicin (Dox) carried by possesses high delivery efficiency and a remarkable therapeutic effect. In experiments, delivers Dox directly to the tumor lesion of nude mice, and tumor volume decreases by approximately 90% after treatment. We have developed a drug nanocarrier by utilizing a homotypic cancer cell membrane for targeted chemotherapy of HCC with excellent active targeting ability. This biomimetic platform not only effectively treats HCC but also provides a sound strategy for the treatment of other cancers changes in the corresponding homotypic cancer cell membrane.
10.7150/thno.34837
Platelet membrane-coated nanoparticles for targeted drug delivery and local chemo-photothermal therapy of orthotopic hepatocellular carcinoma.
Wu Long,Xie Wei,Zan Hui-Ming,Liu Zhongzhong,Wang Ganggang,Wang Yanfeng,Liu Wei,Dong Wenfei
Journal of materials chemistry. B
Specific targeted drug delivery and controllable release of drugs at tumor regions are two of the main challenges for hepatocellular carcinoma (HCC) therapy, particularly post metastasis. Herein, we present a platelet membrane-facilitated local chemo-photothermal therapy strategy, in which polypyrrole (PPy) nanoparticles act as photothermal agents and along with antitumor drug doxorubicin (DOX) are encapsulated into platelet membranes (PLT-PPy-DOX). The particles are endowed with immune evasiveness and tumor targeting abilities from platelet membranes, and are then intravenously injected into an orthotopic mouse model of HCC. As expected, the PLT-PPy-DOX nanoplatforms were abundant in the tumor tissues. Hyperthermia was generated under laser irradiation (808 nm) not only to ablate tumor cells directly but also to increase the triggered release of DOX. This combination of local chemotherapy and photothermal therapy demonstrated excellent antitumor efficiency in suppressing primary tumor growth and inhibiting tumor metastases. This localized therapy which adopts biocompatible natural cell membranes and good biodegradable organic photothermal agents may provide new insights into designing biomimetic nano-vehicles for personalized therapy of HCC.
10.1039/d0tb00735h
Hybrid membrane camouflaged copper sulfide nanoparticles for photothermal-chemotherapy of hepatocellular carcinoma.
Ji Bai,Cai Hongqiao,Yang Yang,Peng Fenghui,Song Meiyu,Sun Kaiju,Yan Fei,Liu Yahui
Acta biomaterialia
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Biomimetic nanoparticles (NPs) coated with cell membranes show enhanced biocompatibility and specificity for homotypic cells, and have gained considerable attention for targeted anti-tumor therapy. We constructed cancer cell-macrophage hybrid membrane-coated near infrared (NIR)-responsive hollow copper sulfide nanoparticles encapsulating sorafenib and surface modified with anti-VEGFR (CuS-SF@CMV NPs). These CuS-SF@CMV NPs expressed the characteristic membrane proteins of both cancer cells and macrophages, and selectively accumulated in cancer cells in vitro and tumors in vivo, compared to the CuS NPs. In addition, the CuS-SF@CMV NPs achieved synergistic photo-thermal and chemotherapy in cancer cells upon NIR irradiation, with 94.3% inhibition of tumor growth in a murine hepatoma model. While the initial increase in temperature rapidly killed the tumor cells, sorafenib and the anti-VEGFR antibody sustained the tumor killing effect by respectively inhibiting tumor cell proliferation and angiogenesis via the Ras/Raf/MEK/ERK and PI3K/AKT pathways. Taken together, the CuS-SF@CMV NPs have immune evasion, tumor cell targeting and drug loading capacities, along with an inherent photo-thermal conversion ability, making them ideal for synergistic photo-thermal/chemo therapy against HCC. STATEMENT OF SIGNIFICANCE: We created cancer cell-macrophage hybrid membrane-coated hollow CuS NPs encapsulating sorafenib and surface modified with anti-VEGFR antibodies (CuS-SF@CMV). These CuS-SF@CMV NPs enhanced synergistic PTT and chemotherapy against hepatoma cells through homotypic cell targeting, immune escape and inhibition of a tumorigenic signaling pathway. A long-term inhibition of tumor growth and metastasis was achieved owing to the rapid destruction of the cancer cells through photo-thermal conversion by the CuS NPs, and sustained clearance of the tumor cells by sorafenib and anti-VEGFR antibodies. Our findings suggest that CuS-SF@CMV NPs present great treating effects in preclinical models of HCC, providing the framework for further study in clinical trials to improve patient outcome in hepatocellular carcinoma.
10.1016/j.actbio.2020.04.046
In vitro and in vivo anti-metastatic effect of the alkaliod matrine from Sophora flavecens on hepatocellular carcinoma and its mechanisms.
Dai Meiqin,Chen Nana,Li Jinzhou,Tan Lizhuan,Li Xiaojuan,Wen Jiayong,Lei Linsheng,Guo Dan
Phytomedicine : international journal of phytotherapy and phytopharmacology
BACKGROUNDS:Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancer with high metastasis and recurrence rates. Hypoxia-induced miRNAs and HIF-1α are demonstrated to play essential roles in tumor metastasis. Matrine (CHNO), an alkaloid extracted from Sophora flavescens Aiton, has been used as adjuvant therapy for liver cancer in China. The anti-metastasis effects of matrine on HCC and the underlying mechanisms remain poorly understood. PURPOSE:We aimed to investigate the effects of matrine on metastasis of HCC both in vitro and in vivo, and explored whether miR-199a-5p and HIF-1α are involved in the action of matrine. METHODS:MTT method, colony formation, wound healing and matrigel transwell assays were performed to evaluate the effects of matrine on cell proliferation, migration and invasion. Nude mice xenograft model and immunohistochemistry (IHC) assay were employed to investigate the anti-metastatic action of matrine in vivo. Quantitative real-time PCR, western blot and dual luciferase reporter assay were conducted to determine the underlying mechanisms of matrine. RESULTS:Matrine exerted stronger anti-proliferative action on Bel7402 and SMMC-7721 cells under hypoxia than that in normoxia. Both matrine and miR-199a-5p exhibited significant inhibitory effects on migration, invasion and EMT in Bel7402 and SMMC-7721 cells under hypoxia. Further study showed that miR-199a-5p was downregulated in HCC cell lines, and this microRNA was identified to directly target HIF-1α, resulting in decreased HIF-1α expression. Matrine induced miR-199a-5p expression, decreased HIF-1α expression and inhibited metastasis of Bel7402 and SMMC-7721 cells, while miR-199a-5p knockdown reversed the inhibitory effects of matrine on cell migration, invasion, EMT and HIF-1α expression. In vivo, matrine showed significant anti-metastatic activity in the nude mouse xenograft model. H&E and IHC analysis indicated that lung and liver metastasis nodules were reduced, and the protein expression of HIF-1α and Vimentin were significantly decreased by i.p injection of matrine. CONCLUSIONS:Matrine exhibits significant anti-metastatic effect on HCC, which is attributed to enhanced miR-199a-5p expression and subsequently impaired HIF-1α signaling and EMT. These findings suggest that miR-199a-5p is a potential therapeutic target of HCC, and matrine may represent a promising anti-metastatic medication for HCC therapy.
10.1016/j.phymed.2021.153580
Matrine suppresses lung metastasis of human hepatocellular carcinoma by directly targeting matrix metalloproteinase-9.
Zhang Juyuan,Gao Yuan,Han Hui,Zou Changlin,Feng Yu,Zhang Hui
Biochemical and biophysical research communications
Matrine is a natural compound derived from Radix Sophora flavescens which is a commonly used Chinese herb. Herein, we report that matrine may inhibit lung metastasis in liver cancer in mice. Invasion chamber assay, scratch-wound assay and orthotopic liver tumor implantation mice were introduced to investigate the potential pharmacological effects of matrine on human hepatocellular carcinoma (HCC). Our results showed that matrine at non-toxic dose could significantly suppress PLC/PRF/5 and MHCC97L cells migration and invasion. Furthermore, matrine treatment (5 mg/kg/day) significantly decreased lung metastasis in orthotopic HCC mouse models. Quantitative polymerase chain reaction, gelatin zymography and immunoblotting assay indicated that matrine could inhibit the activity of matrix metalloproteinase-9 without down-regulating its protein expression in HCC. The docking approach, site-directed mutagenesis, and surface plasmon resonance were applied to identify residues involved in matrine binding in matrix metalloproteinase-9. The biophysical and cell-based assays showed that Pro415, Arg424 residue might contribute to the binding affinity of matrine on matrix metalloproteinase-9 activity. In conclusion, matrine might be a promising anti-cancer agent for inhibiting HCC metastasis.
10.1016/j.bbrc.2019.04.063
Arsenite-loaded albumin nanoparticles for targeted synergistic chemo-photothermal therapy of HCC.
Zhang Ke,Li Dan,Zhou Bin,Liu Jiani,Luo Xiangjie,Wei Ruixue,Wang Lizhu,Hu Xiaojun,Su Zhongzhen,Lin Hongyu,Gao Jinhao,Shan Hong
Biomaterials science
Arsenic trioxide (ATO, AsO), an active ingredient of traditional Chinese medicine, has been approved by the U.S. Food and Drug Administration as an effective therapeutic agent for acute promyelocytic leukemia (APL). However, the application of ATO in treating advanced solid tumors like hepatocellular carcinoma (HCC) is still restricted by limited therapeutic efficacy and insufferable side effects. To solve this problem, we reported a general and facile strategy using human serum albumin (HSA) as a template for synthesizing a series of ATO-based nanoparticles with uniform single-albumin size. Then, we prepared a multifunctional drug delivery system (MDDS) based on MnAs/HSA termed MnAs/ICG/HSA-RGD, and tested its efficacy both and . Our results revealed that the photothermal effect of MnAs/ICG/HSA-RGD can not only cause irreversible damage to the tumor but also accelerate the discharge of As and Mn ions, enabling responsive chemotherapy and magnetic resonance imaging. Interestingly, the expression of HSP90, vimentin, and MMP-9 in tumor cells was inhibited during the treatment, resulting in less metastasis and recurrence. Moreover, no apparent side effect has been observed during the treatment. Therefore, MnAs/ICG/HSA-RGD can be considered as a promising option for HCC with excellent therapeutic efficacy and minimum side effects.
10.1039/d1bm01374b
Ultrasound-Driven Biomimetic Nanosystem Suppresses Tumor Growth and Metastasis through Sonodynamic Therapy, CO Therapy, and Indoleamine 2,3-Dioxygenase Inhibition.
Zhang Da,Lin Ziguo,Zheng Youshi,Song Jibin,Li Juan,Zeng Yongyi,Liu Xiaolong
ACS nano
The rational design of nanoplatforms to bypass reticuloendothelial system (RES) clearance, enhance spatiotemporal controllability, and boost host immune responses to achieve synergized tumor-targeted therapeutic purpose is highly desired. Herein, a biomimetic nanosystem is developed for tumor-targeted delivery of singlet oxygen (O) and carbon monoxide (CO) in response to exogenous stimulus ultrasound (US) and endogenous stimulus hydrogen peroxide (HO) in tumor microenvironment, respectively. Taking advantages of tumor homing and RES evasion abilities of the macrophage membrane coating, our designed nanosystem shows excellent accumulation at the tumor site and effective suppression of tumor growth through US/HO-generated O and CO to induce cell apoptosis and mitochondrial dysfunction. Furthermore, our nanosystem can induce significant tumor immunogenic death by O/CO therapy, then can achieve effective immune responses and long-term immune memory through the combination of indoleamin 2,3-dioxygenase (IDO) signal blocking to effectively against tumor rechallenge and prevent lung metastasis. Taken together, the here-presented therapeutic strategy based on sonodynamic/CO therapy and IDO signaling inhibition might provide a promising perspective for synergistically treating cancer in future clinical translations.
10.1021/acsnano.0c03833
Imaging of Cancer Immunotherapy: Current Approaches and Future Directions.
Nishino Mizuki,Hatabu Hiroto,Hodi F Stephen
Radiology
Cancer immunotherapy using immune-checkpoint inhibitors has emerged as an effective treatment option for a variety of advanced cancers in the past decade. Because of the distinct mechanisms of immunotherapy that activate the host immunity to treat cancers, unconventional immune-related phenomena are encountered in terms of tumor response and progression, as well as drug toxicity. Imaging plays an important role in objectively characterizing immune-related tumor responses and progression and in detecting and monitoring immune-related adverse events. Moreover, emerging data suggest a promise for molecular imaging that can visualize the specific target molecules involved in immune-checkpoint pathways. In this article, the background and current status of cancer immunotherapy are summarized, and the current methods for imaging evaluations of immune-related responses and toxicities are reviewed along with their limitations and pitfalls. Emerging approaches with molecular imaging are also discussed as a future direction to address unmet needs.
10.1148/radiol.2018181349
Nanohybrid liposomal cerasomes with good physiological stability and rapid temperature responsiveness for high intensity focused ultrasound triggered local chemotherapy of cancer.
Liang Xiaolong,Gao Jing,Jiang Lingdong,Luo Jianwen,Jing Lijia,Li Xiaoda,Jin Yushen,Dai Zhifei
ACS nano
The high intensity focused ultrasound (HIFU) and thermosensitive cerasomes (HTSCs) were successfully assembled by employing cerasome-forming lipid (CFL) in combination with the component lipids of conventional low temperature sensitive liposomes (LTSLs) including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000) and 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (MSPC). The HTSCs showed spherical shape with a mean diameter around 200 nm, exhibiting good biocompatibility. Both hydrophilic and lipophilic drugs can be efficiently encapsulated into HTSCs. In addition, the release rate of HTSCs could be conveniently adjusted by varying the molar ratios of CFL to DPPC. The drug loaded HTSCs showed much longer blood circulation time (half-life >8.50 ± 1.49 h) than conventional LTSLs (0.92 ± 0.17 h). An in vitro study demonstrated that the drug loaded HTSCs are highly stable at 37 °C and show a burst release at 42 °C, providing a capability to act synergistically against tumors. We found that the HTSCs with a proportion of 43.25% of CFL could release more than 90% hydrophilic drugs in 1 min at an elevated temperature of 42 °C generated by HIFU exposure. After intravenous injection of doxorubicin (DOX) loaded HTSCs at 5 mg DOX/kg, followed by double HIFU sonication, the tumor growth of the adenocarcinoma (MDA-MB-231) bearing mice could be significantly inhibited. Therefore, the drug loaded HTSCs combined with HIFU hold great potential for efficient local chemotherapy of cancer due to the ability to deliver high concentration of chemotherapy drugs directly to the tumor, achieve maximum therapeutic efficacy and minimal side effects, and avoid the damage to the healthy tissues caused by systemic administration of drugs.
10.1021/nn507482w
Applications of Micro/Nanotechnology in Ultrasound-based Drug Delivery and Therapy for Tumor.
Sun Suhui,Wang Ping,Sun Sujuan,Liang Xiaolong
Current medicinal chemistry
Ultrasound has been broadly used in biomedicine for both tumor diagnosis as well as therapy. The applications of recent developments in micro/nanotechnology promote the development of ultrasound-based biomedicine, especially in the field of ultrasound-based drug delivery and tumor therapy. Ultrasound can activate nano-sized drug delivery systems by different mechanisms for ultrasound- triggered on-demand drug release targeted only at the tumor sites. Ultrasound Targeted Microbubble Destruction (UTMD) technology can not only increase the permeability of vasculature and cell membrane via sonoporation effect but also achieve in situ conversion of microbubbles into nanoparticles to promote cellular uptake and therapeutic efficacy. Furthermore, High Intensity Focused Ultrasound (HIFU), or Sonodynamic Therapy (SDT), is considered to be one of the most promising and representative non-invasive treatment for cancer. However, their application in the treatment process is still limited due to their critical treatment efficiency issues. Fortunately, recently developed micro/nanotechnology offer an opportunity to solve these problems, thus improving the therapeutic effect of cancer. This review summarizes and discusses the recent developments in the design of micro- and nano- materials for ultrasound-based biomedicine applications.
10.2174/0929867327666200212100257
Platelets as platforms for inhibition of tumor recurrence post-physical therapy by delivery of anti-PD-L1 checkpoint antibody.
Han Xiao,Chen Jiawen,Chu Jiacheng,Liang Chao,Ma Qingle,Fan Qin,Liu Zhuang,Wang Chao
Journal of controlled release : official journal of the Controlled Release Society
Cancer local physical therapy (PT) by using heat, cold, electrical stimulation, irradiation or ultrasound to treat tumor is accepted as alternative choice for cancer patients. However, local recurrence and metastasis after such treatments remains to be the major cause of treatment failure and mortality. Therefore, it is necessary to develop a therapeutic strategy to inhibit local recurrence and metastasis. Inspired by the excellent inflammatory targeting ability of platelets, here we expect that the monoclonal antibody against programmed-death ligand 1 (aPDL1) engineered platelets could inhibit tumor local recurrence effectively, by facilitating transport of anti-PD-L1 antibodies to the ablated area with residue tumors. Using triple-negative breast carcinomas (4T1) bearing mouse model, we proved that antibody-coupled platelets could effectively target incompletely ablated tumor with thermal ablation (TA). We found the release of anti-PD-L1 can be triggered upon the platelets activation, together with many pro-inflammatory cytokines. The release of anti-PD-L1 is likely due to the dissociation of platelets upon the activation. Our findings approved that our platelet-based platform could facilitate the delivery of immune checkpoint antibody to tumor residues and remarkably prevent tumor recurrence after ablation. Moreover, this platelet-based delivery strategy may be extended to the targeted delivery of therapeutics post other types of local therapies including photodynamic therapy, high-intensity-focused-ultrasound ablation therapy, and even radiotherapy.
10.1016/j.jconrel.2019.05.008
High Intensity Focused Ultrasound-Responsive and Ultrastable Cerasomal Perfluorocarbon Nanodroplets for Alleviating Tumor Multidrug Resistance and Epithelial-Mesenchymal Transition.
Ma Xiaotu,Yao Meinan,Shi Jiyun,Li Xiaoda,Gao Yu,Luo Qi,Hou Rui,Liang Xiaolong,Wang Fan
ACS nano
Hypoxia is a hostile hallmark of most solid tumors, which often leads to multidrug resistance (MDR) and causes the failure of chemotherapy. Hypoxia also promotes epithelial-mesenchymal transition (EMT), leading to acceleration of tumor metastasis. Many chemotherapeutic drugs can further exacerbate hypoxia and thus promote metastasis. Therefore, relieving hypoxia is necessary for chemotherapy to inhibit both MDR and EMT. Herein, highly stable cerasomal perfluorocarbon nanodroplets with an atomic layer of polyorganosiloxane surface and pH-sensitive tumor-targeting peptide (D-vPCs-O) were fabricated to co-deliver oxygen and therapeutic drug, doxorubicin. High-intensity focused ultrasound (HIFU) was utilized to trigger the co-release of doxorubicin and oxygen and simultaneously enhance ultrasound imaging, therefore achieving imaging-guided drug delivery. Mild-temperature HIFU (M-HIFU) not only triggered oxygen release from nanodroplets but also slightly elevated tumor temperature to accelerate tumor blood flow. The oxygen release and temperature elevation jointly relieved tumor hypoxia and alleviated MDR, which greatly enhanced the drug therapeutic efficacy as compared to clinically used doxorubicin and Doxil. Overall side effects were also largely reduced owing to the ultrastable drug loading of cerasome. The improvement of insufficient chemotherapy and the relief of tumor hypoxia corporately down-regulated TGF-β1, leading to the alleviation of EMT, and therefore significantly inhibited tumor metastasis. When "D-vPCs-O + M-HIFU" was utilized as a neoadjuvant chemotherapy, nanodroplets down-regulated heat shock proteins, reducing tumor relapse after the high-temperature HIFU (H-HIFU)-mediated hyperthermia ablation. The chemo-hyperthermia therapy totally eradicated tumors without any relapse or metastasis, providing a promising way to treat the triple-negative breast cancer, which is highly malignant, easily metastatic, and lacks effective treatments.
10.1021/acsnano.0c07287
Assessment of Gold Nanoparticle-Mediated-Enhanced Hyperthermia Using MR-Guided High-Intensity Focused Ultrasound Ablation Procedure.
Devarakonda Surendra B,Myers Matthew R,Lanier Mathew,Dumoulin Charles,Banerjee Rupak K
Nano letters
High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.
10.1021/acs.nanolett.7b00272
Designing intelligent nano-bomb with on-demand site-specific drug burst release to synergize with high-intensity focused ultrasound cancer ablation.
Mai Xiaoxuan,Chang Yanzhou,You Yuanyuan,He Lizhen,Chen Tianfeng
Journal of controlled release : official journal of the Controlled Release Society
High intensity focused ultrasound (HIFU) has been widely used in clinical treatment of cervical cancer for its non-invasiveness and sharp treatment margins with very low complication rates. However, how to intensify the therapeutic efficacy of HIFU by specifically focusing the ultrasound energy on targeting pathological tissues is still a bottleneck for it to realize successful cancer ablation. Herein, a multifunctional organic-inorganic hybrid nanovesicles, by coating ultrathin silica shell on the surface of poly (lactic-co-glycolic acid) (PLGA) loaded with perfluorocarbon (PFOB), hydrophobic antitumor ruthenium complex (RuPOP) and superparamagnetic FeO, has been designed to achieve synchronous ultrasound (US)/magnetic resonance imaging (MR) dual mode imaging-guided HIFU-triggered chemotherapy. The introduction of PFOB in this nanosystem could cause phase transition and make it gasification to cause collapse of the outer ultrathin silicon shell under HIFU irradiation, which results in enhanced intensive mechanical stress during blasting and enhanced therapeutic effect. The blasting behavior of this nanosystem triggered by HIFU also induced the on-demand RuPOP burst release in tumor site, thus maximizing the inhibition on residual tumor induced by inhomogeneous HIFU ablation. Taken together, this treatment strategy could overcome the inevitable tumor recurrence and significantly reduces systemic side effects of HIFU, thus could be further developed for noninvasive cancer therapy.
10.1016/j.jconrel.2020.09.051
Polylactic acid nano- and microchamber arrays for encapsulation of small hydrophilic molecules featuring drug release via high intensity focused ultrasound.
Gai Meiyu,Frueh Johannes,Tao Tianyi,Petrov Arseniy V,Petrov Vladimir V,Shesterikov Evgeniy V,Tverdokhlebov Sergei I,Sukhorukov Gleb B
Nanoscale
Long term encapsulation combined with spatiotemporal release for a precisely defined quantity of small hydrophilic molecules on demand remains a challenge in various fields ranging from medical drug delivery, controlled release of catalysts to industrial anti-corrosion systems. Free-standing individually sealed polylactic acid (PLA) nano- and microchamber arrays were produced by one-step dip-coating a PDMS stamp into PLA solution for 5 s followed by drying under ambient conditions. The wall thickness of these hydrophobic nano-microchambers is tunable from 150 nm to 7 μm by varying the PLA solution concentration. Furthermore, small hydrophilic molecules were successfully in situ precipitated within individual microchambers in the course of solvent evaporation after sonicating the PLA@PDMS stamp to remove air-bubbles and to load the active substance containing solvent. The cargo capacity of single chambers was determined to be in the range of several picograms, while it amounts to several micrograms per cm. Two different methods for sealing chambers were compared: microcontact printing versus dip-coating whereby microcontact printing onto a flat PLA sheet allows for entrapment of micro-air-bubbles enabling microchambers with both ultrasound responsiveness and reduced permeability. Cargo release triggered by external high intensity focused ultrasound (HIFU) stimuli is demonstrated by experiment and compared with numerical simulations.
10.1039/c7nr01841j
Nano-Enhanced Drug Delivery and Therapeutic Ultrasound for Cancer Treatment and Beyond.
Tharkar Priyanka,Varanasi Ramya,Wong Wu Shun Felix,Jin Craig T,Chrzanowski Wojciech
Frontiers in bioengineering and biotechnology
While ultrasound is most widely known for its use in diagnostic imaging, the energy carried by ultrasound waves can be utilized to influence cell function and drug delivery. Consequently, our ability to use ultrasound energy at a given intensity unlocks the opportunity to use the ultrasound for therapeutic applications. Indeed, in the last decade ultrasound-based therapies have emerged with promising treatment modalities for several medical conditions. More recently, ultrasound in combination with nanomedicines, i.e., nanoparticles, has been shown to have substantial potential to enhance the efficacy of many treatments including cancer, Alzheimer disease or osteoarthritis. The concept of ultrasound combined with drug delivery is still in its infancy and more research is needed to unfold the mechanisms and interactions of ultrasound with different nanoparticles types and with various cell types. Here we present the state-of-art in ultrasound and ultrasound-assisted drug delivery with a particular focus on cancer treatments. Notably, this review discusses the application of high intensity focus ultrasound for non-invasive tumor ablation and immunomodulatory effects of ultrasound, as well as the efficacy of nanoparticle-enhanced ultrasound therapies for different medical conditions. Furthermore, this review presents safety considerations related to ultrasound technology and gives recommendations in the context of system design and operation.
10.3389/fbioe.2019.00324
Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells.
Ding Baoyue,Wahid Md Arif,Wang Zhijun,Xie Chen,Thakkar Arvind,Prabhu Sunil,Wang Jeffrey
Nanoscale
Pancreatic cancer is a lethal disease with a dreadful 5-year survival rate of only 5%. In spite of several treatment options, the prognosis still remains extremely poor. Therefore, novel therapy strategies with combinations of drugs are urgently required to combat this fatal disease. Triptolide (TPL) and celastrol (CL), two main compounds in traditional Chinese medicine isolated from Thunder God Vine, have a broad range of bioactivities including anticancer activity. Silk fibroin (SF), a naturally occurring protein with several unique properties, is an ideal carrier material. In this study, we prepared TPL and CL loaded silk fibroin nanoparticles (TPL-SFNPs and CL-SFNPs) by a modified desolvation method and evaluated their synergistic effects against human pancreatic cancer cells. Both SFNPs were characterized for particle size and zeta potential. The entrapment efficiency, drug loading, and drug release profiles were evaluated by HPLC. The cytotoxicity and synergistic effect of SFNPs were investigated in MIA PaCa-2 and PANC-1 human pancreatic cells. The results showed that the particle sizes of TPL-SFNPs and CL-SFNPs were 166.4 ± 4.6 nm and 170.4 ± 2.3 nm, with a mean zeta potential -27.2 ± 2.0 mV and -25.5 ± 2.57 mV, respectively. TPL-SFNPs and CL-SFNPs have a drug loading of 57.0 ± 4.7 μg mg and 63.5 ± 3.8 μg mg along with an encapsulation efficiency of 81.8 ± 2.8% and 87.0 ± 5.1%, respectively. Drug release studies revealed that a rapid release of the drugs from SFNPs was observed at pH 4.5 (lysosomal pH) and a delayed release was observed at pH 7.4 (plasma pH). TPL-SFNPs (IC 3.80 and 4.75 nM) and CL-SFNPs (IC 0.38 and 0.64 μM) were 2-3 fold more potent against MIA PaCa-2 and PANC-1 cells than free TPL (IC 11.25 and 11.58 nM) and CL (IC 0.84 and 1.23 μM). Furthermore, co-treatment with TPL-SFNPs and CL-SFNPs increased the growth inhibition of the same cells significantly in comparison with TPL-SFNPs or CL-SFNPs alone. Almost all combination index (CI) values, calculated using the CompuSyn software, were <1, suggesting that the growth inhibition effect of TPL-SFNPs in combination with CL-SFNPs was synergistic rather than additive, further suggesting that this novel combination may offer a potential treatment for pancreatic cancer.
10.1039/c7nr03016a
Manganese/iron-based nanoprobes for photodynamic/chemotherapy combination therapy of tumor guided by multimodal imaging.
Fan Shanshan,Zhang Yu,Tan Haisong,Xue Cuili,He Yu,Wei Xiangyu,Zha Yiqian,Niu Jiaqi,Liu Yanlei,Cheng Yingsheng,Cui Daxiang
Nanoscale
Early diagnosis of tumors is crucial in selecting appropriate treatment options to achieve the desired therapeutic effect, but it is difficult to accurately diagnose cancer by a single imaging modality due to technical constraints. Therefore, we synthesized a type of Fe3O4 nanoparticle with manganese dioxide grown on the surface and then prepared it by loading photosensitive drugs and traditional Chinese medicine monomers to create an integrated diagnosis/treatment multifunctional nanoplatform: Fe3O4@MnO2-celastrol (CSL)/Ce6. This nanoplatform can have full advantage of the tumor microenvironment (TME) characteristics of hypoxia (hypoxia), acidic pH (acidosis), and increased levels of reactive oxygen species (e.g., H2O2), even outside the TME. Specific imaging and drug release can also enhance tumor therapy by adjusting the hypoxic state of the TME to achieve the combined effect of chemotherapy (CT) and photodynamic therapy (PDT). Moreover, the obtained Fe3O4@MnO2-CSL/Ce6 has H2O2- and pH-sensitive biodegradation and can release the anticancer drug celastrol (CSL) and photosensitizer Ce6 in TME and simultaneously generate O2 and Mn2+. Therefore, the "dual response" synergistic strategy also confers specific drug release on nanomaterials, relieves tumor hypoxia and antioxidant capacity, and achieves significant optimization of CT and PDT. Furthermore, the resulting Mn2+ ions and Fe3O4 nanoparticles can be used for T1/T2 magnetic resonance imaging on tumor-bearing mice, and the released Ce6 can simultaneously provide fluorescence imaging functions. Therefore, Fe3O4@MnO2-CSL/Ce6 realized the synergistic treatment of PDT and CT under multimodal near-infrared fluorescence/photoacoustic (photoacoustic) imaging monitoring, showing its great potential in the accurate medical treatment of tumors.
10.1039/d0nr08831e
The Anticancer Properties of Herba Epimedii and Its Main Bioactive Componentsicariin and Icariside II.
Chen Meixia,Wu Jinfeng,Luo Qingli,Mo Shuming,Lyu Yubao,Wei Ying,Dong Jingcheng
Nutrients
Cancer is one of the leading causes of deaths worldwide. Compounds derived from traditional Chinese medicines have been an important source of anticancer drugs and adjuvant agents to potentiate the efficacy of chemotherapeutic drugs and improve the side effects of chemotherapy. Herba Epimedii is one of most popular herbs used in China traditionally for the treatment of multiple diseases, including osteoporosis, sexual dysfunction, hypertension and common inflammatory diseases. Studies show Herba Epimedii also possesses anticancer activity. Flavonol glycosides icariin and icariside II are the main bioactive components of Herba Epimedii. They have been found to possess anticancer activities against various human cancer cell lines in vitro and mouse tumor models in vivo via their effects on multiple biological pathways, including cell cycle regulation, apoptosis, angiogenesis, and metastasis, and a variety of signaling pathways including JAK2-STAT3, MAPK-ERK, and PI3k-Akt-mTOR. The review is aimed to provide an overview of the current research results supporting their therapeutic effects and to highlight the molecular targets and action mechanisms.
10.3390/nu8090563
Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects.
Zhang Jianqin,Wu Chuxuan,Gao Li,Du Guanhua,Qin Xuemei
Advances in pharmacology (San Diego, Calif.)
Decoctions prepared from the roots of Astragali Radix are known as "Huangqi" and are widely used in traditional Chinese medicine for treatment of viral and bacterial infections, inflammation, as well as cancer. Astragaloside IV (AS-IV), one of the major compounds from the aqueous extract of Astragalus membranaceus, is a cycloartane-type triterpene glycoside chemical. To date, many studies in cellular and animal models have demonstrated that AS-IV possesses potent protective effects in cardiovascular, lung, kidney and brain. Based on studies over the past several decades, this review systematically summarizes the pharmacological effects, pharmacokinetics and the toxicity of AS-IV. We analyze in detail the pharmacological effects of AS-IV on neuroprotection, liver protection, anti-cancer and anti-diabetes, attributable to its antioxidant, anti-inflammatory, anti-apoptotic properties, and the roles in enhancement of immunity, attenuation of the migration and invasion of cancer cells and improvement of chemosensitivity of chemotherapy drugs. In addition, the latest developments in the combination of AS-IV and other active ingredients of traditional Chinese medicine or chemical drugs are detailed. These pharmacological effects are associated with multiple signaling pathways, including the Raf-MEK-ERK pathway, EGFR-Nrf2 signaling pathway, Akt/PDE3B signaling pathway, AMPK signaling pathway, NF-κB signaling pathway, Nrf2 antioxidant signaling pathways, PI3K/Akt/mTOR signaling pathway, PKC-α-ERK1/2-NF-κB pathway, IL-11/STAT3 signaling pathway, Akt/GSK-3β/β-catenin pathway, JNK/c-Jun/AP-1 signaling pathway, PI3K/Akt/NF-κB pathway, miRNA-34a/LDHA pathway, Nox4/Smad2 pathway, JNK pathway and NF-kB/PPARγ pathway. This review will provide an overall understanding of the pharmacological functions of astragaloside IV on neuroprotection, liver protection, anti-cancer and anti-diabetes. In light of this, AS-IV will be a potent alternative therapeutic agent for treatment of the above mentioned diseases.
10.1016/bs.apha.2019.08.002
Quercetin Remodels the Tumor Microenvironment To Improve the Permeation, Retention, and Antitumor Effects of Nanoparticles.
Hu Kaili,Miao Lei,Goodwin Tyler J,Li Jun,Liu Qi,Huang Leaf
ACS nano
Our previous work demonstrated that Wnt16 expression in cisplatin-damaged tumor-associated fibroblasts is a key factor contributing to cisplatin resistance in malignancies. Natural antifibrotic compounds with low toxicities are promising candidates to downregulate Wnt16 expression, improving the antitumor effect of cisplatin nanoparticles. Upon screening several natural chemicals, we found that a dietary flavonoid, quercetin, significantly suppresses Wnt16 expression in activated fibroblasts. To facilitate drug delivery, we have prepared a targeted lipid/calcium/phosphate nanoparticle formulation consisting of a prodrug of quercetin, i.e., quercetin phosphate, with a high loading efficiency (26.6% w/w). This quercetin nanoparticle with a particle size of around 35 nm significantly improved the bioavailability and metabolic stability of the parent quercetin. Quercetin phosphate is released from the nanoparticles and converted back to the parent quercetin under physiological conditions. Following systemic administration of quercetin phosphate nanoparticles, a significant downregulation in Wnt16 expression was observed and further yielded a synergistic antitumor effect with cisplatin nanoparticles in a stroma-rich bladder carcinoma model. The α-SMA-positive fibroblast and collagen within the tumor decreased significantly after combination treatment. This suggests that the remodeling of the tumor microenvironment induced by quercetin plays a critical role in promoting the synergy. Indeed, our data further confirmed that quercetin phosphate alone significantly remodeled the tumor microenvironment and increased the penetration of second-wave nanoparticles into the tumor nests. Collectively, quercetin phosphate nanoparticles may be a safe and effective way to improve therapeutic treatment for desmoplastic tumors.
10.1021/acsnano.7b01522
Astragaloside III Enhances Anti-Tumor Response of NK Cells by Elevating NKG2D and IFN-γ.
Chen Xingmeng,Chen Xi,Gao Junxiao,Yang Han,Duan Yue,Feng Yuxin,He Xin,Gong Xiaoqun,Wang Hanjie,Wu Xiaoli,Chang Jin
Frontiers in pharmacology
Natural killer (NK) cells play an irreplaceable role in the development of colon cancer, in which antitumor function of NK cells was impaired. Astragaloside III is a natural compound from Astragalus that has been shown to have immunomodulatory effects in various systems. However, few studies have evaluated the antitumor effects of Astragaloside III through stimulating systemic immunity and regulating NK cells. In this study, flow cytometry, immunohistochemical analysis, and immunofunctional assays were performed to elucidate the functions of Astragaloside III in restoring antitumor function of NK cells. We demonstrated that Astragaloside III significantly elevated the expression of natural killer group 2D (NKG2D), Fas, and interferon-γ (IFN-γ) production in NK cells, leading to increased tumor-killing ability. Experiments in cell co-culture assays and CT26-bearing mice model further confirmed that Astragaloside III could effectively impede tumor growth by increasing infiltration of NK cells into tumor and upregulating the antitumor response of NK cells. We further revealed that Astragaloside III increased IFN-γ secretion of NK cells by enhancing the expression of transcription factor T-bet. In conclusion, the effective anti-tumor function of Astragaloside III was achieved through up-regulation of the immune response of NK cells and elevation of NKG2D, Fas, and IFN-γ production.
10.3389/fphar.2019.00898
Prospective therapeutic potential of Tanshinone IIA: An updated overview.
Ansari Mohammad Azam,Khan Farheen Badrealam,Safdari Haaris Ahsan,Almatroudi Ahmad,Alzohairy Mohammad A,Safdari Mohammadreza,Amirizadeh Mehran,Rehman Suriya,Equbal Mohammad Javed,Hoque Mehboob
Pharmacological research
In the past decades, the branch of complementary and alternative medicine based therapeutics has gained considerable attention worldwide. Pharmacological efficacy of various traditional medicinal plants, their products and/or product derivatives have been explored on an increasing scale. Tanshinone IIA (Tan IIA) is a pharmacologically active lipophilic component of Salvia miltiorrhiza extract. Tan IIA shares a history of high repute in Traditional Chinese Medicine. Reckoning with these, the present review collates the pharmacological properties of Tan IIA with a special emphasis on its therapeutic potential against diverse diseases including cardiovascular diseases, cerebrovascular diseases, cancer, diabetes, obesity and neurogenerative diseases. Further, possible applications of various therapeutic preparations of Tan IIA were discussed with special emphasis on nano-based drug delivery formulations. Considering the tremendous advancement in the field of nanomedicine and the therapeutic potential of Tan IIA, the convergence of these two aspects can be foreseen with great promise in clinical application.
10.1016/j.phrs.2020.105364
Nano-realgar suppresses lung cancer stem cell growth by repressing metabolic reprogramming.
Yang Fei-Ran,Zhao Yu-Feng,Hu Xi-Wen,Liu Zong-Kai,Yu Xiao-Dan,Li Chang-Yang,Li Xiu-Rong,Li Hui-Jie
Gene
BACKGROUND:Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. METHODS:The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. RESULTS:Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. CONCLUSIONS:These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.
10.1016/j.gene.2021.145666
Nano-herb medicine and PDT induced synergistic immunotherapy for colon cancer treatment.
Wu Xiaoli,Yang Han,Chen Xingmeng,Gao Junxiao,Duan Yue,Wei Daohe,Zhang Jinchao,Ge Kun,Liang Xing-Jie,Huang Yuanyu,Feng Sizhou,Zhang Rongli,Chen Xi,Chang Jin
Biomaterials
A variety of therapies have been developed and used for the treatment of colon cancer, however, the high mortality rate remains high and more effective strategies are still in urgent needs. In this study, an immunotherapy approach that is composed of innate immune activator Astragaloside III (As) and the photodynamic therapy (PDT) reagent chlorine e6 (Ce6) ((As + Ce6)@MSNs-PEG), was developed for colon cancer treatment. We showed that (As + Ce6)@MSNs-PEG could effectively activate NK cells and inhibit the proliferation of tumor cells in vitro. It could also effectively reach tumor sites, induce infiltration of immune cells into the tumor, and enhance the cytotoxicity of natural killer cells and CD8 T cells in vivo. Without obvious side effects, (As + Ce6)@MSNs-PEG treatment significantly inhibited tumor growth and extended the lifespan of tumor-bearing mice. Further results revealed that treatment of (As + Ce6)@MSNs-PEG led to enhanced IFN secretion by immune cells and increased T-box transcription factor (T-bet), which is highly expressed by T cells. Therefore, (As + Ce6)@MSNs-PEG may serve as an effective and safe platform for combinatory use with nano-herb medicine and PDT to provide a new therapy for colon cancer treatment.
10.1016/j.biomaterials.2021.120654
Realgar Nanoparticles Inhibit Migration, Invasion and Metastasis in a Mouse Model of Breast Cancer by Suppressing Matrix Metalloproteinases and Angiogenesis.
Xiaoxia Xi,Jing Sun,Dongbin Xi,Yonggang Tian,Jingke Zhang,Yanying Zhang,Hulai Wei
Current drug delivery
BACKGROUND:Realgar, a traditional Chinese medicine, has shown antitumor efficacy in several tumor types. We previously showed that realgar nanoparticles (nano-realgar) had significant antileukemia, anti-lung cancer and anti-liver cancer effects. In addition, the anti-tumor effects of nanorealgar were significantly better than those of ordinary realgar. OBJECTIVE:To explore the inhibitory effects and molecular mechanisms of nano-realgar on the migration, invasion and metastasis of mouse breast cancer cells. METHODS:Wound-healing migration assays and Transwell invasion assays were carried out to determine the effects of nano-realgar on breast cancer cell (4T1) migration and invasion. The expression levels of matrix metalloproteinase (MMP)-2 and -9 were measured by Western blot. A murine breast cancer metastasis model was established, administered nano-realgar for 32 days and monitored for tumor growth and metastasis by an in vivo optical imaging system. Finally, living imaging and hematoxylin and eosin (HE) staining were used to measure the morphology and pathology of lung and liver cancer cell metastases, respectively. Angiogenesis was assessed by CD34 immunohistochemistry. RESULTS:Nano-realgar significantly inhibited the migration and invasion of breast cancer 4T1 cells and the expression of MMP-2 and -9. Meanwhile, nano-realgar effectively suppressed the abilities of tumor growth, metastasis and angiogenesis in the murine breast cancer metastasis model in a time- and dosedependent manner. CONCLUSION:Nano-realgar significantly inhibited migration and invasion of mouse breast cancer cells in vitro as well as pulmonary and hepatic metastasis in vivo, which may be closely correlated with the downexpression of MMP-2 and -9 and suppression of tumor neovascularization.
10.2174/1567201817666200115105633
A Modern Technology Applied in Traditional Chinese Medicine: Progress and Future of the Nanotechnology in TCM.
Yan Guojun,Wang Yonglin,Han Xinxin,Zhang Qian,Xie Hui,Chen Jun,Ji De,Mao Chunqin,Lu Tulin
Dose-response : a publication of International Hormesis Society
The application of nanotechnology to traditional Chinese medicine (TCM) enabled the development of Chinese medicine in the international society. The pharmacodynamics of TCM is not only depending on its chemical constituents but also related to its physical state such as particle size. Indeed, there is some new pesticide effect that appeared when the medicine was being made into nanophase. The application of nanotechnology to TCM can expand the use of a range of Chinese medicinal materials. In this review, we introduce the concept of nanometer TCM. We also review the preparation methods, advantages, and development tendency of Nano-TCM; furthermore, we analyze the problems in the process of development of Nano-TCM and put forward varies possible solutions to solve this problems, thereby providing new thought for the development of Nano-TCM.
10.1177/1559325819872854
Traditional Chinese medicine-combination therapies utilizing nanotechnology-based targeted delivery systems: a new strategy for antitumor treatment.
Ma Zhe,Fan Yuqi,Wu Yumei,Kebebe Dereje,Zhang Bing,Lu Peng,Pi Jiaxin,Liu Zhidong
International journal of nanomedicine
Cancer is a major public health problem, and is now the world's leading cause of death. Traditional Chinese medicine (TCM)-combination therapy is a new treatment approach and a vital therapeutic strategy for cancer, as it exhibits promising antitumor potential. Nano-targeted drug-delivery systems have remarkable advantages and allow the development of TCM-combination therapies by systematically controlling drug release and delivering drugs to solid tumors. In this review, the anticancer activity of TCM compounds is introduced. The combined use of TCM for antitumor treatment is analyzed and summarized. These combination therapies, using a single nanocarrier system, namely codelivery, are analyzed, issues that require attention are determined, and future perspectives are identified. We carried out a systematic review of >280 studies published in PubMed since 1985 (no patents involved), in order to provide a few basic considerations in terms of the design principles and management of targeted nanotechnology-based TCM-combination therapies.
10.2147/IJN.S197889
Nano Traditional Chinese Medicine: Current Progresses and Future Challenges.
Huang Yi,Zhao Yinglan,Liu Fang,Liu Songqing
Current drug targets
Nano traditional Chinese medicine (nano TCM) refers to bioactive ingredients, bioactive parts, medicinal materials or complex prescription, being approximately 100 nm in size, which are processed by nanotechnology. Nano TCM is a product of the TCM modernization, and is an application of nanotechnology in the field of TCM. This article reviews literatures on researches of nano TCM, which were published in the past 15 years. Different nanotechnologies have been used in preparation of Nano TCM in view of the varying aims of the study. The mechanical crushing technology is the main approach for nanolization of TCM material and complex prescription, and nanoparticulate drug delivery systems is the main approach for nanolization of bioactive ingredients or bioactive parts in TCM. Nano TCM has a number of advantages, for example, enhancing the bioavailability of TCM, reducing the adverse effects of TCM, achieving sustained release, attaining targeted delivery, enhancing pharmacological effects and improving the administration route of TCM. However, there are still many problems that must be resolved in nano TCM research. The main challenges to nano TCM include the theory system of TCM modernization, preparation technology, safety and stability, etc.
A Nano-Traditional Chinese Medicine Against Lymphoma That Regulates the Level of Reactive Oxygen Species.
Zhao Qiangqiang,Li Jian,Wu Bin,Shang Yinghui,Huang Xueyuan,Dong Hang,Liu Haiting,Gui Rong,Nie Xinmin
Frontiers in chemistry
Jolkinolide B (JB) is a bioactive compound isolated from a Chinese herbal medicine that exerts antitumor activity. However, the anti-lymphoma effect of JB and its mechanism are yet to be revealed. Because free JB has poor pharmacokinetics and weak antitumor efficacy, we opted to use black phosphorus quantum dot (BPQD) nanomaterials as a drug loading platform to synthesize a nano-traditional Chinese medicine (nano-TCM) called BPQDs@JB. Compared with free JB, Raji cells administrated with BPQDs@JB exhibited the cell viability of 19.85 ± 1.02%, and the production of intracellular reactive oxygen species (ROS) was promoted. Likewise, BPQDs@JB was capable of rising the apoptosis rate of Raji cells to 34.98 ± 1.76%. In nude mice transplanted tumor model administrated with BPQDs@JB, the tumor tissue sections administrated with BPQDS@JB achieved a conspicuous red fluorescence, demonstrating the presence of most ROS production in the BPQDS@JB. TUNEL achieved a number of positive (brown) nuclei , revealing that BPQDS@JB could significantly induce tumor tissue apoptosis. As revealed from the mentioned results, BPQDs@JB can generate considerable ROS and interfere with the redox state to inhibit tumor. In brief, BPQDs@JB may be adopted as a treatment option for lymphoma.
10.3389/fchem.2020.00565
The combination of nanotechnology and traditional Chinese medicine (TCM) inspires the modernization of TCM: review on nanotechnology in TCM-based drug delivery systems.
Drug delivery and translational research
Fast development of combination of nanotechnology with traditional Chinese medicine (TCM) broadens the field of application of TCM. Besides, it increases the research ideas and contributes to TCM modernization. As expected, TCM will be developed into the nanodrug delivery system by nanotechnology with careful design, which will enhance the medicinal value of TCM to cure and prevent disease based on benefits brought by nanometer scale. Here, formulations, relevant preparations methods, and characteristics of nano-TCM were introduced. In addition, the main excellent performances of nano-TCM were clearly elaborated. What is more, the review was intended to address the studies committed to application of nanotechnology in TCM over the years, including development of Chinese medicine active ingredients, complete TCM, and Chinese herbal compounds based on nanotechnology. Finally, this review discussed the safety of nano-TCM and presented future development trends in the way to realize the modernization of TCM. Overall, using the emerging nanotechnology in TCM is promising to promote progress of TCM in international platform. Recent researches on modernization of traditional Chinese medicine (TCM) urged by nanotechnology are introduced, and formulations, advantages, and applications of nano-TCM are reviewed to provide strong proofs. | https://www.pubmed.pro/favorite?favoriteId=47728 |
Motives for Illicit Drug Use Among Individuals With Body Dysmorphic Disorder.
Drug use disorders (DUDs) are highly prevalent in body dysmorphic disorder (BDD), but motives for illicit drug use in BDD have not yet been explored. This study examined motives for drug use and clinical correlates of drug use motives in a sample of individuals with BDD and lifetime drug use, using the Drug Use Motives Questionnaire and 3 additional body image-specific drug use motives. As predict...
Catatonia Due to Tacrolimus Toxicity 16 Years After Renal Transplantation: Case Report and Literature Review.
Tacrolimus, a potent posttransplant immunosuppressant, has been associated with major neuropsychiatric complications, including catatonia and psychosis. We report a novel case of tacrolimus-induced encephalopathy that developed 16 years after renal transplantation while the drug was at a therapeutic level. Discontinuation of tacrolimus and switching to an alternative immunosuppressant resulted in ...
Optimization of peptide-drug conjugates for targeted tumor therapy.
In case of cancers with high mortality rate and lacking efficient medication there is a huge need of new, innovative treatments. Targeted tumor therapy, a real breakthrough in this field, is based on the concept that the antitumor agent is linked to a targeting molecule (e.g. peptide) specifically recognizing receptors or antigens that are tumor specific or overexpressed by tumor cells. The effici...
How can we better manage drug-resistant OAB/DO? ICI-RS 2018.
Botulinum toxin A (BTX-A), sacral nerve stimulation (SNM), and posterior tibial nerve stimulation (PTNS) are established treatments for idiopathic overactive bladder (OAB) refractory to oral drug therapy. At the ICI-RS meeting in Bristol in 2018 a think tank was convened to address the question of how to better manage drug-resistant OAB/DO (detrusor overactivity).
Correlates of alcohol and illicit drug use before commercial sex among transgender women with a history of sex work in China.
Research on substance use among transgender female sex workers in China is scarce. The aims of this study were to examine: (1) the prevalence of alcohol or illicit drug use before commercial sex among this population; and (2) correlates of alcohol and illicit drug use. Complete survey data were analysed from 397 transgender female sex workers recruited from three of the largest cities in China: S...
The improved cargo loading and physical stability of ibuprofen orodispersible film: molecular mechanism of ion-pair complexes on drug-polymer miscibility.
High drug cargo loading in polymer and physical stability was essential for the development of orodispersible film (ODFs) due to the small amount of excipients used in a thin film. The present study aimed to investigate the mechanism of ion-pair strategy in improving drug cargo loading and physical stability of drug in ODFs. The results showed that the ion-pair, especially IBU-ethanolamine, improv...
Preparation, characterization and evaluation of antibacterial properties of epirubicin loaded PHB and PHBV nanoparticles.
Poly-3-hydroxybutyrate (PHB) and poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) are considered as ideal drug carriers due to their non-toxic, biodegradable and biocompatible nature. In this study, the epirubicin (EPI) was used as a model drug. The blank (PHB, PHBV) and drug loaded (EPI-PHB-PEG, EPI-PHBV-PEG) nanoparticles were prepared by nanoprecipitation method. The average particle size, po...
Development of photo-magnetic drug delivery system by facile-designed dual stimuli-responsive modified biopolymeric chitosan capped nano-vesicle to improve efficiency in the anesthetic effect and its biological investigations.
Though anesthetic drug delivery system and drug vehicles is generally applied for pain relief, there are have many difficulties and issues due to its short duration carrier and low biocompatibility, effectiveness at the conditions of inflammation at acidic pH. To resolve this issue, we have designed and developed the dual (pH and temperature) responsive bio-nanomaterial to improve the efficiency a...
Prevalence of drug-drug interaction in atrial fibrillation patients based on a large claims data.
This study aimed to compare and determine the prevalence of drug-drug interaction (DDI) and bleeding rate in atrial fibrillation (AF) patients receiving anticoagulants in a clinical setting. We used large claims data of AF patients obtained from the Japan Medical Data Center. The prevalence of DDIs and cases leading to bleeding events were surveyed clinically relevant DDIs extracted from 1) report...
Poly (glycerol adipate) (PGA): From a functionalized nano-carrier to a polymeric-prodrug matrix to create amorphous solid dispersions.
Amorphous Solid Dispersions (ASDs) are a promising strategy to overcome poor-solubility and stability limitations, reducing the crystallinity of the drug through incorporation within a polymer matrix. However, in order to achieve an effective ASD, the polymer and drug must be compatible, otherwise the drug can undergo recrystallisation. In this work, we investigated the potential of the enzymatica...
Drug delivery to macrophages: A review of targeting drugs and drug carriers to macrophages for inflammatory diseases.
Macrophages play a key role in defending against foreign pathogens, healing wounds, and regulating tissue homeostasis. Driving this versatility is their phenotypic plasticity, which enables macrophages to respond to subtle cues in tightly coordinated ways. However, when this coordination is disrupted, macrophages can aid the progression of numerous diseases, including cancer, cardiovascular diseas...
Green synthesis, formulation and biological evaluation of a novel ZnO nanocarrier loaded with paclitaxel as drug delivery system on MCF-7 cell line.
In this study we design green synthesis of a novel ZnO nanocarrier loaded with paclitaxel as a drug delivery system with high cytotoxicity against breast cancer cell line (MCF-7) and low side effects on the normal cell line (fibroblast). Paclitaxel is formulated in high concentration in Cremophor EL because of its low solubility. Zinc oxide nanoparticles (ZnO NPs) were prepared by the ethanolic ex...
Transmural and rate-dependent profiling of drug-induced arrhythmogenic risks through in silico simulations of multichannel pharmacology.
In vitro human ether-à-go-go related gene (hERG) inhibition assay alone might provide insufficient information to discriminate "safe" from "dangerous" drugs. Here, effects of multichannel inhibition on cardiac electrophysiology were investigated using a family of cardiac cell models (Purkinje (P), endocardial (Endo), mid-myocardial (M) and epicardial (Epi)). We found that: (1) QT prolongation alo...
Third Consensus Development Conference on the Safety of Intravenous Drug Delivery Systems-2018.
The Third Consensus Conference on the Safety of Intravenous Drug Delivery Systems was convened to evaluate the benefits and risks of available systems and assess ongoing threats to the safety of intravenous drug delivery.
A role for leptin and ghrelin in the augmentation of heroin seeking induced by chronic food restriction.
Caloric restriction increases the risk of relapse in abstinent drug users. Hormones involved in the regulation of energy balance and food intake, such as leptin and ghrelin, are implicated in drug-related behaviors.
Drug-Induced Pulmonary Arterial Hypertension: Mechanisms and Clinical Management.
Pulmonary arterial hypertension is a rare disease, with drug-induced causes even more uncommon, accounting for only 10% of cases in large registry series. Predisposing factors for drug-induced PAH have not been completely defined. This review summarizes drugs with definite, possible, or likely association to pulmonary hypertension and possible mechanisms involved in the occurrence of pulmonary hyp...
Immunotherapy in pediatric acute lymphoblastic leukemia.
The 5-year survival rate for children and adolescents with acute lymphoblastic leukemia (ALL) has improved to more than 90% in high-income countries. However, further increases in the intensity of conventional chemotherapy would be associated with significant adverse effects; therefore, novel approaches are necessary. The last decade has seen significant advances in targeted therapy with immunothe...
Clarifications regarding the authority and role of FDA in drug approval.
With great concern, we read the editorial entitled, "FDA jeopardizes the lives of lung transplant recipients and in the process severely increases the cost to develop new immunosuppression" by Drs. Klintmalm, Kaplan, and Kirk. The editorial reflects a misunderstanding of FDA's role and authority, as well as of the feasibility of randomized controlled clinical trials (RCTs) in lung transplantation.
Safety implications of combined antiretroviral and anti-tuberculosis drugs.
: Antiretroviral and anti-tuberculosis (TB) drugs are often co-administered in people living with HIV (PLWH). Early initiation of antiretroviral therapy (ART) during TB treatment improves survival in patients with advanced HIV disease. However, safety concerns related to clinically significant changes in drug exposure resulting from drug-drug interactions, development of overlapping toxicities and...
Testing Unconventional Matrices to Monitor for Prenatal Exposure to Heroin, Cocaine, Amphetamines, Synthetic Cathinones, and Synthetic Opioids.
The prevalence of drug use during pregnancy continues to increase despite the associated serious adverse obstetrical outcomes, including increased risk of miscarriage, fetal growth restriction, brain development impairment, neonatal abstinence syndrome (NAS), preterm delivery, and stillbirths. Monitoring drug use during pregnancy is crucial to limit prenatal exposure and provide suitable obstetric...
TDM-guided Crushed Sofosbuvir-velpatasvir Treatment: A case study.
Herein, the authors report the case of a patient diagnosed with hepatitis C virus who was treated with sofosbuvir-velpatasvir (400/100 mg). As the patient was unable to swallow whole tablets, therapeutic drug monitoring was performed to evaluate the effect of crushing sofosbuvir-velpatasvir tablets on drug absorption and global exposure.
Photolichenoid dermatitis: a presenting sign of human immunodeficiency virus.
Photolichenoid dermatitis is an uncommon eruptive dermatitis that often occurs in association with a photosensitizing drug. Photodermatitis, in general, is an uncommon clinical manifestation of human immunodeficiency virus (HIV), most often affecting patients of African and Native American descent. Photolichenoid dermatitis has infrequently been reported in patients with HIV who have not been expo...
Low-abundance drug-resistant HIV-1 variants in antiretroviral drug-naïve individuals: A systematic review of detection methods, prevalence, and clinical impact.
The presence of high-abundance drug-resistant HIV-1 jeopardizes the success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) present at levels
Kinetic stability of amorphous dipyridamole: A fast scanning calorimetry investigation.
One of the main tasks of modern pharmaceutics is enhancing the solubility of drugs. The approaches for solving this problem include producing active pharmaceutical ingredients in the amorphous state. However, the use of amorphous drugs requires the determination of their kinetic stability. The latter is often assessed using isothermal techniques, which are time-consuming. Alternatively, non-isothe...
A combination drug delivery system employing thermosensitive liposomes for enhanced cell penetration and improved in vitro efficacy.
Drug-loaded thermosensitive liposomes are investigated as drug delivery systems in combination with local mild hyperthermia therapy due to their capacity to release their cargo at a specific temperature range (40-42 °C). Additional benefit can be achieved by the development of such systems that combine two different anticancer drugs, have cell penetration properties and, when heated, release thei... | https://www.bioportfolio.com/drug-approvals/research/ |
South Africa’s fiscal position, with its gross-debt-to-GDP expected to exceed 100% between 2021 and 2022, severely limits the government’s room to drive economic recovery, therefore the current emphasis on an investment-led recovery.
To stimulate economic activity, there is a need to specifically focus on sectors that enable the country to address the challenges of joblessness and inequality. Investments that yield positive financial returns without any benefit to society could widen the inequalities that are already unsustainable. For the private sector to lead inclusive growth, one of the critical enablers will be access to finance – more so considering the eroded reserves of corporates currently. Without access to finance, the private sector’s plans to reactivate the economy would be hamstrung.
Financing options for the private sector are traditionally dominated by equity and senior debt. Both options tend to be unsuitable during times of economic crisis, such as the current one. This mismatch between the capital available (through traditional sources such as commercial banks), and the capital required by corporates, should steer us towards designing new financial instruments and scaling up those that already exist at a relatively smaller scale that are aligned to a new economic construct. Two examples of such products that are opportune include raising capital through a special purpose acquisition company (SPAC) and mezzanine debt. | https://www.magzter.com/article/Investment/Finweek-English/A-spurt-for-economic-revival |
The University of Information Technology and Management in Rzeszów, together with the Department of Banking, Finance and Accounting, University of Warsaw invite participants in an International Scientific Conference on to be held on 4-5 December 2015 in Rzeszów, Poland. The deadline for submission is 15 November 2015.
The aim of the conference is to present the problem of financialization and initiate discussion on the subject, to clarify financialization processes, define strategic research directions, promote international studies on the subject and provide a new opportunity for interdisciplinary discussion. The conference will be attended by distinguished researchers on issues of financialization and eminent Polish scholars from various research centers in the country, as well as representatives of major institutions supervising the financial market in Poland and representatives of the business world. Malcolm Sawyer, Gary Dymski, Trevor Evans, Jan Toporowski and Alessandro Vercelli will give key-note addresses.
The growing role of financial markets and institutions in the economy is sometimes referred to as financialization. It means the process by which financial markets determine the behavior of all actors, including financial institutions, enterprises, individual investors and households. Financial markets act on a number of socio-economic categories of society and shape many areas of life, at the same time increasing awareness about corporate social responsibility.
Bearing in mind the importance of financialization the Department of Finance at the University of Information Technology and Management in Rzeszow, together with the Department of Banking and Finance at Warsaw University have made a joint decision to hold an International Scientific Conference "Financialization - impact on the economy and society", which will be held on 04-05 December 2015 in Rzeszow. It is one of the first conferences on the subject in Poland.
Our intention is to integrate the various points of view of academia on this issue. We would like to create field for interdisciplinary discussion, which is why the conference is addressed to representatives of both socio-economic sciences and the humanities.
Research Issues Conference:
- Impact mechanisms of financialization on the economy and society
in particular: legal regulations and the realm of the real, financial sector stability, security of financial services, access to financial services, the relationship between the financial sphere and the real, financial inclusion, financial exclusion
- Changing the paradigm of socio-economic development
in particular: social exclusion and poverty, social exclusion, social capital and social trust, economics of happiness
- Households and the individual in the world of financialization
in particular: financial skills and awareness, responsible financial decisions, behavioral finance, management of home finances, consumption and saving
- Supervision and regulation of financial markets
in particular: financial crises, the stability of the financial sector, corporate governance and banking ethics, asset bubbles, banking risk management,
shadow banking systems
- Sustainable finance
in particular: financial education, social banking innovations, social responsibility of the financial sector
- Regional diversity
in particular, social inequalities, regional disparities, income diversity
Possibility of publication
- e-Finance
9 points according to list B of the Ministry of Science and Higher Education, paper in English
http://www.e-finanse.com
- Economics
8 points according to list B of the Ministry of Science and Higher Education, paper in English or Polish
www.ekonomia.wne.uw.edu.pl
- Economics and Organization of Entreprise
7 points according to list B of the Ministry of Science and Higher Education, paper in English or Polish
www.orgmasz.pl
Conference participants may indicate the title of the magazine in which they would like to place their paper. In such a case please indicate this intention writing the name of the journal in the registration form under “comments” section. The Editing Committee will take the final decision on directing the paper to the chosen journal for publication on the basis of compliance of the subject with the journal profile. Each paper undergoes a review process according to procedure accepted by each of the journals. Upon receiving the acceptance for publication, the authors are obliged to edit the text to editing requirements of the journal. There is also the possibility of preparing a multi-authorship monograph, composed of selected publications. Topics and summaries of articles will be posted on the conference website.
The articles should be sent to [email protected] titling the e-mail “Finacialization conference”.
Conference languages: Polish and English.
The conference is organized with the honorary patronage of the Polish National Bank, the Commission of Financial Supervision, the Association of Polish Banks, the Mayor of the City of Rzeszow and the Marshal of the Podkarpacie Province and with the media patronage of the daily newspaper “Rzeczpospolita”, TVP Rzeszow, along with the e-Finance journal.
Registration details and more information is available here. | https://www.socialcapitalgateway.org/content/call/economic-and-social-impact-financialization |
The Government submits an annual financial markets report to the Storting. This summary corresponds to chapter 1 of the report, which provides an overview of key financial market policy developments, and a summary of the other chapters. Chapter 2 of the report addresses the financial stability outlook. Chapter 3 discusses the financial markets from an industry perspective, and addresses both the financial sector as an industry in its own right and the financial sector as a capital source for other industries. Chapter 4 provides an overview of how consumer protection is attended to in financial market regulations, and discusses the need for changes. An overview of the activities of Norges Bank, Finanstilsynet, Folketrygdfondet and the International Monetary Fund (IMF) in 2019 can be found in chapters 5 to 8 of the report. Chapter 9 outlines amendments to regulatory frameworks and licences in 2019.
At the moment, the financial market situation and outlook are heavily influenced by the ongoing coronavirus outbreak and the strong measures triggered thereby. A number of measures and events have a direct impact on financial markets. These are briefly outlined where relevant, but the Government does not provide any detailed analysis or evaluation of the effects in this report. Reference is also made to propositions submitted by the Government to the Storting this spring with proposed measures to counter the financial effects of the coronavirus disease outbreak, as well as to the Revised National Budget to be submitted in May. This report will largely address structural matters and regulatory developments pertaining to financial markets, and thereby also financial market developments prior to the coronavirus disease outbreak.
Main roles and key figures for the Norwegian financial sector
The financial markets account for a major portion of the Norwegian economy, and provide services of importance to people’s lives. The main role of banks is to receive savings in the form of deposits, and to make loans to households, businesses and municipalities. Bank deposits amount to about NOK 2,800 billion, which corresponds to about two Norwegian fiscal budgets. Banks lend about twice as much as they hold in deposits, and fund the difference through capital market borrowing.
In 2019, life insurance companies and pension funds received pension savings and premiums in excess of NOK 120 billion, and have invested about NOK 1,900 billion in general lending, securities and other assets on behalf of their customers.
Norwegian securities markets, where large businesses and municipalities raise loans and equity directly from savers, represent about NOK 5,000 billion. The saving and borrowing opportunities provided by Norwegian financial markets offer households, businesses and municipalities the freedom to adapt their investments and consumption over time, irrespective of when income is received. This freedom of choice is valuable to individuals, and is fundamental for value creation and economic growth.
The scope for insuring against risk provides predictability for households, and is a prerequisite for stability and profitability in businesses. Last year, non-life insurance companies in Norway paid more than NOK 36 billion in compensation for anything from personal injury to theft and damage to buildings and cars. In addition, businesses use various financial instruments to reduce their financial risk, e.g. the risk of changes in commodity prices, exchange rates and interest rates. Life insurance companies also sell insurance policies that pay compensation in the event of disability or death, either separately or as part of pension plans.
More than 2.5 billion card payments are processed through the Norwegian payment system every year, and the average Norwegian resident uses payment cards more than 500 times a year. The Norwegian system processes payments in a secure manner and at a low cost. This promotes stability and efficiency in the Norwegian economy.
Financial stability outlook (chapter 2)
Stable access to financial services is important for the well-functioning of modern economies. The societal costs of financial market turbulence and crises can be large and persistent. In particular, the interaction between the banking sector and the rest of the economy may result in the build-up of financial imbalances, and trigger turmoil and deep economic setbacks. The Government is therefore committed to ensuring that the financial markets are robust to disturbances, and have the capacity to maintain their services through challenging times.
The positive outlook for the Norwegian economy at the beginning of this year turned sharply negative as a result of the strong measures taken from March this year in response to the coronavirus pandemic. This spring has been characterised by extensive layoffs and steep unemployment growth, low activity levels and considerable uncertainty regarding future developments. In addition, the oil price has declined steeply. The increased turmoil in financial markets and the oil price decline have caused the Norwegian krone to depreciate sharply. Norges Bank has reduced the key policy rate twice, and the key policy rate is currently 0.25 percent. Norges Bank has also launched comprehensive measures to ensure liquidity access for banks, and has stated that it is continuously considering the need for intervening in the market by purchasing Norwegian kroner. The duration of the strict infection control measures and the financial measures is subject to considerable uncertainty. The Ministry will be presenting updated assessments of the economic outlook in Norway and internationally in the Revised National Budget in May.
In recent weeks, economic developments, securities exchanges and financial indicators all over the world have been severely affected by the coronavirus pandemic, and the economic outlook is highly uncertain. Activity will in most countries be sharply reduced for as long as the strictest infection control measures remain in effect, and there is considerable uncertainty as to when and how swiftly economies will rebound. Central banks in several leading economies have reduced policy rates significantly and have provided markets with liquidity through a range of other measures. If the pandemic results in a lengthy economic shutdown, the risk of financial market imbalances having an impact on the real economy will increase. A key risk factor is the increased level of business debt observed ahead of the coronavirus pandemic.
In the somewhat longer run, the risk that new trade barriers will be erected in a number of countries, as well as the unclear effects of Brexit, also add uncertainty to the international growth and financial stability outlook.
Household and financial sector vulnerabilities
The average debt of Norwegian households is now about 2.3 times disposable household income. This is a high level, both historically and compared to other countries. This debt accumulation is linked to steep housing price growth over many years. Housing prices rose in the first half of 2018, after having declined throughout 2017. Housing price developments were fairly moderate in 2019, but price increases were accelerating at the beginning of 2020. There is considerable uncertainty as to how the outbreak of the coronavirus will affect the housing market.
A sustained increase in the debt burden is an indication that financial imbalances have built up. This is one of the most important vulnerabilities in the Norwegian financial system. The rate of household debt growth has declined somewhat in the last year and was 4.9 percent at the beginning of the year; about the same level as the rate of disposable income growth. Consumer credit growth has levelled off after several years of steep increases. The growth rate decline was especially distinct in 2019. The annual growth rate as at yearend 2019 was 1.6 percent, adjusted for the sale of portfolios in default. Consumer credit represent 4 percent of household debt, but the interest expenses account for no less than 13 percent of overall interest expenses, and add to the vulnerability.
For households that have accumulated especially high debt, even minor interest rate changes may require them to curtail consumption. The monetary policy tightening initiated in September 2018 and the subsequent residential mortgage rate increase somewhat increased the interest burden of households. The outbreak of the coronavirus triggered a reversal of the monetary policy tightening, and the key policy rate reduction has reduced residential mortgage rates, which means, when taken in isolation, a lower interest burden. At the same time, many households are currently experiencing an income reduction. These households may experience a significant increase in the proportion of income spent on servicing their debts, and many of these may need to defer interest and instalment payments.
Most financial crises in Norway and internationally have occurred after periods of strong growth in asset prices and rapid build-up of debt. One of the risks is that many households might choose to cut back on consumption if incomes were to decline or interest rates were to increase. Experience shows that households accord priority to servicing their residential mortgage loans, even when incomes are in decline. Lower consumption may reduce the earnings and debt servicing capacity of businesses, which may then result in increased losses on the part of banks, thus impairing their capacity to make new loans to both households and businesses.
In the autumn of 2019, the European Systemic Risk Board (ESRB) warned Norway that high indebtedness and high housing prices represent a systemic risk for the Norwegian economy. A number of other countries, including the other Nordic countries, were given a corresponding warning. The IMF and the OECD have also highlighted household debt and high housing prices as continued material risk factors for the Norwegian economy.
In addition to household lending, banks’ lending to non-financial enterprises may represent a vulnerability. This applies, in particular, to lending to commercial real estate firms, as commercial real estate prices have increased steeply in recent years, especially in Oslo. Such lending accounts for a major portion of overall bank lending. Although losses have been low in normal times, lending to such firms has historically imposed the largest losses on banks. A setback in the economy may cause commercial real estate vacancies, thereby reducing the debt servicing capacity of commercial real estate firms. If this is accompanied by a decline in the prices of the properties that are put up as collateral for the loans, banks may incur large losses. Commercial real estate prices have generally fluctuated more in tune with business cycles than housing prices.
A long period of strong performance in the Norwegian economy is reflected in several years of low loan losses and high earnings on the part of banks. The profitability of Norwegian and other Scandinavian banks is high compared to that of banks elsewhere in Europe. Norwegian banks have also achieved about the same return on equity as Danish and Swedish banks, despite having significantly higher equity. They have strengthened their solvency significantly in recent years, in line with stricter capital requirements, and their ability to withstand setbacks in the Norwegian economy is held to be good. Banks are at the same time facing risks on both the lending and the funding side. If banks incur large losses, they may exacerbate economic setbacks by curtailing their lending.
Customer deposits account for about half of Norwegian banks’ funding, whilst the remainder is borrowing in the form of notes and bonds (wholesale funding). Wholesale funding enables banks to manage their liquidity risk in ways not possible with deposits. Norwegian banks have enjoyed ample access to wholesale funding, which has become slightly cheaper in recent years. However, international market turbulence may affect the price of, and access to, funding for Norwegian banks, and risk premiums have increased sharply in the bond market in the wake of the coronavirus outbreak.
Many banks internationally encountered liquidity problems during the financial crisis. Those banks had become dependent on short-term funding, and found it difficult to refinance during the crisis. Challenges rose quickly and simultaneously for a large number of banks. The crisis demonstrated the importance of strong liquidity risk management on the part of banks. In recent years, a somewhat higher proportion of banks’ wholesale funding is long-term, and banks meet both the liquidity coverage requirement introduced in 2017 and the upcoming net stable funding requirement. This strengthens the resilience of banks.
Covered bonds currently account for about half of Norwegian banks’ wholesale funding. Covered bonds have thus far been a secure and stable source of funding. The relatively low price of covered bond funding is owed to such bonds being secured on residential mortgage portfolios with a low loan-to-asset value ratio and other collateral, thus implying low risk for investors. During the recent bond market risk premium increase, the percentage increase has been less for covered bonds than for other types of bonds. The emergence of covered bonds has reduced the short-term nature of banks’ wholesale funding, but also entails new vulnerability. Housing market developments are a risk factor for banks’ scope for using covered bonds to fund themselves, and banks also make considerable investments in each other’s covered bonds to comply with the liquidity coverage requirement. If many banks need to sell covered bonds simultaneously, both value and liquidity may suffer. Housing market setbacks may exacerbate such a development.
Solvency requirements for insurance companies and pension funds have also been strengthened in recent years. Increasing life expectancy and the persistently low interest rate level have highlighted the need for improved solvency in undertakings and a more risk-sensitive regulatory framework. Undertakings have accumulated reserves to account for higher life expectancy, and meet new solvency requirements. The interest rate reduction in the wake of the coronavirus disease outbreak increases the interest rate risk associated with the liabilities of undertakings with large portfolios of guaranteed pension obligations. At the same time, the investments of such undertakings are directly affected by the financial market turbulence. Also, the current situation may mean that non-life insurance companies need to be prepared to make higher compensation payments.
Macroprudential regulation and bank solvency requirements
Macroprudential regulation means monitoring and regulation of the financial system as a whole aiming to reduce risk in its interaction with the rest of the economy. Traditionally, financial sector regulation has been focused on each individual bank, with the aim of protecting customers and creditors against loss. The financial crisis was a stern reminder that this does not suffice. The traditional approach is now often referred to as microprudential regulation.
Important macroprudential tools are bank capital adequacy requirements based on general systemic risk, such as the countercyclical capital buffer and the systemic risk buffer. The capital requirements are intended to ensure that banks are able to absorb losses without having to excessively tighten lending. Table 1.1 provides an overview of the key macroprudential tools, including liquidity requirements and lending practice requirements, which are discussed in more detail below.
Capital requirements for Norwegian banks have long been stricter than in many other countries, partly in reflection of experience from the Norwegian banking crisis in the 1980s and 1990s. Strong bank solvency benefited the Norwegian economy during the international financial crisis, and it is a strength in the challenging situation facing the Norwegian economy at the moment. Since there is currently considerable uncertainty regarding future developments, it is important that banks refrain from distributing profits in a manner that may impair their solvency. The Ministry of Finance has therefore expressed an expectation that Norwegian banks and insurance companies hold off on payment of dividends, etc., until the considerable uncertainty regarding economic developments has been reduced.
After the financial crisis, Norway increased banks’ capital requirements in line with international recommendations and new EU rules more rapidly than most countries. This was possible because of relatively strong banks and healthy performance in the Norwegian economy, but also reflects a political prioritisation of financial sector resilience. Most of the increase in capital requirements takes the form of various buffer requirements on top of the CET1 minimum requirement. The buffer requirements are national macroprudential tools, and address various forms of systemic risk.
If many banks were to sustain losses at the same time, this might trigger or exacerbate a setback in the economy. An important macroprudential consideration is therefore that there shall be scope for drawing on the various capital buffers without the bank finding itself in breach of its licence conditions. When a bank fails to meet the overall buffer requirements, it is automatically subjected to certain restrictions with regard to, inter alia, dividend and bonus distributions. If the consequences of undershooting the buffer requirements are perceived to be costly or uncertain, for example due to reduced confidence in the bank on the part of customers or the capital market, banks may be unwilling to draw on the buffers, even if faced with major losses. In order to counter this, the buffer requirements may be lowered or deactivated whenever needed, provided that the specific risks addressed by the buffer requirements have been reduced.
The countercyclical capital buffer requirement shall vary over time in response to the financial cycle, and may be tailored to the state of the Norwegian economy. The requirement shall as a main rule be between 0 and 2.5 percent. The Ministry of Finance has gradually increased the buffer requirement in recent years in line with a build-up of financial imbalances. The most recent increase was to 2.5 percent with effect from yearend 2019. The magnitude of the increases has been in conformity with advice from Norges Bank. As a policy response to the coronavirus crisis, the Ministry reduced the countercyclical capital buffer requirement to 1 percent with immediate effect in March at the advice of Norges Bank. A reduced requirement may serve to prevent a tightening of lending practices, which could have added to the downturn in the Norwegian economy. Finance Norway has estimated that this may boost the lending capacity of banks by between NOK 500 and 600 billion.
The current EU prudential framework for banks (CRR/CRD IV) was enacted in 2013, and has in all key respects been implemented in Norway, although it was not incorporated into the EEA Agreement until December 2019. Such incorporation required the Norwegian capital requirements to be amended in some respects. The so-called Basel I floor, the purpose of which has been to ensure that the risk-based requirements are not too low, was abolished, and the solvency requirement for banks’ lending to small and medium-sized enterprises (SMEs) were reduced. This reduces capital requirements for many Norwegian banks.
Table 1.1 Overview of the most important macroprudential tools
Group
Tool
Purpose
Capital requirements for banks
Systemic risk buffer
Make banks more solvent and robust to loan loss and other disruptions that may occur as the result of structural vulnerabilities in the economy and other non-cyclical systemic risk.
Countercyclical buffer
Make banks more solvent and robust to loan loss in a future downturn and reduce the risk that banks will deepen a potential downturn by restricting their lending.
Buffer for systemically important banks
Reduce the likelihood that systemically important banks encounter financial difficulties that may have servere negative implications for the financial system and the real economy.
Risk weight floors for residential and commercial real estate loans
Ensure that banks use prudent risk weights to reflect potential price bubbles in the Norwegian residential and commercial real estate markets.
Requirements applicable to banks’ lending practices
Stress test of ability to withstand interest rate increase
Contribute to more balanced development in the Norwegian housing and credit markets, increase the resilience of households and banks, and reduce the risk posed by consumers loans to the Norwegian economy.
Capping of borrowers’ loan-to-asset value ratio
Capping of borrowers’ debt-to-equity ratio
Instalment payment requirement
Flexibility quota for banks
Liquidity requirements for banks
Liquidity coverage requirement
Improve banks’ resilience to financial market turbulence, by making them less dependent on short-term funding and liquidity from central banks.
Net stable funding requirement
Source Ministry of Finance.
To maintain the real capital requirements for banks, the Ministry of Finance decided in December 2019 to increase the systemic risk buffer requirement from 3 to 4.5 percent, as well as to introduce temporary floors for average risk weighting of property loans in banks that use the internal ratings-based approach (IRB banks). The increased systemic risk buffer requirement enters into effect as at yearend 2020. For smaller banks, which use the standardised approach, or foundation IRB approach, for the treatment of credit risk, the increase will enter into effect two years later. This has to do with such banks only benefiting from the introduction of the SME discounting factor and not from the abolition of the Basel I floor. The Ministry will in accordance with the EU/EEA rules assess the level of this buffer requirement every other year in the years to come. The new systemic risk buffer requirement and the introduction of floors for risk weighting of property loans may serve to increase capital requirements for foreign banks’ operations in Norway, and thereby also contribute to stability and a more level playing field in the Norwegian banking market.
New regulatory amendments in the EU may in a few years’ time have an impact on the real capital requirements faced by Norwegian banks. A number of amendments to the CRR/CRD IV framework and the Bank Recovery and Resolution Directive (BRRD), referred to as the “banking package”, were adopted in the spring of 2019. In addition to an expansion of the SME discounting factor and a new discounting factor for lending to infrastructure projects, the package includes, inter alia, new provisions on the capital requirements which supervisory authorities may impose on individual banks on top of the general requirements (the so-called Pillar 2 requirements), and the MREL requirement. Finanstilsynet has appointed, at the behest of the Ministry of Finance, a working group charged with proposing, inter alia, Norwegian implementation of the banking package by the end of October this year.
Macroprudential regulation and lending practice requirements
The Government has imposed restrictions on banks’ lending practices in order to promote more sustainable household debt development. A temporary regulation on new lending secured by residential mortgage was adopted in the summer of 2015. The Residential Mortgage Regulations have been renewed three times, most recently from 31 December 2019 for a period of one year. The consultative rounds in connection with the renewal of the Regulations and other input received by the Ministry indicate that such lending regulation has received increased support over time, although there is a desire for the regulatory requirements to be evaluated on a regular basis. Some consultative bodies have expressed concern that the Regulations may exclude some groups, such as first-time buyers, from the housing market or hinder construction of new homes in sparsely populated areas. However, the purpose of the Regulations is to reduce vulnerabilities caused by high household debt, and one should as a general rule refrain from using these to pursue other housing policy objectives. Other policy tools, such as for example the Norwegian State Housing Bank, will be better suited in addressing other objectives.
The Residential Mortgage Regulations are likely to have reduced household borrowing. Fewer households are taking out loans that are very large relative to their income or the value of their home. Finanstilsynet conducts an annual survey of new loans granted by banks and secured by residential mortgage. The residential mortgage survey from the autumn of 2019 shows that there has in the last few years been a small increase in the proportion of loans that exceed the limits under the Regulations. The proportion is nonetheless lower than before the Regulations were tightened in 2017:
The Residential Mortgage Regulations are likely to have reduced household borrowing. Fewer households are taking out loans that are very large relative to their income or the value of their home. Finanstilsynet conducts an annual check of a sample of new loans granted by banks and secured by residential mortgage. The residential mortgage survey from the autumn of 2019 shows that there has in the last few years been a small increase in the proportion of loans that exceed the limits under the Regulations, although such proportion is nonetheless lower than before the Regulations were tightened on 1 January 2017:
5 percent of loans exceed the regulatory limit of 5 times annual income, as compared to 16 percent in 2016, prior to the introduction of this requirement.
5 percent of instalment loans had a loan-to-asset value ratio in excess of 85, as compared to 9 percent in 2015.
It is total household debt which poses a risk to financial stability. Housing debt is the main component, but high consumer debt, in many cases on top of high housing debt, may serve to increase the risk of severe consumption retrenchment if income falls or interest rates increase. On 12 February 2019, the Ministry therefore also adopted a temporary regulation on banks’ consumer lending practices, largely mirroring the Residential Mortgage Regulations. The regulation shall apply until 31 December 2020.
The lending regulations are not suited for fine-tuning of housing and credit market developments, but define a framework for banks’ lending practices. The regulations balance the prevention of excessive risk accumulation in the Norwegian economy against the promotion of efficient credit markets. Detailed lending regulations might reduce banks’ incentives to perform independent risk assessments. It is important for banks to continue to perform genuine risk assessments, also in cases where a loan meets the requirements under the regulations. The scope for banks to grant a certain proportion of loans that do not meet the requirements under the regulations serves to ensure that responsibility for the risk assessments still remains with the banks.
In order to ensure predictability on the part of banks and borrowers, the requirements for a maximum loan-to-asset value ratio, stress testing of borrowers’ debt servicing capacity and maximum debt-to-income ratio should not be subject to frequent adjustment. If a sustained levelling off of housing and credit market growth or conditions in the Norwegian economy indicate that lending regulations should be eased, an increased flexibility quota may be a suitable policy tool. This would retain the prudent lending practice framework defined by the regulations, whilst expanding banks’ scope for conducting their own risk assessments. Correspondingly, the flexibility quota may be reduced if developments give cause for renewed concern.
The coronavirus outbreak and its financial implications have caused the Government to provide banks with additional flexibility by expanding the flexibility quota under the Residential Mortgage Regulations to 20 percent, initially for the second quarter of 2020. This initiative is premised on banks’ increased need for flexibility to find solutions for their customers in an extraordinary situation, and not on adapting the regulations to housing and credit market developments. The self-employed may for example need to increase loans secured by residential mortgage. The Ministry has, at the same time, highlighted that both the Residential Mortgage Regulations and the Consumer Loan Regulations permit instalment and interest deferral for up to six months for existing loans to customers whose ability to pay has been temporarily impaired. Repercussions of the coronavirus disease outbreak and the response measures clearly fall within the scope of this provision.
The debt servicing capacity and debt-to-income ratio requirements are the same under both sets of lending regulations, thereby ensuring consistent regulation of lending practices. Concern for uniform regulation suggests that any amendment to these requirements should be implemented simultaneously in both sets of regulations. The Residential Mortgage Regulations were renewed for a period of one year from 1 January 2020, such as to expiry at the same time as the Consumer Loan Regulations. This facilitates a joint assessment of the two sets of regulations, including whether it might be appropriate to have one set of regulations for all bank lending practice requirements, as well as the duration of such regulations. The Ministry of Finance will also examine whether financial stability considerations suggest that limits should also be imposed on loans that fall outside the scope of the current regulations. The Ministry of Finance has in a letter of 24 April 2020 asked Finanstilsynet to evaluate bank lending practice regulations and advise on their renewal and structure from 1 January 2021. Finanstilsynet has been asked to obtain assessments from Norges Bank.
Recovery and resolution in the banking sector
The new framework on recovery and resolution of banks, which entered into effect on 1 January 2019, require, inter alia, each bank to prepare a plan for how to restore the bank’s financial position if it were to be impaired (recovery plan), whilst Finanstilsynet shall prepare plans for dealing with each bank in more severe instances (resolution plan). Bail-in is a key resolution tool under these rules, and involves write-down of own funds and conversion into equity of parts of the failing bank’s debt, thereby covering losses and strengthening solvency sufficiently to enable a continuation of all or part of the operations. This requires the bank to have enough liabilities that can be converted into equity, so-called eligible liabilities. Finanstilsynet shall therefore stipulate a minimum requirement for the sum of own funds and eligible liabilities (the MREL requirement) when relevant. Finanstilsynet has stated that it would be appropriate to stipulate MREL requirements for a majority of Norwegian banks, and has thus far stipulated requirements for the largest banks.
The capital in the Norwegian Banks’ Guarantee Fund has been transferred to two new funds set up to finance the deposit guarantee scheme and crisis management measures, respectively. The capital of the two funds was NOK 17.2 and 21.1 billion, respectively, as of yearend 2019, which is much more than is required under the EU directives. Well-capitalised funds enable any problems in the banking sector to be managed appropriately.
The introduction of the new recovery and resolution rules was accompanied by a continuation and strengthening of the Norwegian deposit guarantee scheme. There is now an unlimited guarantee for up to 12 months on certain deposit types relating to, inter alia, housing purchases, special life events, insurance proceeds and certain forms of compensation. Moreover, the recovery and resolution framework provides higher priority for non-guaranteed deposits from individuals, as well as from small and medium-sized enterprises.
Risk of money laundering and terrorist financing
Banks and other financial market participants are subject to anti-money laundering and terrorist financing regulations. Compliance with such regulations has been attracting mounting attention internationally, especially in the Nordic region, following major revelations of rule violations, some of which are quite extensive, on the part of large banks. These cases have resulted in fines, notices of impending fines, civil compensation litigation and licence revocation. Thus far, there have been no revelations of systematic long-term violations in the same order of magnitude in Norway, but the supervision reports of Finanstilsynet have identified room for improvement on the part of most reporting entities.
The EU has in the last few years considerably expanded its regulations in this regard, but the large-scale revelations have led to calls for further reforms. In December 2019, ECOFIN decided to ask the European Commission to examine whether collaboration between relevant authorities may be strengthened, whether parts of the regulations should be laid down in the form of a commission regulation, and whether supervisory responsibilities and powers should be shifted to an EU body. A supranational supervision structure, similar to those established for banking, insurance, pensions and securities trading, may require modifications to the EEA Agreement.
The new Norwegian anti-money laundering regulations entered into effect on 15 October 2018. Norwegian authorities are currently in the process of introducing the regulatory amendments required to implement the Fifth EU Anti-Money Laundering Directive, which was enacted in May 2018 with an EU implementation deadline of January 2020. The Directive has not been incorporated into the EEA Agreement as yet. Some necessary regulatory amendments circulated in draft form by the Ministry of Finance closed for consultation on 23 March. The Ministry is also preparing regulatory provisions on the creation of a register of beneficial owners to increase transparency regarding ownership and control of legal entities in Norway.
Its strengthened anti-money laundering effort has resulted in Norway no longer being subject to “enhanced follow-up“ by the Financial Action Task Force (FATF), the international collaboration organisation which sets standards on measures to combat money laundering and terrorist financing. This was confirmed upon the publication of a follow-up report in December 2019, in which progress since the country report of 2014 was evaluated and recognised.
Digital vulnerability
Financial stability might be threatened if a major financial undertaking, a key infrastructure undertaking or numerous banks are knocked out for more than a brief period of time as the result of operational fault or cyberattack. The Government has identified financial services as one of 14 critical societal functions, thus meriting special attention to vulnerabilities, security and preparedness.
The financial infrastructure in Norway is considered robust in all key respects, also in the current extraordinary situation. Despite many operational duties being performed from the homes of employees, operations have been stable and customer service provision has functioned as normal. However, alternative methods of operation may entail increased operational risk, and it may be more challenging to carry out systems changes and necessary maintenance.
The number of ICT incidents reported to Finanstilsynet was at about the same level in 2019 as in 2018. The number of reported attacks has remained low, and consequences have been limited. Although a significant increase in unwanted activity has been observed in recent years, only a minor portion of such activity has resulted in security incidents which needed to be reported to Finanstilsynet.
Although the industry is held to be well prepared for handling incidents of both an operational and a malicious nature, certain developments may make the provision of financial services more vulnerable in coming years. This applies, in particular, to the increasing dependence on complex ICT systems in the sector, the growth in outsourcing of operational duties to a small number of key service providers, the digitalisation of customer-oriented services, as well as new technology and new regulation allowing for third-party providers. Both the authorities and the financial industry itself must continue to promote a robust financial infrastructure in the face of these developments.
Financial sector regulation and preparedness form part of the overall effort to secure the digital ecosystem in Norway. The Government published a new digital security strategy in January 2019. The new Security Act, which is under implementation in, inter alia, the financial sector, forms part of this strategy.
Banks have since 2019 been required to tailor their cash solutions to documented and quantitative assessments of the risk of increased cash demand, although they may take electronic preparedness into account in dimensioning the cash solutions. Finanstilsynet has in its follow-up found that most banks have taken appropriate measures, but many of them have room for improvement on, inter alia, testing of the solutions.
Climate risk in financial markets
Climate change and the transition to a low-carbon economy in line with the ambitions in the Paris Agreement will affect how financial markets operate, and may have financial stability implications. Physical climate risk is the result of more frequent and severe episodes of draught, flooding and storms, as well as rising sea levels. Transition risk relates to climate policy change and expansion, development of new technology, as well as changing customer preferences and investor requirements, which may cause sudden changes in the market value of large groups of financial assets. How financial markets are affected by climate change will depend on whether global society takes measures that are sufficient to meet climate targets, and on whether the transition to a low-carbon economy is implemented in accordance with the expectations of market participants or in a disruptive manner.
Central banks, supervisory authorities and regulatory authorities, both in Norway and internationally, are seeking to improve both their own and market participants’ understanding of how climate-related risk may affect financial markets and financial stability. Climate risk management has been highlighted in the Ministry’s letter of allocation to Finanstilsynet in the last three years. Both Finanstilsynet and Norges Bank have joined a network of central banks and supervisory authorities promoting a greener financial system. The network aims to contribute to the development of environment and climate risk management in the financial sector and to mobilize mainstream finance to support the transition toward a sustainable economy.
In March 2018, the European Commission published an action plan on financing sustainable growth. The main objectives of the action plan are to channel private capital into more sustainable investments, to manage climate risk and environmentally-related risk, as well as to promote transparency and a long-term perspective in financial and economic activities. The Government endorses the objectives of the action plan, and is following the EU’s implementation of the plan closely. In March 2020, Norway joined the EU’s International Platform on Sustainable Finance.
The core component of the Commission’s action plan is a taxonomy (classification system) for sustainable economic activity. The objective is to establish a common understanding of which activities and investments can be considered sustainable from an environmental and climate perspective. Pan-European criteria are intended to make it easier for investors to compare investment opportunities across countries and sectors, and will provide companies with incentives to make their business models more sustainable. Political agreement was reached on a commission regulation on the taxonomy framework in 2019. This regulatory framework is EEA-relevant and is scheduled to enter into effect in the EU on 31 December 2021.
Robust reporting of relevant and comparable climate-related information from companies is of decisive importance to the financial sector’s management of climate risk and the channelling of capital into sustainable investments. Frameworks for the reporting of both how companies affect the climate (climate reporting) and how companies’ business models are affected by climate change and climate policy (climate risk reporting) have been developed in the last few decades.
The recommendations of the Task Force on Climate-related Financial Disclosures (TCFD) define a climate risk reporting framework which enjoys broad international support. The Climate Risk Commission recommended that Norwegian businesses make use of the TCFD framework in their corporate reporting, whilst at the same time advising Norwegian authorities against the introduction of detailed statutory climate risk reporting requirements. The Government endorsed the Commission’s assessments in the Financial Markets Report 2019, and expects major Norwegian companies to include information in their corporate reporting on how they are affected by, as well as how they manage, climate risk. In order to ensure comparable reporting across companies, sectors and countries, companies should adhere to international standards such as the TCFD framework.
In the EU, the climate reporting requirements applicable to large enterprises are laid down in the Non-Financial Reporting Directive. In January 2020, the European Commission announced a review of the Directive. It is expected that the Commission will publish a regulatory proposal by the end of 2020. The Government is monitoring the EU evaluation of the Directive and is currently awaiting the regulatory proposal, which will be EEA-relevant.
The financial markets in an industrial perspective (chapter 3)
The Government is of the view that broad diversity in the range of service providers in all parts of the financial markets may serve to reduce the vulnerability of the service offering and promote sound competition. Norwegian markets shall be open to foreign financial undertakings, and there shall be low barriers to establishing new businesses. The regulatory framework should be stable and sound, out of consideration for both the significance of the financial sector to activity in other parts of the Norwegian economy and the important industry the financial sector is in its own right. This includes a stable and secure affiliation with international markets.
Although the quality of international financial market regulation has improved in recent years, national authorities will nonetheless often be best placed to assess the implications of various legal acts in their markets. Hence, there will still be a need for assessing the extent to which the scope for tailored solutions under the EU/EEA provisions should be used to have stricter requirements where merited by national circumstances, as has been done by Norwegian authorities to e.g. ensure appropriate bank solvency requirements. However, the rules shall not be such as to place Norwegian banks at a disproportionate competitive disadvantage internationally or in relation to foreign banks operating in Norway.
The Ministry of Finance is maintaining a constructive dialogue with the financial industry through, inter alia, consultative rounds, ongoing contact on individual issues and scheduled meetings with a broad agenda. The dialogue with Finance Norway and other organisations provides the authorities with valuable insight into the assessments, experience and views of the industry. This provides a sound basis for balancing different regulatory considerations, and for collaborating on helpful solutions for pension savers, consumers and users of public services. A constructive dialogue also provides a sound basis for joint efforts to, inter alia, safeguard financial services as a critical societal function, and for dealing with extraordinary situations that may arise and impose a shock on the economy, as currently observed in the wake of the coronavirus disease outbreak.
Access to capital for businesses
Norwegian businesses need a well-functioning capital market to fund profitable projects at prices that reflect expected return and risk. The Government will continue to promote a well-functioning capital market and easier access to risk capital and competent investors in accordance with the Granavolden platform.
The overall impression of the capital market in Norway in a normal situation is that Norwegian securities markets are well-functioning, that Norwegian financial undertakings are solvent and liquid, and that government schemes serve to fund projects which would not readily attract ordinary market funding. The Norwegian supply side and integration with international markets provide businesses with a diversified range of funding, and the overall outcome appears to be that profitable projects have good access to funding in normal times.
Bank loans have over time been the dominant source of debt funding for Norwegian businesses. Whilst Norwegian banks and major Norwegian businesses may raise capital in international securities markets and from international financial undertakings, new and small business may be more dependent on Norwegian and local sources of capital.
The Government will contribute to making the Norwegian securities market an efficient source of funding for businesses and attractive to investors. This requires market participants to be confident that the market is well-regulated and transparent, that relevant information is in the public domain, and that violations of applicable regulations are prevented, uncovered and dealt with.
The authorities have launched capital market-oriented measures to prevent viable businesses from folding due to liquidity problems in the extraordinary situation brought about by the coronavirus outbreak. A government guarantee scheme for bank loans for small and medium-sized enterprises was established in late March, and this scheme was expanded to also encompass larger enterprises in early April. The Government Bond Fund has been reinstated to improve liquidity and capital access in the bond market. Increased grants for businesses with research and innovation activities are being provided through the direct grant schemes, which is important to maintain restructuring and growth capacity when the outbreak is over.
Securitisation and covered bonds
Securitisation involves bundling and converting loans and other financial assets into transferable securities. Assets will in most cases be securitised by a bank, aiming to manage its risk or fund its lending activities, but any undertaking holding loans and other financial assets may in principle conduct securitisations. Securitisation may improve access to credit for certain borrower groups, and provide additional alternative investment opportunities. However, securitisation may also increase complexity in the financial system, and potentially entail significantly higher systemic risk if regulation is not sufficiently robust, as seen in the US in the leadup to the financial crisis. Securitisation has been little used in Norway as the result, inter alia, of the rules enabling this type of transaction having been abolished upon the enactment of the new Financial Institutions Act in 2016, but it has been widely used elsewhere in Europe and, to an even greater extent, in the US.
The EU has adopted a new regulatory framework intended to promote the prudent use of securitisation. The Securitisation Regulation was enacted in December 2017 and entered into effect in the EU on 1 January 2019. The Securitisation Regulation and related amendments to other EU regulations are EEA-relevant, but have yet to be incorporated into the EEA Agreement. A report on how the new securitisation provisions can be implemented in Norway was circulated by the Ministry of Finance and closed for consultation on 30 September 2019, and the Ministry is in the process of preparing a legislative proposition.
In February 2019, the European Parliament and the Council of the European Union reached agreement on the provisions of a new regulatory framework on covered bonds, based on a proposal from the European Commission in March 2018. The regulatory framework was formally enacted by the EU in November 2019. Its objective is to promote the use of covered bonds in Europe, both as a source of funding and as an investment object. The regulatory framework shall, inter alia, harmonise covered bond definitions and characteristics, including the establishment of “European Covered Bonds“ as a label that meets certain requirements, and strengthen consumer protection through new supervisory duties. It is intended for the regulatory framework to enter into effect in Norway at the same time as in the EU. Finanstilsynet has recently examined how this can be implemented, and the Ministry circulated its report for consultation on 23 March 2020. In the process of adopting national regulations, harmonisation considerations will be emphasised in using the national room for manoeuvre.
The role of the financial industry in the transition to a low-carbon economy
The financial industry plays a key role in the transition to a low-carbon economy. As lender and investor, the industry may be a driver for private sector restructuring. The industry may contribute by developing financial instruments and products which make it easier for investors to identify sustainable investments, and by offering financial products that provide customers with incentives to cut emissions.
The industry currently provides a number of financial products with a “green“ or sustainable profile aimed at the retail and corporate markets. The industry also has a role in managing the issuance of green bonds to fund projects which have positive climate and environmental effects or which facilitate climate change adaptation. The absence of universally accepted principles for classifying green financial instruments and products may inhibit growth in the market, and makes it challenging for customers to compare products. The lack of standards for green financial products also leaves scope for so-called greenwashing, where products are marketed as green without having any demonstrable climate or environmental effects.
The establishment of standards may increase customers’ and investors’ confidence in such products, and facilitate growth in these markets. The development of a classification system for sustainable economic activity and standards and labelling schemes in the EU may reduce the risk of greenwashing, and make it easier for professional and non-professional investors to identify sustainable investments.
Non-life insurance companies are directly exposed to the physical effects of climate change in the form of increased compensation payments due to more frequent natural disasters. Norwegian non-life insurance companies are an important partner for the authorities with regard to climate change adaptation and natural disaster prevention. The companies have accumulated extensive climate and natural disaster risk knowledge through their operations, in the form of loss data which the companies share with the Norwegian Directorate for Civil Protection.
Digitalisation and financial technology
The Norwegian financial industry was an early adopter of digital solutions and of cost-effective digital services to its customers. The rate of financial services innovation remains high and may trigger further market structure changes in coming years. The EU’s revised Payment Services Directive is expected to increase competition in the payment services market over the next few years. Statutory and administrative provisions implementing the key aspects of the directive in Norway entered into effect on 1 April 2019.
Established financial undertakings are challenged by both new fintech operations and large technology companies that have started to provide financial services in recent years. The Financial Stability Board has noted that the entry of major technology companies into the financial services market may increase competition in the short run, although there is a risk of new market concentration in the longer run. Strategic collaboration has recently been emerging between technology companies and established financial undertakings, for example between Google and Citigroup and between Apple and Goldman Sachs. A similar trend has been observed in Norway, with several examples of established financial industry firms collaborating with both global providers and local newcomers.
The emergence of Bitcoin and other virtual currencies has raised a number of new issues. There is a broad international consensus that virtual currencies pose a money laundering and terrorist financing risk. The European Commission has, on the basis of contributions and advice from the supervisory bodies EBA and ESMA, called for consultative input on virtual assets falling within the scope of EU provisions on financial instruments under MiFID II or classified as e-money under the E-Money Directive. For virtual assets currently falling outside the scope of the EU provisions, the Commission is considering joint regulation to address, inter alia, consumer protection and market integrity.
A recent development in the virtual asset market is the emergence of crypto-assets with stabilisation mechanisms (“stablecoins”). The Financial Stability Board has defined stablecoins as crypto-assets designed to maintain a stable value relative to another asset or a basket of assets. These may be collateralised by selected traditional currencies or commodities, or supported by algorithms. A G7-appointed working group has stated that no such global crypto-assets should be launched in the market until the legal and regulatory problems have been resolved.
New market participants and the use of new technology in financial services production may increase demand for regulatory guidance, especially from new providers with little experience of regulation and supervision, but also from established financial undertakings wishing to provide services in new ways through the use of technology. Supervisory authorities in several countries have in the last few years sought to facilitate innovation through the establishment of guidance contact points and so-called regulatory sandboxes.
Regulatory sandboxes enable selected businesses to test specific products, technologies or services on a limited number of customers, for a limited period of time and under the guidance of the supervisory authority. The intention is both to expand supervisory authorities’ understanding of new technological solutions in financial markets and to improve innovative businesses’ understanding of regulatory requirements and how the regulatory framework is applied to new business models, products and services.
In November 2018, the Ministry of Finance asked Finanstilsynet to establish a regulatory sandbox by yearend 2019, as part of a broader information and guidance initiative. Finanstilsynet started taking sandbox applications on 12 December 2019, with an application deadline of 12 February 2020. 12 applications were received, and these are currently being assessed for potential admission to the first sandbox round. In view of experience with the first batch of applications, the Ministry will, in consultation with Finanstilsynet, consider whether to allow continuous admission to the sandbox, as well as other potential modifications.
Digitalisation serves to improve both public and private sector efficiency and productivity, whilst simplifying life for consumers. There are positive feedback effects between public sector and financial sector digitalisation, and the financial industry is a valuable collaboration partner in the government digitalisation effort. In June 2019, the Government, represented by the Ministry of Local Government and Modernisation, published its digitalisation strategy for the 2019–2025 period. Close collaboration with the financial industry will remain a key pillar of this strategy, including the Digital Public Private Collaboration (DSOP) project. The financial industry is through DSOP contributing to the development of digital solutions that may generate major savings for the economy. The coronavirus situation has highlighted the benefits of a digitalised society. The technical solution for the business compensations scheme launched by the Government after the outbreak is, for example, based on earlier DSOP efforts and solutions.
Crowdfunding
Crowdfunding platforms that connect investors with businesses and others who need capital have emerged as a supplement to traditional financial undertakings and marketplaces. The Capital Access Commission (NOU 2018: 5) identified facilitation of crowdfunding, as a source of both debt and equity, as one of several proposals for improving access to capital for Norwegian businesses. The Government will facilitate crowdfunding through both simplifications for the industry and increased safeguarding for consumers. The regulations have been modified to prevent uncertainty about so-called “individual cases” from being an unintended impediment to the expansion of loan-based crowdfunding in Norway. The Ministry will monitor developments in the Norwegian market and assess the need for further regulatory amendments. In particular, the Ministry will monitor regulatory developments in the EU, as well as the implications of pan-European crowdfunding regulations for future Norwegian regulation of financial crowdfunding platforms.
The EEA Agreement and Norway’s relationship with the UK
The EEA Agreement is Norway’s most important trade agreement, through which a single market in financial services has been established. Our financial market is deeply integrated with markets in the Nordic EU member states, and a well-functioning single market is of major importance to Norway. Financial market regulation in Norway is largely based on EEA provisions, which are themselves often aligned with international recommendations.
It is important for the single market affiliation of Norwegian undertakings and markets that relevant EU provisions are swiftly incorporated into the EEA Agreement and implemented in Norwegian law. When the EEA Agreement was signed in 1992, it included 45 legal acts on financial services, and about 135 new legal acts had been added by August 2016. The incorporation rate has increased after the legal acts establishing the European System of Financial Supervision were adapted and incorporated into the EEA Agreement in September 2016. More than 350 legal acts were incorporated between September 2016 and December 2019, of which no less than 267 were incorporated in 2019. 17 legal acts have been incorporated into the EEA Agreement thus far in 2020. As at mid-March, 97 financial legal acts enacted by the EU had yet to be incorporated into the EEA Agreement. The Government will in 2020 continue to pursue the incorporation of EEA-relevant legal acts into the EEA Agreement and the implementation of these in national law.
The Ministry is closely monitoring developments in EU financial market regulations. The Ministry will continue to focus on the importance of equal regulation of equal activities and equal risk, as well as on the maintenance and strengthening of financial stability. We will in this context highlight, inter alia, the need for national flexibility in the preparation of regulations and requirements, including equity and liquidity requirements. Where relevant, the Ministry is pursuing a joint effort with other affected ministries, such as in the follow-up of the Commission’s sustainable finance initiative.
The UK left the EU, and thereby also the EEA Agreement, on 31 January 2020. The EEA terms will continue to apply for a transition period that expires on 31 December this year, unless the EU and the UK agree an extension by 1 July. The transition period may be extended for a maximum of two years. Norway and the two other EEA/EFTA countries are negotiating with the UK in parallel with the EU. A key objective for Norway is to maintain the best economic relations with the UK that are possible within the EEA framework, on the basis of mutuality. The objective is for Norwegian market participants to retain as good access to the UK market and the financial infrastructure in London as the EU member states have.
Consumers in the financial markets (chapter 4)
Consumers need special protection and strong rights in financial markets. Consumers may not be well placed to assess the risks, costs and yield potential of some financial services before entering into contracts. Decisions with a major impact on personal finances, such as taking up residential mortgage loans and choosing pension plans, are only made a few times in a lifetime and there may be little room for trial and error.
The regulatory framework shall ensure that consumers can trade securely with professional financial undertakings, but does not exempt consumers from risk or responsibility. The Government is focused on consumers having the knowledge and information to enable them to make prudent decisions regarding their own finances.
Current regulatory efforts
Consumer protection is a key priority in financial market regulations and supervision, as exemplified by customer service, disclosure and advice requirements. In addition, much of consumer protection is embedded in general regulatory provisions under the auspices of other ministries, such as for example the Competition Act and the Marketing Control Act under the Ministry of Trade, Industry and Fisheries and the Ministry of Children and Families, respectively. The Ministry of Children and Families is also responsible for the Debt Restructuring Act, which the Government is currently in the process of revising. The Ministry of Justice and Public Security is pursuing amendments to the Debt Collection Act on the basis of a proposal which is being circulated for consultation until this summer, and will soon submit a proposal for extensive revision of the Financial Contracts Act. The purpose of such revision of the Financial Contracts Act is to implement EU directives on residential mortgages, consumer credit, payment accounts and payment services, to introduce measures to tackle debt problems, to modernise the structure of the Act and to codify provisions that are currently found in non-statutory contract law.
Finanstilsynet has uncovered that a number of international undertakings and their branches in Norway, but also some Norwegian undertakings, are not affiliated with an approved dispute resolution scheme, such as the Norwegian Financial Services Complaints Board. This implies that the customers of such undertakings have weaker protection of their rights and interests, for example because of the inapplicability of provisions on covering the consumer’s legal costs in certain cases. In the autumn of 2019, the Ministry circulated for consultation a set of draft regulatory provisions requiring all undertakings that provide financial services to consumers in Norway to be affiliated with an approved dispute resolution body. The Ministry intends to follow up on the consultative proposal in the form of a regulation and proposed legislative amendments.
In October 2019, the Government appointed a committee to review the Estate Agency Act and propose forward-looking regulation. The committee shall, in accordance with the Granavolden platform, examine the scope for simplification and improved consumer protection. Confidence that property transactions will be executed in a simple and secure manner is of key importance for a well-functioning housing market. The committee shall submit its report in early 2021.
Customer mobility and competition
It has become easier to switch banks and insurance companies in recent years, partly because Norwegian banks have signed up to Finance Norway’s provisions on bank switching cooperation. The Ministry of Justice and Public Security’s proposal for a new Financial Contracts Act will, inter alia, include codification of most of Finance Norway’s provisions. The legislation shall facilitate swift and secure bank switching, in line with the EU’s Payment Accounts Directive. The scope for providing proof of identity and signing account and loan agreements quickly and digitally by means of BankID has also made bank switching easier.
The proportion of customers switching residential mortgage provider has been about 8–10 percent in recent years, whilst the proportion renegotiating their residential mortgage has been approximately 25 percent, according to a Kantar survey. The main reasons customers give for not switching or renegotiating are that they are satisfied with the bank or that they think there is little to be gained. Few people state that they believe bank switching to be difficult. Even fewer state that they believe that it is difficult to switch non-life insurance company, and switching is indeed more frequent in this market. However, many people find it difficult to compare the life insurance and pension products on offer. Part of the pension product challenge may be resolved through the introduction of designated individual pension accounts, which are intended to gather pension entitlements from pension capital certificates and ongoing accruals in collective pension plans together in one place. This will both make it easier for individuals to access such details and improve competition in the market.
The Government is committed to making it easy to switch banks, insurance companies and other service providers. This requires financial industry participants to agree on good solutions, and legislation and other aspects of the regulatory framework to be tailored to market developments.
The EU’s revised Payment Services Directive (PSD2) entered into effect in Norway in April 2019, thereby opening up the prospect of new market entrants offering services based on account information from banks. This may increase competition between providers, and make it even easier to switch service provider or use multiple providers simultaneously. In the Norwegian market, one has thus far not seen any clear indication of new market entrants having captured any significant share of the payment services market. To the extent that the market structure has indeed changed, it has rather tended to involve cooperation between existing and new market participants and often on services based on digital infrastructure which has been in place for a while.
As and when the impact of new technology in a more open market becomes apparent, it may be appropriate to assess the need for additional regulatory modifications and other measures. The Government will also assess the European Commission’s announced review of portable account numbers, i.e. the scope for customers to keep their account number when switching banks. This review was scheduled for completion in September 2019, but has been delayed. The Government will therefore revert to this issue in a future Financial Markets Report.
The Finansportalen financial services portal is operated by the Norwegian Consumer Council, and is one of the services that has made it easier to get an overview of financial services. and to switch service provider. The portal brings together and presents comparable and easily accessible information on financial market products, thereby enabling consumers to find the best prices and terms. This spring, there has been a steep increase in traffic on Finansportalen, partly as the result of more bank customers accessing residential mortgage interest rate comparisons. This serves to boost competition. Price data from Finansportalen are also used as a basis for the norm interest rate and the interest rate on government loans. The Government is of the view that it is essential that both consumers and authorities can rely on Finansportalen to provide price information which is of a high quality and which is updated at any given time. It must therefore be a priority for the Norwegian Consumer Council, which manages Finansportalen, to ensure that the information from Finansportalen is at all times correct and complete.
Consumer loans and payment problems
Access to unsecured credit, including credit card debt, provides opportunities for smoothing consumption over time, but also creates problems for those who borrow in excess of their debt servicing capacity. Consumer loans are often part of the backdrop to debt problems. In 2019, more than 1 in 10 consumer loans was in default for more than 90 days, whilst this applied to 1 in 14 consumer loans in 2018. In 2017, consumer loans averaged close to NOK 700,000 in debt restructuring proceedings. Banks’ losses on consumer loans increased significantly in 2019, from 1.7 to 2.7 percent of total consumer loans, after having remained fairly stable in recent years.
The increase in defaults and losses on consumer loans is linked to the strong lending growth which characterised this market until recently. Considerable challenges have been observed in the market, including aggressive marketing and inadequate creditworthiness assessments on the part of banks. The Government has launched a number of measures, and additional measures are in the pipeline. Several of these measures have been implemented in 2019. In particular, banks have been required to observe the new lending practice requirements for consumer loans since May last year, whilst debt information service providers entered into operation over the summer. Access to information on the unsecured debt of loan applicants makes it easier for banks to avoid granting consumer loans to individuals who are already highly indebted. The lending practice requirements also serve to prevent consumers from taking on debts they will not be able to service. This represents a major change to the regulatory framework under which consumer loan bank operate, when compared to the situation only one year ago, and this has probably contributed to the observed levelling off of consumer loan market activity. The steep default increase is nonetheless cause for concern. It is important that banks now comply with the numerous new obligations introduced in the last few years. The Government expects that this will also improve default figures over time.
The Government’s proposal for a new Financial Contracts Act will include provisions that strengthen consumer protection upon the conclusion of credit agreements. After the proposal has been submitted to the Storting, the Government will examine, for example, the need for stricter rules on credit marketing. The review of the Debt Collection Act aims, inter alia, to reduce debt collection fees and ensure adequate debt collection procedures.
The Ministry of Children and Families will evaluate the Debt Information Act when debt information service providers have been in ordinary operation for two years, i.e. in 2021. The Act authorises expansion of the disclosure obligation to encompass all secured and unsecured debt. The Norwegian Consumer Council, Finance Norway and Finanstilsynet have all advocated use of these powers. The Government is of the view that such expansion would be in line with the intention behind the Debt Information Act and serve to increase the usefulness of debt information service providers.
Developments over the last year suggest, in the assessment of the Government, that there is no need for the introduction of so-called interest rate ceilings or cost ceilings for consumer loans, as examined in the Financial Markets Report 2019 at the request of the Storting. As long as there has not emerged a sizeable market for small loans with a short duration and very high effective interest rates, as has happened in some countries which have introduced such policy measures, the potential gains cannot justify the disadvantages. An interest rate ceiling may for example establish a norm or facilitate interest rate coordination between banks, thereby resulting in higher interest rates on total consumer loans. However, the Government is closely monitoring market developments and the effect of the introduced and announced measures, and will assess the need for additional measures against that background.
Availability and use of cash
Most payments in Norway currently involve electronic solutions such as payment cards, mobile payment and online banking. In the spring of 2019, fewer than 1 in 10 payments in retail outlets and between individuals were made in cash, whilst the same applied to every fourth payment in 2007. This is the result of an efficient electronic payment system. There is nonetheless still a need for cash as a means of payment and a store of value, as well as a backup in case of electronic payment system failure.
Banks have gradually scaled back their cash services over many years, and individual banks are under no obligation to maintain services on behalf of society. However, the Financial Institutions Act requires banks to provide cash services that meet customers’ expectations and needs. Norges Bank and Finanstilsynet are of the view that current developments give rise to uncertainty as to whether this requirement will be satisfactorily complied with in coming years, and have proposed that specific requirements be imposed on banks in the form of regulations.
The Government has devoted special attention to developments in the cash service offerings of banks in the last two Financial Markets Reports. The general position of the Government is that banks’ responsibility for cash services is probably handled more efficiently through the joint solutions of banks themselves than through regulation of individual elements such as, for example, capacity, opening hours and geographical distribution. In the Financial Markets Report 2019, the Ministry announced that such regulation might nonetheless be contemplated unless banks swiftly agree appropriate joint solutions, or individually conclude agreements that otherwise ensure access to satisfactory cash services for all banking customers.
Banks have over the least year developed a joint framework for depositing and withdrawing cash in shops, through a collaborative effort between Finance Norway and Bits AS, which is the infrastructure company of the financial industry. In December 2019, Bits AS established a set of rules which, inter alia, enables each bank to agree that its customers may use cash services offered by other banks. Banks may also offer their customers to deposit and withdraw cash in shops affiliated with the BankAxept system, including through a service provider such as Vipps AS, which according to Finance Norway has now concluded agreements with a large number of banks. The solution will be available to bank customers in the spring of 2020. When the solutions have been in operation for one year, it will according to Finance Norway be examined whether there is a need for developing additional collaborative solutions, for example for cash deposit machines.
The Ministry of Finance intends to ask Finanstilsynet and Norges Bank to review cash services anew after the banking industry’s new solutions for maintaining cash services have been in operation for a few months. One will by then also have a better understanding of the implications of DNB having terminated the agreement with Posten on the provision of basic banking services, with effect from 1 July. This review will form the basis for a new assessment as to whether cash services for Norwegian bank customers can be considered satisfactory throughout the country, or whether there may be a need for further regulation of the obligations of banks.
Under the Financial Contracts Act, consumers always have the right to make payments to any payee in cash. There have been major changes in access to various payment solutions and in how financial agreements are concluded since the Act was enacted in 1999. There may thus be a need for examining whether the current provisions remain appropriate and whether there is a need for clarification. The Ministry of Justice and Public Security will take a closer look at the provisions on the right to cash payment in the wake of the preparation of the new Financial Contracts Act.
Pension
The persistently low interest rate level and the increasing life expectancy of the population has affected the pensions market. Lower expected return and a longer benefit period has made it more expensive to fund a given life-long annual pension benefit. Traditional defined-benefit schemes have been phased out over time, whilst new pension accruals are largely taking place in defined-contribution schemes. There nonetheless remains considerable capital behind rights under defined-benefit schemes, and especially under paid-up policies. The Government will facilitate a secure and predictable private pension savings framework through regulation of both pension providers and pension products.
A sound regulatory framework needs to be maintained and evolved for both the growing defined-contribution portion of the market and the management of the funds backing the pensions already accrued. For defined-contribution schemes, the introduction of a designated individual pension account and the question of including all wage income in the mandatory calculation basis for pension accrual are key issues, whilst the focus is on pension capital management regulations as far as defined-benefit schemes are concerned. The overarching objectives for the regulatory effort are safeguarding accrued pensions, efficient and rational pension capital management, good information and scope for influencing own pension, as well as effective competition in the pensions market.
The activities of Norges Bank in 2019 (chapter 5)
Norges Bank is Norway’s central bank, and shall promote economic stability and manage assets on behalf of society. Norges Bank monitors the stability of the financial system, and provides assessments of the financial stability outlook in public reports several times a year. It provides quarterly advice to the Ministry of Finance on the level of the countercyclical capital buffer requirement. Norges Bank shall contribute to robust and efficient payment systems, and settles payments between banks in Norway. The central bank provides loans to banks and central counterparties, issues banknotes and coins, supplies banks with cash, and supervises the interbank systems. Norges Bank also manages the foreign exchange reserves.
Norges Bank is charged with the operational implementation of monetary policy pursuant to guidelines laid down in a Regulation on Monetary Policy. The Regulation stipulates that the operational target of monetary policy shall be an annual consumer price inflation of close to 2 percent over time. The inflation targeting shall be forward-looking and flexible so that it can contribute to high and stable output and employment, and to counteract the build-up of financial imbalances.
The Storting enacted a new Central Bank Act on 17 June 2019. The Act includes a new object clause for the activities of the central bank. A new Monetary Policy and Financial Stability Committee has also been established.
The key policy rate is the most important monetary policy tool. Norges Bank increased the key policy rate three times over the course of 2019, from 0.75 percent to 1.5 percent.
The Ministry of Finance performs an annual assessment of Norges Bank’s monetary policy conduct. The Ministry is of the view that monetary policy conduct was sound in 2019. In the Ministry’s view, there is broad confidence in monetary policy among markets participants, academia and the general public.
Norges Bank also manages the Government Pension Fund Global (GPFG) on behalf of the State pursuant to provisions laid down by the Ministry of Finance. The management of the GPFG, including management performance and performance assessment, is addressed in a separate report.
The activities of Finanstilsynet in 2019 (chapter 6)
Finanstilsynet is the financial supervisory authority of Norway, and oversees financial undertakings’ compliance with legislation and regulations. Finanstilsynet regularly conducts analyses of financial industry developments and economic conditions, nationally and internationally. One of the key objectives of Finanstilsynet is to promote financial stability, and its activities are focused on both the risk faced by financial undertakings as the result of macroeconomic developments, and the risk to the financial system and the economy that may be generated by financial undertakings as a whole.
In 2019, Finanstilsynet continued to refine models used to assess developments in the Norwegian economy and for stress testing of banks. Finanstilsynet conducted stress tests of 20 Norwegian banking groups and close to 90 smaller Norwegian banks. In addition, eight consumer loan banks were stress tested. Finanstilsynet participates in the European System of Financial Supervision, and works in close collaboration with other national supervisory authorities.
Finanstilsynet continually conducts document-based supervision on the basis of reporting from undertakings, and this forms the starting point, along with the monitoring of markets and the Norwegian economy, for a risk-based selection of undertakings for on-site inspection. On-site inspection is important in order to identify problems, and to establish close dialogue with senior managers and directors at an early stage, thus enabling necessary measures to be implemented in an effective manner. In 2019, Finanstilsynet carried out a total of 24 on-site inspections with banks, mortgage companies and finance companies. It also carried out nine on-site inspections with follow-up of IRB approvals and five on-site inspections of ICT infrastructure, disaster solutions and contingency planning. Moreover, it carried out 23 special inspections relating to ICT, and 12 on-site inspections with insurance companies and pension funds. Finanstilsynet carried out a number of inspections in other fields, such as securities trading, accounting and auditing, as well as estate agency and debt collection
The activities of Folketrygdfondet in 2019 (chapter 7)
Folketrygdfondet is a special legislation company wholly owned by the Norwegian state through the Ministry of Finance. Folketrygdfondet manages the Government Pension Fund Norway (GPFN) pursuant to specific management provisions laid down by the Ministry of Finance. The asset management objective is to maximise the return over time, measured in Norwegian kroner and net of costs. The market value of the GPFN was NOK 268.7 billion as at yearend 2019. The return on the Fund was 12.4 percent in 2019, which is 0.4 percentage points more than the return on the benchmark index defined by the Ministry. Every spring, the Ministry publishes a separate report on the management of the Government Pension Fund in the previous year, including Folketrygdfondet’s management of the GPFN. The Ministry of Finance has against the background of the current coronavirus pandemic decided to defer the publication of the report The Government Pension Fund 2020.
The activities of the IMF (chapter 8)
The International Monetary Fund (IMF) is charged with promoting international monetary corporation, strengthening financial stability globally and regionally, and facilitating international trade. By the end of February, a total of 18 countries had agreements with the IMF under the institution’s general lending arrangements and 39 countries had agreements under the concessional arrangements reserved for low-income countries.
Norway is currently placing a total of SDR 11.7 billion (equivalent to above NOK 150 billion at the 29 February exchange rate) at the disposal of the general lending arrangements of the IMF. SDR 3.75 billion of this are quota resources which Norway is obliged to contribute. An additional SDR 1.97 billion are made available through the multilateral borrowing arrangement of the IMF (NAB) and SDR 6 billion are made available under a bilateral loan agreement. Participation in NAB and bilateral loans is voluntary, and the current agreements expire in 2022 and 2020, respectively. Norway also contributes resources to the special arrangements for low-income countries. Loans to the IMF are made through reinvestment of the Norges Bank foreign exchange reserves.
The financial obligations and rights of members, as well as their voting power, are linked to their national quotas. The IMF conducts periodic reviews of the level and distribution of quotas. In February, the IMF Board of Governors decided to conclude the current quota review with no change in quotas. This is primarily because the US, which has a blocking minority, did not support an increase. In practice, a quota increase would have increased the voting power of emerging economies.
It is important for Norway to have stable international relations, open markets and a well-functioning global safety net. The Government is of the view that Norway should continue to contribute to maintaining the financial strength of the IMF. The global crisis caused by the coronavirus pandemic makes it especially important to ensure that the IMF has sufficient funding to assist distressed members. Confidence that multinational financial institutions have sufficient resources is also important to reduce capital drain from vulnerable countries in such a crisis situation and to improve countries’ access to international capital markets.
The IMF’s bilateral borrowing agreements will expire at the end of this year. The IMF’s resources will then be considerably depleted unless new agreements are concluded. In January, the IMF Executive Board decided, to partly compensate for this, to double the amount of borrowing under the NAB arrangement with effect from January 2021. Norway has received a request in line with this. Furthermore, the IMF Executive Board approved the framework for a new round of bilateral borrowing in March. This calls for the loan amounts to be the same as under the current agreements, subject to a reduction in such amounts that matches the increases in NAB resources when the new NAB arrangement enters into effect. The IMF’s lending capacity will thereby be maintained at the present level.
New loan agreements with the IMF require the consent of the Storting. The Government intends to ask the Storting for authorisation to double the Norwegian contribution to the NAB arrangement and to conclude a new bilateral loan agreement with the IMF in connection with the National Budget for 2021.
As part of its response to the coronavirus crisis, the IMF has asked member countries for contributions to top up the IMF Catastrophe Containment and Relief Trust, which is used to subsidise debt servicing for the poorest member countries if these are hit by major natural disasters, including epidemics. This targeted debt relief reaches the most vulnerable countries and releases funds for spending on crisis management.
The Government will in response to the IMF’s request for contributions to the Catastrophe Containment and Relief Trust propose, in connection with the Revised National Budget for 2020, that Norway contributes NOK 180 million in the form of an appropriation via the international aid budget.
Surging demand for coronavirus crisis support from poor countries means that the IMF also needs additional resources for the low-income country borrowing arrangements funded through the Poverty Reduction and Growth Trust (PRGT). The Government intends to propose to the Storting, in the Revised National Budget for 202, that Norway makes new loan resources available for these lending arrangements.
Amendments to regulatory frameworks and licences in 2019 (chapter 9)
The financial market regulation predominantly takes the form of legislation and regulations. The Ministry of Finance submits legislative proposals to the Storting, and adopts more detailed rules in regulations. The Ministry also grants licences for the establishment or reorganisation of financial undertakings, and stipulates conditions for such licences. An overview of the most important regulatory amendments in 2019 is provided in chapter 9. The chapter also includes a discussion of licences granted in 2019. | https://www.regjeringen.no/en/dokumenter/meld.-st.-22-20192020/id2699066/?ch=1 |
Why we developed the ISL Consumer Safety Scorecard
With all the current activity in US privacy laws, both at the state and federal level, trying to stay up to date with the changes in proposed legislation can be an overwhelming and time-consuming task due to the sheer volume of dense materials. Just in the past six months alone we’ve seen rulemaking activity arise from both the CPPA and the FTC, as well as multiple drafts of a federal privacy law (ADPPA). Whew!
We review legislation in our Policy and Legal Advisory Panel (PLAP), which is open to everyone. Members of PLAP are thought leaders, subject matter experts, advocates, and passionate users. But the flurry of policy activity has challenged everyone’s ability to keep on top of the latest policy drafts.
We realized that we needed a more efficient and practical way to evaluate proposed regulations. As a result, we developed our ISL Consumer Safety Scorecard for Regulation (Table 3, below).
Introduction to ISL Consumer Safety Scorecard for Regulation
The ISL Consumer Safety Scorecard for Regulation compares the text of proposed regulations against our “must have” regulation safety principles to arrive at an overall ISL safety score for the regulation. This score lets people know how effective the regulation is at keeping people safe while using connected software products and services.
Table 1: Legend
Table 2: Terminology Mapping
Table 3: ISL Consumer Safety Scorecard v1.0
In the coming days and weeks we will be publishing our scorecards for current and proposed legislation. We hope that our ISL Consumer Safety Scorecard helps make it more digestible and accessible for everyone to easily understand how well regulation serves to keep citizens safe online.
A special thank you to all our PLAP members who contributed to this work!
By the way, we know that the diversity of our members’ points of view is crucial to assessing software safety (especially given that many policymakers may not fully understand how technology behaves). Together, we can all co-create a safer online ecosystem by voicing our concerns and contributing meaningful public comments on proposed regulations. It’s easy to join any of our current panels to help make software safer for everyone.
[i] Age must not be remembered, B-s must calculate age every time and forget it every session. Note that if safety principle #1 is in place, there is less of a need for age validation.
[ii] Me2B Relationship refers to the relationship a user (Me) forms with a business (B) and with the products and services that the business provides. Just like human relationships, the Me2B Relationship changes over time, generally increasing in trust and intensity. The state of the Me2B Relationship is therefore crucial context for data sharing norms.
[iii] Direct Relationship means the data subject has an account and has entered into some kind of service agreement with the company and can thus correct/view personal information. Data Brokers typically have no direct relationship with the data subjects.
[iv] A duty of loyalty has well-established roots in the common law of fiduciaries and trusts. A hallmark of the obligation is to have no conflicts of interest between the client and third parties, and to always act in the client’s best interest. Modern examples of entities with these same duties are doctors, lawyers, and certain financial advisors. | https://internetsafetylabs.org/blog/policy/introducing-the-isl-consumer-safety-scorecard-for-regulation/ |
Look back at the chapter by chapter notes you have made about
Hyde's depravities. These break down into:
This material is going to make up the bulk of your essay -
about 700 words. You could go through the material section by
section, or through the novella chronologically - chapter by
chapter - dealing with these issues as they arise. The former
is likely to lead to the more stylish essay.
You won't want to use all the material you've got or your
essay will never end! Be representative and not scanty.
Remember that you need to quote in this section, because the
words you're quoting are answering the first "How?"
of the question.
Deal with how the Jekyll/Hyde relationship is a metaphor for
human nature. We talked about this before we started reading
- how we all have out "Hyde" sides and so can all
relate to the issue raised; we all understand how our worser
natures, if given free rein, can overwhelm our better selves.
In this section you're looking at the idea that Victorian society
had a veneer of morality which hid a seething underbelly of
vice and corruption. Jekyll represents the veneer and Hyde the
underbelly. You'll need to give examples of the moral hypocrisy
and double standards of Victorian society and relate it to Jekyll's
behaviour in the novella.
Sections 2 & 3 will probably amount to about 500 words
between them, so you're looking at an overall essay length of
about 1200 words. It sounds a lot, but isn't in fact.
Good luck. Come and see me if you get stuck. | http://battle-axe.org/English/Jekyll_Hyde.html |
The following shows the syntax of the DENSE_RANK() function:
Syntax: DENSE_RANK() OVER ( [PARTITION BY partition_expression, ... ] ORDER BY sort_expression [ASC | DESC], ... )
The DENSE_RANK() function is applied to every row in each partition defined by the PARTITION BY clause, in the sort order specified by the ORDER BY clause. It will reset the rank when crossing the partition boundary. The PARTITION BY clause is optional. If you skip it, the DENSE_RANK() function will treat the whole result set as a single partition.
Example 1:
First, create a table named dense_ranks that has one column:
CREATE TABLE dense_ranks ( c VARCHAR(10) );
Now insert some data into it:
INSERT INTO dense_ranks(c) VALUES('A'), ('A'), ('B'), ('C'), ('C'), ('D'), ('E');
Now query from the dense_ranks table:
SELECT c from dense_ranks;
It will result in the below depiction:
Fourth, use the DENSE_RANK() function to assign a rank to each row in the result set:
SELECT c, DENSE_RANK() OVER ( ORDER BY c ) dense_rank_number FROM dense_ranks;
Output:
Example 2:
First, create two tables named products and product_groups for the demonstration:
CREATE TABLE product_groups ( group_id serial PRIMARY KEY, group_name VARCHAR (255) NOT NULL ); CREATE TABLE products ( product_id serial PRIMARY KEY, product_name VARCHAR (255) NOT NULL, price DECIMAL (11, 2), group_id INT NOT NULL, FOREIGN KEY (group_id) REFERENCES product_groups (group_id) );
Now insert some data to the table:
INSERT INTO product_groups (group_name) VALUES ('Smartphone'), ('Laptop'), ('Tablet'); INSERT INTO products (product_name, group_id, price) VALUES ('Microsoft Lumia', 1, 200), ('HTC One', 1, 400), ('Nexus', 1, 500), ('iPhone', 1, 900), ('HP Elite', 2, 1200), ('Lenovo Thinkpad', 2, 700), ('Sony VAIO', 2, 700), ('Dell Vostro', 2, 800), ('iPad', 3, 700), ('Kindle Fire', 3, 150), ('Samsung Galaxy Tab', 3, 200);
The below statement uses the DENSE_RANK() function to rank products by list prices:
SELECT product_id, product_name, price, DENSE_RANK () OVER ( ORDER BY price DESC ) price_rank FROM products;
Output: | https://www.geeksforgeeks.org/postgresql-dense_rank-function/?ref=rp |
Comfortable 3 bedroom holiday home with 2 bathrooms and 2 living areas. Easy stroll to the beach and bowling club, shops and all other amenities. Great deck for enjoying the afternoon summer breezes and just having holiday fun.
Sleeps 8 - 2 queen & 2 bunks
July Holidays - $500/pw
Sept/Oct Holidays - $700 p/w
Dec/Jan Holidays - $1200 p/w
April Holidays - $700 p/w
Off Peak - $700 p/w
Booking fee of $20 payable a time of reservation.
Thank you very much for the great service you and your team provided in selling my families’ property. I hope to catch up with you when I am next in the area. All the best,
To Pam & Staff, Thank you for your professionalism, kindness and thoughtful gestures during the purchase of our new home. Regards, Maria & Reg
"Once again, thank you for your compassionate and professional service given to me and my family, Kind regards" | https://www.premises.com.au/2-laverty-crescent-scotts-head-nsw-6174997 |
GOES-16 Visible images combined with the clear-sky Total Precipitable Water product (below) revealed TPW values in the 2.2 to 2.5 inch range in the vicinity of the MCV. This environment of high moisture likely aided the development of new convection as the MCV approached. Nearby 12 UTC soundings from Porto Velho (SBPV) and Vilhena (SBVH) showed minimal instability across far southwestern Brazil, but the sounding TPW values (2.0 to 2.3 inches) were in good agreement with the TPW values derived from GOES-16.GOES-16 Visible images at 1200 UTC and 1800 UTC with plots of GFS wind barbs at 850 hPa and 500 hPa (below) indicated that the MCV was moving through an environment of relatively low wind shear — this helped the MCV to maintain its circulation for the remainder of the daytime hours on 12 November. | https://cimss.ssec.wisc.edu/satellite-blog/archives/43387 |
Ancient Greece was a civilization belonging to a period of Greek history that lasted from the Archaic period of the 8th to 6th centuries BC to the end of antiquity ( 600 AD). Immediately following this period was the beginning of the Early Middle Ages and the Byzantine era. Included in ancient Greece is the period of Classical Greece, which flourished during the 5th to 4th centuries BC. Classical Greece began with the repelling of a Persian invasion by Athenian leadership. Because of conquests by Alexander the Great of Macedonia, Hellenistic civilization flourished from Central Asia to the western end of the Mediterranean Sea.
Classical Greek culture, especially philosophy, had a powerful influence on the Roman Empire, which carried a version of it to many parts of the Mediterranean Basin and Europe. For this reason Classical Greece is generally considered to be the seminal culture which provided the foundation of modern Western culture and is considered as the cradle of Western civilization.〔Bruce Thornton, ''Greek Ways: How the Greeks Created Western Civilization'', Encounter Books, 2002〕〔Richard Tarnas, ''(The Passion of the Western Mind )'' (New York: Ballantine Books, 1991).〕〔Colin Hynson, ''(Ancient Greece )'' (Milwaukee: World Almanac Library, 2006), 4.〕〔Carol G. Thomas, ''(Paths from Ancient Greece )'' (Leiden, Netherlands: E. J. Brill, 1988).〕
==Chronology==
Classical Antiquity in the Mediterranean region is commonly considered to have begun in the 8th century BC (around the time of the earliest recorded poetry of Homer) and ended in the 6th century AD.
Classical Antiquity in Greece is preceded by the Greek Dark Ages ( 1200 – c. 800 BC), archaeologically characterised by the protogeometric and geometric styles of designs on pottery. This period is succeeded, around the 8th century BC, by the Orientalizing Period during which a strong influence of Syro-Hittite, Assyrian, Phoenician and Egyptian cultures becomes apparent. Traditionally, the Archaic period of ancient Greece is considered to begin with Orientalizing influence, which among other things brought the alphabetic script to Greece, marking the beginning of Greek literature (Homer, Hesiod). The end of the Dark Ages is also frequently dated to 776 BC, the year of the first Olympic Games.〔.〕 The Archaic period gives way to the Classical period around 500 BC, in turn succeeded by the Hellenistic period at the death of Alexander the Great in 323 BC.
;Ancient Periods: ''Astronomical year numbering''
ImageSize = width:800 height:100
PlotArea = width:720 height:75 left:65 bottom:20
AlignBars = justify
Colors =
id:time value:rgb(0.7,0.7,1) #
id:period value:rgb(1,0.7,0.5) #
id:age value:rgb(0.95,0.85,0.5) #
id:era value:rgb(1,0.85,0.5) #
id:eon value:rgb(1,0.85,0.7) #
id:filler value:gray(0.8) # background bar
id:black value:black
Period = from:-1200 till:529
TimeAxis = orientation:horizontal
ScaleMajor = unit:year increment:100 start:-1200
ScaleMinor = unit:year increment:50 start:-1200
PlotData =
align:center textcolor:black fontsize:10 mark:(line,black) width:10 shift:(0,-5)
bar:Period color:filler
from: -1200 till: -800 text: Greek Dark Ages
bar:Period color:age
from: -800 till: -500 text: Archaic
from: -500 till: -323 text: Classical
from: -323 till: -146 text: Hellenistic
from: -146 till: 330 text: Roman Greece
from: 330 till: 529 text: Late Antiquity
bar:Phase color:period
from: -1200 till: -1100 shift:(0, 5) text: Mycenaean
from: -1200 till: -700 text: Colonization
from: -800 till: -700 shift:(0, -15) text: Orientalization
from: -700 till: -600 text: Tyrants
from: -600 till: -500 shift:(0, 5) text: Reorganization
from: -500 till: -302 text: Hellenic
from: -302 till: -279 shift:(0, 5) text: Diadochi
from: -302 till: -279 shift:(-10, -15) text: Antipatrid
from: -279 till: -168 text: Antigonid
from: -168 till: -146 shift:(5, 5) text: Invasion
from: -146 till: 330 text: Provincia
from: 330 till: 529 text: Byzantine
bar: color:filler
from: -1200 till: -200 text:Early
from: -200 till: 300 text:Middle
from: 300 till: 529 text:Late
:::''Dates are approximate, consult particular article for details''
The history of Greece during Classical Antiquity may thus be subdivided into the following periods:
* The Archaic period (c. 800 – c. 500 BC), in which artists made larger free-standing sculptures in stiff, hieratic poses with the dreamlike "archaic smile". The Archaic period is often taken to end with the overthrow of the last tyrant of Athens and the start of Athenian Democracy in 508 BC.
* The Classical period (c. 500 – 323 BC) is characterized by a style which was considered by later observers to be exemplary i.e. "classical", as shown in for instance the Parthenon. Politically, the Classical Period was dominated by Athens and the Delian League during the 5th century, but displaced by Spartan hegemony during the early 4th century BC, before power shifted to Thebes and the Boeotian League and finally to the League of Corinth led by Macedon. This period saw the Greco-Persian Wars and the Rise of Macedon.
* In the Hellenistic period (323–146 BC) Greek culture and power expanded into the Near and Middle East. This period begins with the death of Alexander and ends with the Roman conquest.
*Roman Greece, the period between Roman victory over the Corinthians at the Battle of Corinth in 146 BC and the establishment of Byzantium by Constantine as the capital of the Roman Empire in AD 330.
*The final phase of Antiquity is the period of Christianization during the later 4th to early 6th centuries AD, sometimes taken to be complete with the closure of the Academy of Athens by Justinian I in 529. | http://www.kotoba.ne.jp/word/11/Ancient%20Greece |
The Stanley Cup Finals begin Wednesday night in New Jersey with two surprising squads battling it out for hockey’s greatest prize. The Los Angeles Kings, who began the playoffs as the West’s eighth seed with 20/1 odds to win the Cup, are now the favorites at -170. All that stands in their way is the New Jersey Devils, who started the postseason as the East’s sixth seed and at 25/1 to win the Cup.
The Devils do have home-ice advantage, with the first two games in Jersey, but the Kings are still slight favorites to win Wednesday’s Game One (Kings -120, Devils -110).
Vegas oddsmakers see the most likely result of the Finals as the Kings winning in six games, with the least likely scenario a Devils sweep. Here are the odds for all the possible outcomes:
- Kings in Six +300
- Kings in Five +450
- Kings in Seven +500
- Devils in Seven +500
- Kings Sweep +700
- Devils in Five +700
- Devils in Six +700
- Devils Sweep +1400
Kings goaltender Jonathan Quick has the best odds to win the Conn Smythe Trophy for postseason MVP at +110, while his Devils counterpart Martin Brodeur has the best odds of any New Jersey player at +400.
Here are your 2012 Conn Smythe Trophy odds:
- G Jonathan Quick (LA) +110
- RW Dustin Brown (LA) +400
- G Martin Brodeur (NJ) +400
- RW Ilya Kovalchuk (NJ) +550
- C Anze Kopitar (LA) +1000
- D Drew Doughty (LA) +1200
- LW Zach Parise (NJ) +1200
- C Mike Richards (LA) +2500
- C Travis Zajac (NJ) +2500
- RW David Clarkson (NJ) +3000
- LW Dustin Penner (LA) +5000
Leave a Reply
Sign up for the SportsUntapped newsletter and receive free picks and news of the NFL, NBA, NHL, UFC and much more. | http://www.sportsuntapped.com/2012-stanley-cup-finals-odds-kings-devils-127737/ |
Factory made hot-sale Semi Rigid Aluminum Flexible Air Duct - Total Heat Exchanger – Holtop Detail:
Working Principle of Holtop Crossflow Plate Fin Total Heat Exchangers (E.R. Paper for enthalpy exchange core)
|The flat plates and the corrugated plates form channels for fresh or exhaust air stream.
|
When the two air steams passing through the exchanger crossly with temperature difference, the energy is recovered.
Main features
1. Made of E.R. paper, which is featured by high moisture permeability, good air tightness, excellent tear resistance, and aging resistance.
2. Structured with flat plates and corrugated plates.
3. Two air streams flow crossly.
4. Suitable for room ventilation and industrial ventilation system.
5. Heat recovery efficiency up to 70%
|Gas molecules type||Carbon dioxide (CO2)||Ammonia (NH3)||Methane (CH4)||Vapor(H2O)||The clearance of fiber|
|Diameters(nm)||0.324||0.308||0.324||0.288||0.3(for reference)|
Application
Used in comfortable air conditioning ventilation system and technical air conditioning ventilation system. Supply air and ex- haust air totally separated, heat recovery in winter and cold re- covery in Summer
Specifications
|Model||A (mm)||L (mm)||C (mm)||Optional corrugation height (mm)||Remarks|
|HBT-W168/168||168||≤500||240||2.0, 2.5||
|
One module
|HBT -W202/202||202||≤500||288||2.0, 2.5|
|HBT -W222/222||222||≤500||317||2.0, 2.5|
|HBT-W250/250||250||≤700||356||2.0, 2.5, 3.5|
|HBT-W300/300||300||≤700||427||2.0, 2.5, 3.5|
|HBT -W350/350||350||≤700||498||2.5, 3.5|
|HBT -W372/372||372||≤700||529||2.5, 3.5|
|HBT -W400/400||400||≤700||568||3.5|
|HBT -W472/472||472||≤550||670||3.5|
|HBT -W500/500||500||≤550||710||3.5|
|HBT -W552/552||552||≤550||783||3.5|
|HBT -W600/600||600||≤550||851||3.5|
|HBT -W652/652||652||≤550||925||3.5|
|HBT -W700/700||700||≤550||993||3.5||Multi-modulecombined|
|HBT -W800/800||800||≤550||1134||3.5|
|HBT-W1000/1000||1000||≤450||1417||3.5|
|HBT-W1200/1200||1200||≤450||1702||3.5|
|HBT -W1400/1400||1400||≤450||1985||3.5|
|HBT -W1600/1600||1600||≤450||2265||3.5|
Product detail pictures:
Related Product Guide:
Riverpoint Capital Management Boosted By $820,015 Its Schwab Charles New (SCHW) Stake; Last Week Aggreko Plc (LON:AGK) Analysts | Whole House Air Exchanger
Electrical Cabinet Cooling Units Market Size, Growth, Cost Structures, Key Players and Future Forecasts 2018-2023 | Whole House Air Exchanger
Well-run equipment, professional sales team, and better after-sales services; We are also a unified big family, everyone stick to the company value "unification, dedication, tolerance" for Factory made hot-sale Semi Rigid Aluminum Flexible Air Duct - Total Heat Exchanger – Holtop, The product will supply to all over the world, such as: New Delhi, Lisbon, Switzerland, Our objective is "to supply first step products and best service for our customers, thus we are sure you must have a margin benefit through cooperating with us". If you are interested in any of our products or would like to discuss a custom order, please feel free to contact us. We are looking forward to forming successful business relationships with new clients around the world in the near future.
By Lindsay from Hanover - 2016.05.02 18:28
Adhering to the business principle of mutual benefits, we have a happy and successful transaction, we think we will be the best business partner. | https://www.holtop.com/factory-made-hot-sale-semi-rigid-aluminum-flexible-air-duct-total-heat-exchanger-holtop.html |
Hi, Sir.
I want to know this problem.
This problem is number 8 of chapter 13 in Business Analytisc 2ed.
Implement the linear optimization model that you developed for the investment scenario in Problem in Excel and use Solver to find an optimal solution. Save the Answer and Sensitivity reports in your Excel workbook. Interpret the Solver Answer report and identify the binding constraints and verify the values of the slack variables by substituting the optimal solution into the model constraints. Problem A business student has $2, 500 available from a summer job and has identified three potential stocks in which to invest. The cost per share and expected return over the next 2 years is given in the table. a. Identify the decision variables, objective function, and constraints in simple verbal statements. b. Mathematically formulate a linear optimization model. | https://homeworkocean.com/solved-homework-implement-the-linear-optimization-model-that-you-developed-for-the-investment-scenario-in/ |
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LISTSERV Archives
ARSCLIST Home
ARSCLIST March 2011
Subject:
Re: Possibly another reason why Technics is exiting the turntable business
From:
Tom Fine <[log in to unmask]>
Reply-To:
Association for Recorded Sound Discussion List <[log in to unmask]>
Date:
Fri, 11 Mar 2011 22:02:51 -0500
Content-Type:
text/plain
Parts/Attachments:
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(85 lines)
Agree with you about archival playback of 78's! I also love the fluid damping system that Kevin at
KAB came up with. You can track lighter and still track some pretty badly warped shellac.
But for everyday playback, those cheap direct-drive 1200 clones are a lot better than what was
previously available in that price range.
Also agree about 16" playback, but that's a whole other level of equipment.
-- Tom Fine
----- Original Message -----
From: "Milan P Milovanovic" <[log in to unmask]>
To: <[log in to unmask]>
Sent: Friday, March 11, 2011 9:37 PM
Subject: Re: [ARSCLIST] Possibly another reason why Technics is exiting the turntable business
>I think that one of the main difference between legendary Technics 1200 and all the others cloned
>turntables based on this design is in lack of good motor/speed control. One can compare i.e. wow
>and flutter values for Technics and all Stanton, Audiotechnica, JBSystems, Numark etc. tables and
>find that these values are up to 10 times better in case of original table. Also, I can only think
>that all the others details such as main bearing, tonearm tolerances and final finished surfaces,
>as well as all other parts are incomparable for theirs ruggedness, longevity and building quality.
>
> It was terrible day when I first heard Technics stopped their turntable production, and it is
> still unclear if such decision happened or we are in some kind of vacuum until next step.
>
> To my mind Technics 1200 MK4 with 78rpm included and also with special RCA connectors (instead of
> cable attached) was the best thing for everyday archival work on heavy 78rpm records (the only
> lack of usage is, of course, as this turntable is not being suitable for 16" transcription
> discs) - lots of torque and speed stability, fine tonearm, excellent quality in general. But, for
> everything else it was - killer model, far better than some el-cheapo ProJect, than to some so
> called "Thorens" (made in Austrian ProJect facilities, no single connection to the old brand),
> Rega 78 and so on.
>
> Best wishes,
>
> Milan
>
>
> ----- Original Message -----
> From: "Tom Fine" <[log in to unmask]>
> To: <[log in to unmask]>
> Sent: Saturday, March 12, 2011 1:49 AM
> Subject: Re: [ARSCLIST] Possibly another reason why Technics is exiting the turntable business
>
>
>> Quick update on this ...
>>
>> I had a chance to check out a Stanton ST150, which is a step up from the T92USB.
>> http://www.stantondj.com/stanton-turntables/st150.html
>>
>> This shares some of the same stuff as the T92, including SPDIF (but no USB) output. To my ears,
>> the built-in preamp sounded identical, so my bet is it's the same circuit board and SPDIF driver.
>> The tonearm itself looked similar but the counterweight was an upgrade, felt and acted more like
>> a Technics part, and there's an arm-lifter mechanism not present on the T92USB. Also present on
>> the ST150 is an arm-height adjustment, which is useful if you're using a taller- or
>> shorter-than-average cartridge. The whole arm pivot/gimble and lifter mechanism was much more
>> Technics-clone and than Technics-like. Apparently this turntable is so close to a real-deal
>> Technics 1200 that a couple of high-end places have started offering souped-up versions as
>> low-end "super-tables." Such things as a wooden box and disconnecting the digital circuitry and
>> replacing the feet, which may or may not actually effect sound quality. In the case of the
>> T92USB, the two most audible improvements I made were first and foremost swapping in a better
>> cartridge than the stock Stanton 500 (but keep the 500 to play 78's, swapping in a 78 needle of
>> course), and junking the cheap fabric "slip-mat" for a Technics heavy rubber mat. This killed off
>> a metallic resonance that was audible on all records, but more so on thinner records. The mat,
>> combined with a KAB push-on spindle clamp, really quieted down any "wiggly vinyl" noises and also
>> made the turntable more impervious to tapping on the surrounding surface.
>>
>> I concluded that the ST150 is a really close clone to a Technics, but may not be as mechanically
>> rugged. It supposedly has a more powerful motor than the T92USB, but its overall build, while
>> good, did not seem as bulletproof as a 1200. But it costs half as much as 1200's were going for
>> before they were discontinued, and requires not modifications to play 78's.
>>
>> Given that very similar units are sold under other brands, I suspect one Chinese company is
>> behind all of this, and they caused mighty Pansonic to surrender by driving prices too far down
>> for a Japan-made product to compete. One final point -- build-wise and ruggedness-wise, that
>> ST150 ran rings around comparably-priced belt-driven models from Eastern Europe, sold under the
>> Pro-Ject, Rega and MusicHall brands. The Euro-tables usually come with better-grade cartridges,
>> though. | https://listserv.loc.gov/cgi-bin/wa?A2=ind1103&L=ARSCLIST&P=139389 |
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Please be aware that we are transitioning away from RefWorks in Fall 2019 due to low usage and the bevy of free, user-friendly options. You can read more about this transition and see step-by-step instructions for how to export your RefWorks content into a different citation management system. Stay tuned for more information on workshops and other services we'll offer to help you transition!
K-State librarians recommend students and researchers use the citation management software that works best for them, such as Zotero, Mendeley, and EndNote; unfortunately, we currently do not have the resources to provide support for those systems. For your preferred citation management program, we recommend consulting their help and documentation sites. Additionally, many universities and researchers provide excellent tutorials on YouTube. | http://k-state.ask.libraryh3lp.com/questions/30490 |
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