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10.1038/ncomms3848
|
A quantitative telomeric chromatin isolation protocol identifies different telomeric states
|
Telomere composition changes during tumourigenesis, aging and in telomere syndromes in a poorly defined manner. Here we develop a quantitative telomeric chromatin isolation protocol (QTIP) for human cells, in which chromatin is cross-linked, immunopurified and analysed by mass spectrometry. QTIP involves stable isotope labelling by amino acids in cell culture (SILAC) to compare and identify quantitative differences in telomere protein composition of cells from various states. With QTIP, we specifically enrich telomeric DNA and all shelterin components. We validate the method characterizing changes at dysfunctional telomeres, and identify and validate known, as well as novel telomere-associated polypeptides including all THO subunits, SMCHD1 and LRIF1. We apply QTIP to long and short telomeres and detect increased density of SMCHD1 and LRIF1 and increased association of the shelterins TRF1, TIN2, TPP1 and POT1 with long telomeres. Our results validate QTIP to study telomeric states during normal development and in disease.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
] |
10.1021/bm401720z
|
Insights into the coassembly of hydrogelators and surfactants based on aromatic peptide amphiphiles
|
The coassembly of small molecules is a useful means of increasing the complexity and functionality of their resultant supramolecular constructs in a modular fashion. In this study, we explore the assembly and coassembly of serine surfactants and tyrosine-leucine hydrogelators, capped at the N-termini with either fluorenyl-9-methoxycarbonyl (Fmoc) or pyrene. These systems all exhibit self-assembly behavior, which is influenced by aromatic stacking interactions, while the hydrogelators also exhibit β-sheet-type arrangements, which reinforce their supramolecular structures. We provide evidence for three distinct supramolecular coassembly models; cooperative, disruptive, and orthogonal. The coassembly mode adopted depends on whether the individual constituents (I) are sufficiently different, such that effective segregation and orthogonal assembly occurs; (II) adhere to a communal mode of self-assembly; or (III) act to compromise the assembly of one another via incorporation and disruption. We find that a greater scope for controllable coassembly exists within orthogonal systems; which show minimal relative changes in the native gelator's supramolecular structure by Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), and fluorescence spectroscopy. This is indicative of the segregation of orthogonal coassembly constituents into distinct domains, where surfactant chemical functionality is presented at the surface of the gelator's supramolecular fibers. Overall, this work provides new insights into the design of modular coassembly systems, which have the potential to augment the chemical and physical properties of existing gelator systems.
|
[
"Physical and Analytical Chemical Sciences",
"Materials Engineering"
] |
10.3390/molecules18055611
|
Chitosan for gene delivery and orthopedic tissue engineering applications
|
Gene therapy involves the introduction of foreign genetic material into cells in order exert a therapeutic effect. The application of gene therapy to the field of orthopaedic tissue engineering is extremely promising as the controlled release of therapeutic proteins such as bone morphogenetic proteins have been shown to stimulate bone repair. However, there are a number of drawbacks associated with viral and synthetic non-viral gene delivery approaches. One natural polymer which has generated interest as a gene delivery vector is chitosan. Chitosan is biodegradable, biocompatible and non-toxic. Much of the appeal of chitosan is due to the presence of primary amine groups in its repeating units which become protonated in acidic conditions. This property makes it a promising candidate for non-viral gene delivery. Chitosan-based vectors have been shown to transfect a number of cell types including human embryonic kidney cells (HEK293) and human cervical cancer cells (HeLa). Aside from its use in gene delivery, chitosan possesses a range of properties that show promise in tissue engineering applications; it is biodegradable, biocompatible, has anti-bacterial activity, and, its cationic nature allows for electrostatic interaction with glycosaminoglycans and other proteoglycans. It can be used to make nano- and microparticles, sponges, gels, membranes and porous scaffolds. Chitosan has also been shown to enhance mineral deposition during osteogenic differentiation of MSCs in vitro. The purpose of this review is to critically discuss the use of chitosan as a gene delivery vector with emphasis on its application in orthopedic tissue engineering.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Materials Engineering"
] |
3731107
|
Normalization of multimodal brain networks for integral and predictive mapping of neurological disorders
|
Modern network science has introduced exciting new opportunities for understanding the brain as a complex system of interacting units in both health and disease and across the human lifespan. Despite the rapidly growing interdisciplinary science of complex networks, which spans the range from genetic and metabolic networks all the way up to social and economic systems, it remains a formidable challenge to identify the most representative and shared brain alterations caused by a specific disorder (e.g., Alzheimer’s disease), namely ‘disorder signature’, in a population of brain networks, let alone multi-modal brain networks where each brain network is derived from a particular neuroimaging modality (e.g., functional or diffusion magnetic resonance imaging (fMRI or dMRI)). Such integral signature can be revealed by what I name as a multimodal connectional brain template (CBT), which would constitute an unprecedented contribution to network neuroscience, rooted in firstly learning brain connectivity normalization and secondly foreseeing its evolution. During this fellowship, I will develop NormNets, a novel technique leveraging the power of geometric deep-learning to meet this challenge by normalizing a population of multimodal brain networks. Particularly, NormNets tools will substantially advance the field of network neuroscience by estimating not only an integral but also a predictive mapping of neurological disorders. In addition to the multi-disciplinary high-quality training I will receive at both host and secondment institutions, this fellowship will remarkably consolidate and accelerate my career on the international landscape scene in the new cross-disciplinary area of “geometric deep learning & integration connectomics” I will pioneer during this fellowship. With the endorsement of international multi-sectoral stakeholders, open NormNets resources will impact on and contribute towards the development of connectomics-rooted predictive precision medicine.
|
[
"Neuroscience and Disorders of the Nervous System",
"Computer Science and Informatics"
] |
W803108629
|
Multi-Level Search Space Reduction Framework for Face Image Database
|
In face recognition, searching and retrieval of relevant images from a large database form a major task. Recognition time is greatly related to the dimensionality of the original data and the number of training samples. This demands the selection of discriminant features that produce similar results as the entire set and a reduced search space. To address this issue, a Multi-Level Search Space Reduction framework for large scale face image database is proposed. The proposed approach identifies discriminating features and groups face images sharing similar properties using feature-weighted Fuzzy C-Means approach. A hierarchical tree model is then constructed inside every cluster based on the discriminating features which enables a branch based selection, thereby reducing the search space. The proposed framework is tested on three benchmark and two self-created databases. The experimental results show that the proposed method achieved an average accuracy of 93% and an average search time reduction of 66% compared to existing approaches for search space reduction of face recognition.
|
[
"Computer Science and Informatics"
] |
10.1007/978-3-030-04224-0_41
|
Linear periodic discriminant analysis of multidimensional signals
|
Extracting relevant information from noisy multidimensional signals has tremendous impacts in numerous applications, ranging from audio separation to electrophysiological recording analysis. Linear filters are often considered to reconstruct and interpret the latent sources generating the data. Known properties of the sources can be used to guide their separation. In neuroscience, the cortical processes underlying perception in different modalities (visual, auditory,. . ) is often studied using electroencephalography (EEG) during periodic stimulation, eliciting periodic activity in neural sources, some of which being specific to the considered modality. Whereas current approaches extract sources either periodic or discriminative, none of them accounts for both aspects at once. This paper proposes several methods extracting periodic sources specific between two classes, hence termed as Linear Periodic Discriminant Analysis methods. They are validated on synthetic data and EEG recordings of subjects to whom periodic stimulation from two modalities is applied. The methods highlight modality-specific periodic responses.
|
[
"Neuroscience and Disorders of the Nervous System",
"Mathematics"
] |
10.1523/JNEUROSCI.1322-14.2014
|
Regulation Of Axonal Midline Guidance By Prolyl 4 Hydroxylation In Caenorhabditis Elegans
|
Neuronal wiring during development requires that the growth cones of axons and dendrites are correctly guided to their appropriate targets. As in other animals, axon growth cones in Caenorhabditis elegans integrate information in their extracellular environment via interactions among transiently expressed cell surface receptors, their ligands, and the extracellular matrix (ECM). Components of the ECM undergo a wide variety of post-translational modifications that may affect efficacy of binding to neuronal guidance molecules. The most common modification of the ECM is prolyl 4-hydroxylation. However, little is known of its importance in the control of axon guidance. In a screen of prolyl 4-hydroxylase (P4H) mutants, we found that genetic removal of a specific P4H subunit, DPY-18, causes dramatic defects in C. elegans neuroanatomy. In dpy-18 mutant animals, the axons of specific ventral nerve cord neurons do not respect the ventral midline boundary and cross over to the contralateral axon fascicle. We found that these defects are independent of the known role of dpy-18 in regulating body size and that dpy-18 acts from multiple tissues to regulate axon guidance. Finally, we found that the neuronal defects in dpy-18 mutant animals are dependent on the expression of muscle-derived basement membrane collagens and motor neuron-derived ephrin ligands. Loss of dpy-18 causes dysregulated ephrin expression and this is at least partially responsible for the neurodevelopmental defects observed. Together, our data suggest that DPY-18 regulates ephrin expression to direct axon guidance, a role for P4Hs that may be conserved in higher organisms.
|
[
"Neuroscience and Disorders of the Nervous System",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
Q101445
|
DESPUÉS DE UN HILO DE ŁOWICZ. APOYO A LA EXPORTACIÓN PARA LA INDUSTRIA TEXTIL
|
El objetivo principal del proyecto que se implementará para los años 2018-2019 es la promoción económica de la industria textil desde Łódő, teniendo en cuenta el papel de Łowicz mediante la creación de condiciones para la internacionalización de las actividades empresariales y la construcción de vínculos económicos. Objetivos específicos: Establecimiento de nuevos contactos comerciales por parte de las empresas; Establecer nuevas relaciones con posibles inversores extranjeros, lo que contribuirá al aumento del número de inversiones extranjeras, la promoción de Łódő como región en desarrollo dinámico; Aumentar el nivel de comercio exterior en el sector de las PYME mediante la firma de nuevos contratos comerciales; La adquisición de nuevos puntos de venta por parte de las PYME a través de la organización y la participación en proyectos destinados a aumentar el perfil económico internacional de la región; Una mayor identificación de los empresarios de la zona de Łowicz como una buena marca, mejorando así la imagen del municipio y de la región como apoyo a las empresas locales; Aumentar el conocimiento de las ofertas de las empresas; Mejor reconocimiento de la ciudad, región, empresas; Desarrollo de redes y cooperación, por ejemplo, en forma de enlaces de cooperación, agrupaciones; Aumentar el nivel de comercio exterior de los empresarios, haciendo especial hincapié en la industria textil; Expansión y adquisición de nuevos mercados; Tareas: Participación en ferias textiles zagr; Participación en ferias textiles internacionales en Polonia; Campaña de promoción e información; Gestión de proyectos; Los participantes son residentes del Lodz reg, que, gracias a la promoción económica, también serán beneficiarios de su desarrollo. Indicadores: Número de proyectos de información y promoción apoyados de carácter internacional 1 Número de contratos de comercio exterior 3 y firmados por empresas apoyadas en el ámbito de la internacionalización 5 Número de empresas que reciben apoyo y subvenciones 1 Número de empresas beneficiarias de subvenciones 1 Número de empresas que han entrado en nuevos mercados extranjeros 3
|
[
"Individuals, Markets and Organisations",
"Human Mobility, Environment, and Space"
] |
10.1002/admt.201800328
|
Aerosol-Jet Printed Fine-Featured Triboelectric Sensors for Motion Sensing
|
Triboelectric motion sensors, based on the generation of a voltage across two dissimilar materials sliding across each other as a result of the triboelectric effect, have generated interest due to the relative simplicity of the typical grated device structures and materials required. However, these sensors are often limited by poor spatial and/or temporal resolution of motion due to limitations in achieving the required device feature sizes through conventional lithography or printing techniques. Furthermore, the reliance on metallic components that are relatively straightforward to pattern into fine features limits the possibility to develop transparent sensors. Polymers would allow for transparent devices, but these materials are significantly more difficult to pattern into fine features when compared to metals. Here, an aerosol-jet printing (AJP) technique is used to develop triboelectric sensors using a wide variety of materials, including polymers, which can be directly printed into finely featured grated structures for enhanced sensitivity to displacement and speed of motion. A detailed investigation is presented highlighting the role of material selection and feature size in determining the overall resolution of the resulting motion sensor. A three-channel rotary sensor is also presented, demonstrating the versatility of the AJP technique in developing more complex triboelectric motion sensors.
|
[
"Materials Engineering",
"Condensed Matter Physics",
"Synthetic Chemistry and Materials"
] |
978714
|
New heterogeneous catalyst materials for hydrogenation of co2 to formic acid: metallophthalocyanine-based 2d- and 3d covalent organic frameworks
|
In CO2COFs project we will meet the world’s need for new heterogeneous catalyst materials for catalytic CO2 hydrogenation to formic acid (FA) by developing novel metallophthalocyanine (MPc)-based covalent organic frameworks (COFs) with high crystallinity and large surface area for renewable hydrogen storage in formic acid (FA). Althought heterocatalytic CO2 hydrogenation to FA is one of the most promising conversions, relatively few catalytic materials have been reported for this transformation. Furthermore, there are many studies of the development of the homogeneous catalyst for CO2 hydrogenation to FA, but heterogenization of homogeneous Ru complexes by incorporating them onto supporting material is essentially unexplored. In CO2COFs project we will answer the demand by synthesizing MPc-based 2D- and 3D COFs which are highly crystalline materials offering a defined porous structure with definite binding sites for organometallic complexes. Prepared materials will be fully characterized and investigated in hydrogenation of CO2 to FA. One of the main targets of CO2COFs is to achieve recyclable heterogeneous catalysts with catalytic activities and efficiencies among the best reported worldwide. The results of CO2COFs project is expected attract the attention of companies related with catalysts and formic acid processing.
|
[
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
10.1016/j.immuni.2018.12.010
|
Human Fetal TNF-α-Cytokine-Producing CD4 <sup>+</sup> Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life
|
Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α) + CD4 + CD69 + T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4 + T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4 + T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation. CD4 + Tem cell frequencies were higher in inflamed intestines from preterm infants with NEC than in healthy infant intestines and showed enhanced TNF signaling. These findings reveal a distinct population of TNF-α-producing CD4 + T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth. The fetal immune system is considered anti-inflammatory; nonetheless, preterm infants are at risk for necrotizing enterocolitis (NEC), a severe intestinal inflammatory disease. Schreurs et al. demonstrate that fetal TNF-α + CD4 + T cells promote gut development early in life. However, in preterm babies these TNFα + CD4 + T cells can mediate intestinal inflammation, providing a potential mechanism for NEC.
|
[
"Immunity, Infection and Immunotherapy",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
] |
10.1039/C6LC90022D
|
Artificial Micro Swimmers In Simulated Natural Environments
|
Microswimmers, such as bacteria, are known to show different behaviours depending on their local environment. They identify spatial chemical gradients to find nutrient rich areas (chemotaxis) and interact with shear flows to accumulate in high shear regions. Recently, artificial microswimmers have been developed which mimic their natural counterparts in many ways. One of the exciting topics in this field is to study these artificial motors in several natural settings like the ones bacteria interact with. In this Focus article, we summarize recent observations of artificial swimmers in chemical gradients, shear flows and other interesting natural environments simulated in the lab using microfluidics and nanotechnology.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
313626
|
THE GENDER OF JUSTICE: THE PROSECUTION OF SEXUAL VIOLENCE IN ARMED CONFLICT
|
The international community now recognises the impact of ‘gender-based harms’ of conflict, the armed violence that targets or disproportionately affects women. It also acknowledges the obligation to prosecute these crimes. However, many claim that international justice continues to fail women victims of war. So are we witnessing a new age of accountability for these crimes against women? Or does international criminal justice reproduce existing gender inequalities? Some fifteen years after the establishment of the first international criminal tribunal, these questions remain unanswered. The proposed research takes up these fundamental problems of gender and justice, and develops an innovative research ‘gender justice’ framework. This framework engages with the thoroughly social nature of gender and justice. It examines how social actions and norms construct categories of the person, the harmful, and the just by building a social theory of ‘gender justice’. This theory investigates the nature of gender harms, identifies how sexual differentiation shapes law, and provides a normative model of gender justice. It is built upon a unique socio-legal case study of the international and national prosecution of sexual violence in the Yugoslavian conflict. Sexual violence in armed conflict is the most pervasive and visible of criminalised gender-based harms. It is also the area in which international law claims to have made its most significant advances. This case study provides a systematic and rigorous means of building models of highly complex social processes, and of developing explanatory and normative theories of ‘gender justice’. The project proposes a new framework that takes ‘gender justice’ as an object of research. It creates a new field of inquiry, with specific research problems, new conceptual and methodological frameworks, and identifiable normative criteria. Ultimately, the project aims to change our ideas of ‘gender justice’ itself.
|
[
"The Social World and Its Interactions",
"Institutions, Governance and Legal Systems"
] |
2728201
|
Functional keratin kerasol
|
Keratin as a key structural material has been used in cosmetics as a raw material in skin and hair care products in a generalized way since several years, marking a trend in all cosmetic manufacturers offering keratin treatment lines. The human body takes advantage of this cosmetic contribution of keratin through contact with products that Incorporate it, getting the protein to adhere to the damaged areas in order to regenerate the skin and hair. Now, although the exploitation of these keratin sources is a well-known industrial process, most of the methods of obtaining keratin from agricultural waste are based on very aggressive thermal or chemical treatments. As a result of the aggressiveness of these treatments, the protein obtained is much denatured and has lost most of the properties that make keratin a protein of industrial interest.
In this context with our project, we bring to the market a new solution, which will not only reduce the environmental impact of a waste produced in slaughterhouses, but optimize the keratin production process for cosmetics purposes too, in a sustainable, reliable and cost-effective way
Based on an exclusive patent whose rights we have acquired, we obtain a new keratin product as no one has yet achieved it. By its method of obtaining we have got a unique product in the world that preserves all the functional properties of keratin and therefore its bio availability for the human being. We obtain our product at a low cost thanks to the low energy needs in the production and to the raw material that we use at cost 0, the hair and the hooves of pigs, a residual waste of meat processing. Our processing plant will produce 1.500Kg/day of keratin KERASOL, a registered trademark of our property, which will make the difference in the cosmetic keratin market valued at €500M in 2017 an estimated to reach €600M by 2023. This will give us an annual net income of €5 million/year with a production of 386 tons/year for each plant installed.
|
[
"Products and Processes Engineering",
"Materials Engineering",
"Synthetic Chemistry and Materials"
] |
10.1016/j.pt.2015.11.004
|
Microbiota Control of Malaria Transmission
|
Stable mutualistic interactions between multicellular organisms and microbes are an evolutionarily conserved process with a major impact on host physiology and fitness. Humans establish such interactions with a consortium of microorganisms known as the microbiota. Despite the mutualistic nature of these interactions, some bacterial components of the human microbiota express immunogenic glycans that elicit glycan-specific antibody (Ab) responses. The ensuing circulating Abs are protective against infections by pathogens that express those glycans, as demonstrated for Plasmodium, the causative agent of malaria. Presumably, a similar protective Ab response acts against other vector-borne diseases.
|
[
"Immunity, Infection and Immunotherapy",
"Physiology in Health, Disease and Ageing",
"Environmental Biology, Ecology and Evolution"
] |
10.1039/c5nr04906g
|
Unbinding forces and energies between a siRNA molecule and a dendrimer measured by force spectroscopy
|
Single molecule force spectroscopy has been applied to measure the unbinding forces and energies between a siRNA molecule and polyamidoamine dendrimers deposited on a mica surface.
|
[
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
10.1007/978-1-4939-6881-7_6
|
Plasma Membrane Sheets For Studies Of B Cell Antigen Internalization From Immune Synapses
|
Surrogate planar and membrane systems have been employed to study the architecture of immune synapses; however, they often do not recapitulate trans-synaptic extraction and endocytosis of ligands by the immune cells. Transendocytosis (or trogocytosis) of antigen from immune synapses is particularly critical for antigen processing and presentation by B cells. Here we describe a protocol for preparation of plasma membrane sheets (PMSs), which are flexible and fluid membrane substrates that support robust B cell antigen extraction. We show how to attach B cell antigens to the PMSs and how to investigate antigen extraction and endocytosis by fluorescent microscopy and computational image analysis. These techniques should be broadly applicable to studies of transendocytosis in a variety of cellular systems.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1088/1367-2630/14/6/063024
|
Tsirelson S Bound From A Generalized Data Processing Inequality
|
The strength of quantum correlations is bounded from above by Tsirelson's bound. We establish a connection between this bound and the fact that correlations between two systems cannot increase under local operations, a property known as the data processing inequality (DPI). More specifically, we consider arbitrary convex probabilistic theories. These can be equipped with an entropy measure that naturally generalizes the von Neumann entropy, as shown recently in Short and Wehner (2010 New J. Phys. 12 033023) and Barnum et al (2010 New J. Phys. 12 033024). We prove that if the DPI holds with respect to this generalized entropy measure then the underlying theory necessarily respects Tsirelson's bound. We, moreover, generalize this statement to any entropy measure satisfying certain minimal requirements. A consequence of our result is that not all the entropic relations used for deriving Tsirelson's bound via information causality in Pawlowski et al (2009 Nature 461 1101–4) are necessary.
|
[
"Mathematics",
"Fundamental Constituents of Matter"
] |
10.1016/bs.mcb.2014.11.003
|
Mapping forces and kinematics during collective cell migration
|
Fundamental biological processes including morphogenesis and tissue repair require cells to migrate collectively. In these processes, epithelial or endothelial cells move in a cooperative manner coupled by intercellular junctions. Ultimately, the movement of these multicellular systems occurs through the generation of cellular forces, exerted either on the substrate via focal adhesions (cell-substrate forces) or on neighboring cells through cell-cell junctions (cell-cell forces). Quantitative measurements of multicellular forces and kinematics with cellular or subcellular resolution have become possible only in recent years. In this chapter, we describe some of these techniques, which include particle image velocimetry to map cell velocities, traction force microscopy to map forces exerted by cells on the substrate, and monolayer stress microscopy to map forces within and between cells. We also describe experimental protocols to perform these measurements. The combination of these techniques with high-resolution imaging tools and molecular perturbations will lead to a better understanding of the mechanisms underlying collective cell migration in health and disease.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
US 201916533725 A
|
Connection and resistance training system
|
A wearable connection and resistance training system having a waist strap, and left and right upper leg straps and an attachment point device which serves as a connection piece configured to be held underneath a user's torso and between the user's legs to provide rotational resistance to improve and strengthen rotational abilities of a user. An alignment attachment piece and foot straps can also be attached to provide downward force/tension.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
W2001570648
|
The next controversy in genetic testing: clinical data as trade secrets?
|
Sole-source business models for genetic testing can create private databases containing information vital to interpreting the clinical significance of human genetic variations. But incomplete access to those databases threatens to impede the clinical interpretation of genomic medicine. National health systems and insurers, regulators, researchers, providers and patients all have a strong interest in ensuring broad access to information about the clinical significance of variants discovered through genetic testing. They can create incentives for sharing data and interpretive algorithms in several ways, including: promoting voluntary sharing; requiring laboratories to share as a condition of payment for or regulatory approval of laboratory services; establishing - and compelling participation in - resources that capture the information needed to interpret the data independent of company policies; and paying for sharing and interpretation in addition to paying for the test itself. US policies have failed to address the data-sharing issue. The entry of new and established firms into the European genetic testing market presents an opportunity to correct this failure.
|
[
"Prevention, Diagnosis and Treatment of Human Diseases",
"Integrative Biology: from Genes and Genomes to Systems",
"Institutions, Governance and Legal Systems"
] |
10.1002/adma.201700486
|
Tuning Up or Down the Critical Thickness in LaAlO<inf>3</inf>/SrTiO<inf>3</inf> through In Situ Deposition of Metal Overlayers
|
The quasi 2D electron system (q2DES) that forms at the interface between LaAlO3 and SrTiO3 has attracted much attention from the oxide electronics community. One of its hallmark features is the existence of a critical LaAlO3 thickness of 4 unit-cells (uc) for interfacial conductivity to emerge. In this paper, the chemical, electronic, and transport properties of LaAlO3/SrTiO3 samples capped with different metals grown in a system combining pulsed laser deposition, sputtering, and in situ X-ray photoemission spectroscopy are investigated. The results show that for metals with low work function a q2DES forms at 1–2 uc of LaAlO3 and is accompanied by a partial oxidation of the metal, a phenomenon that affects the q2DES properties and triggers the formation of defects. In contrast, for noble metals, the critical thickness is increased above 4 uc. The results are discussed in terms of a hybrid mechanism that incorporates electrostatic and chemical effects.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
268782
|
The Role of Arl Proteins in Retinal and other Ciliary Diseases
|
Arl (Arf-like) proteins, GTP-binding proteins of the Ras superfamily, are molecular switches that cycle between a GDP-bound inactive and GTP-bound active state. There are 16 members of the Arl subfamily in the human genome whose basic mechanistic function is unknown. The interactome of Arl2/3 includes proteins involved in retinopathies and other ciliary diseases such as Leber¿s Congenital Amaurosis (LCA) and kidney diseases such as nephronophthisis. Arl6 has been found mutated in Bardet Biedl Syndrome, another pleiotropic ciliary disease. In the proposed interdisciplinary project I want to explore the function of the protein network of Arl2/3 and Arl6 by a combination of biochemical, biophysical and structural methods and use the knowledge obtained to probe their function in live cells. As with other subfamily proteins of the Ras superfamily which have been found to mediate similar biological functions I want to derive a basic understanding of the function of Arl proteins and how it relates to the development and function of the ciliary organelle and how they contribute to ciliary diseases. The molecules in the focus of the project are: the GTP-binding proteins Arl2, 3, 6; RP2, an Arl3GAP mutated in Retinitis pigmentosa; Regulators of Arl2 and 3; PDE¿ and HRG4, effectors of Arl2/3, which bind lipidated proteins; RPGR, mutated in Retinitis pigmentosa, an interactor of PDE¿; RPGRIP and RPGRIPL, interactors of RPGR mutated in LCA and other ciliopathies; Nephrocystin, mutated in nephronophthisis, an interactor of RPGRIP and Arl6, mutated in Bardet Biedl Syndrome, and the BBS complex. The working hypothesis is that Arl protein network(s) mediate ciliary transport processes and that the GTP switch cycle of Arl proteins is an important element of regulation of these processes.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
] |
W1601442301
|
Characteristics of interfacial signatures on a wind-driven gravity-capillary wave
|
[1] Direct numerical simulation of a wind-driven gravity-capillary wave and the underlying turbulent flow is conducted to identify the characteristic signatures of various surface parameters, including temperature, gas flux, velocities, and roughness, and to reveal the impacts of the nonbreaking surface waves on these surface flow and tracer parameters. Three characteristic surface signatures and the corresponding flow processes are identified: the carrier gravity wave, the parasitic capillary wavelets, and the elongated streaks. The elongated streaks are induced by both the coherent streamwise vortices formed within the turbulent shear layer and the Langmuir circulations arising from nonlinear interaction between the carrier gravity wave and the drift current. All three surface signatures can be observed in the distributions of various quantities, although some are more apparent than the others. Image-processing techniques, employing empirical mode decomposition and phase averaging, are developed to decompose the distinct signatures thus to quantify the contributions by the responsible flow processes. It is found that elongated streaks prevail the distribution of surface temperature and gas flux, indicating that Langmuir cells and the coherent eddies contribute to the major interfacial heat and gas transport. These eddies also induced strong cross-stream velocity divergence at the water surface, which exhibits resemblant elongated distribution as that of gas flux (correlation coefficient � 0.6). High correlation between the surface distributions of temperature and gas flux is observed (correlation coefficient � 0.8 to 0.9), suggesting that the spatial and temporal distribution of surface temperature is a good proxy tracer of interfacial gas transfer.
|
[
"Earth System Science",
"Physical and Analytical Chemical Sciences"
] |
10.1021/jp400418w
|
Minor-groove binding drugs: Where is the second hoechst 33258 molecule?
|
Hoechst 33258 binds with high affinity into the minor groove of AT-rich sequences of double-helical DNA. Despite extensive studies of this and analogous DNA binding molecules, there still remains uncertainty concerning the interactions when multiple ligand molecules are accommodated within close distance. Albeit not of direct concern for most biomedical applications, which are at low drug concentrations, interaction studies for higher drug binding are important as they can give fundamental insight into binding mechanisms and specificity, including drug self-stacking interactions that can provide base-sequence specificity. Using circular dichroism (CD), isothermal titration calorimetry (ITC), and proton nuclear magnetic resonance (1H NMR), we examine the binding of Hoechst 33258 to three oligonucleotide duplexes containing AT regions of different lengths: [d(CGCGAATTCGCG)]2 (A2T2), [d(CGCAAATTTGCG)]2 (A3T 3), and [d(CGAAAATTTTCG)]2 (A4T4). We find similar binding geometries in the minor groove for all oligonucleotides when the ligand-to-duplex ratio is less than 1:1. At higher ratios, a second ligand can be accommodated in the minor groove of A4T4 but not A2T2 or A3T3. We conclude that the binding of the second Hoechst to A4T4 is not cooperative and that the molecules are sitting with a small separation apart, one after the other, and not in a sandwich structure as previously proposed.
|
[
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
306990
|
Material-driven Fibronectin Fibrillogenesis to Engineer Synergistic Growth Factor Microenvironments
|
Cells within tissues are surrounded by fibrillar extracellular matrices (ECM) that support cell adhesion, migration, proliferation and differentiation. Fibronectin (FN) is an ECM protein organized into fibrillar networks by cells through an integrin-mediated process. This assembly allows the unfolding of the molecule, exposing cryptic domains not available in the native globular FN structure and activating intracellular signalling complexes.
This project aims to engineer functional interfaces between living cells and synthetic biomaterials, making use of the fundamental role of fibronectin (FN) to direct cell-material interactions. First, we will engineer material surfaces able to direct the physiological organization of FN into fibrillar networks in absence of cells, so-called material driven fibronectin fibrillogenesis. These surfaces will trigger the organization of FN upon simple adsorption of FN from solutions and will provide a biomimetic interface better recognized by cells, since it resembles the nature ECM environment in tissues. The mechanisms that promote the organization of FN at the material interface will be elucidated making use of different FN fragments and key modifications of the protein. The enhanced cellular activities of the material-driven FN matrices will be used to direct the behavior of human mesenchymal stem cells (hMSCs), seeking to direct either cell lineage or multipotency in combination with the properties of the underlying surface.
Secondly, we will engineer functional – living biointerphases, on which the intermediate layer of proteins between the material surfaces and the cell population is expressed on the surface of non-pathogenic bacteria. This radical idea will provide the field with a living interphase that consists of genetically modified bacteria with FN fragments in the membrane.
These bacteria will be modified to secrete the desired proteins or factors in response to external stimuli, to direct the cell behavior of hMSCs.
|
[
"Materials Engineering",
"Cell Biology, Development, Stem Cells and Regeneration",
"Biotechnology and Biosystems Engineering"
] |
219819
|
Attodna: how electronic motions affect the photostability of the genomic material
|
AttoDNA considers the early (attosecond to few-femtosecond) events following photo-excitation/ionisation in DNA/RNA canonical and non-canonical nucleobases for the first time. This involves the electronic movement before the onset of nuclear dynamics, ascertaining the length in which this initial purely electronic motion extends in time and how it affects the ensuing nuclear dynamics and its outcome with regards to the photostability shown by the genomic material from a bottom-up approach. By monitoring the electronic and nuclear motions in canonical and non-canonical nucleobases, the way in which they couple can be elucidated and the specific motions contributing to photostability extracted from a novel standpoint.
Photostability is one of the main properties thought to play a crucial role in the selection of the nucleobase monomers in prebiotic extreme UV exposure, by encoding the genome using the most suitable (photostable) building blocks as an elegant solution to aid in its photo-protective design and thus defend itself against the threat of photochemical damage. Beyond its intrinsic importance given its essential role towards preserving our genomic material, an in-depth knowledge of this outstanding property also provides a unique perspective on the events where these photo-protection mechanisms fail, namely the photo-damage instances, and in the subsequent repair mechanisms mediated by electron transfers as those put in place by enzymes and/or in specific non-invasive treatments like photodynamic therapies, the most widespread treatment for cancer.
The project therefore aims at extending the foundations rationalising DNA's photostability by exploring the potential role of the electronic dynamics prior to the onset of nuclear dynamics for the first time and is expected to have a large impact in the fields of photochemistry and photobiology.
|
[
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
617659
|
The Great War and Modern Philosophy
|
The First World War was an unprecedented event of destruction, transformation, and renewal that left no aspect of European culture unchanged. Philosophy proved no exception: the war motivated an historically singular mobilization of philosophers to write about the war during the years of conflict; significant works of philosophy were written during the war years and immediately thereafter; the postwar decades of the 1920s and 1930s witnessed a systematic reconfiguration of the landscape of philosophical thought that still largely defines contemporary philosophy. Surprisingly, while the impact of the war on literature, poetry, and the arts, political thought has been a subject of intense inquiry and interpretation, the significance of the war for modern philosophy remains relatively unexamined, often misunderstood or simply taken for granted.
This project aims at understanding the impact of the Great War on modern philosophy. It aims to chart an original course and establish a new standard for the philosophical study of the relation between the First World War and 20th-century philosophy through a comparative and critical approach to a diverse array of thinkers. Specifically, this project will investigate the hypothesis of whether diverse philosophical responses, direct and indirect, immediately or postponed, can be understood as formulations of different questions posed, or better: catalyzed by the war itself. This project will additionally argue that the very idea that war could reveal, challenge or legitimate cultural or philosophical meaning is itself a legacy of a distinctive kind of war-philosophy produced during the war.
This project will be divided into four sub-projects: (1) ""Philosophy of War and the Wars of Philosophy,""; (2) ""The Philosophy of Language and the Languages of Philosophy""; (3) ""The Care of the Soul""; (4) ""Europe after Europe.""
|
[
"Texts and Concepts",
"The Study of the Human Past"
] |
881787
|
Engineering bio-inspired systems for the conversion of solar energy to hydrogen
|
With this proposal, I aim to achieve the efficient conversion of solar energy to hydrogen. The overall objective is to engineer bio-inspired systems able to convert solar energy into a separation of charges and to construct devices by coupling these systems to catalysts in order to drive sustainable and effective water oxidation and hydrogen production.
The global energy crisis requires an urgent solution, we must replace fossil fuels for a renewable energy source: Solar energy. However, the efficient and inexpensive conversion and storage of solar energy into fuel remains a fundamental challenge. Currently, solar-energy conversion devices suffer from energy losses mainly caused by disorder in the materials used. The solution to this problem is to learn from nature. In photosynthesis, the photosystem II reaction centre (PSII RC) is a pigment-protein complex able to overcome disorder and convert solar photons into a separation of charges with near 100% efficiency. Crucially, the generated charges have enough potential to drive water oxidation and hydrogen production.
Previously, I have investigated the charge separation process in the PSII RC by a collection of spectroscopic techniques, which allowed me to formulate the design principles of photosynthetic charge separation, where coherence plays a crucial role. Here I will put these knowledge into action to design efficient and robust chromophore-protein assemblies for the collection and conversion of solar energy, employ organic chemistry and synthetic biology tools to construct these well defined and fully controllable assemblies, and apply a complete set of spectroscopic methods to investigate these engineered systems.
Following the approach Understand, Engineer, Implement, I will create a new generation of bio-inspired devices based on abundant and biodegradable materials that will drive the transformation of solar energy and water into hydrogen, an energy-rich molecule that can be stored and transported.
|
[
"Materials Engineering",
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences",
"Biotechnology and Biosystems Engineering"
] |
10.1088/1475-7516/2019/10/065
|
General Relativistic Cosmological N Body Simulations Part I Time Integration
|
This is the first in a series of papers devoted to fully general-relativistic N-body simulations applied to late-time cosmology. The purpose of this paper is to present the combination of a numerical relativity scheme, discretization method and time-integration algorithm that provides satisfyingly stable evolution. More precisely, we show that it is able to pass a robustness test and to follow scalar linear modes around an expanding homogeneous and isotropic space-time. Most importantly, it is able to evolve typical cosmological initial conditions on comoving scales down to tenths of megaparsecs with controlled constraint and energy-momentum conservation violations all the way down to the regime of strong inhomogeneity.
|
[
"Universe Sciences",
"Fundamental Constituents of Matter"
] |
US 2017/0048635 W
|
CORD LOCK
|
A cord lock includes various components used to slidably adjust a length of cord. The cord lock may include a first cord-clamp bar and a second cord-clamp bar that are movably coupled to each other, to allow control of frictional resistance on a cord threaded through various apertures and cord-receiving channels of the cord lock. The cord lock may be incorporated into an article such that it is at least partially concealed within an article layer.
|
[
"Products and Processes Engineering"
] |
10.1039/C5CP03392F
|
Insights Into Colour Tuning Of Chlorophyll Optical Response In Green Plants
|
First-principles calculations within the framework of real-space time-dependent density functional theory have been performed for the complete chlorophyll (Chl) network of the light-harvesting complex from green plants, LHC-II. A local-dipole analysis method developed for this work has made possible the studies of the optical response of individual Chl molecules subjected to the influence of the remainder of the chromophore network. The spectra calculated using our real-space TDDFT method agree with previous suggestions that weak interaction with the protein microenvironment should produce only minor changes in the absorption spectrum of Chl chromophores in LHC-II. In addition, relative shifting of Chl absorption energies leads the stromal and lumenal sides of LHC-II to absorb in slightly different parts of the visible spectrum providing greater coverage of the available light frequencies. The site-specific alterations in Chl excitation energies support the existence of intrinsic energy transfer pathways within the LHC-II complex.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
Q2692024
|
Subvenção para o fundo de maneio do INDPROD Sławomir Adamczak
|
O projeto diz respeito ao apoio do empresário no fornecimento de liquidez financeira e ao apoio às atividades atuais devido às dificuldades financeiras sentidas pelo empresário em resultado do surto de COVID-19. Assistência financeira prestada ao abrigo do programa n.º SA.57015 (2020/N)
|
[
"Individuals, Markets and Organisations"
] |
10.18653/v1/s17-1012
|
Distributed prediction of relations for entities: The easy, the difficult, and the impossible
|
Word embeddings are supposed to provide easy access to semantic relations such as "male of" (man-woman). While this claim has been investigated for concepts, little is known about the distributional behavior of relations of (Named) Entities. We describe two word embedding-based models that predict values for relational attributes of entities, and analyse them. The task is challenging, with major performance differences between relations. Contrary to many NLP tasks, high difficulty for a relation does not result from low frequency, but from (a) one-to-many mappings; and (b) lack of context patterns expressing the relation that are easy to pick up by word embeddings.
|
[
"Computer Science and Informatics"
] |
10.1016/j.sbi.2019.09.001
|
Amyloid structures: much more than just a cross-β fold
|
In recent years our understanding of amyloid structure has been revolutionised by innovations in cryo-electron microscopy, electron diffraction and solid-state NMR. These techniques have yielded high-resolution structures of fibrils isolated from patients with neurodegenerative disease, as well as those formed from amyloidogenic proteins in vitro. The results not only show the expected cross-β amyloid structure, but also reveal that the amyloid fold is unexpectedly diverse and complex. Here, we discuss this diversity, highlighting dynamic regions, ligand binding motifs, cavities, non-protein components, and structural polymorphism. Collectively, these variations combine to allow the generic amyloid fold to be realised in three dimensions in different ways, and this diversity may be related to the roles of fibrils in disease.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1016/j.ejpb.2017.09.014
|
Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson's disease related toxin 6-hydroxydopamine
|
Neurodegenerative diseases, as Parkinson's disease (PD), involve irreversible neural cell damage and impairment. In PD, there is a selective degeneration of the dopaminergic neurons leading to motor symptoms. A common finding in PD neurodegeneration is the increase of reactive oxygen species (ROS), leading to oxidative stress. To date there are only interventions to relieve PD symptoms, however progress has been made in the development of therapies that target the immune system or use its components as therapeutic agents; among these, mesenchymal stem cells (MSCs), which are able to express neuroprotective factors as cytokines, chemokines and angiogenic molecules, collectively named secretome, that accumulate in MSC culture medium. However, lasting cell-free administration of secretome in vitro or in vivo is challenging. We used the conditioned media from rat adipose tissue-derived MSCs (RAA-MSCs) to check for neuroprotective activity towards pro-oxidizing agents such as hydrogen peroxide (H2O2) or the dopaminergic selective toxin 6-hydroxydopamine (6-OHDA) that is commonly used to model PD neurodegeneration. When neuroblastoma SH-SY5Y cells were pre-conditioned with 100% RAA-MSC media, then treated with H2O2 and 6-OHDA, mortality and ROS generation were reduced. We implemented the controlled release of RAA-MSC secretome from injectable biodegradable hydrogels that offer a possible in situ implant with mini-invasive techniques. The hydrogels were composed of type I bovine collagen (COLL) and low-molecular-weight hyaluronic acid (LMWHA) or COLL and polyethylene glycol (PEG). Hydrogels were suitable for RAA-MSC embedding up to 48 h and secretome from these RAA-MSCs was active and counteracted 6-OHDA toxicity, with upregulation of the antioxidant enzyme sirtuin 3 (SIRT3). These results support a biomaterials-based approach for controlled delivery of MSC-produced neuroprotective factors in a PD-relevant experimental context.
|
[
"Neuroscience and Disorders of the Nervous System",
"Cell Biology, Development, Stem Cells and Regeneration",
"Materials Engineering"
] |
10.1093/mnras/stv996
|
A fast and explicit algorithm for simulating the dynamics of small dust grains with smoothed particle hydrodynamics
|
We describe a simple method for simulating the dynamics of small grains in a dusty gas, relevant to micron-sized grains in the interstellar medium and grains of centimetre size and smaller in protoplanetary discs. The method involves solving one extra diffusion equation for the dust fraction in addition to the usual equations of hydrodynamics. This 'diffusion approximation for dust' is valid when the dust stopping time is smaller than the computational timestep. We present a numerical implementation using smoothed particle hydrodynamics that is conservative, accurate and fast. It does not require any implicit timestepping and can be straightforwardly ported into existing 3D codes.
|
[
"Universe Sciences",
"Computer Science and Informatics"
] |
10.1042/bcj20180748
|
The transmembrane autophagy cargo receptors ATI1 and ATI2 interact with ATG8 through intrinsically disordered regions with distinct biophysical properties
|
Selective autophagy has emerged as an important mechanism by which eukaryotic cells control the abundance of specific proteins. This mechanism relies on cargo recruitment to autophagosomes by receptors that bind to both the ubiquitin-like AUTOPHAGY8 (ATG8) protein through ATG8-interacting motifs (AIMs) and to the cargo to be degraded. In plants, two autophagy cargo receptors, ATG8-interacting protein 1 (ATI1) and 2 (ATI2), were identified early on, but their molecular properties remain poorly understood. Here, we show that ATI1 and ATI2 are transmembrane proteins with long N-terminal intrinsically disordered regions (IDRs). The N-terminal IDRs contain the functional AIMs, and we use nuclear magnetic resonance spectroscopy to directly observe the disorder-order transition of the AIM upon ATG8 binding. Our analyses also show that the IDRs of ATI1 and ATI2 are not equivalent, because ATI2 has properties of a fully disordered polypeptide, while ATI1 has properties more consistent with a collapsed pre-molten globule-like conformation, possibly as a consequence of a higher content of π-orbital-containing amino acid residues. Finally, we show that a sizable fraction of ATI2, but not ATI1, is phosphorylated in planta.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physical and Analytical Chemical Sciences"
] |
10.1109/ISIT.2015.7282410
|
Cooperative Multiple Access Channels With Oblivious Encoders
|
In this paper we study the cooperative multiple access channel (MAC) with oblivious encoders and characterize its capacity region. Cooperation means that one encoder sends a message to the other encoder via a rate-limited link prior to transmission, while partial cribbing means that one encoder obtains a deterministic function of the other encoder's output. Partial cribbing can be done strictly-causally, causally, and non-causally. Prior work in this field dealt with the case where the two encoders are aware of each other's chosen codebook. In this paper we consider the case of oblivious encoding, where each user in a network is unaware of the codebook chosen by other users. Since an oblivious encoder cannot decode the message sent from another encoder, it cannot implement the Decode-and-Forward coding scheme, as is usually done in cases of partial cribbing with codebook-aware encoders. To overcome this, we introduce the method of Bin-and-Forward, which does not require decoding. Since the possible cribbed signals are not known a priori, in our new coding scheme binning is done on all typical possible cribbed sequences. Instead of sending a decoded message, the oblivious encoder sends the bin in which the cribbed sequence lies. We compare the gain achieved using cooperation and partial cribbing with and without codebook knowledge. Evidently, in the cases of causal and non-causal perfect cribbing, the capacity region is the same for oblivious and codebook-aware encoding. As an example, we consider the Gaussian MAC with cooperation and quantized cribbing. For this model, we give an achievability scheme that shows how knowing the codebooks affects the capacity region for cooperation alone, for partial cribbing alone, and for combined cooperation and partial cribbing.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
220301
|
Multi-Level model calibration for the assessment of historical masonry structures
|
The MultiCAMS project will develop an advanced computational strategy including numerical modelling and innovative model calibration for realistic assessment of historical unreinforced masonry structures. The presence of relevant historical heritage in Europe, partly still in use, together with high seismic risk in the Mediterranean areas highlights the need of assessing such structures considering current safety requirements and if necessary strengthened to prevent critical failure. The proposed assessment approach is based on the use of models with different levels of sophistication, comprising detailed mesoscale models where masonry units and mortar joints are modelled separately (low level), homogeneous shell/solid-element models in which masonry is considered as a continuum (intermediate level), and efficient macroscale models where entire structural parts (i.e. piers, spandrels) are represented by appropriate macro-elements (high level). In this respect, I will develop a novel numerical description with macro-elements for an efficient and practical analysis of masonry structures accounting for the interaction between the nonlinear in-plane and out-of-plane behaviour of different URM components. An innovative model calibration strategy utilising inverse analysis techniques will thus be developed to couple the efficiency of the novel simplified mechanical model and the accuracy of existing detailed models, such as the parameters of each model will be determined from the inverse analysis of the numerical response of the lower-level model. The main outcome of MultiCAMS will be a comprehensive and accurate methodology for the seismic assessment of historical masonry buildings, which represents an urgent requirement for the safeguard of human lives in many European urban areas, as shown by recent catastrophic events.
|
[
"Products and Processes Engineering",
"Materials Engineering",
"Computer Science and Informatics"
] |
10.3389/fvets.2020.00183
|
Comparison of Behavior and Genetic Structure in Populations of Family and Kenneled Beagles
|
In dogs, the social and spatial restriction associated with living in a kennel environment could lead to chronic stress and the development of abnormal behaviors (“kennel-dog syndrome”). However, little is known about how kenneled dogs differ from their conspecifics living as pets in human families. In the current study, using a test battery exposing the dogs to novel stimuli, we compared the behavior of three groups of beagles: (1) kenneled dogs living in a restricted environment with limited human contact (N = 78), (2) family dogs living in human families as pets (N = 37), and (3) adopted dogs born in the kenneled population but raised in human families (N = 13). We found one factor comprising most of the test behaviors, labeled as Responsiveness. Family dogs and adopted dogs scored higher in Responsiveness than kenneled dogs. However, 23% of the kenneled dogs were comparable to family and adopted dogs based on a cluster analysis, indicating a similar (positive) reaction to novel stimuli, while 77% of the kenneled dogs were unresponsive (mostly immobile) in at least part of the test. To assess if the behavioral difference between the family and kenneled dogs could be due to genetic divergence of these two populations and/or to lower genetic diversity of the kenneled dogs, we analyzed their genetic structure using 11 microsatellite markers. We found no significant difference between the populations in their genetic diversity (i. e. , heterozygosity, level of inbreeding), nor any evidence that the family and kenneled populations originated from different genetic pools. Thus, the behavior difference between the groups more likely reflects a G × E interaction, that is, the influence of specific genetic variants manifesting under specific environmental conditions (kennel life). Nevertheless, some kenneled individuals were (genetically) more resistant to social and environmental deprivation. Selecting for such animals could strongly improve the welfare of kenneled dog populations. Moreover, exploring the genetic background of their higher resilience could also help to better understand the genetics behind stress- and fear-related behaviors.
|
[
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
W2556142403
|
Reorientation of Sputnik Planitia implies a subsurface ocean on Pluto
|
The deep nitrogen-covered Sputnik Planitia (SP; informal name) basin on Pluto is located very close to the longitude of Pluto's tidal axis[1] and may be an impact feature [2], by analogy with other large basins in the solar system[3,4]. Reorientation[5-7] due to tidal and rotational torques can explain SP's location, but requires it to be a positive gravity anomaly[7], despite its negative topography. Here we argue that if SP formed via impact and if Pluto possesses a subsurface ocean, a positive gravity anomaly would naturally result because of shell thinning and ocean uplift, followed by later modest N2 deposition. Without a subsurface ocean a positive gravity anomaly requires an implausibly thick N2 layer (greater than 40 km). A rigid, conductive ice shell is required to prolong such an ocean's lifetime to the present day[8] and maintain ocean uplift. Because N2 deposition is latitude-dependent[9], nitrogen loading and reorientation may have exhibited complex feedbacks[7].
|
[
"Universe Sciences",
"Earth System Science"
] |
10.1038/nature10925
|
DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation
|
Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription, and is greatly affected by the rate of transcript elongation. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle; this is the functional form of the nascent pre-mRNA and determines the fate of the mature transcript. However, factors that connect the transcribing polymerase with the mRNP particle and help to integrate transcript elongation with mRNA splicing remain unclear. Here we characterize the human interactome of chromatin-associated mRNP particles. This led us to identify deleted in breast cancer 1 (DBC1) and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and DBC1 (ZIRD)) as subunits of a novel protein complex-named DBIRD-that binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in (A + T)-rich DNA, and is present at the affected exons. RNA-interference-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
] |
10.3150/17-BEJ958
|
Applications Of Pathwise Burkholder Davis Gundy Inequalities
|
We present several applications of the pathwise Burkholder-Davis-Gundy (BDG) inequalities. Most importantly we prove them for cadlag semimartingales and a general function $\Phi$, and use this to derive BDG inequalities (non-pathwise ones) for the Bessel process of order $\alpha\geq 1$ and for martingales stopped at $\tau$, with $\tau$ in a well studied class of random times.
|
[
"Mathematics"
] |
10.4155/fmc.15.188
|
Substituted 2-(2-aminopyrimidin-4-yl)pyridine-4-carboxylates as potent inhibitors of Jumonji C domain-containing histone demethylases
|
Background: Aberrant expression of iron(II)- and 2-oxoglutarate-dependent JumonjiC histone demethylases has been linked to cancer. Potent demethylase inhibitors are drug candidates and biochemical tools to elucidate the functional impact of demethylase inhibition. Methods & results: Virtual screening identified a novel lead scaffold against JMJD2A with low-micromolar potency in vitro. Analogs were acquired from commercial sources respectively synthesized in feedback with biological testing. Optimized compounds were transformed into cell-permeable prodrugs. A cocrystal x-ray structure revealed the mode of binding of these compounds as competitive to 2-oxoglutarate and confirmed kinetic experiments. Selectivity studies revealed a preference for JMJD2A and JARID1A over JMJD3. Conclusion: Virtual screening and rational structural optimization led to a novel scaffold for highly potent and selective JMJD2A inhibitors.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Synthetic Chemistry and Materials"
] |
10.1016/j.ymthe.2017.03.001
|
Current Progress in Non-viral RNAi-Based Delivery Strategies to Lymphocytes
|
RNAi-based therapy holds great promise, as it can be utilized for the treatment of multiple conditions in an accurate manner via sequence-specific manipulation of gene expression. To date, RNAi therapeutics have advanced into clinical trials for liver diseases and solid tumors; however, delivery of RNAi to leukocytes in general and to lymphocytes in particular remains a challenge. Lymphocytes are notoriously hard to transduce with RNAi payloads and are disseminated throughout the body, often located in deep tissues; therefore, developing an efficient systemic delivery system directed to lymphocytes is not a trivial task. Successful manipulation of lymphocyte function with RNAi possesses immense therapeutic potential, as it will enable researchers to resolve lymphocyte-implicated diseases such as inflammation, autoimmunity, transplant rejection, viral infections, and blood cancers. This potential has propelled the development of novel targeted delivery systems relying on the accumulating research knowledge from multiple disciplines, including materials science and engineering, immunology, and genetics. Here, we will discuss the recent progress in non-viral delivery strategies of RNAi payloads to lymphocytes. Special emphasis will be made on the challenges and potential opportunities in manipulating lymphocyte function with RNAi. These approaches might ultimately become a novel therapeutic modality to treat leukocyte-related diseases.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Synthetic Chemistry and Materials"
] |
10.1109/TNB.2019.2946124
|
Impact Of Long Term Plasticity On Information Transmission Over Neuronal Networks
|
The realization of bio-compatible nanomachines would pave the way for developing novel diagnosis and treatment techniques for the dysfunctions of intra-body nanonetworks and revolutionize the traditional healthcare methodologies making them less invasive and more efficient. The network of these nanomachines is aimed to be used for treating neuronal diseases such as developing an implant that bridges over the injured spinal cord to regain its normal functionality. Thus, nanoscale communication paradigms are needed to be investigated to facilitate communication between nanomachines. Communication among neurons is one of the most promising nanoscale communication paradigm, which necessitates the thorough communication theoretical analysis of information transmission among neurons. The information flow in neuro-spike communication channel is regulated by the ability of neurons to change synaptic strengths over time, i. e. synaptic plasticity. Thus, the performance evaluation of the nervous nanonetwork is incomplete without considering the influence of synaptic plasticity. In this paper, we focus on information transmission among hippocampal pyramidal neurons and provide a comprehensive channel model for MISO neuro-spike communication, which includes axonal transmission, vesicle release process, synaptic communication and spike generation. In this channel, the spike timing dependent plasticity (STDP) model is used to cover both synaptic depressiofan and potentiation depending on the temporal correlation between spikes generated by input and output neurons. Since synaptic strength changes depending on different physiological factors such as spiking rate of presynaptic neurons, number of correlated presynaptic neurons and the correlation factor among them, we simulate this model with correlated inputs and analyze the evolution of synaptic weights over time. Moreover, we calculate average mutual information between input and output of the channel and find the impact of plasticity and correlation among inputs on the information transmission. The simulation results reveal the impact of different physiological factors related to either presynaptic or postsynaptic neurons on the performance of MISO neuro-spike communication. Moreover, they provide guidelines for selecting the system parameters in a bio-inspired neuronal network according to the requirements of different applications.
|
[
"Neuroscience and Disorders of the Nervous System",
"Systems and Communication Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
W1988275863
|
The Use of Thermowell Bushes at the Triple Point of Water for Improving Repeatability
|
Water triple point cells are essential for realization of the International Temperature Scale of 1990 (ITS-90). There is some evidence that achieving the ultimate performance of water triple point cells may be restricted by the variation in the position of the platinum resistance thermometer at the bottom of the re-entrant well, and that the variation in position is not completely compensated for by correction to zero measurement sensing current. This comparative study focused on the use of quartz bushes (tubular sleeves around the thermometer) of two different lengths, to improve the thermal contact and to help locate the thermometer. It shows that an improvement in repeatability of the resistance readings was achieved. The experiments were conducted over a five-week period using a standard platinum resistance thermometer, a one water cell, and two different lengths of quartz bushes. The resistance measurements were performed using an Automatic Systems Laboratories F900 resistance bridge. A description of the experiment and results is given. Significant improvement in the repeatability of the measurement of resistance was observed (factor >2) when quartz bushes were used.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
W2559960465
|
Simulating the water footprint of woodies in Aquacrop and Apex
|
As the crop cultivation sector is the largest human water consumer, models that simulate its water use are important in global water studies. Within this sector, herbaceous plants and woody plants can be discriminated. Aquacrop is a plant simulation model very capable of simulating herbaceous plants, but the carry-over effects from one year to another, the large number of plant varieties and the more complicated evaporation and transpiration behaviour make the relative simple model not suited for the simulation of woodies. Apex is a model capable of simulating both herbaceous and woody
plants, but the constant that drives biomass growth changes over the seasons and locations and loses
its linearity in stress conditions. This study compares the Aquacrop and Apex in the simulation of woody plants. For this the yield, the evapotranspiration and the water footprint resulting from these are important.
From the plants with the largest harvested areas, the apple tree, the grapevine, the olive tree and
the oil palm are selected as four important plants that will be simulated in this study. Each of these
plants is simulated on a field level in the region where their core production is located. To make a comparison between the two very different models possible, the input and the processes in Aquacrop and Apex are harmonized. To allow for a simulation of woody plants, Aquacrop only simulates the yearly foliage development of an already full-grown tree. Apex can simulate the plant development
in the first years that characterize woodies.
For a full-grown woody plant, Aquacrop and Apex show different yields and evapotranspiration rates because of differences in input, parametrization and model structure. Aquacrop and Apex show roughly the same yield patterns in irrigated conditions, but in rainfed conditions large differences can occur. The evapotranspiration rates are very similar in rainfed conditions, but in irrigated conditions they deviate a lot from each other. When we compare the yield with literature, both models in general overestimate the yield. The evapotranspiration is in accordance with literature values.
The climatic variability influences the yields and evapotranspiration rates. In both models the evapotranspiration responds very realistically to yearly climate fluctuations. The yield in Aquacrop also responds as expected, but the yield in Apex is dominated by a model processes that does not correspond to the climatic variability. The influence of the soil is limited in Apex, while it can have a large effect on especially the yield in Aquacrop. The development phase of woody plants is important for the lifelong average yields, because the
first years of a plants life are characterized by a rather low yield. The evapotranspiration rate also changes over the first years, but the effect of the development phase is negligible for the lifelong
average evapotranspiration. When we take the development of yield into account for the calculation of the water footprint, it becomes visible that the water footprints in irrigated conditions are quite similar between the models, while in rainfed conditions they can differ quite a lot because of the difference in yield underlying the water footprint. Compared to the literature also large differences can occur.
Both models show their limitations. Because of this, additional research is required to compare the models under a wider scope. A case study can help to find more reliable estimates for the parameter values in the models. From this study alone, it cannot be concluded that one model is better than another. When simulating woodies, Aquacrop does not seem to be inferior to Apex, despite the fact that Aquacrop model is not designed for these plants.
|
[
"Computer Science and Informatics",
"Earth System Science"
] |
W2484708630
|
Species delimitation and phylogeographic analyses in the<i>Ectocarpus</i>subgroup<i>siliculosi</i>(Ectocarpales, Phaeophyceae)
|
The genus Ectocarpus (Ectocarpales, Phaeophyceae) contains filamentous algae widely distributed in marine and estuarine habitats of temperate regions in both hemispheres. While E. siliculosus has become a model organism for genomics and genetics of the brown macroalgae, accurate species delineation, distribution patterns and diversity for the genus Ectocarpus remain problematic. In this study, we used three independent species delimitation approaches to generate a robust species hypothesis for 729 Ectocarpus specimens collected mainly along the European and Chilean coasts. These approaches comprised phylogenetic reconstructions and two bioinformatics tools developed to objectively define species boundaries (General Mixed Yule Coalescence Method and Automatic Barcode Gap Discovery). Our analyses were based on DNA sequences of two loci: the mitochondrial cytochrome oxidase subunit 1 and the nuclear internal transcribed spacer 1 of the ribosomal DNA. Our analyses showed the presence of at least 15 cryptic species and suggest the existence of incomplete lineage sorting or introgression between five of them. These results suggested the possible existence of different levels of reproductive barriers within this species complex. We also detected differences among species in their phylogeographic patterns, range and depth distributions, which may suggest different biogeographic histories (e.g., endemic species or recent introductions).
|
[
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
] |
10.1126/scisignal.2001617
|
PI3Kβ plays a critical role in neutrophil activation by immune complexes
|
Neutrophils are activated by immunoglobulin G (IgG)-containing immune complexes through receptors that recognize the Fc portion of IgG (FcγRs). Here, we used genetic and pharmacological approaches to define a selective role for the β isoform of phosphoinositide 3-kinase (PI3KβcγR- dependent activation of mouse neutrophils by immune complexes of IgG and antigen immobilized on a plate surface. At low concentrations of immune complexes, loss of PI3Kβ alone substantially inhibited the production of reactive oxygen species (ROS) by neutrophils, whereas at higher doses, similar suppression of ROS production was achieved only by targeting both PI3KβI3Kδ, suggesting that this pathway displays stimulus strength-dependent redundancy. Activation of PI3Kβmune complexes involved cooperation between FcγRs and BLT1, the receptor for the endogenous proinflammatory lipid leukotriene B4. Coincident activation by a tyrosine kinase-coupled receptor (FcγR) and a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (BLT1) may provide a rationale for the preferential activation of the β isoform of PI3K. PI3Kβ-deficient mice were highly protected in an FcγR-dependent model of autoantibody-induced skin blistering and were partially protected in an FcγR-dependent model of inflammatory arthritis, whereas combined deficiency of PI3Kβ and PI3Kδ resulted in near-complete protection in the latter case. These results define PI3Kβ as a potential therapeutic target in inflammatory disease.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1007/978-3-319-56617-7_2
|
Scrypt Is Maximally Memory Hard
|
Memory-hard functions (MHFs) are hash algorithms whose evaluation cost is dominated by memory cost. As memory, unlike computation, costs about the same across different platforms, MHFs cannot be evaluated at significantly lower cost on dedicated hardware like ASICs. MHFs have found widespread applications including password hashing, key derivation, and proofs-of-work.
|
[
"Computer Science and Informatics"
] |
W1982645109
|
A mechanism stabilizing a long-lived charge-separated state of photosynthetic reaction centers frozen under intense illumination
|
It is experimentally shown that slow chilling of photosynthetic reaction centers from purple bacteria Rhodobacter sphaeroides to <230 K under intense illumination leads to appearance of long-lived chargeseparated states (P+Q −A ). This longevity implies that the recombination is blocked or the charge-separated state is stabilized. The longevity effect is caused by structural relaxation of reaction centers to a new equilibrium state that diminishes the free energy difference of recombination. The possible mechanism of such relaxation involves orientation of the polar water molecules in the semiquinone local electrostatic field. Detailed analysis of the longevity effect has been carried out, and its outcome supports the idea that many electron transfer reactions in biological systems are non-equilibrium.
|
[
"Condensed Matter Physics",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1038/nature11986
|
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
|
Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
] |
W1979337877
|
Challenges of using an AUV to find and map hydrothermal vent sites in deep and rugged terrains
|
In March 2010, the Autosub6000 AUV embarked on a cruise to discover, locate and map hydrothermal vent sites in an active spreading centre, the Cayman trough in the Caribbean sea. The environment provided the challenge of steep and rugged terrain together with deep water (in places greater than 5000 m). Autosub6000 is a flight class, hydrodynamically shaped AUV, with good endurance capability, making it well suited for searching for plume signals and mapping terrain over the required moderately large areas. However, it must fly at a forward speed greater than 0.8 ms- <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> to achieve control, and so it requires a capable forward look collision avoid capability. Another potential challenge is navigation. To make best use of ship time, AutosubSOOO missions are commonly conducted with neither the support ship in attendance, nor an acoustic transponder long baseline network. Hence positioning is dependent upon the AUV autonomous navigation (aided by a position fix after the AUV's descent to within ADCP bottom tracking range of the seabed). For the cruise on the UK research ship RRS James Cook, the AUV was equipped with sensors for EH (redox potential), turbidity, CTD, tri axis magnetometer, and an EM2000 multibeam sonar. The paper describes the Autosub6000 vehicle, its systems, capabilities, the missions it undertook in the deep Caribbean sea, and the discoveries it made. The missions, although ultimately very successful, were not without problems, with, for example, the steep seabed slopes, at times affecting the accuracy for the navigation system. The paper will also discuss these issues and how they might be addressed in the future.
|
[
"Products and Processes Engineering",
"Earth System Science"
] |
10.1038/ncb2381
|
Shaping development with ESCRTs
|
Originally identified for their involvement in endosomal sorting and multivesicular endosome (MVE) biogenesis, components of the endosomal sorting complex required for transport (ESCRT) are now known to control additional cellular functions such as receptor signalling, cytokinesis, autophagy, polarity, migration, miRNA activity and mRNA transport. The diverse cell biological functions of ESCRT proteins are translated into a pleiotropic set of developmental trajectories that reflect the wide repertoire of these evolutionarily conserved proteins.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1515/zpch-2016-0879
|
Tetrazole-Stabilized Gold Nanoparticles for Catalytic Applications
|
Abstract
Herein, we report on a proof-of-concept application of tetrazole-stabilized Au nanoparticles (NPs) for CO oxidation. After impregnation of the support material TiO2 with the tetrazole-stabilized Au NPs (diameter<5 nm), a thermal heat treatment under oxygen is used to remove the tetrazole from the NP surface. The resulting surfactant-free NPs are used in the CO oxidation and show enhanced catalytic activity in comparison to the untreated samples demonstrating the potential of tetrazole-stabilized NPs for various catalytic applications.
|
[
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials",
"Materials Engineering"
] |
10.1016/j.neuron.2012.10.037
|
Nuclear Calcium Signaling in Spinal Neurons Drives a Genomic Program Required for Persistent Inflammatory Pain
|
Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is considered important. Here, we show that persistent nociceptive-like activity triggers calcium transients in neuronal nuclei within the superficial spinal dorsal horn, and that nuclear calcium is necessary for the development of long-term inflammatory hypersensitivity. Using a nucleus-specific calcium signal perturbation strategy in vivo complemented by gene profiling, bioinformatics, and functional analyses, we discovered a pain-associated, nuclear calcium-regulated gene program in spinal excitatory neurons. This includes C1q, a modulator of synaptic spine morphogenesis, which we found to contribute to activity-dependent spine remodelling on spinal neurons in a manner functionally associated with inflammatory hypersensitivity. Thus, nuclear calcium integrates synapse-to-nucleus communication following noxious stimulation and controls a spinal genomic response that mediates the transition between acute and long-term nociceptive sensitization by modulating functional and structural plasticity.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
] |
10.1038/s41893-019-0454-4
|
Human impacts on planetary boundaries amplified by Earth system interactions
|
The planetary boundary framework presents a ‘planetary dashboard’ of humanity’s globally aggregated performance on a set of environmental issues that endanger the Earth system’s capacity to support humanity. While this framework has been highly influential, a critical shortcoming for its application in sustainability governance is that it currently fails to represent how impacts related to one of the planetary boundaries affect the status of other planetary boundaries. Here, we surveyed and provisionally quantified interactions between the Earth system processes represented by the planetary boundaries and investigated their consequences for sustainability governance. We identified a dense network of interactions between the planetary boundaries. The resulting cascades and feedbacks predominantly amplify human impacts on the Earth system and thereby shrink the safe operating space for future human impacts on the Earth system. Our results show that an integrated understanding of Earth system dynamics is critical to navigating towards a sustainable future.
|
[
"Earth System Science",
"Human Mobility, Environment, and Space"
] |
885090
|
Holographic control of visual circuits
|
The aim of this research program is to produce novel all-optical technologies to explore brain functions at the mesoscopic scale with cellular resolution opening a new phase in optogenetics that I named circuit optogenetics.
Revealing the neural codes supporting specific mammalian brain functions is a daunting task demanding to relate in vivo the individual activities of large numbers of neurons recorded jointly within collectives that form distinct nodes of a network and to perform precisely targeted and calibrated interventions in the spatiotemporal dynamics of neural circuits on the scale of naturalistic patterns of activity. Despite recent technical advances, these experiments remain out of reach because we lack a comprehensive approach for large-scale, multi-region, in depth, single cell and millisecond precise manipulation of neural circuits. HOLOVIS will tackle these limitations through the construction of an innovative paradigm combining optogenetics with cutting-edge technology of wave front shaping, compressed sensing, microendoscopy, wave-guide probes, laser developments and opsin engineering.
My lab has pioneered the use of wave front shaping for neuroscience and developed in the past years a number of new optical methods, for patterned optogenetic neuronal stimulation. Here, we will push forward this technology and first demonstrate the performances of these breakthrough systems to reveal how inter, intra-laminar and cortical/sub-cortical wiring construct and refine visual orientation selectivity in mice.
We will focus on the visual system of mice, whose input-output responses to controlled sensory stimulations have been characterized in decades of studies. However, we are persuaded that our approach can be used to reveal the connectivity rules that underlie specific patterns of activity of any neuronal circuit, thus defining the functional building blocks of distinct brain areas.
|
[
"Neuroscience and Disorders of the Nervous System",
"Systems and Communication Engineering",
"Physical and Analytical Chemical Sciences"
] |
10.1038/nm.4046
|
Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing T<inf>H</inf>17 cells and preserving group 3 innate lymphoid cells
|
RAR-related orphan receptor-γt (ROR-γt) directs differentiation of proinflammatory T helper 17 (TH17) cells and is a potential therapeutic target in chronic autoimmune and inflammatory diseases. However, ROR-γt-dependent group 3 innate lymphoid cells ILC3s provide essential immunity and tissue protection in the intestine, suggesting that targeting ROR-γt could also result in impaired host defense after infection or enhanced tissue damage. Here, we demonstrate that transient chemical inhibition of ROR-γt in mice selectively reduces cytokine production from TH17 but not ILCs in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. Temporal deletion of Rorc (encoding ROR-γt) in mature ILCs also did not impair cytokine response in the steady state or during infection. Finally, pharmacologic inhibition of ROR-γt provided therapeutic benefit in mouse models of intestinal inflammation and reduced the frequency of TH17 cells but not ILCs isolated from primary intestinal samples of individuals with inflammatory bowel disease (IBD). Collectively, these results reveal differential requirements for ROR-γt in the maintenance of TH17 cell and ILC3 responses and suggest that transient inhibition of ROR-γt is a safe and effective therapeutic approach during intestinal inflammation.
|
[
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
W2050965561
|
Numerical study on flow behavior of CO2 in an aquifer for risk assessment of carbon capture and storage
|
Abstract It is supposed that the leakage of injected CO 2 as the principal hazard due to the existence of fault occurs when CO 2 storage in an aquifer is targeted. Therefore it is very important to predict the migration of injected CO 2 dependent on time and space under the environment of underground. The quantitative estimation for the amount of storage and leakage of injected CO 2 is necessary for risk assessment of carbon capture and storage (CCS) through simulation study on the basis of the scenario of CO 2 leakage considering the specific geological condition such as permeability, porosity and the existence of fault. In this study, we constructed the reservoir model that aquifer and impermeable layers were alternately located in vertical direction of reservoir. Modeling of the fault was simplified by putting the thin zone that simulated the fault inside of analytical mesh zone. Using the constructed reservoir model, we carried out some simulation run. Changing geological structure containing fault, absolute permeability of fault and flow velocity of groundwater as a calculation parameter, we considered the effect of each parameter on flow behavior of CO 2 in an aquifer and quantified the amount of CO 2 leakage.
|
[
"Earth System Science",
"Products and Processes Engineering"
] |
W2165282058
|
Application of Geo-Spatial Techniques for Precise Demarcation of Village/Panchayat Boundaries
|
Abstract. In order to achieve the overall progress of the country with active and effective participation of all sections of society, the 12th Five Year Plan (FYP) would bring Panchayats centre-stage and achieve the inclusive growth agenda through inclusive governance. The concept of 'democratic decentralization' in the form of a three-tier administration was introduced in the name of "Panchayat Raj". Horizontally, it is a network of village Panchayats. Vertically, it is an organic growth of Panchayats rising up to national level. The Ministry of Panchayati Raj has three broad agenda: Empowerment, Enablement and Accountability. Space based Information Support for Decentralized Planning (SIS-DP) is one of the initiatives taken by Govt. of India with ISRO/DOS for generation and dissemination of spatial information for planning at the grass root level. The boundary layer for villages across different states/district/block is available with line departments. Most of these data exist at a much generalized scale. These boundaries do not overlay exactly with that of ground realities and may not be suitable for accurate analysis in terms of area, shape, position, etc. To deal with this problem, a strategy is adopted, which makes use of High Resolution Satellite Imagery (HRSI) from Indian Remote sensing satellites and cadastral maps at 1:4000 scale integrated with GIS techniques to enhance the accuracy of geo-spatial depiction of Village/Panchayat boundaries. Cadastral maps are used to depict the boundaries of land parcels and other features at the village level. These maps are registered to ortho products of HRSI using Ground Control Points. The cadastral maps are precisely overlaid on ortho-rectified HRSI and each parcel vertex is tagged with the real-world geographical coordinates. Village boundaries are extracted from the geo-referenced village cadastral maps. These boundaries are fine-tuned by considering under lap and overlap of neighboring villages and a mosaic is generated at the subdistrict and district level. Each village is coded with a unique number based on Ministry of Panchayati Raj and Census department codes. Villages are mapped to their respective Panchayat(s) directory and are dissolved in GIS environment based on code/nomenclature to obtain the final Gram Panchayat Layer. The present study attempts to showcase the methodology for deriving precise Village/Panchayat Boundaries using geo-spatial techniques. The final output will immensely help the Ministry of Panchayati Raj and Rural Development for implementing the developmental programs in tune with 73th and 74th constitutional amendments.
|
[
"Human Mobility, Environment, and Space",
"Computer Science and Informatics",
"Earth System Science"
] |
10.3109/03008207.2014.912645
|
Cell Tissue Interactions In Osteoarthritic Human Hip Joint Articular Cartilage
|
AbstractVolume and morphology of chondrocytes in osteoarthritic human hip joint articular cartilage were characterized, and their relationship to tissue structure and function was determined. Human osteochondral articular cartilage samples (n = 16) were obtained from the femoral heads of nine patients undergoing total hip arthroplasty due to osteoarthritis (OA). Superficial chondrocytes (N = 65) were imaged in situ with a confocal laser scanning microscope at 37 °C. This was followed by the determination of the mechanical properties of the tissue samples, depth-wise characterization of cell morphology (height, width; N = 385) as well as structure and composition of the tissues using light microscopy, digital densitometry, Fourier transform infrared microspectroscopy and polarized light microscopy. Significant correlations were found between the cell volume and the orientation angle associated with the collagen fibers (r = 0. 320, p = 0. 009) as well as between the cell volume and the initial dynamic modulus. . .
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
] |
10.1016/j.cub.2018.02.037
|
Accuracy of Rats in Discriminating Visual Objects Is Explained by the Complexity of Their Perceptual Strategy
|
Despite their growing popularity as models of visual functions, it remains unclear whether rodents are capable of deploying advanced shape-processing strategies when engaged in visual object recognition. In rats, for instance, pattern vision has been reported to range from mere detection of overall object luminance to view-invariant processing of discriminative shape features. Here we sought to clarify how refined object vision is in rodents, and how variable the complexity of their visual processing strategy is across individuals. To this aim, we measured how well rats could discriminate a reference object from 11 distractors, which spanned a spectrum of image-level similarity to the reference. We also presented the animals with random variations of the reference, and processed their responses to these stimuli to derive subject-specific models of rat perceptual choices. Our models successfully captured the highly variable discrimination performance observed across subjects and object conditions. In particular, they revealed that the animals that succeeded with the most challenging distractors were those that integrated the wider variety of discriminative features into their perceptual strategies. Critically, these strategies were largely preserved when the rats were required to discriminate outlined and scaled versions of the stimuli, thus showing that rat object vision can be characterized as a transformation-tolerant, feature-based filtering process. Overall, these findings indicate that rats are capable of advanced processing of shape information, and point to the rodents as powerful models for investigating the neuronal underpinnings of visual object recognition and other high-level visual functions. Djurdjevic et al. show that the ability of rats to successfully discriminate visual objects depends on the complexity of their perceptual strategy, which remains largely unchanged under variations in object appearance. This implies that rats process visual objects using mechanisms not dissimilar from those of more evolved species, such as primates.
|
[
"Neuroscience and Disorders of the Nervous System",
"The Human Mind and Its Complexity"
] |
BR 112021025552 A
|
Junta roscada com ressalto produzido por fabricação aditiva
|
junta roscada com ressalto produzido por fabricação aditiva. a presente invenção refere-se a uma junta roscada tubular (1) para a perfuração, a exploração dos poços de hidrocarbonetos ou o transporte de petróleo e de gás, compreendendo um elemento tubular roscado macho (2) e um elemento tubular roscado (fêmea (3), o elemento tubular roscado fêmea (3) compreendendo uma parte roscada interna fêmea (5) e uma parte não roscada fêmea (6), o elemento tubular roscado macho compreendendo uma parte roscada externa macho (7) e uma parte não roscada macho (8), caracterizada pelo fato de que o elemento tubular macho (2) ou fêmea (3) compreende um corpo (4) e uma parte acrescentada (9) por fabricação aditiva que compreende pelo menos uma primeira superfície de topejamento.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
W1974685209
|
7-Substituted pterins provide a new direction for ricin A chain inhibitors
|
Ricin is a potent toxin found in castor seeds. The A chain, RTA, enzymaticlly depurinates a specific adenosine in ribosomal RNA, inhibiting protein synthesis. Ricin is a known chemical weapons threat having no effective antidote. This makes the discovery of new inhibitors of great importance. We have previously used 6-substituted pterins, such as pteroic acid, as an inhibitor platform with moderate success. We now report the success of 7-carboxy pterin (7CP) as an RTA inhibitor; its binding has been monitored using both kinetic and temperature shift assays and by X-ray crystallography. We also discuss the synthesis of various derivatives of 7CP, and their binding affinity and inhibitory effects, as part of a program to make effective RTA inhibitors.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
FR 7731128 A
|
PROCEDE DE SECHAGE DE LINGE ET ARMOIRE DE SECHAGE POUR LA MISE EN PRATIQUE DE CE PROCEDE
|
<P>La présente invention a pour objet une armoire de séchage de linge ou d'autres articles plats. </P><P>Cette armoire, comportant une porte d'alimentation, une ouverture d'aspiration d'air, un ventilateur, un dispositif de séchage de l'air de séchage, et des tiges s'étendant entre une premiere et une seconde paroi, est caractérisée en ce que cette seconde paroi comporte en haut, et le cas échéant en son milieu, une ou plusieurs fentes de sortie d'air de séchage, et en ce que l'armoire est pourvue d'un condenseur ou un échangeur de chaleur où l'air aspiré est préchauffé et où l'air décharge est refroidi. </P><P>Elle se rapporte à des séchoirs industriels.</P>
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
10.1088/1367-2630/15/4/045020
|
Adaptive Tuning Of Majorana Fermions In A Quantum Dot Chain
|
We suggest a way to overcome the obstacles that disorder and high density of states pose to the creation of unpaired Majorana fermions in one-dimensional systems. This is achieved by splitting the system into a chain of quantum dots, which are then tuned to the conditions under which the chain can be viewed as an effective Kitaev model, so that it is in a robust topological phase with well-localized Majorana states in the outermost dots. The tuning algorithm that we develop involves controlling the gate voltages and the superconducting phases. Resonant Andreev spectroscopy allows us to make the tuning adaptive, so that each pair of dots may be tuned independently of the other. The calculated quantized zero bias conductance serves then as a natural proof of the topological nature of the tuned phase.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
] |
10.2140/ant.2019.13.19
|
Variance of arithmetic sums and l-functions in f <inf>q</inf> [t]
|
We compute the variances of sums in arithmetic progressions of arithmetic functions associated with certain L-functions of degree 2 and higher in F q [t], in the limit as q →∞. This is achieved by establishing appropriate equidistribution results for the associated Frobenius conjugacy classes. The variances are thus related to matrix integrals, which may be evaluated. Our results differ significantly from those that hold in the case of degree-1 L-functions (i. e. , situations considered previously using this approach). They correspond to expressions found recently in the number field setting assuming a generalization of the pair correlation conjecture. Our calculations apply, for example, to elliptic curves defined over F q [t].
|
[
"Mathematics"
] |
W2040966157
|
Beyond the Internet:Mētis,Techne, and the Limitations of Online Artifacts for Islamist Terrorists
|
This study challenges the conventional wisdom that the Internet is a reliable source of operational knowledge for terrorists, allowing them to train for terrorist attacks without access to real-world training camps and practical experience. The article distinguishes between abstract technical knowledge (what the Greeks called techne) and practical, experiential knowledge (mētis), investigating how each helps terrorists prepare for attacks. This distinction offers insight into how terrorists acquire the practical know-how they need to perform their activities as opposed to abstract know-what contained in bomb-making manuals. It also underscores the Internet's limitations as a source of operational knowledge for terrorists. While the Internet allows militants to share substantial techne, along with religious and ideological information, it is not particularly useful for disseminating the experiential and situational knowledge terrorists use to engage in acts of political violence. One likely reason why Al Q...
|
[
"The Social World and Its Interactions",
"Institutions, Governance and Legal Systems"
] |
10.1007/s10021-014-9793-1
|
The Carbon Cycle of a Maritime Ancient Temperate Broadleaved Woodland at Seasonal and Annual Scales
|
This study compares different approaches to quantifying the carbon cycle in a temperate deciduous forest at Wytham Woods in England, which is unusual in its maritime climate and mixed age structure, reflecting low levels of past management. We tested whether eddy covariance and biometric measurements gave consistent estimates of woodland productivity and ecosystem respiration at monthly and annual timescales. Biometric methods estimated gross primary productivity (GPP) as 22. 0 ± 1. 6 Mg C ha−1 y−1, close to the eddy covariance GPP value of 21. 1 Mg C ha−1 y−1. Annual ecosystem respiration (RECO) was similar, at 20. 3 ± 1. 5 Mg C ha−1 y−1 for biometric and 19. 8 Mg C ha−1 y−1for eddy covariance. The seasonal cycle of monthly biometric and eddy covariance RECO estimates also closely matched. Net primary productivity (NPP) was 7. 0 ± 0. 8 Mg C ha−1 y−1, 37% of which was allocated below ground. Leaf fluxes were the greatest component of NPP and RECO. Ecosystem carbon-use efficiency (CUE = NPP/GPP) was 0. 32 ± 0. 04; low compared to many temperate broadleaved sites but close to values for old-growth sites. This may reflect the age of some trees, and/or the oceanic climate with relatively mild winters during which there can be substantial autotrophic maintenance respiration in winter but negligible growth. This study demonstrates that biometric measurements can provide robust estimates of site productivity and respiration and that eddy covariance and bottom-up measurements can be combined on seasonal and interannual timescales to enable a detailed understanding of the forest carbon cycle.
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution"
] |
10.1109/ESSDERC.2012.6343381
|
Mtj Based Implication Logic Gates And Circuit Architecture For Large Scale Spintronic Stateful Logic Systems
|
Because of the easy integration with CMOS, non-volatility, reconfiguration capability, and fast-switching speed of magnetic tunnel junctions (MTJs), this work proposes and investigates stateful IMP-based logic gates and circuit architecture for future reconfigurable and nonvolatile computing systems. Stateful logic uses the memory unit (MTJ device) as the main computing element (logic gate) unlike the previously proposed MTJ-based logic circuits, where MTJs are only ancillary devices in logical computations. Spintronic IMP logic gates are analyzed using a SPICE model for spin-transfer torque MTJs to demonstrate the reliability of the IMP operation. The realization of the spintronic stateful logic operations extends nonvolatile electronics from memory to logical computing applications and opens the door for more complex logic functions to be realized with MTJ-based devices.
|
[
"Condensed Matter Physics",
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
10.1007/jhep03(2020)064
|
Asymptotic dynamics of AdS3 gravity with two asymptotic regions
|
The asymptotic dynamics of AdS3 gravity with two asymptotically anti-de Sitter regions is investigated, paying due attention to the zero modes, i. e. , holonomies along non-contractible circles and their canonically conjugates. This situation covers the eternal black hole solution. We derive how the holonomies around the non-contractible circles couple the fields on the two different boundaries and show that their canonically conjugate variables, needed for a consistent dynamical description of the holonomies, can be related to Wilson lines joining the boundaries. The action reduces to the sum of four free chiral actions, one for each boundary and each chirality, with additional non-trivial couplings to the zero modes which are explicitly written. While the Gauss decomposition of the SL(2, ℝ) group elements is useful in order to treat hyperbolic holonomies, the Iwasawa decomposition turns out to be more convenient in order to deal with elliptic and parabolic holonomies. The connection with the geometric action is also made explicit. Although our paper deals with the specific example of two asymptotically anti-de Sitter regions, most of our global considerations on holonomies and radial Wilson lines qualitatively apply whenever there are multiple boundaries, independently of the form that the boundary conditions explicitly take there.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
W2155381325
|
Bayesian neural networks for detecting epistasis in genetic association studies
|
Discovering causal genetic variants from large genetic association studies poses many difficult challenges. Assessing which genetic markers are involved in determining trait status is a computationally demanding task, especially in the presence of gene-gene interactions. A non-parametric Bayesian approach in the form of a Bayesian neural network is proposed for use in analyzing genetic association studies. Demonstrations on synthetic and real data reveal they are able to efficiently and accurately determine which variants are involved in determining case-control status. Using graphics processing units (GPUs) the time needed to build these models is decreased by several orders of magnitude. In comparison with commonly used approaches for detecting genetic interactions, Bayesian neural networks perform very well across a broad spectrum of possible genetic relationships while having the computational efficiency needed to handle large datasets.
|
[
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
] |
3733129
|
Negotiation and mediation sensible issues' solutions
|
Inspired by the greek goddess Nemesis, personification of ""Distribution of Justice"", neither good nor bad, simply in due proportion to each according to what was deserved.
My research is focused on new dispute resolution methods, applying also new technologies, especially online dispute resolution platforms.
Seraphin is an online centre whose proceedings have been entirely digitized. Seraphin is well-known for their arbitration centre, enabling the efficient resolution of commercial disputes, but they are currently developing other platforms for Mediation and Negotiation.
Nemesis will focus on the link between the advanced research on online dispute resolution - from an academic perspective - and the real online world - with all the different cases and practical issues to face off on a daily basis - in order to develop a common path with solid research basis, due to the state of the art and best practices acquired during my academic career,
and a practical/pragmatic mindset, due to the issues faced everyday on the online Seraphin platforms.
This project concerns legal research with interdisciplinary aspects, incorporating insights from disciplines such as computer science, economics, and regulation theory. While scholars and regulators are concerned about forms and numbers of ODR providers, an in-depth study of the practical implications of e-mediation is lacking. This project is among the first to apply academic and practical perspective to e-mediation. The desk research will be enriched with insights from the workshops –
an innovative approach for legal research.
|
[
"Institutions, Governance and Legal Systems",
"Computer Science and Informatics",
"Individuals, Markets and Organisations"
] |
10.1002/hep.27651
|
Potential of Human Induced Pluripotent Stem Cells in Studies of Liver Disease
|
Liver disease is a leading cause of death in the Western world. However, our insight into the underlying disease mechanisms and the development of novel therapeutic agents has been hindered by limited availability of primary tissue, intraspecies variability associated with the use of animal models, and reduced long-term viability of isolated and diseased liver cells. The emergence of human induced pluripotent stem cells and differentiation protocols to generate hepatocyte-like cells has opened the possibility of addressing these issues. Here, we discuss the recent progress and potential in the production of various cell types constituting the liver and their applications to model liver diseases and test drug toxicity in vitro.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1016/j.bpj.2019.11.3383
|
Physiochemical Modeling of Vesicle Dynamics upon Osmotic Upshift
|
We modeled the relaxation dynamics of (lipid) vesicles upon osmotic upshift, taking into account volume variation, chemical reaction kinetics, and passive transport across the membrane. We focused on the relaxation kinetics upon addition of impermeable osmolytes such as KCl and membrane-permeable solutes such as weak acids. We studied the effect of the most relevant physical parameters on the dynamic behavior of the system, as well as on the relaxation rates. We observe that 1) the dynamic complexity of the relaxation kinetics depends on the number of permeable species; 2) the permeability coefficients (P) and the weak acid strength (pKa-values) determine the dynamic behavior of the system; 3) the vesicle size does not affect the dynamics, but only the relaxation rates of the system; and 4) heterogeneities in the vesicle size provoke stretching of the relaxation curves. The model was successfully benchmarked for determining permeability coefficients by fitting of our experimental relaxation curves and by comparison of the data with literature values (in this issue of Biophysical Journal). To describe the dynamics of yeast cells upon osmotic upshift, we extended the model to account for turgor pressure and nonosmotic volume.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
W2060325669
|
Identity-based trapdoor mercurial commitments and applications
|
In this paper, we first introduce the notion of identity-based trapdoor mercurial commitment which enjoys the advantages of both the identity-based trapdoor commitment and trapdoor mercurial commitment, while using the idea of “Customized Identity”. Inherently, an identity-based trapdoor mercurial commitment is an underlying building block for constructing identity-based (non-interactive) zero-knowledge sets. That is, a prover can commit to a set S in a way that reveals nothing about S and prove to a verifier, in zero-knowledge, statements of the form x ∈ S and x ∉ S . Besides, although the (non-interactive) proof is publicly verifiable, it is also bound to the identity of the prover in a way which is recognizable to any verifier.
|
[
"Computer Science and Informatics"
] |
10.1007/978-3-319-23461-8_32
|
Interactively Exploring Supply And Demand In The Uk Independent Music Scene
|
We present an exploratory data mining tool useful for finding patterns in the geographic distribution of independent UK-based music artists. Our system is interactive, highly intuitive, and entirely browser-based, meaning it can be used without any additional software installations from any device. The target audiences are artists, other music professionals, and the general public. Potential uses of our software include highlighting discrepancies in supply and demand of specific music genres in different parts of the country, and identifying at a glance which areas have the highest densities of independent music artists.
|
[
"Computer Science and Informatics",
"Human Mobility, Environment, and Space"
] |
W189981494
|
Fault Detection and Circuit Analysis of INSTRON 1603 Fatigue Testing Machine
|
Instron 1603 is a fatigue testing machine imported from England in 1987. This machine works on electromagnetic principle. Instron is presently supplying 8000’s series which are Hydraulic Based machines. 1603 can be used for testing up to 120 Hz load cycle where as the present machines can be used until 10Hz load cycle, this is where 1603 scores over present machines but strategically company has stopped manufacturing and service to this machine. The machine present in our institute is not in working condition from the past 2 years, the reason behind this is misalignment of circuits, and this is where we pitch in to look into the problem and fix it. The team’s objective was basically concerned with understanding the machine in depth, to make a total record of the machine and to do a strategic design of the controller and other important circuits to run the machine.
|
[
"Systems and Communication Engineering",
"Products and Processes Engineering"
] |
10.1111/j.1474-9726.2009.00463.x
|
Congenital DNA repair deficiency results in protection against renal ischemia reperfusion injury in mice
|
Cockayne syndrome and other segmental progerias with inborn defects in DNA repair mechanisms are thought to be due in part to hypersensitivity to endogenous oxidative DNA damage. The accelerated aging-like symptoms of this disorder include dysmyelination within the central nervous system, progressive sensineuronal hearing loss and retinal degeneration. We tested the effects of congenital nucleotide excision DNA repair deficiency on acute oxidative stress sensitivity in vivo. Surprisingly, we found mouse models of Cockayne syndrome less susceptible than wild type animals to surgically induced renal ischemia reperfusion injury, a multifactorial injury mediated in part by oxidative damage. Renal failure-related mortality was significantly reduced in Csb-/- mice, kidney function was improved and proliferation was significantly higher in the regenerative phase following ischemic injury. Protection from ischemic damage correlated with improved baseline glucose tolerance and insulin sensitivity and a reduced inflammatory response following injury. Protection was further associated with genetic ablation of a different Cockayne syndrome-associated gene, Csa. Our data provide the first functional in vivo evidence that congenital DNA repair deficiency can induce protection from acute stress in at least one organ. This suggests that while specific types of unrepaired endogenous DNA damage may lead to detrimental effects in certain tissues, they may at the same time elicit beneficial adaptive changes in others and thus contribute to the tissue specificity of disease symptoms.
|
[
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
W1988443096
|
Research Integrity in Communication Sciences and Disorders: Preface
|
Purpose A joint program on Research on Research Integrity sponsored by the National Institute of Neurological Disorders and Stroke and the Office of Research Integrity encouraged the examination of practices and policies promoting the responsible conduct of research (RCR). The authors' grant—Research Integrity in ASHA: Education and Publication—enabled American Speech-Language-Hearing Association’s (ASHA) Research Integrity Grant Group to (a) identify patterns of teaching and learning in Communication Sciences and Disorders graduate programs about specific topics of research integrity on the conduct of science, (b) examine perceptions about concepts of research integrity as they apply to scientific journals within the discipline, and (c) evaluate policies and practices established by ASHA to protect the integrity of published scientific work. Method The authors reviewed historical and contemporary literature, conducted surveys, and analyzed ASHA policies. Conclusion This supplement of the Journal of Speech, Language, and Hearing Research has been written with the aim of informing and inspiring scientists, students, research institutions, and professional societies to practice responsible research in the 21st century and beyond.
|
[
"The Social World and Its Interactions"
] |
EP 9701339 W
|
PROCESS FOR PREPARING ALKOXYLATED FATTY ACID ALKYL ESTERS
|
The invention concerns a process for alkoxylating fatty acid alkyl esters, fatty acid esters being reacted in a manner known per se with alkylene oxides in the presence of double-layer mixed oxide catalysts and co-catalysts selected from the group comprising lithium hydroxide, alkaline earth salts and tin salts. The novel catalyst systems produce products which have a narrow homologue distribution and are additionally distinguished by a particularly low content of free alkylester and alkylmonoglycol ester.
|
[
"Synthetic Chemistry and Materials",
"Products and Processes Engineering"
] |
10.7554/eLife.14119
|
A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies
|
The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin b, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior –a key element for the transport selectivity of the NPC –was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
W2353162123
|
Analysis on the Questionnaire Design of Public Meteorological Service Benefit in Jiangsu Province
|
The quality of questionnaire design had a direct influence on the data compilation and results analysis of questionnaire.Combining with the questionnaire design of public meteorological service benefit in Jiangsu Province,the control of questionnaire design quality was put forward,namely,we should develop from three aspects:first,preliminary preparation work,second,following the design rules and skills,third,final questionnaire detection.The rules and skills what should be followed at the time of designing the questionnaire of public meteorological service benefit in Jiangsu Province were elaborated mainly.It indicated that if we want to keep a position of neutrality at the time of questionnaire design,the situation of respondents,colloquial expressions,humanity design,designing few but best open questions,mastering the measure of questionnaire should be considered,thus,the reality and accuracy of investigated data can be ensured basically,finally,the quality of questionnaire was ensured.
|
[
"Earth System Science",
"The Social World and Its Interactions"
] |
W2028104859
|
Integrated biomarker response index using a Neotropical fish to assess the water quality in agricultural areas
|
Aquatic ecosystems in areas with intense agricultural activity are subject to pesticide contamination, which may compromise the health of the fish. In order to verify the quality of the water and the possible effects of pesticides on fish, a method that combines different biomarker responses into an index named "integrated biomarker response" (IBR) was applied using the biological alterations in the Neotropical fish Astyanax altiparanae. Fish were maintained in situ at five sites along a stream that runs in an agricultural area and in a stream within a forest fragment, considered a reference site. After seven days of exposure the following alterations were observed in fish confined at experimental sites: increased activity of glutathione-S-transferase (GST) and catalase (CAT) and increase in the content of reduced glutathione (GSH) in liver and gills, reduction of acetylcholinesterase (AChE) activity in the brain and muscle, increase in the occurrence of DNA strand breaks and in the frequency of micronuclei (MN) and nuclear abnormalities (ENA) in erythrocytes. The IBR highlighted three sites as the most affected, as the animals confined at these sites showed greater variations in biological responses. The biomarkers most important for the IBR results were GST, AChE, DNA breaks and ENA.
|
[
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
] |
W2002036498
|
Sequencing Analysis of the ATOH7 Gene in Individuals with Optic Nerve Hypoplasia
|
The Atonal Homolog 7 (ATOH7) gene has been implicated in association studies with optic nerve head diameter size. Hence, we screened optic nerve hypoplasia (ONH) patient DNA samples from Australia, France, and the United States for sequence variants in theATOH7 gene using Sanger sequencing.Sanger sequencing of theATOH7 gene was performed on 34 affected individual DNA samples. Sequencing was also carried out in three unaffected family members to confirm segregation of identified single nucleotide variations.Seven sequence variations were identified in ATOH7. No disease-causing sequence changes in the ATOH7 gene was discovered in the ONH patient samples.Mutations within the ATOH7 gene are not implicated in the pathogenesis of optic nerve hypoplasia in our patient cohort.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
] |
W1606352554
|
Glottal gap as an early predictor for permanent laryngoplasty in unilateral vocal fold paralysis
|
To assess the possible predictive factors for permanent laryngoplasty (PL) in patients with acute unilateral vocal fold paralysis (UVFP), and to assess the effects of early vocal cord hyaluronic acid injection.Prospective cohort study.Patients diagnosed with UVFP within the previous 6 months were enrolled. Initial and follow-up videolaryngostroboscopy, voice laboratory analysis, laryngeal electromyography, and Voice Outcome Survey were performed.Fifty newly diagnosed UVFP patients were recruited. Eight were excluded after 12 months of follow-up and data for 42 patients were analyzed. In patients treated conservatively, the glottal gap was measured on presentation. Normalized glottal gap area (NGGA) was the only predictor of PL (P = 0.036) according to multivariate logistic regression analysis. A cutoff value of 7.36 resulted in sensitivity of 85.7% and specificity of 80.0% for predicting future PL. The PL rate was significantly higher in patients with an initial NGGA > 7.36 compared with ≤ 7.36. (6/9 vs. 1/13; χ(2) = 6.71; P = 0.010). Among patients with an initial NGGA > 7.36, those who accepted early hyaluronic acid injection had a significantly lower rate of PL (1/11 vs. 6/9; χ(2) = 7.21; P = 0.007) and better social and emotional role functioning at follow-up.The glottal gap on presentation is a robust early predictor of PL. Early, office-based hyaluronic acid intracordal injection can reduce the need for PL in patients with a large NGGA.
|
[
"Prevention, Diagnosis and Treatment of Human Diseases",
"Physiology in Health, Disease and Ageing"
] |
interreg_1201
|
Environmental Park
|
EPA supports the strengthening and promotion of the protected areas involved in the project through their sustainable use. The long-term goal is the seasonal adjustment of tourism in the territories that is not connected only to the sea and to the summer. The specific objectives of the project are:
o to promote sustainable mobility within and between protected areas (Parks, Reserves, Marines Protected Areas, SIC, etc..)
o to provide electric vehicles with solar panels so they can feed itself
o to develop a network of trails connecting for non-motorized transportation with the realization of specific signs and billboards.
o to try to enhance the creation of a historical and archaeological route (involving infrastructure) that will also be a measure on the use of the seabed accessible for the blind, through a training course for guides and instructors for divers who are blind.
o to restore and enhance the landscape and preserve the naturalness of a lake in the eligible area (in Western Greece).
|
[
"Products and Processes Engineering",
"Environmental Biology, Ecology and Evolution"
] |
W2805623367
|
Inflation expectations and the recovery from the Great Depression in Germany
|
Abstract A regime shift toward increased inflation expectations is credited with jump-starting the recovery from the Great Depression in the United States. What role did inflation expectations play in Germany that experienced a similarly successful economic upturn in the 1930s? We study inflation expectations in the German recovery across several methods: we conduct a narrative study of media sources; we estimate inflation expectations from a factor-augmented vector autoregression model, real interest rate forecasts, and quantitative news series. Consistently across these approaches, we do not find a shift to increased expected inflation. This recovery was different, and its causes lie elsewhere.
|
[
"Individuals, Markets and Organisations",
"The Study of the Human Past"
] |
US 84894104 A
|
Dynamic interface software for wireless communication devices
|
The present invention provides an improved wireless communication device capable of detecting the presence of an external device and dynamically updating its communication abilities to facilitate communication with the external device. The wireless communication device, upon detecting a wired or wireless connection from an external device, queries the external device to obtain summary profile information about the external device. The wireless device next formulates a query comprising at least a portion of the summary profile information and sends the query to a remote server to request an appropriate communication interface. The remote server responds with the appropriate communication interface. Upon receipt of the interface, the wireless communication device installs the interface and then proceeds to establish communication with the external device.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
10.1029/2009GL042145
|
Crustal Structure Beneath Montserrat Lesser Antilles Constrained By Xenoliths Seismic Velocity Structure And Petrology
|
[1] Noritic anorthosite, gabbroic anorthosite and hornblende-gabbro xenoliths are ubiquitous in the host andesite at Montserrat. Other xenoliths include quartz diorite, metamorphosed biotite-gabbro, plagioclase-hornblendite and plagioclase-clinopyroxenite. Mineral compositions suggest a majority of the xenoliths are cognate. Cumulate, hypabyssal and crescumulate textures are present. A majority of the xenoliths are estimated to have seismic velocities of 6. 7–7. 0 km/s for pore-free assemblages. These estimates are used in conjunction with petrological models to constrain the SEA CALIPSO seismic data and the structure of the crust beneath Montserrat. Andesitic upper crust is interpreted to overlie a lower crust dominated by amphibole and plagioclase. Xenolith textures and seismic data indicate the presence of hypabyssal intrusions in the shallow crust. The structure of the crust is consistent with petrological models indicating that fractionation is the dominant process producing andesite at Montserrat.
|
[
"Earth System Science",
"Physical and Analytical Chemical Sciences"
] |
222983
|
Accurate intravenous therapy for every patient
|
Intravenous (IV) therapy involves administration of fluids or medications through a needle or a catheter and it is administered to over 90% of hospitalised patients. Although a simple procedure, a balanced IV therapy has a significant impact by reducing the number of complications by 59% and the length of hospital stay by 3.4 days. Currently the everyday IV treatment is administered manually and monitored visually as the infusion pumps that offer accurate treatment monitoring are very expensive and complicated to use, making them suitable only for emergencies.
A Finnish SME, Monidor, has developed high-accuracy IV infusion monitoring device based on patented technology that uses infra-red light beam drop calculation and specific measurement algorithms. This allows to offer state-of-the-art accuracy in a simple and cost effective form bringing balanced IV therapy to every bed in the hospital. Additional features such as touch-screen interface and wireless connectivity will help to lower the associated workload for the medical staff. Monidor has been developing the technology for the past two years and has reached a prototype device currently defined at TRL7. The technological excellence has been tested with Oulu University Hospital and user needs studies have been conducted with medical staff in Finland, UK, Italy and Denmark. The company has a strong team of 8 experts including doctors and engineers with experience in R&D and business development from companies such as Nokia, Microsoft and Broadcom.
Monidor is now looking to conduct the feasibility studies in order to finalize the development process and introduce the novel solution to the market. As a result of the proposed project Monidor will have a validated technology development plan, IPR strategy for EU-wide technology exploitation and a detailed business plan to commercialize the technology. According to the first estimates the company has the potential to generate revenues of more than 30MEUR by 2022.
|
[
"Products and Processes Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.3389/feart.2018.00012
|
Spatial variability in patterns of glacier change across the manaslu range, central himalaya
|
This study assesses changes in glacier area, velocity, and geodetic mass balance for the glaciers in the Manaslu region of Nepal, a previously undocumented region of the Himalayas. We studied changes between 1970 (for select glaciers), 2000, 2005, and 2013 using freely available Landsat satellite imagery, the SRTM Digital Elevation Model (DEM) and a DEM based on Worldview imagery. Our results show a complex pattern of mass changes across the region, with glaciers lowering on average by 0. 25 ±0. 08ma−1 between 2000 and 2013 which equates to a geodetic mass balance of −0. 21 ± 0. 16m w. e. a−1. Over approximately the same time period (1999 to 2013) the glaciers underwent a 16. 0% decrease in mean surface velocity over their debris-covered tongues as well as a reduction in glacier area of 8. 2%. The rates of glacier change appear to vary between the different time periods, with glacier losses increasing in most cases. The glaciers on Manaslu itself underwent a change in surface elevation of −0. 46 ± 0. 03m a−1 between 1970 and 2000 and −0. 99 ±0. 08ma−1 between 2000 and 2013. Rates of glacier area change for the same glaciers increased from−0. 36 km2 a−1 between 1970 and 2001 to −2. 28 km2 a−1 between 2005 and 2013. Glacier change varies across the region and seems to relate to a combination of glacier hypsometry, glacier elevation range and the presence and distribution of supraglacial debris. Lower-elevation, debris-free glaciers with bottom-heavy hypsometries are losing most mass. As the glaciers in the Manaslu region continue to stagnate, an accumulation and thickening of the debris-cover is likely, thereby insulating the glacier and further complicating future glacier responses to climate.
|
[
"Earth System Science"
] |
interreg_3266
|
SHARE - Sustainable Hydropower in Alpine Rivers Ecosystems
|
Hydropower is the most important renewable resource for electricity production in alpine areas: it has advantages for the global CO2 balance but creates serious environmental impacts. RES-e Directives require a renewable electricity enhance but, at the same time, the Water Framework Directive obliges member States to reach or maintain a water bodies "good" ecological status, intrinsically limiting the hydropower exploitation. Administrators daily face an increasing demand of water abstraction but lack reliable tools to rigorously evaluate their effects on mountain rivers and the social and economical outputs on longer time scale. The project intends to develop, test and promote a decision support system to merge on an unprejudiced base, river ecosystems and hydropower requirements. This approach will be led using existing scientific tools, adjustable to transnational, national and local normative and carried on by permanent panel of administrators and stakeholders.
|
[
"Earth System Science",
"Products and Processes Engineering",
"Environmental Biology, Ecology and Evolution"
] |
10.1214/17-EJS1339SI
|
Poisson Intensity Estimation With Reproducing Kernels
|
Despite the fundamental nature of the inhomogeneous Poisson process in the theory and application of stochastic processes, and its attractive generalizations (e. g. Cox process), few tractable nonparametric modeling approaches of intensity functions exist, especially when observed points lie in a high-dimensional space. In this paper we develop a new, computationally tractable Reproducing Kernel Hilbert Space (RKHS) formulation for the inhomogeneous Poisson process. We model the square root of the intensity as an RKHS function. Whereas RKHS models used in supervised learning rely on the so-called representer theorem, the form of the inhomogeneous Poisson process likelihood means that the representer theorem does not apply. However, we prove that the representer theorem does hold in an appropriately transformed RKHS, guaranteeing that the optimization of the penalized likelihood can be cast as a tractable finite-dimensional problem. The resulting approach is simple to implement, and readily scales to high dimensions and large-scale datasets.
|
[
"Mathematics",
"Computer Science and Informatics"
] |
10.1094/MPMI-07-15-0147-R
|
Tomato I2 Immune Receptor Can Be Engineered To Confer Partial Resistance To The Oomycete Phytophthora Infestans In Addition To The Fungus Fusarium Oxysporum
|
Plants and animals rely on immune receptors, known as nucleotide-binding domain and leucine-rich repeat (NLR)-containing proteins, to defend against invading pathogens and activate immune responses. How NLR receptors respond to pathogens is inadequately understood. We previously reported single-residue mutations that expand the response of the potato immune receptor R3a to AVR3a(EM), a stealthy effector from the late blight oomycete pathogen Phytophthora infestans. I2, another NLR that mediates resistance to the will-causing fungus Fusarium oxysporum f. sp. lycopersici, is the tomato ortholog of R3a. We transferred previously identified R3a mutations to I2 to assess the degree to which the resulting I2 mutants have an altered response. We discovered that wild-type I2 protein responds weakly to AVR3a. One mutant in the N-terminal coiled-coil domain, I2(I141N), appeared sensitized and displayed markedly increased response to AVR3a. Remarkably, I2(I141N) conferred partial resistance to P. infestans. Further, I2(I141N) has an expanded response spectrum to F. oxysporum f. sp. lycopersici effectors compared with the wild-type I2 protein. Our results suggest that synthetic immune receptors can be engineered to confer resistance to phylogenetically divergent pathogens and indicate that knowledge gathered for one NLR could be exploited to improve NLR from other plant species.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
US 0213316 W
|
OPTICAL LENS COATING AND METHOD
|
An optical lens having a colored coating affixed to the edge (110) of the lens. The apparatus may enhance the cosmetic appearance of eyeglasses (200) by reducing the appearance of the white ring appearing along the perimeter of the face (120) of lens when viewing eyeglasses from the front, and by reducing the appearance of the white film on the edge of lenses when viewing eyeglasses from the side. The apparatus may also reduce the glare of the optical lens from light entering through the edge of the lens.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
interreg_3380
|
Save Our Lives. A Comprehensive Road Safety Strategy for Central Europe
|
Every year more than 40,000 people lose their lives on Europe’s roads. In the EU, 1 out of every 5 child deaths due to injury are a result of road crashes. While many western European countries are making continuous progress in reducing the number of lives lost, fatality rates in many new Member States in the Central Europe Programme area remain high and in some they are even increasing. With the exception of Hungary all other new Member States in Central Europe have been confronted with a rise in the number of fatalities on their roads in 2007 (in the Czech Republic by 15% and in Ukraine even by 38%).
Central Europe clearly shows a higher number of road fatalities per million inhabitants than Western Europe. Within Central Europe, the highest value is observed in Poland (143 road fatalities per million inhabitants), followed by Slovenia (129), Hungary (128) and the Czech Republic (126)” compared to Italy (96), Austria (88), and Germany (62).
In Central Europe road safety challenge has reached a magnitude that even puts the overall competitiveness, the attractiveness as location for working and investments as well as the quality of life in the most seriously affected parts of the cooperation area at considerable risk. Road crashes have a severe negative impact on the social and economic situation in all countries, costing up to 2 percent or more of the GDP. Even though there are some good practice examples also in the new Member States of the Central Europe area, where road safety has been addressed successfully in the past years, severe joint efforts will be required by all relevant stakeholders on all levels to make a contribution also within Central Europe to reach the overall policy goal set by the European Commission (EC) in 2003 within the 3rd Road Safety Action Programme: to halve the number of lives lost on our roads from 50,000 to 25,000 per year by 2010.
|
[
"Human Mobility, Environment, and Space",
"Institutions, Governance and Legal Systems"
] |
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