id
stringlengths 6
42
| title
stringlengths 3
499
| abstract
stringlengths 0
6.24k
| label
listlengths 0
6
|
|---|---|---|---|
10.1088/0965-0393/24/2/025005
|
An interatomic pair potential with tunable intrinsic ductility
|
A family of interatomic potentials is constructed for which the intrinsic ductility can be tuned systematically. Specifically, the elastic constants and critical energy release rate for Griffith cleavage, GIc, are held constant, while the critical energy release rate for dislocation emission, GIc, can be varied. This behavior is achieved by modifying a standard near-neighbor pair potential; the new potential is applicable to either 2D (hexagonal lattice) or 3D (FCC/HCP). Analytical expressions are provided for GIe and GIc, enabling a potential with a desired intrinsic ductility to be easily developed. Direct atomistic simulations are used to demonstrate that the new potentials control the intrinsic material ductility, i. e. crack tip dislocation emission versus brittle cleavage, under quasi-static loading. For the 2D potential, the mode I crack tip behavior can be tuned from brittle to ductile; for the 3D potential, such tuning is only possible for certain crack orientations. More generally, the new potentials are expected to be useful in a wide range of physical problems in which behavior is controlled by the ability of the material to nucleate dislocations, including problems involving crack tips, grain boundaries, contact and friction, and bi-material interfaces.
|
[
"Condensed Matter Physics",
"Materials Engineering"
] |
10.1371/journal.pmed.1001484
|
Global Burden of Sickle Cell Anaemia in Children under Five, 2010-2050: Modelling Based on Demographics, Excess Mortality, and Interventions
|
Background:The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions. Methods and Findings:First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400-398,800) in 2010 to 404,200 (CI: 242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100-70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900-64,700]). The implementation of basic health interventions (e. g. , prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800-6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800-14,232,700) newborns with SCA globally, 85% (CI: 81%-88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions. Conclusions:Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India. Please see later in the article for the Editors' Summary.
|
[
"Prevention, Diagnosis and Treatment of Human Diseases",
"Integrative Biology: from Genes and Genomes to Systems",
"Human Mobility, Environment, and Space"
] |
10.1016/j.palaeo.2013.09.019
|
Mountain building and the initiation of the greenland ice sheet
|
The effects of a new hypothesis about mountain building in Greenland on ice sheet initiation are investigated using an ice sheet model in combination with a climate model. According to this hypothesis, low-relief landscapes near sea level characterised Greenland in Miocene times until two phases of km-scale uplift in the late Miocene and in the latest Miocene-Pliocene (beginning at 10 and ~. 5. Ma, respectively) initiated the formation of the present-day mountains. The topography of Greenland, prior to these uplift events is reconstructed from the present-day, isostatically compensated bedrock by mapping the two main steps in the landscape that resulted from the two uplift phases. Ice sheet initiation is studied using the topography before uplift and after each phase of uplift by applying different forcing conditions relevant for the late Cenozoic, which was characterised by long-term cooling superimposed by cold and warm excursions. The modelling results show that no ice initiates in the case of the low-lying and almost flat topography prior to the uplifts. However, the results demonstrate a significant ice sheet growth in response to the orographically induced increase in precipitation and the cooling of surface temperatures accompanying the uplift. Large amounts of ice are able to form after the first uplift event, but the ice sheet is sensitive to changes in climate. The results show that the second phase of uplift facilitates ice sheet build-up further and increases the stability of the ice sheet by providing anchoring points which are not available to the same extent in the lower topographies. However, the results also reveal a Föhn effect that inhibits ice sheet expansion into the interior Greenland and thus shifts the threshold of formation of inland ice towards colder temperatures. Under conditions that are colder than the present, the ice can overcome the Föhn effect, flow into the interior and form a coherent ice sheet. The results thus indicate that the Greenland Ice Sheet of today is a relict formed under colder conditions. The modelling results are consistent with the observed climatic variability superimposed on the general cooling trend in the late Cenozoic: e. g. , ice rafted debris in late Miocene deposits off southeast Greenland and the mid-Pliocene Warmth. The late Cenozoic mountain building in Greenland augments the effects of the climatic deterioration leading to the Northern Hemisphere glaciations, and without the second phase of uplift, the Greenland Ice Sheet would have been more sensitive to the changes in climate over the past millions of years.
|
[
"Earth System Science"
] |
10.1039/C5TA01224D
|
Morphology And Local Electrical Properties Of Ptb7 Pc71Bm Blends
|
The power conversion efficiency of single layer organic solar cells can approach 10% with blends such as the polymer PTB7 and the fullerene derivative PC71BM. Here the detailed structure of PTB7:PC71BM blends deposited with and without addition of diiodooctane is studied by transmission electron microscopy and scanning probe microscopy. The details of bulk structure, such as the thickness of the layer covering fullerene domains and the grain structure of the film are examined. We find that fullerene-rich domains can be near the surface of the film or buried deeper, near the substrate. The local electrical properties of these blends are studied by conductive atomic force microscopy for different configurations of electrodes. Different power conversion efficiencies of blends with and without diiodooctane are explained in terms of local photoconductive properties.
|
[
"Condensed Matter Physics",
"Synthetic Chemistry and Materials",
"Materials Engineering"
] |
278636
|
Pliocene Constraints on Earth System Sensitivity
|
The magnitude of long-term global temperature rise due to an increasing concentration of carbon dioxide (CO2) in the atmosphere is a question of relevance to policy makers and society. Previous studies have addressed this issue on the basis of the equilibrium response of the climate system due to fast feedbacks such as clouds and sea ice-albedo, often referred to as Climate Sensitivity. Plio-ESS will use the new concept of Earth System Sensitivity that additionally includes slow feedbacks such as those derived from changes in the major ice sheets and vegetation distribution. This has the potential to revolutionise the scientific debate on anthropogenic emissions of greenhouse gases and climate stabilisation targets. The aim of the project is to produce a robust estimate of the Earth System Sensitivity using the last interval in Earth history when CO2 was at modern or near future levels – the mid-Pliocene Warm Period. Using a combined modelling and geological data approach, Plio-ESS will integrate reconstructions of mid-Pliocene vegetation and ice sheets into climate and Earth system models. In this context Plio-ESS will push the frontier of palaeoclimatology by using state-of-the-art models which will enable the importance of resolution, improved model physics and the inclusion of additional Earth System components on model estimates of Earth System Sensitivity to be identified. Ensembles of experiments exploring the plausible range in model boundary conditions and physics will also quantify the uncertainty on estimates of Earth System Sensitivity. The outcome of the project will be a rigorous estimate of Earth System Sensitivity, which can be used by climate scientists and policy makers in defining stabilisation targets for greenhouse gas emissions and global temperatures to avoid dangerous levels of climate change.
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution"
] |
10.1002/hep.24489
|
Both innate and adaptive immunity mediate protective immunity against hepatitis C virus infection in chimpanzees
|
Understanding the immunological correlates associated with protective immunity following hepatitis C virus (HCV) reexposure is a prerequisite for the design of effective HCV vaccines and immunotherapeutics. In this study we performed a comprehensive analysis of innate and adaptive immunity following HCV reexposure of two chimpanzees that had previously recovered from HCV-JFH1 infection. One of the chimpanzees, CH10274, became protected from active viremia by repeated challenges with homologous HCV-JFH1 and developed neutralizing antibodies, but was later infected with high-level viremia by a heterologous challenge with the HCV H77 virus that persisted for more than 1 year. The other chimpanzee, CH10273, was protected from a similar, heterologous H77 challenge without any evidence of neutralizing antibodies. Peripheral HCV-specific T-cell responses were present in both chimpanzees after challenges and, interestingly, the overall magnitude of response was lower in uninfected CH10273, which, however, exhibited a more robust CD8+ T-cell response. CH10273 showed higher hepatic expression of CD8 and CD56 (natural killer) markers than CH10274 did shortly after inoculation with H77. The heightened T-cell response was associated with an enhanced hepatic production of interferons (both type I and II) and interferon-stimulated genes (ISGs) in CH10273. Therefore, protection or clearance of HCV reinfection upon heterologous rechallenge depends on the activation of both intrahepatic innate and cellular immune responses. Furthermore, our results suggest that serum neutralizing antibodies may contribute to early control of viral replication and spread after homologous HCV rechallenges but may not be sufficient for a long-term protective immunity. Conclusion: Our study shows that protective immunity against HCV reinfection is orchestrated by a complex network of innate and adaptive immune responses.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
CH 9200125 W
|
OSTEOSYNTHETIC FIXATION DEVICE
|
The osteosynthetic fixation device consists of a securing component (1) having a conical head section (11) and an adjoining anchoring component (13) designed for fixing in the bone, and a spherical segment-shaped slotted clamping component (2) with a conical bore (21) to receive the conical head section (11) to clamp inside a connecting component (3) having a spherical segment-shaped bore (31). The securing component (1) has an axially arranged tension component (4) which permits the axial movement and wedging of the conical head section (11) in the corresponding bore (21). The securing device is suitable as a plate/screw system, an external or internal fixing device and especially for fixation of the spinal column.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
10.1038/s41598-019-51326-2
|
Development and application of affordable SNP typing approaches to genotype Mycobacterium tuberculosis complex strains in low and high burden countries
|
The Mycobacterium tuberculosis complex (MTBC) comprises the species that causes tuberculosis (TB) which affects 10 million people every year. A robust classification of species, lineages, and sub-lineages is important to explore associations with drug resistance, epidemiological patterns or clinical outcomes. We present a rapid and easy-to-follow methodology to classify clinical TB samples into the main MTBC clades. Approaches are based on the identification of lineage and sub-lineage diagnostic SNP using a real-time PCR high resolution melting assay and classic Sanger sequencing from low-concentrated, low quality DNA. Thus, suitable for implementation in middle and low-income countries. Once we validated our molecular procedures, we characterized a total of 491 biological samples from human and cattle hosts, representing countries with different TB burden. Overall, we managed to genotype ~95% of all samples despite coming from unpurified and low-concentrated DNA. Our approach also allowed us to detect zoonotic cases in eight human samples from Nigeria. To conclude, the molecular techniques we have developed, are accurate, discriminative and reproducible. Furthermore, it costs less than other classic typing methods, resulting in an affordable alternative method in TB laboratories.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Immunity, Infection and Immunotherapy",
"Biotechnology and Biosystems Engineering"
] |
175567
|
3D printing of cell laden biomimetic materials and biomolecules for joint regeneration
|
Osteoarthritis (OA) is a serious disease of the joints affecting nearly 10% of the population worldwide. Realising an efficacious therapeutic solution for treating OA remains one of the greatest challenges in the field of orthopaedic medicine. This proposal envisions a future where 3D bioprinting systems located in hospitals will provide ‘off-the-shelf’, patient-specific biological implants to treat diseases such as OA. To realise this vision, this project will use 3D bioprinting to generate anatomically accurate, biomimetic constructs that can be used to regenerate both the cartilage and bone in a diseased joint. The first aim of this proposal is to print a mesenchymal stem cell laden biomaterial that is both immediately load bearing and can facilitate the regeneration of articular cartilage in vivo, such that the bioprinted construct will not require in vitro maturation prior to implantation. Mechanical function will be realised by integrating an interpenetrating network hydrogel into a 3D printed polymeric scaffold, while chondro-inductivity will be enhanced by the spatially-defined incorporation of cartilage extracellular matrix components and chondrogenic growth factors into the bioprinted construct. The second aim of the proposal is to use 3D bioprinting to create a cell-free, composite construct to facilitate regeneration of the bony region of a large osteochondral defect, where vascularization will be accelerated by immobilizing spatial gradients of vascular endothelial growth factor into the implant. The third aim of the proposal is to scale-up the proposed 3D bioprinted construct to enable whole joint regeneration. Finite element modelling will be used determine the optimal structural characteristics of the scaled-up implant for it to fulfil its required mechanical function. If successful, such an implant would form the basis of a truly transformative therapy for treating degenerative joint disease.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Materials Engineering"
] |
10.1016/j.bios.2018.03.011
|
Disposable electrochemical detection of breast cancer tumour marker CA 15-3 using poly(Toluidine Blue) as imprinted polymer receptor
|
In this work, electrically-conducting poly(Toludine Blue) was employed for the first time as synthetic receptor film, prepared by Molecular Imprinting strategies and using electrochemical methods, for the specific screening of breast cancer biomarker Carbohydrate Antigen 15-3 (CA 15-3). The protein imprinted poly(Toluidine Blue) film was grown in a pre-formed Toluidine Blue (TB) tailed SAM at the AuSPE surface, which greatly enhanced the stability against degradation of the Molecular Imprinted Polymer (MIP) film at the electrode surface. The MIP receptor film recognition ability towards the protein was investigated by fitting data to Freundlich isotherm. The binding affinity (KF) obtained for the MIP system was significantly higher (~ 12-fold) to that obtained for the NIP system, demonstrating the success of the approach in creating imprinted materials that specifically respond to CA 15-3 protein. The incubation of the MIP modified electrode with increasing concentration of protein (from 0. 10 U mL−1 to 1000 U mL−1) resulted in a decrease of the ferro/ferricyanide redox current. The device displayed linear response from 0. 10 U mL−1 to 100 U mL−1 and LODs below 0. 10 U mL−1 were obtained from calibration curves built in neutral buffer and diluted artificial serum, using DPV technique, enabling the detection of the protein biomarker at clinically relevant levels. The developed MIP biosensor was applied to the determination of CA 15-3 in spiked serum samples with satisfactory results. The developed device provides a new strategy for sensitive, rapid, simple and cost-effective screening of CA 15-3 biomarker. Importantly, the overall approach seems suitable for point-of-care (PoC) use in clinical context.
|
[
"Physical and Analytical Chemical Sciences",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Materials Engineering"
] |
10.1093/pcp/pcz078
|
Biosynthesis of Long Chain Alkyl Diols and Long Chain Alkenols in Nannochloropsis spp. (Eustigmatophyceae)
|
AbstractWe investigated potential biosynthetic pathways of long chain alkenols (LCAs), long chain alkyl diols (LCDs), and long chain hydroxy fatty acids (LCHFAs) in Nannochloropsis oceanica and Nannochloropsis gaditana, by combining culturing experiments with genomic and transcriptomic analyses. Incubation of Nannochloropsis spp. in the dark for 1 week led to significant increases in the cellular concentrations of LCAs and LCDs in both species. Consistently, 13C-labelled substrate experiments confirmed that both LCA and LCD were actively produced in the dark from C14–18 fatty acids by either condensation or elongation/hydroxylation, although no enzymatic evidence was found for the former pathway. Nannochloropsis spp. did, however, contain (i) multiple polyketide synthases (PKSs) including one type (PKS-Clade II) that might catalyze incomplete fatty acid elongations leading to the formation of 3-OH-fatty acids, (ii) 3-hydroxyacyl dehydratases (HADs), which can possibly form Δ2/Δ3 monounsaturated fatty acids, and (iii) fatty acid elongases (FAEs) that could elongate 3-OH-fatty acids and Δ2/Δ3 monounsaturated fatty acids to longer products. The enzymes responsible for reduction of the long chain fatty acids to LCDs and LCAs are, however, unclear. A putative wax ester synthase/acyl coenzyme A (acyl-CoA): diacylglycerol acyltransferase is likely to be involved in the esterification of LCAs and LCDs in the cell wall. Our data thus provide useful insights in predicting the biosynthetic pathways of LCAs and LCDs in phytoplankton suggesting a key role of FAE and PKS enzymes.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Biotechnology and Biosystems Engineering",
"Environmental Biology, Ecology and Evolution"
] |
W622619352
|
CYCLIN-DEPENDENT KINASE G2 regulates salinity stress response and salt mediated flowering in Arabidopsis thaliana
|
Cyclin-dependent protein kinases are involved in many crucial cellular processes and aspects of plant growth and development, but their precise roles in abiotic stress responses are largely unknown. Here, Arabidopsis thaliana CYCLIN-DEPENDENT KINASE G2 (CDKG2) was shown to act as a negative regulator of the salinity stress response, as well as being involved in the control of flowering time. GUS expression experiments based on a pCDKG2::GUS transgene suggested that CDKG2 was expressed throughout plant development, with especially high expression levels recorded in the seed and in the flower. The loss-of-function of CDKG2 led to an increased tolerance of salinity stress and the up-regulation of the known stress-responsive genes SOS1, SOS2, SOS3, NHX3, RD29B, ABI2, ABI3, MYB15 and P5CS1. Flowering was accelerated in the cdkg2 mutants via the repression of FLC and the consequent up-regulation of FT, SOC1, AP1 and LFY. Transgenic lines constitutively expressing CDKG2 showed greater sensitivity to salinity stress and were delayed in flowering. Furthermore, the CDKG2 genotype affected the response of flowering time to salinity stress. Our data connect CDKG2 to undescribed functions related to salt stress tolerance and flowering time through the regulation of specific target genes.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution"
] |
10.1016/j.molcel.2017.08.016
|
SAGA Is a General Cofactor for RNA Polymerase II Transcription
|
Prior studies suggested that SAGA and TFIID are alternative factors that promote RNA polymerase II transcription, with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription in budding yeast. We find that SAGA maps to the UAS elements of most genes, overlapping with Mediator binding and irrespective of previous designations of SAGA- or TFIID-dominated genes. Disruption of SAGA through mutation or rapid subunit depletion reduces transcription from nearly all genes, measured by newly synthesized RNA. We also find that the acetyltransferase Gcn5 synergizes with Spt3 to promote global transcription and that Spt3 functions to stimulate TBP recruitment at all tested genes. Our data demonstrate that SAGA acts as a general cofactor required for essentially all RNA polymerase II transcription and is not consistent with the previous classification of SAGA- and TFIID-dominated genes. Baptista et al. show that SAGA, a transcriptional coactivator conserved in all eukaryotes, is involved in overall RNA polymerase II transcription in budding yeast. Using ChEC-seq, SAGA was shown to be recruited to both TATA-containing and TATA-less genes. In agreement, inactivation of SAGA leads to dramatic effects on nascent transcription.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
] |
interreg_708
|
“COmmunity Nurse Supporting Elderly iN a changing SOciety”
|
European population’s ageing challenges health and social services. Cooperation in several welfare sectors is required, since the demographic change involves both health and social issues. CO.N.S.E.N.SO project accepts the challenge by developing a care model that puts the elderly at the centre of health and social services. It builds on the pivotal role of the Family and Community Nurse (FCN). The FCN plays an innovative role, becoming the key actor who shapes and manages personalised services for the elderly and their families, particularly those living in isolated areas._x000D_
_x000D_
The model aims to allow the elderly to live at home as long as possible: through periodical visits the FCN will evaluate their risk factors, manage minor health and social needs and promote healthier lifestyles. In selected Alpine communities the project will validate a model of transnational governance of processes required to deliver healthcare, prevention and active ageing. Families will benefit from reduced elderly home assistance and Regional Authorities will see a reduction of social and health costs. The project will also build capacity within the social economy by proposing innovative business models. The Alpine space, characterised by significant differences in healthcare models and cultures, is the ideal test area of a simple concept: a model of care that maximises the effect of the human relationship between the elderly and dedicated professionals._x000D_
_x000D_
Information added on 2020-06-02, regarding the mitigation of the effects of COVID-19 (the coronavirus pandemic that started in 2019) (English language only): The Family and Community Nurses enable older people to stay safely at home and avoid hospitalisations. Thanks to the project, the municipality of Piossasco in Piedmont could set up quickly a network of institutions, volunteer association, local Red Cross or parishes to face the COVID-19 by supporting frail families.
|
[
"Physiology in Health, Disease and Ageing",
"The Social World and Its Interactions",
"Human Mobility, Environment, and Space"
] |
10.1039/c3sm52378k
|
Poly(3-hexylthiophene) nanowires in porous alumina: Internal structure under confinement
|
We study the structure of poly(3-hexylthiophene) (P3HT) subjected to nanoscale confinement in two dimensions (2D) as imposed by the rigid walls of nanopore anodic aluminum oxide (AAO) templates. P3HT nanowires with aspect ratios (length-to-diameter) above 1000 and diameters ranging between 15 nm and 350 nm are produced in the pores of the AAO templates via two processing routes. These are, namely, drying a solution or cooling from the melt. Our study focuses on the effects of nanoconfinement on the semicrystalline nature of the nanowires, the orientation of crystals, and the evolution of the structures that P3HT might develop under confinement, which we investigate by combining imaging (SEM), spectroscopic (FTIR, photoluminescence) and structural characterization (WAXS, DSC) techniques. Solution-processed P3HT nanowires are essentially amorphous and porous, whereas melt-processed nanowires are semicrystalline, and present a more compact morphology and smoother surfaces. In the latter case, the orientation of crystals was found to strongly depend on the pore diameter. In large diameter nanowires (250 nm and 120 nm), crystals are oriented laying the π-π stacking direction parallel to the nanowire axis. In contrast, in small diameter nanowires, the π-π stacking direction is mainly perpendicular to the nanowires, as crystals are likely to nucleate at pore walls. The structural evolution of P3HT upon heating into weakly (250 nm in diameter) and strongly (15 nm in diameter) confining pores has been studied. A complex set of structures is observed, i. e. , crystals, a solid layered mesophase, a nematic/smectic mesophase, and the isotropic melt. Interestingly, a rare crystal polymorph (form II) is also observed under strong confinement conditions together with the usual lamellar crystal form I. Furthermore, we show that nanoconfinement stabilizes form II: such crystals are still present at 210 °C while in the bulk they get converted to form I crystals at around 50 °C.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials",
"Materials Engineering"
] |
W3022774600
|
Pandemic Recession: L or V-Shaped?
|
We develop and calibrate a search-theoretic model of the labor market in order to forecast the evolution of the aggregate US labor market during and after the coronavirus pandemic. The model is designed to capture the heterogeneity of the transitions of individual workers across states of unemployment, employment and across different employers. The model is also designed to capture the trade-offs in the choice between temporary and permanent layoffs. Under reasonable parametrizations of the model, the lockdown instituted to prevent the spread of the novel coronavirus is shown to have long-lasting negative effects on unemployment. This is so because the lockdown disproportionately disrupts the employment of workers who need years to find stable jobs.
|
[
"Individuals, Markets and Organisations"
] |
10.1523/JNEUROSCI.1747-14.2014
|
Excitatory Effects Of Parvalbumin Expressing Interneurons Maintain Hippocampal Epileptiform Activity Via Synchronous Afterdischarges
|
Epileptic seizures are characterized by periods of hypersynchronous, hyperexcitability within brain networks. Most seizures involve two stages: an initial tonic phase, followed by a longer clonic phase that is characterized by rhythmic bouts of synchronized network activity called afterdischarges (ADs). Here we investigate the cellular and network mechanisms underlying hippocampal ADs in an effort to understand how they maintain seizure activity. Using in vitro hippocampal slice models from rats and mice, we performed electrophysiological recordings from CA3 pyramidal neurons to monitor network activity and changes in GABAergic signaling during epileptiform activity. First, we show that the highest synchrony occurs during clonic ADs, consistent with the idea that specific circuit dynamics underlie this phase of the epileptiform activity. We then show that ADs require intact GABAergic synaptic transmission, which becomes excitatory as a result of a transient collapse in the chloride (Cl−) reversal potential. The depolarizing effects of GABA are strongest at the soma of pyramidal neurons, which implicates somatic-targeting interneurons in AD activity. To test this, we used optogenetic techniques to selectively control the activity of somatic-targeting parvalbumin-expressing (PV+) interneurons. Channelrhodopsin-2-mediated activation of PV+ interneurons during the clonic phase generated excitatory GABAergic responses in pyramidal neurons, which were sufficient to elicit and entrain synchronous AD activity across the network. Finally, archaerhodopsin-mediated selective silencing of PV+ interneurons reduced the occurrence of ADs during the clonic phase. Therefore, we propose that activity-dependent Cl− accumulation subverts the actions of PV+ interneurons to perpetuate rather than terminate pathological network hyperexcitability during the clonic phase of seizures.
|
[
"Neuroscience and Disorders of the Nervous System",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
] |
10.1042/BST20130234
|
Mitochondrial Trafficking In Neurons And The Role Of The Miro Family Of Gtpase Proteins
|
Correct mitochondrial dynamics are essential to neuronal function. These dynamics include mitochondrial trafficking and quality-control systems that maintain a precisely distributed and healthy mitochondrial network, so that local energy demands or Ca2+-buffering requirements within the intricate architecture of the neuron can be met. Mitochondria make use of molecular machinery that couples these organelles to microtubule-based transport via kinesin and dynein motors, facilitating the required long-range movements. These motors in turn are associated with a variety of adaptor proteins allowing additional regulation of the complex dynamics demonstrated by these organelles. Over recent years, a number of new motor and adaptor proteins have been added to a growing list of components implicated in mitochondrial trafficking and distribution. Yet, there are major questions that remain to be addressed about the regulation of mitochondrial transport complexes. One of the core components of this machinery, the mitochondrial Rho GTPases Miro1 (mitochondrial Rho 1) and Miro2 have received special attention due to their Ca2+-sensing and GTPase abilities, marking Miro an exceptional candidate for co-ordinating mitochondrial dynamics and intracellular signalling pathways. In the present paper, we discuss the wealth of literature regarding Miro-mediated mitochondrial transport in neurons and recently highlighted involvement of Miro proteins in mitochondrial turnover, emerging as a key process affected in neurodegeneration.
|
[
"Neuroscience and Disorders of the Nervous System",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
10.1109/ICTON.2018.8473622
|
Thermally Stable External Cavity Laser Based On Silicon Nitride Periodic Nanostructures
|
In this paper we demonstrate a thermally stable silicon nitride external cavity (SiN EC) laser based on a 250 μm sized Reflective Semiconductor Optical Amplifier (RSOA) butt-coupled to a series of Si 3 N 4 Bragg gratings acting as wavelength selective reflectors. The laser shows power outputs over 3 mW, a very low lasing threshold of 12 mA and with a typical Side-Mode Suppression Ratio of 45 dB. In this configuration a mode-hop free lasing regime over a range of 47 mA has been achieved (from 15 mA to 62 mA). Thermal stability of the lasing wavelength at temperatures up to 80°C is demonstrated. Further on, experimental results on a passive chip based on new 1D photonic crystal cavities are shown to have higher Q-Factors. This paves the way to avoiding thermal wavelength drifts and unlocks the possibility for these devices to be integrated in Dense WDM and optical-interconnect technologies, where transceivers must operate over a wide temperature range without active cooling.
|
[
"Systems and Communication Engineering",
"Condensed Matter Physics"
] |
EP 2008004965 W
|
COMPOSITE FIBER, TEXTILE PRODUCT COMPRISING SUCH A COMPOSITE FIBER, METHOD FOR INSCRIBING OPTICAL CODE ELEMENTS, ARRANGEMENT FOR CARRYING OUT SAID METHOD, AND READING DEVICE
|
In order to make textile products (32) counterfeit-proof, a composite fiber is disclosed which comprises a core (2) extending at least along part of the fiber length and a shell (3) surrounding the core (2). The shell is made of a plastic which can be locally modified, especially melted, with the help of light radiation or laser radiation. Furthermore, the shell is provided with optical code elements (4) at least along part of the length thereof, said optical code elements (4) being formed by locally modifying or melting the shell by means of the light radiation or laser radiation.
|
[
"Materials Engineering",
"Products and Processes Engineering",
"Systems and Communication Engineering"
] |
10.1364/OE.24.000092
|
Optimization Of A Nanotip On A Surface For The Ultrafast Probing Of Propagating Surface Plasmons
|
We theoretically analyze a method for characterizing propagating surface plasmon polaritons (SPPs) on a thin gold film. The SPPs are excited by few-cycle near-infrared pulses using Kretschmann coupling, and a nanotip is used as a local field sensor. This geometry removes the influence of the incident excitation laser from the near fields, and enhances the plasmon electric field strength. Using finite-difference-time-domain studies we show that the geometry can be used to measure SPP waveforms as a function of propagation distance. The effects of the nanotip shape and material on the field enhancement and plasmonic response are discussed.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
W2032434317
|
Efficient assignment respecting priorities
|
Abstract A widespread practice in assignment of heterogeneous indivisible objects is to prioritize some recipients over others depending on the type of the object. Leading examples include assignment of public school seats, and allocation of houses, courses, or offices. Each object comes with a coarse priority ranking over recipients. Respecting such priorities constrains the set of feasible assignments, and therefore might lead to inefficiency, highlighting a tension between respecting priorities and Pareto efficiency. Via an easily verifiable criterion, we fully characterize priority structures under which the constrained efficient assignments do not suffer from such welfare loss, and the constrained efficient rule (CER) is indeed efficient. We also identify the priority structures for which the CER is singleton-valued and group strategy-proof.
|
[
"Computer Science and Informatics",
"Individuals, Markets and Organisations"
] |
10.1016/j.jclepro.2019.119755
|
China's sustainable water-energy-food nexus by 2030: Impacts of urbanization on sectoral water demand
|
In the context of China's rapid and perennial urbanization, it is of profound importance to understand how to enable and accelerate progress towards achieving the country's sustainable water-energy-food nexus by 2030. In this study, a quantitative spatial scenario analysis was performed to identify the provinces that are expected to experience changes in water stress, under the competition for water between food and energy sectors. The results manifested an imbalance of water availability for meeting the demand between those two sectors. First, food sector played the leading role in the baseline water stress. Second, energy sector dominates the increases of the projected water stress index. Third, urbanization is projected to substantially affect the extent of water availability, especially in the eastern provinces. Tackling imbalanced sectoral water demand is the key to China's sustainable water-energy-food nexus, which shall require some corresponding changes in national policy-making. China needs, first, policy coherence and synergies, second, ensuring the adequacy of any follow-up procedures, and third, embracing greater participation and transparency in policy-making.
|
[
"Earth System Science",
"Human Mobility, Environment, and Space",
"Products and Processes Engineering"
] |
10.1038/nature11923
|
CLP1 links tRNA metabolism to progressive motor-neuron loss
|
CLP1 was the first mammalian RNA kinase to be identified. However, determining its in vivo function has been elusive. Here we generated kinase-dead Clp1 (Clp1K/K) mice that show a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. Transgenic rescue experiments show that CLP1 functions in motor neurons. Mechanistically, loss of CLP1 activity results in accumulation of a novel set of small RNA fragments, derived from aberrant processing of tyrosine pre-transfer RNA. These tRNA fragments sensitize cells to oxidative-stress-induced p53 (also known as TRP53) activation and p53-dependent cell death. Genetic inactivation of p53 rescues Clp1K/K mice from the motor neuron loss, muscle denervation and respiratory failure. Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
10.1088/0953-4075/49/7/074003
|
The Virtual Atomic And Molecular Data Centre Vamdc Consortium
|
The Virtual Atomic and Molecular Data Centre (VAMDC) Consortium is a worldwide consortium which federates atomic and molecular databases through an e-science infrastructure and an organisation to support this activity. About 90% of the inter-connected databases handle data that are used for the interpretation of astronomical spectra and for modelling in many fields of astrophysics. Recently the VAMDC Consortium has connected databases from the radiation damage and the plasma communities, as well as promoting the publication of data from Indian institutes. This paper describes how the VAMDC Consortium is organised for the optimal distribution of atomic and molecular data for scientific research. It is noted that the VAMDC Consortium strongly advocates that authors of research papers using data cite the original experimental and theoretical papers as well as the relevant databases.
|
[
"Fundamental Constituents of Matter",
"Universe Sciences",
"Computer Science and Informatics"
] |
W1520706115
|
Adolescent childbearing experiences in Kenya : geographical and socioeconomic determinants
|
Sub-Saharan Africa has one of the highest level of teenage pregnancies in the world. Some studies on this topic highlight the presence of unmet reproductive health needs of adolescent in different regions. Improving maternal health has been established as a key development priority among the Millennium Development Goals, and upgrading reproductive and maternal health is usually associated with the eradication of inequality and poverty and with the presence of health care programs and services devoted to girls’ education. We attempt to investigate the geographical and socioeconomic determinants of both teenage pregnancies and maternal health behaviours among adolescent women in Kenya. We ascertain the influence of the availability of health care facilities mainly oriented to the specific needs of reproductive health. Main data are represented by 2003 Kenyan Demographic and Health Survey. In addition, the DHS data set collects Global Positioning System locators for each of the primary sampling units included in the samples that enable a deep geographical analysis. We perform a multivariate multilevel analysis to estimate the influence that individual, household, and community-level factors have on the risk of adolescent childbearing. Additionally, a spatial component allows for the presence and proximity of maternal health services. We expect that the availability of reproductive health facilities acts together with levels of socio-economic development, individual and household characteristics and community fertility norms, in influencing individual reproductive behavior at very young ages.
|
[
"Human Mobility, Environment, and Space",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1109/CCA.2012.6402682
|
Identification Of A Pulsatile Endocrine Model From Hormone Concentration Data
|
This paper presents two approaches to estimate parameters of a mathematical model of a bipartite endocrine axis. Secretion of one of the involved hormones is stimulated by the concentration of another one, with the latter secreted in a pulsatile manner. The system output can be modeled as the response of a linear time-invariant system to a train of Dirac delta functions with unknown weights and fired at unknown instants. The hormone mechanism in question appears often in animal and human endocrine systems, e. g. in the regulation of testosterone in the human male. The model has been introduced elsewhere and makes use of pulse-modulated feedback for describing pulsatile endocrine regulation. The first identification approach is based on the mathematical machinery of constrained nonlinear least-squares minimization, while the second one is based on Laguerre domain identification of continuous time-delay systems. Both algorithm perform reasonably well on actual biological data yielding accurate fitting of luteinizing hormone concentration profiles.
|
[
"Mathematics",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
] |
10.1080/09500340.2014.920934
|
Advanced Technologies For Future Ground Based Laser Interferometric Gravitational Wave Detectors
|
We present a review of modern optical techniques being used and developed for the field of gravitational wave detection. We describe the current state-of-the-art of gravitational waves detector technologies with regard to optical layouts, suspensions and test masses. We discuss the dominant sources and noise in each of these subsystems and the developments that will help mitigate them for future generations of detectors. We very briefly summarise some of the novel astrophysics that will be possible with these upgraded detectors.
|
[
"Universe Sciences",
"Fundamental Constituents of Matter"
] |
10.1093/nar/gku1043
|
euL1db: The European database of L1HS retrotransposon insertions in humans
|
Retrotransposons account for almost half of our genome. They are mobile genetics elements-also known as jumping genes-but only the L1HS subfamily of Long Interspersed Nuclear Elements (LINEs) has retained the ability to jump autonomously in modern humans. Their mobilization in germline-but also some somatic tissues-contributes to human genetic diversity and to diseases, such as cancer. Here, we present euL1db, the European database of L1HS retrotransposon insertions in humans (available at http://euL1db. unice. fr). euL1db provides a curated and comprehensive summary of L1HS insertion polymorphisms identified in healthy or pathological human samples and published in peer-reviewed journals. A key feature of euL1db is its sample-wise organization. Hence L1HS insertion polymorphisms are connected to samples, individuals, families and clinical conditions. The current version of euL1db centralizes results obtained in 32 studies. It contains >900 samples, >140 000 sample-wise insertions and almost 9000 distinct merged insertions. euL1db will help understanding the link between L1 retrotransposon insertion polymorphisms and phenotype or disease.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
] |
10.1098/rspb.2014.1195
|
Effects of deception in social networks
|
Honesty plays a crucial role in any situation where organisms exchange information or resources. Dishonesty can thus be expected to have damaging effects on social coherence if agents cannot trust the information or goods they receive. However, a distinction is often drawn between prosocial lies ('white' lies) and antisocial lying (i. e. deception for personal gain), with the former being considered much less destructive than the latter. We use an agentbased model to show that antisocial lying causes social networks to become increasingly fragmented. Antisocial dishonesty thus places strong constraints on the size and cohesion of social communities, providing a major hurdle that organisms have to overcome (e. g. by evolving counter-deception strategies) in order to evolve large, socially cohesive communities. In contrast, white lies can prove to be beneficial in smoothing the flow of interactions and facilitating a larger, more integrated network. Our results demonstrate that these group-level effects can arise as emergent properties of interactions at the dyadic level. The balance between prosocial and antisocial lies may set constraints on the structure of social networks, and hence the shape of society as a whole.
|
[
"The Social World and Its Interactions",
"The Human Mind and Its Complexity",
"Computer Science and Informatics"
] |
10.1163/19606028-bja10009
|
The preservation of proto-Japanese tone class 2.5 in the Izumo region explained
|
In 1981, Okumura Mitsuo reported that the dialect of Izumo Taisha in western Japan had preserved remnants of the separate tone class 2. 5, which until then had only been found in dialects in central Japan. His discovery proved that this tone class had formed part of proto-Japanese, but the phonetic realization in Izumo and in central Japan was totally different. The article offers a reconstruction of the proto-system of the Izumo region, as well as an explanation of how class 2. 5 came to be (partly) preserved in Izumo. It is argued that this was through a series of rightward shifts of the /H/ tone. These shifts radiated out from the northwestern part of the region. In the period, when the shifts were active, a contour tone on the second syllable of class 2. 5 blocked rightward /H/ tone shift in this class. In this way, the contour tone, although later lost, left a trace in the modern dialects.
|
[
"The Human Mind and Its Complexity"
] |
W2921623269
|
Experimental and Computational Studies of Unimolecular 1,1-HX (X = F, Cl) Elimination Reactions of C<sub>2</sub>D<sub>5</sub>CHFCl: Role of Carbene:HF and HCl Adducts in the Exit Channel of RCHFCl and RCHCl<sub>2</sub> Reactions
|
The gas-phase unimolecular reactions of C2D5CHFCl molecules with 94 kcal mol-1 of vibrational energy have been studied by the chemical-activation experimental technique and by electronic-structure computations. Products from the reaction of C2D5CHFCl molecules, formed by the recombination of C2D5 and CHFCl radicals in a room temperature bath gas, were measured by gas chromatography-mass spectrometry. The 2,1-DCl (81%) and 1,1-HCl (17%) elimination reactions are the principal processes, but 2,1-DF and 1,1-HF elimination reactions also are observed. Comparison of experimental rate constants to calculated statistical rate constants provides threshold energies. The potential surfaces associated with C2D5(F)C: + HCl and C2D5(Cl)C: + HF reactions are of special interest because hydrogen-bonded adducts with HCl and HF with dissociation energies of 6.4 and 9.3 kcal mol-1, respectively, are predicted by calculations. The relationship between the geometries and threshold energies of transition states for 1,1-HCl elimination and carbene:HCl adducts is complex, and previous studies of related molecules, such as CD3CHFCl, CD2ClCHFCl, C2D5CHCl2, and halogenated methanes are included in the computational analysis. Extensive calculations for CH3CHFCl as a model for 1,1-HCl reactions illustrate properties of the exit-channel potential energy surface. Since the 1,1-HCl transition state is submerged relative to dissociation of the adduct, inner and outer transition states should be considered for analysis of rate constants describing 1,1-HCl elimination and addition reactions of carbenes to HCl.
|
[
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
215451
|
Microrna isoforms for molecular interception of cervical cancer using self-samples
|
With 13,000 deaths each year in the EU, cervical cancer (CC) is one of the deadliest cancers worldwide. This is unnecessary, since CC is well detectable and treatable at early stages. For this reason, most EU countries have screening programs in place. These screening programs have had (varying) success in reducing CC incidence, however, this reduction has reached a plateau and new strategies are needed to improve screening success.
An important reason for the stagnating decline in CC incidence is the relative high rate of non-compliance to screening because the gynaecological procedure to collect a sample is seen as highly uncomfortable and very invasive. Offering self-sampling options increases the participation rate in non-responder women by 30%. However, self-sampling is not compatible with the current cytology-based screening method (e.g. Pap test). There is thus a great need for the development of new, molecular screening assays for CC that can be used on self-samples.
In the ERC-AdG MASS-CARE, we investigate the value of two classes of molecular markers, DNA methylation and miRNA for the detection of cervical disease in self-samples. In our analyses, we frequently observed variations at the 3’ end of the miRNA markers. Such variations (isomiRs) have great impact on their detectability by standard assays and thus specific assay development for these isomiRs constitutes a great improvement compared to using the canonical miRNA sequence.
In MIMICS, we aim to select the isomiRs with the strongest association with CC which therefore have added value as disease biomarker compared to the canonical miRNAs. The identified isomiRs, which improve CC detection compared to the canonical miRNAs will be added to the panel of DNA methylation and canonical miRNAs as identified in the ERC-AdG. This assay will constitute the first full molecular, non-morphology-based, objective screening assay for cervical cancer fully compatible with self-sampling.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1038/s41375-018-0350-3
|
Rps14, Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q- syndrome
|
RPS14, CSNK1A1, and miR-145 are universally co-deleted in the 5q- syndrome, but mouse models of each gene deficiency recapitulate only a subset of the composite clinical features. We analyzed the combinatorial effect of haploinsufficiency for Rps14, Csnk1a1, and miRNA-145, using mice with genetically engineered, conditional heterozygous inactivation of Rps14 and Csnk1a1 and stable knockdown of miR-145/miR-146a. Combined Rps14/Csnk1a1/miR-145/146a deficiency recapitulated the cardinal features of the 5q- syndrome, including (1) more severe anemia with faster kinetics than Rps14 haploinsufficiency alone and (2) pathognomonic megakaryocyte morphology. Macrophages, regulatory cells of erythropoiesis and the innate immune response, were significantly increased in Rps14/Csnk1a1/miR-145/146a deficient mice as well as in 5q- syndrome patient bone marrows and showed activation of the innate immune response, reflected by increased expression of S100A8, and decreased phagocytic function. We demonstrate that Rps14/Csnk1a1/miR-145 and miR-146a deficient macrophages alter the microenvironment and induce S100A8 expression in the mesenchymal stem cell niche. The increased S100A8 expression in the mesenchymal niche was confirmed in 5q- syndrome patients. These data indicate that intrinsic defects of the 5q- syndrome hematopoietic stem cell directly alter the surrounding microenvironment, which in turn affects hematopoiesis as an extrinsic mechanism.
|
[
"Immunity, Infection and Immunotherapy",
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1073/pnas.1514076113
|
An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response
|
Inhibitors of the HIV aspartyl protease [HIV protease inhibitors (HIV-PIs)] are the cornerstone of treatment for HIV. Beyond their well-defined antiretroviral activity, these drugs have additional effects that modulate cell viability and homeostasis. However, little is known about the virus-independent pathways engaged by these molecules. Here we show that the HIV-PI Nelfinavir decreases translation rates and promotes a transcriptional program characteristic of the integrated stress response (ISR). Mice treated with Nelfinavir display hallmarks of this stress response in the liver, including α subunit of translation initiation factor 2 (eIF2α) phosphorylation, activating transcription factor-4 (ATF4) induction, and increased expression of known downstream targets. Mechanistically, Nelfinavir-mediated ISR bypassed direct activation of the eIF2α stress kinases and instead relied on the inhibition of the constitutive eIF2α dephosphorylation and down-regulation of the phophatase cofactor CReP (Constitutive Repressor of eIF2α Phosphorylation; also known as PPP1R15B). These findings demonstrate that the modulation of eIF2α-specific phosphatase cofactor activity can be a rheostat of cellular homeostasis that initiates a functional ISR and suggest that the HIV-PIs could be repositioned as therapeutics in human diseases to modulate translation rates and stress responses.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy"
] |
3738810
|
The developing communicator: pragmatics, sense conventions and non-literal uses of language
|
Children are born communicators. A growing body of developmental evidence suggests that the cognitive abilities enabling the expression and comprehension of communicative intentions – so-called pragmatic abilities – which underlie language use and understanding, develop early. However, a puzzling feature of pragmatic development is young children’s difficulties with non-literal uses of language (e.g., “I love you so much I could eat you up!”). How can children be early experts at a range of pragmatically complex tasks requiring attention to speakers’ intentions, but act like ‘literal listeners’ in other contexts? The objective of DEVCOM is to provide an account of the stages and factors involved in children’s developing competence with non-literal uses of language. The project will investigate the novel hypothesis that children’s growing sensitivity to sense conventions, which determine the publicly accepted meaning of words in their language, impedes children’s pragmatic reasoning with non-literal uses in the pre-school years. The empirical data will be gleaned from experimental studies with typically developing children aged 2-7 years, focusing on lexical innovation, lexical modulation, and figurative language, each highlighting the interaction of pragmatic reasoning with sensitivity to sense conventions in a distinct way. Further, the project will investigate whether the persistent difficulties with non-literal uses faced by children with Autism Spectrum Disorder may be linked to the same source. The project will use a set of novel methodologies combining explicit and implicit measures, assuming that while children’s performance on explicit measures is liable to be affected by a growing sensitivity to sense conventions, implicit measures may be more revealing of their actual pragmatic abilities. The empirical results will provide input to a novel theoretical account of pragmatic development that resolves the developmental puzzle of non-literal uses of language.
|
[
"The Human Mind and Its Complexity",
"Texts and Concepts"
] |
10.1083/jcb.201704119
|
Structure–function insights into direct lipid transfer between membranes by Mmm1–Mdm12 of ERMES
|
The endoplasmic reticulum (ER)–mitochondrial encounter structure (ERMES) physically links the membranes of the ER and mitochondria in yeast. Although the ER and mitochondria cooperate to synthesize glycerophospholipids, whether ERMES directly facilitates the lipid exchange between the two organelles remains controversial. Here, we compared the x-ray structures of an ERMES subunit Mdm12 from Kluyveromyces lactis with that of Mdm12 from Saccharomyces cerevisiae and found that both Mdm12 proteins possess a hydrophobic pocket for phospholipid binding. However in vitro lipid transfer assays showed that Mdm12 alone or an Mmm1 (another ERMES subunit) fusion protein exhibited only a weak lipid transfer activity between liposomes. In contrast, Mdm12 in a complex with Mmm1 mediated efficient lipid transfer between liposomes. Mutations in Mmm1 or Mdm12 impaired the lipid transfer activities of the Mdm12–Mmm1 complex and furthermore caused defective phosphatidylserine transport from the ER to mitochondrial membranes via ERMES in vitro. Therefore, the Mmm1–Mdm12 complex functions as a minimal unit that mediates lipid transfer between membranes.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
W2744250313
|
Using Government Resettlement Projects as a Sustainable Adaptation Strategy for Climate Change
|
Given that increasing migration has been addressed as a major consequence of climate change, a growing number of scholars suggest that the planned relocation of people or Government Resettlement Projects (GRPs) should be included in climate change adaptation. This paper reviews the status of climate change and environmentally induced migration in China, and then presents an empirical case study in Shangnan County in northwest China, where a specific GRP called the ‘Massive Southern Shaanxi Migration Program’ (MSSMP) has been initiated in response to climate change-related impacts. The results showed that the MSSMP helped local residents to adapt better climate change by reducing exposures to risk, enabling mobility, providing financial incentives, raising living standards, and improving emotional status. Furthermore, the MSSMP added additional benefits for migrants compared with traditional GRPs by respecting voluntary participation, preparing for future risks, and reducing social isolation via a short relocation distance. However, GRPs could also be seen as a maladaptation to climate change because they disproportionately increase the burden on the most vulnerable community members, such as those who are financially disadvantaged, new migrants, and people who are left behind. The paper further suggests that the GRPs should be designed by involving multiple adaptation strategies as supplements for GRPs, and broadening the political schemes to consider the special needs of vulnerable groups. This study contributes to an understanding of the roles of GRPs in sustainable climate change adaptation, thereby facilitating the design, organization, and implication of future similar programs.
|
[
"Earth System Science",
"Human Mobility, Environment, and Space",
"The Social World and Its Interactions"
] |
interreg_3721
|
TUDESLOVE II
|
This Decentralized Tourism project between Italy and Slovenia is the natural development of projects “TUDESLOVE” and “CULTUCADSES” (Culture in the North – Cadses area) funded under Community Initiative Programme INTERREG II. Specifically, it serves to implement and enhance the tourist-cultural itineraries set up in the context of past experiences, and to integrate them with new thematic routes that have not yet attracted mass tourism. The project entails the establishment of alternative routes on the Italian and Slovenian territory - mainly by enhancing the existing system of fortifications in Veneto - and the creation of a system of Centres of cultural excellence, also in order to regenerate areas of the territory that would otherwise be most likely abandoned. In order to ensure the dissemination of information on these alternative cultural itineraries and to encourage cultural tourism also in the inland area of Venice and along the Slovenian coast (Piran and Koper/Capodistria), territorial marketing actions are envisaged as well as national and international promotional events. The partnership for “cultural tourism” between Italy and Slovenia aims at a joint planning of cultural events and projects, in order to improve the quality of tourism and to increase the number of jobs in this sector.
|
[
"Human Mobility, Environment, and Space",
"Studies of Cultures and Arts"
] |
10.1088/0957-4484/21/36/365705
|
Nanocompression Of Individual Multilayered Polyhedral Nanoparticles
|
Inorganic layered materials can form hollow multilayered polyhedral nanoparticles. The size of these multi-wall quasi-spherical structures varies from 4 to 300 nm. These materials exhibit excellent tribological and wear-resisting properties. Measuring and evaluating the stiffness of individual nanoparticle is a non-trivial problem. The current paper presents an in situ technique for stiffness measurements of individual WS2 nanoparticles which are 80 nm or larger using a high resolution scanning electron microscope (HRSEM). Conducting the experiments in the HRSEM allows elucidation of the compression failure strength and the elastic behavior of such nanoparticles under uniaxial compression.
|
[
"Condensed Matter Physics",
"Materials Engineering"
] |
EP 2009063970 W
|
DRIVE APPARATUS FOR MOVING A SLIDING DOOR BY MOTOR AND METHOD FOR ACTUATING THE DRIVE APPARATUS
|
A drive apparatus (1) for moving - in particular for opening and/or closing - moving furniture parts by motor, said apparatus being designed, in particular, for opening and/or closing a sliding door (2) on an item (3) of furniture having at least one or more sliding doors (2), and said apparatus having the following: a mounting base (4) which can be fixed to the item of furniture and to which at least one electric motor (6) is fixed, said electric motor acting on the sliding door (2) by means of a gear arrangement, wherein the gear arrangement has two gear elements which disengage after an predefined sliding movement of the furniture part, in particular of the sliding door, and re-engage with one another again in the event of subsequent closing of the furniture part, in particular of the sliding door, and/or wherein the gear arrangement is designed to disengage from the furniture part, in particular from the sliding door, after a predefined sliding movement of the furniture part, in particular of the sliding door, and to re-engage with said furniture part in the event of subsequent closing of the furniture part, in particular of the sliding door.
|
[
"Products and Processes Engineering",
"Systems and Communication Engineering"
] |
W2890486612
|
The rise of inter-firm agreements in the Japanese video game industry
|
The purpose of this paper is to examine inter-firm agreements between small firms and a large well-established firm, focusing on agreements involving complementary products. The well-documented emergence of the Japanese home video game industry is sourced for stylised facts to contribute to literature about the nature of complementary inter-firm agreements. Findings reveal that these agreements between small firms and a large well-established firm can be truly symbiotic, allowing the small firm to build its own reputation and influence the market. Furthermore, the small firm benefits from the user base and core competency of the large firm through economies of scale, and the large firm benefits from the product variety of the small firms through economies of scope. The managerial implications of this paper offer value to both small and large firms in terms of what to look for and how to benefit from inter-firm relationships based on complementary products.
|
[
"Individuals, Markets and Organisations"
] |
10.1109/TMI.2015.2480061
|
Wide Angle Tissue Doppler Imaging At High Frame Rate Using Multi Line Transmit Beamforming An Experimental Validation In Vivo
|
Color tissue Doppler imaging (TDI) is a well-established methodology to assess local myocardial motion/deformation. Typically, a frame rate of $\sim 200~{\rm Hz}$ can be achieved by imaging a narrow sector ( $\sim 30^{\circ}$ , covering one cardiac wall) at moderate line density, using a dedicated pulse sequence and multi-line acquisition. However, a wide angle field-of-view is required in some clinical applications to image the whole left ventricle, which implies a drop in temporal resolution. Hereto, the aim of this study was to propose a novel imaging sequence using a multi-line transmit (MLT) beamforming approach to achieve high frame rate color TDI while preserving a wide field-of-view (i. e. , 90 $^{\circ}$ sector). To this end, a color MLT-TDI sequence achieving a frame rate of 208 Hz with a 90 $^{\circ}$ -sector was implemented on an ultrasound experimental scanner interleaved with a conventional color TDI sequence achieving the same frame rate but only with a 22. 5 $^{\circ}$ -sector. Using this setup, the septal wall of 9 healthy volunteers was imaged and the corresponding velocity was extracted. The M-mode velocity images and the velocity profiles obtained from the MLT-TDI images presented physiologic patterns, very similar to those from conventional TDI. Moreover, for the peak systolic/diastolic velocities, good agreement and strong correlation between MLT-TDI and conventional TDI were found. The results thus demonstrate the feasibility of the novel MLT based TDI methodology to achieve high frame rate color TDI without compromising the field-of-view. This may open the opportunity to simultaneously assess regional myocardial function of the whole left ventricle at high temporal resolution.
|
[
"Systems and Communication Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
W2332797094
|
Review of Existing QSAR/QSPR Models Developed for Properties Used in Hazardous Chemicals Classification System
|
The development of a globally harmonized system (GHS) on an international level requires various countries to classify chemicals according to hazardous properties using similar categories. The classification criteria include physical, toxic (health), and environmental properties. The GHS is also being included in the U.S. regulations through the Notice of Proposed Rulemaking issued in September 2009 by the Occupational Safety & Health Administration (OSHA). It has been suggested in the rulemaking that, in cases where experimental data are not available to predict some types of hazard, quantitative structure–activity relationships/quantitative structure–property relationships (QSAR/QSPR) can be applied as found necessary. Any chemical or physical property of the material can be related to information within an individual molecule and its structure, thereby developing prediction models such as QSAR and QSPR. This review examines the work published for QSARs/QSPRs (in addition to previously published reviews...
|
[
"Physical and Analytical Chemical Sciences",
"Computer Science and Informatics"
] |
US 2007/0086958 W
|
SYSTEM AND METHOD FOR LOW-DELAY, INTERACTIVE COMMUNICATION USING MULTIPLE TCP CONNECTIONS AND SCALABLE CODING
|
Systems and methods for communication of scaleable-coded audiovisual signals over multiple TCP/IP connections are provided. The sender schedules and prioritizes transmission of individual scalable-coded data packets over the plurality of TCP connections according to their relative importance in the scalable coding structure for signal reconstruction quality and according to receiver feedback. Low-latency packet delivery over the multiple TCP/IP connections is maintained by avoiding transmission or retransmission of packets that are less important for reconstructed media quality.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
10.1038/nri.2016.55
|
C-type lectin receptors in the control of T helper cell differentiation
|
Pathogen recognition by C-type lectin receptors (CLRs) expressed by dendritic cells is important not only for antigen presentation, but also for the induction of appropriate adaptive immune responses via T helper (TH) cell differentiation. CLRs act either by themselves or in cooperation with other receptors, such as other CLRs, Toll-like receptors and interferon receptors, to induce signalling pathways that trigger specialized cytokine programmes for polarization of TH cell differentiation. In this Review, we discuss how triggering of the prototypical CLRs leads to distinct pathogen-tailored TH cell responses and how we can harness our expanding knowledge for vaccine design and the treatment of inflammatory and malignant diseases.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.3390/rs11060681
|
A comparative review of manifold learning techniques for hyperspectral and polarimetric sar image fusion
|
In remote sensing, hyperspectral and polarimetric synthetic aperture radar (PolSAR) images are the two most versatile data sources for a wide range of applications such as land use land cover classification. However, the fusion of these two data sources receive less attention than many other, because of their scarce data availability, and relatively challenging fusion task caused by their distinct imaging geometries. Among the existing fusion methods, including manifold learning-based, kernel-based, ensemble-based, and matrix factorization, manifold learning is one of most celebrated techniques for the fusion of heterogeneous data. Therefore, this paper aims to promote the research in hyperspectral and PolSAR data fusion, by providing a comprehensive comparison between existing manifold learning-based fusion algorithms. We conducted experiments on 16 state-of-the-art manifold learning algorithms that embrace two important research questions in manifold learning-based fusion of hyperspectral and PolSAR data: (1) in which domain should the data be aligned—the data domain or the manifold domain; and (2) how to make use of existing labeled data when formulating a graph to represent a manifold—supervised, semi-supervised, or unsupervised. The performance of the algorithms were evaluated via multiple accuracy metrics of land use land cover classification over two data sets. Results show that the algorithms based on manifold alignment generally outperform those based on data alignment (data concatenation). Semi-supervised manifold alignment fusion algorithms performs the best among all. Experiments using multiple classifiers show that they outperform the benchmark data alignment-based algorithms by ca. 3% in terms of the overall classification accuracy.
|
[
"Computer Science and Informatics",
"Earth System Science"
] |
10.1261/rna.038794.113
|
S6:S18 ribosomal protein complex interacts with a structural motif present in its own mRNA
|
Prokaryotic ribosomal protein genes are typically grouped within highly conserved operons. In many cases, one or more of the encoded proteins not only bind to a specific site in the ribosomal RNA, but also to a motif localized within their own mRNA, and thereby regulate expression of the operon. In this study, we computationally predicted an RNA motif present in many bacterial phyla within the 5′ untranslated region of operons encoding ribosomal proteins S6 and S18. We demonstrated that the S6:S18 complex binds to this motif, which we hereafter refer to as the S6:S18 complex-binding motif (S6S18CBM). This motif is a conserved CCG sequence presented in a bulge flanked by a stem and a hairpin structure. A similar structure containing a CCG trinucleotide forms the S6:S18 complex binding site in 16S ribosomal RNA. We have constructed a 3D structural model of a S6:S18 complex with S6S18CBM, which suggests that the CCG trinucleotide in a specific structural context may be specifically recognized by the S18 protein. This prediction was supported by site-directed mutagenesis of both RNA and protein components. These results provide a molecular basis for understanding protein-RNA recognition and suggest that the S6S18CBM is involved in an auto-regulatory mechanism.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
] |
10.1007/s10329-016-0542-2
|
Vertical bipedal locomotion in wild bearded capuchin monkeys (Sapajus libidinosus)
|
When carrying objects, nonhuman primates often show bipedal locomotion. Studies of primate bipedality, however, in both nature and captivity, have concentrated on locomotion on horizontal substrates, either terrestrially or arboreally. No observational or experimental study seems to have looked at non-horizontal bipedality, yet we show here that it occurs often in nature in Sapajus libidinosus, the bearded capuchin monkey. The context is transport of small food items from source to site of consumption, in which the monkeys usually carry handfuls of maize kernels over several meters’ distance, both on the ground and in the trees. Most impressively, over a fifth of such bouts are done vertically, when the tree trunk is fully upright. Such vertical bipedality, with or without transport, apparently has not been reported before.
|
[
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
] |
184495
|
Synthetic viability of homologous recombination-deficient cancers
|
Although various effective anti-cancer drug treatments have become available over the last decades, drug resistance remains the major cause of death of cancer patients. Striking examples are patients with tumors that are defective in DNA repair by homologous recombination (HR). Despite initial responses to cancer therapy, resistance of primary or disseminated tumors eventually emerges, which minimizes therapeutic options and greatly reduces survival. The molecular mechanisms underlying this therapy escape are often poorly understood.
In the SYNVIA project I will address the problem of therapy escape by using powerful genetically engineered mouse models for BRCA1- and BRCA2-deficient breast cancer, which closely mimic the human disease. Due to the BRCA inactivation, the tumors that arise lack HR-directed DNA repair. Similar to the situation in cancer patients, we observe that cancer cells in these models eventually escape the deadly effects of chemotherapy or novel targeted drugs. Thus, these resistance models provide a unique opportunity to explore therapy escape mechanisms.
I propose an approach that will take the in vivo analysis of therapy resistance mechanisms to a new level. By synergizing the advantages of next generation sequencing with functional genetic screens in tractable model systems, I will explore novel mechanisms that cause resistance of HR-deficient cancers by the loss of another gene (“synthetic viability”). I provide evidence that new mechanisms of resistance can be identified with this approach. In an innovative step, I will generate genome-wide alterations using the revolutionizing CRISPR/Cas technology. Mutations will also be introduced into 3D tumor organoid cultures, as we found that these are more physiologically relevant. I am convinced that the combination of these state-of-the-art approaches will yield highly useful information for designing effective approaches to circumvent or reverse therapy escape in human cancer patients.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
W2296244854
|
Correlation functions of three-dimensional Yang-Mills theory from Dyson-Schwinger equations
|
The two- and three-point functions and the four-gluon vertex of three-dimensional Yang-Mills theory are calculated from their Dyson-Schwinger equations and the 3PI effective action. Within a self-contained truncation various effects of truncating Dyson-Schwinger equations are studied. Estimates for the errors induced by truncations are derived from comparisons between results from different equations, comparisons with lattice results, and varying higher Green functions. The results indicate that the two-loop diagrams are important in the gluon propagator, where they are explicitly calculated, but not for the vertices. Furthermore, the influence of the four-gluon vertex on lower Green functions is found to be small.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
W1829809973
|
Survey of Hypoglycemia in Elderly People With Type 2 Diabetes Mellitus in Japan
|
The number of elderly type 2 diabetes mellitus (T2DM) patients in Japan is increasing continuously. Hypoglycemia is a significant issue in their treatment. However, the actual situation and related details of their hypoglycemia remain unclear. In order to elucidate them, the Japan Physicians Association conducted a large-scale questionnaire survey for physicians and their outpatients all over Japan.Targeted elderly T2DM outpatients were 65 years old or older in 2011. Specialized questionnaire survey forms were distributed to both of physicians and patients. The forms for physicians included questions whether patient had hypoglycemia in the last 1 month or 1 year; those for patients included whether they experienced it in the same durations and any of the 28 symptoms that are suggestive of hypoglycemia or pertaining to geriatric syndrome in the last 1 month, as well as questions about knowledge regarding hypoglycemia. We analyzed associations between hypoglycemia and the symptoms, and between hypoglycemia and medications.Of 15,892 T2DM patients (age, 74.2 ± 6.3 years; diabetes duration, 12.8 ± 8.9 years; HbA1c, 7.0±1.0%), dipeptidyl peptidase-4 inhibitor (DPP-4i) was the most prescribed medication among all oral hypoglycemic agents (OHAs). The frequencies of hypoglycemia in the last 1 month recognized by physicians and experienced by patients were 7.8% and 10.4% (P < 0.0001), and in the last 1 year were 15.5% and 21.1% respectively (P < 0.0001). The most common symptom was "weakness, fatigue/feeling languid" and the majority of all patients reported neuroglycopenic or autonomic symptoms. Regarding monotherapy, hypoglycemia was observed in 32.7% of the patients with insulin, 4% in sulfonylurea (SU), 3.8% in glinide, and 3.5% in pioglitazone. The questions asking knowledge about hypoglycemia revealed that SU or insulin users had significantly more knowledge of hypoglycemia than others (P < 0.001); however, 63% of patients using insulin, and 31% of patients using SU always carried glucose or a similar medication with them.The present study suggested two types of "hidden hypoglycemia", one is that physicians did not detect and the other one is that patients were not aware. It is vital that physicians strive to prevent hypoglycemia by paying closer attention to symptoms of "hidden hypoglycemia" in their elderly patients.
|
[
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1016/j.procir.2018.08.275
|
Stability of turning process with tool subjected to compression
|
This study investigates how the stability of the turning process changes when the tangential component of the cutting force is also taken into account as a compressive force acting on the cutting tool. The tool is modelled by a cantilever beam; the mathematical model is based on the Euler-Bernoulli beam theory. The effect of compression appears through the lateral stiffness of the tool. Two cases are separated in connection with the compressive force: constant and varying forces. Since compression reduces the natural frequency of the cutting tool, this also affects the stable region of the turning operation.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
W565412643
|
Palace of Culture: Andrew Carnegie's Museums and Library in Pittsburgh
|
Andrew Carnegie is remembered as one of the world s great philanthropists. As a boy, he witnessed the benevolence of a businessman who lent his personal book collection to laborer s apprentices. That early experience inspired Carnegie to create the Free to the People Carnegie Library in 1895 in Pittsburgh, Pennsylvania. In 1896, he founded the Carnegie Institute, which included a music hall, art museum, and science museum. Carnegie deeply believed that education and culture could lift up the common man and should not be the sole province of the wealthy. Today, his Pittsburgh cultural institution encompasses a library, music hall, natural history museum, art museum, science center, the Andy Warhol Museum, and the Carnegie International art exhibition. In Palace of Culture, Robert J. Gangewere presents the first history of a cultural conglomeration that has served millions of people since its inception and inspired the likes of August Wilson, Andy Warhol, and David McCullough. In this fascinating account, Gangewere details the political turmoil, budgetary constraints, and cultural tides that have influenced the caretakers and the collections along the way. He profiles the many benefactors, trustees, directors, and administrators who have stewarded the collections through the years. Gangewere provides individual histories of the library, music hall, museums, and science center, and describes the importance of each as an educational and research facility. Moreover, Palace of Culture documents the importance of cultural institutions to the citizens of large metropolitan areas. The Carnegie Library and Institute have inspired the creation of similar organizations in the United States and serve as models for museum systems throughout the world.
|
[
"Studies of Cultures and Arts",
"The Study of the Human Past"
] |
interreg_2262
|
Development and promotion of Mediterranean Sustainable Adventure Tourism
|
The Mediterranean region is one of the world’s leading tourist destinations. Facing growing competition and deterioration of the political and security situation, the destination has demonstrated symptoms of a slowdown, which makes the recovery of the sector an economic priority. This downturn may also present an opportunity to transform the tourism model into a sustainable and competitive one, addressing current sectorial challenges as the predominance of mass seaside tourism, dependent on the European market and territorial imbalances. MEDUSA will tackle these joint challenges via targeted and inter-related capacity building and cross-border interventions to develop and promote adventure tourism in the region, a niche which grew by 195% between 2010 and
2014. By designing and testing routes and itineraries that offer improved adventure tourism products, MEDUSA will contribute to job creation and income for local communities in the medium and long term. Moreover, the project has the potential to reveal lesser-known destinations and attract tourists throughout the year.
|
[
"Human Mobility, Environment, and Space",
"Individuals, Markets and Organisations",
"Environmental Biology, Ecology and Evolution"
] |
W2188351152
|
PENGARUH PERBEDAAN TEMPORER ANTARA LABA AKUNTANSI DENGAN LABA KENA PAJAK TERHADAP PERTUMBUHAN LABA KE DEPAN (Studi Empiris pada Perusahaan Manufaktur yang Terdaftar di Bursa Efek Indonesia 2010-2012)
|
This study aims to examine the effect of temporary differences between accounting income and taxes income for future earning growth. The independent variable of this study is deductible temporary differences and taxable temporary differences, the dependent variable is future earning growth, and the control variable are size and leverage. Deductible temporary differences measured by total deductible temporary differences divided by total assets. Taxable temporary differences measured by total taxable temporary differences divided by the total assets. Size measured by logarithm of total assets, and leverage measured by total long-term debt divided by total assets. While this study is the dependent variable future earnings growth as measured by the percentage of profit growth in the coming years. Sample of this study consists of 432 companies from manufacturing sectors listed on Indonesia Stock Exchange in 2010-2012. Samples were selected using purposive random sampling method with certain criteria, and gained as much as 156 companies that meet the criteria. The analysis technique is multiple regression analysis. Results of the analysis showed that the variable deductible temporary differences significant positive effect on future earnings growth and taxable temporary differences significant negative effect on future earnings growth. Based on these results mean future earnings growth is affected temporary differences.
|
[
"Individuals, Markets and Organisations"
] |
277588
|
Advancing the Green Chemistry of Singlet Oxygen and Applying it to Synthetic Challenges
|
Novel synthetic methods are vital to the work of a host of key chemical disciplines; from new materials and nanotechnology to pharmaceuticals, practitioners constantly need cleaner, greener, milder and more efficient ways to synthesize their chosen targets. In this proposal, we seek to develop, and then apply to some very challenging scenarios, a set of particularly powerful and beyond the state-of-the-art new methods, using singlet oxygen, that will meet all these tough criteria.
Singlet oxygen is a remarkable reagent; it is a natural, cheap, green and atom-efficient oxidant. It also makes an ideal initiator for cascade reaction sequences through which molecular complexity is enhanced very rapidly and effectively. With this chemistry protecting groups and toxic heavy metal oxidants, both normally associated with the construction of molecules rich in oxygen functionality, are not needed.
In the projects described within this proposal, singlet oxygen will be manipulated to orchestrate a diverse range of cascade reaction sequences, and “super cascade” reaction sequences, by which complex polyoxygenated and polycyclic molecular architectures will be synthesized, from very simple and readily accessible furan precursors, in one-pot. Polyoxygenated-polycyclic motifs are common synthetic targets across a range of disciplines. In our case, we will focus research efforts towards bioactive natural products because these highly complex and intricate structures provide the best, and most challenging, testing grounds for any new set of chemical methods. The natural products chosen belong to the azaspiracid, pinnatoxin/pteriatoxin, spirolide and pectentoxin families, respectively.
We also hope to further promote the widespread application of these singlet oxygen-based chemical solutions to a host of problems by developing a prototype Continuous Flow Reactor that will facilitate large scale photooxygenations.
|
[
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences",
"Products and Processes Engineering"
] |
10.1038/ncomms8118
|
Photoswitchable fatty acids enable optical control of TRPV1
|
Fatty acids (FAs) are not only essential components of cellular energy storage and structure, but play crucial roles in signalling. Here we present a toolkit of photoswitchable FA analogues (FAAzos) that incorporate an azobenzene photoswitch along the FA chain. By modifying the FAAzos to resemble capsaicin, we prepare a series of photolipids targeting the Vanilloid Receptor 1 (TRPV1), a non-selective cation channel known for its role in nociception. Several azo-capsaicin derivatives (AzCAs) emerge as photoswitchable agonists of TRPV1 that are relatively inactive in the dark and become active on irradiation with ultraviolet-A light. This effect can be rapidly reversed by irradiation with blue light and permits the robust optical control of dorsal root ganglion neurons and C-fibre nociceptors with precision timing and kinetics not available with any other technique. More generally, we expect that photolipids will find many applications in controlling biological pathways that rely on protein-lipid interactions.
|
[
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1007/s10455-012-9341-1
|
Interlacing inequalities for eigenvalues of discrete Laplace operators
|
The term "interlacing" refers to systematic inequalities between the sequences of eigenvalues of two operators defined on objects related by a specific operation. In particular, knowledge of the spectrum of one of the objects then implies eigenvalue bounds for the other one. In this paper, we therefore develop topological arguments in order to derive such analytical inequalities. We investigate, in a general and systematic manner, interlacing of spectra for weighted simplicial complexes with arbitrary weights. This enables us to control the spectral effects of operations like deletion of a subcomplex, collapsing and contraction of a simplex, coverings and simplicial maps, for absolute and relative Laplacians. It turns out that many well-known results from graph theory become special cases of our general results and consequently admit improvements and generalizations. In particular, we derive a number of effective eigenvalue bounds.
|
[
"Mathematics"
] |
interreg_1262
|
EXPERIENCE, DISCOVER & VALORISE HIDDEN TREASURE TOWNS AND SITES OF THE ADRIATIC AREA
|
In Italy and Croatia it is easy to identify many small towns with very relevant historical, cultural and natural assets, but visited by a little number of tourists, lower than the potentiality of the local natural and cultural resources. The main goal of this project is to reduce this gap between resources and tourists, contributing to a better territorial and seasonal distribution of tourist flows in Croatia and Italy. The main goals of EXCOVER will be therefore to identify innovative ways for solving the constraints on the tourist development of the small towns with relevant local assets but with poor tourist flows. The core aspect of EXCOVER is the involvement of the local communities: only the participation of the residents in the small towns will create a Tourist Supply Chain based on the single under-exploited resources instead of the usual heavy investments in accommodation and transport.
|
[
"Human Mobility, Environment, and Space",
"Studies of Cultures and Arts"
] |
10.1021/acs.jpcc.9b00945
|
Tuning the Structure of Pt Nanoparticles through Support Interactions: An in Situ Polarized X-ray Absorption Study Coupled with Atomistic Simulations
|
Interactions of nanoparticles (NPs) with their environment may have a pronounced effect on their structure and shape as well as on their functionality in applications such as catalysis. It is therefore crucial to disentangle the particle-adsorbate and particle-support interaction effects on the particle shape, its local structure, atomic dynamics, and its possible anisotropies. In order to gain insight into the support effect, we carried out an X-ray absorption fine-structure spectroscopy (XAFS) investigation of adsorbate- and ligand-free size-selected Pt NPs deposited on two different supports in ultrahigh vacuum. Polarization-dependent XAFS measurements, neural network-based analysis of X-ray absorption near-edge structure data, and reverse Monte Carlo (RMC) simulations of extended X-ray absorption fine structure (EXAFS) were used to resolve the 3D shape of the NPs and details of their local structure. A synergetic combination of advanced in situ XAFS analysis with atomic force microscopy and scanning tunneling microscopy (STM) imaging provides uniquely detailed information about the particle-support interactions and the NP/support buried interface, not accessible to any experimental technique, when considered alone. In particular, our combined approach reveals differences in the structure of Pt NPs deposited on TiO2(110) and SiO2/Si(111). Pt NPs on SiO2 assume a spherical-like 3D shape and weakly interact with the support. In contrast, the effective shape of analogously synthesized Pt NPs on TiO2(110) after annealing at 600 °C is found to be a truncated octahedron with (100) top and interfacial facets that are encapsulated by the TiO2 support. Modeling disorder effects in these NPs using an RMC approach reveals differences in bond-length distributions for NPs on different supports and allows us to analyze their anisotropy, which may be crucial for the interpretation of support-dependent atomic dynamics and can have an impact on the understanding of the catalytic properties of these NPs.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
10.1111/nyas.12148
|
Vision: Are models of object recognition catching up with the brain?
|
Object recognition has been a central yet elusive goal of computational vision. For many years, computer performance seemed highly deficient and unable to emulate the basic capabilities of the human recognition system. Over the past decade or so, computer scientists and neuroscientists have developed algorithms and systems-and models of visual cortex-that have come much closer to human performance in visual identification and categorization. In this personal perspective, we discuss the ongoing struggle of visual models to catch up with the visual cortex, identify key reasons for the relatively rapid improvement of artificial systems and models, and identify open problems for computational vision in this domain.
|
[
"Neuroscience and Disorders of the Nervous System",
"Computer Science and Informatics"
] |
10.1001/jamaneurol.2014.1358
|
Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid β-Amyloid 42: A cross-validation study against amyloid positron emission tomography
|
Results The agreement between Aβ classification with CSF Aβ42 and 18F-flutemetamol positron emission tomography was very high (? = 0. 85). Of all the cases, 92%were classified identically using an Aβ42 cutoff of 647 pg/mL or less. Cerebrospinal fluid Aβ42 predicted abnormal cortical Aβ deposition accurately (odds ratio, 165; 95%CI, 39-693; area under the receiver operating characteristic curve, 0. 94; 95%CI, 0. 88-0. 97). The association was independent of age, sex, APOE (apolipoprotein E) genotype, hippocampal volume, memory, and global cognition (adjusted odds ratio, 169; 95%CI, 25-1143). Using ratios of CSF Aβ42:tau or Aβ42:phosphorylated tau did not improve the prediction of Aβ deposition. Cerebrospinal fluid Aβ42 correlated significantly with Aβ deposition in all cortical regions. The highest correlations were in regions with high 18F-flutemetamol retention (eg, posterior cingulum and precuneus, r = -0. 72). 18F-flutemetamol retention, but not CSF Aβ42, correlated significantly with global cognition (r = -0. 32), memory function (r = -0. 28), and hippocampal volume (r = -0. 36) among those with abnormal Aβ deposition. Finally, the CSF Aβ42 cutoff derived from the original cohort (≤647 pg/mL) had an equally high agreement (95%; ? = 0. 89) with 18F-flutemetamol positron emission tomography in the validation cohort.
|
[
"Neuroscience and Disorders of the Nervous System",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1109/ECC.2016.7810430
|
Hammerstein System Identification Using Ls Svm And Steady State Time Response
|
In this paper a new system identification approach for Hammerstein systems is proposed. A straightforward estimation of the nonlinear block through the use of LS-SVM is done by making use of the behavior of Hammerstein systems in steady state. Using the estimated nonlinear block, the intermediate variable is calculated. Using the latter and the known output, the linear block can be estimated. The results indicate that the method can effectively identify Hammerstein systems also in the presence of a considerable amount of noise. The well-known capabilities of LS-SVM for the representation of nonlinear functions play an important role in the generalization capabilities of the method allowing to work with a wide range of model classes. The proposed method's main strength lies precisely in the identification of the nonlinear block of the Hammerstein system. The relevance of these findings resides in the fact that a very good estimation of the inner workings of a Hammerstein system can be achieved.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
10.1117/12.2265431
|
Polarization Insensitive Ge Rich Silicon Germanium Waveguides For Optical Interconnects On Silicon
|
We propose germanium-rich silicon germanium waveguides as a basic building block for polarization insensitive circuitry on silicon. In this work a detailed study of SiGe waveguides geometries is performed to find optimal parameters to simultaneously obtain low polarization sensitivity and single mode operation at λ=1. 55μm. The polarization dependence of the effective index, group index and dispersion coefficient is investigated. Optimized geometries are tolerant to fabrication errors and can be realized with the current state of the art CMOS technology. As a next step polarization insensitive multimode interference structures have been designed.
|
[
"Condensed Matter Physics",
"Systems and Communication Engineering"
] |
339787
|
Towards the NEXT generation of bb0nu experimets
|
Neutrinoless double beta decay is a hypothetical, very slow radioactive process whose observation would establish unambiguously that massive neutrinos are Majorana particles --- that is to say, identical to their antiparticles ---, which implies that a new physics scale beyond the Standard Model must exist. Furthermore, it would prove that total lepton number is not a conserved quantity, suggesting that this new physics could also be the origin of the observed asymmetry between matter and antimatter in the Universe.
In recent years, many innovative ideas have been put forward to improve the sensitivity of \bbonu\ experiments. In general, these propositions have sought to increase the number of experimental signatures available to reject backgrounds while attempting to use isotopes and detector techniques which can be more easily scaled to large masses.
The objective of this project is to realize the NEXT experiment, an innovativedetector based on a high-pressure xenon gas (HPXe) TPC that will run at the Laboratorio Subterr\'aneo de Canfranc (LSC), in Spain.
Our primary goal is to complete the construction and commissioning of a 150 kg HPXe TPC (NEXT-100) by 2014, and start a physics run in 2015 that can improve the present bound set by the EXO experiment and perhaps discover the Majorana nature of neutrinos. In addition, we will carry out an R\&D program focused in demonstrating the scalability of the technology to the ton scale.
|
[
"Fundamental Constituents of Matter",
"Systems and Communication Engineering"
] |
221522
|
Synthetic dcs for a t cell production platform
|
Cancer immunotherapy and adoptive transfer of genetically manipulated T cells in particular has shown promising results for the treatment of cancer. Central in cancer immunotherapy is the activation of tumour-specific T cells. However, the wide-spread clinical use of T cell therapies remains limited due to costly, time-consuming and labour-intensive processes associated with the ex vivo activation and expansion of tumour-specific T cells. Artificial antigen presenting cells (aAPCs) have been developed as an alternative for efficient activation of T cells. In the ERC project ‘PATHFINDER’, Prof. Figdor and his team have developed aAPCs or synthetic dendritic cells (sDCs) based on highly flexible polyisocianide (PIC) polymers, that mimic naturally occurring DCs. The semi-flexible polymer backbone allows for proper arrangement and clustering of antigen and (co-)stimulatory markers, resulting in potent activation and expansion of T cells. With the use of PIC based sDCs, we propose a production platform for tumour specific T cells suitable for cancer immunotherapy. In this ERC PoC project, a team of technological and commercial experts will investigate commercial feasibility of this innovative approach.
|
[
"Immunity, Infection and Immunotherapy",
"Biotechnology and Biosystems Engineering",
"Materials Engineering"
] |
10.1145/2600057.2602903
|
Cryptographically Blinded Games Leveraging Players Limitations For Equilibria And Profit
|
In this work we apply methods from cryptography to enable mutually distrusting players to implement broad classes of mediated equilibria of strategic games without trusted mediation. Our implementation uses a pre-play 'cheap talk' phase, consisting of non- binding communication between players prior to play in the original game. In the cheap talk phase, the players run a secure multi-party computation protocol to sample from an equilibrium of a "cryptographically blinded" version of the game, in which actions are encrypted. Coarse correlated equilibrium. Coarse correlated equilibria (CCE) are a generalization of correlated equilibria (CE), invoking a notion of commitment. Suppose a mediator samples an action profile a from a distribution α. We say α is a CCE if no player has incentive not to "promise" in advance -- before seeing his advice ai -- to play according to the advice, if he believes that all other players will commit to do the same. Note that players who do not commit will not see the advice at all, and hence must play an independent strategy. In this paper, we address the following question: How can the players of a strategic game implement any CCE via (cryptographic) pre-play communication without trusting each other or a mediator? In the computational setting, we give an implementation for general strategic games, in the form of an extended game comprising a cryptographic protocol in the pre-play phase, which securely samples an action profile for a "cryptographically blinded" version of the game. The blinded game's action space consists of encryptions of the original game's actions. Our implementation has the strong property that any computational CCE of the original game corresponds to a payoff-equivalent Nash equilibrium of the extended game. Furthermore, it achieves strategic equivalence, in that every computational Nash equilibrium of the extended game corresponds to a computational CCE of the original game. In the information-theoretic setting, we give an implementation for strategic games with four or more players, using a similar cryptographically blinded pre-play phase given pairwise communication channels. This also achieves strategic equivalence. Both the restriction to four or more players and the need for a stronger communication model are unavoidable in this setting, as shown by impossibility results of [Barany 1992; Ben-Or et al. 1988; Pease et al. 1980; Aumann and Hart 2003]. Relation to prior work. The pre-play literature considers the problem of implementing equilibria without mediation. Our work generalizes that of [Barany 1992] in the information-theoretic setting and [Dodis et al. 2000] in the computational setting. It has long been recognized that the possibility to commit to strategies in advance can increase payoffs achievable in a game, starting with [von Stackelberg 1934]; in this work, we achieve the payoffs of CCE without resorting to the usual assumption of binding contracts. Our results are achieved using a very weak (and necessary [Hubacek et al. 2013]) notion of mediation, where the mediator's actions are publicly verifiable, and moreover the mediator's output does not affect players' strategic choices.
|
[
"Computer Science and Informatics",
"Individuals, Markets and Organisations"
] |
10.1109/TMI.2016.2589760
|
Extended Modality Propagation Image Synthesis Of Pathological Cases
|
This paper describes a novel generative model for the synthesis of multi-modal medical images of pathological cases based on a single label map. Our model builds upon i) a generative model commonly used for label fusion and multi-atlas patch-based segmentation of healthy anatomical structures, ii) the Modality Propagation iterative strategy used for a spatially-coherent synthesis of subject-specific scans of desired image modalities. The expression Extended Modality Propagation is coined to refer to the extension of Modality Propagation to the synthesis of images of pathological cases. Moreover, image synthesis uncertainty is estimated. An application to Magnetic Resonance Imaging synthesis of glioma-bearing brains is i) validated on the training dataset of a Multimodal Brain Tumor Image Segmentation challenge, ii) compared to the state-of-the-art in glioma image synthesis, and iii) illustrated using the output of two different tumor growth models. Such a generative model allows the generation of a large dataset of synthetic cases, which could prove useful for the training, validation, or benchmarking of image processing algorithms.
|
[
"Computer Science and Informatics",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1172/JCI74692
|
Identification And Validation Of N Acetyltransferase 2 As An Insulin Sensitivity Gene
|
Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 “A” allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing"
] |
10.1016/j.healthplace.2015.08.010
|
Geographical Text Analysis: A new approach to understanding nineteenth-century mortality
|
This paper uses a combination of Geographic Information Systems (GIS) and corpus linguistic analysis to extract and analyse disease related keywords from the Registrar-General's Decennial Supplements. Combined with known mortality figures, this provides, for the first time, a spatial picture of the relationship between the Registrar-General's discussion of disease and deaths in England and Wales in the nineteenth and early twentieth centuries. Techniques such as collocation, density analysis, the Hierarchical Regional Settlement matrix and regression analysis are employed to extract and analyse the data resulting in new insight into the relationship between the Registrar-General's published texts and the changing mortality patterns during this time.
|
[
"Human Mobility, Environment, and Space",
"The Study of the Human Past",
"Computer Science and Informatics"
] |
10.3390/plants5010014
|
Beyond the canon: Within-plant and population-level heterogeneity in jasmonate signaling engaged by plant-insect interactions
|
Plants have evolved sophisticated communication and defense systems with which they interact with insects. Jasmonates are synthesized from the oxylipin pathway and act as pivotal cellular orchestrators of many of the metabolic and physiological processes that mediate these interactions. Many of these jasmonate-dependent responses are tissue-specific and translate from modulations of the canonical jasmonate signaling pathway. Here we provide a short overview of within-plant heterogeneities in jasmonate signaling and dependent responses in the context of plant-insect interactions as illuminated by examples from recent work with the ecological model, Nicotiana attenuata. We then discuss means of manipulating jasmonate signaling by creating tissue-specific jasmonate sinks, and the micrografting of different transgenic plants. The metabolic phenotyping of these manipulations provides an integrative understanding of the functional significance of deviations from the canonical model of this hormonal pathway. Additionally, natural variation in jasmonate biosynthesis and signaling both among and within species can explain polymorphisms in resistance to insects in nature. In this respect, insect-guided explorations of population-level variations in jasmonate metabolism have revealed more complexity than previously realized and we discuss how different “omic” techniques can be used to exploit the natural variation that occurs in this important signaling pathway.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
] |
W1044702324
|
Design of regeneration recycling water networks by means of concentration potentials and a linear programming method
|
Abstract Regeneration reuse/recycling of industrial wastewater can effectively reduce freshwater consumption and wastewater discharge amount. A new method is presented in this article to design regeneration recycling water networks with multiple contaminants. The concentration potentials and linear programming approach are combined for solving the problem of minimization of freshwater and regenerated stream flow rates. The values of concentration potential of demands are utilized to identify the precedence order of water-using processes. The allocations of sources to demands are formulated as linear programming models. To reduce the consumption amounts of high quality source streams, each source stream is assigned a weighting factor based on the quality of the sources. Two examples are solved to illustrate the effectiveness of the proposed approach. The consumptions of freshwater and regenerated stream obtained by using the proposed method are comparable with those obtained in the literature. The method has the characteristics of converging easily and needing no initial values.
|
[
"Products and Processes Engineering",
"Physical and Analytical Chemical Sciences",
"Computer Science and Informatics"
] |
10.1371/journal.pone.0067521
|
A New Method for the Analysis of Soft Tissues with Data Acquired under Field Conditions
|
Analyzing soft-tissue structures is particularly challenging due to the lack of homologous landmarks that can be reliably identified across time and specimens. This is particularly true when data are to be collected under field conditions. Here, we present a method that combines photogrammetric techniques and geometric morphometrics methods (GMM) to quantify soft tissues for their subsequent volumetric analysis. We combine previously developed methods for landmark data acquisition and processing with a custom program for volumetric computations. Photogrammetric methods are a particularly powerful tool for field studies as they allow for image acquisition with minimal equipment requirements and for the acquisition of the spatial coordinates of points (anatomical landmarks or others) from these images. For our method, a limited number of homologous landmarks, i. e. , points that can be found on any specimen independent of space and time, and further distinctive points, which may vary over time, space and subject, are identified on two-dimensional photographs and their three-dimensional coordinates estimated using photogrammetric methods. The three-dimensional configurations are oriented by the spatial principal components (PCs) of the homologous points. Crucially, this last step orients the configuration such that x and y-information (PC1 and PC2 coordinates) constitute an anatomically-defined plane with the z-values (PC3 coordinate) in the direction of interest for volume computation. The z-coordinates are then used to estimate the volume of the tissue. We validate our method using a physical, geometric model of known dimensions and physical (wax) models designed to approximate perineal swellings in female macaques. To demonstrate the usefulness and potential of our method, we use it to estimate the volumes of Barbary macaque sexual swellings recorded in the field with video images. By analyzing both the artificial data and real monkey swellings, we validate our method's accuracy and illustrate its potential for application in important areas of biological research.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Computer Science and Informatics",
"Environmental Biology, Ecology and Evolution"
] |
US 2014/0030070 W
|
METHODS AND DEVICES FOR SAMPLE COLLECTION AND SAMPLE SEPARATION
|
Methods and devices are provided for sample collection and sample separation. In one embodiment, a device is provided for use with a formed component liquid sample, the device comprising at least one sample inlet for receiving said sample; at least a first outlet for outputting only a liquid portion of the formed component liquid sample; at least a second outlet for outputting the formed component liquid sample at least a first material mixed therein.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
W1911805982
|
Protein gels and emulsions from mixtures of Cape hake and pea proteins
|
Portioning of frozen fish generates by-products such as fish 'sawdust' and cut-offs which can be further processed into protein concentrates and isolates. The objective of the present work was to produce gels and emulsions using recovered Cape hake protein powder (HPP). In previous works, the structures of the gels produced by HPP were found to be strong, with a high rubbery character. In this work, the addition of commercial pea proteins (PPC) to HPP gels and emulsions was studied.Physical properties of gels and emulsions prepared with different proportions of mixtures of PPC and HPP were evaluated. In general, gels and emulsions showed high values for whiteness and, as expected, the higher content of HPP in the protein mixtures led to higher firmness values of the gels. The gel network was rapidly formed upon heating due to the fish protein macromolecules and further reinforced by the pea protein macromolecules when cooled to 5 °C. Both visco-elastic parameters, storage and loss moduli, of the produced gels increased with the HPP proportion in the protein mixtures, corresponding to more structured systems. For the emulsions, two different pH environments were studied: 3.8 and 7.0. At neutral pH a synergy was found between the vegetable and fish protein, which is not so strong when pH is lowered to 3.8, near the isoelectric point of pea proteins (pI = 4.5). This evidence was supported by the results from the texture measurements, viscosity and visco-elastic parameters.Gels made from Cape hake proteins showed a softer texture and were less rubbery with the addition of pea proteins. Emulsions stabilised by these mixtures showed slightly different behaviour when produced at pH 7.0 or pH 3.8.
|
[
"Materials Engineering",
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
223596
|
Functional exploration of the contributions of brainstem-motor thalamic pathways to motor execution and learning
|
Motor learning is a fundamental process enabling an organism to improve movement efficiency during a motor task. It is supported by motor cortex, which organizes movements into complex sequences. Yet, how this structure is informed of planned and generated actions is poorly understood. Anatomically, motor cortex is highly interconnected with the motor thalamus (Mthal). Interestingly, this structure is involved during the acquisition of different motor tasks, but also shows homologous roles in motor function to brainstem areas. In line with these observations, we hypothesize that pathways between the brainstem to Mthal represent an interesting and unexplored way for motor information to reach cortical areas during motor learning.
This project aims at exploring the anatomical organization and functional importance of brainstem-Mthal pathways in motor learning and transmission to the cortex. It will first explore the bidirectional synaptic organization of these pathways according to neuronal subpopulation identity using mouse genetics and viral tools for anatomy. In a second step, it will explore the hypothesis of a specific role of the different brainstem-Mthal pathways in motor learning, including dexterous vs sequential motor learning tasks. The involvement of the observed pathways in these tasks will be explored with in-vivo calcium imaging. This will allow us to determine whether changes in neuronal activity of brainstem-Mthal projection neurons are correlated with ongoing motor behavior and with which phases. Finally, these results will be probed for functionality by direct manipulation of these circuits in behaving mice. To this end, opto- and pharmacogenetic tools will be used in combination with viral technology to target and manipulate the characterized neuronal networks in mice performing motor learning tasks. Together, the results obtained through this project will lead to a better understanding of circuits involved in motor program execution and learning.
|
[
"Neuroscience and Disorders of the Nervous System",
"Integrative Biology: from Genes and Genomes to Systems"
] |
W2171163162
|
LA SUCESIÓN ENTRE LOS INCAS
|
One of the most controversial subjects with regard to the Andean pre Hispanic Organization is the one referring to succession of command. The Incas are not an exception on this matter, and since the sixteenth century the query has been raised and more than one theory has been devised. The subject has not been alien to chroniclers of the Indias nor to modern historians. Basically, two postures have arisen. On the one hand, there is one that interprets the information of the Andean chronicles literally and presents a vision of Inca's succession that incorporates to the Andes, the parameters of the European dynastic succession of the epoch. In this posture intervenes, among others, the concept of bastardy, legitimacy and primogeniture. On the other hand, another posture has been developed, aiming to be more critic with the sources and to offer an alternative structure. From the Ethnohistoric point of view, the thesis on the ability to govern has become stronger as a principal parameters on the subject of Inca's succession. This article reviews the postures proposed on the subject of succession and based on the colonial sources on the Andes. Ipresent an alternative interpretation in which the power from the King to his brothers seems to be previous to the stage of passing power to the next generation.
|
[
"The Study of the Human Past",
"Studies of Cultures and Arts"
] |
10.1161/HYPERTENSIONAHA.118.11382
|
Computed Tomography And Adrenal Venous Sampling In The Diagnosis Of Unilateral Primary Aldosteronism
|
Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral primary aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994-2016) or AVS (526 patients, diagnosed from 1994-2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], <0. 001) and a greater proportion with absent biochemical success (29 of 235 [12%] versus 10 of 526 [2%], <0. 001). A diagnosis by CT was associated with a decreased likelihood of complete biochemical success compared with AVS (odds ratio, 0. 28; 0. 16-0. 50; <0. 001). Clinical outcomes were not significantly different, but the absence of a postsurgical elevated aldosterone-to-renin ratio was a strong marker of complete clinical success (odds ratio, 14. 81; 1. 76-124. 53; =0. 013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS.
|
[
"Prevention, Diagnosis and Treatment of Human Diseases",
"Physiology in Health, Disease and Ageing"
] |
W2288489881
|
Measurement and analysis of 3G WCDMA network performance case study: Yogyakarta Indonesia
|
Yogyakarta is an education and tourism city. The quality of internet services is needed to support the education quality and tourist services. These services are supported by 3G WCDMA technology. This paper will discuss the need of Information Technology (IT) for education and tourism sector, and also assesment of the IT performance in Yogyakarta, specially data sevices for mobile devices. The most of user using 3G WCDMA technology, so we focus measure and evaluate the performance of 3G WCDMA services. In Yogyakarta, education and tourism sector spread to many places like urban, sub urban, and rural area. So In this research we investigate the performance at that areas. Some parameters were measured and analyzed is RSCP (Received Signal Code Power), Ec/No (Energy perchip to Noise ratio), CCSR (Call Completion Success Rate), CSSR (Call Setup Success Rate), and SHOSR (Soft Handover Success Rate). This research find that the lowest of CSSR and CCSR percentage is in urban areas, about 90.41% and 91.78%. Some call requests in this area that can be served, but its still upper than CSSR standards (CSSR ≥ 90%). While in Sub-urban, the value of CSSR about 97.33%. SHOSR percentages in all three areas is very good, there aren't soft handover failure. So by this result, we recommend that services in urban areas should be improved as an impact of large number of user and contour of buildings.
|
[
"Systems and Communication Engineering",
"Products and Processes Engineering"
] |
10.1146/annurev-ecolsys-110512-135825
|
Geographic mode of speciation and genomic divergence
|
Understanding speciation requires determining how inherent barriers to gene flow (reproductive isolation, RI) evolve between populations. The field of population genomics attempts to address this question by characterizing genome-wide patterns of divergence between taxa, often utilizing next-generation sequencing. Here, we focus on a central assumption of such "genome scans": regions displaying high levels of differentiation contain loci contributing to RI. Three major issues are discussed concerning the relationship between gene flow, genomic divergence, and speciation: (a) patterns expected in the presence versus absence of gene flow; (b) processes, such as direct selection and genetic hitchhiking, allowing for divergence with gene flow; and (c) the consequences of the timing of when gene flow occurs during speciation (e. g. , continuous gene flow versus gene flow following secondary contact after a period of initial allopatric divergence). Theory and existing data are presented for each issue, and avenues for future work are highlighted.
|
[
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution"
] |
10.1371/journal.pgen.1004813
|
Genetic Analysis of the Cardiac Methylome at Single Nucleotide Resolution in a Model of Human Cardiovascular Disease
|
Epigenetic marks such as cytosine methylation are important determinants of cellular and whole-body phenotypes. However, the extent of, and reasons for inter-individual differences in cytosine methylation, and their association with phenotypic variation are poorly characterised. Here we present the first genome-wide study of cytosine methylation at single-nucleotide resolution in an animal model of human disease. We used whole-genome bisulfite sequencing in the spontaneously hypertensive rat (SHR), a model of cardiovascular disease, and the Brown Norway (BN) control strain, to define the genetic architecture of cytosine methylation in the mammalian heart and to test for association between methylation and pathophysiological phenotypes. Analysis of 10. 6 million CpG dinucleotides identified 77,088 CpGs that were differentially methylated between the strains. In F1 hybrids we found 38,152 CpGs showing allele-specific methylation and 145 regions with parent-of-origin effects on methylation. Cis-linkage explained almost 60% of inter-strain variation in methylation at a subset of loci tested for linkage in a panel of recombinant inbred (RI) strains. Methylation analysis in isolated cardiomyocytes showed that in the majority of cases methylation differences in cardiomyocytes and non-cardiomyocytes were strain-dependent, confirming a strong genetic component for cytosine methylation. We observed preferential nucleotide usage associated with increased and decreased methylation that is remarkably conserved across species, suggesting a common mechanism for germline control of inter-individual variation in CpG methylation. In the RI strain panel, we found significant correlation of CpG methylation and levels of serum chromogranin B (CgB), a proposed biomarker of heart failure, which is evidence for a link between germline DNA sequence variation, CpG methylation differences and pathophysiological phenotypes in the SHR strain. Together, these results will stimulate further investigation of the molecular basis of locally regulated variation in CpG methylation and provide a starting point for understanding the relationship between the genetic control of CpG methylation and disease phenotypes.
|
[
"Integrative Biology: from Genes and Genomes to Systems",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
] |
10.1039/C5CC00693G
|
Tetrabenzocircumpyrene A Nanographene Fragment With An Embedded Peripentacene Core
|
A new disc-shaped highly symmetric C54H20 nanographene fragment, tetrabenzocircumpyrene, has been synthesized and characterized by scanning tunnelling microscopy, demonstrating the potential of this technique for identifying highly insoluble graphenic molecules.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
170274
|
Identification and characterization of cis-regulatory moduledysfunction in rett syndrome with roq-wach
|
Precise regulation of gene expression is achieved through the coordinated action of genomic cis-regulatory modules (CRMs). The identification of CRMs has long been a goal of functional genomics as CRM dysregulation can have devastating consequences for health and development such as autism. For example, mutations in the MeCP2 gene, which encodes protein that binds methylated DNA and regulates gene expression in neurons, results an Autism Spectrum Disorder termed Rett Syndrome. While thought to modulate CRM activity as a repressor, MeCP2’s function remains ambiguous and would benefit from a functional genomics characterization. To identify CRMs I recently developed a novel approach called FIREWACh. Here, I propose to utilize FIREWACh first to identify active CRMs within a homogenous population of neurons, identifying genomic loci of CRMs whose function may be compromised by MeCP2 mutations. I will adapt FIREWACh to allow the quantification of CRM output in a new method I propose to call ROQ-WACh (regulatory output quantification within accessible chromatin) by addition of barcodes to reporter mRNAs. This will allow high-throughput readout of CRM activity globally in vivo and will be broadly applicable to many biological fields. Lastly, I aim to combine the above approaches to quantify the changes in CRM output in response to pathological mutations in MeCP2. This Marie Sklodowska-Curie Action will allow me (the Experienced Researcher, Matthew Murtha) mobility to Spain to join the laboratory of Dr. Manel Esteller (Host Supervisor), renowned epigeneticist and expert in DNA-methylation biology to perform the research. Together the approaches and data generated by this MSCA action will provide key insights into the relationship between methylated DNA, precise control of gene expression, and high-order phenotypes such as cognitive behaviors.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Neuroscience and Disorders of the Nervous System",
"Integrative Biology: from Genes and Genomes to Systems"
] |
10.1016/j.tplants.2009.09.010
|
When more is better: multigene engineering in plants
|
The genomics revolution has taught us that a great deal of information can be derived from studying many genes or proteins at the same time. We are beginning to see this approach blossoming in applied research. Instead of attempting to generate useful transgenic plants by introducing single genes, we now see an increasing number of researchers embracing multigene transfer (MGT) as an approach to generate plants with more ambitious phenotypes. MGT allows researchers to achieve goals that were once impossible - the import of entire metabolic pathways, the expression of entire protein complexes, the development of transgenic crops simultaneously engineered to produce a spectrum of added-value compounds. The potential appears limitless.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Biotechnology and Biosystems Engineering"
] |
10.1016/j.molcel.2017.05.014
|
Histone Mutants Separate R Loop Formation from Genome Instability Induction
|
R loops have positive physiological roles, but they can also be deleterious by causing genome instability, and the mechanisms for this are unknown. Here we identified yeast histone H3 and H4 mutations that facilitate R loops but do not cause instability. R loops containing single-stranded DNA (ssDNA), versus RNA-DNA hybrids alone, were demonstrated using ssDNA-specific human AID and bisulfite. Notably, they are similar size regardless of whether or not they induce genome instability. Contrary to mutants causing R loop-mediated instability, these histone mutants do not accumulate H3 serine-10 phosphate (H3S10-P). We propose a two-step mechanism in which, first, an altered chromatin facilitates R loops, and second, chromatin is modified, including H3S10-P, as a requisite for compromising genome integrity. Consistently, these histone mutations suppress the high H3S10 phosphorylation and genomic instability of hpr1 and sen1 mutants. Therefore, contrary to what was previously believed, R loops do not cause genome instability by themselves.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1142/S0218202515400059
|
Sparse Stabilization And Control Of Alignment Models
|
Starting with the seminal papers of Reynolds (1987), Vicsek et al. (1995), Cucker–Smale (2007), there has been a lot of recent works on models of self-alignment and consensus dynamics. Self-organization has so far been the main driving concept of this research direction. However, the evidence that in practice self-organization does not necessarily occur (for instance, the achievement of unanimous consensus in government decisions) leads to the natural question of whether it is possible to externally influence the dynamics in order to promote the formation of certain desired patterns. Once this fundamental question is posed, one is also faced with the issue of defining the best way of obtaining the result, seeking for the most "economical" way to achieve a certain outcome. Our paper precisely addressed the issue of finding the sparsest control strategy in order to lead us optimally towards a given outcome, in this case the achievement of a state where the group will be able by self-organization to reach an alignment consensus. As a consequence, we provide a mathematical justification to the general principle according to which "sparse is better": in order to achieve group consensus, a policy maker not allowed to predict future developments should decide to control with stronger action the fewest possible leaders rather than trying to act on more agents with minor strength. We then establish local and global sparse controllability properties to consensus. Finally, we analyze the sparsity of solutions of the finite time optimal control problem where the minimization criterion is a combination of the distance from consensus and of the l1-norm of the control. Such an optimization models the situation where the policy maker is actually allowed to observe future developments. We show that the lacunarity of sparsity is related to the codimension of certain manifolds in the space of cotangent vectors.
|
[
"Mathematics",
"Systems and Communication Engineering"
] |
W2129875228
|
Modelling and control of proton exchange membrane fuel cell
|
Proton exchange membrane fuel cell (PEMFC) has been considered as one of the most promising energy sources due to its many desirable properties, including high power density, low operating temperature and fast start-up. However, significant technical challenges exist before PEMFC can be commercialized. Among them, the modelling and control of PEMFC have been recognized as the most critical technical issues. This is because PEMFC's inherent nonlinearities, time-varying characteristics and tight operating constraints inevitably give rise to great challenges for system modelling and control. The objective of this thesis is then accurate modelling and efficient control of PEMFC. To accomplish these goals, new modelling and control methods are developed and validated.
First, a new empirical model of PEMFC is developed by mapping performance outputs as a function of various operating conditions through regression analysis of support vector machine (SVM). Further, the empirical modelling approach is integrated with the mechanistic modelling method to develop a combined model of PEMFC, which consists of an empirical submodel for the reference voltage and a mechanistic submodel for the correction voltage. Simulation results demonstrate that these models have desirable properties, including good accuracy, fast response and low computational burden. These characteristics lay the solid foundation for the development of control strategies.
Then, various control strategies are developed, including model predictive control (MPC) for regulating PEMFC outputs to the desired value, extreme seeking control (ESC) for tracking the maximum efficiency point and linearized-model-based control for PEMFC thermal management. Simulation results demonstrate that each of the control strategies achieves the control objective that it is supposed to accomplish.
Finally, a full picture of future hydrogen economy in China is given, including drivers for transition to the hydrogen economy, energy resources and their potential role in future hydrogen production, government's policy and support for the research of hydrogen and fuel cell technology.
|
[
"Systems and Communication Engineering",
"Products and Processes Engineering",
"Computer Science and Informatics"
] |
758769
|
Resonant Electromagnetic Microscopy: Imaging Cells Electronically
|
Microfluidics technology has been quite successful in fabricating small, low-cost devices with excellent analyte handling capabilities. However, the main detection paradigm in microfluidics has still been optical microscopy — which is a bulky and expensive technique. A chip-scale detection scheme that can provide multidimensional information is much needed for the widespread adoption of lab-on-a-chip technology. So far, successful capacitive and resonant electrical sensors have been deployed in the field; yet the focus of these sensors has been to obtain the electrical volume or location of a particle — which constitutes only a limited piece of information about the analytes. Here we propose to redesign and utilize resonant electrical sensors in a radically different way to obtain images of cells in a microfluidic channel. The technique proposed can also multiplex on-chip cytometry greatly, accomplish low-cost and high-throughput single-cell transit-time characterization, obtain not only the electrical but also the geometrical size of analytes, determine the dielectric permittivity of analytes, in addition to capturing 1D profile or 2D images of cells. At the basic science level, the project will enhance our understanding of the interaction of electromagnetic fields and living matter at the single cell level and may provide new insights on cell motility, growth and mechanics.
|
[
"Systems and Communication Engineering",
"Condensed Matter Physics",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
10.1073/pnas.1317643111
|
Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection
|
The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 12 (NLRP12) plays a protective role in intestinal inflammation and carcinogenesis, but the physiological function of this NLR during microbial infection is largely unexplored. Salmonella enterica serovar Typhimurium (S. typhimurium) is a leading cause of food poisoning worldwide. Here, we show that NLRP12-deficient mice were highly resistant to S. typhimurium infection. Salmonella-infected macrophages induced NLRP12-dependent inhibition of NF-κB and ERK activation by suppressing phosphorylation of IκBα and ERK. NLRP12-mediated downregulation of proinflammatory and antimicrobial molecules prevented efficient clearance of bacterial burden, highlighting a role for NLRP12 as a negative regulator of innate immune signaling during salmonellosis. These results underscore a signaling pathway defined by NLRP12-mediated dampening of host immune defenses that could be exploited by S. typhimurium to persist and survive in the host.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
W2315628567
|
Determination of environmental radioactivity (238U, 232Th and 40K) and indoor natural background radiation level in Chennai city (Tamilnadu State), India
|
An extensive study on the determination of the natural radioactivity ((238)U, (232)Th and (40)K) levels in soil samples of Chennai city, India has been undertaken and the results of the same are compared with the levels reported in other Indian cities as well as other parts of the world. The radioactivity content in the soil samples, the absorbed dose rate, annual effective dose equivalent, radium equivalent activity, internal and external hazard indices were calculated and compared with UNSCEAR 2000 recommended values. In addition to the above, mapping of indoor natural background gamma radiation levels has been made using thermo luminescent dosemeters throughout Chennai city and the same are reported.
|
[
"Earth System Science",
"Physical and Analytical Chemical Sciences"
] |
10.1007/s00220-014-2031-z
|
Mean-Field Evolution of Fermionic Systems
|
The mean field limit for systems of many fermions is naturally coupled with a semiclassical limit. This makes the analysis of the mean field regime much more involved, compared with bosonic systems. In this paper, we study the dynamics of initial data close to a Slater determinant, whose reduced one-particle density is an orthogonal projection ω N with the appropriate semiclassical structure. Assuming some regularity of the interaction potential, we show that the evolution of such an initial data remains close to a Slater determinant, with reduced one-particle density given by the solution of the Hartree-Fock equation with initial data ωN. Our result holds for all (semiclassical) times, and gives effective bounds on the rate of the convergence towards the Hartree-Fock dynamics.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
interreg_3481
|
Saastal Valle Anzasca Bike
|
The project provides an answer to the tourist vocation of the area by promoting a sustainable enhancement of the environmental heritage. It has specific objectives: the development and promotion of the tourism potential linked to the cycle-hiking in the cross-border area surrounding Monte Rosa; the completion of a route for mountain bikes and e-bikes that connects the Saas Valley with the Anzasca Valley without interruptions, the integrated and shared enhancement of a territory characterized by a common environmental and cultural context (the area of Monte Rosa, Walser). Arrival and departure of the route will be connected to the most important roads and railways. It is estimated that the project will affect the increase and diversification of the number of tourists and the competitiveness of the economic activities present in the territory of the two valleys.
|
[
"Human Mobility, Environment, and Space",
"Products and Processes Engineering"
] |
10.1017/CBO9780511819049.012
|
Selecting Models Of Evolution
|
THEORY Models of evolution and phylogeny reconstruction Phylogenetic reconstruction is a problem of statistical inference. Since statistical inferences cannot be drawn in the absence of probabilities, the use of a model of nucleotide substitution or amino acid replacement – a model of evolution – becomes indispensable when using DNA or protein sequences to estimate phylogenetic relationships among taxa. Models of evolution are sets of assumptions about the process of nucleotide or amino acid substitution (see Chapters 4 and 9). They describe the different probabilities of change from one nucleotide or amino acid to another along a phylogenetic tree, allowing us to choose among different phylogenetic hypotheses to explain the data at hand. Comprehensive reviews of models of evolution are offered elsewhere (Swofford et al . , 1996; Lio & Goldman, 1998). As discussed in the previous chapters, phylogenetic methods are based on a number of assumptions about the evolutionary process. Such assumptions can be implicit, like in parsimony methods (see Chapter 8), or explicit, like in distance or maximum likelihood methods (see Chapters 5 and 6, respectively). The advantage of making a model explicit is that the parameters of the model can be estimated. Distance methods can only estimate the number of substitutions per site. However, maximum likelihood methods can estimate all the relevant parameters of the model of evolution.
|
[
"Mathematics",
"Environmental Biology, Ecology and Evolution"
] |
W2511593010
|
The Xitieshan volcanic sediment-hosted massive sulfide deposit, North Qaidam, China: Geology, structural deformation and geochronology
|
Abstract The Xitieshan deposit (~ 64 Mt at 4.86% Zn, 4.16% Pb, 58 g/t Ag, and 0.68 g/t Au) is hosted by the Middle to Late Ordovician Tanjianshan Group of the North Qaidam tectonic metallogenic belt, NW China. This belt is characterized by island arc volcanic, ultra-high pressure (UHP) metamorphic and ophiolitic rocks. The Tanjianshan Group constitutes a succession of metamorphosed bimodal volcanic and sedimentary rocks, which are interpreted to have formed on the margin of a back-arc ocean basin between the Qaidam block and the Qilian block. Four stratigraphic units are identified within the Ordovician Tanjianshan Group. From northeast to southwest they are: 1) unit a, or the lower volcanic-sedimentary rocks, comprising bimodal volcanic rocks (unit a-1) and sedimentary rocks (unit a-2) ranging from carbonates to black carbonaceous schist; 2) unit b, or intermediate-mafic volcaniclastic rocks, characterized by intermediate to mafic volcaniclastic rocks intercalated with lamellar carbonaceous schist and minor marble lenses; 3) unit c, a purplish red sandy conglomerate that unconformably overlies unit b, representing the product of the foreland basin sedimentation during the Early Silurian; 4) unit d, or mafic volcanic rocks, from base to up, comprising the lower mafic volcaniclastic rocks (unit d-1), middle clastic sedimentary rocks (unit d-2), upper mafic volcaniclastic rocks (unit d-3), and uppermost mafic volcanic rocks (unit d-4). Unit a-2 hosts most of the massive sulfides whereas unit b contains subordinate amounts. The massive stratiform lenses constitute most of the Xitieshan deposit with significant amount of semi-massive and irregularly-shaped sulfides and minor amounts in stringer veins. Pyrite, galena and sphalerite are the dominant sulfide minerals, with subordinate pyrrhotite and chalcopyrite. Quartz is a dominant gangue mineral. Sericite, quartz, chlorite, and carbonate alteration of host rocks accompanies the mineralization. U-Pb zircon geochronology yields three ages of 454 Ma, 452 Ma and 451 Ma for the footwall felsic volcanic rocks in unit a-1, sedimentary host rocks in unit a-2 and hanging-wall unit b, respectively. The Xitieshan deposit is considered to be coeval with the sedimentation of unit a-2 and unit b of the Tanjianshan Group. The Xitieshan deposit has been intensely deformed during two phases (main ductile shear and minor ductile-brittle deformation). The main ductile shear deformation controls the general strike of the ore zones, whereas minor deformation controls the internal geometry of the ore bodies. 40 Ar- 39 Ar age of muscovite from mylonitized granitic gneisses in the ductile shear zone is ~ 399 Ma, which is interpreted to date the Xitieshan ductile shear zone, suggesting that Early Devonian metamorphism and deformation post-dated the Tanjianshan Group. The Xitieshan deposit has many features similar to that of the Bathurst district of Canada, the Iberian Pyrite Belt of Spain, the Wolverine volcanogenic massive sulfide deposit in Canada. Based on its tectonic setting, host-rock types, local geologic setting, metal grades, geochronology, temperatures and salinities of mineralizing fluid and source of sulfur, the Xitieshan deposit has features similar to sedimentary exhalative (SEDEX) and VMS deposits and is similar to volcanic and sediment-hosted massive sulfide (VSHMS) deposits.
|
[
"Earth System Science"
] |
W2593009560
|
Missions involvement and interfaith relations: Forming pathways of commonality
|
The reality of an ever-accelerating globalization, accompanied by an expanding religious pluralism, presents significant challenges to many long-enduring concepts of doing missions. This article will focus on identifying some of those challenges and offering some possible options for ongoing missions involvement. Particular attention will be given to the potential of melding missions practices with the nurturing of interfaith relationships with the prospect of forming covenants of commonality. It is our premise that continuing interfaith conversations will break down barriers of misunderstanding and facilitate the growth of mutually compatible relationships across delicate cultural and religious boundary lines. Within the context of these developing cross-faith relationships, probable new opportunities for effectual missions ministry will emerge. In developing this article, we will draw from multiple sources, including published works by notable scholars of missiology, theology, ethics, and sociology. Songs, hymns, poems, and prayers will provide helpful illustrations. Additional material will come from real-life interfaith interchanges and from our personal experiences while serving as missions practitioners in West Africa and Eastern Europe.
|
[
"The Social World and Its Interactions",
"Studies of Cultures and Arts"
] |
10.1007/s00216-019-01674-9
|
Immobilization of proteolytic enzymes on replica-molded thiol-ene micropillar reactors via thiol-gold interaction
|
We introduce rapid replica molding of ordered, high-aspect-ratio, thiol-ene micropillar arrays for implementation of microfluidic immobilized enzyme reactors (IMERs). By exploiting the abundance of free surface thiols of off-stoichiometric thiol-ene compositions, we were able to functionalize the native thiol-ene micropillars with gold nanoparticles (GNPs) and these with proteolytic α-chymotrypsin (CHT) via thiol-gold interaction. The micropillar arrays were replicated via PDMS soft lithography, which facilitated thiol-ene curing without the photoinitiators, and thus straightforward bonding and good control over the surface chemistry (number of free surface thiols). The specificity of thiol-gold interaction was demonstrated over allyl-rich thiol-ene surfaces and the robustness of the CHT-IMERs at different flow rates and reaction temperatures using bradykinin hydrolysis as the model reaction. The product conversion rate was shown to increase as a function of decreasing flow rate (increasing residence time) and upon heating of the IMER to physiological temperature. Owing to the effective enzyme immobilization onto the micropillar array by GNPs, no further purification of the reaction solution was required prior to mass spectrometric detection of the bradykinin hydrolysis products and no clogging problems, commonly associated with conventional capillary packings, were observed. The activity of the IMER remained stable for at least 1. 5 h (continuous use), suggesting that the developed protocol may provide a robust, new approach to implementation of IMER technology for proteomics research. [Figure not available: see fulltext. ].
|
[
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials",
"Materials Engineering"
] |
803506
|
The Rise and Fall of Populism and Extremism
|
In the recent years in advanced democracies there has been a wave of electoral successes of populist politicians supporting extreme messages. Is populism caused by negative economic shocks? If so, what are the mechanisms? What explains heterogeneity in responses to such shocks? In this project, I will test empirically if personal experiences, information environment, and their interaction with aggregate economic shocks shape people’s political decisions. The project consists of three parts.
First, I will study how personal employment histories, potentially affected by globalization and technological shocks, individual predispositions, and information environment influenced voting for Trump. I will use a unique database of more than 40 million resumes for the period 2010-2016, the largest available repository of resumes of job-seekers in the US, which was not previously used in academic research, and match it with zipcode-level economic and voting variables.
Second, I will study how negative social experiences during the formative years affect subsequent labor market outcomes, antisocial behavior, and the support of populist agenda. I will examine how corporal punishment in schools in UK affected subsequent educational attainment, employment, antisocial behavior, and voting for UKIP and Brexit. I will digitize archival records on regulations and practice of corporal punishment in different educational authorities in the UK during 1970-80s, combining it with contemporary outcomes.
Third, I will examine what makes people actively resist extremist regimes even when it is associated with high personal costs. I will study a historical example of resistance to Nazi regime in Germany during the WWII, which provides unique methodological opportunity to study determinants of resistance to extremism in a high stake environment. I will use a self-collected dataset on treason cases to measure resistance, combining it with data on bombing and exposure to foreign propaganda.
|
[
"Individuals, Markets and Organisations",
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
] |
10.1016/j.celrep.2016.10.007
|
The Phosphatase Dusp7 Drives Meiotic Resumption and Chromosome Alignment in Mouse Oocytes
|
Mammalian oocytes are stored in the ovary, where they are arrested in prophase for prolonged periods. The mechanisms that abrogate the prophase arrest in mammalian oocytes and reinitiate meiosis are not well understood. Here, we identify and characterize an essential pathway for the resumption of meiosis that relies on the protein phosphatase DUSP7. DUSP7-depleted oocytes either fail to resume meiosis or resume meiosis with a significant delay. In the absence of DUSP7, Cdk1/CycB activity drops below the critical level required to reinitiate meiosis, precluding or delaying nuclear envelope breakdown. Our data suggest that DUSP7 drives meiotic resumption by dephosphorylating and thereby inactivating cPKC isoforms. In addition to controlling meiotic resumption, DUSP7 has a second function in chromosome segregation: DUSP7-depleted oocytes that enter meiosis show severe chromosome alignment defects and progress into anaphase prematurely. Altogether, these findings establish the phosphatase DUSP7 as an essential regulator of multiple steps in oocyte meiosis.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
279980
|
Fundamental Physics at the Low Background Frontier
|
The nature of dark matter is one of the fundamental questions in physics today. Direct signals for dark matter have remained elusive, indicating that multi-tonne scale detectors are needed to measure large numbers of dark matter interactions, while current efforts are at the 100 kg scale. The foremost challenge is distinguishing dark matter signals from backgrounds, the most uncertain of which are from neutrons. The research objective of this proposal is a world-leading dark matter search with a novel liquid argon (LAr) detector and a new analysis approach to measuring neutron backgrounds in-situ.
The DEAP/CLEAN program of single-phase LAr detectors is a new direction for dark matter searches. It draws on successful, proven approaches of solar neutrino physics to building low-background detectors that scale simply to multi-tonne target masses. Demonstration of this approach by the current 100 kg stage (MiniCLEAN) will break new ground for future experiments. At the 100 tonne scale, such a detector would be a new kind of observatory for fundamental physics at the low background frontier, testing predicted properties of dark matter, neutrinos, supernovae, and stellar evolution. Success depends critically on demonstrating the required background suppression.
This proposal addresses the key challenges of dark matter detection in two new ways, with the novel single-phase effort for multi-tonne scalability, and by developing new methods to overcome neutron backgrounds. The tasks of this proposal are: (i) to develop a measurement of the in-situ neutron background in LAr; (ii) to develop an active neutron veto for in-situ measurement of the cosmogenic neutron background, beginning with a measurement of the flux and energy spectrum in an existing prototype; and, (iii) to lead the dark matter search, using the measured backgrounds. The MiniCLEAN dark matter sensitivity is a factor of 20 beyond current experimental results, with great potential for discovery.
|
[
"Fundamental Constituents of Matter",
"Universe Sciences"
] |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.