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10.1037/bul0000217
|
Personality and prosocial behavior: A theoretical framework and meta-analysis
|
Decades of research document individual differences in prosocial behavior using controlled experiments that model social interactions in situations of interdependence. However, theoretical and empirical integration of the vast literature on the predictive validity of personality traits to account for these individual differences is missing. Here, we present a theoretical framework that identifies 4 broad situational affordances across interdependent situations (i. e. , exploitation, reciprocity, temporal conflict, and dependence under uncertainty) and more specific subaffordances within certain types of interdependent situations (e. g. , possibility to increase equality in outcomes) that can determine when, which, and how personality traits should be expressed in prosocial behavior. To test this framework, we meta-analyzed 770 studies reporting on 3,523 effects of 8 broad and 43 narrow personality traits on prosocial behavior in interdependent situations modeled in 6 commonly studied economic games (Dictator Game, Ultimatum Game, Trust Game, Prisoner's Dilemma, Public Goods Game, and Commons Dilemma). Overall, meta-analytic correlations ranged between -. 18 ≤ p ≤ . 26, and most traits yielding a significant relation to prosocial behavior had conceptual links to the affordances provided in interdependent situations, most prominently the possibility for exploitation. Moreover, for several traits, correlations within games followed the predicted pattern derived from a theoretical analysis of affordances. On the level of traits, we found that narrow and broad traits alike can account for prosocial behavior, informing the bandwidth-fidelity problem. In sum, the meta-analysis provides a theoretical foundation that can guide future research on prosocial behavior and advance our understanding of individual differences in human prosociality.
|
[
"The Social World and Its Interactions",
"The Human Mind and Its Complexity"
] |
10.1038/s41586-018-0672-3
|
Conformational transitions of the serotonin 5-HT<inf>3</inf> receptor
|
The serotonin 5-HT3 receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane1,2; upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions that result in transient opening of a pore permeable to ions. 5-HT3 receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression3. In spite of several reported pLGIC structures4–8, no clear unifying view has emerged on the conformational transitions involved in channel gating. Here we report four cryo-electron microscopy structures of the full-length mouse 5-HT3 receptor in complex with the anti-emetic drug tropisetron, with serotonin, and with serotonin and a positive allosteric modulator, at resolutions ranging from 3. 2 Å to 4. 5 Å. The tropisetron-bound structure resembles those obtained with an inhibitory nanobody5 or without ligand9. The other structures include an ‘open’ state and two ligand-bound states. We present computational insights into the dynamics of the structures, their pore hydration and free-energy profiles, and characterize movements at the gate level and cation accessibility in the pore. Together, these data deepen our understanding of the gating mechanism of pLGICs and capture ligand binding in unprecedented detail.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Neuroscience and Disorders of the Nervous System",
"Physical and Analytical Chemical Sciences"
] |
W97557810
|
Assessment of Mitochondrial Damage in Retinal Cells and Tissues Using Quantitative Polymerase Chain Reaction for Mitochondrial DNA Damage and Extracellular Flux Assay for Mitochondrial Respiration Activity
|
Mitochondrial dysfunction and genomic instability are associated with a number of retinal pathologies including age-related macular degeneration, diabetic retinopathy, and glaucoma. Consequences of mitochondrial dysfunction within cells include elevation of the rate of ROS production due to damage of electron transport chain proteins, mitochondrial DNA (mtDNA) damage, and loss of metabolic capacity. Here we introduce the quantitative polymerase chain reaction assay (QPCR) and extracellular flux assay (XF) as powerful techniques to study mitochondrial behavior. The QPCR technique is a gene-specific assay developed to analyze the DNA damage repair response in mitochondrial and nuclear genomes. QPCR has proved particularly valuable for the measurement of oxidative-induced mtDNA damage and kinetics of mtDNA repair. To assess the functional consequence of mitochondrial oxidative damage, real-time changes in cellular bioenergetics of cell monolayers can be measured with a Seahorse Biosciences XF24 analyzer. The advantages and limitations of these procedures will be discussed and detailed methodologies provided with particular emphasis on retinal oxidative stress.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
W2530177326
|
On the effect of regrinding cutting tools for high performance milling of titanium alloys
|
The main challenges in high performance milling of difficult-to-machine metals are embedded in the development of innovative machining methods and cutting strategies. The aim is to reduce cycle time, resources and cost while maintaining or enhancing the machined product’s quality and performance. This will assist to increase both productivity and profitability. Many of the same material properties that make titanium alloys attractive for various industrial applications also contribute to its machining challenges. Tooling cost is one of the significant input costs associated with the cutting of titanium, and in order to reduce this, regrinding is used to extend the tool life of solid carbide end mill cutting tools. In an endeavour to increase the competitiveness of titanium machining companies, the effect of regrinding cutting tools on high performance milling of titanium alloys is studied. The research objectives include investigation into the effect of regrinding on the transition of tool wear phenomena, tool life tendency, part quality, cost, production rate and the high efficiency cutting speed range. It was found that the cost per machined volume of the reground cutting tools was significantly lower than that of the new cutting tools. This tendency increased with higher material removal rates. It was possible to recover more than 60 % of the original tool life using regrinding at a cost of 9 % the original purchase price.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
US 2016/0032707 W
|
DOWNHOLE PARAFFIN MELTING TOOL
|
A downhole paraffin melting tool is provided, comprising a heating element housing having a cutting head and a heating element disposed within the heating element housing. A battery pack is disposed within a battery pack housing, wherein the battery pack is operatively connected to the heating element. A control board is disposed between the heating element and the battery pack, wherein the control board is adapted to control power delivered from the battery pack to the heating element. A top sub is connected to the battery pack housing, wherein the top sub includes a retrievable member. The battery pack, delivering power to the heating element through the control board, is adapted to maintain a predetermined temperature of the heating element during operation.
|
[
"Products and Processes Engineering",
"Materials Engineering",
"Systems and Communication Engineering"
] |
10.1080/17530350.2015.1135473
|
Market Innovation As Framing Productive Friction And Bricolage An Exploration Of The Personal Data Market
|
ABSTRACTThis paper explores the possibilities offered by recent Science and Technology Studies (STS) research on markets for engaging with market innovation. Although there exist few reflections on how innovation happens in markets, market innovation has not been singularly theorized in STS-inspired market studies. In this paper, we explore the potential analytic utility of different sets of ideas in the field of market studies, such as ‘framing’ [Callon, M. (1998) ‘Introduction: the embeddedness of economic markets in economics’, in The Laws of Markets, ed. M. Callon, Blackwell, Oxford, pp. 1–57; Callon, M. (2007) ‘An essay on the growing contribution of economic markets to the proliferation of the social’, Theory, Culture & Society, vol. 24, no. 7–8, pp. 136–163], ‘productive friction’ [Stark, D. (2009) The Sense of Dissonance: Accounts of Worth in Economic Life, Princeton University Press, Princeton, NJ] and ‘bricolage’ [MacKenzie, D. & Pardo-Guerra, J. P. (2014) ‘Insurgent capitalism: Island, bricolag. . .
|
[
"Individuals, Markets and Organisations",
"Texts and Concepts",
"The Social World and Its Interactions"
] |
10.1073/pnas.1314112110
|
Protoribosome by quantum kernel energy method
|
Experimental evidence suggests the existence of an RNA molecular prebiotic entity, called by us the "protoribosome," which may have evolved in the RNA world before evolution of the genetic code and proteins. This vestige of the RNA world, which possesses all of the capabilities required for peptide bond formation, seems to be still functioning in the heart of all of the contemporary ribosome. Within the modern ribosome this remnant includes the peptidyl transferase center. Its highly conserved nucleotide sequence is suggestive of its robustness under diverse environmental conditions, and hence on its prebiotic origin. Its twofold pseudosymmetry suggests that this entity could have been a dimer of self-folding RNA units that formed a pocket within which two activated amino acids might be accommodated, similar to the binding mode of modern tRNA molecules that carry amino acids or peptidyl moieties. Using quantum mechanics and crystal coordinates, this work studies the question of whether the putative protoribosome has properties necessary to function as an evolutionary precursor to the modern ribosome. The quantum model used in the calculations is density functional theory-B3LYP/3-21G*, implemented using the kernel energy method to make the computations practical and efficient. It occurs that the necessary conditions that would characterize a practicable protoribosome - namely (i) energetic structural stability and (ii) energetically stable attachment to substrates - are both well satisfied.
|
[
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1080/10256010903388212
|
Biotic And Abiotic Factors Affecting The Δ13C Of Soil Respired Co2 In A Mediterranean Oak Woodland
|
The flux (R s) and carbon isotopic composition (δ13C Rs ) of soil respired CO 2 was measured every 2 h over the course of three diel cycles in a Mediterranean oak woodland, together with measurements of the δ13C composition of leaf, root and soil organic matter (δ13C SOM) and metabolites. Simulations of R s and δ13C Rs were also made using a numerical model parameterised with the SOM data and assuming short-term production rates were driven mainly by temperature. Average values of δ13C Rs over the study period were within the range of root metabolite and average δ13C SOM values, but enriched in 13C relative to the bulk δ13C of leaf, litter, and roots and the upper soil organic layers. There was good agreement between model output and observed CO 2 fluxes and the underlying features of δ13C Rs . Observed diel variations of 0. 5 ‰ in δ13C Rs were predicted by the model in response to temperature-related shifts in production rates along a ∼3 ‰ gradient observed in the profile of δ13C SOM. However, observed δ1. . .
|
[
"Environmental Biology, Ecology and Evolution",
"Earth System Science"
] |
10.1088/1751-8113/47/17/175002
|
Quantum Quenches From Excited States In The Ising Chain
|
We consider the non-equilibrium dynamics after a sudden quench of the magnetic field in the transverse field Ising chain starting from excited states of the pre-quench Hamiltonian. We prove that stationary values of local correlation functions can be described by the generalized Gibbs ensemble. Then we study the full time evolution of the transverse magnetization by means of stationary phase methods. The equal-time two-point longitudinal correlation function is analytically derived for a particular class of excited states for quenches within the ferromagnetic phase, and studied numerically in general. The full time dependence of the entanglement entropy of a block of spins is also obtained analytically for the same class of states and for arbitrary quenches.
|
[
"Condensed Matter Physics",
"Mathematics"
] |
10.1210/clinem/dgz069
|
Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study
|
Aims Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. Methods We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs. We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1. 139 [0. 800–1. 622], P = . 47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.
|
[
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
EP 2008064586 W
|
METHOD FOR CONTROLLING A RINSE CYCLE IN A WATER-BEARING HOUSEHOLD APPLIANCE
|
The invention relates to a method for controlling a rinse cycle in a water-bearing household appliance, particularly a dishwasher or washing machine, to meet a predetermined discharge performance by adapting at least one operating parameter of the water-bearing household device, comprising at least the steps: a) measuring (S10) a fill volume (Vist) admitted into the water-bearing household appliance, b) determining (S12) a fill volume deviation (?V) of the admitted fill volume (Vist) from a predetermined target fill volume (Vsoll), and c) adapting (S24, S26) at least one operating parameter such that the predetermined discharge performance is achieved under consideration of the fill volume deviation (?V).
|
[
"Products and Processes Engineering",
"Systems and Communication Engineering"
] |
10.1007/JHEP10(2013)217
|
The Closed String 3 Loop Amplitude And S Duality
|
The low-energy limit of the four-point 3-loop amplitude (including its overall coefficient) is computed in both type IIA and IIB superstring theories using the pure spinor formalism. The result is shown to agree with the prediction of the coefficient for the type IIB $D^6 R^4$ interaction made by Green and Vanhove based on S-duality considerations.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
10.1088/1367-2630/14/2/023021
|
Experimental characterization of photonic fusion using fiber sources
|
We report on the fusion of photons from two independent photonic crystal fiber sources into polarization entangled states using a fiber-based polarizing beamsplitter. We achieve fidelities of up to F = 0. 74 ±0. 01 with respect to the maximally entangled Bell state (φ +) using a low pump power of 5. 3 mW with a success rate of 3. 2 fourfold detections per second. By increasing the pump power we find that success rates of up to 111. 6 fourfold detections per second can be achieved, with entanglement still present in the fused state. We characterize the fusion operation by providing a full quantum process reconstruction. Here a model is developed to describe the generation of entanglement, including the main causes of imperfection, and we show that this model fits well with the experimental results. Our work shows how non-ideal settings limit the success of the fusion, providing useful information about the practical requirements for an operation that may be used to build large entangled states in bulk and on-chip quantum photonic waveguides.
|
[
"Fundamental Constituents of Matter",
"Systems and Communication Engineering",
"Physical and Analytical Chemical Sciences"
] |
647885
|
Smart Multimodal Microscopy for High-Throughput Developmental Biology in Real-Time
|
Fluorescence microscopy is a key technology in our quest to understand fundamental developmental processes of life. High-resolution images recorded in intact, living organisms deliver insights into the complex interplay of molecules, cells and tissues in real time. Even though the resolution of microscopes has been pushed beyond the diffraction limit, providing important insights into the inner workings of single cells, we still lack an understanding of plasticity in development: How does one embryo differ from another and how can we describe the ""average"", stereotypic embryo?
To address this long-standing multi-disciplinary challenge, we propose to develop an entirely novel microscopy hard- and software platform to systematically image and analyze embryos in real time. We will design and assemble a fast and flexible multimodal light-sheet microscope (SPIM) with adaptive illumination and detection from multiple sides. A fundamentally new concept of this proposal is the ability to adaptively change the recording's spatial and temporal resolution during the experiment: The microscope learns to acquire only the data of interest. Using a high-throughput sample feeder, many samples can be automatically pumped through the microscope and imaged within seconds for large-scale comparative developmental studies. Real-time processing will dramatically reduce the size of the data stream and thus, provide for the first time a platform to collect data from hundreds of samples. At the same time, by establishing a model for the observed embryo, we will integrate information from multiple samples to draw statistically relevant conclusions.
Our ground-breaking concept of smart microscopy speeds up the acquisition, reduces the amount of data and limits photo-toxicity. It enables us to address fundamental questions in embryonic development that are out of reach by traditional methods. Smart microscopy will open up a new field of research: systematic real-time developmental biology.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Computer Science and Informatics",
"Physical and Analytical Chemical Sciences"
] |
10.1371/journal.pone.0080341
|
Strong genetic influence on a UK nationwide test of educational achievement at the end of compulsory education at age 16
|
We have previously shown that individual differences in educational achievement are highly heritable in the early and middle school years in the UK. The objective of the present study was to investigate whether similarly high heritability is found at the end of compulsory education (age 16) for the UK-wide examination, called the General Certificate of Secondary Education (GCSE). In a national twin sample of 11,117 16-year-olds, heritability was substantial for overall GCSE performance for compulsory core subjects (58%) as well as for each of them individually: English (52%), mathematics (55%) and science (58%). In contrast, the overall effects of shared environment, which includes all family and school influences shared by members of twin pairs growing up in the same family and attending the same school, accounts for about 36% of the variance of mean GCSE scores. The significance of these findings is that individual differences in educational achievement at the end of compulsory education are not primarily an index of the quality of teachers or schools: much more of the variance of GCSE scores can be attributed to genetics than to school or family environment. We suggest a model of education that recognizes the important role of genetics. Rather than a passive model of schooling as instruction (instruere, 'to build in'), we propose an active model of education (educare, 'to bring out') in which children create their own educational experiences in part on the basis of their genetic propensities, which supports the trend towards personalized learning.
|
[
"Integrative Biology: from Genes and Genomes to Systems",
"The Social World and Its Interactions"
] |
W1999506585
|
Accurate calibration of resistance ratios between 1 MΩ and 1 GΩ using series resistors
|
As shown in high-resistance key comparisons carried out by the Consultative Committee for Electricity and Magnetism (CCEM), Inter-American Metrology System (SIM) and European Association of National Metrology Institutes (EURAMET), the accuracy of 10 MΩ and 1 GΩ resistances depends on ratio values between the reference resistance and unknown resistance and the accuracy of the reference resistance, which is determined with a quantized Hall resistance standard. This paper presents a method for calibrating 10:1 ratios in a high-resistance bridge using series resistors simply and accurately. By applying the 10:1 ratio errors determined using the presented method, the combined relative standard uncertainty for 1 GΩ resistance measurements using a modified Wheatstone bridge was estimated to be on the 1 × 10−6 level. The method was also applied to 1 GΩ resistance measurements using a direct-current comparator resistance bridge. It was found that the 1 GΩ resistances determined by the two bridges agreed within 2.4 × 10−6 Ω/Ω. We expect that the presented method can also be used to calibrate arbitrary resistance ratios.
|
[
"Systems and Communication Engineering"
] |
10.1103/PhysRevB.94.054522
|
Coherent diffraction of thermal currents in long Josephson tunnel junctions
|
We discuss heat transport in thermally-biased long Josephson tunnel junctions in the presence of an in-plane magnetic field. In full analogy with the Josephson critical current, the phase-dependent component of the heat current through the junction displays coherent diffraction. Thermal transport is analyzed as a function of both the length and the damping of the junction, highlighting deviations from the standard "Fraunhofer" pattern characteristic of short junctions. The heat current diffraction patterns show features strongly related to the formation and penetration of Josephson vortices, i. e. , solitons. We show that a dynamical treatment of the system is crucial for the realistic description of the Josephson junction, and it leads to peculiar results. In fact, hysteretic behaviors in the diffraction patterns when the field is swept up and down are observed, corresponding to the trapping of vortices in the junction.
|
[
"Condensed Matter Physics"
] |
US 2006/0022878 W
|
CROSSLINKED POLYETHYLENE ARTICLE
|
A method of manufacturing an article may include crosslinking a UHMWPE preform, shaping the crosslinked preform, heat-treating the shape in a temperature-controlled oven and low-oxygen environment, and inspecting the heat-treated shape for conformance to article specifications.
|
[
"Materials Engineering",
"Synthetic Chemistry and Materials"
] |
Q4753593
|
JANAS LAB — AGRUPAMENTO CU.L.T.PROJECT (VOZES PRINCIPAIS DO ASTARTE) — CULTURELAB 2018-62
|
INICIATIVA CULTURAL DESTINADA A MELHORAR A NECRÓPOLE DA PRUNITTU E O COMPLEXO NURAGIC DE SU MONTE, DEDICADO À HISTÓRIA PRÉ-NURÁGICA, FIGURAS NURÁGICAS E MÁGICAS DA SARDENHA. ELE PREVÊ A PREPARAÇÃO DOS ATIVOS PARA TORNÁ-LOS INTERATIVOS COM ARQUITETURAS IOT E ITC ATRAVÉS DE DISPOSITIVOS DE COMPUTAÇÃO ABRANGENTES E ONIPRESENTES CAPAZES DE ATIVAR E INTERAGIR EM AUTOMAÇÃO COM UTENTES, GUIAS DE ÁUDIO, CAMINHOS TEMÁTICOS E SENSORIAIS, BILHÉTICA AUTOMATIZADA, ALIMENTADO POR UMA REDE VERDE DE BAIXO CONSUMO, TAMBÉM COM ENERGIA SOLAR, E PONTOS WIIFI BLUETOOTH, VISANDO A SUSTENTABILIDADE QUE PODE CONECTAR LUGARES ABERTOS, DISTANTES UNS DOS OUTROS E NA AUSÊNCIA DE SISTEMAS ELÉTRICOS, PRODUTOS INOVADORES FEITOS ESPECIFICAMENTE PARA O PROJETO
|
[
"The Study of the Human Past",
"Systems and Communication Engineering",
"Products and Processes Engineering"
] |
10.1093/nar/gkw394
|
Comparative transcriptomics across the prokaryotic tree of life
|
Whole-transcriptome sequencing studies from recent years revealed an unexpected complexity in transcriptomes of bacteria and archaea, including abundant non-coding RNAs, cis-antisense transcription and regulatory untranslated regions (UTRs). Understanding the functional relevance of the plethora of non-coding RNAs in a given organism is challenging, especially since some of these RNAs were attributed to 'transcriptional noise'. To allow the search for conserved transcriptomic elements we produced comparative transcriptome maps for multiple species across the microbial tree of life. These transcriptome maps are detailed in annotations, comparable by gene families, and BLAST-searchable by user provided sequences. Our transcriptome collection includes 18 model organisms spanning 10 phyla/subphyla of bacteria and archaea that were sequenced using standardized RNA-seq methods. The utility of the comparative approach, as implemented in our web server, is demonstrated by highlighting genes with exceptionally long 5UTRs across species, which correspond to many known riboswitches and further suggest novel putative regulatory elements. Our study provides a standardized reference transcriptome to major clinically and environmentally important microbial phyla.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution"
] |
10.1016/j.jaut.2013.07.004
|
Novel insights into autoimmune liver diseases provided by genome-wide association studies
|
Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are complex disorders, resulting from the interaction of genetic and environmental factors. For many years, investigators have attempted to delineate the genetic architecture of these conditions, aiming to elucidate disease pathogenesis and identify molecular targets for pharmacotherapy. Early genetic studies consisted of HLA association studies and non-HLA candidate gene association studies, designed to identify association with selected HLA or non-HLA loci. HLA association studies identified HLA risk loci that are now well-established. Non-HLA candidate gene studies were less fruitful because they were mostly underpowered to detect modest effects and were frequently designed to investigate one or two functional polymorphisms, meaning that gene coverage was poor. Furthermore, weak associations detected in one small cohort were often never validated. If replication studies were undertaken, the results were often conflicting. More recently, a series of genome-wide association studies (GWAS) and related study designs have evaluated the impact of common genetic variants (frequency >5% in the general population) across the entire genome. These studies have identified several non-HLA risk loci for autoimmune liver disease. The majority of risk loci detected are similar to those of non-hepatic immune-mediated diseases, suggesting that outcomes from GWAS and related genetic studies reflect broad phenotypic themes rather than traditional clinical conditions. The specific genetic basis of these PBC and PSC associated inflammatory themes as determined by GWAS is described and discussed in the context of interacting genetic and non-genetic (including environmental) factors.
|
[
"Immunity, Infection and Immunotherapy",
"Integrative Biology: from Genes and Genomes to Systems"
] |
268540
|
The population biology of drug resistance:
Key principles for a more sustainable use of drugs
|
The evolution of drug resistance and its control represents a considerable challenge in very different biological contexts ranging from pesticide resistance in agriculture to antimicrobial resistance in clinical settings and even extends beyond infectious pathogens, as resistance also evolves in cancer chemotherapy. Naturally, the recommendations for the optimal use of drugs to minimise resistance differ for different biological contexts. In some cases, similar strategies for vastly different pathogens or biological contexts are recommended, whereas in other cases opposing strategies for similar pathogens are advised. To which extent these discrepancies in treatment recommendations are attributable to specific properties of the pathogen, the host, or the general biological context is currently unclear. The aim of this proposal is to develop an integrative population biological framework for the evolution of resistance and its control. To this end we will develop mathematical models of resistance evolution in viruses, bacteria, parasites, cancer and fungal plant pathogens. Developing detailed population biological models that account for the specific biology of these ¿pathogens¿ as well as the specific context of the application of drugs will allow us to identify those aspects that are common between different biological contexts and those aspects that are specific to the pathogen, the host or the drug. Moreover, working simultaneously on resistance evolution in these different biological contexts will facilitate the translation of findings between fields of research that to date have remained largely separate. We seek to bridge these fields and integrate insight to develop a broad conceptual framework with which to address the ever-growing problem of sustainable drug use.
|
[
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Mathematics"
] |
W1989335596
|
Molecular characterization and functional analysis of duck TRAF6
|
Tumor necrosis factor receptor-associated factor 6 (TRAF6) plays a pivotal role in activating various signaling cascades as an intracellular signal transducer. Although significant progress has been made clarifying TRAF6 function in mammals, the role of TRAF6 in ducks (duTRAF6) remains poorly understood. In the present study, we cloned the full-length duTRAF6 cDNA from duck embryo fibroblasts (DEFs) for the first time. Real-time quantitative reverse transcription-polymerase chain reaction assays showed that duTRAF6 was widely expressed in different tissues. Overexpression of duTRAF6 activated nuclear factor kappa B (NF-κB) and induced interferon-β expression. Furthermore, a deletion mutant analysis revealed that the duTRAF6 region between aa 115 and 375 was essential for activating NF-κB. In addition, duTRAF6 knockdown by RNA interference significantly reduced poly(I:C)- and Sendai virus-induced NF-κB activation in DEFs. Taken together, our results demonstrate that duTRAF6 plays a crucial immunoregulatory role in the duck innate immune response.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy"
] |
10.1073/pnas.1212333110
|
Dependence receptor TrkC is a putative colon cancer tumor suppressor
|
The TrkC neurotrophin receptor belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Such a trait has been hypothesized to confer tumor-suppressor activity. Indeed, cells that express these receptors are thought to be dependent on ligand availability for their survival, a mechanism that inhibits uncontrolled tumor cell proliferation and migration. TrkC is a classic tyrosine kinase receptor and therefore generally considered to be a protooncogene. We show here that TrkC expression is down-regulated in a large fraction of human colorectal cancers, mainly through promoter methylation. Moreover, we show that TrkC silencing by promoter methylation is a selective advantage for colorectal cell lines to limit tumor cell death. Furthermore, reestablished TrkC expression in colorectal cancer cell lines is associated with tumor cell death and inhibition of in vitro characteristics of cell transformation, as well as in vivo tumor growth. Finally, we provide evidence that a mutation of TrkC detected in a sporadic cancer is a loss-ofproapoptotic function mutation. Together, these data support the conclusion that TrkC is a colorectal cancer tumor suppressor.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
] |
10.1016/j.molcel.2018.08.010
|
Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication
|
Chromatin organization is disrupted genome-wide during DNA replication. On newly synthesized DNA, nucleosomes are assembled from new naive histones and old modified histones. It remains unknown whether the landscape of histone post-translational modifications (PTMs) is faithfully copied during DNA replication or the epigenome is perturbed. Here we develop chromatin occupancy after replication (ChOR-seq) to determine histone PTM occupancy immediately after DNA replication and across the cell cycle. We show that H3K4me3, H3K36me3, H3K79me3, and H3K27me3 positional information is reproduced with high accuracy on newly synthesized DNA through histone recycling. Quantitative ChOR-seq reveals that de novo methylation to restore H3K4me3 and H3K27me3 levels occurs across the cell cycle with mark- and locus-specific kinetics. Collectively, this demonstrates that accurate parental histone recycling preserves positional information and allows PTM transmission to daughter cells while modification of new histones gives rise to complex epigenome fluctuations across the cell cycle that could underlie cell-to-cell heterogeneity. Histone modifications are a core component of the epigenome. Reverón-Gómez et al. develop ChOR-seq to profile histone modifications after DNA replication and find that the genomic localization of modified parental histones is preserved on daughter strands while new histone modification to restore pre-replication levels follows mark- and locus-specific kinetics.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
] |
290766
|
Arithmetic of automorphic motives
|
The primary purpose of this project is to build on recent spectacular progress in the Langlands program to study the arithmetic properties of automorphic motives constructed in the cohomology of Shimura varieties. Because automorphic methods are available to study the L-functions of these motives, which include elliptic curves and certain families of Calabi-Yau varieties over totally real fields (possibly after base change), they represent the most accessible class of varieties for which one can hope to verify fundamental conjectures on special values of L-functions, including Deligne's conjecture and the Main Conjecture of Iwasawa theory. Immediate goals include the proof of irreducibility of automorphic Galois representations; the establishment of period relations for automorphic and potentially automorphic realizations of motives in the cohomology of distinct Shimura varieties; the construction of p-adic L-functions for these and related motives, notably adjoint and tensor product L-functions in p-adic families; and the geometrization of the p-adic and mod p Langlands program. All four goals, as well as the others mentioned in the body of the proposal, are interconnected; the final goal provides a bridge to related work in geometric representation theory, algebraic geometry, and mathematical physics.
|
[
"Mathematics"
] |
10.1039/C6CP04345C
|
Dynamic Nuclear Polarisation By Thermal Mixing Quantum Theory And Macroscopic Simulations
|
A theory of dynamic nuclear polarisation (DNP) by thermal mixing is suggested based on purely quantum considerations. A minimal 6-level microscopic model is developed to test the theory and link it to the well-known thermodynamic model. Optimal conditions for the nuclear polarization enhancement and effects of inhomogeneous broadening of the electron resonance are discussed. Macroscopic simulations of nuclear polarization spectra displaying good agreement with experiments, involving BDPA and trityl free radicals, are presented.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
10.1007/JHEP08(2019)034
|
Entanglement On Multiple S 2 Boundaries In Chern Simons Theory
|
Topological entanglement structure amongst disjoint torus boundaries of three manifolds have already been studied within the context of Chern-Simons theory. In this work, we study the topological entanglement due to interaction between the quasiparticles inside three-manifolds with one or more disjoint $S^2$ boundaries in SU($N$) Chern-Simons theory. We focus on the world-lines of quasiparticles (Wilson lines), carrying SU($N$) representations, creating four punctures on every $S^2$. We compute the entanglement entropy by partial tracing some of the boundaries. In fact, the entanglement entropy depends on the SU($N$) representations on these four-punctured $S^2$ boundaries. Further, we observe interesting features on the GHZ-like and W-like entanglement structures. Such a distinction crucially depends on the multiplicity of the irreducible representations in the tensor product of SU($N$) representations.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
10.1103/PhysRevLett.118.117001
|
Proximity-Induced Shiba States in a Molecular Junction
|
Superconductors containing magnetic impurities exhibit intriguing phenomena derived from the competition between Cooper pairing and Kondo screening. At the heart of this competition are the Yu-Shiba-Rusinov (Shiba) states which arise from the pair breaking effects a magnetic impurity has on a superconducting host. Hybrid superconductor-molecular junctions offer unique access to these states but the added complexity in fabricating such devices has kept their exploration to a minimum. Here, we report on the successful integration of a model spin 1/2 impurity, in the form of a neutral and stable all organic radical molecule, in proximity-induced superconducting break junctions. Our measurements reveal excitations which are characteristic of a spin-induced Shiba state due to the radical's unpaired spin strongly coupled to a superconductor. By virtue of a variable molecule-electrode coupling, we access both the singlet and doublet ground states of the hybrid system which give rise to the doublet and singlet Shiba excited states, respectively. Our results show that Shiba states are a robust feature of the interaction between a paramagnetic impurity and a proximity-induced superconductor where the excited state is mediated by correlated electron-hole (Andreev) pairs instead of Cooper pairs.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
] |
interreg_1299
|
Environmental restoration of Selvote peat bog biotope
|
The project aims at the environmental restoration of Karst springs in the Selvote peat bog natural biotope (at Castions di Strada), in order to recreate wetlands where the flora species of greatest naturalistic interest can take root. The management plan of the biotope envisages the maintenance of the habitat naturalistic value and the conservation of biodiversity; the naturalistic restoration of lands that have been abandoned by intensive agriculture, also by experimenting and assessing various types of plans and crops; the removal and the environmental restoration of artificial ditches, drainage, and embankments; interventions on the hydrographical grid in order to restore favourable water conditions for the natural habitat. The main activity on cultivated land is the removal of the surface layer of agricultural soil - tilled and mixed by ploughing - thus favouring the removal of nutrients from cultivated land, bringing to light the deposits with a lower content of nutrients, which are suitable to the oligotrophic species of peat bogs. The removal of the earthy layer tends to bring to the surface the gravelly-sandy deposits, that guarantee a better colonization by autochthonous species. The next stage is the removal of canals and ditches that contribute to the drainage of the water bed to the detriment of the most characteristic and valuable habitats. At the end of the morphological remodelling, the herbaceous cenosis reimplantation will be carried out, after working on the land by bringing in propagation material (seeds, hayseed and chaff, sods) suitable to the specific stational conditions. Scrub-clearance will be performed in the remaining part of the peat bog and on its wooded edges.
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution",
"Products and Processes Engineering"
] |
648688
|
The role of microbial and invertebrate activities in shaping alpine soil respiration: current state and future scenarios
|
The belowground production of CO2 in soil (soil respiration, SR) represents an important terrestrial carbon source. Being correlated with soil temperature, SR is expected to exacerbate climate change. In addition, SR is expected to change considerably and in a patchy manner especially within the Alpine area, reflecting the effects of altitude, land use and climatic conditions. Previous studies measuring SR along altitudinal gradients, however, struggled with strong differences in environmental influences and with distinct unique faunal and microbial communities among samples.
The grand ambition of ACTI-RESP is to provide in-depth knowledge and quantitative information on how microbial and invertebrate communities are influenced by altitude, land use and climate change, and on how microbial activity shapes SR. To quantify the pure effect of altitude and to investigate the effects of climate and land use, I will combine field observations and a manipulative experiment within terraXcube, a facility allowing manipulations of multiple conditions including air pressure to mimic different elevations.
Thereby, I aim to further test the advantages of studying intracellular DNA (iDNA) as opposed to the generally studied environmental DNA (eDNA). Being composed by considerable amounts of extracellular DNA, eDNA does not only contain information about intact and active cells (intracellular DNA, iDNA) but also about extracellular DNA from species that might not be recently present. Here, I will study microbial agents actually shaping SR by extracting iDNA, by performing qPCR and 16S rRNA sequencing and by comparing the results to eDNA as well as RNA-based results.
In doing so, I aim to
- define climate change-related alterations in SR
- jointly examine soil invertebrates and microorganisms
- firstly describe the pure altitude effect on microbial SR, activity and community patterns
- test iDNA quantification as a proxy for microbial activity and SR
|
[
"Environmental Biology, Ecology and Evolution",
"Earth System Science"
] |
268946
|
An Integrated Network of Glucose Sensing Cells in Glucose Homeostasis
|
Glucose sensing cells constantly monitor glucose absorption from food and variations in blood glycemic levels. They control the secretion of GLP-1, insulin and glucagon, and the activity of the autonomic nervous system. These hormonal and nervous signals coordinate glucose utilization by liver, fat and muscle, and endogenous glucose production as well as feeding and energy expenditure. Type 2 diabetes, a disease that afflicts an increasing proportion of the world population, is characterized by insufficient insulin production by pancreatic beta-cells, abnormal secretion of GLP-1 and glucagon, and is often associated with imbalance between feeding and energy expenditure. Type 2 diabetes can thus be considered a disease of glucose sensing. Here, I propose a research program using cell biological, genetic, genomic and physiology techniques to investigate three aspects of this integrated glucose sensing network:
1. The identification of novel molecular pathways activated by GLP-1 and that control adult beta-cell proliferation, glucose competence and apoptosis in order to maintain sufficient insulin secretion capacity.
2. The identification and molecular characterization of brain glucose sensors, which share functional similarities with pancreatic beta-cells, and which control glucose homeostasis and pancreatic islet mass and function.
3. The discovery by unbiased genetic-genomic analysis of loci, genes, and gene networks involved in central hypoglycemia detection and the secretion of glucagon, a process whose deregulation is a major limitation in insulin treatment of both type 1 and type 2 diabetes.
Together these investigations will bring new knowledge on the integrated control of glucose homeostasis that may lead to novel strategies to control diabetes.
|
[
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
W3013177219
|
A Generalized Hausdorff Distance Based Quality Metric for Point Cloud Geometry
|
Reliable quality assessment of decoded point cloud geometry is essential to evaluate the compression performance of emerging point cloud coding solutions and guarantee some target quality of experience. This paper proposes a novel point cloud geometry quality assessment metric based on a generalization of the Hausdorff distance. To achieve this goal, the so-called generalized Hausdorff distance for multiple rankings is exploited to identify the best performing quality metric in terms of correlation with the MOS scores obtained from a subjective test campaign. The experimental results show that the quality metric derived from the classical Hausdorff distance leads to low objective-subjective correlation and, thus, fails to accurately evaluate the quality of decoded point clouds for emerging codecs. However, the quality metric derived from the generalized Hausdorff distance with an appropriately selected ranking, outperforms the MPEG adopted geometry quality metrics when decoded point clouds with different types of coding distortions are considered.
|
[
"Computer Science and Informatics",
"Systems and Communication Engineering"
] |
10.1515/crelle-2014-0075
|
Comparison between two complexes on a singular space
|
AbstractIn this article we generalise the Witten deformation for stratified spaces and a class of Morse functions which we call radial Morse functions. In the first part of the article we perform the Witten deformation on the complex of
|
[
"Mathematics"
] |
642562
|
Unveiling the population of supermassive black hole binaries near merger
|
At the center of nearly every galaxy in the Universe lurks a supermassive black hole with mass millions to billions that of the Sun. When two galaxies collide, their supermassive black holes sink to the center of the newly forming galaxy. There in this nascent galactic nucleus a supermassive black hole binary is formed. Supermassive binaries are the subject of a long standing mystery in astrophysics: will these monstrous black holes merge and what can that tell us about the extreme environments that shape them? I will make great strides towards solving this mystery through advancing the state of the art in simulations of interactions of supermassive black hole binaries and their gaseous environments. From these simulations I will predict binary orbital evolution rates as well as observational signatures of the interaction. I will use the former to build the most accurate binary population models to date and the latter to constrain these models via observational searches in the newest time domain data, possibly leading to the first detections of these elusive black hole pairs.
|
[
"Universe Sciences",
"Computer Science and Informatics"
] |
10.1145/3183713.3183758
|
Incremental View Maintenance With Triple Lock Factorization Benefits
|
We introduce F-IVM, a unified incremental view maintenance (IVM) approach for a variety of tasks, including gradient computation for learning linear regression models over joins, matrix chain multiplication, and factorized evaluation of conjunctive queries. F-IVM is a higher-order IVM algorithm that reduces the maintenance of the given task to the maintenance of a hierarchy of increasingly simpler views. The views are functions mapping keys, which are tuples of input data values, to payloads, which are elements from a task-specific ring. Whereas the computation over the keys is the same for all tasks, the computation over the payloads depends on the task. F-IVM achieves efficiency by factorizing the computation of the keys, payloads, and updates. We implemented F-IVM as an extension of DBToaster. We show in a range of scenarios that it can outperform classical first-order IVM, DBToaster's fully recursive higher-order IVM, and plain recomputation by orders of magnitude while using less memory.
|
[
"Computer Science and Informatics"
] |
724321
|
Surviving salinity: How do plants sense Na+?
|
A major gap in our knowledge of how plants respond to soil salinity is their initial perception of sodium (Na+) ions. Salt is detrimental to plants and soil salinization is an increasing threat to global food security; 6% of the world’s total land area and 20% of irrigated land is affected by salinity. I recently discovered Na+-specific root growth responses of plants and will now exploit these to identify the elusive sodium sensing mechanism of plants. I will use an innovative approach combining genome-wide genetic screens in the model plant Arabidopsis thaliana with dedicated biochemical assays.
I will identify candidate Na+-sensor genes through a natural genetic variation screen for the Na+-specific inhibition bending of the root in response to gravity (WP1). In parallel, I will follow a chemical genomics approach to find novel compounds that impair Na+ sensing, and their target proteins in plants (WP2). Subsequent complementary in silico and biochemical approaches will characterize Na+-affinity of the candidates (WP3). Selected putative Na+ sensors will be characterized in planta, by studying their localization, activity, their interactors, and by salt response phenotyping of mutants (WP4). Finally, mutant varieties of sensors will be introduced in the economically relevant crop plant tomato, to provide proof-of-concept for improving salt tolerance by modulating sensor function and implementation in crop improvement programs (WP5).
The impact of elucidation of plant Na+ sensing will be monumental; it will reveal how plant responses to salinity stress are driven, and ultimately what is required to cope with salinity. In addition, it will open up new applied directions for agriculture, where improved sodium sensing modules will be used to allow crop growth on marginal, saline soils.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
] |
278801
|
Electrochemistry in fluidic nanodevices: From fundamentals to integrated sensor platforms
|
I propose to explore the frontiers of electrochemistry at the nanometer scale by developing new experimental approaches based on lithographically fabricated fluidic nanodevices. This will allow groundbreaking experiments on a broad range of fundamental topics including double layer structure, screening in ionic liquids, nanoscale hydrodynamics and the dielectric response of single macromolecules. It will also lay the foundations for new analytical techniques based on electrochemical single molecule recognition and targeted at integration with state-of-the-art electronics on a single chip. The latter combination could potentially bring about a revolution in (bio)sensing technology on a scale comparable to those which have already taken place in computing and communications. My first focus will be on nanofabricating sub-femtolitre channels and chambers in which single or small numbers of redox-active molecules can be detected and manipulated using electrochemistry at pairs of embedded electrodes. Simultaneously, I will explore the capabilities electrochemical impedance spectroscopy using nanoelectrodes at frequencies up to 200 MHz. Such a combination of ultra-short length scales and high frequencies has heretofore remained inaccessible and will be made possible here by using electrodes that form an intrinsic part of an integrated detection circuit. This research has a truly exploratory character, as few investigators so far have attempted to combine nanofluidics, modern microelectronics and electrochemistry. Doing so will test our microscopic understanding of electrochemical processes, enable new classes of experiments, and push the limits of electrochemistry as an analytical method. There is thus a high likelihood that further new concepts and applications will emerge over the course of this multidisciplinary program.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics",
"Systems and Communication Engineering"
] |
EP 2004011856 W
|
METHOD FOR DRYING LAUNDRY AND LAUNDRY DRYER FOR CARRYING OUT SAID METHOD
|
The invention relates to a method for drying laundry and to a laundry dryer for carrying out said method, comprising a drying chamber and process air conduct wherein a blower is arranged for conveying dry air through the drying chamber and a fresh air supply element and used air discharge element are arranged. Means for separating the dry air flow into a used air part and a circulating air part are provided in the process air conduct. The laundry dryer comprises sensors for detecting process parameters and the means for separating the dry air flow in order to modify the used air/circulating air are controlled according to the detected parameters. A sensor (20) detects the pressure of the process flow in the area (19) where the dry air enters the drying chamber (1) in order to prevent laundry damage from occurring if the dry air flow in the drying drum is interrupted and in order to obtain an optimum drying result. The pressure value and/or pressure evolution is evaluated and according to said evaluation, the means (14,22) for separating the dry air flow are controlled in such a way that the amount of circulating air is reduced or adjusted to zero and the drying process is continued with a reduced volume flow through the drying chamber (1).
|
[
"Products and Processes Engineering",
"Systems and Communication Engineering"
] |
10.1007/978-3-030-45721-1_18
|
Blackbox Secret Sharing Revisited A Coding Theoretic Approach With Application To Expansionless Near Threshold Schemes
|
A blackbox secret sharing (BBSS) scheme works in exactly the same way for all finite Abelian groups G; it can be instantiated for any such group G and only black-box access to its group operations and to random group elements is required. A secret is a single group element and each of the n players’ shares is a vector of such elements. Share-computation and secret-reconstruction is by integer linear combinations. These do not depend on G, and neither do the privacy and reconstruction parameters t, r. This classical, fundamental primitive was introduced by Desmedt and Frankel (CRYPTO 1989) in their context of “threshold cryptography. ” The expansion factor is the total number of group elements in a full sharing divided by n. For threshold BBSS with t-privacy (\(1\le t \le n-1\)), \(t+1\)-reconstruction and arbitrary n, constructions with minimal expansion \(O(\log n)\) exist (CRYPTO 2002, 2005).
|
[
"Computer Science and Informatics",
"Mathematics"
] |
10.1111/1462-2920.13054
|
High-resolution analysis of the m-xylene/toluene biodegradation subtranscriptome of Pseudomonas putida mt-2
|
Pseudomonas putida mt-2 metabolizes m-xylene and other aromatic compounds through the enzymes encoded by the xyl operons of the TOL plasmid pWW0 along with other chromosomally encoded activities. Tiling arrays of densely overlapping oligonucleotides were designed to cover every gene involved in this process, allowing dissection of operon structures and exposing the interplay of plasmid and chromosomal functions. All xyl sequences were transcribed in response to aromatic substrates and the 3′-termini of both upper and lower mRNA operons extended beyond their coding regions, i. e. the 3′-end of the lower operon mRNA penetrated into the convergent xylS regulatory gene. Furthermore, xylR mRNA for the master m-xylene responsive regulator of the system was decreased by aromatic substrates, while the cognate upper operon mRNA was evenly stable throughout its full length. RNA sequencing confirmed these data at a single nucleotide level and refined the formerly misannotated xylL sequence. The chromosomal ortho route for degradation of benzoate (the ben, cat clusters and some pca genes) was activated by this aromatic, but not by the TOL substrates, toluene or m-xylene. We advocate this scenario as a testbed of natural retroactivity between a pre-existing metabolic network and a new biochemical pathway implanted through gene transfer.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Biotechnology and Biosystems Engineering"
] |
10.1039/C7CC04977C
|
An Atypical Interaction Explains The High Affinity Of A Non Hydrolyzable S Linked 1 6 Α Mannanase Inhibitor
|
The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener.
|
[
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
W906676302
|
Binary versus weighted interaction networks
|
Abstract Interaction networks (IN) have been used in ecology to model different kinds of interactions in ecological communities. Historically there are two basic ways to construct an IN: binary networks (BN) that represent unweighted links among species in the web, and weighted networks (WN) that weight each interaction among species by its relative or absolute frequency in the web. We call binary reduction the transition from WN to BN which obviously entails loss of information. We performed an analysis with 69 WN on which we worked the binary reduction. For both WN and BN we computed: the coefficient of variation, skewness, kurtosis, Shannon entropy and the Gini coefficient on the population statistics. We also computed the dependence asymmetry, the pairwise Jaccard distance and two different measures of nestedness, (W)NODF and τ-temperature, for the WN and BN. From correlations between the values for WN and BN we concluded that, for most of the indices, the loss of information due to the binary reduction is not significant. Using a statistical evaluation, for most indices, BN give similar results to their corresponding WN.
|
[
"Earth System Science",
"Mathematics"
] |
10.1016/j.celrep.2019.08.102
|
Shank Proteins Couple the Endocytic Zone to the Postsynaptic Density to Control Trafficking and Signaling of Metabotropic Glutamate Receptor 5
|
mGluR5 activity is critical for neuronal functioning, but it is unclear how membrane trafficking of mGluR5 is controlled at excitatory synapses. Scheefhals et al. show that Shank proteins anchor the endocytic machinery to the postsynaptic density to govern the efficient trafficking and signaling of mGluR5 at synapses to modulate neuronal functioning.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1177/0957926514536963
|
Small stories transposition and social media: A micro-perspective on the ‘Greek crisis’
|
In this article, I employ small stories research as a micro-perspective for the scrutiny of any crisis-related positionings of ‘Greece’ and ‘the Greeks’ that accompany the circulation of news stories from Greece in social media. My claim is that such positionings cannot be fully understood without reference to what stories get circulated, where, by whom, for/with whom and how. To substantiate this, I draw on a particular incident involving the assault of two female MPs by a male MP on a Greek TV breakfast show (June 2012). My analysis will show that the ways in which the Greek crisis is invoked or disregarded and erased in the social media transpositions of the incident are intimately linked with two key-narrative processes, which I call narrative stancetaking and resemiotizations (i. e. video-based or text-based) that involve a rescripting of the initial incident. In both cases, I will show how processes of story making are important for what is signalled as relevant and for how the context of the Greek crisis is made sense of, critiqued and ultimately backgrounded or erased in favour of more personalized and localized interpretations, grounded in the original and the transposed tales and tellings.
|
[
"The Social World and Its Interactions",
"Texts and Concepts",
"Studies of Cultures and Arts"
] |
EP 2011061296 W
|
X-RAY EMITTING ANODE AND PROCESS FOR MANUFACTURING SUCH AN ANODE
|
An X-ray emitting anode comprises a substrate and, over a portion of the surface of the substrate, a coating (4) comprising a plurality of superposed or stacked groups (7) of sublayers (8, 9) and an intermediate sublayer (6) between the substrate and the coating, each group comprising at least a first sublayer (8) and a second sublayer (9) that are superposed or stacked, at least one surface sublayer (9n) being capable of producing X-rays under the effect of an incident electron beam. Process for manufacturing this anode in which, for each group, the structure is heated before the sublayers (8, 9) are deposited and cooled after they have been deposited.
|
[
"Materials Engineering",
"Products and Processes Engineering",
"Synthetic Chemistry and Materials"
] |
10.3233/AIC-150691
|
The Cade 25 Automated Theorem Proving System Competition Casc 25
|
The CADE ATP System Competition (CASC) is an annual evaluation of fully automatic, classical logic Automated Theorem Proving (ATP) systems. CASC-25 was the twentieth competition in the CASC series. Twenty-seven ATP systems and system variants competed in the various competition divisions. An outline of the competition design, and a commentated summary of the results, are presented.
|
[
"Computer Science and Informatics",
"Mathematics"
] |
10.1075/sll.15.1.02cra
|
On the weight of phrase-final prosodic words in a sign language
|
This article seeks to explore a prosodic explanation for the frequent occurrence of pointing signs phrase-finally. Corpus data from Sign Language of the Netherlands (NGT) show that indeed pointing signs occur highly frequently at the end of sentences, and an elicitation study shows that pointing signs, other light lexical elements, and phonetic phenomena like final holds occur in alternation in NGT. The addition of a final mora to the end of a phrase is argued not to be sufficient to account for these alternations. A complementary analysis in terms of prosodic and metrical phonology is sketched, whereby the final foot or prosodic word is required to be minimally trimoraic.
|
[
"The Human Mind and Its Complexity"
] |
W2053688925
|
Far scrape-off layer particle and heat fluxes in high density – High power scenarios
|
Abstract The far scrape-off layer transport is studied in ASDEX Upgrade H-mode discharges with high divertor neutral density N 0 , div , high power across the separatrix P sep and nitrogen seeding to control the divertor temperature. Such conditions are expected for ITER but usually not investigated in terms of turbulent SOL transport. At high N 0 , div and P sep the H-mode discharges enter a regime of high cross-field particle and power transport in the SOL which is accompanied by a significant change of the turbulence characteristic analogous to the transition from conductive to convective transport in L-mode. Parallel particle and power flux densities of several 10 23 m−2 s−1 and 10 MW m−2 have been detected about ∼40 to 45 mm outside the separatrix mapped to the outer mid-plane. The particle flux fall-off length reached up to 45 mm. This paper presents for the first time an empirical condition to enter the high transport regime in H-mode and the relation of this regime to changes in the filamentary transport.
|
[
"Fundamental Constituents of Matter",
"Products and Processes Engineering"
] |
10.1007/s12132-012-9146-0
|
Discourses of Infrastructure and Citizenship in Post-Apartheid Soweto
|
In this article, I locate Soweto at the epicentre of the changing relationship between state infrastructural capacity on the one hand, and imaginations of citizenship on the other. Far from the 'hidden' or merely technical functioning of urban governance, infrastructure has always been central to the urban politics and everyday life of townships in South Africa. The infrastructural capacity of the apartheid state entrenched the segregated apartheid urban system, and was simultaneously the target of political protest in the 1980s. Infrastructure plays a significant role in political expectations in post-apartheid South Africa. Through policies such as the Reconstruction and Development Program and Developmental Local Government, the post-apartheid state has attempted to re-frame citizenship of South Africans, especially in townships, through the provision of housing and basic services. The emergence, therefore, of service delivery protests in townships and informal settlements in the early 2000s marked the possible limits of a post-apartheid citizenship. Based on field research conducted in Soweto in the mid 2000s, and a number of follow-up interviews in 2010 and 2011, I trace the shifting relationship between infrastructure and citizenship as it emerges in the everyday life of contemporary Soweto. I show how electricity disconnections by the municipality and state electricity utility Eskom in the early 2000s-and the subsequent protests they sparked-provided the context for challenging the limits of post-apartheid citizenship. Residents of Soweto were able to link the 'hidden' infrastructure of electricity cables and wires to a particular narrative of place. Returning to Soweto in 2010, in the midst of protest action against water prepaid metres in Phiri neighbourhood, issues of access to basic services, housing evictions and unemployment still characterise the everyday life of Soweto. As with protests against electricity disconnections, protests against water prepaid metres have linked urban infrastructure to articulations of citizenship that reside in particular narratives of place. But so too do newer forms of 'consumer citizenship', particularly in the form of a new shopping mall that was opened in 2008, and which stands in stark contrast to the politics of basic services.
|
[
"The Social World and Its Interactions",
"Institutions, Governance and Legal Systems",
"Human Mobility, Environment, and Space"
] |
2724150
|
Deciphering the cellular origin and evolution of malignant rhabdoid tumors
|
Introduction How tumors adapt to changing environmental conditions and treatment is a major unsolved problem frustrating effective therapy. Rhabdoid tumors are highly aggressive pediatric tumors with a low survival rate. They occur in multiple tissues, including brain and kidney, and likely originate as a consequence of aberrant differentiation during development. Understanding the origin of rhabdoid tumors and the relationship with normal development is crucial for investigating new treatment options. The almost certain appearance of therapy resistance, low mutation burden, and recent epigenetic profiling suggest the existence of epigenetic heterogeneity within rhabdoid tumors. We hypothesize that epigenetic heterogeneity within rhabdoid tumors underlies their aggressive behavior. Goal I previously exploited organoid models and CRISPR technology to study colorectal cancer progression. My lab now developed a protocol to, for the first time, efficiently grow rhabdoid tumor organoids from patient tissue. We are in the unique position to identify the cellular origin of rhabdoid tumors and the key molecular mechanisms driving disease progression and therapy resistance. Approach We will I) apply single-cell epigenomic and transcriptomic analyses on tumor tissue for in-depth characterization of the cellular identity and heterogeneity within rhabdoid tumors II) combine our unique rhabdoid tumor organoids with genetic lineage tracing technology to reveal clonal dynamics in rhabdoid tumor progression and therapy resistance III) perform retrospective lineage tracing using somatic mutations to track down the cell-of-origin of rhabdoid tumors. Innovation Our integrative use of state-of-the-art technologies on unique patient-derived tissue and tumor organoids will provide comprehensive insights into the origin, heterogeneity and progression of rhabdoid tumors. This will also establish novel approaches for other cancer research as well as new concepts for improving therapy.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
IL 2005001044 W
|
COMMUNICATING WITH BUSINESS CUSTOMERS
|
A method including providing a business with a unified communications number for all types of customer communication and mapping the unified communications number to each address for the business issued by the communication service providers of the business. The method may also include routing communications addressed to the unified communications number to the appropriate the address as a function of the type of communication.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
10.1109/ICCW.2015.7247608
|
Caching At The Edge A Green Perspective For 5G Networks
|
Endowed with context-awareness and proactive capabilities, caching users' content locally at the edge of the network is able to cope with increasing data traffic demand in 5G wireless networks. In this work, we focus on the energy consumption aspects of cache-enabled wireless cellular networks, specifically in terms of area power consumption (APC) and energy efficiency (EE). We assume that both base stations (BSs) and mobile users are distributed according to homogeneous Poisson point processes (PPPs) and we introduce a detailed power model that takes into account caching. We study the conditions under which the area power consumption is minimized with respect to BS transmit power, while ensuring a certain quality of service (QoS) in terms of coverage probability. Furthermore, we provide the optimal BS transmit power that maximizes the area spectral efficiency per unit total power spent. The main takeaway of this paper is that caching seems to be an energy efficient solution.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
10.1016/j.geb.2014.10.006
|
Beliefs and actions in the trust game: Creating instrumental variables to estimate the causal effect
|
In many economic contexts, an elusive variable of interest is the agent's belief about relevant events, e. g. about other agents' behavior. A growing number of surveys and experiments asks participants to state beliefs explicitly but little is known about the causal relation between beliefs and actions. This paper discusses the possibility of creating exogenous instrumental variables for belief statements, by informing the agent about exogenous manipulations of the relevant events. We conduct trust game experiments where the amount sent back by the second player (trustee) is exogenously varied. The procedure allows detecting causal links from beliefs to actions under plausible assumptions. The IV-estimated effect is significant, confirming the causal role of beliefs.
|
[
"Individuals, Markets and Organisations"
] |
10.1016/j.insmatheco.2010.10.002
|
Multivariate density estimation using dimension reducing information and tail flattening transformations
|
We propose a nonparametric multiplicative bias corrected transformation estimator designed for heavy tailed data. The multiplicative correction is based on prior knowledge and has a dimension reducing effect at the same time as the original dimension of the estimation problem is retained. Adding a tail flattening transformation improves the estimation significantly-particularly in the tail-and provides significant graphical advantages by allowing the density estimation to be visualized in a simple way. The combined method is demonstrated on a fire insurance data set and in a data-driven simulation study.
|
[
"Mathematics",
"Computer Science and Informatics"
] |
10.1088/1475-7516/2014/07/017
|
Optimal Bispectrum Constraints On Single Field Models Of Inflation
|
We use WMAP 9-year bispectrum data to constrain the free parameters of an 'effective field theory' describing fluctuations in single-field inflation. The Lagrangian of the theory contains a finite number of operators associated with unknown mass scales. Each operator produces a fixed bispectrum shape, which we decompose into partial waves in order to construct a likelihood function. Based on this likelihood we are able to constrain four linearly independent combinations of the mass scales. As an example of our framework we specialize our results to the case of 'Dirac-Born-Infeld' and 'ghost' inflation and obtain the posterior probability for each model, which in Bayesian schemes is a useful tool for model comparison. Our results suggest that DBI-like models with two or more free parameters are disfavoured by the data by comparison with single parameter models in the same class.
|
[
"Universe Sciences",
"Fundamental Constituents of Matter"
] |
10.7554/eLife.05279
|
Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo
|
Cell migration and polarization is controlled by signals in the environment. Migrating cells typically form filopodia that extend from the cell surface, but the precise function of these structures in cell polarization and guided migration is poorly understood. Using the in vivo model of zebrafish primordial germ cells for studying chemokine-directed single cell migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions play an important role in cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and Rac1 activity at the cell front. The establishment of this polarity is at the basis of effective cell migration towards the target. Together, we show that filopodia allow the interpretation of the chemotactic gradient in vivo by directing single-cell polarization in response to the guidance cue.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
715361
|
Quantitative analysis of variability and robustness in spatial pattern formation
|
During embryonic development a single cell turns into a complex organism. This process is characterized by an antagonism between variation and stability. On the one hand, development is a tightly controlled process; tissues need to be specified at the right time, at the correct spatial position, and with a defined size. On the other hand, regulation should not be too rigid, since embryos need to adjust to environmental perturbations and correct errors caused by noisy gene expression. We will study variation and stability during pattern formation in the zebrafish heart. We seek to understand the origin of embryo-to-embryo variability as well as robustness against perturbation.
The zebrafish heart is a powerful model system for studying variability, since heart positioning is inverted along the left/right axis in 5-10% of wildtype embryos. We aim to identify the mechanism underlying variability in heart positioning and understand its function. To this end, we will combine two innovative approaches: Tomo-seq, a novel method for spatially-resolved transcriptomics developed by the applicant; and single-molecule FISH, a technique that allows absolute quantification of gene expression in single cells.
To expand our study of embryo-to-embryo variability beyond gene expression analysis, we will optimize a method for massively parallel single-cell lineage tracing based on CRISPR-Cas. This novel approach will allow us to study embryo-to-embryo variability in developmental lineage specification on the single cell level. We will use this strategy to systematically explore the corrective capacity of the zebrafish heart upon perturbation of progenitor cell pools, and to determine which mechanisms for error correction are activated in the embryo.
These quantitative experiments will provide unprecedented insight into variability and robustness during development. The concepts developed here will also be relevant for improving our understanding of variable outcomes in human disease.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
W4226320720
|
Seismic Site Response Assessment Using Predominant Periods and Shear Wave Velocity Estimation in Nador (N-E of Morocco)
|
Local seismic hazard is influenced by the variation of soil parameters which modulates the propagation of seismic waves through soil. Nador is one of the cities in Morocco which is located in a seismically hazardous region. Investigations using ambient noise and SPT-N values were conducted in order to characterize site effects in the urban area of Nador. The predominant period values obtained vary between 0.2 and 0.5 s; whereas shear wave velocity in superficial soft sediment varies from 156 to 212 m/s. The geotechnical conditions are also used to identify the areas of high impedance contrast. It is found that soil with high predominant period undergoes significant amplification. This is observed in the center and near to the shore of Nador city which is underlaying deep soils with clay and sandy clay deposits. The provided results can be useful for seismic risk studies in the region.
|
[
"Earth System Science",
"Products and Processes Engineering"
] |
W1966863366
|
Synergistic Effects of Combination Treatment with Bortezomib and Doxorubicin in Human Neuroblastoma Cell Lines
|
Neuroblastoma (NB) is the most common extracranial solid tumor in infants. Currently, the mainstay of NB chemotherapy is combination treatment with some traditional drugs, but these combination regimens are always inefficient.The aim of this study was to evaluate the inhibitory effect of a combination of doxorubicin and bortezomib, a novel anticancer drug and the first prote-asome inhibitor approved for the treatment of human malignant tumors, on the proliferation of two human NB cell lines, SK-N-SH and SH-SY5Y. The general mechanism underlying this combined effect was also investigated. Synergistic inhibitory effects on human NB cell proliferation were evaluated using the median-effect principle. The pro-apoptotic effects of these drugs were evaluated using double staining with annexin-V-FITC and propidium iodide.Synergistic inhibitory effects on proliferation were observed when a combination of bortezomib and doxorubicin was applied to cultured NB cells. A similar synergistic effect on apoptosis was also observed when the two drugs were used concurrently, which suggested that the possible mechanism underlying the observed synergistic inhibitory effect might be related to apoptosis.The combination of bortezomib and doxorubicin appears to be a promising strategy to treat NB.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
10.3389/fphys.2018.00242
|
Moderate modulation of cardiac PGC-1α expression partially affects age-associated transcriptional remodeling of the heart
|
Aging is associated with a decline in cardiac function due to a decreased myocardial reserve. This adverse cardiac remodeling comprises of a variety of changes, including a reduction in mitochondrial function and a decline in the expression of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a central regulator of mitochondrial biogenesis and metabolic adaptation in the myocardium. To study the etiological involvement of PGC-1α in cardiac aging, we used mouse models mimicking the modest down- and upregulation of this coactivator in the old and the exercised heart, respectively. Young mice with reduced cardiac expression of PGC-1α recapitulated part of the age-related impairment in mitochondrial gene expression, but otherwise did not aggravate the aging process. Inversely however, moderate overexpression of PGC-1α counteracts numerous key age-related remodeling changes, e. g. , by improving blood pressure, age-associated apoptosis, and collagen accumulation, as well as in the expression of many, but not all cardiac genes involved in mitochondrial biogenesis, dynamics, metabolism, calcium handling and contractility. Thus, while the reduction of PGC-1α in the heart is insufficient to cause an aging phenotype, moderate overexpression reduces pathological remodeling of older hearts and could thereby contribute to the beneficial effects of exercise on cardiac function in aging.
|
[
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1038/s41467-020-14947-0
|
One-dimensional flat bands in twisted bilayer germanium selenide
|
AbstractExperimental advances in the fabrication and characterization of few-layer materials stacked at a relative twist of small angle have recently shown the emergence of flat energy bands. As a consequence electron interactions become relevant, providing inroads into the physics of strongly correlated two-dimensional systems. Here, we demonstrate by combining large scale ab initio simulations with numerically exact strong correlation approaches that an effective one-dimensional system emerges upon stacking two twisted sheets of GeSe, in marked contrast to all moiré systems studied so far. This not only allows to study the necessarily collective nature of excitations in one dimension, but can also serve as a promising platform to scrutinize the crossover from two to one dimension in a controlled setup by varying the twist angle, which provides an intriguing benchmark with respect to theory. We thus establish twisted bilayer GeSe as an intriguing inroad into the strongly correlated physics of lowdimensional systems.
|
[
"Condensed Matter Physics",
"Synthetic Chemistry and Materials"
] |
175051
|
All-In-One cell screening chip: device for affordable high-throughput cell screenings
|
Experiments with live cells are fundamentally important in biology, pharmaceutical industry, biotechnology or in medicine and diagnostics. One important example of cell experiments is the prescreening of cells from cancer biopsies with anticancer drugs in order to identify the most effective and least toxic combination of drugs for a particular patient also known as personalized medicine.
The goal of this ERC Proof-of-Concept project is to develop, fabricate and optimize a device (CellScreenChip) for performing miniaturized, parallel and, therefore, more affordable and faster cell screening experiments for the areas of diagnostics and personalized medicine. Applications of the CellScreenChip include (but not limited to) cell based disease diagnosis (e.g. cancer diagnostics), drug screening (e.g. body on a chip) or personalized medicine (e.g. personalized drug compatibility tests). The CellScreenChip will be based on our recent development of the superhydrophobic-superhydrophilic micropatterning methods and the ability to create high-density arrays of droplet microreservoirs on superhydrophobic-superhydrophilic patterns that can be used for parallelized and miniaturized cell experiments.
|
[
"Products and Processes Engineering",
"Cell Biology, Development, Stem Cells and Regeneration",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1890/11-0889.1
|
Robustness Of Variance And Autocorrelation As Indicators Of Critical Slowing Down
|
Ecosystems close to a critical threshold lose resilience, in the sense that perturbations can more easily push them into an alternative state. Recently, it has been proposed that such loss of resilience may be detected from elevated autocorrelation and variance in the fluctuations of the state of an ecosystem due to critical slowing down; the underlying generic phenomenon that occurs at critical thresholds. Here we explore the robustness of autocorrelation and variance as indicators of imminent critical transitions. We show both analytically and in simulations that variance may sometimes decrease close to a transition. This can happen when environmental factors fluctuate stochastically and the ecosystem becomes less sensitive to these factors near the threshold, or when critical slowing down reduces the ecosystem's capacity to follow high-frequency fluctuations in the environment. In addition, when available data is limited, variance can be systematically underestimated due to the prevalence of low frequencies close to a transition. By contrast, autocorrelation always increases toward critical transitions in our analyses. To exemplify this point, we provide cases of rising autocorrelation and increasing or decreasing variance in time series prior to past climate transitions.
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution",
"Mathematics"
] |
W2012237769
|
Mucus extravasation and retention phenomena: a 24-year study
|
Abstract Background Mucoceles are benign lesions related to the minor salivary glands and their respective ducts frequently affecting oral structures which are generally asymptomatic. Mucoceles are generally characterized by swollen nodular lesions preferentially located on the lower lip and differ from the so-called ranulas, which are lesions located on the floor of the mouth and related to the sublingual or submandibular glands. Methods The objective of the present study was to analyze data such as age, gender, race and site of the lesion of 173 mucocele cases diagnosed at the Discipline of Stomatology, São José dos Campos Dental School, UNESP, over a period of 24 years (April 1980 to February 2003). Results Of the 173 cases analyzed, 104 (60.12%) were females and 69 (39.88%) were males. Age ranged from 4 to 70 years (mean ± SD: 17 ± 9.53) and most patients were in the second decade of life (n = 86, 49.42%); white (n = 124, 71.68%). The lower lip was the site most frequently affected by the lesions (n = 135, 78.03%), whereas the lowest prevalence was observed for the soft palate, buccal mucosa, and lingual frenum. Conclusion In this study, mucoceles predominated in white female subjects in the second decade of life, with the lower lip being the most frequently affected site.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1016/j.epsl.2017.03.030
|
Subarctic physicochemical weathering of serpentinized peridotite
|
Frost weathering is effective in arctic and subarctic climate zones where chemical reactions are limited by the reduced availability of liquid water and the prevailing low temperature. However, small scale mineral dissolution reactions are nevertheless important for the generation of porosity by allowing infiltration of surface water with subsequent fracturing due to growth of ice and carbonate minerals. Here we combine textural and mineralogical observations in natural samples of partly serpentinized ultramafic rocks with a discrete element model describing the fracture mechanics of a solid when subject to pressure from the growth of ice and carbonate minerals in surface-near fractures. The mechanical model is coupled with a reaction–diffusion model that describes an initial stage of brucite dissolution as observed during weathering of serpentinized harzburgites and dunites from the Feragen Ultramafic Body (FUB), SE-Norway. Olivine and serpentine are effectively inert at relevant conditions and time scales, whereas brucite dissolution produces well-defined cm to dm thick weathering rinds with elevated porosity that allows influx of water. Brucite dissolution also increases the water saturation state with respect to hydrous Mg carbonate minerals, which are commonly found as infill in fractures in the fresh rock. This suggests that fracture propagation is at least partly driven by carbonate precipitation. Dissolution of secondary carbonate minerals during favorable climatic conditions provides open space available for ice crystallization that drives fracturing during winter. Our model reproduces the observed cm-scale meandering fractures that propagate into the fresh part of the rock, as well as dm-scale fractures that initiate the breakup of larger domains. Rock disintegration increases the reactive surface area and hence the rate of chemical weathering, enhances transport of dissolved and particulate matter in the weathering fluid, and facilitates CO2 uptake by carbonate precipitation. Our observations have implications for element cycling and CO2 sequestration in natural gravel and mine tailings.
|
[
"Earth System Science",
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
] |
10.1038/s41467-018-03692-0
|
Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms
|
Incomplete delivery to the target cells is an obstacle for successful gene therapy approaches. Here we show unexpected effects of incomplete targeting, by demonstrating how heterogeneous inhibition of a growth promoting signaling pathway promotes tissue hyperplasia. We studied the function of the lymphangiogenic VEGFR3 receptor during embryonic and post-natal development. Inducible genetic deletion of Vegfr3 in lymphatic endothelial cells (LECs) leads to selection of non-targeted VEGFR3+ cells at vessel tips, indicating an indispensable cell-autonomous function in migrating tip cells. Although Vegfr3 deletion results in lymphatic hypoplasia in mouse embryos, incomplete deletion during post-natal development instead causes excessive lymphangiogenesis. Analysis of mosaically targeted endothelium shows that VEGFR3- LECs non-cell-autonomously drive abnormal vessel anastomosis and hyperplasia by inducing proliferation of non-targeted VEGFR3+ LECs through cell-contact-dependent reduction of Notch signaling. Heterogeneity in VEGFR3 levels thus drives vessel hyperplasia, which has implications for the understanding of mechanisms of developmental and pathological tissue growth.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1007/s10670-013-9591-8
|
A Constitutive Account of ‘Rationality Requires’
|
The requirements of rationality are fundamental in practical and theoretical philosophy. Nonetheless, there exists no correct account of what constitutes rational requirements. This paper attempts to provide a correct constitutive account of ‘rationality requires’. I argue that rational requirements are grounded in ‘necessary explanations of subjective incoherence’, as I shall put it. Rationality requires of you to X if and only if your rational capacities, in conjunction with the fact that you not-X, explain necessarily why you have a non-maximal degree of subjective coherence.
|
[
"Texts and Concepts"
] |
819543
|
Metabolic integration by nutrient SENSing
|
Nutrient sensing enables metabolic homeostasis by matching energy use with fuel availability. The vast body of knowledge on pro-anabolic nutrient sensors, such as insulin and class 1 phosphoinositol-3 kinase (PI3K) signalling exposed the missing links in molecular coordination of catabolism. The cellular catabolism relies on mitochondrial activities and on lysosomal pathway of autophagy, both paced by the biological clock. However, how pro-catabolic nutrient sensors synchronize these catabolic activities is not well understood. We discovered that class 3 PI3K, the only PI3K present in all eukaryotes, is essential for catabolic homeostasis in vivo, but the mechanisms of its metabolic functions are still lacking. We found novel roles for class 3 PI3K in metabolic adaptation to fasting and mitochondrial activity, beyond its established functions in autophagy and endosomal trafficking. These findings form the basis of our innovative interdisciplinary research program that will investigate the molecular bases of Metabolic integration in vivo by a nutrient SENSing pathway of class 3 PI3K (MetaboSENS). In the MetaboSENS research program, we seek to identify transcription factor networks and regulatory complexes of class 3 PI3K that serve its catabolic integrator function. We aim to reveal the physiological oscillation of class 3 PI3K signalling and its reciprocal impact on metabolic timekeeping. Finally, the MetaboSENS project will combine patient analyses and the medical expertise of my team to reveal, for the first time, genetic alterations in class 3 PI3K signalling in inborn metabolic disease. The new mechanisms that we discover may provide therapeutic targets that we will test in the pre-clinical models. Altogether, the MetaboSENS project will redefine our view of systemic catabolism.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing"
] |
CA 2397908 A
|
PILOT OPERATED RELIEF VALVE
|
A pilot operated safety relief valve (14) in which a pilot valve (32) controls the opening and closing of the main valve member (26). The pilot valve (32) has a spindle valve member (70) between an intermediate dome fluid chamber (52) and an exhaust chamber (54) communicating with exhaust port (52) and exhaust line (38). Spindle valve member (70) has an annular sealing mem-ber of membrane (104) having a relatively thin body (105) with op-posed beads (106, 108) along inner and outer peripheries of body (105) for sealing between spindle valve member (70) and the ad-jacent retainer sleeve (94). Any positive backpressure forces from exhaust line (38) are balanced against spindle valve member (70) by annular seal (80) and membrane (104). Membrane (104) is effective for sealing between spindle valve membre (70) and retainer sleeve (94) without generation of frictional forces therebetween thereby to permit precise actuation of main valve member (70) within the tol-erance of the relieving pressure specified for pilot valve (32).
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
10.1016/j.orggeochem.2014.07.012
|
Evaluation of long chain 1,14-alkyl diols in marine sediments as indicators for upwelling and temperature
|
Long chain alkyl diols form a group of lipids occurring widely in marine environments. Recent studies have suggested several palaeoclimatological applications for proxies based on their distributions, but have also revealed uncertainty about their applicability. Here we evaluate the use of long chain 1,14-alkyl diol indices for reconstruction of temperature and upwelling conditions by comparing index values, obtained from a comprehensive set of marine surface sediments, with environmental factors such as sea surface temperature (SST), salinity and nutrient concentration. Previous studies of cultures indicated a strong effect of temperature on the degree of saturation and the chain length distribution of long chain 1,14-alkyl diols in Proboscia spp. , quantified as the diol saturation index (DSI) and diol chain length index (DCI), respectively. However, values of these indices for surface sediments showed no relationship with annual mean SST of the overlying water. It remains unknown as to what determines the DSI, although our data suggest that it may be affected by diagenesis, while the relationship between temperature and DCI may be different for different Proboscia species. In addition, contributions from algae other than Proboscia diatoms may affect both indices, although our data provide no direct evidence for additional long chain 1,14-alkyl diol sources. Two other indices using the abundance of 1,14-diols vs. 1,13-diols and C30 1,15-diols have been applied previously as indicators for upwelling intensity at different locations. The geographical distribution of their values supports the use of 1,14 diols vs. 1,13 diols [C28+C30 1,14-diols]/[(C28+C30 1,13-diols)+(C28+C30 1,14-diols)] as a general indicator for high nutrient or upwelling conditions.
|
[
"Physical and Analytical Chemical Sciences",
"Earth System Science"
] |
W2329855082
|
Imaging first order multiples in VSP data: a detailed field study
|
Summary A detailed field study focused on constructively using the water surface multiples recorded in marine seismic VSP data for improved subsurface depth imaging is presented. Traditionally, up-going and down-going wavefields are separated during VSP signal processing and only the up-going wavefield is used to image the subsurface below the receivers. However with using the down-going wavefield, structures above the receivers are also imaged and wider horizontal coverage is achieved. Our field study consists of two perpendicular 2D walk away surveys: SW-NE and NW-SE. Images constructed using first order water surface multiples are presented and compared with each other as well as with the 3D surface seismic cube. VSP images have higher resolution than the 3D surface seismic image. Both VSP surveys image the shallower part of the subsurface very well. However, in the deeper parts of the sections, qualities of the VSP images are substantially different from each other. The SWNE line images the deeper section of the subsurface rather well whereas the NW-SE line fails to image the deeper section of the subsurface. 3D ray tracing modeling shows that there are considerable amounts of unfocused and out-plane energies reflected from the deeper reflectors in NW-SE survey. This can explain why line NW-SE fails to image the deeper reflectors.
|
[
"Earth System Science",
"Systems and Communication Engineering"
] |
10.1093/nar/gkv1259
|
CRISPR interference and priming varies with individual spacer sequences
|
CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) systems allow bacteria to adapt to infection by acquiring 'spacer' sequences from invader DNA into genomic CRISPR loci. Cas proteins use RNAs derived from these loci to target cognate sequences for destruction through CRISPR interference. Mutations in the protospacer adjacent motif (PAM) and seed regions block interference but promote rapid 'primed' adaptation. Here, we use multiple spacer sequences to reexamine the PAM and seed sequence requirements for interference and priming in the Escherichia coli Type I-E CRISPR-Cas system. Surprisingly, CRISPR interference is far more tolerant of mutations in the seed and the PAM than previously reported, and this mutational tolerance, as well as priming activity, is highly dependent on spacer sequence. We identify a large number of functional PAMs that can promote interference, priming or both activities, depending on the associated spacer sequence. Functional PAMs are preferentially acquired during unprimed 'naïve' adaptation, leading to a rapid priming response following infection. Our results provide numerous insights into the importance of both spacer and target sequences for interference and priming, and reveal that priming is a major pathway for adaptation during initial infection.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Immunity, Infection and Immunotherapy"
] |
10.1007/JHEP11(2012)071
|
Stable Non Uniform Black Strings Below The Critical Dimension
|
The higher-dimensional vacuum Einstein equation admits translationally non-uniform black string solutions. It has been argued that infinitesimally non-uniform black strings should be unstable in 13 or fewer dimensions and otherwise stable. We construct numerically non-uniform black string solutions in 11, 12, 13, 14 and 15 dimensions. Their stability is investigated using local Penrose inequalities. Weakly non-uniform solutions behave as expected. However, in 12 and 13 dimensions, strongly non-uniform solutions appear to be stable and can have greater horizon area than a uniform string of the same mass. In 14 and 15 dimensions all non-uniform black strings appear to be stable.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
834203
|
From the accretion disk to the cluster halo: the multi-scale physics of black hole feedback
|
It is firmly established that supermassive black holes (SMBHs) have a profound influence on the evolution of galaxies and galaxy groups/clusters. Yet, almost 20 years after this realization, fundamental questions remain. What determines the efficiency with which an active galactic nucleus (AGN) couples to its surroundings? Why does AGN feedback appear to be ineffective in low-mass galaxies? In maintenance-mode feedback, how does the AGN regulate to closely balance cooling? How does the nature of AGN feedback change as we consider higher redshifts and push back to the epoch of the first galaxies? AGN feedback is a truly multi-scale phenomenon. Observations show that AGN have an energetic impact on galactic-, group-, and cluster-halo scales. Yet the efficiency with which an accreting SMBH releases energy, and the partitioning of that energy into radiation, winds, and relativistic jets, is dictated by complex processes in the accretion disk on AU scales, 10^10 times smaller than the halo. Furthermore, especially in massive systems where feedback proceeds via the heating of a hot circumgalactic or intracluster medium (CGM/ICM), the relevant microphysics of the hot baryons is unclear, requiring an understanding of plasma instabilities on 10^-9pc scales. We propose a set of projects that explore the multiscale physics of AGN feedback. Magnetohydrodynamic models of accretion disks will be constructed to study the AGN radiation/winds/jets and calibrate observable proxies of SMBH mass and accretion rate. We will use the machinery of plasma physics to characterize the CGM/ICM microphysics relevant to the thermalization of AGN-injected energy. Finally, we will produce new galaxy-, group- and cluster-scale models incorporating the new microphysical prescriptions and AGN models. Our new theoretical understanding of AGN feedback as a function of halo mass, environment, and cosmic time is essential for interpreting the torrent of data from current and future observatories
|
[
"Universe Sciences",
"Fundamental Constituents of Matter"
] |
10.1111/1365-2745.12480
|
Traits Of Neighbouring Plants And Space Limitation Determine Intraspecific Trait Variability In Semi Arid Shrublands
|
Understanding how intraspecific trait variability (ITV) responds to both abiotic and biotic constraints is crucial to predict how individuals are assembled in plant communities, and how they will be impacted by ongoing global environmental change. Three key functional traits [plant height, leaf area (LA) and specific leaf area (SLA)] were assessed to quantify the range of ITV of four dominant plant species along a rainfall gradient in semi-arid Mediterranean shrublands. Variance partitioning and confirmatory multilevel path analyses were used to assess the direct and indirect effects of rainfall, space limitation (crowding) and neighbouring plant traits on ITV. The direct effect of the local neighbourhood on the trait values of subordinate individuals was as strong as the effect of rainfall. The indirect effect of rainfall, however, mediated by the effect of the local neighbourhood on the trait values of subordinate individuals, was weak. Rainfall decreased the height and SLA of subordinate individuals, but increased their LA. Neighbouring plant traits were just as strong predictors as crowding in explaining changes in ITV. Synthesis. Our study provides a framework to disentangle the direct effects of abiotic factors and their indirect effects on ITV mediated by the local neighbourhood. Our results highlight that abiotic and biotic constraints are both substantial sources of trait variations at the individual level, and can blur processes underlying changes in ITV. Considering and disentangling combined sources with an individual perspective would help to refine our predictions for community assembly and functional ecology.
|
[
"Environmental Biology, Ecology and Evolution",
"Earth System Science"
] |
W2197795379
|
HTLV-1 et don de lait maternel
|
In France, the screening for human T-cell leukemia/ lymphoma virus type 1 and 2 (HTLV-1 and HTLV-2) during the donation of human milk has been carried out from 1992 with the application of the circular DGS 24 November 1992. The screening for antibodies against these viruses is regulated and done systematically during every donation of milk. Breast feeding being the main mode of transmission of the HTLV-1, the last ministerial decree of 25 August 2010 has made the screening test compulsory for the anonymous donation and for the personalized donation (of a mother for her own child) from all women including those affected by the infection. The milk delivered by milk banks is pasteurized (62.5 °C for 30 minutes) before freezing at -18 °C, which inactivates the pathogens. This double means of prevention of the transmission of the HTLV-1 paradoxically seems disproportionate in the absence of any precautionary measure in the case of direct breast-feeding and the use of mother's raw milk. Indeed, in most neonatal intensive care units in maternity hospitals, unpasteurized milk is administered to the neonates without any systematic preliminary testing of the serological HTLV-1 status of the mother. An increased sensitization of the community of the obstetricians, midwives and neonatologists by the Association of the Milk Banks of France (ADLF) and the Société de pathologie exotique could address the issue of screening for HTLV-1 in "donated" milk and breast-feeding.
|
[
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1126/science.1205669
|
A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins
|
The isolation of broadly neutralizing antibodies against influenza A viruses has been a long-sought goal for therapeutic approaches and vaccine design. Using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (HA) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses. Passive transfer of this antibody conferred protection to mice and ferrets. Complexes with HAs from the group 1 H1 and the group 2 H3 subtypes analyzed by x-ray crystallography showed that the antibody bound to a conserved epitope in the F subdomain. This antibody may be used for passive protection and to inform vaccine design because of its broad specificity and neutralization potency.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy"
] |
W4292658440
|
Diálogos críticos y perspectivas actuales de investigación y pensamiento sobre comunicación en Latinoamérica en el 50 aniversario de Chasqui
|
A partir de la década de los años sesenta del siglo pasado se ha ido dando en Latinoamérica un conjunto de iniciativas investigativas orientado a constituir una escuela crítica de estudios de la comunicación. En un sentido amplio se pueden identificar estas experiencias como antecedentes relevantes de la rica discusión en materia de un nuevo orden mundial de la información y comunicación que se diera desde la mitad de los setenta hasta la mitad de los ochenta. Los aportes significativos de Luis Ramiro Beltrán, sus lúcidos análisis tendientes a desnudar la dominación mediática de agencias de información y medios norteamericanos, presente en la mayoría del panorama mediático latinoamericano, fueron un aliciente para las reflexiones dentro de UNESCO, que la condujo a convencerse de la necesidad histórica de modificar las condiciones desiguales que definían a la comunicación mundial. Fueron sin duda alguna, años en los que Latinoamérica cobraba un lugar importantísimo en el campo de los estudios de la comunicación, con una perspectiva no solo original desde el punto de vista académico o investigativo sino de alcance político, que contribuía a mostrar la necesidad de desentrañar la compleja articulación entre comunicación y poder.
|
[
"Texts and Concepts",
"The Social World and Its Interactions"
] |
W1578617549
|
Utilising Tree-Based Ensemble Learning for Speaker Segmentation
|
AbstractIn audio and speech processing, accurate detection of the changing points between multiple speakers in speech segments is an important stage for several applications such as speaker identification and tracking. Bayesian Information Criteria (BIC)-based approaches are the most traditionally used ones as they proved to be very effective for such task. The main criticism levelled against BIC-based approaches is the use of a penalty parameter in the BIC function. The use of this parameters consequently means that a fine tuning is required for each variation of the acoustic conditions. When tuned for a certain condition, the model becomes biased to the data used for training limiting the model’s generalisation ability.In this paper, we propose a BIC-based tuning-free approach for speaker segmentation through the use of ensemble-based learning. A forest of segmentation trees is constructed in which each tree is trained using a sampled version of the speech segment. During the tree construction process, a set of randomly selected points in the input sequence is examined as potential segmentation points. The point that yields the highest ΔBIC is chosen and the same process is repeated for the resultant left and right segments. The tree is constructed where each node corresponds to the highest ΔBIC with the associated point index. After building the forest and using all trees, the accumulated ΔBIC for each point is calculated and the positions of the local maximums are considered as speaker changing points. The proposed approach is tested on artificially created conversations from the TIMIT database. The approach proposed show very accurate results comparable to those achieved by the-state-of-the-art methods with a 9% (absolute) higher F 1 compared with the standard ΔBIC with optimally tuned penalty parameter.KeywordsRandom ForestBayesian Information CriterionGaussian Mixture ModelPenalty FactorBroadcast NewsThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
W2008556567
|
Evaluating the global energy balance of Titan
|
To understand the weather and climate on Earth as well as on other planets and their moons, scientists need to know the global energy balance, the balance between energy coming in from solar radiation and thermal energy radiated back out of the planet. The energy balance can provide interesting information about a planet. For instance, Jupiter, Saturn, and Neptune emit more energy than they absorb, implying that these planets have an internal heat source. Earth, on the other hand, is in near equilibrium, with energy coming in approximately equaling energy going out, though a small energy imbalance can lead to global climate change.
|
[
"Universe Sciences",
"Earth System Science"
] |
10.1007/s12232-017-0281-8
|
‘Better off, as judged by themselves’: a reply to Cass Sunstein
|
This paper is a reply to Sunstein’s comment on my paper ‘Do people really want to be nudged towards healthy lifestyles?’ The central claim of that paper was that, in their book Nudge, Thaler and Sunstein switch between two different interpretations of the ‘better off, as judged by themselves’ criterion, and that consistent use of one or other interpretation would have blunted the persuasive power of the book. In this reply, I defend that claim against Sunstein’s counter-arguments.
|
[
"Texts and Concepts",
"The Human Mind and Its Complexity",
"Individuals, Markets and Organisations"
] |
10.1007/s11098-017-0860-2
|
Threefoldness
|
Theories of picture perception aim to understand our perceptual relation to both the picture surface and the depicted object. I argue that we should talk about not two, but three entities when understanding picture perception: (A) the picture surface, (B) the three dimensional object the picture surface visually encodes and (C) the three dimensional depicted object. As (B) and (C) can come apart, we get a more complex picture of picture perception than normally assumed and one where the notion of twofoldness, which has played an important albeit controversial role in understanding picture perception is replaced by the concept of threefoldness.
|
[
"Texts and Concepts",
"The Human Mind and Its Complexity"
] |
10.1145/2897824.2925918
|
Wasserstein Barycentric Coordinates Histogram Regression Using Optimal Transport
|
This article defines a new way to perform intuitive and geometrically faithful regressions on histogram-valued data. It leverages the theory of optimal transport, and in particular the definition of Wasserstein barycenters, to introduce for the first time the notion of barycentric coordinates for histograms. These coordinates take into account the underlying geometry of the ground space on which the histograms are defined, and are thus particularly meaningful for applications in graphics to shapes, color or material modification. Beside this abstract construction, we propose a fast numerical optimization scheme to solve this backward problem (finding the barycentric coordinates of a given histogram) with a low computational overhead with respect to the forward problem (computing the barycenter). This scheme relies on a backward algorithmic differentiation of the Sinkhorn algorithm which is used to optimize the entropic regularization of Wasserstein barycenters. We showcase an illustrative set of applications of these Wasserstein coordinates to various problems in computer graphics: shape approximation, BRDF acquisition and color editing.
|
[
"Mathematics",
"Computer Science and Informatics"
] |
W95277928
|
Role of Cytokines in Treatment-Resistant Depression
|
The exact pathophysiology of major depressive disorder (MDD) has yet to be fully elucidated. The belief that depression is strictly a disorder of monoaminergic consequences is undergoing great reconsideration due to the lack of efficacy of the current pharmacotherapeutics. There is compelling clinical literature implicating a role for cytokines in the pathophysiology of MDD. IL-6 and IL-1β are pleiotropic inflammatory cytokines that have been reported to be elevated in patients with MDD. The present studies were undertaken to investigate the relationship between IL-6 and IL-1β in animal models of depressive-like behavior. In rats subjected to learned helplessness or a submissive behavior paradigm, analysis of brain tissue homogenates revealed elevated levels of IL-6 protein in the absence of elevations in IL-1β. Central administration of recombinant mouse IL-6 produced depressive-like phenotypes in mice in the absence of IL-1β induced increases in brain tissue or IL-1β related sickness behavior typical of a general CNS inflammatory response. These data therefore suggest that IL-6 and IL-1β have distinct roles in mediating depressive-like and sickness behaviors, respectively. Administration of the SSRI fluoxetine in the presence of centrally administered IL-6 failed to produce the expected antidepressant-like response in mice. Further, administration of fluoxetine to mice with endogenous overexpression of brain IL-6 (MRL/MpJ-Faslpr/lpr (LPR mice)) failed to produce the expected antidepressant-like effect relative to fluoxetine-treated WT control mice (MRL/MpJ+/+). Interestingly, blockade of IL-6 trans-signaling by co-administration of a gp130/Fc monomer or an anti-mouse IL-6 antibody with IL-6 prevented the IL-6-induced depressive-like behavior as well as attenuated IL-6-induced increases in brain protein levels. Taken together these data indicate that depressive-like behavior may be related to elevated levels of IL-6 in the brain and suggest that modulation of the IL-6 signaling pathway by way of preventing de novo IL-6 production may have therapeutic potential for treatment-resistant depression.
|
[
"Neuroscience and Disorders of the Nervous System",
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
W2758325318
|
Bionomics of the rice meal moth, Corcyra cephalonica (Stainton) reared under laboratory condition on different diets
|
The rice meal moth, Corcyra cephalonica Stainton is one of the serious insect pests of stored milled rice and other milled cereal products in India. But another economic importance of this insect is that the eggs of these insects are used as diet to mass multiply the bio-agent like Trichogramma spp. We studied the biology and bionomics of this pest under controlled laboratory conditions. An experiment was conducted during July 2015 to October 2015 in the Biological Control laboratory, Department of Entomology, IGKV, Raipur at 27 0C + 20 0C (and 75+5% RH to study the different diet performance on the biology and bionomics of rice moth, C. cephalonica. Five cereals viz., rice, wheat, pearlmillet (jowar), sorghum (bajra) and maize were tested solely along with their combinations. The female moth had longer body length and weight as compared to male moth. Both male and female reared on mixed diet with a combination of (rice+jowar+maize) had maximum body weight and body length. There was a high positive co-relation between fecundity and female body weight. The mixed diet of rice +jowar +maize was highly superior, in comparison to others for mass production of C. cephalonica. The shortest life cycle was found in the combinations of bajra + jowar + maize up to 35 and 40 days respectively and longest life cycle was found in rice extending of 60 to 70 days.
|
[
"Environmental Biology, Ecology and Evolution",
"Biotechnology and Biosystems Engineering"
] |
10.1007/s10797-012-9251-y
|
Official forecasts and management of oil windfalls
|
Official forecasts for oil revenues and the burden of pensioners are used to estimate forward-looking fiscal policy rules for Norway and compared with permanent-income and bird-in-hand rules. The results suggest that fiscal reactions have been partial forward-looking with respect to the rising pension bill, but backward-looking with respect to oil and gas revenues. Solvency of the government finances might be an issue with the fiscal rules estimated from historical data. Simulation suggests that declining oil and gas revenue and the costs of a rapidly graying population will substantially deteriorate the net government asset position by 2060 unless fiscal policy becomes more prudent or current pension and fiscal reforms are successful.
|
[
"Individuals, Markets and Organisations"
] |
W1991149258
|
ON ELASTIC STRESS WAVES IN AN IMPACTED PLATE
|
Elastic stress wave theory is developed and the stress waves in the impacted plate are examined in the paper. Generalized linear elasticity is adopted where the couple stress and curvature tensor are both deviatoric tensors and they meet a linear constitutive relation. It is found that there exist volumetric, rotational, and deviatoric waves in the generalized elastic solids. However, for macro-scale elastic solids only two wave modes, namely a volumetric wave and a deviatoric wave should be taken into account. Wave motion in plate impact tests is studied that a volumetric wave and a deviatoric wave are proposed. A set of exact solutions is attained for elastic stress waves in an impact plate. Excitation of stress waves at impact surface and reflection at free surface are formulated. Propagation of stress waves in the plate is analyzed in the waveforms. The predicted stress history in a ceramic plate under impact is agreed very well with the experiment measurement.
|
[
"Condensed Matter Physics",
"Materials Engineering"
] |
TW 105139810 A
|
Dispersion assis5tant for suspension polymerization, method for producing vinyl polymer in which said assistant is used, and vinyl chloride resin
|
The purpose of the present invention is to provide a dispersion assistant with which it is possible to stably obtain an excellent polymeric substance (vinyl resin) with minimal adhering of scale to a polymerization vessel even when the dispersion assistant is used in a large amount in the suspension polymerization of a vinyl compound. The additive for suspension polymerization contains a polyvinyl alcohol polymer (A) that has a gelling degree of 60 mol% or less and has acetal groups (a) having olefinically unsaturated double bonds.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
10.18632/aging.100563
|
Deficiency in the metabolite receptor SUCNR1 (GPR91) leads to outer retinal lesions
|
Age-related macular degeneration (AMD) is a prominent cause of blindness in the Western world. To date, its molecular pathogenesis as well as the sequence of events leading to retinal degeneration remain largely ill-defined. Whilethe invasion of choroidal neovasculature in the retina is the primary mechanism that precipitates loss of sight, an earlierdry form may accompany it. Here we provide the first evidence for the protective role of the Retinal Pigment Epithelium(RPE)-resident metabolite receptor, succinate receptor 1 (SUCNR1; G-Protein coupled Receptor-91 (GPR91), in preventingdry AMD-like lesions of the outer retina. Genetic analysis of 925 patients with geographic atrophy and 1199 AMD-freepeers revealed an increased risk of developing geographic atrophy associated with intronic variants in the SUCNR1 gene. Inmice, outer retinal expression of SUCNR1 is observed in the RPE as well as microglial cells and decreases progressively withage. Accordingly, Sucnr1-/- mice show signs of premature sub-retinal dystrophy with accumulation of oxidized-LDL,abnormal thickening of Bruch's membrane and a buildup of subretinal microglia. The accumulation of microglia in Sucnr1-deficient mice is likely triggered by the inefficient clearance of oxidized lipids by the RPE as bone marrow transfer of wild-type microglia into Sucnr1-/- mice did not salvage the patho phenotype and systemic lipolysis was equivalent betweenwild type and control mice. Our findings suggest that deficiency in SUCNR1 is a possible contributing factor to the pathogenesis of dry AMD and thus broaden our understanding of this clinically unmet need.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Integrative Biology: from Genes and Genomes to Systems"
] |
US 70442776 A
|
Composite pile and tapered concrete tip therefor
|
A composite pile includes a tubular pile and a tapered, reinforced concrete tip having a central passage opening through its larger upper end and a seat exposed in its bottom. The passage is of a cross sectional area greater than that of the pile and freely receives the boot end thereof. With the boot end of the pile in engagement with the seat the pile is secured thereto in a centered position once the space between the pile and the wall of the passage is filled with a suitable packing.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
804334
|
Moduli spaces of stable varieties and applications
|
Stable varieties, originally introduced by Kollár and Shepherd-Barron, are higher dimensional generalizations of the algebro-geometric notion of stable curves from many perspectives. Their partially conjectural moduli space classifies smooth projective varieties of general type up to birational equivalence, and it also provides a projective compactification for this classifying space. The latter is essential for applying algebraic geometry to the moduli space itself. Furthermore, over the complex numbers, stable varieties can be also defined surprisingly as the projective varieties admitting a negative curvature (singular) Kähler-Einstein metric by the work of Berman and Guenancia, or as the canonically polarized K-stable varieties by Odaka.
The fundamental objective of the project is to construct the coarse moduli space of stable surfaces with fixed volume over the integers (possibly excluding finitely many primes, not depending on the volume). In particular this involves showing the Minimal Model Program for 3-folds that are projective over a 1 dimensional mixed characteristic base. The main motivations are applications to the general algebraic geometry and arithmetic of higher dimensional varieties.
The above fundamental goal is also an incarnation of Grothendieck's philosophy that algebraic geometry statements should be proved in a relative setting. This was implemented right at the beginning for stable curves, but it has not been possible to attain for stable varieties of higher dimensions, due to the lack of technology. Hence, the project aims to establish new technology in mixed and positive characteristic geometry based on recent developments, such as modern Minimal Model Program, the vanishings given by balanced big Cohen-Macaulay algebras (the existence of which was shown by André using Scholze's perfectoid theory), trace method for lifting sections, p-torsion cohomology killing via alterations (by Bhatt), torsor method on singular varieties, etc.
|
[
"Mathematics"
] |
10.1007/JHEP07(2017)017
|
Higgs Differential Cross Section At Nnlo In Dimensional Regularisation
|
We present an analytic computation of the Higgs production cross section in the gluon fusion channel, which is differential in the components of the Higgs momentum and inclusive in the associated partonic radiation through NNLO in perturbative QCD. Our computation includes the necessary higher order terms in the dimensional regulator beyond the finite part that are required for renormalisation and collinear factorisation at N$^3$LO. We outline in detail the computational methods which we employ. We present numerical predictions for realistic final state observables, specifically distributions for the decay products of the Higgs boson in the $\gamma\gamma$ decay channel.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
W2800878814
|
A review on the applications of image logs in structural analysis and sedimentary characterization
|
Abstract Image logs provide important information on lithology, sedimentary textures, paleoflow directions, fractures and in situ stress analysis. Lacking of criteria used for establishing the image log facies limits the applications of image logs in sedimentary reservoir interpretation. This paper provides a thoroughgoing review focusing on the recent applications of borehole image logs for sedimentological and structural description and interpretation, and aims to establish image log facies which can provide guidelines in sedimentary reservoir interpretation. This paper firstly summarizes the principles and basic characteristics of various imaging logging tools, and then briefly introduces the pre-processing workflow of the image log data. Then the generated images are used for depth and orientation shifts of cores by calibrating individual sedimentary and structural features. Descriptive and concise image log facies are established based on combinations of image textures including dip type, dip pattern, and color scheme, and the characteristics as well as physical criteria for each individual image facies are summarized. The established image log facies are then interpreted in terms of structural and sedimentological features such as lithology, sedimentary structures, vugs, fractures and faults. The image log facies and its stacking patterns are then used to interpret the lithofacies associations by calibrating with cores and conventional logs. Natural fractures and induced fractures are recognized by image logs, and the principles of breakouts and drilling-induced fractures for in-situ stress analysis are reviewed. Then the applications of image logs in investigation of fracture attitudes and states, as well as in computation of fracture parameters are summarized. The procedures to evaluate fracture effectiveness through image logs are discussed. At last, the application of image logs for structural dip analysis is reviewed, and image logs are used for recognizing faults, fracture sets, and attitudes of stratum through the dip patterns. The basic procedures for paleocurrent reconstruction, which includes dip picking of cross beddings, structural dip determination and structural dip removal, are reviewed. Then the paleocurrent directions of the Lower Cretaceous Bashijiqike Formation in the Kuqa depression were reconstructed, which could help further understanding of the depositional systems. This review will help extend the utility of image logs in interpreting small to large -scale sedimentary and structural features, and bridges the gaps between well log analysis and sedimentary and structural interpretation.
|
[
"Earth System Science",
"Products and Processes Engineering"
] |
10.1128/mBio.01802-14
|
Septins arrange F-Actin-Containing fibers on the chlamydia trachomatis inclusion and are required for normal release of the inclusion by extrusion
|
Chlamydia trachomatis is an obligate intracellular human pathogen that grows inside a membranous, cytosolic vacuole termed an inclusion. Septins are a group of 13 GTP-binding proteins that assemble into oligomeric complexes and that can form higher-order filaments. We report here that the septins SEPT2, -9, -11, and probably -7 form fibrillar structures around the chlamydial inclusion. Colocalization studies suggest that these septins combine with F actin into fibers that encase the inclusion. Targeting the expression of individual septins by RNA interference (RNAi) prevented the formation of septin fibers as well as the recruitment of actin to the inclusion. At the end of the developmental cycle of C. trachomatis, newly formed, infectious elementary bodies are released, and this release occurs at least in part through the organized extrusion of intact inclusions. RNAi against SEPT9 or against the combination of SEPT2/7/9 substantially reduced the number of extrusions from a culture of infected HeLa cells. The data suggest that a higher-order structure of four septins is involved in the recruitment or stabilization of the actin coat around the chlamydial inclusion and that this actin recruitment by septins is instrumental for the coordinated egress of C. trachomatis from human cells. The organization of F actin around parasite-containing vacuoles may be a broader response mechanism of mammalian cells to the infection by intracellular, vacuole-dwelling pathogens.
|
[
"Immunity, Infection and Immunotherapy",
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
Q123355
|
Improving the quality of the dental practice’s offer through the implementation of innovative comprehensive services and processes in the latest standards of dentistry.
|
The implementation of the project is the implementation of innovative services through the purchase of dental equipment with innovative technological solutions. The selection of devices is a thought-out concept, the result of which is the comprehensiveness of services, both at the stage of diagnosis and treatment. This comprehensiveness will be based on advanced, innovative technology, which will ensure that the patient on-site in the office will have a complete package of services, ranging from the simplest care treatments to those that require highly specialised diagnostic equipment. The aim of the project is to enable comprehensive diagnosis and treatment, thanks to the use of innovative diagnostic devices and devices that will enable the treatment process to be performed in optimal patient comfort. It will be achieved through the purchase of 4 fixed assets: smart laser, dental microscope, bone surgery equipment and innovative digital X-ray system.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
10.1038/ncomms2996
|
Two distinct secretion systems facilitate tissue invasion by the rice blast fungus Magnaporthe oryzae
|
To cause plant diseases, pathogenic micro-organisms secrete effector proteins into host tissue to suppress immunity and support pathogen growth. Bacterial pathogens have evolved several distinct secretion systems to target effector proteins, but whether fungi, which cause the major diseases of most crop species, also require different secretory mechanisms is not known. Here we report that the rice blast fungus Magnaporthe oryzae possesses two distinct secretion systems to target effectors during plant infection. Cytoplasmic effectors, which are delivered into host cells, preferentially accumulate in the biotrophic interfacial complex, a novel plant membrane-rich structure associated with invasive hyphae. We show that the biotrophic interfacial complex is associated with a novel form of secretion involving exocyst components and the Sso1 t-SNARE. By contrast, effectors that are secreted from invasive hyphae into the extracellular compartment follow the conventional secretory pathway. We conclude that the blast fungus has evolved distinct secretion systems to facilitate tissue invasion.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy"
] |
10.1002/bies.201100102
|
Wnt-Notch signalling: An integrated mechanism regulating transitions between cell states
|
The activity of Wnt and Notch signalling is central to many cell fate decisions during development and to the maintenance and differentiation of stem cell populations in homeostasis. While classical views refer to these pathways as independent signal transduction devices that co-operate in different systems, recent work has revealed intricate connections between their components. These observations suggest that rather than operating as two separate pathways, elements of Wnt and Notch signalling configure an integrated molecular device whose main function is to regulate transitions between cell states in development and homeostasis. Here, we propose a general framework for the structure and function of the interactions between these signalling systems that is focused on the notion of 'transition states', i. e. intermediates that arise during cell fate decision processes. These intermediates act as checkpoints in cell fate decision processes and are characterised by the mixed molecular identities of the states involved in these processes.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
336716
|
High-speed chip-based nanoscopy to discover real-time sub-cellular dynamics
|
Optical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in present nanoscopy. In this project, I propose a paradigm-shift in the field of advanced microscopy by developing optical nanoscopy based on a photonic integrated circuit. The project will take advantage of nanotechnology to fabricate an advance waveguide-chip, while fast telecom optical devices will provide switching of light to the chip, enhancing the speed of imaging. This unconventional route will change the field of optical microscopy, as a simple chip-based system can be added to a normal microscope. In this project, I will build a waveguide-based structured-illumination microscope (W-SIM) to acquire fast images (25 Hz or better) from a living cell with an optical resolution of 50-100 nm. I will use W-SIM to discover the dynamics (opening and closing) of fenestrations (100 nm) present in the membrane of a living liver sinusoidal scavenger endothelial cell. It is believed among the Hepatology community that these fenestrations open and close dynamically, however there is no scientific evidence to support this hypothesis because of the lack of suitable tools. The successful imaging of fenestration kinetics in a live cell during this project will provide new fundamental knowledge and benefit human health with improved diagnoses and drug discovery for liver. Chip-based nanoscopy is a new research field, inherently making this a high-risk project, but the possible gains are also high. The W-SIM will be the first of its kind, which may open a new era of simple, integrated nanoscopy. The proposed multiple-disciplinary project requires a near-unique expertise in the field of laser physics, integrated optics, advanced microscopy and cell-biology that I have acquired at leading research centers on three continents.
|
[
"Condensed Matter Physics",
"Cell Biology, Development, Stem Cells and Regeneration",
"Systems and Communication Engineering"
] |
W1846138270
|
Effect of the maize–soybean intercropping system on the potential bioavailability of magnesium, iron and zinc
|
This study concerned the effect of different intercropping systems (alternating rows and alternating strips) of maize and soybean compared with single cropping, in combination with different fertilisers (biofertiliser, organic fertiliser, and urea) on the potential availability of magnesium (Mg), iron (Fe) and zinc (Zn) from grain, through their ratio with phytate (as inhibitor) and β-carotene (as promoter). The higher grain yield and land equivalent ratio obtained under alternating rows + biofertiliser treatment demonstrated the improved ability of crops in close proximity for better utilisation of existing agro-ecological conditions. Alternating rows + organic fertiliser decreased the molar ratios phytate : β-carotene, phytate : Fe, phytate : Mg and phytate : Zn, indicating increased availability of the mineral elements in both crops. However, alternating strips + organic fertiliser contributed mostly to an increase in β-carotene, Mg, Fe and Zn concentrations in soybean. Increased grain yield of both crops was followed by decrease in β-carotene and increase in phytate, particularly in maize. In soybean, β-carotene could be considered as the main contributor to Fe availability. Accordingly, cropping in alternating rows or strips, combined with biofertilisers, could serve as fortification measures for improved nutritional quality of maize and soybean grain, without grain yield losses.
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution",
"Biotechnology and Biosystems Engineering"
] |
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