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10.1053/j.gastro.2019.09.026
Mouse Models of Human Gastric Cancer Subtypes With Stomach-Specific CreERT2-Mediated Pathway Alterations
Background & Aims: Patterns of genetic alterations characterize different molecular subtypes of human gastric cancer. We aimed to establish mouse models of these subtypes. Methods: We searched databases to identify genes with unique expression in the stomach epithelium, resulting in the identification of Anxa10. We generated mice with tamoxifen-inducible Cre recombinase (CreERT2) in the Anxa10 gene locus. We created 3 mouse models with alterations in pathways that characterize the chromosomal instability (CIN) and the genomically stable (GS) subtypes of human gastric cancer: Anxa10-CreERT2;KrasG12D/+;Tp53R172H/+;Smad4fl/f (CIN mice), Anxa10-CreERT2;Cdh1fl/fl;KrasG12D/+;Smad4fl/fl (GS-TGBF mice), and Anxa10-CreERT2;Cdh1fl/fl;KrasG12D/+;Apcfl/fl (GS-Wnt mice). We analyzed tumors that developed in these mice by histology for cell types and metastatic potential. We derived organoids from the tumors and tested their response to chemotherapeutic agents and the epithelial growth factor receptor signaling pathway inhibitor trametinib. Results: The gastric tumors from the CIN mice had an invasive phenotype and formed liver and lung metastases. The tumor cells had a glandular morphology, similar to human intestinal-type gastric cancer. The gastric tumors from the GS–TGFB mice were poorly differentiated with diffuse morphology and signet ring cells, resembling human diffuse-type gastric cancer. Cells from these tumors were invasive, and mice developed peritoneal carcinomatosis and lung metastases. GS-Wnt mice developed adenomatous tooth-like gastric cancer. Organoids derived from tumors of GS-TGBF and GS-Wnt mice were more resistant to docetaxel, whereas organoids from the CIN tumors were more resistant to trametinib. Conclusions: Using a stomach-specific CreERT2 system, we created mice that develop tumors with morphologic similarities to subtypes of human gastric cancer. These tumors have different patterns of local growth, metastasis, and response to therapeutic agents. They can be used to study different subtypes of human gastric cancer.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1109/ISCAS.2014.6865574
Ultra Low Leakage Synaptic Scaling Circuits For Implementing Homeostatic Plasticity In Neuromorphic Architectures
Homeostatic plasticity is a property of biological neural circuits that stabilizes their neuronal firing rates in face of input changes or environmental variations. Synaptic scaling is a particular homeostatic mechanism that acts at the level of the single neuron over long time scales, by changing the gain of all its afferent synapses to maintain the neuron's mean firing within proper operating bounds. In this paper we present ultra low leakage analog circuits that allow the integration of compact integrated filters in multi-neuron chips, able to achieve time constants of the order of hundreds of seconds, and describe automatic gain control circuits that when interfaced to neuromorphic neuron and synapse circuits implement faithful models of biologically realistic synaptic scaling mechanisms. We present simulation results of the low leakage circuits and describe the control circuits that have been designed for a neuromorphic multi-neuron chip, fabricated using a standard 180nm CMOS process.
[ "Neuroscience and Disorders of the Nervous System", "Computer Science and Informatics" ]
10.1209/0295-5075/99/26003
The Plastic Response Of Magnetoelastic Amorphous Solids
We address the cross-effects between mechanical strains and magnetic fields on the plastic response of magnetoelastic amorphous solids. It is well known that plasticity in non-magnetic amorphous solids under external strain ? is dominated by the codimension-1 saddle-node bifurcation in which an eigenvalue of the Hessian matrix vanishes at ?P like . This square-root singularity determines much of the statistical physics of elasto-plasticity, and in particular that of the stress-strain curves under athermal-quasistatic conditions. In this letter we discuss the much richer physics that can be expected in magnetic amorphous solids. Firstly, magnetic amorphous solids exhibit codimension-2 plastic instabilities, when an external strain and an external magnetic field are applied simultaneously. Secondly, the phase diagrams promise a rich array of new effects that have been barely studied; this opens up a novel and extremely rich research program for magnetoplastic materials.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
10.1051/0004-6361/201935518
Ic 4665 Dance I Members Empirical Isochrones Magnitude Distributions Present Day System Mass Function And Spatial Distribution
Context. The study of star formation is extremely challenging, due to the lack of complete and clean samples of young nearby clusters and star-forming regions. The recent Gaia DR2 catalogue complemented with the deep ground-based COSMIC DANCe catalogue offers a new database of unprecedented accuracy to revisit the membership of clusters and star-forming regions. The 30 Myr open cluster IC 4665 is one of the few well-known clusters of this age and it is an excellent target where evolutionary models can be tested and planetary formation studied. Aims. We provide a comprehensive membership analysis of IC 4665 and study the following properties: empirical isochrones, distance, magnitude distribution, present-day system mass function, and spatial distribution. Methods. We used the Gaia DR2 catalogue together with the DANCe catalogue to look for members via a probabilistic model of the distribution of the observable quantities in both the cluster and background populations. Results. We obtained a final list of 819 candidate members that cover a 12. 4 magnitude range (7 <  J <  19. 4). We find that 50% are new candidates, and we estimate a conservative contamination rate of 20%. This unique sample of members allows us to obtain a present-day system mass function in the range of 0. 02–6 M⊙, which reveals a number of details not seen in previous studies. In addition, we find that a spherically symmetric spatial distribution is favoured by our final list of members for this young open cluster. Conclusions. Our membership analysis represents a significant increase in the quantity and quality (low contamination) with respect to previous studies. It offers an excellent opportunity to revisit other fundamental parameters such as age.
[ "Universe Sciences" ]
W936616234
LOCATING THE SOURCE OF PACIOLI'S BOOKKEEPING TREATISE
ABSTRACT There is much we do not know about the early development of double entry bookkeeping. What, for example, caused it to be used by sufficient merchants for it to be formally taught to their sons in Northern Italy before anyone had apparently written anything about it? And, what did Pacioli use as the source for his 1494 treatise, the earliest known detailed written description of the method, something that has challenged researchers for at least the past 130 years? Discovering Pacioli's sources could broaden our knowledge of the Renaissance roots of accounting and of its early role and place in business practice; may provide some insights into the reasons for the emergence of double entry bookkeeping; and may give us further insight into the early instruction of double entry bookkeeping. But, previous attempts to find his sources have failed. Making use of hitherto overlooked information, this paper identifies two periods for which knowledge of Pacioli's whereabouts would indicate where to focus any search for his sources and suggests where to initiate the search.
[ "The Study of the Human Past", "Texts and Concepts" ]
10.1016/j.cmet.2016.11.003
Transcription Factor EB Controls Metabolic Flexibility during Exercise
The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism.
[ "Physiology in Health, Disease and Ageing", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1063/1.4983371
Broadband Terahertz Pulse Generation By Optical Rectification In Gap Crystals
We demonstrate a broadband (0. 3–7 THz) terahertz pulse generation using GaP generation and detection crystals with an 80-MHz-repetition-rate Ti:Sapphire laser. We also use simulations of cascaded terahertz generation to model the observed terahertz gain profiles. The efficient generation of the broadband terahertz pulses is based on optimizing the phase matching between the optical and terahertz pulses, which is achieved by tuning the wavelength of the laser. We observed further improvement in the generation efficiency due to a mismatching of the imaginary part of the complex wavevectors. Together, these effects allow the use of thicker crystals and thus lead to increased terahertz emission. Our results show that optical rectification by GaP can be used to generate broadband terahertz pulses with MHz-repetition-rate lasers up to a dynamic range that is comparable to commonly used sources like ZnTe and photo-conductive antennas.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
980871
Commercialisation of novel ultra-fast 3d laser scanning technology
Understanding how the brain processes information is one of the unsolved grand challenges in science. Moreover, neurological disorders, which disrupt information processing, have an enormous societal and economic impact. Studying information processing in the brain requires measurements of signals as they flow through neural circuits. However, the 3D nature of brain circuits and the speed of information transfer makes it difficult for neuroscientists to measure their properties with sufficiently high spatial and temporal resolution. During the NEUROGAIN ERC project, we developed a novel type of Acousto-Optic Lens (AOL)-based high-speed 3D laser scanner. This technology enables the focusing and scanning of a laser beam at 20-40 kHz. This scanning technology can be added to existing two-photon microscopes to enable 3D imaging of neurons and circuits with unprecedented spatio-temporal resolution. Moreover, it also automatically corrects for brain movement in real-time providing sharper images. This ERC PoC will facilitate commercialization of this 3D scanning technology by providing support to explore the markets in biosciences and beyond, protect the IP and facilitate early stage manufacture and assembly of AOL 3D scanners to supply biomedical researchers.
[ "Neuroscience and Disorders of the Nervous System", "Products and Processes Engineering", "Systems and Communication Engineering" ]
10.1007/JHEP04(2010)064
On Subextensive Corrections To Fluid Dynamics From Gravity
We use the fluid-gravity correspondence to compute subextensive corrections, proportional to the shear tensor, to the energy-momentum tensor of fluids on three-spheres. The dual configurations we consider are charged black hole solutions of N = 2 gauged supergravity theories in five dimensions.
[ "Fundamental Constituents of Matter", "Mathematics" ]
10.1515/nanoph-2019-0101
Singularities in the flying electromagnetic doughnuts
Flying doughnuts (FDs) are exact propagating solutions of Maxwell equations in the form of single-cycle, space-time non-separable toroidal pulses. Here we review their properties and reveal the existence of a complex and robust fine topological structure. In particular, the electric and magnetic fields of the FD pulse vanish across a number of planes, spherical shells and rings, and display a number of point singularities including saddle points and vortices. Moreover, the instantaneous Poynting vector of the field exhibits a large number of singularities, which are often accompanied by extended areas energy backflow.
[ "Fundamental Constituents of Matter", "Systems and Communication Engineering", "Mathematics" ]
10.1080/13549839.2020.1835849
Young Families And Children In Gentrifying Neighbourhoods How Gentrification Reshapes Use And Perception Of Green Play Spaces
It has been well established that gentrification can undermine access to green amenities for socially vulnerable residents through socio-cultural or physical displacement from working-class and min. . .
[ "Human Mobility, Environment, and Space", "The Social World and Its Interactions" ]
10.1038/s41598-020-63113-5
Author Correction: All semiconductor enhanced high-harmonic generation from a single nanostructured cone
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
2726034
Basajaun - building a sustainable joint between rural and urban areas through circular and innovative wood construction value chains
European rural areas will boost when their natural resources constitute the basis of innovative and sustainable value chains with a high positive economic impact. In this sense, forests constitute an asset that provide not only ecosystems and biodiversity, but also a valuable and sustainable raw material, “wood”. Wood is consumed by various sectors, including one of the most “raw materials” demanding sector, the construction. The BASAJAUN project is a puzzle composed of 1st and 2nd transformation companies, research organizations, associations and public bodies that are focused on maximizing the forest value through its use in wood construction. Its main goal is to optimize the wood forest resources to enable the construction of a medium sized building (16 dwellings with 4 floors) with the lowest possible forest hectares – that will depends on the tree species and the forest local peculiarities (climate, surface, ..). The whole process will be optimised to maximize the consumption of wood products from the forest (solid wood, fibers, veneers, bark, sawdust, etc.). For this purpose, a) innovative wood-based construction materials (thermal insulation, composites, varnishes, SIPs) and systems (structure, facades, floors, walls, roof and fixings) will be developed and upscaled, b) two full -scale demo buildings (Finland and France) that use those products will be constructed, c) digitalization of the whole construction value chain (from forest to building) will be done and d) the rural development impact will be studied at regional level. The environmental impact of the products of these value chains will be assessed as well. Besides, to assure a sustainable impact of the project a novel thematic platform to integrate the stakeholders of the wood region with urban areas will be developed. Besides, BASAJAUN leverages the previous results of successful projects where the innovative materials and systems were designed at laboratory and semi-industrial scale.
[ "Products and Processes Engineering", "Environmental Biology, Ecology and Evolution", "Materials Engineering" ]
10.1155/2011/986491
The Role Of Natural Killer Cells In Sepsis
Severe sepsis and septic shock are still deadly conditions urging to develop novel therapies. A better understanding of the complex modifications of the immune system of septic patients is needed for the development of innovative immunointerventions. Natural killer (NK) cells are characterized as CD3−NKp46+CD56+ cells that can be cytotoxic and/or produce high amounts of cytokines such as IFN-γ. NK cells are also engaged in crosstalks with other immune cells, such as dendritic cells, macrophages, and neutrophils. During the early stage of septic shock, NK cells may play a key role in the promotion of the systemic inflammation, as suggested in mice models. Alternatively, at a later stage, NK cells-acquired dysfunction could favor nosocomial infections and mortality. Standardized biological tools defining patients' NK cell status during the different stages of sepsis are mandatory to guide potential immuno-interventions. Herein, we review the potential role of NK cells during severe sepsis and septic shock.
[ "Immunity, Infection and Immunotherapy", "Physiology in Health, Disease and Ageing" ]
W2123788297
Predicting elections from biographical information about candidates: A test of the index method
Abstract This study uses 59 biographical variables to create a “bio-index” for forecasting U.S. presidential elections. The bio-index method counts the number of variables for which each candidate rates favorably, and the forecast is that the candidate with the highest score would win the popular vote. The bio-index relies on different information and includes more variables than traditional econometric election forecasting models. The method is useful in combination with simple linear regression to estimate a relationship between the index score of the candidate of the incumbent party and his share of the popular vote. The study tests the model for the 29 U.S. presidential elections from 1896 to 2008. The model's forecasts, calculated by cross-validation, correctly predicted the popular vote winner for 27 of the 29 elections; this performance compares favorably to forecasts from polls (15 out of 19), prediction markets (22 out of 26), and three econometric models (12 to 13 out of 15 to 16). Out-of-sample forecasts of the two-party popular vote for the four elections from 1996 to 2008 yielded a forecast error almost as low as the best of seven econometric models. The model can help parties to select the candidates running for office, and help to improve on the accuracy of election forecasting, especially for longer-term forecasts.
[ "Individuals, Markets and Organisations", "Institutions, Governance and Legal Systems" ]
10.1109/ICASSP.2015.7178359
Active learning of self-concordant like multi-index functions
We study the problem of actively learning a multi-index function of the form f(x) = g0(A0x) from its point evaluations, where A0 ∈ k×d with k 蠑 d. We build on the assumptions and techniques of an existing approach based on low-rank matrix recovery (Tyagi and Cevher, 2012). Specifically, by introducing an additional self-concordant like assumption on g0 and adapting the sampling scheme and its analysis accordingly, we provide a bound on the sampling complexity with a weaker dependence on d in the presence of additive Gaussian sampling noise. For example, under natural assumptions on certain other parameters, the dependence decreases from O(d3/2) to O(d).
[ "Mathematics", "Computer Science and Informatics" ]
10.1145/3123024.3124459
Wahm 4Th Workshop On Ubiquitous Technologies To Augment The Human Mind Sharing Experiences
A recurring science fiction theme is the downloading of abilities from another human to one's own mind. Emerging technologies beyond simple audio/video recordings such as: 360° videos, tactile recorders and odor recorders are promising tools to enable skill transfer and empathy. However, the produced large datasets require new means for selecting, displaying and sharing experiences. This workshop will bring together researchers from a wide range of computing disciplines, such as virtual reality, mobile computing, privacy and security, social computing and ethnography, usability, and systems research. Furthermore, we will invite researchers from related disciplines such as psychology and economics. The objective is to discuss how these trends are changing our existing research on sharing experiences and knowledge to augment the human mind.
[ "Computer Science and Informatics", "The Human Mind and Its Complexity" ]
10.1145/2925416
On Problems As Hard As Cnf Sat
The field of exact exponential time algorithms for non-deterministic polynomial-time hard problems has thrived since the mid-2000s. While exhaustive search remains asymptotically the fastest known algorithm for some basic problems, non-trivial exponential time algorithms have been found for a myriad of problems, including Graph Coloring, Hamiltonian Path, Dominating Set, and 3-CNF-Sat. In some instances, improving these algorithms further seems to be out of reach. The CNF-Sat problem is the canonical example of a problem for which the trivial exhaustive search algorithm runs in time O(2n), where n is the number of variables in the input formula. While there exist non-trivial algorithms for CNF-Sat that run in time o(2n), no algorithm was able to improve the growth rate 2 to a smaller constant, and hence it is natural to conjecture that 2 is the optimal growth rate. The strong exponential time hypothesis (SETH) by Impagliazzo and Paturi [JCSS 2001] goes a little bit further and asserts that, for every e
[ "Computer Science and Informatics", "Mathematics" ]
W1893240525
A new species ofCryptotis(Mammalia, Eulipotyphla, Soricidae) from the Sierra de Perijá, Venezuelan-Colombian Andes
The Sierra de Perija is the northern extension of the Cordillera Oriental of the Andes and includes part of the border between Colombia and Venezuela. The population of small-eared shrews (Mammalia, Eulipotyphla, Soricidae, Cryptotis) inhabiting the Sierra de Perija previously was known from only a single skull from an individual collected in Colombia in 1989. This specimen had been referred to alternatively as C. thomasi and C. meridensis, but a more precise definition of the known Colombian and Venezuelan species of Cryptotis has since excluded the Sierra de Perija population from any named species. The recent collection of a specimen from the Venezuelan slope of Sierra de Perija prompted us to re-evaluate the taxonomic status of this population and determine its relationship with other Andean shrews. Our examination of the available specimens revealed that they possess a unique suite of morphological and morphometrical characters, and we describe the Sierra de Perija population as a new species in the ...
[ "Environmental Biology, Ecology and Evolution", "Earth System Science" ]
280145
Energy-Efficient Multi-Terabit/s Photonic Interconnects
The rapid growth of data traffic requires radically new approaches for high-speed data transmission to increase the bandwidth and power efficiency by orders of magnitude. The proposed research aims at novel system and device concepts for low-energy high-capacity optical interconnects in data centers. Data rates of 10 Tbit/s and beyond are envisaged by coherent multicarrier transmission. Parametric frequency conversion in high-Q Kerr-nonlinear resonators will be used to generate broadband combs of frequency-locked optical carriers. Integrated silicon photonic systems will allow for power-efficient multichannel modulation and detection. Novel reconfigurable optical signal processors will avoid excessive digital post-processing and hence reduce overall energy consumption.
[ "Systems and Communication Engineering", "Physical and Analytical Chemical Sciences", "Materials Engineering" ]
715975
Mechanism of DNA-protein cross-link repair in S phase
DNA-protein cross-links (DPCs) are common DNA lesions caused by endogenous, environmental, and chemotherapeutic agents. Cells are susceptible to these lesions during S phase, as DPCs impede replication fork progression and are likely to induce genomic instability, a cause of cancer and aging. Despite its relevance to human health, the repair of DPCs is poorly understood. Research on DPC repair has mainly involved testing cellular responses to compounds such as formaldehyde, but these agents induce a wide variety of DNA lesions, and conflicting results have been reported. To overcome these obstacles, I have developed the first in vitro system that recapitulates replication-coupled DPC repair. In this system, a plasmid containing a site-specific DPC is replicated in Xenopus egg extracts. Using this approach, I demonstrated that DPC repair requires DNA replication. When a replication fork encounters a DPC, the DPC is degraded into a peptide-adduct, which allows replication bypass by translesion DNA synthesis. Importantly, these experiments identified a novel proteolytic pathway whose activity is regulated by replication. This in vitro system now provides a powerful means to identify and characterize the different factors that participate in S phase DPC repair. I speculate that for DPC processing to occur, the protein-adduct must first be detected, then marked for degradation and ultimately degraded. Using a series of complementary strategies, which will take advantage of the in vitro system combined with proteome and genome wide approaches, I seek to uncover the different players that participate in each of these events. This project will enable a detailed mechanistic outlook of a complex multi-step reaction that has not been feasible to achieve using existing methodologies. It will also improve our understanding of how DPCs impact genomic stability and the consequences of not repairing these lesions for human health.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Physiology in Health, Disease and Ageing" ]
10.1371/journal.pone.0072514
Migraine Strikes as Neuronal Excitability Reaches a Tipping Point
Self-propagating waves of cerebral neuronal firing, known as spreading depolarisations, are believed to be at the roots of migraine attacks. We propose that the start of spreading depolarisations corresponds to a critical transition that occurs when dynamic brain networks approach a tipping point. We show that this hypothesis is consistent with current pathogenetic insights and observed dynamics. Our view implies that migraine strikes when modulating factors further raise the neuronal excitability in genetically predisposed subjects to a level where even minor perturbations can trigger spreading depolarisations. A corollary is that recently discovered generic early warning indicators for critical transitions may be used to predict the onset of migraine attacks even before patients are clinically aware. This opens up new avenues for dissecting the mechanisms for the onset of migraine attacks and for identifying novel prophylactic treatment targets for the prevention of attacks.
[ "Neuroscience and Disorders of the Nervous System", "Integrative Biology: from Genes and Genomes to Systems", "Physiology in Health, Disease and Ageing" ]
10.1088/1751-8113/46/17/175001
Entanglement Evolution Across Defects In Critical Anisotropic Heisenberg Chains
We study the out-of-equilibrium time evolution after a local quench connecting two anisotropic spin-1/2 XXZ Heisenberg open chains via an impurity bond. The dynamics is obtained by means of the adaptive time-dependent densitymatrix renormalization group. We show that the entanglement entropies (von Neumann and R´ enyi) in the presence of a weakened bond depend on the sign of the bulk interaction. For an attractive interaction ( � 0), the defect is relevant and the entanglement saturates to a finite value. This out-of-equilibrium behavior generalizes the well-known results for the ground-state entanglement entropy of the model.
[ "Condensed Matter Physics", "Fundamental Constituents of Matter" ]
10.1016/j.celrep.2018.11.027
MadID, a Versatile Approach to Map Protein-DNA Interactions, Highlights Telomere-Nuclear Envelope Contact Sites in Human Cells
Mapping the binding sites of DNA- or chromatin-interacting proteins is essential to understanding biological processes. DNA adenine methyltransferase identification (DamID) has emerged as a comprehensive method to map genome-wide occupancy of proteins of interest. A caveat of DamID is the specificity of Dam methyltransferase for GATC motifs that are not homogenously distributed in the genome. Here, we developed an optimized method named MadID, using proximity labeling of DNA by the methyltransferase M. EcoGII. M. EcoGII mediates N6-adenosine methylation in any DNA sequence context, resulting in deeper and unbiased coverage of the genome. We demonstrate, using m6A-specific immunoprecipitation and deep sequencing, that MadID is a robust method to identify protein-DNA interactions at the whole-genome level. Using MadID, we revealed contact sites between human telomeres, repetitive sequences devoid of GATC sites, and the nuclear envelope. Overall, MadID opens the way to identification of binding sites in genomic regions that were largely inaccessible. Mapping the binding sites of DNA- or chromatin-interacting proteins is essential to understanding biological processes. Sobecki et al. developed an optimized method named MadID based on proximity labeling of DNA by the bacterial methyltransferase M. EcoGII. MadID results in deep and unbiased coverage for genome-wide mapping studies.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1364/ACOFT.2016.JM6A.19
Unified Description Of Dispersive Wave Emission In Normal And Anomalous Dispersion Regimes
We present a novel theoretical framework where dispersive wave emission in normal and anomalous dispersion is interpreted based on four-wave mixing processes. It is a powerful tool for designing supercontinuum sources along analytical guidelines.
[ "Physical and Analytical Chemical Sciences", "Fundamental Constituents of Matter", "Systems and Communication Engineering" ]
10.1039/C4FD00187G
Percolating Plasmonic Networks For Light Emission Control
Optical nanoantennas have revolutionised the way we manipulate single photons emitted by individual light sources in a nanostructured photonic environment. Complex plasmonic architectures allow for multiscale light control by shortening or stretching the light wavelength for a fixed operating frequency, meeting the size of the emitter and that of propagating modes. Here, we study self-assembled semi-continuous gold films and lithographic gold networks characterised by large local density of optical state (LDOS) fluctuations around the electrical percolation threshold, a regime where the surface is characterised by large metal clusters with fractal topology. We study the formation of plasmonic networks and their effect on light emission from embedded fluorescent probes in these systems. Through fluorescence dynamics experiments we discuss the role of global long-range interactions linked to the degree of percolation and to the network fractality, as well as the local near-field contributions coming from the local electro-magnetic fields and the topology. Our experiments indicate that local properties dominate the fluorescence modification.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1002/smll.201501223
Surface Conductive Graphene-Wrapped Micromotors Exhibiting Enhanced Motion
Surface-conductive Janus spherical motors are fabricated by wrapping silica particles with reduced graphene oxide capped with a thin Pt layer. These motors exhibit a 100% enhanced velocity as compared to standard SiO2-Pt motors. Furthermore, the versatility of graphene may open up possibilities for a diverse range of applications from active drug delivery systems to water remediation.
[ "Synthetic Chemistry and Materials", "Materials Engineering", "Condensed Matter Physics" ]
W2513054618
S09-5 Precarious employment in chile: macroeconomic determinants of the association with self-reported health
Introduction Employment and working conditions are key determinants of health and health inequities in middle and high-income countries like Chile. They are also key determinants of occupational health outcomes and occupational health inequities. Individual determinants of poor employment conditions and health have been abundantly studied, mainly related to the axes of inequalities and disadvantage in the labour market. Contextual determinants, however, including policies and regulatory frameworks, but especially macroeconomic conditions and economic structure, have seldom been analysed as determinants of health through the mediation of employment conditions. In Chile, questions pertaining to individuals and their eco-social context can be answered by comparing across the Chilean Regions given their differentiated economic structures and macro-economic outcomes. Methods This study addresses these questions through the three following specific stages: i) a multilevel study assessing the association between employment precariousness and self-reported health in Chilean workers by region estimating regional risk ratios (RRR), with individual-level data from the first Chilean Work, employment health and quality of life survey (2009-2010); ii) assessing to which extent such association is varying across Chilean regions using the I² statistic; iii) investigating which regional-level macro-economic factors are associated with the magnitude of the RRR, performing random effects meta-regression analyses. Results We found that there is a regional variation in the probability of reporting poor health across levels of employment precariousness (I² = 44%). We particularly found that GDP variability, especially during the 2008 economic crisis period, was associated with the magnitude of the RRR. Specifically, we found that the higher the economic crisis impact on regional GDP, the higher the impact of employment precariousness on workers’ self-reported health. Conclusion Results show that macro-economic factors can play a role in employment conditions’ impact on occupational health, highlighting the necessity of designing occupational prevention policies that integrate macroeconomic conditions and economic structures.
[ "Individuals, Markets and Organisations", "Human Mobility, Environment, and Space", "Prevention, Diagnosis and Treatment of Human Diseases" ]
W2086674260
Model-based diagnosis of spreadsheet programs: a constraint-based debugging approach
Spreadsheet programs are probably the most successful example of end-user software development tools and are used for a variety of purposes. Like any type of software, they are prone to error, in particular as they are usually developed by non-programmers. While various techniques exist to support the developer in finding errors in procedural programs, the tool support for spreadsheet debugging is still limited. In this paper, we show how techniques from model-based diagnosis can be applied and extended for spreadsheet debugging by translating the relevant parts of a spreadsheet to a constraint satisfaction problem. We additionally propose both problem-specific and generalizable extensions to the classical diagnosis algorithms which help to detect potential problems in a spreadsheet based on user-provided test cases more efficiently. The proposed techniques were integrated into a modular framework for spreadsheet debugging and evaluated with respect to scalability based on a number of real-world and artificially created spreadsheets. An additional error detection exercise involving 24 subjects was performed to assess the general applicability of such advanced spreadsheet debugging techniques for end users.
[ "Computer Science and Informatics" ]
770877
Mechanisms of stem cell population dynamics and reprogramming
How complex but stereotyped tissues are formed, maintained and regenerated through local growth, differentiation and remodeling is a fundamental open question in biology. Understanding how single cell behaviors are coordinated on the population level and how population-level dynamics is coupled to tissue architecture is required to resolve this question as well as to develop stem cell (SC) therapies and effective treatments against cancers. As a self-renewing organ maintained by multiple distinct SC populations, the epidermis represents an outstanding, clinically highly relevant research paradigm to address this question. A key epidermal SC population are the hair follicle stem cells (HFSCs) that fuel hair follicle regeneration, repair epidermal injuries and, when deregulated, initiate carcinogenesis. The major obstacle in mechanistic understanding of HFSC regulation has been the lack of an in vitro culture system enabling their precise monitoring and manipulation. We have overcome this barrier by developing a method for long-term maintenance of multipotent HFSCs that recapitulates the complexity of HFSC fate decisions and dynamic crosstalk between HFSCs and their progeny. This breakthrough invention puts me in the unique position to investigate how HFSCs self-organize into a network of SCs and progenitors through population-level signaling crosstalk and phenotypic plasticity. This project will uncover the spatiotemporal dynamics of HFSCs fate decisions and establish the role of the niche in this process (Aim1), decipher key gene-regulatory networks and epigenetic barriers that control phenotypic plasticity (Aim2), and discover druggable signaling networks that drive bi-directional reprogramming of HFSCs and their progeny (Aim3). By deconstructing complex tissue-level behaviors at an unprecedented spatiotemporal resolution this study has the potential to transform the fundaments of adult SC biology with immediate implications to regenerative medicine.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1063/1.5040184
Reversible And Magnetically Unassisted Voltage Driven Switching Of Magnetization In Ferh Pmn Pt
Reversible control of magnetization by electric fields without assistance from a subsidiary magnetic field or electric current could help reduce the power consumption in spintronic devices. When increasing temperature above room temperature, FeRh displays an uncommon antiferromagnetic to ferromagnetic phase transition linked to a unit cell volume expansion. Thus, using the strain exerted by an adjacent piezoelectric layer, the relative amount of antiferromagnetic and ferromagnetic regions can be tuned by an electric field applied to the piezoelectric material. Indeed, large variations in the saturation magnetization have been observed when straining FeRh films grown on suitable piezoelectric substrates. In view of its applications, the variations in the remanent magnetization rather than those of the saturation magnetization are the most relevant. Here, we show that in the absence of any bias external magnetic field, permanent and reversible magnetization changes as high as 34% can be induced by an electric field, which remain after this has been zeroed. Bulk and local magnetoelectric characterization reveals that the fundamental reason for the large magnetoelectric response observed at remanence is the expansion (rather than the nucleation) of ferromagnetic nanoregions.
[ "Condensed Matter Physics", "Materials Engineering", "Physical and Analytical Chemical Sciences" ]
10.1029/2010GL042498
Three Dimensional Seismic Velocity Tomography Of Montserrat From The Sea Calipso Offshore Onshore Experiment
[1] The SEA-CALIPSO experiment in December 2007 incorporated a sea-based airgun source, and seismic recorders both on Montserrat and on the adjacent sea floor. A high quality subset of the data was used for a first arrival P-wave velocity tomographic study. A total of more than 115,000 traveltime data from 4413 airgun shots, and 58 recording stations, were used in this high-resolution tomographic inversion. The experiment geometry limited the depth of well resolved structures to about 5 km. The most striking features of the tomography are three relatively high velocity zones below each of the main volcanic centers on Montserrat, and three low velocity zones flanking Centre Hills. We suggest that the high velocity zones represent the solid andesitic cores of the volcano complexes, characterized by wave speeds faster than adjacent volcaniclastic material. The low velocity zones may reflect porous volcaniclastic material and/or alteration by formerly active hydrothermal systems.
[ "Earth System Science", "Systems and Communication Engineering" ]
10.1021/jp312323b
Mechanism of alcohol-water separation in metal-organic frameworks
The metal-organic framework Zn2(BDC)2(TED) (1) has been reported to be water-stable and highly selective toward the adsorption of water and alcohols, suggesting the application of this material as a separation membrane for the production of bioethanol. We have studied the adsorption mechanism of water, methanol, ethanol, and dimethylether in this framework by means of density-functional theory with corrections for London dispersion. We show that the combination of the hydrogen bond between the hydroxyl group in ethanol with the oxy group in 1 and the van der Waals interaction between the ethanol alkyl chain with the phenyl ring in 1 is responsible for the preferential adsorption of ethanol over water in the framework. The calculated enthalpy of adsorption for the four compounds in 1 is in excellent agreement with experimental results. We further note that the computational approach has to be chosen with care: It is essential to account for London dispersion interactions, as well as the use of large models, preferably the full periodic structure, to obtain correct adsorption geometries and energies.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1016/j.jet.2018.01.019
Cultural leader and the dynamics of assimilation
This paper studies the population dynamics of cultural traits in a model of intergenerational cultural transmission with a perfectly-forward looking cultural leader. We show that there exists a threshold size in terms of population above which the cultural leader becomes active. We also show that a policy affecting some key parameters (such as the cost of providing the religious good) has a different impact in the short run and in the long run due to over-reactions or under-reactions of the different cultural groups. Finally, we study the cultural competition between two forward-looking cultural leaders with opposite objectives. We show that the steady-state cultural equilibrium depends on the time preference structure of the two leaders.
[ "Individuals, Markets and Organisations", "The Social World and Its Interactions" ]
10.1016/j.pbiomolbio.2016.06.001
Mapping cardiac microstructure of rabbit heart in different mechanical states by high resolution diffusion tensor imaging: A proof-of-principle study
Myocardial microstructure and its macroscopic materialisation are fundamental to the function of the heart. Despite this importance, characterisation of cellular features at the organ level remains challenging, and a unifying description of the structure of the heart is still outstanding. Here, we optimised diffusion tensor imaging data to acquire high quality data in ex vivo rabbit hearts in slack and contractured states, approximating diastolic and systolic conditions. The data were analysed with a suite of methods that focused on different aspects of the myocardium. In the slack heart, we observed a similar transmural gradient in helix angle of the primary eigenvector of up to 23. 6°/mm in the left ventricle and 24. 2°/mm in the right ventricle. In the contractured heart, the same transmural gradient remained largely linear, but was offset by up to +49. 9° in the left ventricle. In the right ventricle, there was an increase in the transmural gradient to 31. 2°/mm and an offset of up to +39. 0°. The application of tractography based on each eigenvector enabled visualisation of streamlines that depict cardiomyocyte and sheetlet organisation over large distances. We observed multiple V- and N-shaped sheetlet arrangements throughout the myocardium, and insertion of sheetlets at the intersection of the left and right ventricle. This study integrates several complementary techniques to visualise and quantify the heart's microstructure, projecting parameter representations across different length scales. This represents a step towards a more comprehensive characterisation of myocardial microstructure at the whole organ level.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing", "Condensed Matter Physics" ]
10.1115/1.4043148
Multidimensional Approximation of Nonlinear Dynamical Systems
A key task in the field of modeling and analyzing nonlinear dynamical systems is the recovery of unknown governing equations from measurement data only. There is a wide range of application areas for this important instance of system identification, ranging from industrial engineering and acoustic signal processing to stock market models. In order to find appropriate representations of underlying dynamical systems, various data-driven methods have been proposed by different communities. However, if the given data sets are high-dimensional, then these methods typically suffer from the curse of dimensionality. To significantly reduce the computational costs and storage consumption, we propose the method multidimensional approximation of nonlinear dynamical systems (MANDy) which combines data-driven methods with tensor network decompositions. The efficiency of the introduced approach will be illustrated with the aid of several high-dimensional nonlinear dynamical systems.
[ "Mathematics", "Computer Science and Informatics" ]
10.1002/cbic.201402377
Single-MOLECULE IMAGING REVEALS THAT SMALL AMYLOID-β<inf>1-42</inf> oligomers interact with the cellular prion protein (PrP<sup>C</sup>)
Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer's disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by Aβ42 have obscured the nature of the oligomeric species that bind to a given receptor. Here, we have used single-molecule imaging to characterize Aβ42 oligomers (oAβ42) and to confirm the controversial interaction of oAβ42 with the cellular prion protein (PrPC) on live neuronal cells. Our results show that, at nanomolar concentrations, oAβ42 interacts with PrPC and that the species bound to PrPC are predominantly small oligomers (dimers and trimers). Single-molecule biophysical studies can thus aid in deciphering the mechanisms that underlie receptor-mediated oAβ-induced neurotoxicity, and ultimately facilitate the discovery of novel inhibitors of these pathways.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W3011507114
Deep-learning approach to predict a severe plastic anisotropy of caliber-rolled Mg alloy
Abstract Mg alloys have a strong plastic anisotropy due to their intrinsic crystal structure. In particular, an anisotropy of caliber-rolled Mg alloy is difficult to anticipate using a traditional method due to the unique texture developed by this process. This study adopted a deep neural network (DNN) with optimized hyperparameters to predict the severe plastic anisotropy. The DNN model was trained with 85,967 examples, and then evaluated in comparison with other approaches, such as ‘shallow’ neural networks, multiple linear regression, and constitutive analytical equations. The optimized DNN model exhibited the best prediction among these approaches. Furthermore, it showed a high generalization ability, which is indispensable for interpreting a plastic anisotropy. It has been verified that the deep-learning approach has a vast potential for interpreting the anisotropy problem of Mg alloys.
[ "Condensed Matter Physics", "Materials Engineering" ]
10.1103/PhysRevB.95.104509
Spatial variation of the two-fold anisotropic superconducting gap in a monolayer of FeS e0.5 T e0.5 on a topological insulator
We present a low temperature scanning tunneling spectroscopy (STS) study of the superconducting properties of monolayers of FeSe0. 5Te0. 5 grown on the three-dimensional (3D) topological insulator Bi2Se1. 2Te1. 8. While the morphology and the overall transition temperature resembles those of similarly doped bulk crystals, we find a two-fold anisotropic s-wave gap function. The two-fold nature of the gap symmetry is evident from the Bogoliubov quasiparticle interference (QPI) pattern, which shows distinct C2 symmetric scattering intensities. Spatially resolved spectroscopic data shows a strong inhomogeneity in the size and anisotropy strength of the energy gaps, which cannot be correlated merely to the local chemical disorder. Instead, we argue that the gap inhomogeneity emerges with a similar mechanism as in disordered superconductors. Our sample system provides an ideal platform to study unconventional superconductivity in close proximity to a topological insulator.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences" ]
10.1093/nar/gkt305
Small molecule induced reactivation of mutant p53 in cancer cells
The p53 cancer mutant Y220C is an excellent paradigm for rescuing the function of conformationally unstable p53 mutants because it has a unique surface crevice that can be targeted by small-molecule stabilizers. Here, we have identified a compound, PK7088, which is active in vitro: PK7088 bound to the mutant with a dissociation constant of 140 μM and raised its melting temperature, and we have determined the binding mode of a close structural analogue by X-ray crystallography. We showed that PK7088 is biologically active in cancer cells carrying the Y220C mutant by a battery of tests. PK7088 increased the amount of folded mutant protein with wild-type conformation, as monitored by immunofluorescence, and restored its transcriptional functions. It induced p53-Y220C-dependent growth inhibition, cell-cycle arrest and apoptosis. Most notably, PK7088 increased the expression levels of p21 and the proapoptotic NOXA protein. PK7088 worked synergistically with Nutlin-3 on up-regulating p21 expression, whereas Nutlin-3 on its own had no effect, consistent with its mechanism of action. PK7088 also restored non-transcriptional apoptotic functions of p53 by triggering nuclear export of BAX to the mitochondria. We suggest a set of criteria for assigning activation of p53.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Prevention, Diagnosis and Treatment of Human Diseases" ]
760081
Principles of Musical Structure Building: Theory, Computation, and Cognition
Music is a central human trait across all cultures and historical periods, involving a great rich variety of parameters, cognitive processes, and forms of structure building. The proposed project aims at advancing the understanding of human cognition and, specifically, the capacity to represent and process complex auditory sequences and syntactic structures by exploring the rich potential of music perception. Building on the PI’s previous work, this interdisciplinary research programme will be divided into three core strands: (A) The theoretical strand will be devoted to the investigation of formal principles that govern musical syntax and structure building in Western and non-Western music. Many current approaches share the expressive power of (tree-based) context-free grammars and are mostly confined to harmonic syntax only. Therefore, they face difficulty in expressing certain crucial syntactic phenomena in music. To address this lacuna, the theoretical strand will develop a novel unified theory of musical syntax that exceeds context-free complexity and reconciles harmonic structure with the constraints of voice leading within a single coherent framework. (B) Addressing the lack of machine-readable corpora in music research, a large corpus of digitized syntactic analyses will be compiled and published in the context of the project’s computational strand. Further, the unified syntax theory will be implemented based on a generalized parsing approach and graph grammars, and trained and evaluated using the analytical corpus. (C) The formal framework developed in (A) entails specific predictions about mental representations of musical structure that will be empirically tested in the experimental strand of the project. Particular focus will be on aspects of nonlocal dependency relations, learnability, revision, and tension. The outcomes of the project will make a significant contribution to both the field of music cognition and to the cognitive sciences in general.
[ "Computer Science and Informatics", "The Human Mind and Its Complexity" ]
W331879009
Bioeconomic analysis of giant kelp Macrocystis pyrifera cultivation (Laminariales; Phaeophyceae) in northern Chile
This study analyzed the economic feasibility of offshore commercial cultivation of Macrocystis pyrifera in northern Chile. To achieve this objective, a continuous-time model including biological, technological, and economic aspects was developed. To implement this model, the biomass growth until marketable size is reached was estimated for three periods of the year. A periodic system of cultivation and harvesting is described, and the main investments, operation costs, remunerations, and operational costs of cultivation and harvesting are defined. The results of the baseline model show that cultivation is not profitable in the long term considering the selling price and the harvest yield. Additionally, at baseline, the revenue is unable to cover the investment costs or the operation costs. However, in a scenario in which productivity is 211 % higher than the base harvest and prices are 25 % higher, cultivation becomes profitable, with positive net present values (NPV) after 14 years. Despite the aforementioned considerations, the opportunity for generating greater value from this type of cultivation is discussed, taking into account its characteristics as units that provide ecosystem services, which is a feature that is starting to be discussed in relation to marine environments.
[ "Environmental Biology, Ecology and Evolution", "Individuals, Markets and Organisations", "Products and Processes Engineering" ]
885252
Multi-Layered security technologies to ensure hyper connected smart cities with blockchain, bigdata, cloud and iot
IoT systems today tend to be built around the concept of IoT/cloud convergence, integrating heterogeneous data streams within cloud infrastructures, and thus benefiting from the scalability, performance and capacity of the cloud. This approach is very efficient for some IoT applications such as big data processing problems. However, these architectures promote a centralized data collection and processing approach, which introduces several limitations in terms of supported applications and business models that they enable. The main goal of M-Sec project is to empower IoT stakeholders to develop, deploy and operate novel IoT applications based on a scalable highly decentralized paradigm, which facilitates incentivized peer-to-peer interactions between objects and people. The project will explore semantically interoperable interactions between people/objects according to a given social context, beyond their simple peer-to-peer information exchange and internetworking. Overall, the M-Sec paradigm will enable the introduction and implementation of specific classes of applications and services that are not efficiently supported by state-of-the-art architectures. The M-Sec project will deliver a set of concrete and added value main results: 1. M-Sec distributed, self-organized, robust and trusted IoT infrastructure that empowers IoT stakeholders to develop, deploy and operate novel multipurpose IoT applications for smart cities on top of smart objects. 2. An open IoT market of applications, data and services that provides the framework upon which objects and people can exchange value and defines the motivation incentives for humans and smart objects to interact. 3. A sustainable ecosystem of stakeholders, roles, tools and infrastructures upon which new entrants and other players can build and experiment with the future application services. 4. A parameterized model on how to replicate the M-Sec approach further and guarantee its return of investment and benefits.
[ "Computer Science and Informatics", "Systems and Communication Engineering", "Products and Processes Engineering" ]
10.1086/653668
Pair Bonding Modifies The Age Specific Intensities Of Natural Selection On Human Female Fecundity
Abstract: In many animals, including humans, the ability of females to reproduce depends not only on their survival to each age but also on being pair‐bonded to a mate. Exposure of the genetic variation underlying fecundity to natural selection should therefore depend on the proportion of females both alive and pair‐bonded. In spite of this, female “marital” status is seldom considered to impact the strength of selection on age‐specific fecundity. We used marriage‐history data of preindustrial Finns who experienced conditions of natural mortality and fertility to investigate how assortative mating by age and socioeconomic status affected female fitness and underlay age‐specific female marriage patterns. The probability that a female was married peaked at age 30–40 years; females who married in their early 20s to high‐socioeconomic‐status husbands had the highest levels of lifetime reproductive success. Greater age difference between the pair, which is typical for females who are married to high‐socioecono. . .
[ "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems", "The Social World and Its Interactions" ]
10.1007/JHEP02(2016)113
Associated Production Of A Top Quark Pair With Vector Bosons At Nlo In Qcd Impact On T Bar T H Searches At The Lhc
We study the production of a top-quark pair in association with one and two vector bosons, $t \bar t V$ and $t \bar t VV$ with $V=\gamma, Z, W^\pm$, at the LHC. We provide predictions at next-to-leading order in QCD for total cross sections and top-quark charge asymmetries as well as for differential distributions. A thorough discussion of the residual theoretical uncertainties related to missing higher orders and to parton distribution functions is presented. As an application, we calculate the total cross sections for this class of processes (together with $t \bar t H$ and $t \bar t t \bar t$ production) at hadron colliders for energies up to 100 TeV. In addition, by matching the NLO calculation to a parton shower, we determine the contribution of $t \bar t V$ and $t \bar t VV$ to final state signatures (two-photon and two-same-sign-, three- and four-lepton) relevant for $t \bar t H$ analyses at the Run II of the LHC.
[ "Fundamental Constituents of Matter" ]
249377
Distortions of Normativity: The NS-System and Morality
The Nazi system was not amoralism in the classical textbook sense but a specific, though contorted normative order. The basic argument was that political emergency conditions made it necessary to replace the unstable liberal-democratic framework of the Weimar Republic by a &apos;new source of law : the authority and political will of the Führer. The claim to correctly interpret the Führer s will and intentions became the new foundation of legitimate political action . Consequently emergency decrees, political initiatives, and party agitation replaced the rule of law. The Nazis worked, however, with a highly moralized conception of social reality, based on perverted notions of duty, honor, loyalty, fidelity, and sincerity. The Nazi regime provided people with justifications of policies and measures that for many followers amounted to a &apos;meaningful story . They managed to set a normative framework within which even fulfilling killing orders &apos;made sense . A perverted model of practical reasoning was propagated by the highest authorities according to which immediate reactions of resistance and revulsion counted as &apos;natural temptations&apos; which had to be overcome. The aim of the project is to: - provide a detailed account of the normative order of the Nazi system and the transformations of the key political and legal institutions that it brought about; - analyze in detail the distorted notions of duty, obedience, and decency and the corresponding self-conceptions the Nazi regime encouraged; - explore the implications of our findings for the following broader questions: * How should we assess conceptions of normativity under non-ideal conditions? * What is the relationship between legality and legitimacy under non-ideal conditions? * What exactly are the standards for acting morally under non-ideal conditions?
[ "Texts and Concepts", "The Study of the Human Past", "Institutions, Governance and Legal Systems" ]
IB 2012052919 W
SYSTEM FOR VIEWING AND INTERACTING WITH A VIRTUAL 3-D SCENE
A system is described for enabling one or more user devices to view and interact with a three-dimensional (3-D) scene. The system comprises a data server (12) having a processor executing a program to create a virtual 3-D scene, and a user device (10) communicating remotely with the data server by way of a wired or wireless network. The user device (10) runs a user interface program for transmitting commands to the data server to modify the virtual 3-D scene and for displaying on a user screen an image that includes image data received from the data server as an encoded stream. The data server (12) is operative additionally to transmit commands to the user device for the purpose of altering the user interface.
[ "Computer Science and Informatics", "Systems and Communication Engineering" ]
10.1080/17470218.2017.1307432
Is The Hebb Repetition Task A Reliable Measure Of Individual Differences In Sequence Learning
The Hebb repetition task, an operationalization of long-term sequence learning through repetition, is the focus of renewed interest, as it is taken to provide a laboratory analogue for naturalistic vocabulary acquisition. Indeed, recent studies have consistently related performance in the Hebb repetition task with a range of linguistic (dis)abilities. However, despite the growing interest in the Hebb repetition effect as a theoretical construct, no previous research has ever tested whether the task used to assess Hebb learning offers a stable and reliable measure of individual performance in sequence learning. Since reliability is a necessary condition to predictive validity, in the present work, we tested whether individual ability in visual verbal Hebb repetition learning displays basic test-retest reliability. In a first experiment, Hebrew-English bilinguals performed two verbal Hebb tasks, one with English and one with Hebrew consonant letters. They were retested on the same Hebb tasks after a period of about 6 months. Overall, serial recall performance proved to be a stable and reliable capacity of an individual. By contrast, the test-retest reliability of individual learning performance in our Hebb task was close to zero. A second experiment with French speakers replicated these results and demonstrated that the concurrent learning of two repeated Hebb sequences within the same task minimally improves the reliability scores. Taken together, our results raise concerns regarding the usefulness of at least some current Hebb learning tasks in predicting linguistic (dis)abilities. The theoretical implications are discussed.
[ "The Human Mind and Its Complexity" ]
10.1126/sciimmunol.aan1487
Human blood T<inf>fr</inf> cells are indicators of ongoing humoral activity not fully licensed with suppressive function
Germinal center (GC) responses are controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells and are crucial for the generation of high-affinity antibodies. Although the biology of human circulating and tissue Tfh cells has been established, the relationship between blood and tissue Tfr cells defined as CXCR5+Foxp3+ T cells remains elusive. We found that blood Tfr cells are increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially in patients with high autoantibody titers, as well as in healthy individuals upon influenza vaccination. Although blood Tfr cells correlated with humoral responses, they lack full B cell–suppressive capacity, despite being able to suppress T cell proliferation. Blood Tfr cells have a naïve-like phenotype, although they are absent from human thymus or cord blood. We found that these cells were generated in peripheral lymphoid tissues before T-B interaction, as they are maintained in B cell–deficient patients. Therefore, blood CXCR5+Foxp3+ T cells in human pathology indicate ongoing humoral activity but are not fully competent circulating Tfr cells.
[ "Immunity, Infection and Immunotherapy", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1186/1471-2164-15-222
Reliable Reference Mirnas For Quantitative Gene Expression Analysis Of Stress Responses In Caenorhabditis Elegans
Quantitative real-time PCR (qPCR) has become the “gold standard” for measuring expression levels of individual miRNAs. However, little is known about the validity of reference miRNAs, the improper use of which can result in misleading interpretation of data. Here we undertook a systematic approach to identify highly stable miRNAs in different stress conditions such as low oxygen (hypoxia), UV-stress and high temperature (heat-stress) in the nematode Caenorhabditis elegans. We conducted genome-wide RNA-seq for small RNAs and selected abundant miRNAs with minimal variation of expression between the different conditions. We further validated the stable expression of a selection of those constitutively expressed candidates in the different stress conditions by SYBR Green qPCR. The selected miRNA candidates were analyzed for stability by applying the widely used geNorm logarithm. With this approach, we were able to successfully identify suitable reference miRNAs for each stress condition. Interestingly, we also found that 3 miRNAs, namely mir-2-5p, mir-46-3p and mir-47-3p, are stable in all the above-mentioned conditions suggesting that they might have general functions independent of stress. Our analysis offers a comprehensive list of stably expressed miRNAs in different stress conditions that can be confidently used as reference miRNAs for qPCR analysis in C. elegans.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
223078
General relativistic moving-mesh simulations of neutron-star mergers
In the arising era of gravitational-wave (GW) astronomy the demand for the next-generation of neutron-star (NS) merger models has never been so great. By developing the first relativistic moving-mesh simulations of NS mergers, we will be able to reliably link observables of these spectacular events to fundamental questions of physics. Our approach will allow us to maximize the information that can be obtained from different GW oscillations of the postmerger remnant. In this way we will demonstrate the scientific potential of future postmerger GW detections to unravel unknown properties of NSs and high-density matter. Based on our models we will work out the optimal GW data analysis strategy towards this goal. Employing a revolutionary numerical technique we will be able to achieve an unprecedented resolution of the merger outflow. High-resolution simulations of these ejecta are critical to uncover the detailed conditions for nucleosynthesis, specifically, for the rapid-neutron capture process (r-process). The r-process forges the heaviest elements such as gold and uranium, but its astrophysical production site still has to be clarified. Moreover, the nuclear decays in the expanding outflow power electromagnetic counterparts, which are targets of optical survey telescopes (iPTF, ZTF, BlackGEM, LSST). Our multi-disciplinary approach combines hydrodynamical models, nuclear network calculations and light-curve computations to facilitate the interpretation of future electromagnetic observations within a multi-messenger picture. Linking these observables to the underlying outflow properties is pivotal to unravel the still mysterious origin of heavy elements created by the r-process.
[ "Universe Sciences", "Fundamental Constituents of Matter", "Computer Science and Informatics" ]
10.1142/9789814304634_0032
A New Physical Space Approach To Decay For The Wave Equation With Applications To Black Hole Spacetimes
We present a new general method for proving global decay of energy through a suitable spacetime foliation, as well as pointwise decay, starting from an integrated local energy decay estimate. The method is quite robust, requiring only physical space techniques, and circumvents use of multipliers or commutators with weights growing in t. In particular, the method applies to a wide class of perturbations of Minkowski space as well as to Schwarzschild and Kerr black hole exteriors.
[ "Universe Sciences", "Mathematics" ]
10.22323/1.335.0038
Is Dark Energy Simulated By Structure Formation In The Universe
The standard model of cosmology assumes that the Universe can be described to hover around a homogeneous-isotropic solution of Einstein's general theory of relativity. This description needs (sometimes hidden) hypotheses that restrict the generality, and relaxing these restrictions is the headline of a new physical approach to cosmology that refurnishes the cosmological framework. Considering a homogeneous geometry as a template geometry for the in reality highly inhomogeneous Universe must be considered a strong idealization. Unveiling the limitations of the standard model opens the door to rich consequences of general relativity, giving rise to effective (i. e. , spatially averaged) cosmological models that may even explain the longstanding problems of dark energy and dark matter. \\ We explore in this talk the influence of structure formation on average properties of the Universe by discussing: (i) general thoughts on why considering average properties, on the key-issue of non-conserved curvature, and on the global gravitational instability of the standard model of cosmology; (ii) the general set of cosmological equations arising from averaging the scalar parts of Einstein's equations, the generic property of structure formation interacting with the average properties of the Universe in a scale-dependent way, and the description of cosmological backreaction in terms of an effective scalar field.
[ "Universe Sciences", "Fundamental Constituents of Matter" ]
10.1146/annurev-genet-112414-055214
Cell Competition during Growth and Regeneration
Tissue growth and regeneration are autonomous, stem-cell-mediated processes in which stem cells within the organ self-renew and differentiate to create new cells, leading to new tissue. The processes of growth and regeneration require communication and interplay between neighboring cells. In particular, cell competition, which is a process in which viable cells are actively eliminated by more competitive cells, has been increasingly implicated to play an important role. Here, we discuss the existing literature regarding the current landscape of cell competition, including classical pathways and models, fitness fingerprint mechanisms, and immune system mechanisms of cell competition. We further discuss the clinical relevance of cell competition in the physiological processes of tissue growth and regeneration, highlighting studies in clinically important disease models, including oncological, neurological, and cardiovascular diseases.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Physiology in Health, Disease and Ageing" ]
W1791860518
The Reproductive Biology of Shirbot (Barbus grypus Heckel, 1843) in the Maroon River, Iran
Shirbot ( Barbus grypus ) is one of the species in south and southwest of Iran which is greatly favorable to residents of the region. Unfavorable ecological conditions in habitat of this species and overfishing have led to the reduction of the population of shirbot. Therefore, to restore the natural stock of this species, identifying its reproductive cycle associated with its habitat is of a great importance. In this study, the reproductive status of shirbot in the Maroon River in Khuzestan Province was studied in six sampling steps during four seasons. Also, morphological indicators, sex ratio, age of fish, gonadosomatic and hepatosomatic indices, histological changes in the testis and ovary of the fish were studied. The ratio of male fish to female was 2.35 to 1. The maximum value of gonadosomatic index (GSI) is among the specimens aged 3 to 5 years and in March and April. An increase of hepatosomatic index (HIS) during March may indicate the increased activity of liver during vitellogenesis and vitellogenin synthesis which is well verified by histological results of ovarian tissue. Based on our findings we recommend that the maximum reproductive activity of shirbot in the Maroon River starts around the end of March and continues to middle of July.
[ "Environmental Biology, Ecology and Evolution" ]
10.1038/nmeth.4033
Random-access scanning microscopy for 3D imaging in awake behaving animals
Understanding how neural circuits process information requires rapid measurements of activity from identified neurons distributed in 3D space. Here we describe an acousto-optic lens two-photon microscope that performs high-speed focusing and line scanning within a volume spanning hundreds of micrometers. We demonstrate its random-access functionality by selectively imaging cerebellar interneurons sparsely distributed in 3D space and by simultaneously recording from the soma, proximal and distal dendrites of neocortical pyramidal cells in awake behaving mice.
[ "Neuroscience and Disorders of the Nervous System", "Systems and Communication Engineering" ]
10.1007/s00114-011-0853-5
A novel marine silk
The discovery of a novel silk production system in a marine amphipod provides insights into the wider potential of natural silks. The tube-building corophioid amphipod Crassicorophium bonellii produces from its legs fibrous, adhesive underwater threads that combine barnacle cement biology with aspects of spider silk thread extrusion spinning. We characterised the filamentous silk as a mixture of mucopolysaccharides and protein deriving from glands representing two distinct types. The carbohydrate and protein silk secretion is dominated by complex β-sheet structures and a high content of charged amino acid residues. The filamentous secretion product exits the gland through a pore near the tip of the secretory leg after having moved through a duct, which subdivides into several small ductules all terminating in a spindle-shaped chamber. This chamber communicates with the exterior and may be considered the silk reservoir and processing/mixing space, in which the silk is mechanically and potentially chemically altered and becomes fibrous. We assert that further study of this probably independently evolved, marine arthropod silk processing and secretion system can provide not only important insights into the more complex arachnid and insect silks but also into crustacean adhesion cements.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Materials Engineering" ]
US 2017/0044569 W
METHOD AND ASSEMBLY FOR A MULTIPLE COMPONENT CORE ASSEMBLY
A component is formed from a component material introduced into a mold assembly (700). The mold assembly includes a mold (702) that has a cavity (708) defined therein by an interior wall (706). The cavity receives the component material in a molten state to form the component. A multiple component core (400) assembly is positioned with respect to the mold and has a first core component (402) attached to a second core component (404) at a core split line (602). A core connection component (500) is attached to each of the first and second core components at the core split line, such that the first core component is held adjacent the second core component at the core split line. The core connection component is formed from a connection component material that is at least partially absorbable by the component material.
[ "Products and Processes Engineering", "Materials Engineering" ]
651288
Composite solid electrolyte development for all solid state lithium batteries (cse-lbatts)
Rechargeable lithium batteries are a game-changing technology for electric vehicles and portable electronics due to their benefits in energy density. However, safety is a concern because of the use of flammable organic liquid electrolytes in lithium batteries. Solid state electrolytes not only address the safety issue but also eliminate the issues related to Li metal anode and thus improve gravimetric as well as volumetric energy density, cycle life, and operable temperature range. Whilst there have been recent efforts to create solid state batteries, no real transformative progress has yet been made in this area. The work performed in this proposal will address the limitations of commercialization of solid-state lithium batteries whilst utilizing novel composite solid electrolyte (CSE) fabrication techniques to design composite solid electrolytes. The proposed undertaking presents an excellent training and career acceleration opportunity - enabling me to apply my academic research in an industrial setting whilst also gaining world class advanced innovation management and product development techniques. This will help transform my career and my applied academic profile into a leading authority in solid state lithium batteries and composite solid electrolyte technology.
[ "Materials Engineering", "Synthetic Chemistry and Materials", "Condensed Matter Physics" ]
203239
Nanoscale Magnetization Dynamics
The aim of NOMAD is to develop frontier approaches to control the magnetodynamic properties of nanometer-sized molecular and metallic elements. The first part of the project recognizes the importance of molecular materials for future technologies based on magnetoelectronic devices. It addresses the stabilization of the magnetic moment of individual molecules beyond their intrinsic limits (slow timescale). Moreover, the construction of spin-sensitive probes with spatial atomic-resolution and a dynamic range extending up to the GHz regime is proposed. These shall be used to characterize magnetodynamic phenomena of individual molecules and metal particles in a nanoscopic environment (fast timescale). The second part relates to the control of magnetic relaxation and coercivity in nanoscale metallic particles. Electric-field manipulation of ferromagnetism has been proven in dilute magnetic semiconductors at temperatures below 50 K. Here, the aim is to demonstrate and optimize electric field-induced changes of the magnetic anisotropy energy in metal layers and nanoparticles embedded in a double tunnel junction, providing a direct or indirect (transition-driven) handle to their magnetic dynamics at room temperature. Metal-based materials constitute the mainstay of present magnetic technology; their electric-field actuation would lead to simpler and power-saving devices that process magnetic information using electrical signals.
[ "Condensed Matter Physics", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1021/cm200399t
Hybrid, silica-coated, Janus-like plasmonic-magnetic nanoparticles
Hybrid plasmonic-magnetic nanoparticles possess properties that are attractive in bioimaging, targeted drug delivery, in vivo diagnosis, and therapy. The stability and toxicity, however, of such nanoparticles challenge their safe use today. Here, biocompatible, SiO2-coated, Janus-like Ag/Fe2O3 nanoparticles are prepared by one-step, scalable flame aerosol technology. A nanothin SiO2 shell around these multifunctional nanoparticles leaves intact their morphology and magnetic and plasmonic properties but minimizes the release of toxic Ag+ ions from the nanosilver surface and its direct contact with live cells. Furthermore, this silica shell hinders flocculation and allows for easy dispersion of such nanoparticles in aqueous and biological buffer (PBS) solutions without any extra functionalization step. As a result, these hybrid particles exhibited no cytotoxicity during bioimaging and remained stable in suspension with no signs of agglomeration and sedimentation or settling. Their performance as biomarkers was explored by selectively binding them with live tagged Raji and HeLa cells enabling their detection under dark-field illumination. Therefore, these SiO2-coated Ag/Fe2O3 nanoparticles do not exhibit the limiting physical properties of each individual component but retain their desired functionalities facilitating thus, the safe use of such hybrid nanoparticles in bioapplications.
[ "Condensed Matter Physics", "Materials Engineering", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Prevention, Diagnosis and Treatment of Human Diseases" ]
W1911331113
Humidity sensing properties of Cu2O-PEPC nanocomposite films
A blend of copper oxide nanopowder (Cu2O), 3 wt.%, and poly-N-epoxypropylcarbazole (PEPC), 2 wt.%, in benzol was drop-casted on glass substrates with pre-deposited surface-type silver electrodes for the fabrication of Cu2O-PEPC nanocomposite thin films. The thicknesses of the Cu2O-PEPC films were in the range of 10–13 μm. The effect of humidity on the electrical properties of the nanocomposite films was investigated by measuring the capacitance and dissipation of the samples at two different frequencies of the applied voltage: 120 Hz and 1 kHz. The AC resistance of the samples was determined from the dissipation values, and the DC resistance was measured directly. The effect of ageing on the humidity sensing properties of the nanocomposite was observed. After ageing, it was observed that at 120 Hz and 1 kHz, under a humidity of up to 86% RH, the capacitance of the cell increased by 85 and 8 times, and the resistance decreased by 345 and 157 times, accordingly, with respect to 30% RH conditions. It was found that with an increase in frequency, the capacitance and resistance of the samples decreased. It is assumed that the humidity response of the cell is associated with the diffusion of water vapors and doping of the semiconductor nanocomposite by water molecules.
[ "Condensed Matter Physics", "Materials Engineering", "Physical and Analytical Chemical Sciences" ]
10.1080/17546559.2014.889321
Sign Of The Cross Contexts For The Ivory Cross Of San Millan De La Cogolla
This article focuses on the surviving arms of the ivory cross of San Millan de la Cogolla and proposes a new interpretation for its striking Cordoban visual aesthetic. The article rejects an interpretive framework privileging religious divisions between Muslims and Christians. Instead this essay emphasizes the kinship and political ties that connected the Andalusi caliph ‘Abd al- Raḥmān III (r. 912–61) and Toda, Queen of Pamplona. Queen Tota, as she is named in Latin charters, or Tuta bint Asnar, as she is named in the Umayyad court chronicle, has long been recognized as a key figure in the political milieu of tenth-century Iberia. Using the material evidence of the cross as a departure point, the article considers the Arabic and Latin texts that point to Tota's centrality not only to the politics, but also to cultural transfer between al-Andalus and Hispania. The presence of the ivory cross at San Millan, and its Cordoban aesthetic, I argue, are symptomatic of Tota's strategic use of her kinship connecti. . .
[ "Texts and Concepts", "The Study of the Human Past", "Studies of Cultures and Arts" ]
10.1080/23745118.2015.1061806
Citizenship And The Practice Of Governance In South East Europe
The key objective of this Conclusion is to highlight the broader conceptual, empirical and methodological contributions of this edited volume. Reflecting on the paired articles, the conclusion explores the implications of the collection on the interplay between the modes of governance that constitute citizenship regimes and their effects on ‘lived citizenship’ that characterise individuals' experiences of this governance.
[ "Institutions, Governance and Legal Systems", "The Social World and Its Interactions" ]
10.1021/acs.langmuir.6b02343
Thermodynamic Description of Synergy in Solvent Extraction: I. Enthalpy of Mixing at the Origin of Synergistic Aggregation
Revisiting aggregation of extractant molecules into water-poor mixed reverse micelles, we propose in this paper to identify the thermodynamic origins of synergy in solvent extraction. Considering that synergistic extraction properties of a mixture of extractants is related to synergistic aggregation of this mixture, we identify here the elements at the origin of synergy by independently investigating the effect of water, acid, and extracted cations. Thermodynamic equations are proposed to describe synergistic aggregation in the peculiar case of synergistic solvent extraction by evaluating critical aggregation concentration (CAC) as well as specific interactions between extractants due to the presence of water, acid and cations. Distribution of two extractant molecules in the free extractants and in reverse micelles was assessed, leading to an estimation of the in-plane interaction parameter between extractants in the aggregates as introduced by Bergström and Eriksson (Bergström, M. ; Eriksson, J. C. A Theoretical Analysis of Synergistic Effects in Mixed Surfactant Systems. Langmuir 2000, 16, 7173−7181). Based on this model, we study the N,Nand-dimethyl-N,Nand-dioctylhexylethoxymalonamide (DMDOHEMA) and di(2-ethylexyl) phosphoric acid (HDEHP) mixture and show that adding nitric acid enhances synergistic aggregation at the equimolar ratio of the two extractants and that this configuration can be related to a favored enthalpy of mixing.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
175415
The materials genome in action
It is now possible to make an enormous spectrum of different, novel nanoporous materials simply by changing the building blocks in the synthesis of Metal Organic Frameworks (MOF) or related materials. This unique chemical tunability allows us to tailor-make materials that are optimal for a given application. The promise of finding just the right material seems remote however: because of practical limitations we can only ever synthesize, characterize, and test a tiny fraction of all possible materials. To take full advantage of this development, therefore, we need to develop alternative techniques, collectively referred to as Materials Genomics, to rapidly screen large numbers of materials and obtain fundamental insights into the chemical nature of the ideal material for a given application. The PI will tackle the challenge and promise posed by this unprecedented chemical tunability through the development of a multi-scale computational approach, which aims to reliably predict the performance of novel materials before synthesis. We will develop methodologies to generate libraries of representative sets of synthesizable hypothetical materials and perform large-scale screening of these libraries. These studies should give us fundamental insights into the common molecular features of the top-performing materials. The methods developed will be combined into an open access infrastructure in which our hypothetical materials are publicly accessible for data mining and big-data analysis. The project is organized in three Work Packages, each centered around finding better materials for carbon capture: (1) screen materials for gas separations and develop the tools to predict the best materials for carbon capture; (2) gain insights into and develop a computational methodology for screening the mechanical properties of nanoporous materials; (3) achieve an understanding of the amine-CO2 chemistry in diamine-appended MOFs and use this to predict their performance.
[ "Materials Engineering", "Synthetic Chemistry and Materials", "Computer Science and Informatics", "Physical and Analytical Chemical Sciences" ]
US 2007/0078959 W
WALKER HAVING AUTOMATICALLY ACTIVATED PROTECTIVE DYNAMIC PADDING
A walking aid (100, 200) has been configured with static padding (112) and air bags (114) to protect the user in case of a fall. The air bags (114) are generally not deployed. However, the walking aid has a tilt sensor (128) which, when a fall is detected, triggers air bag ignitors (116). In one embodiment, the tilt sensor (128) may comprise one or an array of sensors, and may further be coupled through microprocessor control to a dynamic active suspension ( 102) that controls both the height of the walker and the height of individual legs such that the walker will land softly, while adjusting individual leg heights where necessary or appropriate to stabilize the user to reduce the chance of a fall. In addition to providing more extensive protection for the user, the walking aid has several additional options which increase the comfort and convenience it offers. Such options can include locking hinges (120), allowing the walking aid to fold up; rubber (124) on the end of the legs where they contact the ground; wheels (126) on the legs; brakes for the wheels; height adjustable legs (102, 122); a water bottle holder; a basket; a removable or folding seat; a dashboard (140) including various communications devices such as cellular telephones, emergency call buttons, locators, and the like; and audio-video devices.
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]
692739
Expecting Ourselves: Embodied Prediction and the Construction of Conscious Experience
This project (short name, XSPECT) aims to harness the emerging science of the predictive brain to deliver new insights into the nature, scope, mechanisms and (most importantly) the very possibility of conscious experience. The project thus explores and extends the vision of the brain as an inner engine continuously striving to predict the incoming sensory barrage. The key innovation is to consider this increasingly popular vision in the special context of embodied agents able to predict many of their own evolving states and responses – agents able to ‘expect themselves’. These crucial self-expectations span the interoceptive (targeting the internal sensory flows signaling our own physiological states, such as hunger, arousal, itch, and muscular and visceral sensations) and the exteroceptive (targeting the world, and our own behaviors as they might unfold over multiple scales of space and time). XSPECT explores the idea that such interacting states of complex, layered self-prediction hold the key to understanding much that is puzzling about conscious experience. The project is divided into three simultaneously active sub-projects. The first sub-project concerns relations between prediction, motor action, and experience. The second sub-project targets the role of interoceptive prediction in the construction of experience. The third sub-project considers ways in which more reflective forms of conscious experience (involving agency, selfhood, and the introspection of own experiential states) are further enriched by a spiraling array of socially mediated higher-level self-predictions. XSPECT will combine integrative philosophical argument, collaborative experimentation, and leading edge interdisciplinary research and discussion, leveraging two very successful but under-communicating research programs (‘embodied cognition’ and ‘the predictive brain’) to offer new perspectives on the puzzle of conscious experience.
[ "Neuroscience and Disorders of the Nervous System", "The Human Mind and Its Complexity" ]
185128
Port-Cities: integrating sustainability
Port Cities can be seen as multidimensional laboratories where challenges connected with urban mobility are more complex due to the dual system of gravity centre: the city, the port, not to mention their shared hinterland.These peculiarities are at once a challenge and an opportunity, as they provide scope for planning, researching and implementing integrated mobility solutions in distinctively complex urban contexts. Civitas PORTIS designs, demonstrates and evaluates integrated sets of sustainable mobility measures in 5 major port cities located on the North Sea (Aberdeen and Antwerp), the Mediterranean Sea (Trieste), the Black Sea (Constanta), and Baltic Sea (Klaipeda). The project also involves a major international follower port city on the East China Sea (Ningbo). Thanks to the Civitas Initiative, the partner cities expect to prove that more efficient and sustainable mobility is conducive to the establishment of vital and multi-modal hubs for urban, regional, national and International movements of passengers and goods. To do this, they establish integrated living laboratories clustering local measures according to four major aspects of sustainable urban mobility: 1. Governance: to increase port-city collaborative planning and participation, leading to enhanced forms of SUMPs. 2. People: to foster less car-dependent mobility styles, leading to modal shift in favour of collective and more active transport. 3. Transport system: to strengthen the efficiency of road traffic management to/from the port and through the city, and foster the use of clean vehicles. 4. Goods: to enhance logistics and freight transport, improving the efficiency and coordination of city, port and regional freight movements. Working with port cities, Civitas PORTIS will generate a strong and twofold replication potential: 1) specifically to other port cities, and 2) more generally to cities presenting major transport nodes and attractors for the benefit of the whole CIVITAS Initiative.
[ "Human Mobility, Environment, and Space", "Products and Processes Engineering", "Institutions, Governance and Legal Systems" ]
10.1021/acs.jpcc.6b06447
Grafting Spiropyran Molecular Switches on TiO<inf>2</inf>: A First-Principles Study
To explore the optoelectronic properties of spiropyran molecular switches adsorbed onto TiO2 anatase surfaces, we performed a density functional theory (DFT)/time-dependent density functional theory (TD-DFT) study considering the two isomeric forms of the photochromes anchored by both their sides. A comparison between the features of the hybrid and isolated systems is proposed to probe the adsorption effects on both subsystems. This comparison considered, on the one hand, the density of states and the alignment of the energy levels, and, on the other hand, the UV-visible spectra of these systems. We show that several electronic and optical characteristics of the hybrid systems are modulated by the open/closed state of the photochromes. These properties are also modified by the localization of the anchor group on the photochrome.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1101/cshperspect.a004564
Calcium signaling in synapse-to-nucleus communicationI
Changes in the intracellular concentration of calcium ions in neurons are involved in neurite growth, development, and remodeling, regulation of neuronal excitability, increases and decreases in the strength of synaptic connections, and the activation of survival and programmed cell death pathways. An important aspect of the signals that trigger these processes is that they are frequently initiated in the form of glutamatergic neurotransmission within dendritic trees, while their completion involves specific changes in the patterns of genes expressed within neuronal nuclei. Accordingly, two prominent aims of research concerned with calcium signaling in neurons are determination of the mechanisms governing information conveyance between synapse and nucleus, and discovery of the rules dictating translation of specific patterns of inputs into appropriate and specific transcriptional responses. In this article,we present an overviewof the avenues bywhich glutamatergic excitation of dendrites may be communicated to the neuronal nucleus and the primary calcium-dependent signaling pathways by which synaptic activity can invoke changes in neuronal gene expression programs.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
CA 2012000202 W
MAGNETIC INSTALLATION AND RETRIEVAL TOOL FOR FLUID LIFT PLUNGERS
A plunger installation and retrieval tool incorporates a magnet which magnetically supports a fluid lift plunger during insertion into or retrieval from a lubricator on a natural gas wellhead. The magnet is housed in a magnet holder suspended from an elongate hanger member the upper end of which is connected to a hanger support. An actuating rod slidably extends through the hanger support and through bores in the magnet and magnet holder, such that a downward force applied to the actuating rod will cause the lower end of the actuating rod to project below the magnet and break its magnetic bond with the plunger, thus releasing the plunger from the tool. The tool may be provided with a cylindrical skirt fitting closely around the upper end of the plunger to prevent laterally loading that could break the magnetic bond during plunger insertion and retrieval.
[ "Products and Processes Engineering", "Materials Engineering" ]
Q4250812
APOYO A LA LIQUIDEZ PARA LAS MICROEMPRESAS AFECTADAS POR LA EMERGENCIA DE LA COVID
APOYO A LA LIQUIDEZ DE LAS MICROEMPRESAS Y LAS PEQUEÑAS EMPRESAS DE LOS SECTORES MINORISTA, DE SUMINISTRO Y DE SERVICIOS PERSONALES CUYA ACTIVIDAD HA SIDO SUSPENDIDA COMO CONSECUENCIA DEL DECRETO DEL PRIMER MINISTRO DE 11 DE MARZO DE 2020
[ "Individuals, Markets and Organisations", "Institutions, Governance and Legal Systems" ]
W4220743234
Pius XI. in der spanischen Arena
Abstract Der Autor beleuchtet die Haltung des Heiligen Stuhls im Spanischen Bürgerkrieg. Er analysiert, warum Papst Pius XI. Partei zugunsten der Aufständischen unter General Franco ergriff, lange bevor der Ausgang des Konflikts absehbar war. Quellen aus den Archiven des Vatikan eröffnen neue Perspektiven auf Entscheidungen und Strategien des Heiligen Stuhls. Sie lassen darauf schließen, dass der Papst vor allem aus einem Grund auf Franco zuging: Er wollte der Gefahr einer nationalsozialistischen Infiltration des Franco-Staats in statu nascendi begegnen. Nachdem im Deutschen Reich 1937 der „Kirchenkampf“ eskaliert war, vollzog der Heilige Stuhl einen radikalen Strategiewechsel in seiner Spanienpolitik. Der völkerrechtlichen Anerkennung Francos folgte ein intensives diplomatisches Engagement mit dem Ziel, den deutschen Einfluss wenn nicht zu brechen, so doch zu marginalisieren. Der Vatikan gewann das ideologische Ringen gegen Hitler: Franco gründete sein Regime auf das Fundament einer traditionalistisch-reaktionären Weltanschauung; die katholische Kirche wurde zu einem seiner Eckpfeiler.
[ "The Study of the Human Past", "Institutions, Governance and Legal Systems" ]
10.1007/s11051-018-4217-3
Functional metabolite assemblies—a review
Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Physiology in Health, Disease and Ageing" ]
W1936898905
The burden of behavioral risk factors for cardiovascular disease in Europe. A significant prevention deficit
The study objective was to assess the burden of major cardiovascular disease (CVD) behavioral risk factors (BRFs) (i.e., smoking, excess body weight, physical inactivity, risky alcohol consumption) among individuals in the community with and without CVD history.For the current study, a subset of the data from the Survey of Health, Ageing and Retirement in Europe (SHARE) was analyzed, which were collected from 26,743 individuals aged 50+ years old, during the 1st wave of SHARE in 2004/05 in eleven European countries.Among those with CVD, there is a statistically significant higher percentage of inactive individuals (81.4% vs. 69.5 among those without CVD), and of individuals with excess body weight (64.3%) or obese (21.6%). Patients with CVD had a lower prevalence of smoking and risky alcohol consumption in most countries, whereas the prevalence of high body weight and physical inactivity was higher in CVD patients compared to individuals without CVD in almost all countries. More than half of the population has at least two BRFs, with a significantly higher prevalence of multiple BRFs among those diagnosed with CVD.Study findings suggest that a significant burden of behavioral risk factors for CVD remains in the population overall but also among patients diagnosed with CVD. Given the significant prevalence of BRFs, the prevention benefits would be immense for all stakeholders involved and negligence would be perilous.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physiology in Health, Disease and Ageing" ]
10.1073/pnas.1418450112
β-Helical architecture of cytoskeletal bactofilin filaments revealed by solid-state NMR
Bactofilins are a widespread class of bacterial filament-forming proteins, which serve as cytoskeletal scaffolds in various cellular pathways. They are characterized by a conserved architecture, featuring a central conserved domain (DUF583) that is flanked by variable terminal regions. Here, we present a detailed investigation of bactofilin filaments fromCaulobacter crescentusby high-resolution solid-state NMR spectroscopy. De novo sequential resonance assignments were obtained for residues Ala39 to Phe137, spanning the conserved DUF583 domain. Analysis of the secondary chemical shifts shows that this core region adopts predominantly β-sheet secondary structure. Mutational studies of conserved hydrophobic residues located in the identified β-strand segments suggest that bactofilin folding and polymerization is mediated by an extensive and redundant network of hydrophobic interactions, consistent with the high intrinsic stability of bactofilin polymers. Transmission electron microscopy revealed a propensity of bactofilin to form filament bundles as well as sheet-like, 2D crystalline assemblies, which may represent the supramolecular arrangement of bactofilin in the native context. Based on the diffraction pattern of these 2D crystalline assemblies, scanning transmission electron microscopy measurements of the mass per length of BacA filaments, and the distribution of β-strand segments identified by solid-state NMR, we propose that the DUF583 domain adopts a β-helical architecture, in which 18 β-strand segments are arranged in six consecutive windings of a β-helix.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physical and Analytical Chemical Sciences" ]
10.1103/PhysRevLett.121.013601
Emergent Universal Dynamics for an Atomic Cloud Coupled to an Optical Waveguide
We study the dynamics of a single collective excitation in a cold ensemble of atoms coupled to a one-dimensional waveguide. The coupling between the atoms and the photonic modes provides a coherent and a dissipative dynamics for this collective excitation. While the dissipative part accounts for the collectively enhanced and directed emission of photons, we find a remarkable universal dynamics for increasing atom numbers exhibiting several revivals under the coherent part. While this phenomenon provides a limit on the intrinsic dephasing for such a collective excitation, a setup is presented where the universal dynamics can be explored.
[ "Condensed Matter Physics", "Fundamental Constituents of Matter" ]
628563
The “extended-personal reality”: augmented recording and transmission of virtual senses through artificial-intelligence
Social media has transformed the way we communicate through text, images, and videos. Despite recent technological avenues, virtual reality (VR) has not been incorporated in social platforms, hence limiting the comprehensive sharing of an EXPERIENCE. This project makes real the complex interplay between multisensory perception, emotional responses, past experiences, and perspective of the future also by disentangling the mental representation of self in space and time. The new Extended-Personal Reality technological and scientific paradigms will move Europe to the future generation of extended social interactions by allowing the public at large to i) create their own VR environments as they do photos and videos without the need for technical skills, ii) create virtual simulations eliciting unique psychological, cognitive, neurophysiological, and behavioural responses, iii) automatically generate VR environments from neurophysiological data, iv) easily manipulate VR environments to communicate and elicit specific emotions, v) manipulate perceived reality to effectively treat psychiatric disorders. EXPERIENCE embeds advanced artificial intelligence routines merging information from a person’s Extended-Personal Reality to inform manipulation tools including neuromodulation, multisensory biofeedback (audio, video, haptics), and subjective perception of time-space. EXPERIENCE will produce extremely realistic reproductions of the user's past and may re-administer it by modulating the associated emotional states on demand. Within a large number of research and innovation avenues, EXPERIENCE will prioritise novel diagnosis and treatment of affective disorders commonly associated with altered multisensory perception like depression, anxiety, and eating disorders. A plethora of innovative technological paradigms including gaming, e-learning, and neuroeconomics will be in the commercial exploitations, including the opening of a new market for actually selling EXPERIENCEs
[ "Neuroscience and Disorders of the Nervous System", "Computer Science and Informatics", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1145/3408302
Why Developers Refactor Source Code A Mining Based Study
Refactoring aims at improving code non-functional attributes without modifying its external behavior. Previous studies investigated the motivations behind refactoring by surveying developers. With the aim of generalizing and complementing their findings, we present a large-scale study quantitatively and qualitatively investigating why developers perform refactoring in open source projects. First, we mine 287,813 refactoring operations performed in the history of 150 systems. Using this dataset, we investigate the interplay between refactoring operations and process (e. g. , previous changes/fixes) and product (e. g. , quality metrics) metrics. Then, we manually analyze 551 merged pull requests implementing refactoring operations and classify the motivations behind the implemented refactorings (e. g. , removal of code duplication). Our results led to (i) quantitative evidence of the relationship existing between certain process/product metrics and refactoring operations and (ii) a detailed taxonomy, generalizing and complementing the ones existing in the literature, of motivations pushing developers to refactor source code.
[ "Computer Science and Informatics" ]
10.1186/1471-2164-11-693
The Venom Composition Of The Parasitic Wasp Chelonus Inanitus Resolved By Combined Expressed Sequence Tags Analysis And Proteomic Approach
Parasitic wasps constitute one of the largest group of venomous animals. Although some physiological effects of their venoms are well documented, relatively little is known at the molecular level on the protein composition of these secretions. To identify the majority of the venom proteins of the endoparasitoid wasp Chelonus inanitus (Hymenoptera: Braconidae), we have randomly sequenced 2111 expressed sequence tags (ESTs) from a cDNA library of venom gland. In parallel, proteins from pure venom were separated by gel electrophoresis and individually submitted to a nano-LC-MS/MS analysis allowing comparison of peptides and ESTs sequences. About 60% of sequenced ESTs encoded proteins whose presence in venom was attested by mass spectrometry. Most of the remaining ESTs corresponded to gene products likely involved in the transcriptional and translational machinery of venom gland cells. In addition, a small number of transcripts were found to encode proteins that share sequence similarity with well-known venom constituents of social hymenopteran species, such as hyaluronidase-like proteins and an Allergen-5 protein. An overall number of 29 venom proteins could be identified through the combination of ESTs sequencing and proteomic analyses. The most highly redundant set of ESTs encoded a protein that shared sequence similarity with a venom protein of unknown function potentially specific of the Chelonus lineage. Venom components specific to C. inanitus included a C-type lectin domain containing protein, a chemosensory protein-like protein, a protein related to yellow-e3 and ten new proteins which shared no significant sequence similarity with known sequences. In addition, several venom proteins potentially able to interact with chitin were also identified including a chitinase, an imaginal disc growth factor-like protein and two putative mucin-like peritrophins. The use of the combined approaches has allowed to discriminate between cellular and truly venom proteins. The venom of C. inanitus appears as a mixture of conserved venom components and of potentially lineage-specific proteins. These new molecular data enrich our knowledge on parasitoid venoms and more generally, might contribute to a better understanding of the evolution and functional diversity of venom proteins within Hymenoptera.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
W2069723146
A flexible modelling environment for integrated urban water harvesting and re-use
The steady increase of urban population and the possible effects of climate change that may adversely affect the amount of water available in current water supply systems, makes the study of stormwater and rainwater harvesting and wastewater recycling a high priority. The basic proposition is that any system of water supply that can reduce the amount of water drawn from main reservoirs will be of benefit to the whole supply region especially in terms of drought security. This paper describes a versatile modelling framework which can simulate a wide variety of combinations of centralised and decentralised Integrated Urban Water Management schemes from the allotment to the whole suburb scale. The framework combines two modelling approaches. The first, called urbanCycle, simulates water supply and demand, stormwater and wastewater using allotments as the basic building block. Although urbanCycle can simulate processes in great detail, it assumes that the network forms a directed acyclic graph. This simplifies the connectivity logic but precludes investigation of systems with decentralised storage, feedbacks and multiple supply paths. To overcome this, a second model, called urbanNet, based on network linear programming, is embedded in the urbanCycle framework to enable the modelling of recycling and harvesting options, as well as on-the-fly supply and demand decision making, based on objectives rather than pre-set operating rules.
[ "Products and Processes Engineering", "Earth System Science", "Systems and Communication Engineering" ]
10.1145/3360589
Scala Implicits Are Everywhere A Large Scale Study Of The Use Of Scala Implicits In The Wild
The Scala programming language offers two distinctive language features implicit parameters and implicit conversions, often referred together as implicits. Announced without fanfare in 2004, implicits have quickly grown to become a widely and pervasively used feature of the language. They provide a way to reduce the boilerplate code in Scala programs. They are also used to implement certain language features without having to modify the compiler. We report on a large-scale study of the use of implicits in the wild. For this, we analyzed 7,280 Scala projects hosted on GitHub, spanning over 8. 1M call sites involving implicits and 370. 7K implicit declarations across 18. 7M lines of Scala code.
[ "Computer Science and Informatics" ]
10.1126/sciadv.aau5363
Multicomponent new particle formation from sulfuric acid, ammonia, and biogenic vapors
A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NOx) and sulfur oxides (SOx) from fossil fuel combustion, as well as ammonia (NH3) from livestock and fertilizers. Here, we show how NOxsuppresses particle formation, while HOMs, sulfuric acid, and NH3have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
W2257004173
High doses of alcohol during pregnancy cause DNA damages in osteoblasts of newborns rats
Alcohol exerts teratogenic effects and its consumption during pregnancy can cause deficit of bone development. The aim of the current study was to evaluate the genotoxic effects of prenatal exposure to ethanol on newborn rat osteoblasts.Wistar rats were initially divided into two groups: Ethanol group which received Ethanol 20% V/V in liquid diet and solid diet ad libitum, and Control group, which received solid diet and water ad libitum. Each group received a specific diet for 8 weeks before breeding and throughout three weeks of gestation and the treatment was finished on the day the pups were killed. On the fifth day of life, the pups from each group were killed for removal of the calvaria and isolation of osteogenic cells by sequential enzymatic digestion. The cells were cultured for a maximum period of 14 days. The detection of genotoxic effects of alcohol was investigated by the comet and the micronucleus assay.Micronucleus and comet assay showed significant increases in DNA damage at 7 days in Ethanol group (p = 0.0302, p = 0.0446, respectively). However, at 14 days both assay showed no significant difference between the groups (p = 0.6194, p = 0.8326, respectively).Our results showed that prenatal exposure to ethanol induced DNA damage in osteoblasts, as shown by micronucleus formation and higher percentage of DNA in the comet tail. It can be concluded that prenatal exposure to ethanol damages osteoblast DNA in newborns exposed to high doses of ethanol during pregnancy, suggesting that prenatal ethanol consumption has a direct effect on fetal osteoblasts.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Physiology in Health, Disease and Ageing" ]
10.2752/174589311X12893982233632
Taste In Two Tongues A Southeast Asian Study Of Semantic Convergence
ABSTRACTThis article examines vocabulary for taste and flavor in two neighboring but unrelated languages (Lao and Kri) spoken in Laos, southeast Asia. There are very close similarities in underlying semantic distinctions made in the taste/flavor domain in these two languages, not just in the set of basic tastes distinguished (sweet, salty, bitter, sour, umami or glutamate), but in a series of further basic terms for flavors, specifying texture and other sensations in the mouth apart from pure taste (e. g. starchy, dry in the mouth, minty, tingly, spicy). After presenting sets of taste/flavor vocabulary in the two languages and showing their high degree of convergence, the article discusses some methodological and theoretical issues that arise from the observation of close convergence in semantic structure across languages, in particular the issue of how much inter-speaker variation is possible not only across apparently highly convergent systems, but also within languages. The final section raises possible. . .
[ "The Human Mind and Its Complexity", "Studies of Cultures and Arts" ]
US 4534501 A
Methods for forming rough ruthenium-containing layers and structures/methods using same
A method for forming a rough ruthenium-containing layer on the surface of a substrate assembly includes providing a ruthenium-containing precursor into the reaction chamber. A rough ruthenium layer may be deposited on the surface of the substrate assembly at a rate of about 100 Å/minute to about 500 Å/minute using the ruthenium-containing precursor. Further, a rough ruthenium oxide layer may be formed by providing a ruthenium-containing precursor and an oxygen-containing precursor into the reaction chamber to deposit the rough ruthenium oxide layer on the surface of the substrate assembly at a rate of about 100 Å/minute to about 1200 Å/minute. An anneal of the layers may be performed to further increase the roughness. In addition, conductive structures including a rough ruthenium layer or a rough ruthenium oxide layer are provided. Such layers may be used in conjunction with non-rough ruthenium and/or non-rough ruthenium oxide layers to form conductive structures. For example, such structures may be part of a capacitor structure, e.g., bottom electrode of a capacitor.
[ "Materials Engineering", "Synthetic Chemistry and Materials" ]
W1625365640
Sudden cardiac and sudden unexpected death related to antipsychotics: A meta-analysis of observational studies
To estimate the risk of sudden cardiac death (SCD) or sudden unexpected death (SUD) related to individual antipsychotics, a meta-analysis of observational studies was performed. Adjusted odds ratio (OR) of SCD/SUD with 95% confidence intervals (CI) were extracted and pooled; heterogeneity was studied using Q statistic and I(2) index, and its potential causes (e.g., hERG blockade potency) explored using meta-regression. Two cohort (740,306 person-years) and four case-control (2,557 cases; 17,670 controls) studies, investigating nine antipsychotics, were included. Compared with nonusers, the risk was increased for quetiapine (OR = 1.72, 95% CI: 1.33-2.23), olanzapine (OR = 2.04, 1.52-2.74), risperidone (OR = 3.04, 2.39-3.86), haloperidol (OR = 2.97, 1.59-5.54), clozapine (OR = 3.67, 1.94-6.94), and thioridazine (OR = 4.58, 2.09-10.05). Heterogeneity was found (Q = 20.0, P = 0.01; I(2) = 60.0%), and the increasing mean hERG blockade potency (P = 0.01) accounted for 43% of this. The SCD/SUD risk differed between individual antipsychotics, and mean hERG blockade potency could be an explanatory factor. This should be considered when initiating antipsychotic treatment.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physiology in Health, Disease and Ageing" ]
678899
Elucidation of autophagy using novel chemical probes
The interest on autophagy, an evolutionarily conserved process in eukaryotes, has enormously increased in the last years, since autophagy is involved in many diseases such as cancer and neurodegenerative disorders. Autophagosome formation is the key process in autophagy. Despite extensive work, the model of autophagosome formation is not yet well established. Some important questions on autophagosome biogenesis remain to be elusive, such as where the bona fide marker protein of autophagosome, LC3, is lipidated, how lipidated LC3 functions in autophagosome formation, and how the proteins for LC3 lipidation and delipidation are involved in autophagosome formation. Although genetic approaches have been useful to identify genes involved in autophagy, they are chronic and thereby the dynamics of phenotypic change cannot be followed, making them not suited for study highly dynamic process such as autophagosome formation. Herein, I propose to develop and use novel chemical probes to address these issues. First, I plan to prepare semi-synthetic caged LC3 proteins and apply them to monitor dynamics of autophagosome formation in the cell in order to address those questions on autophagosome formation. The semi-synthetic LC3 proteins are expected to confer a temporal control and to realize manipulation of protein structure, which renders such studies possible. Second, I intend to develop a versatile approach targeting specific endogenous proteins using a reversible chemically induced dimerization (CID) system, termed as “knock on and off” strategy. I plan to use this approach to elucidate the function of two distinct PI3K complexes in autophagosome formation. On one hand, the establishment of novel approaches will open up a new avenue for studying biological processes. On the other hand, the use of the tool will reveal the mechanism of autophagy.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Physical and Analytical Chemical Sciences" ]
10.21809/rilemtechlett.2016.13
On the use of the Jander equation in cement hydration modelling
The equation of Jander [W. Jander, Z. Anorg. Allg. Chem. (1927) 163: 1-30] is often used to describe the kinetics of dissolution of solid cement grains, as a component of mathematical descriptions of the broader cement hydration process. The Jander equation can be presented as kt/R2 =[1-(1-α) (1/3) ]2 where k is a constant, t is time, R is the initial radius of a solid reactant particle, and α is the fractional degree of reaction. This equation is attractive for its simplicity and apparently straightforward derivation. However, the derivation of the Jander equation involves an approximation related to neglect of particle surface curvature which means that it is strictly not correct for anything beyond a very small extent of reaction. This is well documented in the broader literature, but this information has not been effectively propagated to the field of cement science, which means that researchers are continuing to base models on this erroneous equation. It is recommended that if the assumptions of diffusion control and unchanging overall particle size which lead to the selection of the Jander equation are to be retained, it is preferable to instead use the Ginstling-Brounshtein equation [A. M. Ginstling, B. I. Brounshtein, J. Appl. Chem. USSR (1950) 23: 1327-1338], which does correctly account for particle surface curvature without significant extra mathematical complication. Otherwise, it is possible (and likely desirable) to move to more advanced descriptions of particle-fluid reactions to account for factors such as dimensional changes during reaction, and the possibility of rate controlling influences other than diffusion.
[ "Physical and Analytical Chemical Sciences", "Materials Engineering" ]
10.1017/s1743921311015365
Global magnetic cycles in rapidly rotating younger suns
AbstractObservations of sun-like stars rotating faster than our current sun tend to exhibit increased magnetic activity as well as magnetic cycles spanning multiple years. Using global simulations in spherical shells to study the coupling of large-scale convection, rotation, and magnetism in a younger sun, we have probed effects of rotation on stellar dynamos and the nature of magnetic cycles. Major 3-D MHD simulations carried out at three times the current solar rotation rate reveal hydromagnetic dynamo action that yields wreaths of strong toroidal magnetic field at low latitudes, often with opposite polarity in the two hemispheres. Our recent simulations have explored behavior in systems with considerably lower diffusivities, achieved with sub-grid scale models including a dynamic Smagorinsky treatment of unresolved turbulence. The lower diffusion promotes the generation of magnetic wreaths that undergo prominent temporal variations in field strength, exhibiting global magnetic cycles that involve polarity reversals. In our least diffusive simulation, we find that magnetic buoyancy coupled with advection by convective giant cells can lead to the rise of coherent loops of magnetic field toward the top of the simulated domain.
[ "Universe Sciences", "Condensed Matter Physics" ]
10.1093/mnras/stz2579
Long-term variability of a black widow’s eclipses – A decade of PSR J2051$-$0827
ABSTRACT In this paper we report on $\sim 10$  yr of observations of PSR J2051$-$0827, at radio frequencies in the range 110–4032 MHz. We investigate the eclipse phenomena of this black widow pulsar using model fits of increased dispersion and scattering of the pulsed radio emission as it traverses the eclipse medium. These model fits reveal variability in dispersion features on time-scales as short as the orbital period, and previously unknown trends on time-scales of months–years. No clear patterns are found between the low-frequency eclipse widths, orbital period variations, and trends in the intrabinary material density. Using polarization calibrated observations we present the first available limits on the strength of magnetic fields within the eclipse region of this system; the average line of sight field is constrained to be $10^{-4}$ G $\lesssim B_{||} \lesssim 10^2$ G, while for the case of a field directed near-perpendicular to the line of sight we find $B_{\perp } \lesssim 0. 3$ G. Depolarization of the linearly polarized pulses during the eclipse is detected and attributed to rapid rotation measure fluctuations of $\sigma _{\text{RM}} \gtrsim 100$ rad m$^{-2}$ along, or across, the line of sights averaged over during a subintegration. The results are considered in the context of eclipse mechanisms, and we find scattering and/or cyclotron absorption provide the most promising explanation, while dispersion smearing is conclusively ruled out. Finally, we estimate the mass-loss rate from the companion to be $\dot{M}_{\text{C}} \sim 10^{-12}\, \mathrm{M}_\odot$ yr$^{-1}$, suggesting that the companion will not be fully evaporated on any reasonable time-scale
[ "Universe Sciences" ]
10.1364/OL.38.001404
Real Time Handheld Multispectral Optoacoustic Imaging
Multispectral optoacoustic tomography (MSOT) of functional and molecular contrast has the potential to find broad deployment in clinical practice. We have developed the first handheld MSOT imaging device with fast wavelength tuning achieving a frame rate of 50 Hz. In this Letter, we demonstrate its clinical potential by dynamically resolving multiple disease-relevant tissue chromophores, including oxy-/deoxyhemoglobin, and melanin, in human volunteers.
[ "Physical and Analytical Chemical Sciences", "Systems and Communication Engineering", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1090/conm/717/14441
Interacting fermions with quasi-random disorder
We discuss the effect of many-body interactions in fermionic systems with strong quasi-random disorder (quasi-periodic potential). By assuming Diophantine conditions on the frequency and density and using renormalization-group methods, we prove the convergence of the expansion of the many-body correlations up to zero temperature and their exponential decay. This is true, in particular, for the interacting spinless fermionic Aubry-André model, for two coupled chains of spinless interacting disordered fermions, and for an array of noninteracting chains with the same disorder in all the chains. Zero-temperature exponential decay is a signal of persistence of localization in the many-body ground state in presence of an interaction. In other systems, however, as in the presence of spin or when more than two interacting chains are coupled, additional relevant processes prevent convergence up to zero temperature, suggesting a lack of localization at least for certain quantities. This is in agreement with recent experiments performed on cold atoms and with numerical simulations.
[ "Condensed Matter Physics", "Mathematics" ]
W2262270641
Product Counterfeiting and Survival of Selected Pharmaceutical Firms in Anambra State
This research is centered on Product Counterfeiting and the Survival of selected Pharmaceutical Firms. The poor consumer enlightenment campaign and security challenges make it difficult to combat the problem of Product counterfeiting, ineffective enforcement of the existing law, ignorance, corruption, lack of capacity in terms of work force, loose control system, non health professional in the drug business and lack of appropriate legislature. The study determines the nature of relationship between counterfeited product and attitude of the consumers with purchase intention. The study is anchored on Ajzen theory of planned behavior. The study employed descriptive research design, the primary source of data are the major instrument use for this study. Pearson product moment correlation was used to analyze the data with aid of SPSS version 22.The findings reveal that there is a positive relationship counterfeit product and the attitude of consumers with purchase intention. Base on the findings, the researcher recommends that government should equip the Agencies involve in combating Product counterfeiting proliferation with every logistics support needed to fight the nefarious crime.
[ "Institutions, Governance and Legal Systems", "The Social World and Its Interactions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
648143
Spore killer genomics: elucidating causes and consequences of a fungal meiotic drive element
The traditional view of the genome is that of a highly coordinated network that has evolved to produce a successful individual. However, the alternative view of the genome as containing intrinsically conflicting parts that coevolve antagonistically, has recently emerged. Today, it is widely accepted that conflicts caused by selfish genetic elements is a driving force for evolutionary innovation, and hence, is of fundamental importance for all aspects of evolution. Nevertheless, empirical data on the topic is largely lacking. Here, I introduce the fungus Neurospora as a novel study system of the evolutionary significance of meiotic drive. In this sexual eukaryote model system, the meiotic drive element Spore killer is found. The cytological properties and natural distribution of Spore killing in Neurospora has been investigated for several decades, and preliminary data suggests that it is an important driver of both genome evolution and of higher-order evolutionary processes. The existing knowledge and resources of this system provide a foundation for the proposed research program, in which I plan to build a tool-kit of genomic and experimental resources to I) identify and characterize the gene(s) encoding Spore killer elements, II) assess the strength of Spore killer as a meiotic drive, III) unravel the evolutionary history of the Spore killer complex in Neurospora, IV) investigate the association between Spore killer and genome evolution, and V) analyze the role of Spore killer as a driver of speciation and mating system transitions. This research program will manifest the Spore killer as a primary and pioneering model for the study of meiotic drive, and profoundly impact our understanding of segregation distorters as drivers of eukaryote genome evolution. Furthermore, insights emerging from the project presented are conceptually important for basic evolutionary biology, in the study of natural selection acting at multitudinal levels in a biological hierarchy.
[ "Integrative Biology: from Genes and Genomes to Systems", "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1371/journal.ppat.1004815
cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission
Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.3389/fgene.2019.00093
Insights into an unexplored component of the mosquito repeatome: Distribution and variability of viral sequences integrated into the genome of the arboviral vector aedes albopictus
The Asian tiger mosquito Aedes albopictus is an invasive mosquito and a competent vector for public-health relevant arboviruses such as Chikungunya (Alphavirus), Dengue and Zika (Flavivirus) viruses. Unexpectedly, the sequencing of the genome of this mosquito revealed an unusually high number of integrated sequences with similarities to non-retroviral RNA viruses of the Flavivirus and Rhabdovirus genera. These Non-retroviral Integrated RNA Virus Sequences (NIRVS) are enriched in piRNA clusters and coding sequences and have been proposed to constitute novel mosquito immune factors. However, given the abundance of NIRVS and their variable viral origin, their relative biological roles remain unexplored. Here we used an analytical approach that intersects computational, evolutionary and molecular methods to study the genomic landscape of mosquito NIRVS. We demonstrate that NIRVS are differentially distributed across mosquito genomes, with a core set of seemingly the oldest integrations with similarity to Rhabdoviruses. Additionally, we compare the polymorphisms of NIRVS with respect to that of fast and slow-evolving genes within the Ae. albopictus genome. Overall, NIRVS appear to be less polymorphic than slow-evolving genes, with differences depending on whether they occur in intergenic regions or in piRNA clusters. Finally, two NIRVS that map within the coding sequences of genes annotated as Rhabdovirus RNA-dependent RNA polymerase and the nucleocapsid-encoding gene, respectively, are highly polymorphic and are expressed, suggesting exaptation possibly to enhance the mosquito's antiviral responses. These results greatly advance our understanding of the complexity of the mosquito repeatome and the biology of viral integrations in mosquito genomes.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1371/journal.pgen.1004806
Heat-Induced Release of Epigenetic Silencing Reveals the Concealed Role of an Imprinted Plant Gene
Epigenetic mechanisms suppress the transcription of transposons and DNA repeats; however, this suppression can be transiently released under prolonged heat stress. Here we show that the Arabidopsis thaliana imprinted gene SDC, which is silent during vegetative growth due to DNA methylation, is activated by heat and contributes to recovery from stress. SDC activation seems to involve epigenetic mechanisms but not canonical heat-shock perception and signaling. The heat-mediated transcriptional induction of SDC occurs particularly in young developing leaves and is proportional to the level of stress. However, this occurs only above a certain window of absolute temperatures and, thus, resembles a thermal-sensing mechanism. In addition, the re-silencing kinetics during recovery can be entrained by repeated heat stress cycles, suggesting that epigenetic regulation in plants may conserve memory of stress experience. We further demonstrate that SDC contributes to the recovery of plant biomass after stress. We propose that transcriptional gene silencing, known to be involved in gene imprinting, is also co-opted in the specific tuning of SDC expression upon heat stress and subsequent recovery. It is therefore possible that dynamic properties of the epigenetic landscape associated with silenced or imprinted genes may contribute to regulation of their expression in response to environmental challenges.
[ "Integrative Biology: from Genes and Genomes to Systems", "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1137/120880665
The Flutter Shutter Paradox
Photography is the art of acquiring as many photons as possible of a given scene. In classic cameras, the aperture time is irremediably limited by the risk of a motion blur when the camera and the scene are in relative motion. Nevertheless, two recent camera concepts, the Agrawal et al. flutter shutter and the Levin et al. motion-invariant photography permit one to extend indefinitely the exposure time while guaranteeing an invertible motion blur. In this paper, a complete mathematical theory of these new technologies is proposed. Modeling the capture noise, the theory furnishes explicit formulas for the signal to noise ratio $(SNR)$ of the final image after deconvolution when the motion is uniform. It puts in evidence the existence of two variants, the analog flutter shutter and the numerical flutter shutter. The results of the resulting quantitative comparison are slightly paradoxical. First, it is shown that the best camera aperture strategies are always flutter shutters, even when the aperture time is. . .
[ "Mathematics", "Computer Science and Informatics" ]