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W1982937915
Formation of Nano-Textured Silicon Surface Layer (or Nanowires) by Silver Ion-Assisted Etching
To obtain an ultralow surface reflectance and reach broadband antireflection effects,in this paper, silicon nanowires (SiNWs) layer has been fabricated by low-cost and easy-made silver-assisted etching techniques.The morphologies, reflectance and surface recombination of the samples were separately characterized. The ultralow reflectance below 3% from 300 to 800 nm under normal incidence has been realized in the case of ~ 1 μm long SiNWs whose geometry structures approximate to multi-layer gratings stack and the refractive index gradually increases from the top to the bottom of substrate. However, surface recombination of SiNWs deteriorates due to numerous dangling bonds and residual silver. Therefore, a trade-off between antireflection effect and recombination loss is the key to the electronic device.
[ "Condensed Matter Physics", "Materials Engineering", "Physical and Analytical Chemical Sciences" ]
185108
Understanding small rna-mediated transposon control at the level of chromatin in the animal germline
Transposable elements—universal components of genomes—pose a major threat to genome integrity due to their mutagenic character. In all eukaryotic lineages small RNA pathways act as defense systems to protect the host genome against the activity of transposons. The central pathway in animals is the gonad-specific PIWI interacting RNA (piRNA) pathway, one of the most elaborate but also least understood small RNA silencing systems. Here I propose to study the interplay between the piRNA pathway and chromatin biology in Drosophila with two aims: First, we will identify the factors and investigate the processes that underlie piRNA-guided silencing in the nucleus. Our objective is to understand how recruitment of an Argonaute protein to a nascent RNA mechanistically leads to the assembly of effector proteins that govern heterochromatin formation and transcriptional silencing. Second, we will study the biology of piRNA clusters, heterochromatic loci that encompass a library of transposon fragments and that act as the pathway’s memory system. Our goal is to uncover how a group of proteins—several of which are germline-specific variants of basic cellular factors—enable transcription within heterochromatin and control the downstream fate of the emerging non-coding RNAs. Our work centers on the piRNA pathway in Drosophila ovaries, undeniably the model system at the forefront of the field. By combining the strength of fly genetics with the power of genome-wide approaches we will uncover how heterochromatin on the one hand governs silencing and how the piRNA pathway on the other hand exploits it to facilitate the transcription of piRNA precursors. This will reveal fundamental insights into the co-evolution of transposons and host genomes. At the same time, by studying the piRNA pathway’s intersection with chromatin biology and transcription, we expect to reveal new insights into basic principles of gene expression.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1016/j.actamat.2016.04.035
Synchrotron X-ray microbeam diffraction measurements of full elastic long range internal strain and stress tensors in commercial-purity aluminum processed by multiple passes of equal-channel angular pressing
Synchrotron X-ray microbeam diffraction was used to measure the full elastic long range internal strain and stress tensors of low dislocation density regions within the submicrometer grain/subgrain structure of equal-channel angular pressed (ECAP) aluminum alloy AA1050 after 1, 2, and 8 passes using route BC. This is the first time that full tensors were measured in plastically deformed metals at this length scale. The maximum (most tensile or least compressive) principal elastic strain directions for the unloaded 1 pass sample for the grain/subgrain interiors align well with the pressing direction, and are more random for the 2 and 8 pass samples. The measurements reported here indicate that the local stresses and strains become increasingly isotropic (homogenized) with increasing ECAP passes using route BC. The average maximum (in magnitude) LRISs are -0. 43 σa for 1 pass, -0. 44 σa for 2 pass, and 0. 14 σa for the 8 pass sample. These LRISs are larger than those reported previously because those earlier measurements were unable to measure the full stress tensor. Significantly, the measured stresses are inconsistent with the two-component composite model.
[ "Condensed Matter Physics", "Materials Engineering" ]
EP 2021079619 W
HIGH-POROSITY NANOFIBER NONWOVENS AS A SUPPORT STRUCTURE FOR STROMAL TISSUE
The present invention relates to nanofiber nonwovens comprising a network of nanofibers, which are composed of at least one nanofiber material and which enclose pores, to methods for producing nanofiber nonwovens, to the use thereof as well as to artificial tissue comprising these nanofiber nonwovens and methods for producing these artificial tissues.
[ "Materials Engineering", "Synthetic Chemistry and Materials", "Cell Biology, Development, Stem Cells and Regeneration" ]
240324
Proteomimetic Foldamers: Towards Future Therapeutics and Designer Enzymes
The purpose of this project is to develop a RULE-BASED APPROACH for the design and synthesis of proteomimetics of the alpha-helix and in doing so establish to what extent the structural and functional role of the alpha-helix can be reproduced with non-natural molecules in a PREDICTABLE manner We will focus on developing aromatic oligoamide proteomimetics (compounds that mimic the secondary structure from which they are derived) of one of the dominant secondary structural motifs observed in proteins the alpha-helix. Helices play a key role in mediating many protein-protein interactions, they interact with proteins and contribute residues to the resulting complex that form part of a catalytic site and they operate within the context of an entire protein structure as scaffolding upon which other helices, sheets, turns and coils pack to generate an active 3D structure. We will therefore: (i) develop a general approach for the inhibition of alpha-helix mediated protein-protein interactions, (ii) develop proteomimetics that can bind to an inactive protein and restore catalytic activity (iii) develop proteomimetics that can be covalently incorporated into the primary sequence of a protein without abolishing its function. This will lead to immense opportunities for development of new therapeutics and proteins with new functionality. More significantly, re-engineering nature to the extent of replacing whole segments of protein backbone with non-natural prostheses as proposed here will begin to answer the fundamental question: Is the astonishing structural and functional complexity achieved through precise secondary and tertiary organisation of primary protein structure confined to sequences of alpha-amino acids?
[ "Synthetic Chemistry and Materials", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1016/j.semcdb.2016.01.032
Molecular and cellular mechanisms involved in leg joint morphogenesis
In summary, the patterning of the presumptive leg depends on gradients of Dpp and Wg morphogens, which lead to the establishment of the proximo-distal axis marked by the expression of Hth, Dac and Dll in broad domains along the leg. Then, EGFR signaling specifies the tarsal region by regulating the expression of tarsal gap genes in different tarsal segments. This patterning is closely linked to the formation of rings of Notch activation in the distal part of each leg segment. These rings of Notch activation are further regulated by different mechanisms: (1) the maintenance of a sharp border of Dl expression, (2) the inhibition of N activation in cells located proximally to the ligands, thus restricting N activity specifically to the distal part of cells. This localised activation of Notch induces the expression of Dysfusion which controls the expression of both pro-apoptotic genes and RhoGTPase regulators. Finally, apoptotic cells appear within the pro-apoptotic domain, and while dying, generate a transient pulling force. This force constitutes a mechanical signal that propagates to the rest of the tissue and triggers cytoskeleton reorganisation specifically in the presumptive fold, where RhoGTPase regulators are expressed. Altogether, this complex array of patterning and signaling leads to precise cellular mapping of the developing leg to correctly position local cell shape modifications, inducing tissue folding.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1063/1.4945656
Heat And Mass Transfer Over Slippery Superhydrophobic Surfaces
The classical Graetz-Nusselt problem is extended to describe heat and mass transfer over heterogeneously slippery, superhydrophobic surfaces. The cylindrical wall consists of segments with a constant temperature/concentration and areas that are insulating/impermeable. Only in the case of mass transport do the locations of hydrodynamic slip and mass exchange coincide. This makes advection near the mass exchanging wall segments larger than near the heat exchanging regions. Also the direction of radial fluid flow is reversed for heat and mass transport, which has an influence on the location where the concentration or temperature boundary layer is compressed or extended. As a result, mass transport is more efficient than heat transfer. Also the influence of axial diffusion on the Nusselt and Sherwood numbers is investigated for various Peclet numbers Pe. When Pe < 102, which is characteristic for heat transfer over superhydrophobic surfaces, axial conduction should be taken into account. For Pe ≥ 102, which are typical numbers for mass transport in microfluidic systems, axial diffusion can be neglected.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
787171
The PIDDosome in Centrosome and Ploidy-Surveillance
Tight control of the number of chromosome sets in a cell (ploidy) is fundamental for normal development and organismal health. Most cells in our body are diploid, yet, some cells, including cardiomyocytes or hepatocytes require a balanced increase in ploidy for proper function. Polyploidization is accompanied by an accumulation of centrosomes, structures needed for nucleating the mitotic spindle and ciliogenesis. Extra centrosomes, however, promote aneuploidy in proliferating cells by causing errors in chromosome segregation, underlying a series of human pathologies, most notably cancer and premature ageing. How polyploidization is controlled in organogenesis and how errors in ploidy control contribute to disease is poorly understood. We recently demonstrated that the “PIDDosome” complex polices centrosome numbers in mammalian cells, alerting the tumor suppressor p53 in response to extra centrosomes. This is achieved by inactivating MDM2, the key-inhibitor of p53, by targeted proteolysis. MDM2-processing is mediated by caspase-2, a neglected member in a protease family that controls cell death and inflammation, activated in the PIDDosome. This exciting finding allows examining the consequences of deregulated ploidy and centrosome number in development and disease without interfering with p53, nor the cell fusion or cytokinesis machineries. This puts us in pole position to carry out an integrative study that aims to develop the PIDDosome as a new therapeutic target in cancer, related inflammation and in regenerative medicine. To meet this aim, we will define (i) the relevance of the PIDDosome in aneuploidy tolerance of cancer (ii) the role of the PIDDosome in controlling sterile inflammation and immunity (iii) the PIDDosome as a key-regulator of organ development and regeneration POLICE will open new lines of research at the interface of cell cycle, cell death & inflammation control and promote the PIDDosome as new target in our efforts to improve human health.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases", "Immunity, Infection and Immunotherapy" ]
10.1007/s00572-015-0631-x
High functional diversity within species of arbuscular mycorrhizal fungi is associated with differences in phosphate and nitrogen uptake and fungal phosphate metabolism
Plant growth responses following colonization with different isolates of a single species of an arbuscular mycorrhizal (AM) fungus can range from highly beneficial to detrimental, but the reasons for this high within-species diversity are currently unknown. To examine whether differences in growth and nutritional benefits are related to the phosphate (P) metabolism of the fungal symbiont, the effect of 31 different isolates from 10 AM fungal morphospecies on the P and nitrogen (N) nutrition of Medicago sativa and the P allocation among different P pools was examined. Based on differences in the mycorrhizal growth response, high, medium, and low performance isolates were distinguished. Plant growth benefit was positively correlated to the mycorrhizal effect on P and N nutrition. High performance isolates increased plant biomass by more than 170 % and contributed substantially to both P and N nutrition, whereas the effect of medium performance isolates particularly on the N nutrition of the host was significantly lower. Roots colonized by high performance isolates were characterized by relatively low tissue concentrations of inorganic P and short-chain polyphosphates and a high ratio between long- to short-chain polyphosphates. The high performance isolates belonged to different morphospecies and genera, indicating that the ability to contribute to P and N nutrition is widespread within the Glomeromycota and that differences in symbiotic performance and P metabolism are not specific for individual fungal morphospecies.
[ "Environmental Biology, Ecology and Evolution", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1098/rsbl.2014.0978
Reported maternal tendencies predict the reward value of infant facial cuteness, but not cuteness detection
The factors that contribute to individual differences in the reward value of cute infant facial characteristics are poorly understood. Here we show that the effect of cuteness on a behavioural measure of the reward value of infant faces is greater among women reporting strong maternal tendencies. By contrast, maternal tendencies did not predict women's subjective ratings of the cuteness of these infant faces. These results show, for the first time, that the reward value of infant facial cuteness is greater among women who report being more interested in interacting with infants, implicating maternal tendencies in individual differences in the reward value of infant cuteness. Moreover, our results indicate that the relationship between maternal tendencies and the reward value of infant facial cuteness is not due to individual differences in women's ability to detect infant cuteness. This latter result suggests that individual differences in the reward value of infant cuteness are not simply a by-product of low-cost, functionless biases in the visual system.
[ "The Human Mind and Its Complexity", "Neuroscience and Disorders of the Nervous System" ]
10.1002/wcms.1250
Rh chemistry through the eyes of theory
We discuss the properties of Rh and its compounds from a theoretical chemistry perspective. Like its neighbors in the platinum metal group, this element exhibits a remarkable spectrum of catalytic activity both as an elemental metal and as the central ion of transition metal complexes. This property is reflected in a comparatively weak chemical bond dominated by d-p interactions, varying oxidation states and a highly flexible coordination shell. In turn, theoretical methods and their generalization as empirical concepts have to be able to deal with a multitude of binding situations and the strong electron-electron interaction within the Rh valence orbitals. Whereas density functional theory has greatly enhanced the computational accessibility of Rh compounds, quantitative models of catalytic cycles require a more explicit treatment of static electron correlation, such as integrated density functional-coupled cluster schemes. WIREs Comput Mol Sci 2016, 6:311-320. doi: 10. 1002/wcms. 1250 For further resources related to this article, please visit the WIREs website.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1016/j.celrep.2019.11.111
Reconstitution of the Human Nigro-striatal Pathway on-a-Chip Reveals OPA1-Dependent Mitochondrial Defects and Loss of Dopaminergic Synapses
Stem cell-derived neurons are generally obtained in mass cultures that lack both spatial organization and any meaningful connectivity. We implement a microfluidic system for long-term culture of human neurons with patterned projections and synaptic terminals. Co-culture of human midbrain dopaminergic and striatal medium spiny neurons on the microchip establishes an orchestrated nigro-striatal circuitry with functional dopaminergic synapses. We use this platform to dissect the mitochondrial dysfunctions associated with a genetic form of Parkinson's disease (PD) with OPA1 mutations. Remarkably, we find that axons of OPA1 mutant dopaminergic neurons exhibit a significant reduction of mitochondrial mass. This defect causes a significant loss of dopaminergic synapses, which worsens in long-term cultures. Therefore, PD-associated depletion of mitochondria at synapses might precede loss of neuronal connectivity and neurodegeneration. In vitro reconstitution of human circuitries by microfluidic technology offers a powerful system to study brain networks by establishing ordered neuronal compartments and correct synapse identity.
[ "Neuroscience and Disorders of the Nervous System", "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1126/science.1193654
Transient middle eocene atmospheric CO<inf>2</inf> and temperature variations
The long-term warmth of the Eocene (∼56 to 34 million years ago) is commonly associated with elevated partial pressure of atmospheric carbon dioxide (pCO2). However, a direct relationship between the two has not been established for short-term climate perturbations. We reconstructed changes in both pCO2 and temperature over an episode of transient global warming called the Middle Eocene Climatic Optimum (MECO; ∼40 million years ago). Organic molecular paleothermometry indicates a warming of southwest Pacific sea surface temperatures (SSTs) by 3° to 6°C. Reconstructions of pCO 2 indicate a concomitant increase by a factor of 2 to 3. The marked consistency between SST and pCO2 trends during the MECO suggests that elevated pCO2 played a major role in global warming during the MECO.
[ "Earth System Science" ]
852957
Modelling to Optimize Vector Elimination: Destabilising mosquito populations
Control of vector-borne diseases from Chagas to Malaria to Dengue largely relies on reducing or eliminating the arthropod vector populations. These public health initiatives routinely lead to at least initial declines in vector populations. The challenge is that as populations decline, unexpected evolutionary (such as insecticide resistance) and ecological changes (such as population fragmentation and altered density-dependence) can occur that might facilitate or undermine control efforts. However, the relative importance of these ecological intra- and inter-specific processes in regulating vector populations is almost unknown, which hinders the prediction of vector population dynamics and how different interventions might be most effectively deployed to sustainably suppress vectors. Although vector surveillance has generated extensive high-resolution time series datasets to assess the factors that underpin population persistence and regulation, the cutting-edge analytical tools required to overcome the complexity of these data have been mostly developed by ecologists and have rarely been applied in medical entomology. Filling both these knowledge and methodological gaps will require closer integration of public health science, medical entomology and ecology that I intend to deliver through this proposal. As a quantitative ecologist, I will work closely with medical entomologists and public health scientists, to develop and apply sophisticated state-space models to longitudinal vector surveillance data from five malaria endemic countries. I will determine how interventions impact vector: 1) population regulation, 2) metapopulation connectivity and persistence, and 3) community composition. This unprecedented demographic dissection of vector populations will simultaneously challenge ecological theory and explore how to harness intra- and inter-specific processes in vector populations to accelerate 'end-game' strategies that move from vector control to elimination.
[ "Environmental Biology, Ecology and Evolution", "Prevention, Diagnosis and Treatment of Human Diseases", "Mathematics" ]
Q4209155
DÉPÔT INTERNATIONAL DE BREVET DE COLONNE TÉLESCOPIQUE EN VERSION COMPACTE
CETTE INVENTION PRÉSENTE UNE SOLUTION INNOVANTE POUR LES COLONNES TÉLESCOPIQUES ÉLECTROMÉCANIQUES. LE SYSTÈME DE VERROUILLAGE UTILISE LA VIS DU CONDUCTEUR, PRÉSENTE DANS LA PARTIE FIXE DE LA COLONNE, POUR CONTRÔLER LE SYSTÈME DE CONTRAINTE ENTRE LES TUYAUX QUI COMPOSENT LA COLONNE. LES SERRURES, DÉFINIES COMME LA SERRURE, SONT INSÉRÉES ET DISIN-NESTANO À L’INTÉRIEUR DE LA COLONNE PERMETTANT L’EXTENSION ET LA RÉTRACTION DE LA MÊME. L’ENSEMBLE DU MÉCANISME RÉSIDE À L’INTÉRIEUR DE LA COLONNE ET N’EST PAS VISIBLE EXTÉRIEUREMENT DONNANT AU PRODUIT UN BON ESTETICO CONTRIBUTION.LE PRODUIT, NÉ DE LA FAMILLE DES COLONNES TÉLESCOPIQUES ÉLECTROMÉCANIQUES, A POUR OBJECTIF L’OPTIMISATION DES DIMENSIONS EN HAUTEUR. L’ESPACE EN HAUTEUR LORSQU’IL EST FERMÉ EST INFÉRIEUR AU PRODUIT PRÉCÉDENT ÉGAL À LA HAUTEUR ATTEINTE LORS DE L’OUVERTURE. LA COLONNE EST ÉQUIPÉE D’UN MOTEUR ÉLECTRIQUE À FAIBLE TENEUR EN IONS AVEC TECHNOLOGIE SANS BALAIS ET DE RACCORDS AVEC LES MATÉRIAUX POLYMÈRES DE DERNIÈRE GÉNÉRATION
[ "Products and Processes Engineering", "Materials Engineering", "Systems and Communication Engineering" ]
640488
Doing Intimacy: A Multi-sited Ethnography of Modern Chinese Family Life
Families in Western countries have received a great deal of attention from social scientists but there is less information on family life in other regions of the world. Given its growing rapidly in global influence, China represents a crucial region for sociological advancement and understanding. There have been profound changes in the Chinese family over the last century as a result of industrialization, urbanization, the influence of the West and the political interventions carried out by the Communist Party since 1949. Existing scholarship has shown how the structure and function of Chinese families have adapted to changing political and economic circumstances but little is known about the changes in intimate spheres of Chinese families. This project will approach the subject of modern Chinese family life from an unconventional angle, analysing it as a process of practices and experiences. By setting a new agenda that moves from structures of family relationships to the quality of relationships and through examining ‘doing intimacy’, this project will take a closer, fresher, critical look at the Chinese family dynamics as they are lived. Informed by the emerging literature on gender, intimacy and modernity, this project will examine intergenerational relations as well as gender and sexual relations in the family. Is there an intimate revolution taking place? How is ‘modernity’/’tradition’ closely linked with practices of intimacy? To what extent can doing intimacy be a site of empowerment/domination for women? What will the study of Chinese families tell us about agency and local/global change? Through a multi-sited ethnography (mainland China, Hong Kong and Taiwan), this study will also compare practices of intimacy in various sites and examine whether/how they are by-products of particular socio-cultural configurations. It will identify the extent to which changes in Chinese families mirror changes in the West and the factors that contribute to these changes.
[ "The Social World and Its Interactions", "Studies of Cultures and Arts", "Human Mobility, Environment, and Space" ]
10.1007/978-3-319-11970-0_6
G Brownian Motion As Rough Paths And Differential Equations Driven By G Brownian Motion
The present article is devoted to the study of sample paths of G-Brownian motion and stochastic differential equations (SDEs) driven by G-Brownian motion from the viewpoint of rough path theory. As the starting point, by using techniques in rough path theory, we show that quasi-surely, sample paths of G-Brownian motion can be enhanced to the second level in a canonical way so that they become geometric rough paths of roughness 2 < p < 3. This result enables us to introduce the notion of rough differential equations (RDEs) driven by G-Brownian motion in the pathwise sense under the general framework of rough paths. Next we establish the fundamental relation between SDEs and RDEs driven by G-Brownian motion. As an application, we introduce the notion of SDEs on a differentiable manifold driven by G-Brownian motion and construct solutions from the RDE point of view by using pathwise localization technique. This is the starting point of developing G-Brownian motion on a Riemannian manifold, based on the idea of Eells-Elworthy-Malliavin. The last part of this article is devoted to such construction for a wide and interesting class of G-functions whose invariant group is the orthogonal group. In particular, we establish the generating nonlinear heat equation for such G-Brownian motion on a Riemannian manifold. We also develop the Euler-Maruyama approximation for SDEs driven by G-Brownian motion of independent interest.
[ "Mathematics" ]
10.1039/C3NR34213A
Poisoning Of Bubble Propelled Catalytic Micromotors The Chemical Environment Matters
Self-propelled catalytic microjets have attracted considerable attention in recent years and these devices have exhibited the ability to move in complex media. The mechanism of propulsion is via the Pt catalysed decomposition of H2O2 and it is understood that the Pt surface is highly susceptible to poisoning by sulphur-containing molecules. Here, we show that important extracellular thiols as well as basic organic molecules can significantly hamper the motion of catalytic microjet engines. This is due to two different mechanisms: (i) molecules such as dimethyl sulfoxide can quench the hydroxyl radicals produced at Pt surfaces and reduce the amount of oxygen gas generated and (ii) molecules containing –SH, –SSR, and –SCH3 moieties can poison the catalytically active platinum surface, inhibiting the motion of the jet engines. It is essential that the presence of such molecules in the environment be taken into consideration for future design and operation of catalytic microjet engines. We show this effect on catalytic micromotors prepared by both rolled-up and electrodeposition approaches, demonstrating that such poisoning is universal for Pt catalyzed micromotors. We believe that our findings will contribute significantly to this field to develop alternative systems or catalysts for self-propulsion when practical applications in the real environment are considered.
[ "Physical and Analytical Chemical Sciences", "Materials Engineering" ]
US 2017/0028468 W
NANOPORE SENSOR, STRUCTURE AND DEVICE INCLUDING THE SENSOR, AND METHODS OF FORMING AND USING SAME
The present disclosure provides an improved device that can be used to sense and characterize a variety of materials. The device may be used for a variety of applications, including genome sequencing, protein sequencing, biomolecular sequencing, and detection of ions, molecules, chemicals, biomolecules, metal atoms, polymers, nanoparticles and the like.
[ "Materials Engineering", "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
W2019251125
On the influence of the geometry on skin effect in electromagnetism
We consider the equations of electromagnetism set on a domain made of a dielectric and a conductor subdomain in a regime where the conductivity is large. Assuming smoothness for the dielectric--conductor interface, relying on recent works we prove that the solution of the Maxwell equations admits a multiscale asymptotic expansion with profile terms rapidly decaying inside the conductor. This skin effect is measured by introducing a skin depth function that turns out to depend on the mean curvature of the boundary of the conductor. We then confirm these asymptotic results by numerical experiments in various axisymmetric configurations. We also investigate numerically the case of a nonsmooth interface, namely a cylindrical conductor.
[ "Mathematics", "Condensed Matter Physics" ]
278867
Relevance of double strand break repair pathway choice in human disease and cancer
Double strand breaks (DSBs) repair is essential for normal development. While the complete inability to repair DSBs leads to embryonic lethality and cell death, mutations that hamper this repair cause genetically inherited syndromes, with or without cancer predisposition. The phenotypes associated with these syndromes are extremely varied, and can include growth and mental retardation, ataxia, skeletal abnormalities, immunodeficiency, premature aging, etc. Moreover, DSBs play an extremely relevant role in the biology of cancer. Alterations in the DSBs repair pathways facilitate tumour progression and are selected early on during cancer development. On the other hand, DSBs are the molecular base of radiotherapies and chemotherapies. This double role of DSBs in both, the genesis and treatment of cancer makes the understanding of the mechanisms that control their repair of capital importance in cancer research. DSBs are repaired by two major mechanisms that compete for the same substrate. Both ends of the DSB can be simple re-joined with little or no processing, a mechanism known as non-homologous end-joining. On the other hand, DSBs can be processed and engaged in a more complex repair pathway called homologous recombination. This pathway uses the information present in a homologue sequence. The balance between these two pathways is exquisitely controlled and its alteration leads to the appearance of chromosomal abnormalities and contribute to the diseases aforementioned. However, and despite its importance, the network controlling the choice between both is poorly understood. Here, we propose a series of research lines designed to investigate how the choice between both DSBs repair pathways is made, its relevance for cellular and organismal survival and disease, and its potential as a therapeutic target for the treatment of cancer and some genetically inherited disorders.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1086/705561
More Than A Sorting Machine Ethnic Boundary Making In A Stratified School System1
This article examines the structural conditions that shape ethnic boundary making in the school setting. While previous work has focused on the ethnic composition of student bodies, this study places schools in their institutional and local contexts. The authors argue that the formation of identities and networks varies across local areas depending on the extent of ethnic stratification across schools. Empirically, the authors turn to the case of Germany, where the role of schools as producers of categorical inequalities is particularly obvious. The analysis links large-scale survey data on adolescents’ identification and networks with administrative geocoded information on local stratification across secondary schools. The authors find that minority students in schools with identical ethnic compositions show different inclinations to identify as a majority group member and to form friendships with majority peers, depending on the local extent of ethnic stratification across schools. To place these findin. . .
[ "The Social World and Its Interactions", "Institutions, Governance and Legal Systems" ]
10.1038/ncomms9111
Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel
Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0. 1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants.
[ "Integrative Biology: from Genes and Genomes to Systems", "Computer Science and Informatics" ]
10.1111/j.1365-2745.2009.01626.x
Integral projection models for trees: A new parameterization method and a validation of model output
Matrix models are popular tools for plant demographic studies, but their application to long-lived, slow-growing species is hampered by the fact that (i) model output is highly sensitive to category width and (ii) growth variation between individuals can only be partially accounted for. Integral Projection Models (IPMs) - an extension of matrix models - offer a solution to these problems. Here, we introduce a new method to parameterize IPMs for trees - the 'integration method'- which allows constructing IPMs for long-lived, slow-growing species. This approach is more suitable than the 'midpoint rule', which is customarily used. We built IPMs for six tree species from Vietnamese (sub)tropical forests. For four of these species, population growth rate (λ) was highly sensitive to the number of categories in the transition matrix. Population growth stabilized for IPMs with 100-1000 categories, corresponding to categories of 0. 1-1 cm in trunk diameter. This preferred width is much narrower than the 10-cm-wide categories customarily used in tree models. The distribution of elasticity values over transition types (stasis, progression to next and further categories) is also highly sensitive to matrix dimension in IPMs. In addition, elasticity distribution is influenced by including or excluding growth variation. Age estimates obtained from IPMs were also highly sensitive to matrix dimension: an IPM with 1000 size categories yielded 2-4 times higher age estimates for large trees than one with 10 size categories. Observed ages obtained from tree ring analyses for four of the study species allowed validating these estimates. IPMs with 10 categories strongly underestimated age, while those with 1000 categories yielded slight age overestimates. Underestimating age in small matrices is caused by the occurrence of unrealistically fast pathways through the life cycle and is probably widespread among tree models with broad categories. Overestimating ages in IPMs with narrow categories may be due to temporally autocorrelated growth or errors in fitting growth curves. Synthesis. IPMs are highly suitable tools to analyse tree demography. We recommend that tree IPMs (and classical matrix models) apply narrow diameter categories (0. 1-1 cm width) to obtain reliable model output.
[ "Environmental Biology, Ecology and Evolution", "Mathematics" ]
W4226214269
Percepciones de género y factores de influencia. Evidencia en estudiantes universitarios de Barcelona (España) y Cartagena de Indias (Colombia)
A lo largo de la segunda mitad del siglo XX, ha habido una importante evolución en el pensamiento y las actitudes de mujeres y hombres hacia la igualdad de género. Pero esta evolución no se ha producido de forma homogénea en todos los ámbitos, incluida la universidad, a pesar de ser una institución de generación y transmisión de conocimiento. Estudiar las percepciones de los estudiantes actuales sobre los roles de género y la igualdad es importante para analizar el cambio en estas actitudes. El objetivo de este trabajo es explorar los factores que pueden determinar la evolución de estas percepciones durante la etapa universitaria. Para este propósito se diseñó una encuesta que se envió a 716 estudiantes de las universidades de Barcelona y Cartagena de Indias. Se utilizó un modelo de regresión logística para estimar los factores que determinan dichos cambios. Los resultados muestran la importancia de la formación en perspectiva de género, destacando especialmente la relevancia de la formación transversal. Sin embargo, se observan diferencias en función del contexto socioeconómico al que está adscrita cada universidad. Mientras que en Barcelona la formación preuniversitaria y la transmisión de valores y movimientos feministas son relevantes; en Cartagena, cabe destacar la existencia de factores relacionados con la socialización en entornos igualitarios. Estos resultados resaltan la conveniencia de introducir la perspectiva de género en los planes de estudio y la práctica docente.
[ "The Social World and Its Interactions", "The Human Mind and Its Complexity" ]
10.1155/2016/4590817
A Note On The Vec Operator Applied To Unbalanced Block Structured Matrices
The vec operator transforms a matrix to a column vector by stacking each column on top of the next. It is useful to write the vec of a block-structured matrix in terms of the vec operator applied to each of its component blocks. We derive a simple formula for doing so, which applies regardless of whether the blocks are of the same or of different sizes.
[ "Mathematics" ]
10.1093/mnras/stz1882
The impact of baryonic physics and massive neutrinos on weak lensing peak statistics
ABSTRACT We study the impact of baryonic processes and massive neutrinos on weak lensing peak statistics that can be used to constrain cosmological parameters. We use the BAHAMAS suite of cosmological simulations, which self-consistently include baryonic processes and the effect of massive neutrino free-streaming on the evolution of structure formation. We construct synthetic weak lensing catalogues by ray tracing through light-cones, and use the aperture mass statistic for the analysis. The peaks detected on the maps reflect the cumulative signal from massive bound objects and general large-scale structure. We present the first study of weak lensing peaks in simulations that include both baryonic physics and massive neutrinos (summed neutrino mass Mν = 0. 06, 0. 12, 0. 24, and 0. 48 eV assuming normal hierarchy), so that the uncertainty due to physics beyond the gravity of dark matter can be factored into constraints on cosmological models. Assuming a fiducial model of baryonic physics, we also investigate the correlation between peaks and massive haloes, over a range of summed neutrino mass values. As higher neutrino mass tends to suppress the formation of massive structures in the Universe, the halo mass function and lensing peak counts are therefore modified as a function of Mν. Over most of the S/N range, the impact of fiducial baryonic physics is greater (less) than neutrinos for 0. 06 and 0. 12 (0. 24 and 0. 48) eV models. Both baryonic physics and massive neutrinos should be accounted for when deriving cosmological parameters from weak lensing observations.
[ "Universe Sciences", "Fundamental Constituents of Matter" ]
W1988640023
A comparative study of the adsorption of uranium on commercial and natural (Cypriot) sea sand samples
The adsorption of hexavalent uranium on two different types of sea sand [e.g. a local, Cypriot (N_SS) and a commercially available marine sediment (C_SS)] has been investigated as a function of pH, initial metal concentration, ionic strength and contact time under normal atmospheric conditions. Before carrying out the adsorption experiments, the sea sand samples have been characterized by XRD, XRF, N2-adsorption, acid/base titrations and FTIR spectroscopy. Sample characterization showed clearly that the two sea sand types differ significantly in their composition, particularly in their calcite and FeOOH content. According to experimental data obtained from acid/base titrations and adsorption batch experiments sea sand composition affects the acid/base and the adsorption properties of the adsorbents. The extraordinary high affinity of N_SS for hexavalent uranium in the alkaline pH region can be attributed to the formation of mixed U(VI)–carbonato surface species on the FeOOH crystall phases present in N_SS, which effectively compete the formation of U(VI)–carbonato complexes in solution. On the other hand, data obtained by adsorption experiments carried out in solution of different ionic strengths don’t differ significantly from one another indicating the formation of inner-sphere complexes. Finally, the adsorption on sea sands is a relatively fast two-step process.
[ "Physical and Analytical Chemical Sciences", "Earth System Science" ]
2717150
The graphene-based resistance temperature sensors application
Many fast-growing industries, such as aerospace, automotive, power generation, oil & gas require fast-response, light-weight, flexible, stable, large-area temperature measurement. These requirements are particularly relevant for the battery industry which faces renaissance and booming demand both, in electric vehicle (EV) market and grid battery storage. Managing of an even distribution of temperature is key to operating of EV batteries close to their performance limits. The detailed monitoring of the battery temperature can bring great benefits and prevent potential negative effects of overheating which implicitly improves the state of health, i.e., a lifetime of batteries as well as prevents their technical failures. Danubia NanoTech developed an effective solution - graphene temperature sensor which can be, in the form of extremely thin film, applied on any non-metallic substrate (e.g., foil, glass). The sensor confirmed the high accuracy in the industrial validation; it is very thin, ultra-light, and while produced by spray-coating, it is also very variable for application on flexible (curved) surfaces and practically unlimited in terms of coverage area. On self-adhesive film, the sensor's application is very easy, with lower material costs, with fast response and excellent accuracy. All these properties of our graphene sensor provide a great value proposition particularly for EV batteries and also for grid battery storage. Danubia NanoTech is a dynamic technology-based company with long-term expertise in R&D of advanced materials focused on applications of graphene and carbon nanotubes. We produce excellent quality graphene with applicability in flexible electronics and conductive composites. Currently, we focus on the development of graphene-based sensors (temperature, thermo-physical, strain) for applications in different industries. Research, development, and production of carbon nanomaterials are ISO 9001:2015 certified.
[ "Materials Engineering", "Condensed Matter Physics", "Products and Processes Engineering" ]
10.1038/ejhg.2012.305
Phenotypic spectrum and prevalence of INPP5E mutations in Joubert Syndrome and related disorders
Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain-hindbrain malformation known as the 'molar tooth sign'. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. We previously identified the INPP5E gene as causative of JSRD in seven families linked to the JBTS1 locus, yet the phenotypic spectrum and prevalence of INPP5E mutations in JSRD and MKS remain largely unknown. To address this issue, we performed INPP5E mutation analysis in 483 probands, including 408 JSRD patients representative of all clinical subgroups and 75 MKS fetuses. We identified 12 different mutations in 17 probands from 11 JSRD families, with an overall 2. 7% mutation frequency among JSRD. The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS fetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1039/c6dt04253h
Bipyridine based metallogels: an unprecedented difference in photochemical and chemical reduction in the in situ nanoparticle formation
Reduction of silver containing metallogels led to formation of silver nanoparticles (AgNP's). Considerable size and morphological differences of the AgNP's were observed between the standard chemical and photochemical reduction of the metallogels.
[ "Physical and Analytical Chemical Sciences", "Materials Engineering" ]
10.1007/JHEP04(2016)157
Axion Monodromy And The Weak Gravity Conjecture
Axions with broken discrete shift symmetry (axion monodromy) have recently played a central role both in the discussion of inflation and the ‘relaxion’ approach to the hierarchy problem. We suggest a very minimalist way to constrain such models by the weak gravity conjecture for domain walls: while the electric side of the conjecture is always satisfied if the cosine-oscillations of the axion potential are sufficiently small, the magnetic side imposes a cutoff, Λ3 ∼ mf M pl, independent of the height of these ‘wiggles’. We compare our approach with the recent related proposal by Ibanez, Montero, Uranga and Valenzuela. We also discuss the non-trivial question which version, if any, of the weak gravity conjecture for domain walls should hold. In particular, we show that string compactifications with branes of different dimensions wrapped on different cycles lead to a ‘geometric weak gravity conjecture’ relating volumes of cycles, norms of corresponding forms and the volume of the compact space. Imposing this ‘geometric conjecture’, e. g. on the basis of the more widely accepted weak gravity conjecture for particles, provides at least some support for the (electric and magnetic) conjecture for domain walls.
[ "Fundamental Constituents of Matter", "Mathematics" ]
10.1038/ki.2012.463
Endogenous and exogenous pentraxin-3 limits postischemic acute and chronic kidney injury
Ischemia-reperfusion activates innate immunity and sterile inflammation, resulting in acute kidney injury. Since pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation, we tested whether PTX3 would be involved in renal ischemia-reperfusion injury. Renal pedicle clamping increased PTX3 serum levels, as well as PTX3 expression, inside the kidney but predominantly in CD45/CD11c + cells, a subpopulation of intrarenal mononuclear phagocytes. Lack of PTX3 aggravated postischemic acute kidney injury as evidenced by massive tubular necrosis, and TNF and IL-6 release, as well as massively increased neutrophil and macrophage infiltrates at 24 h. This was followed by tubular atrophy, interstitial fibrosis, and kidney shrinking 10 weeks later. In vivo microscopy uncovered increased leukocyte adhesion and transmigration in postischemic microvessels of Ptx3-deficient mice. Furthermore, injection of recombinant PTX3 up to 6 h after reperfusion prevented renal leukocyte recruitment and postischemic kidney injury. Thus, local PTX3 release from a subpopulation of intrarenal mononuclear phagocytes or delayed PTX3 treatment limits postischemic renal inflammation. Conversely, Ptx3 loss-of-function mutations predispose to postischemic acute kidney injury and subsequent chronic kidney disease.
[ "Physiology in Health, Disease and Ageing", "Immunity, Infection and Immunotherapy" ]
10.1093/nar/gkx1231
Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria
Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1137/11085390X
Subexponential Parameterized Algorithm For Minimum Fill In
The Minimum Fill-in problem is used to decide if a graph can be triangulated by adding at most $k$ edges. In 1994, Kaplan, Shamir, and Tarjan showed that the problem is solvable in time $\mathcal{O}(2^{\mathcal{O}({k})}+k^2 nm)$ on graphs with $n$ vertices and $m$ edges and thus is fixed parameter tractable. Here, we give the first subexponential parameterized algorithm solving Minimum Fill-in in time $\mathcal{O}(2^{\mathcal{O}(\sqrt{k}\log{k})} +k^2 nm)$. This substantially lowers the complexity of the problem. Techniques developed for Minimum Fill-in can be used to obtain subexponential parameterized algorithms for several related problems, including Minimum Chain Completion, Chordal Graph Sandwich, and Triangulating Colored Graph.
[ "Computer Science and Informatics" ]
10.1002/adma.201805985
An Artificial Nocturnal Flower via Humidity-Gated Photoactuation in Liquid Crystal Networks
Beyond their colorful appearances and versatile geometries, flowers can self-shape-morph by adapting to environmental changes. Such responses are often regulated by a delicate interplay between different stimuli such as temperature, light, and humidity, giving rise to the beauty and complexity of the plant kingdom. Nature inspires scientists to realize artificial systems that mimic their natural counterparts in function, flexibility, and adaptation. Yet, many of the artificial systems demonstrated to date fail to mimic the adaptive functions, due to the lack of multi-responsivity and sophisticated control over deformation directionality. Herein, a new class of liquid-crystal-network (LCN) photoactuators whose response is controlled by delicate interplay between light and humidity is presented. Using a novel deformation mechanism in LCNs, humidity-gated photoactuation, an artificial nocturnal flower is devised that is closed under daylight conditions when the humidity level is low and/or the light level is high, while it opens in the dark when the humidity level is high. The humidity-gated photoactuators can be fueled with lower light intensities than conventional photothermal LCN actuators. This, combined with facile control over the speed, geometry, and directionality of movements, renders the “nocturnal actuator” promising for smart and adaptive bioinspired microrobotics.
[ "Materials Engineering", "Synthetic Chemistry and Materials", "Physical and Analytical Chemical Sciences" ]
W2004773387
Domestic Violence during Pregnancy and Mental Health: Exploratory Study in Primary Health Centers in Peñalolén
Objective . To determine the prevalence of domestic violence in a sample of pregnant women attending Primary Health Centers in Peñalolén (Peñalolén is a low income district in the Metropolitan Region in Santiago de Chile.), to explore risk facts for domestic violence during pregnancy, and to establish associations with their psychological health. Method and Materials . 256 pregnant women were assessed with a domestic violence screening and a questionnaire on mental symptoms. Frequency and correlations analysis were developed. Results . 5, 9% of the participants reported physical violence during current pregnancy. Emotional violence ascended to 30, 1% of the cases. Main risk facts found were as follows: having suffered violence along lifetime and physical violence during the last year. Anxiety and depressive symptoms positively correlated to domestic violence during pregnancy, but also to previous domestic violence experiences. Conclusions . Domestic violence during pregnancy is a prevalent problem and domestic violence history constitutes an alert to its occurrence. Positive and significant association to psychological disturbances suggests the need to detect it early during antenatal care.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "The Social World and Its Interactions", "The Human Mind and Its Complexity" ]
2716511
Valorization trajectory of a 3d particle image velocimetry instrument
Actual implementation of impactful applications for microfluidic devices in a commercial setting has been surprisingly limited so far. The cause can be to a great extent attributed to the main feature of microfluidic devices: their small dimensions. While miniaturized structures are essential in generating key functionalities, they are also ideal nucleation and anchor sites for solid material present in the liquid that flows through the channels, a phenomenon called fouling. This subsequently results in a reduced or loss of functionality and eventually plugging of the entire flow system. The solution to avoiding fouling is measuring the flow in microfluidic devices in 3D, by particle image velocimetry (PIV), either when designing or using them. However, achieving 3D imaging of flows is currently an extremely difficult task due to the amount of work, high costs and lengthy timelines required. Our value proposition in the ERC Proof of Concept project ‘3D-PIV’ is a table-top device able to efficiently analyse the velocimetry of particles in 3D, offering an unprecedented level of detail of the fluid motion through micron-sized channels/inlets/outlets, opening new possibilities in microfluidics design and validation with significant impact on multiple applications. One of the killer applications we envision, and our focus in this ERC Proof of Concept project, is in the pharmaceutical and chemical industries, for the manufacturing of drugs or chemical components, to enable, adjust or improve their separation. In this project we will focus on building a strong business case for our 3D-PIV technology through prototyping, optimizing software, market analysis and business development.
[ "Products and Processes Engineering", "Physical and Analytical Chemical Sciences", "Materials Engineering" ]
174933
The hall plateau transition and non-unitary quantum field theory
I propose to solve the Quantum Field Theory (QFT) describing the transition between plateaus of quantized Hall conductance in the Integer Quantum Hall Effect (IQHE). The existence of the plateaus and their topological origin are certainly well understood. In sharp contrast, the transition, which mixes the effects of disorder, magnetic field and possibly interactions, remains very mysterious. Numerical studies of lattice models are plagued by disorder. The QFT description involves physics at very strong coupling, and requires a non-perturbative solution before quantitative predictions can be made. Finding such a solution is very difficult because the QFT for the plateau transition is ‘non-unitary’ - it involves a non-Hermitian ‘Hamiltonian’. Non-unitary QFT is a challenging, almost unexplored topic, that must be first developed before the plateau transition can be addressed. I propose to carry out this task with a cross-disciplinary strategy that uses ideas and tools from conformal field theory, statistical mechanics, and mathematics. Key to this strategy is a new and powerful way of analyzing lattice regularizations of the QFTs by focussing on their algebraic properties directly on the lattice, with a mix of advanced representation theory and numerical techniques. The results - in particular, concerning conformal invariance and renormalization group flows in the non-unitary case - will then be used to solve the QFT models for the plateau transition in the IQHE and in other universality classes of 2D Anderson insulators. This will be a landmark step in our understanding of the localization/delocalization transition in two dimensions, and allow a long delayed comparison of theory with experiment. The results will, more generally, impact many other areas of physics where non-unitary QFT plays a central role - from disordered systems of statistical mechanics to the string theory side of the AdS/CFT duality, to the effective description of open quantum systems.
[ "Condensed Matter Physics", "Mathematics" ]
10.1080/02699931.2016.1177489
More Than Words And Faces Evidence For A Stroop Effect Of Prosody In Emotion Word Processing
Humans typically combine linguistic and nonlinguistic information to comprehend emotions. We adopted an emotion identification Stroop task to investigate how different channels interact in emotion communication. In experiment 1, synonyms of "happy" and "sad" were spoken with happy and sad prosody. Participants had more difficulty ignoring prosody than ignoring verbal content. In experiment 2, synonyms of "happy" and "sad" were spoken with happy and sad prosody, while happy or sad faces were displayed. Accuracy was lower when two channels expressed an emotion that was incongruent with the channel participants had to focus on, compared with the cross-channel congruence condition. When participants were required to focus on verbal content, accuracy was significantly lower also when prosody was incongruent with verbal content and face. This suggests that prosody biases emotional verbal content processing, even when conflicting with verbal content and face simultaneously. Implications for multimodal communication and language evolution studies are discussed.
[ "The Human Mind and Its Complexity", "Neuroscience and Disorders of the Nervous System" ]
W2038233326
Education in organ donation among students in Germany – results of an intervention study
In Germany, organ donation remains low and is not sufficient to duly address all patients on the waiting lists. It is likely that lack of information and subsequent insecurity in the adult population relate to this imbalance. Virtually no data exist about teenagers' knowledge of organ donation.A questionnaire-based survey was performed among all 11th and 12th-grade students of secondary schools in Mainz, Germany. All students were subsequently offered an information event. The survey consisting of 17 questions was repeated later. The survey was voluntary and performed in class without the students using any information sources.1165 (48%) students participated in the first survey, and 1491 (61.7%) in the second survey. 11.3% in the first and 19.55% in the second survey had an organ donor card. 38.83% reported having informed themselves within the last 12 months on organ donation. 56.56% would have filled out an organ donor card with an approval if they had had to decide at the time of survey.When young people discuss organ donation in their families or when they seek information themselves, the acceptance of organ donation greatly improves. Our data suggest that education on organ donation can double the number of carriers of an organ donor card among students.
[ "The Social World and Its Interactions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1088/0951-7715/27/10/2579
Well Posedness And Accuracy Of The Ensemble Kalman Filter In Discrete And Continuous Time
The ensemble Kalman filter (EnKF) is a method for combining a dynamical model with data in a sequential fashion. Despite its widespread use, there has been little analysis of its theoretical properties. Many of the algorithmic innovations associated with the filter, which are required to make a useable algorithm in practice, are derived in an ad hoc fashion. The aim of this paper is to initiate the development of a systematic analysis of the EnKF, in particular to do so for small ensemble size. The perspective is to view the method as a state estimator, and not as an algorithm which approximates the true filtering distribution. The perturbed observation version of the algorithm is studied, without and with variance inflation. Without variance inflation well-posedness of the filter is established; with variance inflation accuracy of the filter, with respect to the true signal underlying the data, is established. The algorithm is considered in discrete time, and also for a continuous time limit arising when observations are frequent and subject to large noise. The underlying dynamical model, and assumptions about it, is sufficiently general to include the Lorenz '63 and '96 models, together with the incompressible Navier–Stokes equation on a two-dimensional torus. The analysis is limited to the case of complete observation of the signal with additive white noise. Numerical results are presented for the Navier–Stokes equation on a two-dimensional torus for both complete and partial observations of the signal with additive white noise.
[ "Mathematics", "Computer Science and Informatics", "Systems and Communication Engineering" ]
185582
Adaptive adas to support incapacitated drivers mitigate effectively risks through tailor made hmi under automation
ADAS&ME (“Adaptive ADAS to support incapacitated drivers &Mitigate Effectively risks through tailor made HMI under automation”) will develop adapted Advanced Driver Assistance Systems, that incorporate driver/rider state, situational/environmental context, and adaptive interaction to automatically transfer control between vehicle and driver/rider and thus ensure safer and more efficient road usage. To achieve this, a holistic approach will be taken which considers automated driving along with information on driver/rider state. The work is based around 7 provisionally identified Use Cases for cars, trucks, buses and motorcycles, aiming to cover a large proportion of driving on European roads. Experimental research will be carried out on algorithms for driver state monitoring as well as on HMI and automation transitions. It will develop robust detection/prediction algorithms for driver/rider state monitoring towards different driver states, such as fatigue, sleepiness, stress, inattention and impairing emotions, employing existing and novel sensing technologies, taking into account traffic and weather conditions via V2X and personalizing them to individual driver’s physiology and driving behaviour. In addition, the core development includes multimodal and adaptive warning and intervention strategies based on current driver state and severity of scenarios. The final outcome is the successful fusion of the developed elements into an integrated driver/rider state monitoring system, able to both be utilized in and be supported by vehicle automation of Levels 1 to 4. The system will be validated with a wide pool of drivers/riders under simulated and real road conditions and under different driver/rider states; with the use of 2 cars (1 conventional, 1 electric), 1 truck, 2 PTWs and 1 bus demonstrators. This challenging task has been undertaken by a multidisciplinary Consortium of 30 Partners, including an OEM per vehicle type and 7 Tier 1 suppliers.
[ "Products and Processes Engineering", "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1038/s41586-018-0144-9
Reciprocal signalling by Notch�Collagen V�CALCR retains muscle stem cells in their niche
The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix 1-3 . Although Notch and other signalling pathways have previously been reported to regulate quiescence of stem cells 4-9, the composition and source of molecules that maintain the stem cell niche remain largely unknown. Here we show that adult muscle satellite (stem) cells in mice produce extracellular matrix collagens to maintain quiescence in a cell-autonomous manner. Using chromatin immunoprecipitation followed by sequencing, we identified NOTCH1/RBPJ-bound regulatory elements adjacent to specific collagen genes, the expression of which is deregulated in Notch-mutant mice. Moreover, we show that Collagen V (COLV) produced by satellite cells is a critical component of the quiescent niche, as depletion of COLV by conditional deletion of the Col5a1 gene leads to anomalous cell cycle entry and gradual diminution of the stem cell pool. Notably, the interaction of COLV with satellite cells is mediated by the Calcitonin receptor, for which COLV acts as a surrogate local ligand. Systemic administration of a calcitonin derivative is sufficient to rescue the quiescence and self-renewal defects found in COLV-null satellite cells. This study reveals a Notch-COLV-Calcitonin receptor signalling cascade that maintains satellite cells in a quiescent state in a cell-autonomous fashion, and raises the possibility that similar reciprocal mechanisms act in diverse stem cell populations.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2111387169
Cosmic censorship in overcharging a Reissner-Nordström black hole via charged particle absorption
There is a claim that a static charged black hole (Reissner-Nordstr\"{o}m black hole) can be overcharged by absorbing a charged test particle. If it is true, it might give a counter example to the weak cosmic censorship conjecture, which states that spacetime singularities are never observed by a distant observer. However, so far the proposed process has only been analyzed within a test particle approximation. Here we claim that the back reaction effects of a charged particle cannot be neglected when judging whether the suggested process is really a counter example to the cosmic censorship conjecture or not. Furthermore, we argue that all the back reaction effects can be properly taken into account when we consider the trajectory of a particle on the border between the plunge and bounce orbits. In such marginal cases we find that the Reissner-Nordstr\"{o}m black hole can never be overcharged via the absorption of a charged particle. Since all the plunge orbits are expected to have a higher energy than the marginal orbit, we conclude that there is no supporting evidence that indicates the violation of the cosmic censorship in the proposed overcharging process.
[ "Fundamental Constituents of Matter", "Universe Sciences" ]
10.1093/mnras/stx2729
Predicting the locations of possible long-lived low-mass first stars: Importance of satellite dwarf galaxies
The search for metal-free stars has so far been unsuccessful, proving that if there are surviving stars from the first generation, they are rare, they have been polluted or we have been looking in the wrong place. To predict the likely location of Population III (Pop III) survivors, we semi-analytically model early star formation in progenitors of Milky Way-like galaxies and their environments. We base our model on merger trees from the high-resolution dark matter only simulation suite Caterpillar. Radiative and chemical feedback are taken into account self-consistently, based on the spatial distribution of the haloes. Our results are consistent with the non-detection of Pop III survivors in the MilkyWay today. We find that possible surviving Pop III stars are more common in Milky Way satellites than in the main Galaxy. In particular, low-mass Milky Way satellites contain a much larger fraction of Pop III stars than the Milky Way. Such nearby, low-mass Milky Way satellites are promising targets for future attempts to find Pop III survivors, especially for high-resolution, high signal-to-noise spectroscopic observations. We provide the probabilities of finding a Pop III survivor in the red giant branch phase for all known Milky Way satellites to guide future observations.
[ "Universe Sciences" ]
10.1523/JNEUROSCI.0014-18.2018
Anterior Thalamic Excitation And Feedforward Inhibition Of Presubicular Neurons Projecting To Medial Entorhinal Cortex
The presubiculum contains head direction cells that are crucial for spatial orientation. Here, we examined the connectivity and strengths of thalamic inputs to presubicular layer 3 neurons projecting to the medial entorhinal cortex in the mouse. We recorded pairs of projection neurons and interneurons while optogenetically stimulating afferent fibers from the anterior thalamic nuclei. Thalamic input differentially affects presubicular neurons: layer 3 pyramidal neurons and fast-spiking parvalbumin-expressing interneurons are directly and monosynaptically activated, with depressing dynamics, whereas somatostatin-expressing interneurons are indirectly excited, during repetitive anterior thalamic nuclei activity. This arrangement ensures that the thalamic excitation of layer 3 cells is often followed by disynaptic inhibition. Feedforward inhibition is largely mediated by parvalbumin interneurons, which have a high probability of connection to presubicular pyramidal cells, and it may enforce temporally precise head direction tuning during head turns. Our data point to the potential contribution of presubicular microcircuits for fine-tuning thalamic head direction signals transmitted to medial entorhinal cortex. SIGNIFICANCE STATEMENT How microcircuits participate in shaping neural inputs is crucial to understanding information processing in the brain. Here, we show how the presubiculum may process thalamic head directional information before transmitting it to the medial entorhinal cortex. Synaptic inputs from the anterior thalamic nuclei excite layer 3 pyramidal cells and parvalbumin interneurons, which mediate disynaptic feedforward inhibition. Somatostatin interneurons are excited indirectly. Presubicular circuits may switch between two regimens depending on the angular velocity of head movements. During immobility, somatostatin-pyramidal cell interactions could support maintained head directional firing with attractor-like dynamics. During rapid head turns, in contrast, parvalbumin-mediated feedforward inhibition may act to tune the head direction signal transmitted to medial entorhinal cortex.
[ "Neuroscience and Disorders of the Nervous System" ]
W2175430741
Analysis of Rooftop Solar PV System Implementation Barrier in Puducherry Smart Grid Pilot Project
Abstract India is on a growth trajectory in terms of population as well as development. To maintain the pace of development along with environmental and fuel consideration, the country is desperate to explore and implement various emerging features like smart grids,renewable technologies,etc, with the policy of “go green”, several initiatives are being taken by GoI and echoed by respective authorities. The smart grid project in Puducherry is one of such initial pilot project in India. Rooftop solar PV system has been used as renewable sources in this Smart Grid. This paper presents an analysis of rooftop solar PV system implementation barrier in Puducherry smart grid pilot project. A survey has been performed with electricity consumers, considering questions regarding consumption over different period, space availability for roof top PV system and users experience with this technology. Result of the survey and impact of government initiatives are also discussed in detail.
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]
802986
QUAntum nanophotonics in Rolled-Up Metamaterials
Novel sophisticated technologies that exploit the laws of quantum physics form a cornerstone for the future well-being, economic growth and security of Europe. Here photonic devices have gained a prominent position because the absorption, emission, propagation or storage of a photon is a process that can be harnessed at a fundamental level and render more practical ways to use light for such applications. However, the interaction of light with single quantum systems under ambient conditions is typically very weak and difficult to control. Furthermore, there are quantum phenomena occurring in matter at nanometer length scales that are currently not well understood. These deficiencies have a direct and severe impact on creating a bridge between quantum physics and photonic device technologies. aQUARiUM, precisely address the issue of controlling and enhancing the interaction between few photons and rolled-up nanostructures with ability to be deployed in practical applications. With aQUARiUM, we will take epsilon (permittivity)-near-zero (ENZ) metamaterials into quantum nanophotonics. To this end, we will integrate quantum emitters with rolled-up waveguides, that act as ENZ metamaterial, to expand and redefine the range of light-matter interactions. We will explore the electromagnetic design freedom enabled by the extended modes of ENZ medium, which “stretches” the effective wavelength inside the structure. Specifically, aQUARiUM is built around the following two objectives: (i) Enhancing light-matter interactions with single emitters (Enhance) independent of emitter position. (ii) Enabling collective excitations in dense emitter ensembles (Collect) coherently connect emitters on nanophotonic devices to obtain coherent emission. aQUARiUM aims to create novel light-sources and long-term entanglement generation and beyond. The envisioned outcome of aQUARiUM is a wholly new photonic platform applicable across a diverse range of areas.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics", "Systems and Communication Engineering" ]
W1433129784
Automatic Construction of Temporally Extended Actions for MDPs Using Bisimulation Metrics
Temporally extended actions are usually effective in speeding up reinforcement learning. In this paper we present a mechanism for automatically constructing such actions, expressed as options [24], in a finite Markov Decision Process (MDP). To do this, we compute a bisimulation metric [7] between the states in a small MDP and the states in a large MDP, which we want to solve. The shape of this metric is then used to completely define a set of options for the large MDP. We demonstrate empirically that our approach is able to improve the speed of reinforcement learning, and is generally not sensitive to parameter tuning.
[ "Computer Science and Informatics" ]
10.1088/1742-6596/527/1/012016
Transport Coefficients Of Quark Gluon Plasma In A Kinetic Theory Approach
One of the main results of heavy ions collision at relativistic energy experiments is the very small shear viscosity to entropy density ratio of the Quark-Gluon Plasma, close to the conjectured lower bound η/s = 1/4π for systems in the infinite coupling limit. Transport coefficients like shear viscosity are responsible of non-equilibrium properties of a system: Green- Kubo relations give us an exact expression to compute these coefficients. We computed shear viscosity numerically using Green-Kubo relation in the framework of Kinetic Theory solving the relativistic transport Boltzmann equation in a finite box with periodic boundary conditions. We investigated different cases of particles, for one component system (gluon matter), interacting via isotropic or anisotropic cross-section in the range of temperature of interest for HIC. Green-Kubo results are in agreement with Chapman-Enskog approximation while Relaxation Time approximation can underestimates the viscosity of a factor 2. Another transport coefficient of interest is the electric conductivity σel which determines the response of QGP to the electromagnetic fields present in the early stage of the collision. We study the σel dependence on microscopic details of interaction and we find also in this case that Relaxation Time Approximation is a good approximation only for isotropic cross-section.
[ "Fundamental Constituents of Matter", "Condensed Matter Physics" ]
284094
Living With Remnants: Politics, Materiality and Subjectivity in the Aftermath of Past Atrocities in Turkey
The proposed project aims to study 'remnants' from past atrocities in contemporary Turkey and its associated migrant and diaspora communities elsewhere. 'Remnants' are conceptualized as multiplex phenomena which have an enduring effect in the after-life of persons and communities which were once associated with them. These may be material remains in the form of houses, temples, and other forms of built and spatial structure once used and inhabited by communities that were displaced, deported, ethnically cleansed, or exterminated. They may also be immaterial affects, in the form of memory or the imagination as associated with past atrocities, such as accounts of haunting and/or loss in the aftermath of violence. 'Remnants' figure in subjective worlds in embodied forms, where contemporary inhabitants of Turkey have begun to claim Armenian, Greek, or Kurdish ancestry. They are also 'political' insofar as they constitute the context for ongoing inter-communitarian relations in and outside Turkey, relations which sometimes take 'legal' and 'economic' forms. This project proposes to ethnographically study 'remnants' in Turkey and its diaspora communities at a time when Turkey is being challenged to face its past of mass atrocities. We propose to actualize this research by focusing on four key city-sites (Tunceli-Elazig, Mardin, Diyarbakir-Batman, and Antakya) in Turkey's under-studied south and south Eastern regions, relevant from the point of view of the mass atrocities targeting Armenians, Assyrian-Syriacs, Alevis, Kurds and other local communities which this project aims to focus on. The project will be composed of four ethnographic sub-projects in these sites and their respective diasporas outside Turkey (Syria, Cyprus, Germany, Sweden) composed of migrants, deportees, survivors, or refugees from the sites of mass atrocity. The project will employ innovative methodologies in ethnographic and archival research in addressing the aftermath of violence in Turkey.
[ "The Study of the Human Past", "The Social World and Its Interactions", "Human Mobility, Environment, and Space", "Studies of Cultures and Arts" ]
10.1016/j.bbadis.2017.12.013
Protective effect of genetic deletion of pannexin1 in experimental mouse models of acute and chronic liver disease
Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation. To this end, wild-type and pannexin1−/− mice were overdosed with acetaminophen for 1, 6, 24 or 48 h or were fed a choline-deficient high-fat diet for 8 weeks. Evaluation of the effects of genetic pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, lipid accumulation, protein adduct formation, oxidative stress and inflammation. In parallel, in order to elucidate molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. The results of this study show that pannexin1−/− diseased mice present less liver damage and oxidative stress, while inflammation was only decreased in pannexin1−/− mice in which non-alcoholic steatohepatitis was induced. A multitude of genes related to inflammation, oxidative stress and xenobiotic metabolism were differentially modulated in both liver disease models in wild-type and in pannexin1−/− mice. Overall, the results of this study suggest that pannexin1 may play a role in the pathogenesis of liver disease.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Physiology in Health, Disease and Ageing" ]
261302
Priming epithelial cell activation to regenerate the lung
Chronic obstructive pulmonary disease (COPD), a global health problem, will be the third leading cause of death by 2020. No effective therapy exists for COPD, which is characterized by a progressive loss of lung tissue, in particular functional alveolar epithelium, due to the inability of the lung to regenerate. Thus, regeneration of functional lung tissue would be a tremendous step forward, which has not been demonstrated as of yet. The alveolar epithelium is essential for normal lung function and composed of alveolar type I (ATI) and type II (ATII) cells. ATII cells serve as progenitors for alveolar epithelial restoration via differentiation into ATI cells. Induction of lung regeneration requires a tight interplay between initiating and differentiating factors acting on the alveolar epithelium. The overall aim of this proposal is to explore the regenerative potential of the adult human lung, driven by the alveolar epithelium. We will utilize an ex vivo lung regeneration model, characterize ATI/II cells in diseased lungs, and explore novel initiating and differentiating factors in vivo and ex vivo. WNT/²-catenin signaling is a promising initiating factor for lung regeneration. We have recently demonstrated a crucial role of WNT/²-catenin signaling in alveolar epithelial cell repair in lung disease. Further, embryos lacking WNT2/2b expression exhibited complete lung agenesis, demonstrating the requirement of WNT/²-catenin signaling in lung generation. We will explore WNT/²-catenin signaling in ATI/II cells, and the regenerative potential thereof. We will analyze the ATI/II cell phenotype in mouse and human COPD specimen, to identify novel differentiation factors facilitating lung regeneration. We will consolidate our findings by testing the therapeutic applicability of initiating and differentiating factors in COPD in our ex vivo human lung regeneration model. This will lead to reliable and validated results that will be successfully translated into the clinic.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases" ]
3734274
Artificial microtubules based on switchable cyclic peptides
Naturally occurring living materials, for e.g. the cell cytoskeleton, consist of intricate supramolecular polymers whose self-assembly is controlled by high energy molecules such as guanosine triphosphate GTP. MiNaturally occurring living materials, such as the cell cytoskeleton, consist of intricate supramolecular polymers whose self-assembly is controlled by high energy molecules such as guanosine triphosphate GTP. Microtubules for example, are incredibly strong, but because they are chemically fueled by GTP, they can be built up or broken down at specific times and locations inside the cell. The tubules are in so-called non-equilibrium steady states, and are kept away from the thermodynamic equilibrium for extended periods of time. In the recent years, artificial supramolecular polymers have been made that are transiently out-of-equilibrium by addition of a single shot of chemical fuel, or for long times by continuous addition of fuel and removal of waste. The mechanical properties of the latter artificial systems are quite poor in comparison with real microtubules. The aim of this CYCLOTUBES project is to make artificial microtubules from cyclic peptides that can chemically or enzymatically be switched between the assembled and disassembled state. To this end, we will use oxidation and reduction reactions in a cell-like environment, that is, in a membrane enclosed chamber. In the latter, chemical fuel can be added and waste be removed continuously. In addition, the assembly/disassembly of the artificial tubules can be monitored using microscopy. Our work will give fundamentally new insights into out-of-equilibrium self-assembly, and could lead to novel life-like materials that are capable of performing significant mechanical work due to the unique mechanical properties of the cyclic peptide tubules. The candidate will work at the forefront of the field of systems chemistry and supramolecular chemistry, which are very important for the competitiveness of Europe.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
681746
A Probe of the Periodic Elements for Life in the Sea
Chemical elements are the building blocks of life. The major elements, C, H. O, N, P, S are easily recognised as essential nutrients, but their use by life relies on metalloproteins. The identity of the metal centres of these metalloproteins and even the broader palette of trace elements fundamental to life are remarkably poorly known. Whole genomes remain opaque to decoding of this bioinorganic dimension, and optimal trace element concentrations for physiological function. Defining the elemental requirements for maximum growth rate of photosynthesising phytoplankton in the ocean, is critical to understanding Earth's climate. Although microscopic in stature, phytoplankton exert a gigantic influence on the biological pumping of carbon from the atmosphere to the deep ocean. Yet their metal requirements are poorly constrained, being inferred from cellular quotas and ""nutrient-like"" ocean metal distributions, susceptible to ambiguity between mistaken cellular uptake and use. APPELS will undertake a two-pronged approach to define the modern marine metallome/metalloproteome. I will explore the expanse of the periodic table for novel required elements by growing phytoplankton, representative of the broadest chemotypes, in manipulated media, to delineate optimal conditions for growth whereby any limitation at lowered concentrations implies use. The second prong uses cutting-edge techniques that unite methods from proteomics with geochemical mass-spectrometry to allow both metals and their associated proteins to be examined comprehensively. APPELS will transform our understanding of the essential elements in the ocean and how the biological pump of carbon is geared to ocean chemistry in an evolving world. More broadly, APPELS will provide a step change in documented protein-metal binding centres, with implications for discovery of novel biochemical pathways, and optimal nutrition.
[ "Earth System Science", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Environmental Biology, Ecology and Evolution", "Physical and Analytical Chemical Sciences" ]
320769
Origins of integrability in AdS/CFT correspondence
Fundamental interactions in nature are well described by quantum gauge fields in 4 space-time dimensions (4d). When the strength of gauge interaction is weak the Feynman perturbation techniques are very efficient for the description of most of the experimentally observable consequences of the Standard model and for the study of high energy processes in QCD. But in the intermediate and strong coupling regime, such as the relatively small energies in QCD, the perturbation theory fails leaving us with no reliable analytic methods (except the Monte-Carlo simulation). The project aims at working out new analytic and computational methods for strongly coupled gauge theories in 4d. We will employ for that two important discoveries: 1) the gauge-string duality (AdS/CFT correspondence) relating certain strongly coupled gauge Conformal Field Theories to the weakly coupled string theories on Anty-deSitter space; 2) the solvability, or integrability of maximally supersymmetric (N=4) 4d super Yang-Mills (SYM) theory in multicolor limit. Integrability made possible pioneering exact numerical and analytic results in the N=4 multicolor SYM at any coupling, effectively summing up all 4d Feynman diagrams. Recently, we conjectured a system of functional equations - the AdS/CFT Y-system – for the exact spectrum of anomalous dimensions of all local operators in N=4 SYM. The conjecture has passed all available checks. My project is aimed at the understanding of origins of this, still mysterious integrability. Deriving the AdS/CFT Y-system from the first principles on both sides of gauge-string duality should provide a long-awaited proof of the AdS/CFT correspondence itself. I plan to use the Y-system to study the systematic weak and strong coupling expansions and the so called BFKL limit, as well as for calculation of multi-point correlation functions of N=4 SYM. We hope on new insights into the strong coupling dynamics of less supersymmetric gauge theories and of QCD.
[ "Fundamental Constituents of Matter", "Mathematics" ]
10.1051/0004-6361/201833140
The Alma Pils Survey First Detection Of Methyl Isocyanide Ch3Nc In A Solar Type Protostar
Context. Methyl isocyanide (CH3NC) is the isocyanide with the largest number of atoms confirmed in the interstellar medium (ISM), but it is not an abundant molecule, having only been detected towards a handful of objects. Conversely, its isomer, methyl cyanide (CH3CN), is one of the most abundant complex organic molecules detected in the ISM, with detections in a variety of low-and high-mass sources. Aims. The aims of this work are to determine the abundances of methyl isocyanide in the solar-type protostellar binary IRAS 16293-2422 and to understand the stark abundance differences observed between methyl isocyanide and methyl cyanide in the ISM. Methods. We use Atacama Large Millimeter/submillimeter Array (ALMA) observations from the Protostellar Interferometric Line Survey (PILS) to search for methyl isocyanide and compare its abundance with that of its isomer methyl cyanide. We use a new line catalogue from the Cologne Database for Molecular Spectroscopy (CDMS) to identify methyl isocyanide lines. We also model the chemistry with an updated version of the three-phase chemical kinetics model MAGICKAL, presenting the first chemical modelling of methyl isocyanide to date. Results. We detect methyl isocyanide for the first time in a solar-type protostar, IRAS 16293-2422 B, and present upper limits for its companion protostar, IRAS 16293-2422 A. Methyl isocyanide is found to be at least 20 times more abundant in source B compared to source A, with a CH3CN/CH3NC abundance ratio of 200 in IRAS 16293-2422 B and >5517 in IRAS 16293-2422 A. We also present the results of a chemical model of methyl isocyanide chemistry in both sources, and discuss the implications for methyl isocyanide formation mechanisms and the relative evolutionary stages of both sources. The chemical modelling is unable to match the observed CH3CN/CH3NC abundance ratio towards the B source at densities representative of that source. The modelling, however, is consistent with the upper limits for the A source. There are many uncertainties in the formation and destruction pathways of methyl isocyanide, and it is therefore not surprising that the initial modelling attempts do not reproduce observations. In particular, it is clear that some destruction mechanism of methyl isocyanide that does not destroy methyl cyanide is needed. Furthermore, these initial model results suggest that the final density plays a key role in setting the abundance ratio. The next steps are therefore to obtain further detections of methyl isocyanide in more objects, as well as undertaking more detailed physico-chemical modelling of sources such as IRAS16293.
[ "Physical and Analytical Chemical Sciences", "Universe Sciences" ]
10.1093/sysbio/syw115
A Unifying Comparative Phylogenetic Framework Including Traits Coevolving Across Interacting Lineages
Models of phenotypic evolution fit to phylogeneticcomparative data are widely used tomake inferences regarding the tempo and mode of trait evolution. A wide range of models is already available for this type of analysis, and the field is still under active development. One of the most needed development concerns models that better account for the effect of within- and between-clade interspecific interactions on trait evolution, which can result from processes as diverse as competition, predation, parasitism, or mutualism. Here, we begin by developing a very general comparative phylogenetic framework for (multi)-trait evolution that can be applied to both ultrametric and nonultrametric trees. This framework not only encapsulates many previous models of continuous univariate and multivariate phenotypic evolution, but also paves the way for the consideration of a much broader series of models in which lineages coevolve, meaning that trait changes in one lineage are influenced by the value of traits in other, interacting lineages. Next, we provide a standard way for deriving the probabilistic distribution of traits at tip branches under our framework. We show that a multivariate normal distribution remains the expected distribution for a broad class of models accounting for interspecific interactions. Our derivations allow us to fit various models efficiently, and in particular greatly reduce the computation time needed to fit the recently proposed phenotype matching model. Finally, we illustrate the utility of our framework by developing a toy model for mutualistic coevolution. Our framework should foster a new era in the study of coevolution from comparative data.
[ "Environmental Biology, Ecology and Evolution", "Mathematics", "Computer Science and Informatics" ]
170008
National contact points for climate action, raw materials, environment and resource efficiency
The National Contact Points perform valuable services in guiding and supporting national applicants in preparing proposals for Horizon 2020 funding. We expect that through an enhanced cooperation and networking between these national entities, a higher quality of their consulting services and thus of proposals and projects can be achieved. Therefore, the overall objective of NCPs CaRE is to form a joint cooperation network of experienced and less experienced NCPs on SC5 “Climate action, environment, resource efficiency and raw materials” which aims at pooling their resources and know-how to raise the overall quality of services provided to their clients. By involving 23 formally nominated National Contact Points across Europe, the NCPs CaRE project will significantly strengthen trans-national cooperation. In addition, NCPs CaRE will extensively involve the 26 NCPs that have decided to become “associated partner”. To harness synergies is especially relevant to SC5 NCPs, since potential applicants within this Challenge are very diverse with respect to their scientific or organisational background, level of experience, involvement in transnational networks. Concretely, activities of NCPs CaRE towards this goal include, amongst others, teaming and twinning schemes, the compilation of best practices handbooks and manuals, events, meetings and trainings both on-line and on a face-to-face basis, as well as a wide range of other communication and dissemination tools and platforms. These activities foreseen by NCPs CaRE will contribute to enhancing the impact of R&I in SC5 and ensure a more efficient use of resources and R&I developments by improving the work flow between NCPs, applicants, the Commission, and other parties with a stake in SC5. Tailor-made like they are for the SC5 constituency, these activities will make it easier for all participating and benefitting NCPs to enhance the number of proposals with regards to both quantity and quality.
[ "Earth System Science", "Institutions, Governance and Legal Systems" ]
10.1080/1369801X.2013.798472
Indigenous Performance Of History Loss And Remembrance In Whispering In Our Hearts
This essay undertakes a cultural analysis that draws from the authors' different disciplinary and media backgrounds – Romaine Moreton in Indigenous philosophy, spoken-word performance and filmmaking and Therese Davis in film and cultural studies – to examine the Australian historical documentary film Whispering In Our Hearts: The Mowla Bluff Massacre (2001). Directed by Mitch Torres in collaboration with her community, the Nyikina, Mangala and Karrajarri people of northwestern Australia, the film uses a range of performance modes to expose how Indigenous accounts of a massacre in 1916 have been systematically covered over in and through written history. We examine ways in which the film ‘translates’ the meanings of the Indigenous community's songs and stories, making their content available to a wider audience and argue that the film is more than a contested or competing history in the western sense. The community innovates to produce a new historiography by adopting and adapting film technology as a mean. . .
[ "The Study of the Human Past", "Studies of Cultures and Arts" ]
10.1007/JHEP04(2011)037
Chronology Protection And The Stringy Exclusion Principle
We construct a family of supersymmetric solutions to AdS supergravity in three dimensions, that correspond to type IIB seven branes wrapped on an internal S3xT4. These solutions are generalizations of the three dimensional Goedel universe and have closed timelike curves. We propose an enhancon-like mechanism for excising the closed timelike curve region by including the effects of additional light degrees of freedom. These take the form of tensionless 7-brane probes, effectively described through the backreaction of a smeared domain wall. The absence of closed timelike curves in the asymptotic AdS3 geometries obtained in this way is shown to be equivalent to a unitarity bound in the dual CFT, known as the stringy exclusion principle.
[ "Fundamental Constituents of Matter", "Mathematics" ]
10.1038/nature19081
Tumour hypoxia causes DNA hypermethylation by reducing TET activity
Hypermethylation of the promoters of tumour suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. How these changes arise is poorly understood. Here we show that the activity of oxygen-dependent ten-eleven translocation (TET) enzymes is reduced by tumour hypoxia in human and mouse cells. TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation. This reduction in activity occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, hypoxia-inducible factor activity or reactive oxygen species, and depends directly on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. In patients, tumour suppressor gene promoters are markedly more methylated in hypoxic tumour tissue, independent of proliferation, stromal cell infiltration and tumour characteristics. Our data suggest that up to half of hypermethylation events are due to hypoxia, with these events conferring a selective advantage. Accordingly, increased hypoxia in mouse breast tumours increases hypermethylation, while restoration of tumour oxygenation abrogates this effect. Tumour hypoxia therefore acts as a novel regulator of DNA methylation.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1038/nature11070
RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation
Evolution of the mammalian sex chromosomes has resulted in a heterologous X and Y pair, where the Y chromosome has lost most of its genes. Hence, there is a need for X-linked gene dosage compensation between XY males and XX females. In placental mammals, this is achieved by random inactivation of one X chromosome in all female somatic cells. Upregulation of Xist transcription on the future inactive X chromosome acts against Tsix antisense transcription, and spreading of Xist RNA in cis triggers epigenetic changes leading to X-chromosome inactivation. Previously, we have shown that the X-encoded E3 ubiquitin ligase RNF12 is upregulated in differentiating mouse embryonic stem cells and activates Xist transcription and X-chromosome inactivation. Here we identify the pluripotency factor REX1 as a key target of RNF12 in the mechanism of X-chromosome inactivation. RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. Using chromatin immunoprecipitation sequencing, REX1 binding sites were detected in Xist and Tsix regulatory regions. Overexpression of REX1 in female embryonic stem cells was found to inhibit Xist transcription and X-chromosome inactivation, whereas male Rex1 embryonic stem cells showed ectopic X-chromosome inactivation. From this, we propose that RNF12 causes REX1 breakdown through dose-dependent catalysis, thereby representing an important pathway to initiate X-chromosome inactivation. Rex1 and Xist are present only in placental mammals, which points to co-evolution of these two genes and X-chromosome inactivation.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems" ]
224496
Enhanced data management techniques for real time logistics planning and scheduling
The EU faces the challenge to maintain and increase its economic growth and cope with the problem of freight transport efficiency in Europe. Integration of transport volumes and modes, better use of capacity, flexibility, resource efficiency and cooperation between all actors along the logistic chain are required. Aligned with the European policies and the ALICE roadmap, LOGISTAR objective is to allow effective planning and optimizing of transport operations in the supply chain by taking advantage of horizontal collaboration, relying on the increasingly real-time data gathered from the interconnected environment. For this, a real-time decision making tool and a real-time visualization tool of freight transport will be developed, with the purpose of delivering information and services to the various agents involved in the logistic supply chain, i.e. freight transport operators, their clients, industries and other stakeholders such as warehouse or infrastructure managers. LOGISTAR will address several advances beyond the State of the Art in the interdisciplinary field of the smart algorithms for data processing: Artificial Intelligence focussed onr prediction, parallel hybrid metaheuristics for optimization, automated negotiation techniques, and constraint satisfaction problem solving techniques. The resulting platform will outperform other market products and services such as Freight Exchange Systems, Collaborative Platforms, Transport Control Towers or Routing Systems. LOGISTARS involves RTD organisations (DEUSTO, UCC, CSIC), technology developers (DNET, SWC), consultancy firms (MDST, PRESTON), ICT services developers (SAG, DBH, GENEGIS) and stakeholders from different stages of the supply chain (AHLERS, ZAILOG, NESTLÉ, PLADIS, CODOGNOTTO). The duration of the project is estimated to be 36 months and has an approximate budget of 5 million euros.
[ "Computer Science and Informatics", "Products and Processes Engineering", "Systems and Communication Engineering" ]
10.3390/cells8050386
Rainbow Trout Red Blood Cells Exposed to Viral Hemorrhagic Septicemia Virus Up-Regulate Antigen-Processing Mechanisms and MHC I&II, CD86, and CD83 Antigen-presenting Cell Markers
Nucleated teleost red blood cells (RBCs) are known to express molecules from the major histocompatibility complex and peptide-generating processes such as autophagy and proteasomes, but the role of RBCs in antigen presentation of viruses have not been studied yet. In this study, RBCs exposed ex vivo to viral hemorrhagic septicemia virus (VHSV) were evaluated by means of transcriptomic and proteomic approaches. Genes and proteins related to antigen presentation molecules, proteasome degradation, and autophagy were up-regulated. VHSV induced accumulation of ubiquitinated proteins in ex vivo VHSV-exposed RBCs and showed at the same time a decrease of proteasome activity. Furthermore, induction of autophagy was detected by evaluating LC3 protein levels. Sequestosome-1/p62 underwent degradation early after VHSV exposure, and it may be a link between ubiquitination and autophagy activation. Inhibition of autophagosome degradation with niclosamide resulted in intracellular detection of N protein of VHSV (NVHSV) and p62 accumulation. In addition, antigen presentation cell markers, such as major histocompatibility complex (MHC) class I & II, CD83, and CD86, increased at the transcriptional and translational level in rainbow trout RBCs exposed to VHSV. In summary, we show that nucleated rainbow trout RBCs can degrade VHSV while displaying an antigen-presenting cell (APC)-like profile.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1111/j.1468-2354.2007.00469.x
Nonparametric continuous/discrete choice models
Modeling choices that are both discrete and continuous is important in several settings. The purpose of this article is to explore formulation and identification of such models when indirect utility functions are specified nonparametrically. Here we consider general nonseparable disturbances. We give identification results for nonseparable sample selection models and use these to analyze identification of discrete/continuous choice models.
[ "Mathematics", "Individuals, Markets and Organisations" ]
174558
Ecosystem mechanisms of noise impact on marine fauna
Defining a Good Environmental Status for ocean noise within the EU Marine Framework Strategy is challenged by our limited knowledge about noise effects on marine fauna.ECOSOUND proposes that there are two broad types of mechanisms of noise impact on individual animals, both with potential population-level effects: bottom-up, i.e. noise responses that operate at the genetic, cellular or physiological level, which are likely to be conserved across taxa; and top-down, i.e. behavioural reactions driven by the life style of each species, which may result in physiological damage and even death.ECOSOUND will study bottom-up effects exploring if noise may induce morphological changes in several invertebrate taxa, selecting study species known to show phenotypic plasticity when exposed to stressors. Identifying developmental mechanisms of noise-effects is critical to predict potential common physiological paths over a wide range of taxa.Top-down effects will be investigated by comparing the life style of four species of deep-diving whales, and developing models to identify the reasons and potential consequences at the individual and population level of the different vulnerability of these species to noise. ECOSOUND will use the largest existing dataset of multi-sensor acoustic tag recordings of these whales, and apply quantitative ecology methods to develop bioenergetics models linking foraging and diving behaviour, metabolic rate, life history and social structure of the species.The results will inform transfer functions for PCAD models of population consequences of acoustic disturbance.ECOSOUND will strengthen the multidisciplinary research profile of the fellow with the fields of developmental biology and quantitative ecology, while contributing expertise on cetacean biologging studies and a new research line on the impacts of noise on marine invertebrates to USTAN.Results are relevant for the EU Marine Framework Strategy in the emergent field of management of ocean noise
[ "Environmental Biology, Ecology and Evolution", "Earth System Science", "Cell Biology, Development, Stem Cells and Regeneration", "Physiology in Health, Disease and Ageing" ]
10.15252/embj.201694253
CLPP coordinates mitoribosomal assembly through the regulation of ERAL1 levels
Despite being one of the most studied proteases in bacteria, very little is known about the role of ClpXP in mitochondria. We now present evidence that mammalian CLPP has an essential role in determining the rate of mitochondrial protein synthesis by regulating the level of mitoribosome assembly. Through a proteomic approach and the use of a catalytically inactive CLPP, we produced the first comprehensive list of possible mammalian ClpXP substrates involved in the regulation of mitochondrial translation, oxidative phosphorylation, and a number of metabolic pathways. We further show that the defect in mitoribosomal assembly is a consequence of the accumulation of ERAL1, a putative 12S rRNA chaperone, and novel ClpXP substrate. The presented data suggest that the timely removal of ERAL1 from the small ribosomal subunit is essential for the efficient maturation of the mitoribosome and a normal rate of mitochondrial translation.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1109/CDC.2015.7402313
Randomized Dual Proximal Gradient For Large Scale Distributed Optimization
In this paper we consider distributed optimization problems in which the cost function is separable (i. e. , a sum of possibly non-smooth functions all sharing a common variable) and can be split into a strongly convex term and a convex one. The second term is typically used to encode constraints or to regularize the solution. We propose an asynchronous, distributed optimization algorithm over an undirected topology, based on a proximal gradient update on the dual problem. We show that by means of a proper choice of primal variables, the dual problem is separable and the dual variables can be stacked into separate blocks. This allows us to show that a distributed gossip update can be obtained by means of a randomized block-coordinate proximal gradient on the dual function.
[ "Computer Science and Informatics" ]
249580
State Capacity, Development, Conflict, and Climate Change
The proposed research concerns two sets of issues. The first concerns the role of state building in the development process, and the role played by violent conflict whether internal or external to the state. In this research, we will build a sequence of theoretical models, taking a stepping stone in a basic framework where new infrastructure that expands the state s capacity to raise revenue and to support private markets is viewed as outcome of investments under uncertainty. Our objective in model building is to provide guidance for the collection of historical and contemporary data and for econometric testing, which will both be central to the project. The overall goal of this project is to bring the analysis of state capacity into the mainstream of economics, and thereby shed light on the complex interactions between state building, conflict and development. The second set of issues ultimately concerns the economics of climate change. A first subproject aims at estimating the historical effects of weather on infant mortality in Africa, using a variety of data sources: individual data based on retrospective DHS surveys, finely-gridded weather data based on so-called re-analyis with large-scale climate models, and spatial data on harvest times based on satellite data on plant growth. Exploiting the random component of historical weather fluctuation allows us to estimate causal effects on health outcomes via mechanisms like malnutrition and malaria. This initial research will serve as a pilot study, to develop a methodology for studying the weather impacts on any outcome of interest anywhere in the world. Eventually such estimates will serve to estimate the future costs of climate change.
[ "Individuals, Markets and Organisations", "Earth System Science" ]
10.1038/nmeth.2772
Quantitative single-cell RNA-seq with unique molecular identifiers
Single-cell RNA sequencing (RNA-seq) is a powerful tool to reveal cellular heterogeneity, discover new cell types and characterize tumor microevolution. However, losses in cDNA synthesis and bias in cDNA amplification lead to severe quantitative errors. We show that molecular labels - random sequences that label individual molecules - can nearly eliminate amplification noise, and that microfluidic sample preparation and optimized reagents produce a fivefold improvement in mRNA capture efficiency.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1016/S1473-3099(14)70963-6
Safety And Immunogenicity Of A Modified Vaccinia Virus Ankara Based Influenza A H5N1 Vaccine A Randomised Double Blind Phase 1 2A Clinical Trial
Summary Background Modified vaccinia virus Ankara (MVA) is a promising viral vector platform for the development of an H5N1 influenza vaccine. Preclinical assessment of MVA-based H5N1 vaccines showed their immunogenicity and safety in different animal models. We aimed to assess the safety and immunogenicity of the MVA-haemagglutinin-based H5N1 vaccine MVA-H5-sfMR in healthy individuals. Methods In a single-centre, double-blind phase 1/2a study, young volunteers (aged 18–28 years) were randomly assigned with a computer-generated list in equal numbers to one of eight groups and were given one injection or two injections intramuscularly at an interval of 4 weeks of a standard dose (10 8 plaque forming units [pfu]) or a ten times lower dose (10 7 pfu) of the MVA-H5-sfMR (vector encoding the haemagglutinin gene of influenza A/Vietnam/1194/2004 virus [H5N1 subtype]) or MVA-F6-sfMR (empty vector) vaccine. Volunteers and physicians who examined and administered the vaccine were masked to vaccine assignment. Individuals who received the MVA-H5-sfMR vaccine were eligible for a booster immunisation 1 year after the first immunisation. Primary endpoint was safety. Secondary outcome was immunogenicity. The trial is registered with the Dutch Trial Register, number NTR3401. Findings 79 of 80 individuals who were enrolled completed the study. No serious adverse events were identified. 11 individuals reported severe headache and lightheadedness, erythema nodosum, respiratory illness (accompanied by influenza-like symptoms), sore throat, or injection-site reaction. Most of the volunteers had one or more local (itch, pain, redness, and swelling) and systemic reactions (rise in body temperature, headache, myalgia, arthralgia, chills, malaise, and fatigue) after the first, second, and booster immunisations. Individuals who received the 10 7 dose had fewer systemic reactions. The MVA-H5-sfMR vaccine at 10 8 pfu induced significantly higher antibody responses after one and two immunisations than did 10 7 pfu when assessed with haemagglutination inhibition geometric mean titre at 8 weeks against H5N1 A/Vietnam/1194/2004 (30·2 [SD 3·8] vs 9·2 [2·3] and 108·1 [2·4] vs 15·8 [3·2]). 27 of 39 eligible individuals were enrolled in the booster immunisation study. A single shot of MVA-H5-sfMR 10 8 pfu prime immunisation resulted in higher antibody responses after the booster immunisation than did two shots of MVA-H5-sfMR at the ten times lower dose. Interpretation The MVA-based H5N1 vaccine was well tolerated and immunogenic and therefore the vaccine candidates arising from the MVA platform hold great promise for rapid development in response to a future influenza pandemic threat. However, the immunogenicity of this vaccine needs to be compared with conventional H5N1 inactivated non-adjuvanted vaccine candidates in head-to-head clinical trials. Funding European Research Council.
[ "Immunity, Infection and Immunotherapy", "Prevention, Diagnosis and Treatment of Human Diseases" ]
714233
Dissecting the interplay between the dynamics of immune responses and pathogen proliferation in vivo
Pathogen proliferation has profound implications for its persistence, treatment strategies, and the induction and execution of protective immune responses. In vivo, pathogen proliferation rates are heterogenic, confronting the immune system with a variety of microbial physiological states. It is unknown if, and by what molecular mechanism, the immune response can distinguish these different states on a cellular level. Also, understanding the link between pathogen proliferation and immune cell dynamics could provide critical information on how infections can be controlled, and how to counteract pathogen persistence and antibiotic resistance. However, this question has never been addressed due to difficulties in studying the dynamics of immune cells and at the same time probing pathogen proliferation. In this project, we will make use of a novel in vivo reporter system that I have developed, in order to determine the role of the pathogen's proliferation for its interaction with the immune system. Specifically, we will (1) determine the tissue niche in which the pathogen proliferates, (2) investigate the differential dynamics of phagocyte-pathogen- and of T cell-APC-interactions related to pathogen proliferation rate, (3) manipulate the relationship between pathogen proliferation and immune cell dynamics by using proliferation-deficient mutants and optogenetic pathogen inactivation, (4) identify signaling pathways that are differentially induced in cells infected by high versus low proliferating pathogens, and test their involvement in differential immune cell dynamics related to pathogen proliferation. ImmProDynamics will for the first time provide insights into how cells of the immune system react to distinct pathogen proliferative states in vivo. This will greatly expand our knowledge of host-pathogen interactions, which will be critical for the design of efficient vaccines and antimicrobial therapy.
[ "Immunity, Infection and Immunotherapy", "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems" ]
10.3324/haematol.2019.220889
Somatic mutations and T-cell clonality in patients with immunodeficiency
Common variable immunodeficiency and other late-onset immunodeficiencies often co-manifest with autoimmunity and lymphoproliferation. The pathogenesis of most cases is elusive, as only a minor subset harbors known monogenic germline causes. The involvement of both B and T cells is however implicated. To study whether somatic mutations in CD4+ and CD8+ T cells associate with immunodeficiency, we recruited 17 patients and 21 healthy controls. Eight patients had late-onset common variable immunodeficiency and nine patients other immunodeficiency and/or severe autoimmunity. In total, autoimmunity occurred in 94% and lymphoproliferation in 65%. We performed deep sequencing of 2533 immune-associated genes from CD4+ and CD8+ cells. Deep T-cell receptor beta sequencing was used to characterize CD4+ and CD8+ T-cell receptor repertoires. The prevalence of somatic mutations was 65% in all immunodeficiency patients, 75% in common variable immunodeficiency and 48% in controls. Clonal hematopoiesis-associated variants in both CD4+ and CD8+ cells occurred in 24% of immunodeficiency patients. Results demonstrated mutations in known tumor suppressors, oncogenes, and genes that are critical for immune- and proliferative functions, such as STAT5B (two patients), C5AR1 (two patients), KRAS (one patient), and NOD2 (one patient). Additionally, as a marker of T-cell receptor repertoire perturbation, common variable immunodeficiency patients harbored increased frequencies of clones with identical complementarity determining region 3 sequences despite unique nucleotide sequences when compared to controls. In conclusion, somatic mutations in genes implicated for autoimmunity and lymphoproliferation are common in CD4+ and CD8+ cells of patients with immunodeficiency. They may contribute to immune dysregulation in a subset of immunodeficiency patients.
[ "Immunity, Infection and Immunotherapy", "Integrative Biology: from Genes and Genomes to Systems", "Cell Biology, Development, Stem Cells and Regeneration", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1016/j.chembiol.2014.08.018
Structural and functional analysis of bacillus subtilis yisp reveals a role of its product in biofilm production
YisP is involved in biofilm formation in Bacillus subtilis and has been predicted to produce C30 isoprenoids. We determined the structure of YisP and observed that it adopts the same fold as squalene and dehydrosqualene synthases. However, the first aspartate-rich motif found in essentially all isoprenoid synthases is aspartate poor in YisP and cannot catalyze head-to-head condensation reactions. We find that YisP acts as a phosphatase, catalyzing formation of farnesol from farnesyl diphosphate, and that it is the first phosphatase to adopt the fold seen in the head-to-head prenyl synthases. Farnesol restores biofilm formation in a Δyisp mutant and modifies lipid membrane structure similarly to the virulence factor staphyloxanthin. This work clarifies the role of YisP in biofilm formation and suggests an intriguing possibility that many of the YisP-like homologs found in other bacteria may also have interesting products and functions.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
176761
Open digital research environment toolkit for the advancement of mathematics
OpenDreamKit will deliver a flexible toolkit enabling research groups to set up Virtual Research Environments, customised to meet the varied needs of research projects in pure mathematics and applications and supporting the full research life-cycle from exploration, through proof and publication, to archival and sharing of data and code. OpenDreamKit will be built out of a sustainable ecosystem of community-developed open software, databases, and services, including popular tools such as LinBox, MPIR, Sage(sagemath.org), GAP, PariGP, LMFDB, and Singular. We will extend the Jupyter Notebook environment to provide a flexible UI. By improving and unifying existing building blocks, OpenDreamKit will maximise both sustainability and impact, with beneficiaries extending to scientific computing, physics, chemistry, biology and more and including researchers, teachers, and industrial practitioners. We will define a novel component-based VRE architecture and the adapt existing mathematical software, databases, and UI components to work well within it on varied platforms. Interfaces to standard HPC and grid services will be built in. Our architecture will be informed by recent research into the sociology of mathematical collaboration, so as to properly support actual research practice. The ease of set up, adaptability and global impact will be demonstrated in a variety of demonstrator VREs. We will ourselves study the social challenges associated with large-scale open source code development and of publications based on executable documents, to ensure sustainability. OpenDreamKit will be conducted by a Europe-wide demand-steered collaboration, including leading mathematicians, computational researchers, and software developers long track record of delivering innovative open source software solutions for their respective communities. All produced code and tools will be open source.
[ "Mathematics", "Computer Science and Informatics" ]
US 2021/0037349 W
TECHNIQUES FOR DETERMINING BEAM FAILURE OR RADIO LINK FAILURE
Methods, systems, and devices for wireless communications are described. In some networks, a user equipment (UE) may perform radio link monitoring according to one or more radio link monitoring configurations. The UE may select a radio link monitoring configuration from a first radio link monitoring configuration associated with radio link monitoring over a duration that a hybrid automatic repeat request (HARQ) process is enabled and a second radio link monitoring configuration associated with radio link monitoring over a duration that the HARQ process is disabled. The UE may monitor reference signals using the selected radio link monitoring configuration, and may determine a radio link failure, a beam failure, or both has occurred based on monitoring the one or more reference signals using the selected radio link monitoring configuration. The UE may subsequently transmit a measurement report based on determining the radio link failure, the beam failure, or both.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1021/acs.biomac.9b00681
Synthetically Scalable Poly(ampholyte) Which Dramatically Enhances Cellular Cryopreservation
The storage and transport of frozen cells underpin the emerging/existing cell-based therapies and are used in every biomedical research lab globally. The current gold-standard cryoprotectant dimethyl sulfoxide (DMSO) does not give quantitative cell recovery in suspension or in two-dimensional (2D) or three-dimensional (3D) cell models, and the solvent and cell debris must be removed prior to application/transfusion. There is a real need to improve this 50-year-old method to underpin emerging regenerative and cell-based therapies. Here, we introduce a potent and synthetically scalable polymeric cryopreservation enhancer which is easily obtained in a single step from a low cost and biocompatible precursor, poly(methyl vinyl ether-alt-maleic anhydride). This poly(ampholyte) enables post-thaw recoveries of up to 88% for a 2D cell monolayer model compared to just 24% using conventional DMSO cryopreservation. The poly(ampholyte) also enables reduction of [DMSO] from 10 wt % to just 2. 5 wt % in suspension cryopreservation, which can reduce the negative side effects and speed up post-thaw processing. After thawing, the cells have reduced membrane damage and faster growth rates compared to those without the polymer. The polymer appears to function by a unique extracellular mechanism by stabilization of the cell membrane, rather than by modulation of ice formation and growth. This new macromolecular cryoprotectant will find applications across basic and translational biomedical science and may improve the cold chain for cell-based therapies.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1103/PhysRevLett.119.051801
Case for an EeV Gravitino
We consider the possibility that supersymmetry is broken above the inflationary mass scale and that the only "low" energy remnant of supersymmetry is the gravitino with a mass of the order of the EeV scale. The gravitino in this class of models becomes a candidate for the dark matter of the Universe. To avoid the overproduction of gravitinos from the decays of the next-to-lightest supersymmetric particle we argue that the supersymmetric spectrum must lie above the inflationary mass scale (MSUSY>10-5MP∼1013 GeV). Since m3/2≃MSUSY2/MP, we expect m3/2≳0. 2 EeV. Cosmological constraints then predict a relatively large reheating temperature between 1010 and 1012 GeV.
[ "Fundamental Constituents of Matter", "Universe Sciences" ]
10.1016/j.cub.2017.09.005
Viscoelastic Dissipation Stabilizes Cell Shape Changes during Tissue Morphogenesis
Tissue morphogenesis relies on the production of active cellular forces. Understanding how such forces are mechanically converted into cell shape changes is essential to our understanding of morphogenesis. Here, we use myosin II pulsatile activity during Drosophila embryogenesis to study how transient forces generate irreversible cell shape changes. Analyzing the dynamics of junction shortening and elongation resulting from myosin II pulses, we find that long pulses yield less reversible deformations, typically a signature of dissipative mechanics. This is consistent with a simple viscoelastic description, which we use to model individual shortening and elongation events. The model predicts that dissipation typically occurs on the minute timescale, a timescale commensurate with that of force generation by myosin II pulses. We test this estimate by applying time-controlled forces on junctions with optical tweezers. Finally, we show that actin turnover participates in dissipation, as reducing it pharmacologically increases the reversibility of contractile events. Our results argue that active junctional deformation is stabilized by actin-dependent dissipation. Hence, tissue morphogenesis requires coordination between force generation and dissipation. Clément et al. investigate the mechanics underlying the irreversibility of morphogenetic deformations. They show that deformations caused by contractile pulses of myosin II or by optical tweezers are stabilized by dissipation on the minute timescale. Inhibiting actin turnover reduces dissipation and yields more reversible deformations.
[ "Condensed Matter Physics", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1038/msb.2011.80
Mapping the interaction of Snf1 with TORC1 in Saccharomyces cerevisiae
Nutrient sensing and coordination of metabolic pathways are crucial functions for all living cells, but details of the coordination under different environmental conditions remain elusive. We therefore undertook a systems biology approach to investigate the interactions between the Snf1 and the target of rapamycin complex 1 (TORC1) in Saccharomyces cerevisiae. We show that Snf1 regulates a much broader range of biological processes compared with TORC1 under both glucose-and ammonium-limited conditions. We also find that Snf1 has a role in upregulating the NADP +-dependent glutamate dehydrogenase (encoded by GDH3) under derepressing condition, and therefore may also have a role in ammonium assimilation and amino-acid biosynthesis, which can be considered as a convergence of Snf1 and TORC1 pathways. In addition to the accepted role of Snf1 in regulating fatty acid (FA) metabolism, we show that TORC1 also regulates FA metabolism, likely through modulating the peroxisome and Î 2-oxidation. Finally, we conclude that direct interactions between Snf1 and TORC1 pathways are unlikely under nutrient-limited conditions and propose that TORC1 is repressed in a manner that is independent of Snf1.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1016/j.jplph.2012.05.006
Methyl esterification of pectin plays a role during plant-pathogen interactions and affects plant resistance to diseases
The cell wall is a complex structure mainly composed by a cellulose-hemicellulose network embedded in a cohesive pectin matrix. Pectin is synthesized in a highly methyl esterified form and is de-esterified in muro by pectin methyl esterases (PMEs). The degree and pattern of methyl esterification affect the cell wall structure and properties with consequences on both the physiological processes of the plants and their resistance to pathogens. PME activity displays a crucial role in the outcome of the plant-pathogen interactions by making pectin more susceptible to the action of the enzymes produced by the pathogens. This review focuses on the impact of pectin methyl esterification in plant-pathogen interactions and on the dynamic role of its alteration during pathogenesis.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Immunity, Infection and Immunotherapy", "Cell Biology, Development, Stem Cells and Regeneration" ]
337702
Genetics and cell biology of K2P channels
Two-pore domain potassium channels (K2P) maintain the resting membrane potential of animal cells and therefore play a central role in the control of cellular excitability. In the vertebrate nervous system, various neuromodulators promote K2P closure, which depolarizes neurons, increases neuronal excitability and ultimately affects action potential firing. Knockout studies have revealed important roles of K2Ps in physiopathological processes tied to cellular excitability. K2Ps are major targets of volatile anaesthetics. Analysis of task1/3 knockouts established a direct role of these channels in anaesthetics-induced immobilization and sedation. trek1 knockout mice are hypersensitive to kainate-induced seizures and display depression-resistant phenotypes, similar to naive mice treated with selective serotonine reuptake inhibitors. In sensory neurons, genetic ablation of trek1 or inhibition by noxious stimuli (heat, external acidosis) leads to increased neuronal activity and pain perception. Despite the fundamental functions of these channels, comparatively little is known about the cellular processes that control K2P function. I propose to use comprehensive and powerful genetic screening strategies in the nematode C. elegans to identify novel genes and conserved cellular processes that regulate the biology of K2Ps in a native context. I will decipher the precise functions of novel K2P regulators by using the full array of techniques available in C. elegans including genetics, live imaging, electrophysiology and state-of-the-art genome engineering and deep sequencing. This will provide new leads to understand the cellular pathways that control K2P function in other organisms. This work may have wide-ranging applications since K2Ps are increasingly implicated in a variety of physiopathological processes in the nervous system but also in cardiac muscle, endocrine and immune system. However, the precise molecular factors involved are mostly unknown.
[ "Neuroscience and Disorders of the Nervous System", "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
885049
Swarms of underwater robots for fast & accurate water quality measurements
The world's oceans & lakes are under increasing stress caused by the climate change & increasing pollution (primarily driven by increasing urbanization in developing countries), but littleThe world's oceans & lakes are under increasing stress caused by the climate change & increasing pollution (primarily driven by increasing urbanization in developing countries), but little is known about them as data is difficult & expensive to obtain. State-of-the-art technology is mostly high OPEX dedicated ships with a lot of labor needed to survey for hours. Hydromea has developed the miniature robotic Vertex submersible that can operate in swarms & measure the quality of large bodies of water much faster & more cost efficiently than the existing alternatives. Using swarms of miniature underwater robots. Hydromea provides a high-resolution underwater sensing service. Using the Vertex AUV, a small underwater robot, specifically designed in-house to be deployed in large swarms by 1-2 operators, Hydromea can provide consistent, high-density, 3D maps of many physical & chemical water parameters. Vertex swarms can collect 10-100x more information about environmental qualities in a single pass than is possible to collect with the current methods. With this technology we will commercialize a service where we will detect & map oil spills or discharged wastewater plumes, assess the environmental impact of construction projects & create detailed high-resolution maps charting the health of marine ecosystems. We will improve the state-of-the-art in coastal oceanology & limnology by drastically cutting the measurement costs with swarms of Vertex underwater drones. We have already had 1st market traction by selling custom high-performance components, developed in-house & signed commercial NDAs with major global oil/gas, dredging & research prospects like Schlumberger, Boskalis & Deltares. By 2022 we are aiming to build ~400+ AUVs reaching the overall sales revenues of ~15m & ~35 employees.
[ "Earth System Science", "Products and Processes Engineering", "Systems and Communication Engineering" ]
3736523
Semi-Autonomous border surveillance platform combining next generation unmanned aerial vehicles with ultra-high-resolution multi-sensor surveillance payload
The project will combine for the first time a multi-role lighter-than-air (LTA) unmanned aerial vehicle (UAV) with an ultra-high resolution multi-sensor surveillance payload supporting border surveillance as well as search & rescue applications, and specifically rough terrain detection. The sensor payload will include synthetic aperture radar (SAR), laser detection and ranging (LADAR), shortwave/longwave infrared (SWIR/LWIR) and acoustic cameras for direct target detection, as well as optical and hyperspectral cameras for indirect detection (via vegetation disturbance). The project will use the ground-based infrastructure of border police units (command & control centres), innovative data models (to identify illegal crossing patterns and preferred routes) and advanced audio/video analytics and storage (to provide additional detection capabilities). The technology concepts will be validated in the field by 6 border police units (Greece, Bulgaria, Romania, Moldova, Ukraine, Belarus) covering 3 major illegal migration routes into Europe (Eastern Mediterranean, Western Balkan and Eastern Borders Routes), which represent 58% of all illegal border crossings detected and are also the most used for smuggling of drugs, weapons and stolen vehicles. The combined solution will provide high coverage, resolution and revisit time with a lower cost (4 EUR/kg/hr) than satellites and higher endurance (100 kg payload for 12 hours) than drones. Based on the field trial results, the consortium expects to develop a solution that can be deployed further by European border polices after project completion. The project will also involve the contribution of NGOs working with illegal migration and human right protection issues, as well as regulatory experts dealing with the ethics and privacy requirements of border surveillance solutions
[ "Products and Processes Engineering", "Computer Science and Informatics", "Systems and Communication Engineering", "Human Mobility, Environment, and Space" ]
291198
Structure and dynamics of biomolecules by two-dimensional ultraviolet spectroscopy
Two-dimensional (2D) nuclear magnetic resonance is a diagnostic technique that has revolutionized structural biology. A wealth of spectroscopic information can be obtained by extrapolating 2D techniques to the optical frequency domain, using ultrashort light pulses. 2D electronic spectroscopy (2DES) allows fundamentally new insights into the structure and dynamics of multi-chromophore systems, by measuring how the electronic states of chromophores interact with one another and transfer electronic excitations. Due to technical difficulties, 2DES has been limited so far to the visible range, while most biomolecules absorb in the ultraviolet (UV). This project aims at extending 2DES to the challenging and still uncharted UV-domain and applying it to the study of the photophysics of genomic systems and of the secondary structure of proteins. Nature has engineered DNA molecules to be photostable, so that harmful photochemical processes are minimized. 2DES will unravel the molecular mechanisms of the photoinduced electronic intra/inter-chromophore events in DNA, exposing the energy dissipation pathways which are responsible for its photoprotection. 2DES will be also established as a new diagnostic tool for structural studies of polypeptides and proteins, relying on the UV absorbing peptide bonds and aromatic residues, the latter acting as native local structural probes. 2DES will provide sensitive information on the misfolding/aggregation processes responsible for a wide class of diseases, with the speed of standard optical techniques but with a much greater information content. This will bridge the experimental gap between crude estimates of protein unfolding and full structure determination, enabling rapid assessment of which variants are worth of deeper structural studies. To realize the full power of 2DES, experiments will be combined with simulations and electronic calculations that are necessary to correlate the data with molecular states and structures.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.22323/2.18010202
What Do Volunteers Want From Citizen Science Technologies A Systematic Literature Review And Best Practice Guidelines
Although hundreds of citizen science applications exist, there is lack of detailed analysis of volunteers' needs and requirements, common usability mistakes and the kinds of user experiences that citizen science applications generate. Due to the limited number of studies that reflect on these issues, it is not always possible to develop interactions that are beneficial and enjoyable. In this paper we perform a systematic literature review to identify relevant articles which discuss user issues in environmental digital citizen science and we develop a set of design guidelines, which we evaluate using cooperative evaluation. The proposed research can assist scientists and practitioners with the design and development of easy to use citizen science applications and sets the basis to inform future Human-Computer Interaction research in the context of citizen science.
[ "Environmental Biology, Ecology and Evolution", "Computer Science and Informatics" ]
W2589314611
Fine-tuning π-spacer for high efficiency performance DSSC: A theoretical exploration with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif" overflow="scroll"><mml:mrow><mml:mi>D</mml:mi><mml:mo>−</mml:mo><mml:mi>π</mml:mi><mml:mo>−</mml:mo><mml:mi>A</mml:mi></mml:mrow></mml:math> based organic dye
Abstract Based on density functional theory (DFT) and time-dependent DFT (TD-DFT) approaches, a series of triphenylamine based organic dyes that modified by electron-withdrawing (EW) or electron-deficient (ED) substituent groups are investigated. The properties of all the isolated dyes, including frontier molecular orbital, intramolecular charge transfer, absorption spectra, maximal photon generated current ( J p h ) and intermolecular interaction between dye and I2 are investigated theoretically to confirm which dyes can produce great performance for dye-sensitized solar cell (DSSC). Subsequently, the structures of dye combined with (TiO2)64 cluster are optimized by means of Vienna ab initio simulation package (VASP) code. Then the interfacial interaction between the dye and semiconductor is further discussed to reveal the interfacial charge injection process by means of interfacial electron transfer code. The importance of fine-tuning π-spacer is also demonstrated by the density of state (DOS) plot and photo-induced charge transfer dynamics. Compared with other dyes, TA-CN dye shows outstanding performance because of the strong coupling of the absorbed dye's orbitals with substrate orbitals and the fast as well as complete charge injection process. The purpose of our study is expected to provide a promising way to design possible candidate sensitizers for DSSC.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Condensed Matter Physics" ]
Q2870767
staysafe@conventodoseixohotel
Adaptation of the Convent of Seixo Boutique Hotel & SPA to the new operating conditions in the context of the COVID-19 pandemic, ensuring compliance with the established standards and recommendations of the competent authorities in order to ensure the minimum impact on public health.
[ "Products and Processes Engineering", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1007/s11196-020-09766-x
From Fingers to Faces: Visual Semiotics and Digital Forensics
Identification is a primary need of societies. It is even more central in law enforcement. In the history of crime, a dialectics takes place between felonious attempts at concealing, disguising, or forging identities and societal efforts at unmasking the impostures. Semiotics offers specialistic skills at studying the signs of societal detection and identification, including those of forensics and criminology. In human history, no sign more than the face is attached a value of personal identity. Yet, modern forensics realizes that the face can mislead and, inspired by eastern models (China, Japan, India), adopts fingerprinting. In the digital era, however, fingerprinting first goes digital, then it is increasingly replaced by facial recognition. The face is back in digital AI forensics, together with a tangle of sociocultural biases. Semiotics can play a key role in studying their surreptitious influence.
[ "Texts and Concepts", "The Social World and Its Interactions", "Computer Science and Informatics" ]
10.1073/pnas.1518752113
Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers
Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women's health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among leiomyomas harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen, type IV, alpha 5 and collagen, type IV, alpha 6 (COL4A5-COL4A6) deletions. We also explored the transcriptional consequences of 7q22, 22q, and 1p deletions, aiming to identify possible target genes. We investigated 94 leiomyomas and 60 corresponding myometrial tissues using exon arrays, whole genome sequencing, and SNP arrays. This integrative approach revealed subtype-specific expression changes in key driver pathways, including Wnt/β-catenin, Prolactin, and insulin-like growth factor (IGF)1 signaling. Leiomyomas with HMGA2 aberrations displayed highly significant up-regulation of the proto-oncogene pleomorphic adenoma gene 1(PLAG1), suggesting that HMGA2 promotes tumorigenesis through PLAG1 activation. This was supported by the identification of genetic PLAG1 alterations resulting in expression signatures as seen in leiomyomas with HMGA2 aberrations. RAD51 paralog B (RAD51B), the preferential translocation partner of HMGA2, was up-regulated in MED12 mutant lesions, suggesting a role for this gene in the genesis of leiomyomas. FH-deficient leiomyomas were uniquely characterized by activation of nuclear factor erythroid 2-related factor 2 (NRF2) target genes, supporting the hypothesis that accumulation of fumarate leads to activation of the oncogenic transcription factor NRF2. This study emphasizes the need for molecular stratification in leiomyoma research and possibly in clinical practice as well. Further research is needed to determine whether the candidate biomarkers presented herein can provide guidance for managing the millions of patients affected by these lesions.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems" ]
EP 2019065857 W
DUAL MODE FREE-DRIVE OF ROBOT ARM
Method and robot arm, where the motor torques of the joint motors of a robot arm are controlled based on a static motor torque indicating the motor torque needed to maintain the robot arm in a static posture, where the static motor torque is adjusted in response to a change in posture of the robot arm caused by an external force different from gravity applied to the robot arm. Further the motor torque of the joint motors is controlled based on an additional motor torque obtained based on a force-torque provided to the robot tool flange, where the force-torque is obtained by a force-torque sensor integrated in the tool flange of the robot arm.
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]
10.1063/1.4752432
Molecular Gradient For Second Order Moller Plesset Perturbation Theory Using The Divide Expand Consolidate Dec Scheme
We demonstrate that the divide-expand-consolidate (DEC) scheme – which has previously been used to determine the second-order Moller–Plesset (MP2) correlation energy – can be applied to evaluate the MP2 molecular gradient in a linear-scaling and embarrassingly parallel manner using a set of local Hartree–Fock orbitals. All manipulations of four-index quantities (describing electron correlation effects) are carried out using small local orbital fragment spaces, whereas two-index quantities are treated for the full molecular system. The sizes of the orbital fragment spaces are determined in a black-box manner to ensure that the error in the DEC-MP2 correlation energy compared to a standard MP2 calculation is proportional to a single input threshold denoted the fragment optimization threshold (FOT). The FOT also implicitly controls the error in the DEC-MP2 molecular gradient as substantiated by a theoretical analysis and numerical results. The development of the DEC-MP2 molecular gradient is the initial step towards calculating higher order energy derivatives for large molecular systems using the DEC framework, both at the MP2 level of theory and for more accurate coupled-cluster methods.
[ "Physical and Analytical Chemical Sciences", "Computer Science and Informatics" ]
10.1109/MWSYM.2018.8439364
Micromachined Waveguides With Integrated Silicon Absorbers And Attenuators At 220 325 Ghz
This paper reports for the first time on micromachined waveguides with integrated micromachined silicon absorbers. In contrast to epoxy-based microwave absorbers, micromachined lossy silicon absorbers are fully compatible with high temperature fabrication and assembly processes for micromachined waveguides. Furthermore, micromachining enables the fabrication of exact, near ideal taper tips for the silicon absorbers, whereas the tip of epoxy-based absorbers cannot be shaped accurately and reproducibly for small waveguides. Silicon of different conductivity is a very well understood and characterized dielectric material, in contrast to conventional absorber materials which are not specified above 60 GHz. Micromachined silicon waveguides with integrated absorbers and attenuators were designed, fabricated and characterized in the frequency band of 220 – 325 GHz. The return and insertion loss for various taper-geometry variations of double-tip tapered absorbers and attenuators was studied. The average return loss for the best investigated device is 19 dB over the whole band. The insertion loss of the two-port attenuators is 16 – 33 dB for different designs and shows an excellent agreement to the simulated results. The best measured devices of the one-port absorbers exhibit an average and worst-case return loss of 22 dB and 14 dB, respectively, over the whole band. The return loss is not characterized by a good simulation-measurement match, which is most likely attributed to placement tolerances of the absorbers in the waveguide cavities affecting the return but not the insertion loss.
[ "Systems and Communication Engineering", "Materials Engineering" ]
641952
Hodgkin lymphoma: insights from genomic studies of mutations in coding and non-coding regions
Classical Hodgkin Lymphoma (cHL) is one of the most common cancers in young adults. While chemo-radiotherapy is effective, many patients continue to die of cHL or to suffer long-term treatment toxicities, such that more effective and less toxic drugs are needed. Studying the mechanisms underlying the puzzling biology of cHL (the only B cell-derived lymphoma loosing its B-cell identity) should illuminate its pathogenesis and possibly aid in developing better therapeutic strategies. In this project, I will study the function of mutations in the DNA binding domain of the STAT6 transcription factor, which the host laboratory identified as one of the most frequent genetic lesions in cHL. I will perform genome-wide ChIP- and RNA-seq studies to uncover aberrant gene expression regulation and occupancy by mutant versus wild-type STAT6 in cHL versus non-Hodgkin lymphoma (NHL) cell lines, and investigate their functional consequences at the cellular level. I will then express mutant STAT6 in germinal center (GC) B cells, the cHL cell of origin, to evaluate their role in early lymphomagenesis. Because genes mutated in cHL greatly overlap with those altered in NHLs, from which cHL is strikingly different, I will also explore whether unidentified mutations in non-coding regulatory regions may underlie the peculiar cHL pathogenesis. Recurrent somatic non-coding mutations will be identified through whole-genome sequencing of primary cases and will be annotated to the non-coding elements specifically active in cHL cell lines, which I will identify through RNA- and ChIP-seq for key histone marks. Finally, I will use appropriate techniques (e.g., genome topology and CRISPR editing) to assess how such mutations may alter regulatory networks important for cHL biology and identity. The project will also expand my expertise in genomic regulation in lymphomas, boost my research productivity after a career break, and support my transition to an independent investigator.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Cell Biology, Development, Stem Cells and Regeneration", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1039/c7ee01292f
A triboelectric generator based on self-poled Nylon-11 nanowires fabricated by gas-flow assisted template wetting
Highly crystalline and “self-poled” δ′-phase Nylon-11 nanowires, fabricated using a novel gas-flow assisted nano-template infiltration method, exhibit enhanced triboelectric energy harvesting performance.
[ "Condensed Matter Physics", "Materials Engineering" ]
10.1145/3203197
3D Sketching Using Multi View Deep Volumetric Prediction
Sketch-based modeling strives to bring the ease and immediacy of drawing to the 3D world. However, while drawings are easy for humans to create, they are very challenging for computers to interpret due to their sparsity and ambiguity. We propose a data-driven approach that tackles this challenge by learning to reconstruct 3D shapes from one or more drawings. At the core of our approach is a deep convolutional neural network (CNN) that predicts occupancy of a voxel grid from a line drawing. This CNN provides us with an initial 3D reconstruction as soon as the user completes a single drawing of the desired shape. We complement this single-view network with an updater CNN that refines an existing prediction given a new drawing of the shape created from a novel viewpoint. A key advantage of our approach is that we can apply the updater iteratively to fuse information from an arbitrary number of viewpoints, without requiring explicit stroke correspondences between the drawings. We train both CNNs by rendering synthetic contour drawings from hand-modeled shape collections as well as from procedurally-generated abstract shapes. Finally, we integrate our CNNs in a minimal modeling interface that allows users to seamlessly draw an object, rotate it to see its 3D reconstruction, and refine it by re-drawing from another vantage point using the 3D reconstruction as guidance. The main strengths of our approach are its robustness to freehand bitmap drawings, its ability to adapt to different object categories, and the continuum it offers between single-view and multi-view sketch-based modeling.
[ "Computer Science and Informatics" ]
10.1002/2015JD023283
Lagrangian Dust Model Simulations For A Case Of Moist Convective Dust Emission And Transport In The Western Sahara Region During Fennec Ladunex
Due to the harshness and inaccessibility of desert regions, the uncertainties concerning the processes of dust mobilization at the surface, airborne transport, and sedimentation are still considerable, limiting the ability to perform model simulations. In June 2011, a comprehensive data set of ground-based and airborne in situ measurements and remote sensing observations was acquired within the Fennec/Lagrangian Dust Source Inversion Experiment (LADUNEX) field campaign in the western Sahara region. Here we evaluate the ability of the state-of-the-art Lagrangian particle dispersion model FLEXPART, newly fitted with a dust mobilization capability, to simulate dust transport in this region. We investigate a case where a large mesoscale convective system (MCS) triggered dust emissions in central Mali, which subsequently moved as a large cold pool dust front toward northern Mauritania. Specifying dust mobilization for this case is shown to be an important obstacle to simulating dust transport during this event, since neither the MCS nor the associated cold pool-causing dust emission is represented in the meteorological analysis. Obtaining a realistic dust transport simulation for this case therefore requires an inversion approach using a manual specification of the dust sources supported by satellite imagery. When compared to in situ and remote sensing data from two aircraft, the Lagrangian dust transport simulations represent the overall shape and evolution of the dust plume well. While accumulation and coarse mode dust are well represented in the simulation, giant mode particles are considerably underestimated. Our results re-emphasize that dust emission associated with deep moist convection remains a key issue for reliable dust model simulations in northern Africa.
[ "Earth System Science", "Systems and Communication Engineering" ]
EP 2018084751 W
TAMPER PREVENTION SYSTEM AND METHOD FOR REMOTELY MONITORED SEALING AND UNSEALING OF CONTAINERS
The invention provides a tamper prevention system (1) comprising a storage unit (10). The storage unit (10) comprises at least one storage compartment (11) for storing a sealing element (40) for containers (50), and a control system (13) configured for detecting opening of the at least one storage compartment (11). Each storage compartment (11) comprises a leash element (12) connected to the control system (13) and provided for being connected to a sealing element (40) to be stored in the storage compartment (11). The control system (13) is configured for monitoring the integrity of the leash element (12). The tamper prevention system (1) comprises movement protection means configured for detecting and/or preventing movement of the storage unit (10).
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]