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10.1002/2016JB013824
|
Vaporization Of Fault Water During Seismic Slip
|
Laboratory and numerical studies, as well as field observations, indicate that phase transitions of pore water might be an important process in large earthquakes. We present a model of the thermo-hydro-chemo-mechanical processes, including a two-phase mixture model to incorporate the phase transitions of pore water, occurring during fast slip (i. e. , a natural earthquake) in order to investigate the effects of vaporization on the coseismic slip. Using parameters from typical natural faults, our modeling shows that vaporization can indeed occur at the shallow depths of an earthquake, irrespective of the wide variability of the parameters involved (sliding velocity, friction coefficient, gouge permeability and porosity, and shear-induced dilatancy). Due to the fast kinetics, water vaporization can cause a rapid slip weakening even when the hydrological conditions of the fault zone are not favorable for thermal pressurization, e. g. , when permeability is high. At the same time, the latent heat associated with the phase transition causes the temperature rise in the slip zone to be buffered. Our parametric analyses reveal that the amount of frictional work is the principal factor controlling the onset and activity of vaporization and that it can easily be achieved in earthquakes. Our study shows that coseismic pore fluid vaporization might have played important roles at shallow depths of large earthquakes by enhancing slip weakening and buffering the temperature rise. The combined effects may provide an alternative explanation for the fact that low-temperature anomalies were measured in the slip zones at shallow depths of large earthquakes.
|
[
"Earth System Science",
"Physical and Analytical Chemical Sciences"
] |
10.1016/j.cell.2016.07.019
|
The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity
|
Methionine-1 (M1)-linked ubiquitin chains regulate the activity of NF-κB, immune homeostasis, and responses to infection. The importance of negative regulators of M1-linked chains in vivo remains poorly understood. Here, we show that the M1-specific deubiquitinase OTULIN is essential for preventing TNF-associated systemic inflammation in humans and mice. A homozygous hypomorphic mutation in human OTULIN causes a potentially fatal autoinflammatory condition termed OTULIN-related autoinflammatory syndrome (ORAS). Four independent OTULIN mouse models reveal that OTULIN deficiency in immune cells results in cell-type-specific effects, ranging from over-production of inflammatory cytokines and autoimmunity due to accumulation of M1-linked polyubiquitin and spontaneous NF-κB activation in myeloid cells to downregulation of M1-polyubiquitin signaling by degradation of LUBAC in B and T cells. Remarkably, treatment with anti-TNF neutralizing antibodies ameliorates inflammation in ORAS patients and rescues mouse phenotypes. Hence, OTULIN is critical for restraining life-threatening spontaneous inflammation and maintaining immune homeostasis.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1002/anie.201510650
|
Expanding the landscape of diterpene structural diversity through stereochemically controlled combinatorial biosynthesis
|
Plant-derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of class I and II diterpene synthases, 41 of which are "new-to-nature". Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae.
|
[
"Synthetic Chemistry and Materials",
"Biotechnology and Biosystems Engineering"
] |
10.1073/pnas.1424030112
|
Evolutionary signals of symbiotic persistence in the legume–rhizobia mutualism
|
Understanding the origins and evolutionary trajectories of symbiotic partnerships remains a major challenge. Why are some symbioses lost over evolutionary time whereas others become crucial for survival? Here, we use a quantitative trait reconstruction method to characterize different evolutionary stages in the ancient symbiosis between legumes (Fabaceae) and nitrogen-fixing bacteria, asking how labile is symbiosis across different host clades. We find that more than half of the 1,195 extant nodulating legumes analyzed have a high likelihood (>95%) of being in a state of high symbiotic persistence, meaning that they show a continued capacity to form the symbiosis over evolutionary time, even though the partnership has remained facultative and is not obligate. To explore patterns associated with the likelihood of loss and retention of the N2-fixing symbiosis, we tested for correlations between symbiotic persistence and legume distribution, climate, soil and trait data. We found a strong latitudinal effect and demonstrated that low mean annual temperatures are associated with high symbiotic persistence in legumes. Although no significant correlations between soil variables and symbiotic persistence were found, nitrogen and phosphorus leaf contents were positively correlated with legumes in a state of high symbiotic persistence. This pattern suggests that highly demanding nutrient lifestyles are associated with more stable partnerships, potentially because they “lock” the hosts into symbiotic dependency. Quantitative reconstruction methods are emerging as a powerful comparative tool to study broad patterns of symbiont loss and retention across diverse partnerships.
|
[
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
] |
864182
|
Protecting the Right to Culture of Persons with Disabilities and Enhancing Cultural Diversity through European Union Law: Exploring New Paths
|
The right of people with disabilities to participate in cultural life - which encompasses the rights of access to, and to be involved in cultural activities, as well as the recognition of disability identities, such as Deaf culture – has been for long denied. The cultural exclusion of disabled people has engendered their marginalisation. It has also entailed a loss for society as a whole, because of the lack of cultural diversity resulting from an inaccessible and exclusionary cultural realm. DANCING will investigate the extent to which the protection of the right to take part in culture of people with disabilities and the promotion of cultural diversity intersect and complement each other in the European Union (EU) legal order. It will disrupt the conventional approach adopted by EU law scholarship by using a combination of legal, empirical and arts-based research to pursue three complementary objectives, experiential, normative and theoretical respectively. First, it will identify and categorise barriers and facilitators to cultural participation experienced by disabled people and how they affect the wider cultural domain. Secondly, it will provide a normative exploration of how the EU has used and can use its competence to combat discrimination and its supporting competence on cultural matters, in synergy with its wide internal market powers, to ensure the accessibility of cultural activities, to promote disability identities, while achieving cultural diversity. In doing so, it will bridge, in an unprecedented way, the implementation of the UN Convention on the Rights of Persons with Disabilities and the UNESCO Convention on the Protection and Promotion of the Diversity of Cultural Expressions. Thirdly, it will advance the understanding of the legal concept of cultural diversity, which stems from the intersection of different sources of law, and will propose a new theorization of the promotion of cultural diversity within the EU legal order.
|
[
"Institutions, Governance and Legal Systems",
"Studies of Cultures and Arts"
] |
10.1371/journal.pbio.3000665
|
Orange: A CRISPR/Cas9-based genome editing toolbox for epitope tagging of endogenous proteins in neurons
|
The correct subcellular distribution of proteins establishes the complex morphology and function of neurons. Fluorescence microscopy techniques are invaluable to investigate subcellular protein distribution, but they suffer from the limited ability to efficiently and reliably label endogenous proteins with fluorescent probes. We developed ORANGE: Open Resource for the Application of Neuronal Genome Editing, which mediates targeted genomic integration of epitope tags in rodent dissociated neuronal culture, in organotypic slices, and in vivo. ORANGE includes a knock-in library for in-depth investigation of endogenous protein distribution, viral vectors, and a detailed two-step cloning protocol to develop knock-ins for novel targets. Using ORANGE with (live-cell) superresolution microscopy, we revealed the dynamic nanoscale organization of endogenous neurotransmitter receptors and synaptic scaffolding proteins, as well as previously uncharacterized proteins. Finally, we developed a mechanism to create multiple knock-ins in neurons, mediating multiplex imaging of endogenous proteins. Thus, ORANGE enables quantification of expression, distribution, and dynamics for virtually any protein in neurons at nanoscale resolution.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
] |
AU 2015/284411 A
|
Patterned surfaces
|
The present disclosure provides patterned materials that may be useful in reducing certain negative effects associated with damaged tissue in vivo. The patterned materials can modify the healing process, and may minimize the formation of scar tissue. Such effects can provide inhibition of adhesion between tissues and/or reduction of fibrotic encapsulation around implanted medical devices.
|
[
"Prevention, Diagnosis and Treatment of Human Diseases",
"Materials Engineering"
] |
10.1007/978-4-431-54270-4_26
|
Construction of the noncommutative rank I Bergman domain
|
In this paper we present a harmonic oscillator realization of the most degenerate discrete series representations of the SU(2,1) group and the deformation quantization of the coset space D = SU(2,1)/U(2) with the method of coherent state quantization. This short article is based on a talk given at the 9-th International Workshop, Varna "Lie Theory and Its Applications in Physics" (LT-9).
|
[
"Mathematics"
] |
10.1088/0022-3727/49/29/294003
|
Local Charge Measurement Using Off Axis Electron Holography
|
A model-independent approach based on Gauss' theorem for measuring the local charge in a specimen from an electron-optical phase image recorded using off-axis electron holography was recently proposed. Here, we show that such a charge measurement is reliable when it is applied to determine the total charge enclosed within an object. However, the situation is more complicated for a partial charge measurement when the integration domain encloses only part of the object. We analyze in detail the effects on charge measurement of the mean inner potential of the object, of the presence of induced charges on nearby supports/electrodes and of noise. We perform calculations for spherical particles and highlight the differences when dealing with other object shapes. Our analysis is tested using numerical simulations and applied to the interpretation of an experimental dataset recorded from a sapphire particle.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
] |
10.1038/s41467-019-09799-2
|
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
|
The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
] |
10.1109/TAC.2018.2835380
|
K4Sid Large Scale Subspace Identification With Kronecker Modeling
|
In this paper, we consider the identification of matrix state-space models (MSSM) of the following form: \begin{align*} \mathbf {X}(k+1) &= \mathbf {A}_2 \mathbf {X}(k) \mathbf {A}_1^T + \mathbf {B}_2 \mathbf {U}(k) \mathbf {B}_1^T \\ \mathbf {Y}(k) &= \mathbf {C}_2 \mathbf {X}(k) \mathbf {C}_1^T + \mathbf {E}(k) \end{align*} for all time dependent quantities and matrices of appropriate dimensions. Due to the large size of these matrices, vectorization does not allow the use of standard multivariable subspace methods such as N4SID or MOESP. In this paper, the resulting Kronecker structure that appears in the system matrices due to vectorization is exploited for developing a scalable subspace-like identification approach. This approach consists of first estimating the Markov parameters associated to the MSSM via the solution of a regularized bilinear least-squares problem that is solved in a globally convergent manner. Second, a bilinear low-rank minimization problem is tackled which allows to write a three-dimensional low-rank tensor and consequently to estimate the state sequence and the lower-dimensional matrices $\mathbf {A}_1,\mathbf {A}_2,\mathbf {B}_1,\mathbf {B}_2,\mathbf {C}_1,\mathbf {C}_2$ . A numerical example on a large-scale adaptive optics system demonstrates the ability of the algorithm to handle the identification of state-space models within the class of Kronecker structured matrices in a scalable manner which results in more compact models.
|
[
"Computer Science and Informatics",
"Mathematics"
] |
10.1086/698431
|
Beyond Ethics Conscience Pacifism And The Political In Wartime Britain
|
The central intervention of this article concerns the contingency of the relationship between ethics and politics. The empirical focus is Second World War Britain, where the refusal to fight was often framed as a conscientious objection. More broadly, one of the central propositions in the anthropology of ethics has been that ethics is ubiquitous. However, ethical practices—such as conscience—are not always prioritized in public life. It is not simply, for example, that we might have different ways of answering “how ought I to live?”, but that the question itself is not always thought to be socially significant. We therefore need to pay attention to how and why the question is posed, and what this means for who can speak and about what issues. As such, the paper argues that the valorization of conscience can reproduce forms of privilege.
|
[
"Texts and Concepts",
"The Social World and Its Interactions",
"The Study of the Human Past"
] |
10.1016/j.nanoen.2018.12.037
|
Surface potential tailoring of PMMA fibers by electrospinning for enhanced triboelectric performance
|
Triboelectric generators rely on contact-generated surface charge transfer between materials with different electron affinities to convert mechanical energy into useful electricity. The ability to modify the surface chemistry of polymeric materials can therefore lead to significant enhancement of the triboelectric performance. Poly(methyl methacrylate) (PMMA) is a biocompatible polymer commonly used in medical applications, but its central position on the triboelectric series, which empirically ranks materials according to their electron-donating or electron accepting tendencies, renders it unsuitable for application in triboelectric generators. Here, we show that the surface potential of PMMA fibers produced by electrospinning can be tailored through the polarity of the voltage used during the fabrication process, thereby improving its triboelectric performance, as compared to typically spin-coated PMMA films. The change in surface chemistry of the electrospun PMMA fibers is verified using X-ray photoelectron spectroscopy, and this is directly correlated to the changes in surface potential observed by Kelvin probe force microscopy. We demonstrate the enhancement of triboelectric energy harvesting capability of the electrospun PMMA fibers, suggesting that this surface potential modification approach can be more widely applied to other materials as well, for improved triboelectric performance.
|
[
"Materials Engineering",
"Synthetic Chemistry and Materials",
"Physical and Analytical Chemical Sciences"
] |
10.1126/science.1248725
|
Structure of the mitochondrial translocator protein in complex with a diagnostic ligand
|
The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane α helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physical and Analytical Chemical Sciences",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1002/hbm.22787
|
Immediate memory for "when, where and what": Short-delay retrieval using dynamic naturalistic material
|
We investigated the neural correlates supporting three kinds of memory judgments after very short delays using naturalistic material. In two functional magnetic resonance imaging (fMRI) experiments, subjects watched short movie clips, and after a short retention (1. 5-2. 5 s), made mnemonic judgments about specific aspects of the clips. In Experiment 1, subjects were presented with two scenes and required to either choose the scene that happened earlier in the clip ("scene-chronology"), or with a correct spatial arrangement ("scene-layout"), or that had been shown ("scene-recognition"). To segregate activity specific to seen versus unseen stimuli, in Experiment 2 only one probe image was presented (either target or foil). Across the two experiments, we replicated three patterns underlying the three specific forms of memory judgment. The precuneus was activated during temporal-order retrieval, the superior parietal cortex was activated bilaterally for spatial-related configuration judgments, whereas the medial frontal cortex during scene recognition. Conjunction analyses with a previous study that used analogous retrieval tasks, but a much longer delay (>1 day), demonstrated that this dissociation pattern is independent of retention delay. We conclude that analogous brain regions mediate task-specific retrieval across vastly different delays, consistent with the proposal of scale-invariance in episodic memory retrieval.
|
[
"Neuroscience and Disorders of the Nervous System"
] |
10.1038/s41467-020-16496-y
|
Blockade of VEGF-C signaling inhibits lymphatic malformations driven by oncogenic PIK3CA mutation
|
AbstractLymphatic malformations (LMs) are debilitating vascular anomalies presenting with large cysts (macrocystic) or lesions that infiltrate tissues (microcystic). Cellular mechanisms underlying LM pathology are poorly understood. Here we show that the somatic PIK3CAH1047R mutation, resulting in constitutive activation of the p110α PI3K, underlies both macrocystic and microcystic LMs in human. Using a mouse model of PIK3CAH1047R-driven LM, we demonstrate that both types of malformations arise due to lymphatic endothelial cell (LEC)-autonomous defects, with the developmental timing of p110α activation determining the LM subtype. In the postnatal vasculature, PIK3CAH1047R promotes LEC migration and lymphatic hypersprouting, leading to microcystic LMs that grow progressively in a vascular endothelial growth factor C (VEGF-C)-dependent manner. Combined inhibition of VEGF-C and the PI3K downstream target mTOR using Rapamycin, but neither treatment alone, promotes regression of lesions. The best therapeutic outcome for LM is thus achieved by co-inhibition of the upstream VEGF-C/VEGFR3 and the downstream PI3K/mTOR pathways.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing"
] |
10.1007/978-3-319-33628-2_18
|
Local Food Systems And Their Climate Impacts A Life Cycle Perspective
|
The creation and maintenance of local food sovereignty and security is a top priority on political agendas. Food systems are characterized by complex dynamic nexuses at different levels and scales, and sustainability assessments necessarily need to approach social, economic, and environmental dimensions. While the provision of food is limited, among other factors, by the quantity of fertile areas, these areas are also attractive for other land uses, e. g. , for the cultivation of energy plants or afforestation, which can result in socioeconomic conflicts related to land-use competition. Numerous studies have looked at the global picture, using integrated assessment models, in which biophysical and economic models are coupled to derive potential future pathways and related greenhouse gas (GHG) emissions of feeding and fueling the rising global population. While such models can be useful to show global boundary conditions, their representation of complex local-to-global interdependencies is necessarily limited. Looking at local structures, life cycle assessment (LCA) is a useful tool to analyze a product supply chain and gain detailed insights in order to provide apparently complex data in a simple way for detecting option spaces or informing civic societies. This chapter addresses the local food system of Vienna. It shows what we can learn from LCA about, for example, potential savings of food-related GHG emissions and about gaining efficiencies of local produce in contrast to imports from the international market.
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution"
] |
US 68180601 A
|
Light-emitting diode (LED) package and packaging method for shaping the external light intensity distribution
|
An LED package (10) includes LED die (12) mounted onto lead frame (14) and electrically connected thereto whereby LED die (12) is electrically energized through leads (16, 18). An encapsulant (20), preferably an epoxy resin, encapsulates and preferably hermetically seals LED die (12). Encapsulant (20) includes depression (24) defined by preselected curved surfaces (28), at least a portion of which are coated by reflective coating (26). Encapsulant (20) preferably also includes sides (22) with preselected curvature. In operation, LED die (12) emits light (32) directed approximately along LED die surface normal (36). Light rays (32) reflect from reflective surface (26) and reflected rays (38) are subsequently refracted by refracting surface (22) so that refracted rays (40) exit the capsule. The reflecting surface (26) and refracting surface (22) cooperate to convert LED die light distribution (32) into light distribution (40) which appears to emanate from an approximate point source (42).
|
[
"Systems and Communication Engineering",
"Materials Engineering"
] |
10.1109/IECON.2016.7793426
|
Power Hardware In Loop Harmonic Analysis Of A Smart Transformer Fed Distribution Grid
|
The Smart Transformer (ST) offers ancillary services in the low voltage grids. These new services in a real distribution grid can be demonstrated by means of simulation software, but it is difficult to prove them in lab due to the complexity and heterogeneity of the distribution grids. The Power-Hardware-In-Loop (PHIL) evaluation is an interesting solution for emulating the interaction between the real grid, simulated in a Real Time Digital Simulator (RTDS), and the ST. However the PHIL evaluation requires careful analysis. Depending on the interface topology the stability and the accuracy of the loop can be affected. This is mostly true when the interface converter is not a linear power amplifier, but just a simple DC/AC switching converter. Actually, no considerations have been made in the literature about the accuracy and stability of the PHIL in case of non-linear interface converter. This paper focuses on evaluating the harmonic behavior of the PHIL in case of current harmonic content in the grid. Depending on the bandwidth of the interface converter, the accuracy of the PHIL in simulating harmonic currents can be affected. The analytical considerations on the accuracy of the loop have been verified experimentally in a complex LV grid.
|
[
"Systems and Communication Engineering",
"Products and Processes Engineering"
] |
W2561691587
|
FOREIGN DIRECT INVESTMENT AND TECHNOLOGICAL INNOVATION IN DEVELOPING COUNTRIES
|
A large number of countries have enacted laws aimed at making it easier for firms to invest in their country, while many countries offer various monetary incentives and tax incentives to encourage inward Foreign Direct Investment (FDI). The desire to attract FDI is due not only to the fact that FDI brings in new investment boosting national income and employment, but also due to the expectation that inward FDI would also provide additional spillover benefits to the local economy that can result in higher productivity growth and increased export growth. This study aims to examine the impact of foreign direct investment on innovation in developing countries. The estimation of a panel threshold model on a sample of 54 developing countries for the 1980-2009 period shows the presence of non linear effects in the relationship between FDI and innovation. We find a threshold value of technological development below which FDI has a negative impact on innovation and above which FDI has a significant positive impact on innovation. We conclude that it is not enough for economic policy to attract foreign investments, it is still necessary to support domestic firms to build an absorptive capacity allowing them to enjoy the benefits of multinational firms.
|
[
"Individuals, Markets and Organisations",
"Institutions, Governance and Legal Systems"
] |
10.1016/j.tins.2017.03.002
|
The Role of Mental Maps in Decision-Making
|
A growing body of work is investigating the use of mental maps during decision-making. Here we discuss how decision-making organizes experiences according to an internal model of the current task, thereby structuring memory. Likewise, we consider how the structure of mental maps contributes to decision-making.
|
[
"The Human Mind and Its Complexity"
] |
10.1523/JNEUROSCI.4228-15.2016
|
Reduced Efficacy Of The Kcc2 Cotransporter Promotes Epileptic Oscillations In A Subiculum Network Model
|
Pharmacoresistant epilepsy is a chronic neurological condition in which a basal brain hyperexcitability results in paroxysmal hypersynchronous neuronal discharges. Human temporal lobe epilepsy has been associated with dysfunction or loss of the potassium-chloride cotransporter KCC2 in a subset of pyramidal cells in the subiculum, a key structure generating epileptic activities. KCC2 regulates intraneuronal chloride and extracellular potassium levels by extruding both ions. Absence of effective KCC2 may alter the dynamics of chloride and potassium levels during repeated activation of GABAergic synapses due to interneuron activity. In turn, such GABAergic stress may itself affect Cl− regulation. Such changes in ionic homeostasis may switch GABAergic signaling from inhibitory to excitatory in affected pyramidal cells and also increase neuronal excitability. Possibly these changes contribute to periodic bursting in pyramidal cells, an essential component in the onset of ictal epileptic events. We tested this hypothesis with a computational model of a subicular network with realistic connectivity. The pyramidal cell model explicitly incorporated the cotransporter KCC2 and its effects on the internal/external chloride and potassium levels. Our network model suggested the loss of KCC2 in a critical number of pyramidal cells increased external potassium and intracellular chloride concentrations leading to seizure-like field potential oscillations. These oscillations included transient discharges leading to ictal-like field events with frequency spectra as in vitro . Restoration of KCC2 function suppressed seizure activity and thus may present a useful therapeutic option. These simulations therefore suggest that reduced KCC2 cotransporter activity alone may underlie the generation of ictal discharges. SIGNIFICANCE STATEMENT Ion regulation in the brain is a major determinant of neural excitability. Intracellular chloride in neurons, a partial determinant of the resting potential and the inhibitory reversal potentials, is regulated together with extracellular potassium via kation chloride cotransporters. During temporal lobe epilepsy, the homeostatic regulation of intracellular chloride is impaired in pyramidal cells, yet how this dysregulation may lead to seizures has not been explored. Using a realistic neural network model describing ion mechanisms, we show that chloride homeostasis pathology provokes seizure activity analogous to recordings from epileptogenic brain tissue. We show that there is a critical percentage of pathological cells required for seizure initiation. Our model predicts that restoration of the chloride homeostasis in pyramidal cells could be a viable antiepileptic strategy.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Computer Science and Informatics"
] |
10.1016/j.bbapap.2019.140335
|
Characterization of pyranose oxidase variants for bioelectrocatalytic applications
|
Pyranose oxidase (POx) catalyzes the oxidation of D-glucose to 2-ketoglucose with concurrent reduction of oxygen to H2O2. POx from Trametes ochracea (ToPOx) is known to react with alternative electron acceptors including 1,4-benzoquinone (1,4-BQ), 2,6-dichlorophenol indophenol (DCPIP), and the ferrocenium ion. In this study, enzyme variants with improved electron acceptor turnover and reduced oxygen turnover were characterized as potential anode biocatalysts. Pre-steady-state kinetics of the oxidative half-reaction of ToPOx variants T166R, Q448H, L545C, and L547R with these alternative electron acceptors were evaluated using stopped-flow spectrophotometry. Higher kinetic constants were observed as compared to the wild-type ToPOx for some of the variants. Subsequently, the variants were immobilized on glassy carbon electrodes. Cyclic voltammetry measurements were performed to measure the electrochemical responses of these variants with glucose as substrate in the presence of 1,4-BQ, DCPIP, or ferrocene methanol as redox mediators. High catalytic efficiencies (Imaxapp/KMapp) compared to the wild-type POx proved the potential of these variants for future bioelectrocatalytic applications, in biosensors or biofuel cells. Among the variants, L545C showed the most desirable properties as determined kinetically and electrochemically.
|
[
"Physical and Analytical Chemical Sciences",
"Biotechnology and Biosystems Engineering"
] |
10.1016/j.anbehav.2020.04.006
|
How do backward-walking ants (Cataglyphis velox) cope with navigational uncertainty?
|
Current opinion in insect navigation assumes that animals need to align with the goal direction to recognize familiar views and approach it. Yet, ants sometimes drag heavy food items backwards to the nest and it is still unclear to what extent they rely on visual memories while doing so. In this study displacement experiments and alterations of the visual scenery revealed that ants indeed recognized and used the learnt visual scenery to guide their path towards the nest while walking backwards. In addition, the occurrence of forward-peeking behaviours revealed that backward-walking ants continually estimated their directional uncertainty by integrating multiple cues such as visual familiarity, the state of their path integrator and the time spent backwards. A simple mechanical model based on repulsive and attractive visual memories captured the results and explained how visual navigation can be performed backwards.
|
[
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution"
] |
interreg_1073
|
CROSS-BORDER EDUCATION NETWORK 4.0
|
The Industrial revolution n4is on progress: Schools, Universities and SMEs are fully involved to provide necessary skills and innovation processes. The Alpine Area is involved and several local and EU actions are addressing this challenging topic. The transboarder area interested by E-EDU4.0 is on this topic with assistance and services provided by local intermediaries to SMEs, but needs additional efforts to provide necessary skills both for the educational programmes for Schools and Universities and the training actions addressed to SMEs. E-EDU4.0aims to support the Industry 4.0 process strengthening the impact of training and educational programmes with a much more effective transboarder cooperation and a better synergy concerning training and educational programmes from one side, laboratories and didactic infrastructures from the other. The project builds necessary networks of actors dealing with skills and learning programmes, organize their activities and provide necessary tools and necessary equipment to complete the instruments and the infrastructures available for the learning process both at local and transnational level. The concrete testing of the qualification programmes with local and transboarder actions addressed to SMEs and students will improve the project impact and open to new synergies and transferring actions. An overall platform with materials and mapping will support the networking, the cooperation and the durability of the project actions undertaken.
|
[
"Products and Processes Engineering",
"Computer Science and Informatics",
"The Social World and Its Interactions"
] |
10.1093/cid/ciy938
|
The importance of heterogeneity to the epidemiology of tuberculosis
|
Although less well-recognized than for other infectious diseases, heterogeneity is a defining feature of tuberculosis (TB) epidemiology. To advance toward TB elimination, this heterogeneity must be better understood and addressed. Drivers of heterogeneity in TB epidemiology act at the level of the infectious host, organism, susceptible host, environment, and distal determinants. These effects may be amplified by social mixing patterns, while the variable latent period between infection and disease may mask heterogeneity in transmission. Reliance on notified cases may lead to misidentification of the most affected groups, as case detection is often poorest where prevalence is highest. Assuming that average rates apply across diverse groups and ignoring the effects of cohort selection may result in misunderstanding of the epidemic and the anticipated effects of control measures. Given this substantial heterogeneity, interventions targeting high-risk groups based on location, social determinants, or comorbidities could improve efficiency, but raise ethical and equity considerations.
|
[
"Environmental Biology, Ecology and Evolution",
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1007/JHEP09(2011)050
|
Lifting Asymptotic Degeneracies With The Mirror Tba
|
We describe a qualitative feature of the AdS_5 x S^5 string spectrum which is not captured by the asymptotic Bethe ansatz. This is reflected by an enhanced discrete symmetry in the asymptotic limit, whereby extra energy degeneracy enters the spectrum. We discuss how finite size corrections should lift this degeneracy, through both perturbative (Luscher) and non-perturbative approaches (the Mirror TBA), and illustrate this explicitly on two such asymptotically degenerate states.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
10.1007/s12678-016-0340-z
|
Pt Nanoparticles Supported on Niobium-Doped Tin Dioxide: Impact of the Support Morphology on Pt Utilization and Electrocatalytic Activity
|
Two synthesis routes were used to design high surface area niobium-doped tin dioxide (Nb-doped SnO2, NTO) nanostructures with either loose-tube (fibre-in-tube) morphology using electrospinning or aerogel morphology using a sol-gel process. A higher specific surface area but a lower apparent electrical conductivity was obtained on the NTO aerogel compared to the loose tubes. The NTO aerogels and loose tubes and two reference materials (undoped SnO2 aerogel and Vulcan XC72) were platinized with a single colloidal suspension and tested as oxygen reduction reaction (ORR) electrocatalysts for proton-exchange membrane fuel cell (PEMFC) applications. The specific surface area of the supports strongly influenced the mass fraction of deposited Pt nanoparticles (NPs) and their degree of agglomeration. The apparent electrical conductivity of the supports determined the electrochemically active surface area (ECSA) and the catalytic activity of the Pt NPs for the ORR. Based on these findings, electrospinning appears to be the preferred route to synthesize NTO supports for PEMFC cathode application. [Figure not available: see fulltext. ]
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics",
"Materials Engineering"
] |
W4220954082
|
CNN-LSTM: An efficient hybrid deep learning architecture for predicting short-term photovoltaic power production
|
Climate change is pushing an increasing number of nations to use green energy resources, particularly solar power as an applicable substitute to traditional power sources. However, photovoltaic power generation is highly weather-dependent, relying mostly on solar irradiation that is highly unstable, and unpredictable which makes power generation challenging. Accurate photovoltaic power predictions can substantially improve the operation of solar power systems. This is vital for supplying prime electricity to customers and ensuring the resilience of power plants’ operation. This research is motivated by the recent adoption and advances in DL models and their successful use in the sector of energy. The suggested model merges two deep learning architectures, the long short-term memory (LSTM) and convolutional neural network (CNN). Using a real-world dataset from Rabat, Morocco, as a case study to illustrate the effectiveness of the suggested topology. According to error metrics, MAE, MAPE, and RMSE, the suggested architecture CNN-LSTM performance exceeds that of standard machine learning and single DL models in terms of prediction, precision, and stability.
|
[
"Systems and Communication Engineering",
"Computer Science and Informatics"
] |
172260
|
Evolution of fungal mating-type chromosomes
|
Sex chromosomes often show extensive areas of suppressed recombination and cytological differentiation, a well-documented phenomenon in animals and plants. Lack of recombination is expected to limit the efficacy of natural selection, leading to degeneration in gene content. Similarly, fungal mating-type chromosomes, which are responsible for controlling compatibility during mating, can display patterns of suppressed recombination encompassing up to 90% of the chromosome length. The mechanisms responsible for lack of recombination and consequent degeneration remain unclear.
Here, I propose to use comparative genomics to investigate the patterns and underlying mechanisms involved in recombination suppression and genomic degeneration in Microbotryum, a model fungal system with a range of dimorphic mating-type chromosomes. I will complement the currently available high-quality genome assemblies for twenty species in the genus with three outgroups, which will allow to polarize all genomic data. I will then use the genomic dataset to: 1) test hypotheses on the origin of recombination suppression in fungal mating-type chromosomes; 2) study the evolution of non-recombining regions in fungal mating-type chromosomes, e.g., their size and age, and the existence of evolutionary strata; and 3) study the patterns and mechanisms of genomic degeneration in non-recombining regions, namely non-synonymous substitution accumulation, transposable elements, disrupted genes, and non-optimal codon usage.
Results will not only shed light on the origins and consequences of suppressed recombination and genome degradation in fungal mating-type chromosomes, but will also yield unprecedented insights into the dynamics of sexual reproduction in eukaryotes and contribute for a unified view of the evolution of dimorphic chromosomes.
|
[
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1016/j.aop.2020.168125
|
The unreasonable effectiveness of Eliashberg theory for pairing of non-Fermi liquids
|
The paradigmatic Migdal–Eliashberg theory of the electron–phonon problem is central to the understanding of superconductivity in conventional metals. This powerful framework is justified by the smallness of the Debye frequency relative to the Fermi energy, and allows an enormous simplification of the full many-body problem. However, superconductivity is found also in many families of strongly-correlated materials, in which there is no a priori justification for the applicability of Eliashberg theory. In these systems, superconductivity emerges out of an anomalous metallic state, calling for a new theoretical framework to describe pairing out of a non-Fermi liquid. In this article, we review two model systems in which such behavior is found: a Fermi sea coupled to gapless bosonic fluctuations, and a system of fermions with local, strongly frustrated interactions. In both models, there is a well-defined limit in which the Eliashberg equations are asymptotically exact even in the strongly coupled regime. These models thus provide tractable examples of how superconductivity can emerge in the absence of coherent electronic quasiparticles; they also demonstrate the surprisingly wide applicability of the Eliashberg formalism, well beyond the conventional regime for which it was originally designed.
|
[
"Condensed Matter Physics"
] |
W1969419593
|
Effects of acidic conditions on the physiology of a green alga (Micractiniumsp.) before and after a 5-year interaction withTetrahymena thermophilain an experimental microcosm
|
The mechanisms through which algae evolve physiological characteristics related to endosymbiotic associations with heterotrophic organisms remain unclear. We previously showed that a green alga (Micractinium sp.) was able to evolve a host (ciliate)-benefiting phenotype that prolonged the longevity of Tetrahymena thermophila in the absence of bacteria during a 5-year culture period in an experimental microcosm. Comparative experiments between the ancestral alga (i.e. original) and evolved algal clones of the same lineage can be performed to analyse the mechanisms that underlie algal evolution during interactions with ciliates. Here, we investigated the effects of acidic conditions on algal physiology because the acidic conditions within the food vacuoles of Tetrahymena could potentially affect algal evolution during long-term interactions. It might be expected that algal clones isolated from T. thermophila hosts would have developed the ability to resist acidic conditions in order to establish within the h...
|
[
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1073/pnas.1712530114
|
DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line
|
Meiotic synapsis and recombination between homologs permits the formation of cross-overs that are essential for generating chromosomally balanced sperm and eggs. In mammals, surveillance mechanisms eliminate meiotic cells with defective synapsis, thereby minimizing transmission of aneuploidy. One such surveillance mechanism is meiotic silencing, the inactivation of genes located on asynapsed chromosomes, via ATR-dependent serine-139 phosphorylation of histone H2AFX (γH2AFX). Stimulation of ATR activity requires direct interaction with an ATR activation domain (AAD)-containing partner. However, which partner facilitates the meiotic silencing properties of ATR is unknown. Focusing on the best-characterized example of meiotic silencing, meiotic sex chromosome inactivation, we reveal this AAD-containing partner to be the DNA damage and checkpoint protein TOPBP1. Conditional TOPBP1 deletion during pachynema causes germ cell elimination associated with defective X chromosome gene silencing and sex chromosome condensation. TOPBP1 is essential for localization to the X chromosome of silencing “sensors,” including BRCA1, and effectors, including ATR, γH2AFX, and canonical repressive histone marks. We present evidence that persistent DNA double-strand breaks act as silencing initiation sites. Our study identifies TOPBP1 as a critical factor in meiotic sex chromosome silencing.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1007/s00445-016-1006-7
|
Conduit margin heating and deformation during the AD 1886 basaltic Plinian eruption at Tarawera volcano, New Zealand
|
During explosive eruptions, a suspension of gas and pyroclasts rises rapidly within a conduit. Here, we have analysed textures preserved in the walls of a pyroclastic feeder dyke of the AD 1886 Tarawera basaltic Plinian fissure eruption. The samples examined consist of basaltic ash and scoria plastered onto a conduit wall of a coherent rhyolite dome and a welded rhyolitic dome breccia. We examine the textural evidence for the response of the wall material, built of ∼75 vol. % glass and ∼25 vol. % crystals (pore-free equivalent), to mass movement in the adjacent conduit. In the rhyolitic wall material, we quantify the orientation and aspect ratio of biotite crystals as strain markers of simple shear deformation, and interpret juxtaposed regions of vesiculation and vesicle collapse as evidence of conduit wall heating. Systematic changes occur close to the margin: (1) porosity is highly variable, with areas locally vesiculated or densified, (2) biotite crystals are oriented with their long axis parallel to the margin, (3) the biotites have greater aspect ratios close to the margin and (4) the biotite crystals are fractured. We interpret the biotite phenocryst deformation to result from crystal fracture, rotation and cleavage-parallel bookcase translation. These textural observations are inferred to indicate mechanical coupling between the hot gas-ash jet and the conduit wall and reheating of wall rock rhyolite. We couple these observations with a simple 1D conductive heating model to show what minimum temperature the conduit wall needs to reach in order to achieve a temperature above the glass transition throughout the texturally-defined deformed zone. We propose that conduit wall heating and resulting deformation influences conduit margin outgassing and may enhance the intensity of such large basaltic eruptions.
|
[
"Earth System Science",
"Materials Engineering",
"Physical and Analytical Chemical Sciences"
] |
US 17190793 A
|
Non-invasive method for in-vivo bone-growth stimulation
|
A method and apparatus for preventing osteopenia, promoting bone tissue growth, ingrowth, and healing of bone tissue includes the step of and means for applying a mechanical load to the bone tissue at a relatively low level on the order of between about 50 and about 500 microstrain, peak-to-peak, and at a relatively high frequency in the range from about 10 and about 100 Hz. Mechanical loading at such strain levels and such frequencies has been found to prevent bone loss and enhance new bone formation.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
10.3389/fnbeh.2015.00167
|
Evidence from a rare case study for hebbian-like changes in structural connectivity induced by long-term deep brain stimulation
|
It is unclear whether Hebbian-like learning occurs at the level of long-range white matter connections in humans, i. e. , where measurable changes in structural connectivity (SC) are correlated with changes in functional connectivity. However, the behavioral changes observed after deep brain stimulation (DBS) suggest the existence of such Hebbian-like mechanisms occurring at the structural level with functional consequences. In this rare case study, we obtained the full network of white matter connections of one patient with Parkinson’s disease (PD) before and after long-term DBS and combined it with a computational model of ongoing activity to investigate the effects of DBS-induced long-term structural changes. The results show that the long-term effects of DBS on resting-state functional connectivity is best obtained in the computational model by changing the structural weights from the subthalamic nucleus (STN) to the putamen and the thalamus in a Hebbian-like manner. Moreover, long-term DBS also significantly changed the SC towards normality in terms of model-based measures of segregation and integration of information processing, two key concepts of brain organization. This novel approach using computational models to model the effects of Hebbianlike changes in SC allowed us to causally identify the possible underlying neural mechanisms of long-term DBS using rare case study data. In time, this could help predict the efficacy of individual DBS targeting and identify novel DBS targets.
|
[
"Neuroscience and Disorders of the Nervous System",
"Computer Science and Informatics"
] |
10.1016/j.cell.2019.05.010
|
The Translational Landscape of the Human Heart
|
Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appears to be frequent, suggesting inefficient translation termination. We identify hundreds of previously undetected microproteins, expressed from lncRNAs and circRNAs, for which we validate the protein products in vivo. The translation of microproteins is not restricted to the heart and prominent in the translatomes of human kidney and liver. We associate these microproteins with diverse cellular processes and compartments and find that many locate to the mitochondria. Importantly, dozens of microproteins are translated from lncRNAs with well-characterized noncoding functions, indicating previously unrecognized biology. Translational profiling in a primary human tissue reveals frequent translation downstream of predicted disease-causing variants as well as translation of hundreds of microproteins from long noncoding RNAs and circular RNAs.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing"
] |
10.1051/0004-6361/201834086
|
Broadening Of The Dem By Multi Shelled And Turbulent Loops
|
Broad differential emission measure (DEM) distributions in the corona are a sign of multi-thermal plasma along the line-of-sight. Traditionally, this is interpreted as evidence of multi-stranded loops. Recently, however, it has been shown that multi-stranded loops are unlikely to exist in the solar corona, because of their instability to transverse perturbations. We aim to test if loop models subject to the Transverse Wave-Induced Kelvin-Helmholtz (TWIKH) instability result in broad DEMs, potentially explaining the observations. We took simulation snapshots and compute the numerical DEM. Moreover, we performed forward-modelling in the relevant AIA channels before reconstructing the DEM. We find that turbulent loop models broaden their initial DEM, because of the turbulent mixing. The width of the DEM is determined by the initial temperature contrast with the exterior. We conclude that impulsively excited loop models have a rather narrow DEM, but that continuously driven models result in broad DEMs that are comparable to the observations.
|
[
"Universe Sciences",
"Fundamental Constituents of Matter"
] |
10.1016/j.bpj.2015.01.029
|
Revisiting the interaction between the chaperone skp and lipopolysaccharide
|
The bacterial outer membrane comprises two main classes of components, lipids and membrane proteins. These nonsoluble compounds are conveyed across the aqueous periplasm along specific molecular transport routes: the lipid lipopolysaccharide (LPS) is shuttled by the Lpt system, whereas outer membrane proteins (Omps) are transported by chaperones, including the periplasmic Skp. In this study, we revisit the specificity of the chaperone-lipid interaction of Skp and LPS. High-resolution NMR spectroscopy measurements indicate that LPS interacts with Skp nonspecifically, accompanied by destabilization of the Skp trimer and similar to denaturation by the nonnatural detergent lauryldimethylamine-N-oxide (LDAO). Bioinformatic analysis of amino acid conservation, structural analysis of LPS-binding proteins, and MD simulations further confirm the absence of a specific LPS binding site on Skp, making a biological relevance of the interaction unlikely. Instead, our analysis reveals a highly conserved salt-bridge network, which likely has a role for Skp function.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physical and Analytical Chemical Sciences"
] |
W2114835337
|
Prevalence of labyrinthine ossification in CT and MR imaging of patients with acute deafness to severe sensorineural hearing loss
|
To evaluate the prevalence of labyrinthine ossification, and especially cochlear ossification, in a cohort of patients with unilateral sudden deafness or severe sensorineural hearing loss.Retrospective data collection.Sixty-four consecutive patients with unilateral sudden deafness or severe sensorineural hearing loss and either high-resolution CT (HRCT) of the temporal bone (isotropic spatial resolution ≤ 0.8 mm; n = 18) or high resolution CISS MRI (isotropic spatial resolution ≤ 1 mm; n = 55) were included. Nine patients underwent both imaging modalities. A standardized reading regarding labyrinthine ossifications was performed by an experienced head and neck radiologist blinded to clinical symptoms.Radiologic signs of cochlear ossification were present in 14 patients (12 CT and 2 MRI). Eight patients showed unilateral and six patients bilateral signs of cochlear ossification. In all except one of the unilateral cases, the deafened ear was affected.Signs of cochlear ossification were found in an unexpectedly high rate (14/64, 22%) of patients with acute deafness. The data suggest HRCT of the temporal bone to be more sensitive to detect labyrinthine ossification than MRI. HRCT of the temporal bone should therefore be considered in patients with impaired recovery of acute deafness to exclude cochlear ossification; if present, and, in cases of early signs, the patient should be evaluated further to facilitate early cochlear implantation before progression impedes electrode insertion, reflecting latest developments considering cochlea implants for single-sided deafness to be effective.
|
[
"Prevention, Diagnosis and Treatment of Human Diseases",
"Neuroscience and Disorders of the Nervous System"
] |
EP 2017072407 W
|
IMPROVED METHOD FOR DYEING TEXTILES CONTAINING SYNTHETIC MATERIALS IN THE WASHING MACHINE USING MODIFIED SILICONES
|
The present invention relates to a method for machine-dyeing textiles, more particularly textiles which contain synthetic materials such as polyester.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
W2188489921
|
Topographic surveys at the SDT km6 farm, Buasvm Timisoara, Romania (Timisoara-Arad NR).
|
This paper aims at presenting the topographic surveys on the Didactic Station Farm of Timisoara, Romania, at the km 6, on the Timisoara-Arad NR. The farm belongs to the Commune of Dumbravita; it has the cadastral number CC49 and it consists, according to the Land Cadastre (no. 4631) of agricultural and zootechnic administrative buildings, greenhouses, silos, warehouses, winter stables, fuel storages, pump house, drill, water plant, concrete platforms, access roads, and courtyard. The total area of the farm is 12 ha and 7138 m. In 2005, according to the no. 14597 from April 26, 2005, recorded by the A.N.C.P.I.-O.C.P.I. TIMIS, Timisoara Land Cadastre Office, it was recorded in the Land Cadastre of the estate according to the Licence no. 1051/2003 issues by the Mayor of the Commune of Dumbravita as follows: in the 1 step, opening a land cadastre with indefinite character for the territory of the Commune of Dumbravita on the grounds of the art. 61 of Law no. 7/1996 where it is recorded in the database as a unitary compulsory system of technical, economic and legal recording system, plot no. CC49, made up of the “SDT Farm located at the km 6 of the Timisoara-Arad NR”; in the 2 step, they recorded the ownership right on the estate from the public domain consisting of the buildings and terrain described above in favour of the ROMANIAN STATE in 1/1 quotas as “localisation ownership” as stipulated by the GD no. 123/1993 and GD no. 1225/1996; in the 3 step, they recorded the right “for administration” on the buildings and terrain described above on the grounds of the same legal acts mentioned above in favour of the BANAT’S UNIVERSITY OF AGRICULTURAL SCIENCES AND VETERINARY MEDICINE OF TIMISOARA, for the DIDACTIC EXPERIMENTAL STATION. Topographic survey was carried out with a Leica TC 805 total station and the support points used were GPS-determined with a Leica Geo Office Combined Programme; the resulting files were transformed with DXF Generate, after which the points were reported in AutoCad with a TopoLT Programme. TopoSys is a special geodesic soft that uses modern calculus conception and procedures to solve the geodesic reference of the observations made with total stations or through the GNSS technology. TopoSys encloses all the functions needed to define and use Coordinate Reference Systems according to international Standards with a larger number of Coordinate Systems defined on local or global geodesic data. Inner methods of filtering errors and compensating data through the Smallest Square Method are the result of scientific research in the field, tested on numerous topographic and geodesic measurements on both local geodesic and national GNSS networks. Coordinates were determined in the Stereographic 1970 projection system and point quotas were determined in relation to the Black Sea level. The TopoSys programme system is special software destined for the processing of 1D, 2D, and 3D geodesic networks, to the compensation of observations through statistic methods, to topographic calculus and to coordinate transformation. Reduced observation compensation is done with the Smallest Square Method with correction equations developed through the indirect method. To filer greater errors, we sued the robust (Danish) method and the TAU test to determine the thrust threshold. After downloading, data processing and turning coordinates from ETRS89 into STEREO’70 with the TransDatRO 4.01 application, we calculated the 3D land model with the TopoLT Programme, a programme functioning on the AutoCad platform.
|
[
"Earth System Science",
"Systems and Communication Engineering"
] |
W2903531556
|
Assuming Direct Control: The Beguiling Allure of Incomes Policies in Postwar America
|
Abstract: Histories of American economic policymaking after World War II often describe a “Fiscal Revolution,” in which Keynesian macroeconomic tools replaced the microeconomic regulations and reforms of the New Deal. This article challenges that narrative by demonstrating how the Keynesian economists responsible for the Fiscal Revolution relied upon incomes policies to ensure that inflation would not sabotage efforts to achieve full employment. In the 1960s, the White House Council of Economic Advisers pressed the Kennedy and Johnson administrations to enforce “wage-price guideposts” in order to realize the potential of the Fiscal Revolution. Yet incomes policies also encouraged policymakers to deflect responsibility for inflation onto the private sector’s behavior as an alternative to adopting the painful but necessary fiscal and monetary restraint. As a reliance on the microeconomic control of inflation persisted into the late 1970s, this approach ultimately undercut the Keynesians’ macroeconomic promises and prolonged the misery of stagflation.
|
[
"Individuals, Markets and Organisations",
"The Study of the Human Past",
"Institutions, Governance and Legal Systems"
] |
10.1007/JHEP12(2016)079
|
Improved jet substructure methods: Y-splitter and variants with grooming
|
It has recently been demonstrated with Monte Carlo studies that combining the well-known Y-splitter and trimming techniques gives rise to important gains in the signal significance achievable for boosted electroweak boson tagging at high pt. Here we carry out analytical calculations that explain these findings from first principles of QCD both for grooming via trimming and via the modified mass-drop tagger (mMDT). We also suggest modifications to Y-splitter itself, which result in great simplifications to the analytical results both for pure Y-splitter as well as its combination with general grooming methods. The modifications also lead to further performance gains, while making the results largely independent of choice of groomer. We discuss the implications of these findings in the broader context of optimal methods for boosted object studies at hadron colliders.
|
[
"Fundamental Constituents of Matter"
] |
896138
|
Next generation of mechanics with hazard-responsive surface
|
80%+ of failures in machines using lubricated moving parts (bearings, gears, camshafts etc.) is due to the damaging operational condition called starved oil lubrication. Recurrent exposure to this state is the bottleneck of performance and durability for such machinery. End-users are happy to pay more for reliable and durable engineering products, but state of the art offers only costly and deficient workarounds to the key peformance-limiting problem.
A disruptive approach to enhance oil lubrication specifically under the critical damaging conditions is recently viable due to high-frequency ultra-short pulse lasers (HFUSPL) having become affordable outside the realm of high-end applications. By using HFUSPLs the micro- and nanoscale patterning of surfaces is possible with unprecedented precision. Such patterning activates a novel and highly effective oil lubricant delivery mechanism expressly under critical contact conditions, resulting in 3x reduction of friction coefficient, improved performance and reliability, reduced maintenance – doubling the lifetime of the entire machinery.
This technology has been advanced to TRL6: real textured engine parts demonstrated in model engines. To make NGenMech available for industry it needs to be automatised using an optoelectric control unit, duly parametrised for the market entry use case, and piloted by a selected industrial partner. To engineer this workplan, a feasibility study will assess potential markets, analyse business model and partnership options, and evaluate commercialisation and IPR strategies to select Primary Use Case and define Strategic Business Plan. As R&D and tech transfer company, IfU Diagnostic Systems GmbH is engaged with several large industrial companies interested in commercialising NGenMech technology.
NGenMech will double the lifetime of machinery while reducing maintenance need. The powerful cascade impact over the entire value chain of mechanical engineering cannot be overestimated.
|
[
"Products and Processes Engineering",
"Materials Engineering"
] |
W1600703341
|
Sharpening Bounds on Principal Effects with Covariates
|
Estimation of treatment effects in randomized studies is often hampered by possible selection bias induced by conditioning on or adjusting for a variable measured post-randomization. One approach to obviate such selection bias is to consider inference about treatment effects within principal strata, that is, principal effects. A challenge with this approach is that without strong assumptions principal effects are not identifiable from the observable data. In settings where such assumptions are dubious, identifiable large sample bounds may be the preferred target of inference. In practice these bounds may be wide and not particularly informative. In this work we consider whether bounds on principal effects can be improved by adjusting for a categorical baseline covariate. Adjusted bounds are considered which are shown to never be wider than the unadjusted bounds. Necessary and sufficient conditions are given for which the adjusted bounds will be sharper (i.e., narrower) than the unadjusted bounds. The methods are illustrated using data from a recent, large study of interventions to prevent mother-to-child transmission of HIV through breastfeeding. Using a baseline covariate indicating low birth weight, the estimated adjusted bounds for the principal effect of interest are 63% narrower than the estimated unadjusted bounds.
|
[
"Mathematics",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.5194/se-11-1275-2020
|
Mantle flow below the central and greater Alpine region: Insights from SKS anisotropy analysis at AlpArray and permanent stations
|
The Alpine chain in western and central Europe is a complex orogen developed as a result of the African-Adriatic plate convergence towards the European continent and the closure of several Tethys oceanic branches. Seismic tomography studies detected high-wave-speed slabs plunging beneath the orogen to variable depths and a potential change in subduction polarity beneath the Central Alps. Alpine subduction is expected to leave a significant imprint on the surrounding mantle fabrics, although deformation associated with the Hercynian Orogeny, which affected Europe prior to the collision with Adria, may have also been preserved in the European lithosphere. Here we estimate SKS anisotropy beneath the central and greater Alpine region at 113 broadband seismic stations from the AlpArray experiment as well as permanent networks from Italy, Switzerland, Austria, Germany, and France. We compare the new improved dataset with previous studies of anisotropy, mantle tomography, lithospheric thickness, and absolute plate motion, and we carry out Fresnel analysis to place constraints on the depth and origin of anisotropy. Most SKS directions parallel the orogen strike and the orientation of the Alpine slabs, rotating clockwise from west to east along the chain, from <span classCombining double low line"inline-formula">-45</span> to 90<span classCombining double low line"inline-formula"> </span> over a <span classCombining double low line"inline-formula">1/4700</span> km distance. No significant changes are recorded in Central Alps at the location of the putative switch in subduction polarity, although a change in direction variability suggests simple asthenospheric flow or coupled deformation in the Swiss Central Alps transitions into more complex structures beneath the Eastern Alps. SKS fast axes follow the trend of high seismic anomalies across the Alpine Front, far from the present-day boundary, suggesting slabs act as flow barriers to the ambient mantle surrounding them for hundreds of km. Further north across the foreland, SKS fast axes parallel Hercynian geological structures and are orthogonal to the Rhine Graben and crustal extension. However, large splitting delay times (<span classCombining double low line"inline-formula">>1. 4</span> s) are incompatible with a purely lithospheric contribution but rather represent asthenospheric flow not related to past deformational events. West of the Rhine Graben, in northeastern France, anisotropy directions are spatially variable in the proximity of a strong positive seismic anomaly in the upper mantle, perhaps perturbing the flow field guided by the nearby Alpine slabs.
|
[
"Earth System Science"
] |
949899
|
Verified physics-aware machine learning to transform non-linear power system stability and optimization
|
Measures against global warming require disruptive changes in the electricity sector. Drastically reducing CO2 emissions involves replacing bulk generation units with millions of renewable energy sources, along with a rapid increase of electricity demand. Maintaining the stability of the system with current approaches becomes not only computationally intractable, but also extremely costly. Recently proposed data-driven methods have been shown to handle the sheer complexity and have an impressive performance, achieving higher accuracy while being 250-1000 times faster than traditional methods. However, power systems are safety-critical systems, where data-driven methods will never be applied if they remain a black-box.
This proposal removes the barriers for the application of data-driven approaches in power system problems, proposing methods that exploit the underlying physical properties of power systems. We propose the development of physics-aware verifiable neural networks and a neural network training procedure that can supply by-design guarantees of the neural network prediction accuracy. Accuracy does no longer need to be a statistical metric. Instead, our methods can supply a provable upper bound of the prediction error over the whole input space, that the power system operators can trust. We further show how neural networks can capture non-linear constraints impossible to capture before, and can reduce any non-linear optimization problem to a tractable mixed-integer linear program with verified accuracy, potentially boosting computation speed and tractability. From a power systems context, this enables us to treat power system dynamics and optimization in a unified framework that accurately captures the true feasible region, removes various approximations, and eliminates redispatching costs, saving billions of euros per year. The proposed methods naturally extend beyond power systems, finding application to a wide range of physical safety-critical systems.
|
[
"Computer Science and Informatics",
"Systems and Communication Engineering",
"Products and Processes Engineering"
] |
10.1074/jbc.M114.549980
|
Rabies virus envelope glycoprotein targets lentiviral vectors to the axonal retrograde pathway in motor neurons
|
Rabies pseudotyped lentiviral vectors have great potential in gene therapy, not least because of their ability to transduce neurons following their distal axonal application. However, very little is known about the molecular processes that underlie their retrograde transport and cell transduction. Using multiple labeling techniques and confocal microscopy, we demonstrated that pseudotyping with rabies virus envelope glycoprotein (RV-G) enabled the axonal retrograde transport of two distinct subtypes of lentiviral vector in motor neuron cultures. Analysis of this process revealed that these vectors trafficked through Rab5-positive endosomes and accumulated within a non-acidic Rab7 compartment. RV-G pseudotyped vectors were co-transported with both the tetanus neurotoxin-binding fragment and the membrane proteins thought to mediate rabies virus endocytosis (neural cell adhesion molecule, nicotinic acetylcholine receptor, and p75 neurotrophin receptor), thus demonstrating that pseudotyping with RV-G targets lentiviral vectors for transport along the same pathway exploited by several toxins and viruses. Using motor neurons cultured in compartmentalized chambers, we demonstrated that axonal retrograde transport of these vectors was rapid and efficient; however, it was not able to transduce the targeted neurons efficiently, suggesting that impairment in processes occurring after arrival of the viral vectorin the somais responsible for the low transduction efficiency seen in vivo, which suggests a novel area for improvement of gene therapy vectors.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
SE 9801193 W
|
METHOD AND ARRANGEMENT FOR COMPOSTING BIODEGRADABLE MATERIAL
|
Arrangement for collecting and composting night-soil and other biodegradable material, comprising a space (23) in which a starting bed (29) has been spread out in order to accelerate the breakdown of material (30) which is dropped down onto the starting bed. The space (23) is lined with an inner layer of a flexible, liquid-impermeable material forming a sack-like container (8) which is open at the top. The starting bed (29) is arranged in the sack-like container, and the arrangement comprises members (40) for pressing the upper edge portion of the container against a ceiling (36) which is located under the floor (32) of at least one overhead toilet and is provided with at least one opening for attachment to a toilet bowl. The sack-like container (8) is designed to enclose the material (30) while the latter is being broken down, and the container comprises members for conveying liquid, which has been separated off from the material, via a screen arrangement (31). The sack-like container (8) is also designed to serve as an enclosure for transporting the completely or partially broken down material. The invention also relates to a method for collecting and composting night-soil.
|
[
"Products and Processes Engineering",
"Environmental Biology, Ecology and Evolution"
] |
10.1016/j.neuron.2020.08.016
|
The Sound of Silence: Hidden Responses of Neural Circuits to Alzheimer-Linked Mutations
|
Dysfunctions of cortico-hippocampal circuits represent a hallmark of Alzheimer's disease. In this issue of Neuron, Jun et al. illuminate the spatial coding failures by familial Alzheimer's disease mutations that may underlie the progressive decline in spatial mnemonic processing.
|
[
"Neuroscience and Disorders of the Nervous System",
"Integrative Biology: from Genes and Genomes to Systems"
] |
10.1103/PhysRevFluids.3.084002
|
Wetting over pre-existing liquid films
|
Wetting of a liquid over another, pre-existing liquid film governs several natural phenomena and technical applications, such as coating and oil recovery. The dynamics of this everyday process are poorly understood due to the lack of space and time-resolved techniques, which can discriminate between the two liquids. Here we image a water front moving on a micrometer-thick film of a solid supported silicone oil using laser scanning confocal microscopy. The silicone oil forms a meniscus around the water front. We resolve the spreading dynamics within the meniscus in 3D using tracer microparticles. Capillary suction induces local thinning of the oil film adjacent to the meniscus. When moving the water front forward, viscous forces deform the oil meniscus, giving rise to a wavelike film profile with local backflows. For high velocities, the film profile can be modeled within the Landau-Levich-Bretherton framework. The theory fails to predict the film profile at low velocities where strong capillary-suction-induced backflows occur.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
] |
10.1021/ja303309e
|
Release of high-energy water as an essential driving force for the high-affinity binding of cucurbit[n]urils
|
Molecular dynamics simulations and isothermal titration calorimetry (ITC) experiments with neutral guests illustrate that the release of high-energy water from the cavity of cucurbit[n]uril (CBn) macrocycles is a major determinant for guest binding in aqueous solutions. The energy of the individual encapsulated water molecules decreases with increasing cavity size, because larger cavities allow for the formation of more stable H-bonded networks. Conversely, the total energy of internal water increases with the cavity size because the absolute number of water molecules increases. For CB7, which has emerged as an ultrahigh affinity binder, these counteracting effects result in a maximum energy gain through a complete removal of water molecules from the cavity. A new design criterion for aqueous synthetic receptors has therefore emerged, which is the optimization of the size of cavities and binding pockets with respect to the energy and number of residing water molecules.
|
[
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
10.1209/0295-5075/114/26005
|
Analog Simulation Of Weyl Particles With Cold Atoms
|
In this letter we report on a novel approach to study the dynamics of harmonically confined Weyl particles using magnetically trapped fermionic atoms. We find that after a kick of its center of mass, the system relaxes towards a steady state even in the absence of interactions, in stark contrast with massive particles which would oscillate without damping. Remarkably, the equilibrium distribution is non-Boltzmann, exhibiting a strong anisotropy which we study both numerically and experimentally.
|
[
"Condensed Matter Physics",
"Fundamental Constituents of Matter"
] |
3729137
|
Scalable structured micro illumination light engines
|
The SMILE idea is based on the results of FET-Open “ChipScope”, which gave us unique technology skills in the processing of nanoLED arrays. In contrast to the ChipScope’s nanoLEDs for superresolution microscopy, larger SMILE microLEDs arrays can also be used for activating and manipulating chemical or biological reactions. With microLEDs, light intensities can be orders of magnitude higher. Larger dimensions enable hybrid integration with CMOS microelectronics, leading to a full scalability of the microLED platform in terms of number of pixels, intensity, switching speed and cost in a mass production situation. MicroLEDs can also be combined with existing colour converter technology, resulting in substantial flexibility concerning wavelength control. SMILE will develop microLED platforms giving access to an enormous variety of novel applications, when used as “Scalable Structured Micro-Illumination Light Engines” (SMILE). The approach is completely different to conventional structured illumination strategies used today. SMILE workplan includes GaN chip technology, CMOS design, chip-chip hybrid integration and system integration (housing and software). SMILE gives very high priority to market replication, preparing for discussions with future investors by the following approach: an “End-User Board” (EUB) of experts from various applications will discuss requirements to be met and perform SMILE test experiments. Therefore, SMILE prototypes will be made available to the EUB for testing and market validation in at least 5 different Pilot Applications (PA), which have already been chosen for analysing importance, relevance and high market potential: (1) DNA chip fabrication; (2) Maskless photolithography; (3) Optogenetics; (4) High-throughput fluorescence microscopy; (5) Chip-based holographic microscopy. All PA are addressing quickly increasing markets. The direct participation of a dedicated start-up company secures the long-term exploitation of SMILE technology.
|
[
"Systems and Communication Engineering",
"Condensed Matter Physics",
"Materials Engineering",
"Physical and Analytical Chemical Sciences",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1038/s41586-018-0045-y
|
Earthquake-induced transformation of the lower crust
|
The structural and metamorphic evolution of the lower crust has direct effects on the lithospheric response to plate tectonic processes involved in orogeny, including subsidence of sedimentary basins, stability of deep mountain roots and extension of high-topography regions. Recent research shows that before orogeny most of the lower crust is dry, impermeable and mechanically strong 1. During an orogenic event, the evolution of the lower crust is controlled by infiltration of fluids along localized shear or fracture zones. In the Bergen Arcs of Western Norway, shear zones initiate as faults generated by lower-crustal earthquakes. Seismic slip in the dry lower crust requires stresses at a level that can only be sustained over short timescales or local weakening mechanisms. However, normal earthquake activity in the seismogenic zone produces stress pulses that drive aftershocks in the lower crust 2. Here we show that the volume of lower crust affected by such aftershocks is substantial and that fluid-driven associated metamorphic and structural transformations of the lower crust follow these earthquakes. This provides a 'top-down' effect on crustal geodynamics and connects processes operating at very different timescales.
|
[
"Earth System Science"
] |
10.1002/bit.25562
|
An optogenetic upgrade for the Tet-OFF system
|
The rapid development of mammalian optogenetics has produced an expanding number of gene switches that can be controlled with the unprecedented spatiotemporal resolution of light. However, in the "pre-optogenetic" era many networks, cell lines and transgenic organisms have been engineered that rely on chemically-inducible transgene expression systems but would benefit from the advantages of the traceless inducer light. To open the possibility for the effortless upgrade of such systems from chemical inducers to light, we capitalized on the specific Med25VBD inhibitor of the VP16/VP64 transactivation domain. In a first step, we demonstrated the efficiency and selectivity of Med25VBD in the inhibition of VP16/VP64-based transgene expression systems. Then, we fused the inhibitor to the blue light-responsive B-LID degron and optimized the performance of this construct with regard to the number of Med25VBD repeats. This approach resulted in an optogenetic upgrade of the popular Tet-OFF (TetR-VP64, tetO7-PhCMVmin) system that allows tunable, blue light-inducible transgene expression in HEK-293T cells.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physical and Analytical Chemical Sciences"
] |
171527
|
Enhanced satellite laser ranging system
|
The EO-SLR is a next generation satellite laser ranging system that incorporates latest advances in the field to assure ease of setup, use and sustainable economic operation. Packaged in standard sea container with modular design for laser systems, climate control, calibration equipment, data systems, and power systems it can be made operational with manufacturer settings within days and is potentially mobile.
The EO-SLR is being designed to address the rapid growth in the number of objects in space that must be tracked. Google and other private firms are planning to launch hundreds of satellites. The Cubesat revolution has opened space to public and private sector of smaller or less technically developed countries, their universities, research institutes and even private SMEs. Simultaneously problem of space debris is an increasing global public concern.
The International Laser Ranging Service has identified geographic market gaps, lack of standard components, absence of next generation equipment and other concerns. The EO-SLR is being designed to meet those needs with a packaged system with new features and functionality unmatched by systems in the market:
• Data for space object orbit calculations from one observation site
• Improved ranging accuracy of scattered light space objects including closely located (groups of) space objects
• Advanced calibration and testing system, that significantly speeds up the measurement process
• Easily convertible
Highly complex products like SLR systems demand a broad range of multidisciplinary skills to design. HEE Photonic Labs emerged from the research center of the University of Latvia that had developed SLR systems and other advanced equipment for the Soviet space program from 1970-ties.This is an substantial advantage allowing to design project proposal offering innovative and unique in design EO-SLR instrument as a flexible and fast response to emerging needs in the market of ground segment of space technologies
|
[
"Products and Processes Engineering",
"Systems and Communication Engineering",
"Universe Sciences"
] |
10.1029/2011JB008801
|
Slow Slip Events And Strain Accumulation In The Guerrero Gap Mexico
|
[1] Global positioning system (GPS) time series in Guerrero (Mexico) reveal the existence of large slow slip events (SSEs) at the boundary between the Cocos and North American plates. In this study, we examined the last three SSEs that occurred in 2001/2002, 2006 and 2009/2010, and their impact on the strain accumulation along the Guerrero subduction margin. GPS displacements were inverted to retrieve the slip distribution during each SSE and the inter-SSE coupling of the subduction interface. The three analyzed SSEs have equivalent moment magnitudes of between 7. 50 and 7. 65, their lateral extents are variable, and they all show significant slip in the Guerrero seismic gap. During the inter-SSE epochs, the interplate coupling is high in the area where slow slip subsequently occurs. In the Guerrero gap, the shallow portion of the plate interface from the trench to the coast is weakly coupled. The average slip deficit accumulated in the Guerrero gap over a period of 12 years, which corresponds to three cycles of SSE, is only 1/4 of the slip deficit accumulated on both sides of the gap. Moreover, the regions of large slip deficit coincide with the rupture areas of recent large earthquakes. We conclude that the SSEs in the Guerrero gap release a significant part of the strain accumulated during the inter-SSE period. If large subduction thrust earthquakes occur in the Guerrero gap, their recurrence time is probably increased compared to adjacent regions.
|
[
"Earth System Science"
] |
interreg_1183
|
EMAS as a Nest to Help And Nurture the Circular Economy
|
Organizations, large and Small and Medium sized enterprises (SMEs),are increasingly aware of the benefits of closing loops by improving resource efficiency: saving material costs, creating competitive advantages and new markets are among the main reasons for organisations to take action.At this respect, the EcoManagement and Audit Scheme (EMAS) is considered as a driver of the Circular Economy by encouraging organisations to develop techniques which make better use of resources in the production phase and retain physical goods longer and more efficiently in productive use, thus increasing their competitiveness.Starting from these considerations, ENHANCE project overall objective is to improve the implementation of regional policy instruments oriented to increasing the efficiency of resources by the exchange of experiences and practices on supporting EMAS registration.
Main barriers perceived by EMAS adopters are:lack of EMAS recognition from the market and Public Authorities (PA),technical support from PA and external incentives; high cost, etc. In this regard, the role of PA supporting EMAS as a competent body becomes essential in order to remove these barriers and to encourage organizations to adopt EMAS through various means, such as reducing the technical barriers for EMAS adoption,enhancing benefits derived from EMAS, public subsidies and rewarding EMAS implementers with reduced enforcement (e.g.,regulatory relief).Derived from the activities to be carried, such expected changes shall become effective upon the production of these main outputs:
1)Regional Studies on supporting EMAS registration
2)Methodology to assess the feasibility of good practices on supporting EMAS registration
3)EMAS Joint Database. 4)Thematic workshops to exchange experiences
5)Regional Studies on the exchange process
6)Toward EMAS Action Plans.Main beneficiaries from the cooperation will be PA, but direct effects resulting from the project will also affect organizations as EMAS adopters
|
[
"Products and Processes Engineering",
"Individuals, Markets and Organisations",
"Institutions, Governance and Legal Systems"
] |
10.1098/rspb.2014.1622
|
Evolution of cultural traits occurs at similar relative rates in different world regions
|
A fundamental issue in understanding human diversity is whether or not there are regular patterns and processes involved in cultural change. Theoretical and mathematical models of cultural evolution have been developed and are increasingly being used and assessed in empirical analyses. Here, we test the hypothesis that the rates of change of features of human socio-cultural organization are governed by general rules. One prediction of this hypothesis is that different cultural traits will tend to evolve at similar relative rates in different world regions, despite the unique historical backgrounds of groups inhabiting these regions. We used phylogenetic comparative methods and systematic cross-cultural data to assess how different socio-cultural traits changed in (i) island southeast Asia and the Pacific, and (ii) sub-Saharan Africa. The relative rates of change in these two regions are significantly correlated. Furthermore, cultural traits that are more directly related to external environmental conditions evolve more slowly than traits related to social structures. This is consistent with the idea that a form of purifying selection is acting with greater strength on these more environmentally linked traits. These results suggest that despite contingent historical events and the role of humans as active agents in the historical process, culture does indeed evolve in ways that can be predicted from general principles
|
[
"Environmental Biology, Ecology and Evolution",
"The Social World and Its Interactions",
"The Study of the Human Past"
] |
10.1144/M39.1
|
Chapter 1 An Overview Of The Eruption Of Soufriere Hills Volcano Montserrat From 2000 To 2010
|
Abstract The 1995–present eruption of Soufriere Hills Volcano on Montserrat has produced over a cubic kilometre of andesitic magma, creating a series of lava domes that were successively destroyed, with much of their mass deposited in the sea. There have been five phases of lava extrusion to form these lava domes: November 1995–March 1998; November 1999–July 2003; August 2005–April 2007; July 2008–January 2009; and October 2009–February 2010. It has been one of the most intensively studied volcanoes in the world during this time, and there are long instrumental and observational datasets. From these have sprung major new insights concerning: the cyclicity of magma transport; low-frequency earthquakes associated with conduit magma flow; the dynamics of lateral blasts and Vulcanian explosions; the role that basalt–andesite magma mingling in the mid-crust has in powering the eruption; identification using seismic tomography of the uppermost magma reservoir at a depth of 5. 5 > 7. 5 km; and many others. Parallel to the research effort, there has been a consistent programme of quantitative risk assessment since 1997 that has both pioneered new methods and provided a solid evidential source for the civil authority to use in mitigating the risks to the people of Montserrat.
|
[
"Earth System Science",
"Products and Processes Engineering"
] |
10.5194/acp-12-9977-2012
|
Impact of HONO on global atmospheric chemistry calculated with an empirical parameterization in the EMAC model
|
The photolysis of HONO is important for the atmospheric HO x (OH + HO 2) radical budget and ozone formation, especially in polluted air. Nevertheless, owing to the incomplete knowledge of HONO sources, realistic HONO mechanisms have not yet been implemented in global models. We investigated measurement data sets from 15 field measurement campaigns conducted in different countries worldwide. It appears that the HONO/NO x ratio is a good proxy predictor for HONO mixing ratios under different atmospheric conditions. From the robust relationship between HONO and NO x, a representative mean HONO/NO x ratio of 0. 02 has been derived. Using a global chemistry-climate model and employing this HONO/NO x ratio, realistic HONO levels are simulated, being about one order of magnitude higher than the reference calculations that only consider the reaction OH + NO → HONO. The resulting enhancement of HONO significantly impacts HO x levels and photo-oxidation products (e. g, O 3, PAN), mainly in polluted regions. Furthermore, the relative enhancements in OH and secondary products are higher in winter than in summer, thus enhancing the oxidation capacity in polluted regions, especially in winter when other photolytic OH sources are of minor importance. Our results underscore the need to improve the understanding of HONO chemistry and its representation in atmospheric models.
|
[
"Physical and Analytical Chemical Sciences",
"Earth System Science"
] |
W2022700714
|
Demographic Situation and the Level of Human Development of the Republic of Kazakhstan: Regional Aspects
|
Demographic Situation and the Level of Human Development of the Republic of Kazakhstan: Regional Aspects The objects of research are indicators of human development in Kazakhstan from the moment of independence acquisition by the republic until today. The subject of scientific research is spatial-existential patterns of socio-demographic processes as a key factor of human potential development in the Republic of Kazakhstan. The importance of scientific work is that the results permit to estimate the level of human development of the Republic of Kazakhstan on the basis of socio-demographic processes. For the first time the basic indicators defining human potential in Kazakhstan have been studied in detail and systematized. The aim of the work is to define the laws of the spatial organization of human potential and its basic spatial analyses of human development of Kazakhstan. The database, created with the help of ArcGIS, allows to monitor the changes of human development level, to analyze, estimate and manage human potential of the Republic of Kazakhstan.
|
[
"Human Mobility, Environment, and Space",
"The Social World and Its Interactions"
] |
US 202117236007 A
|
CHARGED PARTICLE BEAM WRITING APPARATUS, CHARGED PARTICLE BEAM WRITING METHOD, AND A NON-TRANSITORY COMPUTER-READABLE STORAGE MEDIUM
|
Position shifts caused by charging phenomena can be corrected with high accuracy. A charged particle beam writing apparatus includes an exposure-amount distribution calculator calculating an exposure amount distribution of a charged particle beam using a pattern density distribution and a dose distribution, a fogging charged particle amount distribution calculator calculating a plurality of fogging charged particle amount distributions by convoluting each of a plurality of distribution functions for fogging charged particles with the exposure amount distribution, a charge-amount distribution calculator calculating a charge amount distribution due to direct charge using the pattern density distribution, the dose distribution, and the exposure amount distribution, and calculating a plurality of charge amount distributions due to fogging charge using the plurality of fogging charged particle amount distributions, a position shift amount calculator calculating a position shift amount of a writing position based on the charge amount distribution due to direct charge and the plurality of charge amount distributions due to fogging charge, a corrector correcting an exposure position using the position shift amount, and a writer exposing the corrected exposure position to a charged particle beam.
|
[
"Physical and Analytical Chemical Sciences",
"Systems and Communication Engineering"
] |
10.1101/207571
|
Pseudo Dollo Models For The Evolution Of Binary Characters Along A Tree
|
The stochastic Dollo model is a model for capturing evolution of features, for example cognate data in language evolution. However, it is rather sensitive to borrowing events, coding errors, semantic shift and other anomalies, so other models, in particular the covarion model, tends to have a better fit to the data. Here, we introduce the pseudo Dollo model, a model of character evolution along a tree that can be formulated as a three-state continuous time Markov chain (CTMC) model. The initial state represent absence of a feature, then a birth event allows the feature to be present. A death event can follow so that the feature becomes absent again. However, no new birth events are allowed after a death event has taken place. We examine the model in a fully Bayesian setting, and demonstrate it can have a better fit than some of the popular alternative models on some real world datasets. Some variations on the pseudo Dollo model are introduced as well, including the multi-state pseudo Dollo model and pseudo Dollo covarion model. The model is implemented in open source software Babel, a package to BEAST licensed under LGPL. A user friendly way to set up an analysis is available through BEAUti, the graphical user interface of BEAST.
|
[
"Mathematics",
"Computer Science and Informatics"
] |
10.3390/catal9070567
|
P450BM3-Catalyzed Oxidations Employing Dual Functional Small Molecules
|
A set of dual functional small molecules (DFSMs) containing different amino acids has been synthesized and employed together with three different variants of the cytochrome P450 monooxygenase P450BM3 from Bacillus megaterium in H2O2-dependent oxidation reactions. These DFSMs enhance P450BM3 activity with hydrogen peroxide as an oxidant, converting these enzymes into formal peroxygenases. This system has been employed for the catalytic epoxidation of styrene and in the sulfoxidation of thioanisole. Various P450BM3 variants have been evaluated in terms of activity and selectivity of the peroxygenase reactions.
|
[
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
] |
10.1021/acs.nanolett.7b04227
|
Affinity Purification and Single-Molecule Analysis of Integral Membrane Proteins from Crude Cell-Membrane Preparations
|
The function of integral membrane proteins is critically dependent on their naturally surrounding lipid membrane. Detergent-solubilized and purified membrane proteins are therefore often reconstituted into cell-membrane mimics and analyzed for their function with single-molecule microscopy. Expansion of this approach toward a broad range of pharmaceutically interesting drug targets and biomarkers however remains hampered by the fact that these proteins have low expression levels, and that detergent solubilization and reconstitution often cause protein conformational changes and loss of membrane-specific cofactors, which may impair protein function. To overcome this limitation, we here demonstrate how antibody-modified nanoparticles can be used to achieve affinity purification and enrichment of selected integral membrane proteins directly from cell membrane preparations. Nanoparticles were first bound to the ectodomain of β-secretase 1 (BACE1) contained in cell-derived membrane vesicles. In a subsequent step, these were merged into a continuous supported membrane in a microfluidic channel. Through the extended nanoparticle tag, a weak (∼fN) hydrodynamic force could be applied, inducing directed in-membrane movement of targeted BACE1 exclusively. This enabled selective thousand-fold enrichment of the targeted membrane protein while preserving a natural lipid environment. In addition, nanoparticle-targeting also enabled simultaneous tracking analysis of each individual manipulated protein, revealing how their mobility changed when moved from one lipid environment to another. We therefore believe this approach will be particularly useful for separation in-line with single-molecule analysis, eventually opening up for membrane-protein sorting devices analogous to fluorescence-activated cell sorting.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physical and Analytical Chemical Sciences",
"Materials Engineering"
] |
10.1007/JHEP01(2018)035
|
Quantum Gravity From Conformal Field Theory
|
We bootstrap loop corrections to AdS5 supergravity amplitudes by enforcing the consistency of the known classical results with the operator product expansion of $$ \mathcal{N} $$
= 4 super Yang-Mills theory. In particular this yields much new information on the spectrum of double-trace operators which can then be used, in combination with superconformal symmetry and crossing symmetry, to obtain a prediction for the one-loop amplitude for four graviton multiplets in AdS. This in turn yields further new results on subleading O(1/N 4) corrections to certain double-trace anomalous dimensions.
|
[
"Fundamental Constituents of Matter",
"Mathematics"
] |
818943
|
Deciphering the metabolic roles of the urea-cycle pathway in carcinogenesis for improving diagnosis and therapy
|
Almost 100 years ago, Warburg described a metabolic change in energy flux that occurs during carcinogenesis. Since then, multiple studies have demonstrated how anabolic synthesis of macromolecules can be altered to support cancer cell progression. Yet, the potential effect of altered catabolic degradation of macromolecules on tumour carcinogenesis has been much less studied.
The urea cycle (UC) is the main catabolic pathway by which mammals excrete waste nitrogen. Although the complete UC pathway is liver-specific, most tissues express different combinations of UC enzymes according to the cellular needs. Surprisingly, we find that changes in expression of UC components causing UC dysregulation, (UCD) is a global phenomenon in cancer, metabolically augmenting net nitrogen usage for the synthesis of macromolecules by reducing nitrogen waste. This metabolic alteration is associated with poor patient prognosis. Thus, we hypothesise that UCD provides a major metabolic advantage to multiple aspects of carcinogenesis and as such, leads to specific, identifiable genomic and biochemical signatures, with implications for cancer diagnosis and therapy.
To pursue our hypothesis, we will incorporate state-of-the-art comparative genomic, peptidomic, metabolomic, and molecular approaches to explore this scientific “blind spot” of nitrogen metabolism in carcinogenesis. We will investigate how UCD causally affects carcinogenesis, by characterising tumour-specific functions of UC enzymes (Aim I), correlating tumour phenotypes with systemic biomarkers (Aim II), and testing the treatment efficacy of drug combinations targeting UCD in cancers (Aim III).
Our proposal, strengthened by my training as a physician scientist, harbours considerable potential for translational diagnostic and therapeutic utility of our findings, enabling us to i) identify new diagnostic biomarkers for monitoring cancer initiation and progression and ii) predict and enhance the therapeutic response.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
interreg_3049
|
Storm ALEX impact response
|
The storm Alex is a serious event that has put a strain on the entire territory ALCOTRA, without administrative boundaries between states and without natural barriers as can be the Alps.
This hostile circumstance urges us to gather our strength and act collectively on climate change.
It is necessary to prepare the territory to the impacts of these events by acting quickly and planning a long-term strategy, to mitigate the effects.
The RITA project responds to some of these phenomena, proposing a combination of structural interventions and cognitive knowledge that will allow to predict with great precision the aggravating impact, starting from real experiences acquired on both sides of the border and optimizing a solid working method used in RISBA and RESBA.
|
[
"Products and Processes Engineering",
"Earth System Science"
] |
10.1103/PhysRevLett.115.138301
|
Colloidal Microworms Propelling via a Cooperative Hydrodynamic Conveyor Belt
|
We study propulsion arising from microscopic colloidal rotors dynamically assembled and driven in a viscous fluid upon application of an elliptically polarized rotating magnetic field. Close to a confining plate, the motion of this self-assembled microscopic worm results from the cooperative flow generated by the spinning particles which act as a hydrodynamic "conveyor belt. " Chains of rotors propel faster than individual ones, until reaching a saturation speed at distances where induced-flow additivity vanishes. By combining experiments and theoretical arguments, we elucidate the mechanism of motion and fully characterize the propulsion speed in terms of the field parameters.
|
[
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
] |
10.3168/jds.2015-10202
|
Linking bone development on the caudal aspect of the distal phalanx with lameness during life
|
Claw horn disruption lesions (CHDL; sole hemorrhage, sole ulcer, and white line disease) cause a large proportion of lameness in dairy cattle, yet their etiopathogenesis remains poorly understood. Untreated CHDL may be associated with damage to the internal anatomy of the foot, including to the caudal aspect of the distal phalanx upon which bone developments have been reported with age and with sole ulcers at slaughter. The primary aim of this study was to assess whether bone development was associated with poor locomotion and occurrence of CHDL during a cow's life. A retrospective cohort study imaged 282 hind claws from 72 Holstein-Friesian dairy cows culled from a research herd using X-ray micro-computed tomography (μ-CT; resolution: 0. 11 mm). Four measures of bone development were taken from the caudal aspect of each distal phalanx, in caudal, ventral, and dorsal directions, and combined within each claw. Cow-level variables were constructed to quantify the average bone development on all hind feet (BD-Ave) and bone development on the most severely affected claw (BD-Max). Weekly locomotion scores (1-5 scale) were available from first calving. The variables BD-Ave and BD-Max were used as outcomes in linear regression models; the explanatory variables included locomotion score during life, age, binary variables denoting lifetime occurrence of CHDL and of infectious causes of lameness, and other cow variables. Both BD-Max and BD-Ave increased with age, CHDL occurrence, and an increasing proportion of locomotion scores at which a cow was lame (score 4 or 5). The models estimated that BD-Max would be 9. 8 mm (SE 3. 9) greater in cows that had been lame at >50% of scores within the 12 mo before slaughter (compared with cows that had been assigned no lame scores during the same period), or 7. 0 mm (SE 2. 2) greater if the cow had been treated for a CHDL during life (compared with cows that had not). Additionally, histology demonstrated that new bone development was osteoma, also termed "exostosis. " Age explained much of the variation in bone development. The association between bone development and locomotion score during life is a novel finding, and bone development appears specific to CHDL. Bone development on the most severely affected foot was the best explained outcome and would seem most likely to influence locomotion score. To stop irreparable anatomical damage within the foot, early identification of CHDL and effective treatment could be critical.
|
[
"Physiology in Health, Disease and Ageing",
"Cell Biology, Development, Stem Cells and Regeneration",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1093/mnras/stz2266
|
On the role of supermassive black holes in quenching star formation in local central galaxies
|
ABSTRACT
We analyse the role of AGN feedback in quenching star formation for massive, central galaxies in the local Universe. In particular, we compare the prediction of two semi-analytic models (l-galaxies and sage) featuring different schemes for AGN feedback, with the SDSS DR7 taking advantage of a novel technique for identifying central galaxies in an observational data set. This enables us to study the correlation between the model passive fractions, which is predicted to be suppressed by feedback from an AGN, and the observed passive fractions in an observationally motivated parameter space. While the passive fractions for observed central galaxies show a good correlation with stellar mass and bulge mass, passive fractions in l-galaxies correlate with the halo and black hole mass. For sage, the passive fraction correlate with the bulge mass as well. Among the two models, sage has a smaller scatter in the black hole–bulge mass $({M_{\rm BH}-M_{\rm Bulge}})$ relation and a slope that agrees better with the most recent observations at z ∼ 0. Despite the more realistic prescription of radio-mode feedback in sage, there are still tensions left with the observed passive fractions and the distribution of quenched galaxies. These tensions may be due to the treatment of galaxies living in non-resolved substructures and the resulting higher merger rates that could bring cold gas which is available for star formation.
|
[
"Universe Sciences",
"Computer Science and Informatics"
] |
10.1080/09546553.2019.1668781
|
What Do Closed Source Data Tell Us About Lone Actor Terrorist Behavior A Research Note
|
This article contributes to the growing body of knowledge on lone-actor terrorism with the incorporation of closed-source data. The analyses presented investigate the antecedent behaviors of U. K. -b. . .
|
[
"The Social World and Its Interactions"
] |
10.1038/s41380-018-0198-y
|
Sex-specific impact of prenatal androgens on social brain default mode subsystems
|
AbstractEarly-onset neurodevelopmental conditions (e. g. , autism) affect males more frequently than females. Androgens may play a role in this male-bias by sex-differentially impacting early prenatal brain development, particularly neural circuits that later develop specialized roles in social cognition. Here, we find that increasing prenatal testosterone in humans is associated with later reduction of functional connectivity between social brain default mode (DMN) subsystems in adolescent males, but has no effect in females. Since testosterone can work directly via the androgen receptor (AR) or indirectly via the estrogen receptor through aromatase conversion to estradiol, we further examined how a potent non-aromatizable androgen, dihydrotestosterone (DHT), acts via the AR to influence gene expression in human neural stem cells (hNSC)—particularly for genes of high-relevance for DMN circuitry. DHT dysregulates a number of genes enriched for syndromic causes of autism and intellectual disability and for genes that in later development are expressed in anatomical patterns that highly correspond to the cortical midline DMN subsystem. DMN-related and DHT-affected genes (e. g. , MEF2C) are involved in a number of synaptic processes, many of which impact excitation-inhibition balance. Androgens have male-specific prenatal influence over social brain circuitry in humans and may be relevant towards explaining some component of male-bias in early-onset neurodevelopmental conditions.
|
[
"Neuroscience and Disorders of the Nervous System",
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems"
] |
Q4772621
|
TRUNCHINI SIMONE
|
UMA EMPRESA INDIVIDUAL FUNDADA EM 2014 COMO UM SIMPLES MEDIADOR DE SEGUROS COMO COLABORADORA DE VÁRIOS AGENTES E CORRETORES DESDE 2019 TEM UM MANDATO DIRETO DE AGÊNCIA PARA A REPRESENTAÇÃO DA EMPRESA HELVETIA. O OBJETIVO É PROPOR AO CLIENTE UMA SOLUÇÃO COMPLETA E PERSONALIZADA, COM ESPECIAL ATENÇÃO PARA AS EMPRESAS QUE PARTICIPAM EM CONCURSOS PÚBLICOS, TANTO PARA A OFERTA FIDEJUSSORIA/CAUZIONI COMO PARA A OFERTA DE GARANTIAS DE INCÊNDIO EM GERAL. O OBJETIVO A LONGO PRAZO É CONSOLIDAR OS SEUS RESULTADOS E EXPANDIR A ESTRUTURA COM A INCLUSÃO DE UM RECURSO ESTÁVEL.
|
[
"Individuals, Markets and Organisations"
] |
172725
|
African governance and space: transport corridors, border towns and port cities in transition
|
AFRIGOS investigates the process of 'respacing' Africa, a political drive towards regional and continental integration, on the one hand, and the re-casting of Africa's engagement with the global economy, on the other. This is reflected in unprecedented levels of investment in physical and communications infrastructure, and the outsourcing of key functions of Customs, Immigration and security agencies. AFRIGOS poses the question of how far respacing is genuinely forging institutions that are facilitating or obstructing the movement of people and goods; that are enabling or preventing urban and border spaces from being more effectively and responsively governed; and that take into account the needs of African populations whose livelihoods are rooted in mobility and informality. The principal research questions are approached through a comparative study of port cities, border towns and other strategic nodes situated along the busiest transport corridors in East, Central, West and Southern Africa. These represent sites of remarkable dynamism and cosmopolitanism, which reflects their role in connecting African urban centres to each other and to other global cities.
AFRIGOS considers how governance 'assemblages' are forged at different scales and is explicitly comparative. It works through 5 connected Streams that address specific questions: 1. AGENDA-SETTING is concerned with policy (re-)formulation. 2. PERIPHERAL URBANISM examines governance in border towns and port cities. 3. BORDER WORKERS addresses everyday governance emerging through the interaction of officials and others who make their livelihoods from the border. 4. CONNECTIVE INFRASTRUCTURE looks as the transformative effects of new technologies. 5. PEOPLE & GOODS IN MOTION traces the passage of people and goods and the regimes of regulation to which they are subjected. AFRIGOS contributes to interdisciplinary research on borderland studies, multi-level governance and the everyday state.
|
[
"Human Mobility, Environment, and Space",
"Institutions, Governance and Legal Systems"
] |
10.1080/16000889.2018.1471913
|
On The Early Studies Recognizing The Role Of Sulphuric Acid In Atmospheric Haze And New Particle Formation
|
Atmospheric aerosols have been a subject to scientific interest at least since the Age of Enlightenment, including theories concerning the origins of atmospheric haze and dust. Early studies associ. . .
|
[
"Earth System Science",
"Physical and Analytical Chemical Sciences"
] |
222531
|
Overcoming the selectivity challenge in chemistry and chemical biology via innovative tethering strategies
|
In the last two centuries, synthetic organic chemistry has undergone an unprecedented revolution. The ability to understand and modify the molecular structure of matter has changed our life in many areas, such as medicine, agriculture or commodity materials. These major successes gave the impression that synthetic chemistry is a mature field. However, this impression is completely misleading, as current synthetic methods still lack the selectivity needed for the modification of complex molecules. Both selecting between different reactive groups and functionalizing inert bonds in their presence represent formidable challenges.
In this project, we propose to develop highly selective “molecular tethers” for the functionalization of both natural/synthetic organic compounds and biomolecules. The envisioned tethers are bifunctional small organic molecules having three fundamental properties:
1) A “biting end” with unique reactivity to be selectively installed in situ onto naturally occurring thiols, alcohols and amines. We will use tethers based on acetals and hypervalent iodine reagents.
2) A “functional end”, whose reactivity can be revealed “at will” to functionalize bonds that cannot be accessed with the current state of the art of synthetic chemistry, especially inert C-H and C=C bonds.
3) Being traceless, meaning that they can be removed easily once the desired functionalization has been achieved.
The main impact of this project will be in fundamental synthetic organic chemistry, as it will contribute to overcoming major selectivity hurdles in the functionalization of complex molecules. It will therefore result in faster progress in all the fields depending on synthetic molecules, such as medicine, agriculture or materials. A more efficient functionalization of biomolecules will allow us to soften the boundaries between synthetic chemistry and biology, leading to major progress in our understanding of living systems and our ability to modify them.
|
[
"Synthetic Chemistry and Materials",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1016/j.cobeha.2015.09.006
|
Phasic dopamine signals: From subjective reward value to formal economic utility
|
Although rewards are physical stimuli and objects, their value for survival and reproduction is subjective. The phasic, neurophysiological and voltammetric dopamine reward prediction error response signals subjective reward value. The signal incorporates crucial reward aspects such as amount, probability, type, risk, delay and effort. Differences of dopamine release dynamics with temporal delay and effort in rodents may derive from methodological issues and require further study. Recent designs using concepts and behavioral tools from experimental economics allow to formally characterize the subjective value signal as economic utility and thus to establish a neuronal value function. With these properties, the dopamine response constitutes a utility prediction error signal.
|
[
"Neuroscience and Disorders of the Nervous System",
"Individuals, Markets and Organisations"
] |
10.1038/s41467-017-00249-5
|
Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry
|
Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale. While previous SWATH-mass spectrometry studies have shown high intra-lab reproducibility, this has not been evaluated between labs. In this multi-laboratory evaluation study including 11 sites worldwide, we demonstrate that using SWATH-mass spectrometry data acquisition we can consistently detect and reproducibly quantify >4000 proteins from HEK293 cells. Using synthetic peptide dilution series, we show that the sensitivity, dynamic range and reproducibility established with SWATH-mass spectrometry are uniformly achieved. This study demonstrates that the acquisition of reproducible quantitative proteomics data by multiple labs is achievable, and broadly serves to increase confidence in SWATH-mass spectrometry data acquisition as a reproducible method for large-scale protein quantification.
|
[
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
222990
|
Open ground truth training network : magnetic resonance image simulation for training and validation of image analysis algorithms
|
This action aims to optimally prepare three young researchers for the evolving medical imaging world by offering a unique set of targeted interdisciplinary training and research assignments in the areas of anatomy, pathology, imaging techniques, quantitative image analysis and segmentation, Magnetic Resonance (MR) physics and MR image simulation.
MR imaging is the major imaging modality for brain and spine anatomy and pathology. A clear trend can be observed from visual to computer-assisted diagnosis by quantification of disease-specific biomarkers, derived from the MR images. The major components in image quantification applications are tissue and organ segmentation and classification. Manual segmentation is too tedious and cumbersome for daily clinical practice and would lead to large inter-user variability. Much research is therefore performed on automatic segmentation techniques. Training, validation and benchmarking of these techniques is currently impeded by the lack of MR image databases with exact reference segmentations.
The research will follow an innovative approach to overcome the current barriers for wide uptake of automatic segmentation. By combining mathematical organ models with physical and biological tissue properties and image simulation methods, substantial public image databases will be established providing ample MR images with ground truth (exact) segmentations, by which fast and accurate optimization and validation of image segmentation algorithms will be enabled.
Based on sound career development plans, and coached by experienced supervisors a training is offered by leading image analysis research groups from Philips (global leader in medical imaging) and the Eindhoven University of Technology (world-wide recognized authority in education and research on image analysis, esp. on MRI) and supported by researchers from leading clinical centers as UMC Utrecht, TU Munich, Kings College London and the German Center for Neurodegenerative Diseases.
|
[
"Computer Science and Informatics",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Systems and Communication Engineering"
] |
10.1038/nature09790
|
Aberrant chromosome morphology in human cells defective for Holliday junction resolution
|
In somatic cells, Holliday junctions can be formed between sister chromatids during the recombinational repair of DNA breaks or after replication fork demise. A variety of processes act upon Holliday junctions to remove them from DNA, in events that are critical for proper chromosome segregation. In human cells, the BLM protein, inactivated in individuals with Bloom's syndrome, acts in combination with topoisomerase IIIα, RMI1 and RMI2 (BTR complex) to promote the dissolution of double Holliday junctions. Cells defective for BLM exhibit elevated levels of sister chromatid exchanges (SCEs) and patients with Bloom's syndrome develop a broad spectrum of early-onset cancers caused by chromosome instability. MUS81-EME1 (refs 47), SLX1SLX4 (refs 811) and GEN1 (refs 12, 13) also process Holliday junctions but, in contrast to the BTR complex, do so by endonucleolytic cleavage. Here we deplete these nucleases from Bloom's syndrome cells to analyse human cells compromised for the known Holliday junction dissolution/resolution pathways. We show that depletion of MUS81 and GEN1, or SLX4 and GEN1, from Bloom's syndrome cells results in severe chromosome abnormalities, such that sister chromatids remain interlinked in a side-by-side arrangement and the chromosomes are elongated and segmented. Our results indicate that normally replicating human cells require Holliday junction processing activities to prevent sister chromatid entanglements and thereby ensure accurate chromosome condensation. This phenotype was not apparent when both MUS81 and SLX4 were depleted from Bloom's syndrome cells, suggesting that GEN1 can compensate for their absence. Additionally, we show that depletion of MUS81 or SLX4 reduces the high frequency of SCEs in Bloom's syndrome cells, indicating that MUS81 and SLX4 promote SCE formation, in events that may ultimately drive the chromosome instabilities that underpin early-onset cancers associated with Bloom's syndrome.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration"
] |
324139
|
Precision dating of the Palaeolithic: chronological mapping of the Middle and Upper Palaeolithic of Eurasia
|
This proposal addresses the chronology of the Middle to Upper Palaeolithic transition of Eurasia, the period between ~60-30,000 years ago, during which the first modern humans dispersed out of Africa into the Old World and Neanderthals disappeared. This is a crucially important interval for understanding late human evolution and the reasons leading to the global dominance of our species. The project will allow, for the first time, the construction of a robust chronology for more than 50 key Palaeolithic sites dating to this period from Eastern Europe to Siberia. We will use advanced radiocarbon techniques, as well as other increasingly refined dating methods (OSL, U-series) and Bayesian statistics. Previous radiocarbon dating, the main chronological tool for this period, is known now to be severely problematic, principally because of difficulties in removing contaminants from the samples. The PI and his team have been to the forefront of developing new chemical pretreatment methods, such as the use of ‘ultrafiltration’ to purify bone proteins, which have revolutionized our ability to radiocarbon date reliably old samples. Over the last 5 years, application of these methods in the dating of western European Palaeolithic sites has led to a significant revision in the chronology of the Middle to Upper Palaeolithic transition. New dating is urgently required to clarify the wider picture of the transition in a much broader geographic area. The proposal will apply these methods to sites in northern Eurasia, principally Russia and Central Asia, which have yet to see the benefits of these recent methodological developments. This project builds on expertise from a wide collaborative network and on the PIs work in the field over the last 8 years. We will obtain groundbreaking new data that will contribute to an improved understanding of the dispersal, extinction and co-existence of different human species, within a concise spatio-temporal framework and environmental context.
|
[
"The Study of the Human Past",
"Earth System Science"
] |
W1973050880
|
Mining Historical Traffic Data using Back Propagation Neural Network for Accurate Location Estimation
|
Therefore, in this presented work the neural network based location approximation technique is evaluated. During implementation of neural network based predictive algorithm two key deficiencies are observed first the long training time and quality of training patterns. In order to improve both the issues in neural network the data pre-processing technique is proposed and implemented. The presented improvement helps in initializing neural network and frequent learning. Therefore, the neural network is effectively trained in less amount of time with higher accuracy. The implementation of the proposed technique and traditional neural network technique is provided using NS2 network simulation environment and the neural network is implemented using JAVA environment. The performance evaluation of both the technique is given in terms of memory consumption, time consumption and predictive accuracy. According to the obtained results the performance of modified neural network is much higher than the traditional neural network. In addition of that the modified algorithm is able to train less amount of time as compared to the traditional neural network.
|
[
"Computer Science and Informatics",
"Systems and Communication Engineering"
] |
10.1126/science.1245711
|
Precise and ultrafast molecular sieving through graphene oxide membranes
|
Graphene-based materials can have well-defined nanometer pores and can exhibit low frictional water flow inside them, making their properties of interest for filtration and separation. We investigate permeation through micrometer-thick laminates prepared by means of vacuum filtration of graphene oxide suspensions. The laminates are vacuum-tight in the dry state but, if immersed in water, act as molecular sieves, blocking all solutes with hydrated radii larger than 4. 5 angstroms. Smaller ions permeate through the membranes at rates thousands of times faster than what is expected for simple diffusion. We believe that this behavior is caused by a network of nanocapillaries that open up in the hydrated state and accept only species that fit in. The anomalously fast permeation is attributed to a capillary-like high pressure acting on ions inside graphene capillaries.
|
[
"Condensed Matter Physics",
"Materials Engineering",
"Physical and Analytical Chemical Sciences"
] |
10.1016/j.biopsycho.2017.07.012
|
“Lacking warmth”: Alexithymia trait is related to warm-specific thermal somatosensory processing
|
Alexithymia is a personality trait involving deficits in emotional processing. The personality construct has been extensively validated, but the underlying neural and physiological systems remain controversial. One theory suggests that low-level somatosensory mechanisms act as somatic markers of emotion, underpinning cognitive and affective impairments in alexithymia. In two separate samples (total N = 100), we used an established Quantitative Sensory Testing (QST) battery to probe multiple neurophysiological submodalities of somatosensation, and investigated their associations with the widely-used Toronto Alexithymia Scale (TAS-20). Experiment one found reduced sensitivity to warmth in people with higher alexithymia scores, compared to individuals with lower scores, without deficits in other somatosensory submodalities. Experiment two replicated this result in a new group of participants using a full-sample correlation between threshold for warm detection and TAS-20 scores. We discuss the relations between low-level thermoceptive function and cognitive processing of emotion.
|
[
"Neuroscience and Disorders of the Nervous System",
"Physiology in Health, Disease and Ageing"
] |
10.1038/s41587-020-0442-2
|
Dissecting cellular crosstalk by sequencing physically interacting cells
|
Crosstalk between neighboring cells underlies many biological processes, including cell signaling, proliferation and differentiation. Current single-cell genomic technologies profile each cell separately after tissue dissociation, losing information on cell–cell interactions. In the present study, we present an approach for sequencing physically interacting cells (PIC-seq), which combines cell sorting of physically interacting cells (PICs) with single-cell RNA-sequencing. Using computational modeling, PIC-seq systematically maps in situ cellular interactions and characterizes their molecular crosstalk. We apply PIC-seq to interrogate diverse interactions including immune–epithelial PICs in neonatal murine lungs. Focusing on interactions between T cells and dendritic cells (DCs) in vitro and in vivo, we map T cell–DC interaction preferences, and discover regulatory T cells as a major T cell subtype interacting with DCs in mouse draining lymph nodes. Analysis of T cell–DC pairs reveals an interaction-specific program between pathogen-presenting migratory DCs and T cells. PIC-seq provides a direct and broadly applicable technology to characterize intercellular interaction-specific pathways at high resolution.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Immunity, Infection and Immunotherapy",
"Integrative Biology: from Genes and Genomes to Systems"
] |
10.1109/TPEL.2017.2657644
|
An Active Trap Filter For Switching Harmonic Attenuation Of Low Pulse Ratio Inverters
|
Switching harmonic attenuation has always been challenging for inverters used in high-power conversion applications, where ratio of switching to fundamental frequency is low. Addition of multiple LC -trap filters is no doubt a feasible cost-effective method, which has increasingly been used, but generally susceptible to filter parameter variations and harmonic resonances. This paper hence presents an alternative active trap filter (ATF), based on a series- LC -filtered inverter, for attenuating switching harmonics in a flexible, while yet not cost burdensome, approach. A direct impedance synthesis method has also been proposed for the ATF to better enforce its active switching harmonic bypassing ability. Compared with conventional schemes for controlling active power filters, the proposed method is more readily implemented, since it requires neither current reference generation nor high-bandwidth current control loop. Moreover, the use of a series LC filter at its ac side helps the ATF to reduce its inverter voltage and power ratings. Compensated frequency range of the ATF can hence be enlarged by using a comparably higher switching frequency and a proper step-by-step design procedure to be presented in this paper. Simulation and experimental results have confirmed the design procedures, and hence expected performance of the ATF.
|
[
"Systems and Communication Engineering",
"Products and Processes Engineering"
] |
637305
|
Ocean deoxygenation effects on threatened top predators: new understanding and predictions from novel bio-logging instruments and data
|
Climate-driven reductions in dissolved oxygen (DO) of the global ocean interior (ocean deoxygenation) is leading to expansion of permanent oxygen minimum zones (OMZ) that comprise about 7% of ocean volume. Impacts on marine animal distributions and abundance may be particularly significant for high-oxygen-demand top predators, such as warm-bodied tunas and sharks, by reducing habitat volumes as OMZs expand (habitat compression) and concentrating fish further in surface waters where they become more vulnerable to fisheries. But predictions of how exploited oceanic fish actually respond to OMZ expansions are not based on mechanistic understandings, principally because direct measurements of oxygen tolerances and associated metabolic costs have not been determined. OCEAN DEOXYFISH will bring about a step change in understanding of OMZ impacts on oceanic ecology by applying our existing expertise in animal movement studies and by developing new biologging technologies and in situ physiology for measuring oxygen tolerances and metabolism directly in free-living fish. This will enable major unknowns to be addressed concerning how oceanic fish respond physiologically and behaviourally to hypoxia, the role of OMZs in upper-trophic-level ecology, how oceanic fish habitats change with predicted OMZ expansion, and whether this will increase fish vulnerability to fishing gear. We will achieve objectives through linked field, experimental and modelling studies. By focusing on key processes underlying fish responses to DO in situ, new modelling approaches will establish effects of future warming and OMZ shoaling on fish niches and determine how these shift distributions and alter capture risk by fisheries. The project represents a discipline-spanning approach linking physiology to ecology and oceanography, with wide-ranging outcomes for understanding global biotic responses to warming and ocean deoxygenation with direct relevance to sustainable fisheries and species conservation.
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution",
"Physiology in Health, Disease and Ageing"
] |
10.1038/cr.2017.116
|
A vital sugar code for ricin toxicity
|
Ricin is one of the most feared bioweapons in the world due to its extreme toxicity and easy access. Since no antidote exists, it is of paramount importance to identify the pathways underlying ricin toxicity. Here, we demonstrate that the Golgi GDP-fucose transporter Slc35c1 and fucosyltransferase Fut9 are key regulators of ricin toxicity. Genetic and pharmacological inhibition of fucosylation renders diverse cell types resistant to ricin via deregulated intracellular trafficking. Importantly, cells from a patient with SLC35C1 deficiency are also resistant to ricin. Mechanistically, we confirm that reduced fucosylation leads to increased sialylation of Lewis X structures and thus masking of ricin-binding sites. Inactivation of the sialyltransferase responsible for modifications of Lewis X (St3Gal4) increases the sensitivity of cells to ricin, whereas its overexpression renders cells more resistant to the toxin. Thus, we have provided unprecedented insights into an evolutionary conserved modular sugar code that can be manipulated to control ricin toxicity.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Prevention, Diagnosis and Treatment of Human Diseases"
] |
10.1080/17550874.2012.762812
|
On The Delineation Of Tropical Vegetation Types With An Emphasis On Forest Savanna Transitions
|
Background: There is no generally agreed classification scheme for the many different vegetation formation types occurring in the tropics. This hinders cross-continental comparisons and causes confusion as words such as ‘forest’ and ‘savanna’ have different meanings to different people. Tropical vegetation formations are therefore usually imprecisely and/or ambiguously defined in modelling, remote sensing and ecological studies. Aims: To integrate observed variations in tropical vegetation structure and floristic composition into a single classification scheme. Methods: Using structural and floristic measurements made on three continents, discrete tropical vegetation groupings were defined on the basis of overstorey and understorey structure and species compositions by using clustering techniques. Results: Twelve structural groupings were identified based on height and canopy cover of the dominant upper stratum and the extent of lower-strata woody shrub cover and grass cover. Structural classifications di. . .
|
[
"Earth System Science",
"Environmental Biology, Ecology and Evolution"
] |
W1973831471
|
The RADICAL framework for implementing and monitoring healthcare risk management
|
Purpose – The purpose of this paper is to facilitate an integrative approach to the implementation, monitoring and reporting of risk management in healthcare settings.Design/methodology/approach – A framework, identified by the acronym RADICAL, is presented. The underlying principles and the strengths of the framework are described.Findings – The framework comprises the following domains in an integrated grid: raise awareness, design for safety, involve users, collect and analyse patient safety data, and learn from patient safety incidents.Practical implications – The RADICAL framework provides a simple but comprehensive approach to the implementation, monitoring and reporting of healthcare risk management. It is designed to facilitate learning and accountability at both individual and organisational levels, advocating a balance between “person” and “system”. It covers all domains of patient safety while also being flexible to allow local customisation of the content and metrics for each domain.Originalit...
|
[
"Prevention, Diagnosis and Treatment of Human Diseases",
"Individuals, Markets and Organisations"
] |
10.1093/sleep/zsz182
|
Dynamic modulation of theta–gamma coupling during rapid eye movement sleep
|
Abstract
Theta phase modulates gamma amplitude in hippocampal networks during spatial navigation and rapid eye movement (REM) sleep. This cross-frequency coupling has been linked to working memory and spatial memory consolidation; however, its spatial and temporal dynamics remains unclear. Here, we first investigate the dynamics of theta–gamma interactions using multiple frequency and temporal scales in simultaneous recordings from hippocampal CA3, CA1, subiculum, and parietal cortex in freely moving mice. We found that theta phase dynamically modulates distinct gamma bands during REM sleep. Interestingly, we further show that theta–gamma coupling switches between recorded brain structures during REM sleep and progressively increases over a single REM sleep episode. Finally, we show that optogenetic silencing of septohippocampal GABAergic projections significantly impedes both theta–gamma coupling and theta phase coherence. Collectively, our study shows that phase-space (i. e. cross-frequency coupling) coding of information during REM sleep is orchestrated across time and space consistent with region-specific processing of information during REM sleep including learning and memory.
|
[
"Neuroscience and Disorders of the Nervous System",
"Integrative Biology: from Genes and Genomes to Systems"
] |
10.1016/j.smim.2013.10.019
|
Negative regulatory receptors of the IL-1 family
|
The IL-1 family of ligands and receptors has a central role in both innate and adaptive immune responses and is tightly controlled by antagonists, decoy receptors, scavengers, dominant negative molecules, miRNAs and other mechanisms, acting extracellularly or intracellularly. During evolution, the development of multiple mechanisms of negative regulation reveals the need for tight control of the biological consequences of IL-1 family ligands in order to balance local and systemic inflammation and limit immunopathology. Indeed, studies with gene targeted mice for negative regulators and genetic studies in humans provide evidence for their non-redundant role in controlling inflammation, tissue damage and adaptive responses. In addition, studies have revealed the need of negative regulation of the IL-1 family not only in disease, but also in homeostatic conditions. In this review, the negative regulation mediated by decoy receptors are presented and include IL-1R2 and IL-IL-18BP as well as atypical receptors, which include TIR8/SIGIRR, IL-1RAcPb, TIGIRR-1 and IL-1RAPL. Particular emphasis is given to IL-1R2, since its discovery is the basis for the formulation of the decoy paradigm, now considered a general strategy to counter the primary inflammatory activities of cytokines and chemokines. Emphasis is also given to TIR8, a prototypical negative regulatory receptor having non-redundant roles in limiting inflammation and adaptive responses.
|
[
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1039/C2CP43705H
|
Exciton Diffusion In Near Infrared Absorbing Solution Processed Organic Thin Films
|
We report on singlet-singlet annihilation and exciton diffusion in as-prepared p-type and annealed n-type thin films of the low-bandgap quinoidal quaterthiophene [QQT(CN)4] using ultrafast transient absorption measurements. The decay dynamics of exciton populations are well described by a one-dimensional diffusion-limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction. Our results show that the exciton diffusion constants in QQT(CN)4 films do not vary significantly upon thermal annealing. Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as-prepared and annealed QQT(CN)4 films, respectively. We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering. Because of the possibility of patterning p-n regions in QQT(CN)4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high-performance p-n nanostructured near infrared light-sensing devices.
|
[
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics",
"Materials Engineering"
] |
681798
|
Biomimetic trick to re-balance Osteblast-Osteoclast loop in osteoporoSis treatment: a Topological and materials driven approach
|
One out of 5 people in their fifties will experience a bone fracture due to osteoporosis (OP)-induced fragility in their lifetime. The OP socio-economic burden is dramatic and involves tens of millions of people in the EU, with a steadily increasing number due to population ageing. Current treatments entail drug-therapy coupled with a healthy lifestyle but OP fractures need mechanical fixation to rapidly achieve union: the contribution of biomaterial scientists in this field is still far from taking its expected leading role in cutting-edge research. Bone remodelling is a well-coordinated process of bone resorption by osteoclasts followed by the production of new bone by osteoblasts. This process occurs continuously throughout life in a coupling with a positive balance during growth and negative with ageing, which can result in OP. We believe that an architecture driven stimulation of the osteoclast/osteoblast coupling, with an avant-garde focus on osteoclasts activity, is the key to success in treating unbalanced bone remodelling. We aim to manufacture a scaffold that mimics healthy bone features which will establish a new microenvironment favoring a properly stimulated and active population of osteoclasts and osteoblasts, i.e. a well-balanced bone cooperation. After 5 years we will be able to prove the efficacy of this approach. A benchmark will be set up for OP fracture treatment and for the realization of smart bone substitutes that will be able to locally “trick” aged bone cells stimulating them to act as healthy ones. BOOST results will have an unprecedented impact on the scientific research community, opening a new approach to set up smart, biomimetic strategies to treat aged, unbalanced bone tissues and to reduce OP-associated disabilities and financial burdens.
|
[
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing",
"Materials Engineering"
] |
10.1016/j.celrep.2015.10.057
|
Evolving Models of Pavlovian Conditioning: Cerebellar Cortical Dynamics in Awake Behaving Mice
|
Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs). However, trial-by-trial quantification of this link in awake behaving animals is lacking, and current hypotheses regarding the underlying plasticity mechanisms have diverged from the classical parallel fiber one to the Purkinje cell synapse LTD hypothesis. Here, we establish that acquired simple spike suppression, acquired conditioned stimulus (CS)-related complex spike responses, and molecular layer interneuron (MLI) activity predict the expression of CRs on a trial-by-trial basis using awake behaving mice. Additionally, we show that two independent transgenic mouse mutants with impaired MLI function exhibit motor learning deficits. Our findings suggest multiple cerebellar cortical plasticity mechanisms underlying simple spike suppression, and they implicate the broader involvement of the olivocerebellar module within the interstimulus interval.
|
[
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
] |
10.1016/j.tim.2018.12.011
|
The Road Not Taken: The Rumen Microbiome, Functional Groups, and Community States
|
The rumen ecosystem represents a classic example of host–microbiome symbiosis. In this obligatory relationship, the host feeds on plant fibers that can only be degraded through a set of complex metabolic cascades, exclusively encoded in rumen-associated microbes. These various metabolic pathways are distributed across a multitude of microbial populations. Application of basic ecological principles to this ecosystem can contribute to profound understanding of the rules that shape it. Here, we discuss recent studies by examining the mapping between host attributes, rumen ecosystem composition, and functionality to propose simple, yet powerful concepts to guide the interpretation of microbiome data and enable a better understanding of how the system responds to perturbations.
|
[
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems"
] |
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