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802145 | Entrepreneurs, Firms and the Macroeconomy | New micro-level data reveals enormous heterogeneity across firms in terms of their growth and survival. Young firms are the engines of aggregate job creation and productivity growth even though most startups fail or do not grow. Therefore, only a small share of high-growth firms generates the documented macroeconomic gains. Despite the aggregate importance, we know very little about why firm performance is so heterogeneous, whether these differences are predictable based on characteristics of business founders (entrepreneurs), and how choices of different entrepreneurs to start firms shape, and are shaped by, macroeconomic conditions.
This research agenda studies the nexus of entrepreneurs, firms and the macroeconomy. First, I will estimate to what extent firm growth and survival are predictable from the time of entry and whether characteristics of business founders help explain such patterns. To do so, I will use detailed micro-level data from four countries and adopt a methodology not yet used in this context. Second, I will build a new macroeconomic model of firm dynamics in which business growth and survival profiles are shaped by heterogeneous entrepreneurs in accordance with the empirical evidence.
While the link between heterogeneity of firms and their founders is absent in existing research, without it we cannot study current key policy questions. How does rising income and wealth inequality impact the macroeconomy by affecting choices to start new firms? How can policy promote the founding of high-growth firms, which are less plentiful in Europe compared to the U.S.? What general equilibrium feedback effects do such policies have on workers?
The large degree of firm and founder heterogeneity makes both the empirical and theoretical parts of this agenda very challenging. At the same time, the importance of a better understanding of firm growth for further academic research and for economic policy makes this proposal particularly high-return. | [
"Individuals, Markets and Organisations"
]
|
W2070272960 | Energy-Efficient Distributed Data Storage for Wireless Sensor Networks Based on Compressed Sensing and Network Coding | Recently, distributed data storage (DDS) for Wireless Sensor Networks (WSNs) has attracted great attention, especially in catastrophic scenarios. Since power consumption is one of the most critical factors that affect the lifetime of WSNs, the energy efficiency of DDS in WSNs is investigated in this paper. Based on Compressed Sensing (CS) and network coding theories, we propose a Compressed Network Coding based Distributed data Storage (CNCDS) scheme by exploiting the correlation of sensor readings. The CNCDS scheme achieves high energy efficiency by reducing the total number of transmissions Nttot and receptions Nrtot during the data dissemination process. Theoretical analysis proves that the CNCDS scheme guarantees good CS recovery performance. In order to theoretically verify the efficiency of the CNCDS scheme, the expressions for Nttot and Nrtot are derived based on random geometric graphs (RGG) theory. Furthermore, based on the derived expressions, an adaptive CNCDS scheme is proposed to further reduce Nttot and Nrtot. Simulation results validate that, compared with the conventional ICStorage scheme, the proposed CNCDS scheme reduces Nttot, Nrtot, and the CS recovery mean squared error (MSE) by up to 55%, 74%, and 76% respectively. In addition, compared with the CNCDS scheme, the adaptive CNCDS scheme further reduces Nttot and Nrtot by up to 63% and 32% respectively. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
10.1038/s41596-019-0179-x | Sequencing cell-type-specific transcriptomes with SLAM-ITseq | Analysis of cell-type-specific transcriptomes is vital for understanding the biology of tissues and organs in the context of multicellular organisms. In this Protocol Extension, we combine a previously developed cell-type-specific metabolic RNA labeling method (thiouracil (TU) tagging) and a pipeline to detect the labeled transcripts by a novel RNA sequencing (RNA-seq) method, SLAMseq (thiol (SH)-linked alkylation for the metabolic sequencing of RNA). By injecting a uracil analog, 4-thiouracil, into transgenic mice that express cell-type-specific uracil phosphoribosyltransferase (UPRT), an enzyme required for 4-thiouracil incorporation into newly synthesized RNA, only cells expressing UPRT synthesize thiol-containing RNA. Total RNA isolated from a tissue of interest is then sequenced with SLAMseq, which introduces thymine to cytosine (T>C) conversions at the sites of the incorporated 4-thiouracil. The resulting sequencing reads are then mapped with the T>C-aware alignment software, SLAM-DUNK, which allows mapping of reads containing T>C mismatches. The number of T>C conversions per transcript is further analyzed to identify which transcripts are synthesized in the UPRT-expressing cells. Thus, our method, SLAM-ITseq (SLAMseq in tissue), enables cell-specific transcriptomics without laborious FACS-based cell sorting or biochemical isolation of the labeled transcripts used in TU tagging. In the murine tissues we assessed previously, this method identified ~5,000 genes that are expressed in a cell type of interest from the total RNA pool from the tissue. Any laboratory with access to a high-throughput sequencer and high-power computing can adapt this protocol with ease, and the entire pipeline can be completed in <5 d. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1002/adom.201600646 | Structural Color in Marine Algae | Structural coloration is widespread in the marine environment. Within the large variety of marine organisms, macroalgae represent a diverse group of more than 24 000 species. Some macroalgae have developed complex optical responses using different nanostructures and material compositions. In this review, we describe the mechanisms that are employed to produce structural color in algae and provide a discussion on the functional relevance by analyzing the geographical distribution and ecology in detail. In contrast to what is observed in the animal kingdom, we hypothesize that structural color in algae predominantly functions for a non-communicative purpose, most likely protection from radiation damage, e. g. , by harmful UV light. We suggest that the presence of structural color in algae is likely influenced by local factors such as radiation intensity and turbidity of the water. | [
"Environmental Biology, Ecology and Evolution",
"Materials Engineering"
]
|
W1983446513 | Enhanced Cu(II) rejection and fouling reduction through fabrication of PEG-PES nanocomposite ultrafiltration membrane with PEG-coated cobalt doped iron oxide nanoparticle | Membrane modified by adding nanoparticles coined as nanomodified membrane is another latest trend in membrane technology. This paper investigates the influence of polyethylene glycol (PEG) coated cobalt doped iron oxide (Co-Fe2O3) nanoparticles on the morphological and properties of (PES) ultrafiltration membrane (UF). The synthesized Co-Fe2O3 nanoparticles were coated with different concentrations of PEG solutions to prevent them from agglomeration and then added to the PES/DMF dope solutions. The performance of the nanomodified membranes was then compared to the control PEG/PES/DMF dope solutions in terms of flux rates and Cu(II) removal at various operating conditions. The antifouling properties were determined using bovine serum albumin (BSA) as the model foulant. Findings revealed that the Cu(II) removal efficiency of the nanomodified membranes was enhanced considerably (as high as 96%) and the antifouling properties improved. In order to obtain membranes with high Cu(II) removal and reasonable flux rates the concentration of nanoparticles must be kept at 6% but PEG coating concentration high (6-9%); with ratio of PEG coating to Co-Fe2O3 kept more than 1.0. (C) 2014 Taiwan Institute of Chemical Engineers. | [
"Materials Engineering",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
10.1016/j.cities.2019.102521 | Spatializing gentrification in situ: A critical cartography of resident perceptions of neighbourhood change in Vallcarca, Barcelona | In this paper, we link the tools of critical cartography and cognitive mapping with more traditional gentrification studies in order to capture in situ the shifts associated with nascent processes of change in bodies, environment, and minds in Vallcarca, a liminal gentrifying neighbourhood of Barcelona, Spain. We ask: How do the simultaneous and conflicting ways that people shape, perceive, and respond to gentrification processes affect how space and place are politicized within global urbanization processes? We build our maps through an analysis based primarily on listening to a diverse range of residents and constructing with them a combined cartography of the perceived type, degree, and location of changes in the neighbourhood. The results reveal an important dual role for greening and tourism, a differential geography of perceived gentrification risk across different social groups, and a limited reach in terms of who perceives gentrification. These results have important implications for how space and place are politicized and de-politicized and offer guidance useful to grassroots efforts to combat gentrification and displacement. | [
"Human Mobility, Environment, and Space",
"The Social World and Its Interactions"
]
|
W1976478158 | An Effective Method of Introducing the Periodic Table as a Crossword Puzzle at the High School Level | A simple method to introduce the modern periodic table of elements at the high school level as a game of solving a crossword puzzle is presented here. A survey to test the effectiveness of this new method relative to the conventional method, involving use of a wall-mounted chart of the periodic table, was conducted on a convenience sample. This sample comprised over 200 school students learning introductory chemistry in India. The study sample of about 100 students was identified on the basis of a test. In the new method, a blank chart of the modern periodic table was used as an educational aid. Students entered symbols of elements in the blank chart in a manner very similar to solving a crossword puzzle by making use of clues provided to them. The scores of the tests conducted before and after the introduction to the periodic table to the treatment and control groups of the students, by the new and the conventional method, respectively, were analyzed. The comparison demonstrated the new method to be more... | [
"Physical and Analytical Chemical Sciences",
"The Social World and Its Interactions"
]
|
W2137019198 | Investigation of the motion of particles in magnetorheological elastomers by X-μCT | The behavior of magnetic particles inside elastomeric matrices is a complex issue and can be influenced in many ways, e.g. by applying a magnetic field or external mechanical stimuli. It is of fundamental interest for theoretical descriptions and technological applications to study processes like structure formation of these particles in a magnetic field. For a better understanding of the microstructure and the motion of particles in magnetorheological elastomers (MRE), x-ray micro-computed tomography (Xμ-CT) investigations were carried out. A MRE with a quantity of 2 wt.% of iron powder and an isotropic allocation of the particles inside the matrix was prepared. By means of quantitative analysis with image processing software, information regarding the geometrical properties of the particles and their individual motion under the influence of a magnetic field was obtained. Therefore a set of three tomograms—a reference taken without magnetic field, a second tomogram in presence of an applied field and third one again taken at B = 0 mT—has been taken and compared. It is shown that the combination of Xμ-CT and digital image processing provides a tool for a quantitative analysis of single particle motion in a MRE forced by external stimuli. | [
"Condensed Matter Physics",
"Materials Engineering"
]
|
W1981130750 | Long-term groundwater variations in Northwest India from satellite gravity measurements | Abstract Satellite gravity data from the Gravity Recovery and Climate Experiment (GRACE) provides quantitative measures of terrestrial water storage (TWS) change at large spatial scales. Combining GRACE-observed TWS changes and model estimates of water storage changes in soil and snow at the surface offers a means for measuring groundwater storage change. In this study, we re-assess long-term groundwater storage variation in the Northwest India (NWI) region using an extended record of GRACE time-variable gravity measurements, and a fully unconstrained global forward modeling method. Our new assessments based on the GRACE release-5 (RL05) gravity solutions indicate that during the 10 year period January 2003 to December 2012, the NWI groundwater depletion remains pronounced, especially during the first 5 years (01/2003–12/2007). The newly estimated depletion rates are ~ 20.4 ± 7.1 Gigatonne (Gt)/yr averaged over the 10 year period, and 29.4 ± 8.4 Gt/yr during the first 5 years. The yearly groundwater storage changes in the NWI region are strongly correlated with yearly precipitation anomalies. In 2009, the driest season of the decade, the groundwater depletion reaches nearly 80 Gt, while in the two relatively wet seasons, 2008 and 2011, the groundwater storages even see net increases of about 24 and 35 Gt, respectively. The estimated mean groundwater depletion rates for the first 5 years are significantly higher than previous assessments. The larger depletion rates may reflect the benefits from improved data quality of GRACE RL05 gravity solutions, and improved data processing method, which can more effectively reduce leakage error in GRACE estimates. Our analysis indicates that the neighboring Punjab Province of Pakistan (especially Northern Punjab) apparently also experiences significant groundwater depletion during the same period, which has partly contributed to the new regional groundwater depletion estimates. | [
"Earth System Science",
"Systems and Communication Engineering"
]
|
W4296506879 | Gastrointestinal parasites in non-human primates in zoological institutions in France | Gastrointestinal parasites are frequently encountered in captive non-human primates and infestation may have severe consequences on the animal's health status. Most of these parasites are also transmissible to humans. Nevertheless, little is known about the prevalence and monitoring modalities of gastrointestinal parasitoses in non-human primates housed in zoological institutions and there are currently no guidelines available for their detection and identification. The objective of this study was to identify the main gastrointestinal parasites that may be observed in non-human primates in zoological institutions in France, as well as to develop a decision-making tree to ease their identification. Twenty-four zoological institutions were surveyed, most of which performed fecal examinations routinely on their non-human primates (91.7%). Most institutions used flotation enrichment protocols to detect gastrointestinal parasites (95.2%) and nematodes were the most frequently encountered parasites (73.0%). A total of 252 fecal samples corresponding to 68 different non-human primate species from these institutions were analyzed using sedimentation and flotation protocols. Protozoa (47.3%) were found to be more frequent than helminths (15.6%). Furthermore, old-world monkeys exhibited a higher parasite load (93.6%) than any other non-human primate species category. Compiled data from fecal examinations allowed the development of a decision-making tree and diagnostic atlas to facilitate parasite diagnosis in captive non-human primates.Parasites gastro-intestinaux chez les primates non-humains dans les parcs zoologiques français.Les parasites gastro-intestinaux sont fréquemment rencontrés chez les primates non-humains en captivité et peuvent avoir des conséquences graves sur l’état de santé de l’animal. La plupart sont également transmissibles à Homme. Néanmoins, on sait peu de choses sur la prévalence et les modalités de surveillance des parasitoses gastro-intestinales chez les primates non-humains hébergés dans des institutions zoologiques et il n’existe actuellement aucune ligne directrice disponible pour leur détection et leur identification. L’objectif de cette étude était d’identifier les principaux parasites gastro-intestinaux pouvant être observés chez les primates non-humains dans les institutions zoologiques françaises, ainsi que de développer un arbre décisionnel pour faciliter leur identification. Vingt-quatre institutions zoologiques françaises ont été interrogées : la plupart (91,7 %) effectuaient des examens fécaux en routine sur leurs primates non-humains. La plupart des établissements utilisaient des protocoles d’enrichissement par flottation pour détecter les parasites gastro-intestinaux (95,2 %) et les nématodes étaient les parasites les plus fréquemment rencontrés (73,0 %). Un total de 252 échantillons fécaux correspondant à 68 espèces différentes de primates non-humains provenant de ces institutions ont été analysés à l’aide de protocoles de sédimentation et de flottation. Les protozoaires (47,3 %) étaient plus fréquents que les helminthes (15,6 %). De plus, les singes de l’ancien monde présentaient une charge parasitaire plus élevée (93,6 %) que toute autre catégorie d’espèces de primates non-humains. Les données compilées des examens fécaux ont permis le développement d’un arbre décisionnel et d’un atlas diagnostique pour faciliter le diagnostic des parasites chez les primates non-humains en captivité. | [
"Environmental Biology, Ecology and Evolution",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Immunity, Infection and Immunotherapy"
]
|
884901 | Upsurgeon academy: a multilevel educational platform for neurosurgical training. | UpSurgeOn is an Italian SME established in 2017, by Neurosurgeons for Neurosurgeons, with a focus on creating a educational platform composed by different educational apps, training and simulation devices actually in the Neurosurgical arena. We have 15 employees, including a combination of neurosurgeons, software developers, technicians and commercial people.
Neurological diseases are a global healthcare priority as they include a wide category of conditions from head injuries, strokes, infections, dementia, Parkinson’s disease and even headaches. These conditions affect more than 1 billion people in the world irrespectively of age, sex or income and have estimate mortality rates of 6.8 million people a year. As of 2004 the economic burden of these diseases in Europe was estimated to be €139 billion, a number which has risen over the years due to higher incidence rates. Even though these diseases have such a large impact on the global population and the economy, access to appropriate care is very difficult for most people.
In response to this challenge we have developed UpSurgeOn Academy, a series of educational apps, augmented reality simulator and anatomically accurate training devices with the objective of facilitating the learning curve for future neurosurgeons, decreasing time and cost of their studies. Our goal is to improve the accessibility of neurosurgical care worldwide, especially in less developed countries with fewer facilities by helping train more neurosurgeons. This solution will in turn boost the growth of our company, generating, by the fifth year after phase 2 execution, a turnover of €25.5 million, with €2.2 million in profits, 130 new people hired and a ROI of 2.67 per euro invested. | [
"Neuroscience and Disorders of the Nervous System",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Computer Science and Informatics"
]
|
803082 | Spatio-temporal measurement and plasma-based control of crossflow instabilities for drag reduction | Delay of laminar-turbulent flow transition on aircraft wings can potentially reduce aerodynamic drag by up to 15%, reducing emissions and fuel consumption considerably. The main cause of laminar-turbulent transition on commonly used swept wings is the development of crossflow (CF) instabilities. Despite their importance, our fundamental understanding of CF instabilities is limited due to inability of current measurement techniques to capture their complex and multi-scale spatio-temporal features. This severely limits our ability to delay CF transition, which is further impeded by the lack of simple, robust and efficient control concepts.
In this proposal I will achieve unprecedented spatio-temporal measurements of CF instabilities and develop a novel active flow control system that can successfully delay transition on swept wings. To achieve these goals, I bring forth a unique combination of cutting-edge technologies, such as tomographic particle image velocimetry, advanced plasma-based actuators and linear/non-linear stability and control theory.
Spatio-temporal volumetric velocity measurements of CF instabilities will be achieved at three important stages of their life, namely inception, growth and breakdown, providing breakthrough insights into the underlying physics of swept wing transition and turbulence production. The results will be used to postulate and validate linear and non-linear stability and control theory models and provide top benchmarks for high-fidelity CFD. The unprecedented wealth of information, enabled through these advances, will be used to design and demonstrate the first synergetic plasma-based laminar flow control system. This system will feature minimum-thickness plasma actuators, able to suppress the growth of CF instabilities and achieve and sustain considerable transition delay at high Reynolds numbers. These advances will finally enable robust and efficient laminar flow on future air transport. | [
"Products and Processes Engineering",
"Systems and Communication Engineering"
]
|
10.1051/0004-6361/201321353 | Surface Flux Concentrations And Spherical Alpha Square Dynamo | In the presence of strong density stratification, turbulence can lead to a large-scale instability of a horizontal magnetic field if its strength is in a suitable range (within a few percent of the turbulent equipartition value). This instability is related to a suppression of the turbulent pressure so that the turbulence contribution to the mean magnetic pressure becomes negative. This results in the excitation of a negative effective magnetic pressure instability (NEMPI). This instability has so far only been studied for an imposed magnetic field. We want to know how NEMPI works when the mean magnetic field is generated self-consistently by an $\alpha^2$ dynamo, whether it is affected by global spherical geometry, and whether it can influence the properties of the dynamo itself. We adopt the mean-field approach which has previously been shown to provide a realistic description of NEMPI in direct numerical simulations. We assume axisymmetry and solve the mean-field equations with the Pencil-Code for an adiabatic stratification at a total density contrast in the radial direction of approximately 4 orders of magnitude. NEMPI is found to work when the dynamo-generated field is about 4% of the equipartition value, which is achieved through strong $\alpha$ quenching. This instability is excited in the top 5% of the outer radius provided the density contrast across this top layer is at least 10. NEMPI is found to occur at lower latitudes when the mean magnetic field is stronger. For weaker fields, NEMPI can make the dynamo oscillatory with poleward migration. NEMPI is a viable mechanism for producing magnetic flux concentrations in a strongly stratified spherical shell in which a magnetic field is generated by a strongly quenched $\alpha$ effect dynamo. | [
"Universe Sciences",
"Fundamental Constituents of Matter"
]
|
222757 | Maximizing the upscaling and replication potential of high level urban transformation strategies | MAtchUP project aims at strengthening the planning processes for urban transformation, consolidating the benefits of deploying large scale demonstration projects of innovative technologies in the energy, mobility and ICT sectors, by means of substantially improved models for replication and upscaling, based on impacts evaluation, and ensuring the bankability of the solutions by means of innovative business models, which lead to achieve real deployment further than the pilots carried out in the lighthouse cities. With this, it is sought a high penetration of the validated technologies in those cities less prepared to adopt very innovative solutions and formalize it in a standard commitment, accompanied by capacity building strategies, to guarantee at least medium term implementation.
The expected results will be achieved working in parallel in demonstration and upscaling/replication levels, so the lighthouse cities (Valencia-Spain, Dresden-Germany and Antalya-Turkey) and followers (Ostend-Belgium, Herzliya-Israel, Skopje-FYROM and Kerava-Finland) will assume a huge commitment in this project in order to:
- deploy innovative solutions in the energy, mobility and ICT sectors with a strong monitoring program to validate all of them,
- develop very rigorous upscaling and replication plans that will be the basis to update at least the SEAPs/SECAPs, that are the major standard commitment at European level that a city can assume in terms of city transformation, and other existing city plans as Sustainable Mobility Plans or Digital Agendas. | [
"Products and Processes Engineering",
"Human Mobility, Environment, and Space",
"Systems and Communication Engineering"
]
|
10.1523/JNEUROSCI.0735-18.2018 | Differentiating Between Models Of Perceptual Decision Making Using Pupil Size Inferred Confidence | During perceptual decisions, subjects often rely more strongly on early, rather than late, sensory evidence, even in tasks when both are equally informative about the correct decision. This early psychophysical weighting has been explained by an integration-to-bound decision process, in which the stimulus is ignored after the accumulated evidence reaches a certain bound, or confidence level. Here, we derive predictions about how the average temporal weighting of the evidence depends on a subject9s decision confidence in this model. To test these predictions empirically, we devised a method to infer decision confidence from pupil size in 2 male monkeys performing a disparity discrimination task. Our animals9 data confirmed the integration-to-bound predictions, with different internal decision bounds and different levels of correlation between pupil size and decision confidence accounting for differences between animals. However, the data were less compatible with two alternative accounts for early psychophysical weighting: attractor dynamics either within the decision area or due to feedback to sensory areas, or a feedforward account due to neuronal response adaptation. This approach also opens the door to using confidence more broadly when studying the neural basis of decision making. SIGNIFICANCE STATEMENT An animal9s ability to adjust decisions based on its level of confidence, sometimes referred to as “metacognition,” has generated substantial interest in neuroscience. Here, we show how measurements of pupil diameter in macaques can be used to infer their confidence. This technique opens the door to more neurophysiological studies of confidence because it eliminates the need for training on behavioral paradigms to evaluate confidence. We then use this technique to test predictions from competing explanations of why subjects in perceptual decision making often rely more strongly on early evidence: the way in which the strength of this effect should depend on a subject9s decision confidence. We find that a bounded decision formation process best explains our empirical data. | [
"Neuroscience and Disorders of the Nervous System",
"The Human Mind and Its Complexity"
]
|
10.1038/nsmb.1809 | The SM protein Vps33 and the t-SNARE H abc domain promote fusion pore opening | Intracellular membrane fusion proceeds via distinct stages of membrane docking, hemifusion and fusion pore opening and depends on interacting families of Rab, SNARE and SM proteins. Trans-SNARE complexes dock the membranes in close apposition. Efficient fusion requires further SNARE-associated proteins. They might increase the number of trans-SNARE complexes or the fusogenic potential of a single SNARE complex. We investigated the contributions of the SM protein Vps33 to hemifusion and pore opening between yeast vacuoles. Mutations in Vps33 that weaken its interactions with the SNARE complex allowed normal trans-SNARE pairing and lipid mixing but retarded content mixing. Deleting the H abc domain of the vacuolar t-SNARE Vam3, which interacts with Vps33, had the same effect. This suggests that SM proteins promote fusion pore opening by enhancing the fusogenic activity of a SNARE complex. They should thus be considered integral parts of the fusion machinery. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
10.1002/2017GL074476 | Underlying Causes Of Eurasian Midcontinental Aridity In Simulations Of Mid Holocene Climate | Climate model simulations uniformly show drier and warmer summers in the Eurasian midcontinent during the mid-Holocene, which is not consistent with paleoenvironmental observations. The simulated climate results from a reduction in the zonal temperature gradient, which weakens westerly flow and reduces moisture flux and precipitation in the midcontinent. As a result, sensible heating is favored over evaporation and latent heating, resulting in substantial surface-driven atmospheric warming. Thus, the discrepancy with the paleoenvironmental evidence arises initially from a problem in the simulated circulation and is exacerbated by feedback from the land surface. This region is also drier and warmer than indicated by observations in the preindustrial control simulations, and this bias arises in the same way: zonal flow and hence moisture flux into the midcontinent are too weak, and feedback from the land surface results in surface-driven warming. These analyses suggest the need to improve those aspects of climate models that affect the strength of westerly circulation. | [
"Earth System Science"
]
|
10.1088/1748-3190/11/5/055008 | Systematic Comparison Of Model Polymer Nanocomposite Mechanics | Polymer nanocomposites render a range of outstanding materials from natural products such as silk, sea shells and bones, to synthesized nanoclay or carbon nanotube reinforced polymer systems. In contrast to the fast expanding interest in this type of material, the fundamental mechanisms of their mixing, phase behavior and reinforcement, especially for higher nanoparticle content as relevant for bio-inorganic composites, are still not fully understood. Although polymer nanocomposites exhibit diverse morphologies, qualitatively their mechanical properties are believed to be governed by a few parameters, namely their internal polymer network topology, nanoparticle volume fraction, particle surface properties and so on. Relating material mechanics to such elementary parameters is the purpose of this work. By taking a coarse-grained molecular modeling approach, we study an range of different polymer nanocomposites. We vary polymer nanoparticle connectivity, surface geometry and volume fraction to systematically study rheological/mechanical properties. Our models cover different materials, and reproduce key characteristics of real nanocomposites, such as phase separation, mechanical reinforcement. The results shed light on establishing elementary structure, property and function relationship of polymer nanocomposites. | [
"Materials Engineering",
"Condensed Matter Physics",
"Synthetic Chemistry and Materials"
]
|
884228 | The digital insurance assistant for european consumers | Consumers are vastly uninformed when it comes to contracting insurance and using their coverages. Although the average insurance cost per capita in the EU is 2,670€ per year, European users do NOT have the tools to easily compare, select and buy the best insurance policies; those that provide the best insurance coverage at the best price. Furthermore, insurance policies are usually difficult to understand and cumbersome to manage. Our new product COMPARO BRAIN employs state-of-the-art Machine-Learning algorithms to offer an app-based personal insurance assistant that will help European consumers get customised information about the best insurance policies, obtain recommendations and contract with the best providers. BRAIN offers comprehensive data on coverages included in the insurance policies of the user and adapts to their needs by implementing the most advanced context-aware technologies that adapt accordingly to create a more relevant and interactive user experience. BRAIN saves 10 hours (35% reduction) of annoying research and bureaucracy in the contracting process. Users obtain optimal insurance policies, avoid paying for redundant insurance coverages, saving on average 20% on their insurance costs annually and avoid paying for everyday services already included in their coverages. Thanks to this project we expect to internationalise our customer base entering Norway, Denmark and Sweden in a first phase. We plan to serve more than 400 thousand households in Europe after 5 years of commercialization. | [
"Computer Science and Informatics",
"Individuals, Markets and Organisations"
]
|
W1976061562 | Stochastic Source Seeking by Mobile Robots | We consider the problem of designing controllers to steer mobile robots to the source (the minimizer) of a signal field. In addition to the mobility constraints, e.g., posed by the nonholonomic dynamics, we assume that the field is completely unknown to the robot and the robot has no knowledge of its own position. Furthermore, the unknown field is randomly switching. In the case where the information of the field (e.g., the gradient) is completely known, standard motion planning techniques for mobile robots would converge to the known source. In the absence of mobility constraints, convergence to the minimum of unknown fields can be pursued using the framework of numerical optimization. By considering these facts, this paper exploits an idea of the stochastic approximation for solving the problem mentioned in the beginning and proposes a source seeking controller which sequentially generates the next waypoints such that the resulting discrete trajectory converges to the unknown source and which steers the robot along the waypoints, under the assumption that the robot can move to any point in the body fixed coordinate frame. To this end, we develop a rotation-invariant and forward-sided version of the simultaneous-perturbation stochastic approximation algorithm as a method to generate the next waypoints. Based on this algorithm, we design source seeking controllers. Furthermore, it is proven that the robot converges to a small set including the source in a probabilistic sense if the signal field switches periodically and sufficiently fast. The proposed controllers are demonstrated by numerical simulations. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
10.1017/9781108303873 | The victorian palace of science: Scientific knowledge and the building of the houses of parliament | The Palace of Westminster, home to Britain's Houses of Parliament, is one of the most studied buildings in the world. What is less well known is that while Parliament was primarily a political building, when built between 1834 and 1860, it was also a place of scientific activity. The construction of Britain's legislature presents an extraordinary story in which politicians and officials laboured to make their new Parliament the most radical, modern building of its time by using the very latest scientific knowledge. Experimentalists employed the House of Commons as a chemistry laboratory, geologists argued over the Palace's stone, natural philosophers hung meat around the building to measure air purity, and mathematicians schemed to make Parliament the first public space where every room would have electrically-controlled time. Through such dramatic projects, Edward J. Gillin redefines our understanding of the Palace of Westminster and explores the politically troublesome character of Victorian science. Provides a dramatic new interpretation of the Palace of Westminster, probably the most studied Victorian building in architectural history Makes an original case for the role of science in politics in Victorian Britain Presents a unique combination of the histories of science, architecture, and politics. | [
"The Study of the Human Past",
"Studies of Cultures and Arts",
"Institutions, Governance and Legal Systems"
]
|
10.1214/14-BJPS258 | Noise Interaction Nonlinear Dynamics And The Origin Of Rhythmic Behaviors | Large families of noisy interacting units (cells, individuals, components in a circuit, …) exhibiting synchronization often exhibit oscillatory behaviors too. This is a well established empirical observation that has attracted a remarkable amount of attention, notably in life sciences, because of the central role played by internally generated rhythms. A certain number of elementary models that seem to capture the essence, or at least some essential features, of the phenomenon have been set forth, but the mathematical analysis is in any case very challenging and often out of reach. We focus on phase models, proposed and repeatedly considered by Y. Kuramoto and coauthors, and on the mathematical results that can be established. In spite of the fact that noise plays a crucial role, and in fact these models in abstract terms are just a special class of diffusions in high dimensional spaces, the core of the analysis is at the level of the PDE that provides an accurate description of the limit of a very large number of units in interaction. We will stress how the fundamental difficulty in dealing with these models is in their non-equilibrium character and the results we present for phase models are crucially related to the fact that, with a very special choice of the parameters, they reduce to an equilibrium statistical mechanics model. | [
"Mathematics",
"Condensed Matter Physics"
]
|
W613546246 | Coercion and Social Welfare in Public Finance | 1. Coercion, welfare, and the study of public finance Jorge Martinez-Vazquez and Stanley L. Winer Part I. Violence, Structured Anarchy, and the State: 2. The constitution of coercion: Wicksell, violence, and the ordering of society John J. Wallis 3. Proprietary public finance: on its emergence and evolution out of anarchy Stergios Skaperdas Part II. Voluntary and Coercive Transactions in Welfare Analysis: 4. Coercion, taxation, and voluntary association Roger D. Congleton 5. Kaldor-Hicks coercion, Coasian bargaining, and the state Michael C. Munger Part III. Coercion in Public Sector Economics: Theory and Application: 6. Non-coercion, efficiency and incentive compatibility in public goods John O. Ledyard 7. Social welfare and coercion in public finance Stanley L. Winer, George Tridimas and Walter Hettich 8. Lindahl fiscal incidence and the measurement of coercion Saloua Sehili and Jorge Martinez-Vazquez 9. Fiscal coercion in federal systems, with special attention to highly divided societies Giorgio Brosio Part IV. Coercion in the Laboratory: 10. Cooperating to resist coercion: an experimental study Lucy F. Ackert, Ann B. Gillette and Mark Rider 11. Partial coercion, conditional cooperation, and self-commitment in voluntary contributions to public goods Elena Cettolin and Arno Riedl. | [
"Institutions, Governance and Legal Systems",
"Individuals, Markets and Organisations"
]
|
10.1038/s41586-018-0466-7 | Role of glutamine synthetase in angiogenesis beyond glutamine synthesis | Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physiology in Health, Disease and Ageing"
]
|
637831 | MOLECULAR CARPETS ON INSULATING SURFACES: RATIONAL DESIGN OF COVALENT NETWORKS | Inspired by the possibility to create artificial, three-dimensional covalent organic frameworks, the overall aim of this project is to construct novel two-dimensional (2D), covalently-linked, organic networks in a bottom-up approach on insulating surfaces. 2D materials have unique properties suitable for many scientific and technological applications including nano-electronic devices and sensors. On-surface synthesis of covalent structures is mainly limited to metal surfaces, as controlled growth procedures of molecules on insulators are often hindered by the weak, unspecific interaction with the substrate. We will establish suitable concepts for the covalent linking of molecules on insulators by balancing the molecule-molecule and molecule-surface interactions. That will greatly advance the atomic-scale understanding of molecular structures on insulators. Specially designed molecular building blocks doped with heteroatoms will be used to create functional 2D networks with tunable electronic properties and nanometer-sized pores. Novel concepts will be developed to achieve high quality structures with long-range order; one of the great challenges in all covalently-linked structures.
The SURFLINK project uses a surface science approach in ultra-high vacuum to understand the fundamental mechanisms and properties of covalently-linked networks at the atomic level. The covalent networks will be studied by high-resolution scanning probe microscopy and spectroscopy at the atomic-scale. We will determine the electronic properties of the novel nano-porous networks that can be tailored by their geometry. The functionalized pores included in the network will be studied with respect to their size and their prospects to adsorb guest molecules. The rational design of the networks proposed in the SURFLINK project has great potential for materials research and will ultimately result in the development of new materials with adjustable electronic properties. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics",
"Materials Engineering"
]
|
10.1093/gbe/evx187 | The Novel Evolution of the Sperm Whale Genome | The sperm whale, made famous by Moby Dick, is one of the most fascinating of all ocean-dwelling species given their unique life history, novel physiological adaptations to hunting squid at extreme ocean depths, and their position as one of the earliest branching toothed whales (Odontoceti). We assembled the sperm whale (Physeter macrocephalus) genome and resequenced individuals from multiple ocean basins to identify new candidate genes for adaptation to an aquatic environment and infer demographic history. Genes crucial for skin integrity appeared to be particularly important in both the sperm whale and other cetaceans. We also find sperm whales experienced a steep population decline during the early Pleistocene epoch. These genomic data add new comparative insight into the evolution of whales. | [
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1515/flih-2015-0005 | Event-centrality and the pragmatics–semantics interface in Kikongo: From predication focus to progressive aspect and vice versa | AbstractAcross Bantu, several polysemic markers expressing progressive aspect and so-called predication focus have been reported ( | [
"Texts and Concepts",
"The Human Mind and Its Complexity"
]
|
850593 | Mereological Reconstruction of the Metaphysical System in the Daodejing | The project is a mereological reconstruction of the metaphysical system in the Daodejing. The general motivation for the project is to fill the gap in Chinese and comparative philosophy the state of the art, where mereological as well as analytic reconstructions are scarce. The specific motivation is that mereological approach enables precise reconstruction that (a) offers a comprehensive conceptualization of Daoist metaphysical system and (b) allows to generate the issues and plausibly debates that so far have not been present in Chinese metaphysics. My project begins with the conceptualization of the Daoist system as monistic-materialistic one, after which I proceed to the mereological reconstruction. By resorting to the latest mereological research, I will analyze the status of the two fundamental elements of Daoist metaphysics, dao and you. Accordingly, I will show that these two ontic subregions should be reconstructed as two different mereological sums determined by atemporal unrestricted composition and temporal restricted composition respectively. Next, I will proceed to reconstructing the relation between the two sums, which will be conceptualized within the framework of Chinese causation theory. I will show that causality applies to the relations between parts that that the two mereological sums overlap. Next, I will proceed to a detailed reconstruction of the whole system, which will involve among others proving that with regard to parthood, the “atomless gunk” conception is more plausible than that of mereological singles. I will also discuss how the reconstruction is related to location, an issue that has been under intense discussion in contemporary mereological literature. | [
"Texts and Concepts"
]
|
10.1021/acsnano.7b03421 | How to Identify Plasmons from the Optical Response of Nanostructures | A promising trend in plasmonics involves shrinking the size of plasmon-supporting structures down to a few nanometers, thus enabling control over light-matter interaction at extreme-subwavelength scales. In this limit, quantum mechanical effects, such as nonlocal screening and size quantization, strongly affect the plasmonic response, rendering it substantially different from classical predictions. For very small clusters and molecules, collective plasmonic modes are hard to distinguish from other excitations such as single-electron transitions. Using rigorous quantum mechanical computational techniques for a wide variety of physical systems, we describe how an optical resonance of a nanostructure can be classified as either plasmonic or nonplasmonic. More precisely, we define a universal metric for such classification, the generalized plasmonicity index (GPI), which can be straightforwardly implemented in any computational electronic-structure method or classical electromagnetic approach to discriminate plasmons from single-particle excitations and photonic modes. Using the GPI, we investigate the plasmonicity of optical resonances in a wide range of systems including: the emergence of plasmonic behavior in small jellium spheres as the size and the number of electrons increase; atomic-scale metallic clusters as a function of the number of atoms; and nanostructured graphene as a function of size and doping down to the molecular plasmons in polycyclic aromatic hydrocarbons. Our study provides a rigorous foundation for the further development of ultrasmall nanostructures based on molecular plasmonics. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
W2046614306 | State Disparities in Time Trends of Adolescent Body Mass Index Percentile and Weight-Related Behaviors in the United States | Evidence is conflicting as to whether youth obesity prevalence has reached a plateau in the United States overall. Trends vary by state, and experts recommend exploring whether trends in weight-related behaviors are associated with changes in weight status trends. Thus, our objective was to estimate between-state variation in time trends of adolescent body mass index (BMI) percentile and weight-related behaviors from 2001 to 2007. A time series design combined cross-sectional Youth Risk Behavior Survey data from 272,044 adolescents in 29 states from 2001 to 2007. Self-reported height, weight, sports participation, physical education, television viewing, and daily consumption of 100% fruit juice, milk, and fruits and vegetables were collected. Linear mixed models estimated state variance in time trends of behaviors and BMI percentile. Across states, BMI percentile trends were consistent despite differences in behavioral trends. Boys experienced a modest linear increase in BMI percentile (ß = 0.18, 95% CI: 0.07, 0.30); girls experienced a non-linear increase, as the rate of increase declined over time from 1.02 units in 2001-2002 (95% CI: 0.68, 1.36) to 0.23 units in 2006-2007 (95% CI: -0.09, 0.56). States in which BMI percentile decreased experienced a greater decrease in TV viewing than states where BMI percentile increased. Otherwise, states with disparate BMI percentile trends did not differ with respect to behaviors. Future research should explore the role of other behaviors (e.g., soda consumption), measurement units (e.g., portion size), and societal trends (e.g., urban sprawl) on state and national adiposity trends. | [
"Physiology in Health, Disease and Ageing",
"The Social World and Its Interactions"
]
|
980457 | Glutamate dynamics during visual stimulation and ketamine challenge in the human brain | While clinical experience confirmed ketamine, a glutamate (Glu) N-methyl-D-aspartate receptor antagonist, as a potent therapy of treatment-resistant major depressive disorder (TRD), the exact mechanism of ketamine’s action in the brain is unclear. Thus, a method to reliably and reproducibly monitor minute changes in Glu metabolism in the human brain is urgently needed to understand ketamine dynamics in vivo. So far, the pioneering work at the Medical University Vienna (MUW) showed ketamine-induced increase of vascular and metabolic responses measured as blood oxygenation level dependent (BOLD) signals in healthy subjects in thalamus, insula and anterior cingulate cortex (ACC), while others observed elevated glucose uptake using positron emission tomography, suggesting higher energetic demands and Glu response after ketamine infusion. Yet, a reliable and non-invasive method for direct monitoring of pharmacologically-induced dynamic Glu changes is still missing. Our group at MUW has recently developed a novel ground-breaking accelerated method for ultra-short echo time MRS imaging (UTE-MRSI) providing optimal Glu measures with critical sensitivity improvements compared to conventional proton single-voxel MRS (SV-MRS) and previously utilized MRSI approaches. Our method allows monitoring of Glu responses selectively in activated voxels and overcomes low spatial resolution, and limited coverage of SV-MRS that is the current gold standard for measurement of Glu concentrations and its dynamic changes in vivo (functional SV-MRS). The further improvement of UTE-MRSI by the implementation of the novel real-time motion correction will boost its applicability in clinical human studies. Thus, our UTE-MRSI will offer image-based multi-slice measurements of baseline Glu concentrations and its responses to ketamine administration with the potential to clarify ketamine’s mechanism of action in patients with TRD, and will allow monitoring of other novel glutamatergic therapies. | [
"Neuroscience and Disorders of the Nervous System",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Physical and Analytical Chemical Sciences"
]
|
IL 9700096 W | ODOR-REMOVING SYSTEM FOR A TOILET | A system for removing odors from a toilet bowl (I) during its use consists mainly of a blower (2) having its inlet connected to the bowl (I) and its outlet connected to piping (5). The blower (2) is driven by a rotary water motor (15) which is actuated by water entering the initially empty flushing cistern (II). Water from the domestic supply is admitted to the water motor (15) by a valve (3) opened by depression of the toilet seat (7) which is supported on the bowl (I) by a flexible ring (40). The flexible ring (40) serves to seal the gap between bowl (I) and seat (7) and permits downward motion of the seat (7) for opening the valve (3). | [
"Products and Processes Engineering",
"Systems and Communication Engineering"
]
|
757957 | Unveiling Planet Formation by Observations and Simulations | With each newly detected exoplanet system, the planet formation theory is constantly gaining weight in the astrophysical research. The planets origin is a mystery which can only be solved by understanding the protoplanetary disks evolution. Recent disk observations by the new class of interferometer telescopes are challenging the existing theory of planet formation. They reveal astonishing detailed structures of spirals and rings in the dust emission which have never been seen before. Those structures are often claimed to be caused by embedded planets, which is difficult to explain with current models. This growing discrepancy between observation and theory forces us to realize: a novel disk modeling is essential to move on. Separate gas or dust evolution models have reached their limit and the gap between those has to be closed.
With the UFOS project, I propose an unique and ambitious approach to unite gas and dust evolution models for protoplanetary disks. For the first time, a single global model will mutually link self-consistently: a) the transport of gaseous disk material, b) the radiative transfer, c) magnetic fields and their dissipation and d) the transport and growth of the solid material in form of dust grains.
The development, performing and post-analysis of the models will initiate a new age for the planet formation research. The project results will achieve 1) unprecedented self-consistent precision to answer the question if those novel observed structures are caused by embedded planets or by the gas dynamics itself; 2) to find the locations of dust concentration and growth to unveil the birth places of planets and 3) to close the gap and finally unify self-consistent models of the disk evolution with the new class of observations.
Only such advanced models combined with multi-wavelength observations, can show us the process of planet formation, and so explain the origin of the various of planets and exoplanets in our solar neighborhood and beyond. | [
"Universe Sciences",
"Computer Science and Informatics"
]
|
US 2005/0041793 W | AN EFFICIENT MECHANISM FOR FAST RECOVERY IN CASE OF BORDER ROUTER NODE FAILURE IN A COMPUTER NETWORK | A technique protects traffic (IP) against the failure of a border router between two domains in a computer network using Fast Reroute and backup tunnels. The border router (i.e., the "protected border router") announces/advertises a list of all its adjacent next-hop routers (i.e., its "neighbors") residing in first and second domains interconnected by the protected border router. A neighbor in the first domain that is immediately upstream to the protected border router and that is configured to protect the border router (i.e., the "protecting router") learns address prefixes (i.e., "protected prefixes") reachable from the next-hop router in the second domain (i.e., "next-next-hops," NNHOPs to the protected prefixes from the protecting router). The protecting router calculates a backup tunnel to each NNHOP that excludes the protected border router, and associates each backup tunnel with protected prefixes accordingly. When the protected border router fails, Fast Reroute is triggered, and the protected prefixes are rerouted by the protecting router onto an appropriate backup tunnel to a corresponding is NNHOP. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
10.1002/num.22123 | Finite element approximation of nonlocal parabolic problem | In this article, we present a finite element scheme combined with backward Euler method to solve a nonlocal parabolic problem. An important issue in the numerical solution of nonlocal problems while using Newton's method is related to its structure. In fact differently from the local case where the Jacobian matrix is sparse and banded, in the nonlocal case the Jacobian matrix is dense and computations are much more onerous compared to that for differential equations. In order to avoid this difficulty, we use the technique given by Gudi (SIAM J Numer Anal 50 (2012), 657–668) for elliptic nonlocal problem of Kirchhoff type. We discuss the well-posedness of the weak formulation at continuous as well as at discrete levels. We also derive a priori error estimates for semidiscrete and fully discrete formulations in L2 and H1 norms. Results based on the usual finite element method are provided to confirm the theoretical estimates. | [
"Mathematics",
"Computer Science and Informatics"
]
|
W1592185778 | Concerns about falling in wheelchair users with spinal cord injury—validation of the Swedish version of the spinal cord injury falls concern scale | Translation of the Spinal Cord Injury Falls Concern Scale (SCI-FCS); validation and investigation of psychometric properties.Translation, adaptation and validation study.Eighty-seven wheelchair users with chronic SCI attending follow-up at Rehab Station Stockholm/Spinalis, Sweden.The SCI-FCS was translated to Swedish and culturally adapted according to guidelines. Construct validity was examined with the Mann-Whitney U-test, and psychometric properties with factor and Rasch analysis.Participants generally reported low levels of concerns about falling. Participants with higher SCI-FCS scores also reported fear of falling, had been injured for a shorter time, reported symptoms of depression, anxiety and fatigue, and were unable to get up from the ground independently. Falls with or without injury the previous year, age, level of injury, sex and sitting balance did not differentiate the level of SCI-FCS score. The median SCI-FCS score was 21 (range 16-64). Cronbachs alpha (0.95), factor and Rasch analysis showed similar results of the Swedish as of the original version.The Swedish SCI-FCS showed high internal consistency and similar measurement properties and structure as the original version. It showed discriminant ability for fear of falling, time since injury, symptoms of depression or anxiety, fatigue and ability to get up from the ground but not for age, gender or falls. Persons with shorter time since injury, psychological concerns, fatigue and decreased mobility were more concerned about falling. In a clinical setting, the SCI-FCS might help identifying issues to address to reduce the concerns about falling. | [
"Neuroscience and Disorders of the Nervous System",
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1103/PhysRevB.96.115202 | Anomalous Nernst and thermal Hall effects in tilted Weyl semimetals | We study the anomalous Nernst and thermal Hall effects in a linearized low-energy model of a tilted Weyl semimetal, with two Weyl nodes separated in momentum space. For inversion symmetric tilt, we give analytic expressions in two opposite limits: For a small tilt, corresponding to a type-I Weyl semimetal, the Nernst conductivity is finite and independent of the Fermi level; for a large tilt, corresponding to a type-II Weyl semimetal, it acquires a contribution depending logarithmically on the Fermi energy. This result is in a sharp contrast to the nontilted case, where the Nernst response is known to be zero in the linear model. The thermal Hall conductivity similarly acquires Fermi surface contributions, which add to the Fermi level-independent, zero-tilt result, and is suppressed as one over the tilt parameter at half filling in the type-II phase. In the case of inversion-breaking tilt, with the tilting vector of equal modulus in the two Weyl cones, all Fermi surface contributions to both anomalous responses cancel out, resulting in zero Nernst conductivity. We discuss two possible experimental setups, representing open and closed thermoelectric circuits. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences"
]
|
260864 | Evolutionary reconstruction of viral spread in time and space | To identify the causal mechanisms leading to disease emergence, endemic maintenance and epidemic expansion,
epidemiologists would benefit tremendously from a full characterization of pathogen spread in space and time. The extensive
sequencing efforts for the ongoing swine-origin H1N1 influenza A epidemic testify that analyses of pathogen genetic data are
becoming increasingly important source of information in epidemiology. The new era of metagenomics promises to harvest
such data in unprecedented quantities with remarkable rapidity. With the objective to assist in designing effective intervention
and prevention strategies, we propose to develop a comprehensive statistical framework for uncovering the spatial and
temporal dynamics of pathogen genomes. To this aim, we will design and extend a series of computationally tractable models
that use the rapidly proliferating viral genome data to their full potential, connect molecular evolution to underlying spatial
processes, and pave the path to rigorous and powerful phylogeographic hypothesis testing approaches. Armed with these
tools, we will investigate how genetic variation within important viral pathogens, such as influenza, rabies and HIV, arises and
persists across a diverse range of hosts and environments. | [
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Mathematics"
]
|
W2028499077 | Strategies of the Stakeholders Related with the Behavior of Fare Evasions Based on Game Theory | More and more people choose to have a trip in holidays meanwhile more and more tourism areas begin to jack up the price of the tickets. This outcome results in more and more tickets evaders emerged around. And the behavior of sneaking through without a ticket has affected the interest of the stakeholders such as the attraction administration, the local residents and the tourists. So the attractions administration has to take some measures to stop that behavior and the local residents will decide whether they should help the tourists at the risk of being punished. Then the game among the attraction administration, the local residents and the tourists begins. | [
"Individuals, Markets and Organisations",
"The Social World and Its Interactions"
]
|
10.1016/j.jcp.2017.05.010 | Computational reduction strategies for the detection of steady bifurcations in incompressible fluid-dynamics: Applications to Coanda effect in cardiology | We focus on reducing the computational costs associated with the hydrodynamic stability of solutions of the incompressible Navier–Stokes equations for a Newtonian and viscous fluid in contraction–expansion channels. In particular, we are interested in studying steady bifurcations, occurring when non-unique stable solutions appear as physical and/or geometric control parameters are varied. The formulation of the stability problem requires solving an eigenvalue problem for a partial differential operator. An alternative to this approach is the direct simulation of the flow to characterize the asymptotic behavior of the solution. Both approaches can be extremely expensive in terms of computational time. We propose to apply Reduced Order Modeling (ROM) techniques to reduce the demanding computational costs associated with the detection of a type of steady bifurcations in fluid dynamics. The application that motivated the present study is the onset of asymmetries (i. e. , symmetry breaking bifurcation) in blood flow through a regurgitant mitral valve, depending on the Reynolds number and the regurgitant mitral valve orifice shape. | [
"Mathematics",
"Condensed Matter Physics",
"Products and Processes Engineering"
]
|
10.1130/G34804.1 | Rapid High Amplitude Variability In Baltic Sea Hypoxia During The Holocene | Hypoxia (oxygen concentrations of <2 ml/L) and so-called "dead zones" are a growing concern in coastal marine environments. The Baltic Sea is a shelf sea that is highly sensitive to hypoxia, and may serve as a laboratory for studying the interplay between natural and anthropogenic forcing of redox conditions in the global coastal zone. Past occurrences of hypoxia in the Baltic Sea have been shown by previous studies, but high-resolution, quantitative reconstructions of past hypoxia intensity are lacking. Here we present bulk sediment geochemical records from the deep basins of the Baltic Sea that show multicentennial oscillations during intervals of past hypoxia, suggesting rapid alternations between hypoxic and relatively oxic conditions. While the onset of past hypoxic events was likely forced by climatic variability, these events intensified and terminated rapidly due to feedbacks in the phosphorus (P) cycle. The modern intensity of hypoxia is similar to several past events, suggesting that hypoxia in the Baltic Sea has a maximum potential intensity. However, using ultrahigh-resolution laser ablation–inductively coupled plasma–mass spectrometry scanning of sediment blocks, we show that modern hypoxia intensified more rapidly than any past event. This confirms the role of anthropogenic nutrient loading in driving this system into its current hypoxic state. | [
"Earth System Science",
"Environmental Biology, Ecology and Evolution",
"Physical and Analytical Chemical Sciences"
]
|
W1950882288 | Delayed Exciton Emission and Its Relation to Blinking in CdSe Quantum Dots | The efficiency and stability of emission from semiconductor nanocrystal quantum dots (QDs) is negatively affected by "blinking" on the single-nanocrystal level, that is, random alternation of bright and dark periods. The time scales of these fluctuations can be as long as many seconds, orders of magnitude longer than typical lifetimes of exciton states in QDs. In this work, we investigate photoluminescence from QDs delayed over microseconds to milliseconds. Our results prove the existence of long-lived charge-separated states in QDs. We study the properties of delayed emission as a direct way to learn about charge carrier separation and recovery of the exciton state. A new microscopic model is developed to connect delayed emission to exciton recombination and blinking from which we conclude that bright periods in blinking are in fact not characterized by uninterrupted optical cycling as often assumed. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
10.3847/0004-637X/825/2/135 | Detection Of Three Gamma Ray Burst Host Galaxies At Z 6 | Long-duration gamma-ray bursts (GRBs) allow us to pinpoint and study star-forming galaxies in the early universe, thanks to their orders of magnitude brighter peak luminosities compared to other astrophysical sources, and their association with the deaths of massive stars. We present Hubble Space Telescope Wide Field Camera 3 detections of three Swift GRB host galaxies lying at redshifts z = 5. 913 (GRB 130606A), z = 6. 295 (GRB 050904), and z = 6. 327 (GRB 140515A) in the F140W (wide-JH band, ${\lambda }_{{\rm{obs}}}\sim 1. 4\;\mu {\rm{m}}$) filter. The hosts have magnitudes (corrected for Galactic extinction) of ${m}_{{\lambda }_{\mathrm{obs}},\mathrm{AB}}={26. 34}_{-0. 16}^{+0. 14},{27. 56}_{-0. 22}^{+0. 18},$ and ${28. 30}_{-0. 33}^{+0. 25}$, respectively. In all three cases, the probability of chance coincidence of lower redshift galaxies is $\lesssim 2 \% $, indicating that the detected galaxies are most likely the GRB hosts. These are the first detections of high-redshift ($z\gt 5$) GRB host galaxies in emission. The galaxies have luminosities in the range 0. 1–0. 6 ${L}_{z=6}^{* }$ (with ${M}_{1600}^{* }=-20. 95\pm 0. 12$) and half-light radii in the range 0. 6–0. 9 ${\rm{kpc}}$. Both their half-light radii and luminosities are consistent with existing samples of Lyman-break galaxies at $z\sim 6$. Spectroscopic analysis of the GRB afterglows indicate low metallicities ($[{\rm{M/H}}]\lesssim -1$) and low dust extinction (${A}_{{\rm{V}}}\lesssim 0. 1$) along the line of sight. Using stellar population synthesis models, we explore the implications of each galaxy's luminosity for its possible star-formation history and consider the potential for emission line metallicity determination with the upcoming James Webb Space Telescope. | [
"Universe Sciences"
]
|
639750 | Vibronic control of organic electronic devices | Organic electronics (OE) is an expanding research field that exploits the electronic functionalities of organic molecules to make them robust and cost-efficient building blocks for future electronic devices. Due to the ‘soft’ character of organic materials, their electronic properties are defined by vibronic coupling (VC) phenomena which are a result of the interaction between electron and nuclear dynamics of the molecule.
This research program aims to unlock a new direction of experimental studies investigating and exploiting VC in OE devices by using optical control of nuclear motion.
The growing awareness that VC underlies diverse phenomena from physics to biology stimulates a broad interdisciplinary effort to address this issue. However, in the field of OE, the lack of synergy between device and optical studies holds the potential functionality offered by VC effects from being attained. In 2012, I proposed a direct route to control the performance of OE devices by optically switching the vibronic states of the molecules. Though this work came specifically in connection with organic photovoltaics, it provides the starting point for a more fundamental and broad reaching of VC phenomena. The proposed research program will use this opportunity. I will apply state-of-the-art developments in infrared light shaping to create a well-defined coherent superposition of molecular vibrational motions inside devices and study their influence on electron dynamics with device-specific spectroscopic techniques.
This approach combines recent advances in ultrafast spectroscopy and OE to extend our fundamental understanding of molecular charge transport. Our methodology will become a tool for elucidating current pathways in organic nanodevices and offer access to non-equilibrium phenomena down to the level of molecular junctions. This research will lead to the development of new design rules for OE materials serving future advances in molecular electronics, computing and sensing. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
10.1021/acs.jpcc.7b10515 | Atomic-Scale Structure of the Hematite α-Fe<inf>2</inf>O<inf>3</inf>(11-02) "r-Cut" Surface | The α-Fe2O3(11-02) surface (also known as the hematite r-cut or (012) surface) was studied using low-energy electron diffraction (LEED), X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), scanning tunneling microscopy (STM), noncontact atomic force microscopy (nc-AFM), and ab initio density functional theory (DFT)+U calculations. Two surface structures are stable under ultrahigh vacuum (UHV) conditions; a stoichiometric (1 × 1) surface can be prepared by annealing at 450 °C in ≈10-6 mbar O2, and a reduced (2 × 1) reconstruction is formed by UHV annealing at 540 °C. The (1 × 1) surface is close to an ideal bulk termination, and the undercoordinated surface Fe atoms reduce the surface bandgap by ≈0. 2 eV with respect to the bulk. The work function is measured to be 5. 7 ± 0. 2 eV, and the VBM is located 1. 5 ± 0. 1 eV below EF. The images obtained from the (2 × 1) reconstruction cannot be reconciled with previously proposed models, and a new "alternating trench" structure is proposed based on an ordered removal of lattice oxygen atoms. DFT+U calculations show that this surface is favored in reducing conditions and that 4-fold-coordinated Fe2+ cations at the surface introduce gap states approximately 1 eV below EF. The work function on the (2 × 1) termination is 5. 4 ± 0. 2 eV. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
10.1111/j.1751-908X.2015.00388.x | High-Precision Mass-Dependent Molybdenum Isotope Variations in Magmatic Rocks Determined by Double-Spike MC-ICP-MS | Small mass-dependent variations of molybdenum isotope ratios in oceanic and island arc rocks are expected as a result of recycling altered oceanic crust and sediments into the mantle at convergent plate margins over geological timescales. However, the determination of molybdenum isotope data precise and accurate enough to identify these subtle isotopic differences remains challenging. Large sample sizes – in excess of 200 mg – need to be chemically processed to isolate enough molybdenum in order to allow sufficiently high-precision isotope analyses using double-spike MC-ICP-MS techniques. Established methods are either unable to process such large amounts of silicate material or require several distinct chemical processing steps, making the analyses very time-consuming. Here, we present a new and efficient single-pass chromatographic exchange technique for the chemical isolation of molybdenum from silicate and metal matrices. To test our new method, we analysed USGS reference materials BHVO-2 and BIR-1. Our new data are consistent with those derived from more involved and time-consuming methods for these two reference materials previously published. We also provide the first molybdenum isotope data for USGS reference materials AGV-2, the GSJ reference material JB-2 as well as metal NIST SRM 361. | [
"Physical and Analytical Chemical Sciences",
"Earth System Science"
]
|
757585 | C° symplectic geometry | The objective of this proposal is to study ""continuous"" (or C^0) objects, as well as C^0 properties of smooth objects, in the field of symplectic geometry and topology. C^0 symplectic geometry has seen spectacular progress in recent years, drawing attention of mathematicians from various background. The proposed study aims to discover new fascinating C^0 phenomena in symplectic geometry.
One circle of questions concerns symplectic and Hamiltonian homeomorphisms. Recent studies indicate that these objects possess both rigidity and flexibility, appearing in surprising and counter-intuitive ways. Our understanding of symplectic and Hamiltonian homeomorphisms is far from being satisfactory, and here we intend to study questions related to action of symplectic homeomorphisms on submanifolds. Some other questions are about Hamiltonian homeomorphisms in relation to the celebrated Arnold conjecture. The PI suggests to study spectral invariants of continuous Hamiltonian flows, which allow to formulate the C^0 Arnold conjecture in higher dimensions. Another central problem that the PI will work on is the C^0 flux conjecture.
A second circle of questions is about the Poisson bracket operator, and its functional-theoretic properties. The first question concerns the lower bound for the Poisson bracket invariant of a cover, conjectured by L. Polterovich who indicated relations between this problem and quantum mechanics. Another direction aims to study the C^0 rigidity versus flexibility of the L_p norm of the Poisson bracket. Despite a recent progress in dimension two showing rigidity, very little is known in higher dimensions. The PI proposes to use combination of tools from topology and from hard analysis in order to address this question, whose solution will be a big step towards understanding functional-theoretic properties of the Poisson bracket operator. | [
"Mathematics"
]
|
10.1007/s00221-013-3489-1 | Isolating shape from semantics in haptic-visual priming | The exploration of a familiar object by hand can benefit its identification by eye. What is unclear is how much this multisensory cross-talk reflects shared shape representations versus generic semantic associations. Here, we compare several simultaneous priming conditions to isolate the potential contributions of shape and semantics in haptic-to-visual priming. Participants explored a familiar object manually (haptic prime) while trying to name a visual object that was gradually revealed in increments of spatial resolution. Shape priming was isolated in a comparison of identity priming (shared semantic category and shape) with category priming (same category, but different shapes). Semantic priming was indexed by the comparisons of category priming with unrelated haptic primes. The results showed that both factors mediated priming, but that their relative weights depended on the reliability of the visual information. Semantic priming dominated in Experiment 1, when participants were free to use high-resolution visual information, but shape priming played a stronger role in Experiment 2, when participants were forced to respond with less reliable visual information. These results support the structural description hypothesis of haptic-visual priming (Reales and Ballesteros in J Exp Psychol Learn Mem Cogn 25:644-663, 1999) and are also consistent with the optimal integration theory (Ernst and Banks in Nature 415:429-433, 2002), which proposes a close coupling between the reliability of sensory signals and their weight in decision making. | [
"Neuroscience and Disorders of the Nervous System",
"The Human Mind and Its Complexity"
]
|
Q4940038 | (19474.04112021.194000099) THE MINE 2021 | WITH THIS PROJECT, THE COMPANY WANTS TO OVERSEE MORE THE TWO TARGET TARGET MARKETS (UNITED STATES AND UK), THROUGH TRADE FAIR EXPENSES, IMPLEMENTATION OF COMMUNICATION ACTIONS FOR ACTIVITIES? BRANDING AND MARKET RESEARCH IN THE UK TO START AN ENTRY ACTION ON THIS MARKET. | [
"Individuals, Markets and Organisations"
]
|
10.1093/bioinformatics/bty1011 | Insights on protein thermal stability: a graph representation of molecular interactions | Abstract
Motivation
Understanding the molecular mechanisms of thermal stability is a challenge in protein biology. Indeed, knowing the temperature at which proteins are stable has important theoretical implications, which are intimately linked with properties of the native fold, and a wide range of potential applications from drug design to the optimization of enzyme activity. Results
Here, we present a novel graph-theoretical framework to assess thermal stability based on the structure without any a priori information. In this approach we describe proteins as energy-weighted graphs and compare them using ensembles of interaction networks. Investigating the position of specific interactions within the 3D native structure, we developed a parameter-free network descriptor that permits to distinguish thermostable and mesostable proteins with an accuracy of 76% and area under the receiver operating characteristic curve of 78%. Availability and implementation
Code is available upon request to edoardo. milanetti@uniroma1. it
Supplementary information
Supplementary data are available at Bioinformatics online. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Computer Science and Informatics"
]
|
10.1177/0022343312469979 | Fresh carnations or all thorn, no rose? Nonviolent campaigns and transitions in autocracies | Whereas optimists see the so-called Arab Spring as similar to the revolutions of 1989, and likely to bring about democratic rule, skeptics fear that protest bringing down dictators may simply give way to new dictatorships, as in the Iranian revolution. Existing research on transitions has largely neglected the role of protest and direct action in destabilizing autocracies and promoting democracy. We argue that protest and direct action can promote transitions in autocracies, and that the mode of direct action, that is, whether violent or nonviolent, has a major impact on the prospects for autocratic survival and democracy. We present empirical results supporting our claim that nonviolent protests substantially increase the likelihood of transitions to democracy, especially under favorable international environments, while violent direct action is less effective in undermining autocracies overall, and makes transitions to new autocracies relatively more likely. | [
"Institutions, Governance and Legal Systems",
"The Social World and Its Interactions"
]
|
10.1145/3152156 | Steklov Spectral Geometry For Extrinsic Shape Analysis | We propose using the Dirichlet-to-Neumann operator as an extrinsic alternative to the Laplacian for spectral geometry processing and shape analysis. Intrinsic approaches, usually based on the Laplace–Beltrami operator, cannot capture the spatial embedding of a shape up to rigid motion, and many previous extrinsic methods lack theoretical justification. Instead, we consider the Steklov eigenvalue problem, computing the spectrum of the Dirichlet-to-Neumann operator of a surface bounding a volume. A remarkable property of this operator is that it completely encodes volumetric geometry. We use the boundary element method (BEM) to discretize the operator, accelerated by hierarchical numerical schemes and preconditioning; this pipeline allows us to solve eigenvalue and linear problems on large-scale meshes despite the density of the Dirichlet-to-Neumann discretization. We further demonstrate that our operators naturally fit into existing frameworks for geometry processing, making a shift from intrinsic to extrinsic geometry as simple as substituting the Laplace–Beltrami operator with the Dirichlet-to-Neumann operator. | [
"Mathematics",
"Computer Science and Informatics"
]
|
10.1016/j.cryobiol.2015.12.001 | The Grand Challenges of Organ Banking: Proceedings from the first global summit on complex tissue cryopreservation | The first Organ Banking Summit was convened from Feb. 27 - March 1, 2015 in Palo Alto, CA, with events at Stanford University, NASA Research Park, and Lawrence Berkeley National Labs. Experts at the summit outlined the potential public health impact of organ banking, discussed the major remaining scientific challenges that need to be overcome in order to bank organs, and identified key opportunities to accelerate progress toward this goal. Many areas of public health could be revolutionized by the banking of organs and other complex tissues, including transplantation, oncofertility, tissue engineering, trauma medicine and emergency preparedness, basic biomedical research and drug discovery - and even space travel. Key remaining scientific sub-challenges were discussed including ice nucleation and growth, cryoprotectant and osmotic toxicities, chilling injury, thermo-mechanical stress, the need for rapid and uniform rewarming, and ischemia/reperfusion injury. A variety of opportunities to overcome these challenge areas were discussed, i. e. preconditioning for enhanced stress tolerance, nanoparticle rewarming, cyroprotectant screening strategies, and the use of cryoprotectant cocktails including ice binding agents. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Cell Biology, Development, Stem Cells and Regeneration",
"Physical and Analytical Chemical Sciences",
"Materials Engineering",
"Products and Processes Engineering"
]
|
10.1007/978-3-642-15558-1_6 | Real Time Spherical Mosaicing Using Whole Image Alignment | When a purely rotating camera observes a general scene, overlapping views are related by a parallax-free warp which can be estimated by direct image alignment methods that iterate to optimise photoconsistency. However, building globally consistent mosaics from video has usually been tackled as an off-line task, while sequential methods suitable for real-time implementation have often suffered from long-term drift. In this paper we present a high performance real-time video mosaicing algorithm based on parallel image alignment via ESM (Efficient Second-order Minimisation) and global optimisation of a map of keyframes over the whole viewsphere. We present real-time results for drift-free camera rotation tracking and globally consistent spherical mosaicing from a variety of cameras in real scenes, demonstrating high global accuracy and the ability to track very rapid rotation while maintaining solid 30Hz operation. We also show that automatic camera calibration refinement can be straightforwardly built into our framework. | [
"Computer Science and Informatics",
"Systems and Communication Engineering"
]
|
10.1111/jtxs.12356 | Aging-related changes in quantity and quality of saliva: Where do we stand in our understanding? | Saliva is crucial to oral processing of food and consequently is also related to the sensory and textural experience. It is often assumed that the secretion and properties of saliva change with age, which can result in dry mouth conditions, taste aberrations. Such changes may result in reduced nutrient intake and malnutrition besides adversely affecting the quality of life. Based on some recent research findings, this article reviews our current understandings on age-dependent changes on quantity (bulk salivary flow rate) as well as quality of saliva (e. g. , composition, viscosity, lubrication) in healthy elderly individuals. The review begins with a short introduction to histological changes of salivary glands upon aging. This is followed by covering different aspects of salivary changes with key articles highlighting decreased flow rate, increased ionic concentration, decreased calcium and mucin content in saliva of elderly subjects consequently affecting the oral coating and flavor perception. We also highlight issues in data associated with respect to variance in saliva collection protocols as well as factors influencing such results other than age, such as health conditions and polypharmacy. Clear gaps in literature have been highlighted with respect to lack of quantitative data in viscoelasticity, rheology, and lubrication properties of saliva in healthy elderly population and the potential impact of changes in these material properties on sensory and textural perception of food and consequently food intake. Such insights will not only have clinical implications for maintaining optimal oral health in elderly population but also serve to optimize food for elderly population. Practical applications: The population has undergone a fundamental change in its age structure globally, with a rapid increase in elderly population. Innovation of tailored foods is still in its early stage to satisfy the needs of growing aging population. One of the biggest challenges in such food product development is lack of adequate understanding and characterization of endogenous factors, that is, age-related changes in saliva, which may influence oral processing of food and subsequently nutrient intake. Aging affects the salivary glands and alters quantity (flow rate) and quality (e. g. , ion and protein composition, rheology, tribology) of saliva. Thus, older adults may suffer from dry mouth, taste aberration, and poor oral hygiene, greatly affecting their quality of life. This review provides insights into how age versus other health conditions influence salivary properties. Understanding of age-dependent changes in salivary rheology and tribology will be of paramount importance to optimize food for elderly population. | [
"Physiology in Health, Disease and Ageing",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1038/s41598-017-10232-1 | Three-Dimensional Geometric Morphometric Analysis of Fossil Canid Mandibles and Skulls | Much of the fossil record for dogs consists of mandibles. However, can fossil canid mandibles be reliably identified as dogs or wolves? 3D geometric morphometric analysis correctly classifies 99. 5% of the modern dog and wolf mandibles. However, only 4 of 26 Ust'-Polui fossil mandibles, a Russian Arctic site occupied from 250BCE to 150CE, were identified as dogs and none of the 20 Ivolgin mandibles, an Iron Age site in southern Russia, were identified as dogs. Three of the Ust'-Polui mandibles and 8 of the Ivolgin mandibles were identified as wolves. In contrast, all 12 Ivolgin skulls and 5 Ust'-Polui skulls were clearly identified as dogs. Only the classification of the UP6571 skull as a dog (Dog Posterior Probability = 1. 0) was not supported by the typical probability. Other evidence indicates these canids were domesticated: They were located within human dwellings, remains at both sites have butchery marks indicating that they were consumed, and isotope analysis of canid and human remains from Ust'-Polui demonstrate that both were consuming freshwater protein; indicating that the humans were feeding the canids. Our results demonstrate that the mandible may not evolve as rapidly as the cranium and the mandible is not reliable for identifying early dog fossils. | [
"The Study of the Human Past",
"Earth System Science"
]
|
US 23325781 A | Floor cutter bit | A floor cutter bit for a coal plough has a cutter body which supports a floor cutter plate and a coal-face cutter plate. The two cutter plates are made of hard metal, and have respective cutting edges. The cutter plates are soldered into respective apertures in the cutter body. The cutting edge of the floor cutter plate extends the entire length of the floor cutter plate, and the floor cutter plate extends over the entire width of the cutter body. The base of the coal-face cutter plate adjoins the upper side of the floor cutter plate thereby defining an L-shaped cutter plate configuration. The depth of the floor cutter plate, at least in the region where the two cutter plates meets, is greater than about 15 millimeters. | [
"Products and Processes Engineering",
"Materials Engineering"
]
|
803087 | Enteric-nervous-system-mediated regulation of intestinal inflammation | Environmental and internal stimuli are constantly sensed by the body’s two large sensory units, the nervous system and the immune system. Integration of these sensory signals and translation into effector responses are essential for maintaining body homeostasis. While some of the intrinsic pathways of the immune or nervous system have been investigated, how the two sensory interfaces coordinate their responses remains elusive. We have recently investigated neuro-immune interaction at the mucosa of the intestine, which is densely innervated by the enteric nervous system (ENS). Our research has exposed a previously unrecognized pathway used by enteric neurons to shape type 2 immunity at mucosal barriers. Cholinergic enteric neurons produce the neuropeptide Neuromedin U (NMU) to elicit potent activation of type 2 innate lymphoid cells (ILC2s) via Neuromedin U receptor 1, selectively expressed by ILC2s. Interestingly, NMU stimulated protective immunity against the parasite Nippostrongylus brasiliensis but also triggered allergic lung inflammation. Therefore, the NMU-NMUR1 axis provides an excellent opportunity to study how neurons and immune cells interact to regulate immune responses and maintain body homeostasis. We propose to generate and use elegant genetic tools, which will allow us to systematically investigate the consequences of neuro-immune crosstalk at mucosal surfaces in various disease models. These tools will enable us to selectively measure and interfere with neuronal and ILC2 gene expression and function, thereby leading to an unprecedented understanding of how the components of neuro-immune crosstalk contribute to parasite immunity or allergic disease development. Furthermore, we will progress into translational aspects of NMU-regulated immune activation for human immunology. Therefore, our research has the potential to develop basic concepts of mucosal immune regulation and such discoveries could also be harnessed for therapeutic intervention. | [
"Immunity, Infection and Immunotherapy",
"Neuroscience and Disorders of the Nervous System"
]
|
Q2702943 | Aumentare la competitività dell'impresa attuando i risultati del lavoro di R & S attraverso l'innovazione di prodotto | L'obiettivo principale del progetto è quello di aumentare la competitività dell'azienda implementando i risultati del lavoro di R & S utilizzando l'innovativo software "Kettlo". Il lavoro di R & S è stato svolto da un ricercatore presso UMCS, la sig.ra Bartłomiej Bielecki, assistente del Dipartimento di Cybersecurity. Il risultato del lavoro è il modulo SELPRS dt.: regolazione dei valori di carico e intervalli di esercizio — la prima applicazione di questo tipo, riducendo al minimo gli infortuni durante l'allenamento, perché i sistemi esistenti non offrono la possibilità di regolare il carico, sia prima che durante l'allenamento, cioè il sistema in situazione di non esecuzione con il carico giusto, proporrò una variazione di valore, il modulo effettuerà anche aggiustamenti di peso nella situazione di esercizio eccessivamente lungo. Il sistema Kettlo avrà anche un modulo "Smart Virtual Personal Trainer" responsabile della selezione del piano di formazione appropriato, correggendo l'esercizio in assenza di possibilità di esecuzione a breve o permanente a causa ad esempio di impilatore danneggiato a lungo termine, temporanea mancanza di disponibilità eseguendo esercizi da parte di un altro cliente, mancanza di piacere nell'esecuzione di esercizi con un determinato dispositivo. Il sistema offrirà durante l'allenamento un esercizio con parametri simili o identici relativi al coinvolgimento delle parti muscolari, incluso l'esercizio con il proprio peso corporeo. Si tratta di un innovativo software automatizzato su scala internazionale, altri sistemi di questo tipo non hanno le funzionalità di cui sopra. Attraverso l'implementazione del progetto, l'azienda aumenterà l'occupazione di un dipendente, aumenterà la propria attività nei lavori di R & S e internazionalizzerà il prodotto sui nuovi mercati esteri. Il gruppo target del progetto è molto ampio, si tratta di persone che trascorrono attivamente il tempo, sono utenti di fitness club, così come persone che vogliono iniziare l'attività utilizzando un sistema avanzato. Il progetto offre un'ottima opportunità per l'azienda di sviluppare i propri obiettivi. | [
"Products and Processes Engineering",
"Computer Science and Informatics"
]
|
819815 | Dissecting and Overcoming Innate Immune Barriers for Therapeutically Efficient Hematopoietic Stem Cell Gene Engineering | The low gene manipulation efficiency of human hematopoietic stem cells (HSC) remains a major hurdle for sustainable and broad clinical application of innovative therapies for a wide range of disorders. Indeed, high vector doses and prolonged ex vivo culture are still required for clinically relevant levels of gene transfer even with the most established lentiviral vector-based delivery platforms.
Current and emerging gene transfer and editing technologies expose HSC to components potentially recognized by host antiviral factors and nucleic acid sensors that likely restrict their genetic engineering and contribute to broad individual variability in clinical outcomes observed in recent gene therapy trials. Nevertheless, specific effectors are yet to be identified in HSC. We have recently identified an antiviral factor that potently blocks gene transfer in HSC and have discovered small molecules that efficiently counteract it. This is the first example of how manipulating a single host factor can significantly impact gene transfer efficiencies in HSC but likely represents the mere tip of the iceberg of the plethora of innate sensing mechanisms potentially hampering genetic manipulation of this primitive cell compartment.
This proposal aims to identify the antiviral factors and innate sensing pathways that prevent efficient modification of HSC and to mitigate their effects using methods developed through a thorough understanding of their mechanisms of action. My approach builds on the innovative concept that understanding the crosstalk between HSC and viral vectors will instruct us on which immune sensors and effectors to avoid and how, with direct implications for all gene engineering technologies. Successful completion of this project will deliver broadly exportable novel paradigms of innate pathogen recognition that will allow ground-breaking progress in the development of cutting-edge cell and gene therapies and to fight infectious and autoimmune diseases. | [
"Immunity, Infection and Immunotherapy",
"Cell Biology, Development, Stem Cells and Regeneration",
"Integrative Biology: from Genes and Genomes to Systems",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1109/EMBC.2015.7318348 | Theoretical Model And Experimental Validation Of The Estimated Proportions Of Common And Independent Input To Motor Neurons | Motor neurons in the spinal cord receive synaptic input that comprises common and independent components. The part of synaptic input that is common to all motor neurons is the one regulating the production of force. Therefore, its quantification is important to assess the strategy used by Central Nervous System (CNS) to control and regulate movements, especially in physiological conditions such as fatigue. In this study we present and validate a method to estimate the ratio between strengths of common and independent inputs to motor neurons and we apply this method to investigate its changes during fatigue. By means of coherence analysis we estimated the level of correlation between motor unit spike trains at the beginning and at the end of fatiguing contractions of the Tibialis Anterior muscle at three different force targets. Combining theoretical modeling and experimental data we estimated the strength of the common synaptic input with respect to the independent one. We observed a consistent increase in the proportion of the shared input to motor neurons during fatigue. This may be interpreted as a strategy used by the CNS to counteract the occurrence of fatigue and the concurrent decrease of generated force. | [
"Neuroscience and Disorders of the Nervous System",
"Physiology in Health, Disease and Ageing"
]
|
10.1021/cr400207r | Single-molecule studies of RNA polymerases | Single-molecule experiments have already provided a wealth of quantitative and direct information about transcriptional structures and dynamics. For example, by imaging a transcription complex at various stages during the transcription cycle using an AFM, one can map its mechanical architecture. More detailed structural information as well as kinetic data of transient states of transcription or of reaction intermediates can be obtained from single-molecule fluorescence methods, in particular, single-molecule FRET measurements. Moreover, information about the nucleosomal barrier and its effect on transcription elongation come from AFM as well as optical tweezer experiments. Also, most recently, single-molecule studies have advanced to the complex environments of living cells, obtaining quantitative information about single-molecule events in real live situations. While the field of single-molecule transcription is still at its early stages, already a number of excellent review articles have appeared. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1021/acs.nanolett.6b04137 | Fabry-Pérot resonances in a graphene/hBN Moiré superlattice | While Fabry-Pérot (FP) resonances and Moiré superlattices are intensively studied in graphene on hexagonal boron nitride (hBN), the two effects have not been discussed in their coexistence. Here we investigate the FP oscillations in a ballistic pnp-junctions in the presence and absence of a Moiré superlattice. First, we address the effect of the smoothness of the confining potential on the visibility of the FP resonances and carefully map the evolution of the FP cavity size as a function of densities inside and outside the cavity in the absence of a superlattice, when the cavity is bound by regular pn-junctions. Using a sample with a Moirésuperlattice, we next show that an FP cavity can also be formed by interfaces that mimic a pn-junction but are defined through a satellite Dirac point due to the superlattice. We carefully analyze the FP resonances, which can provide insight into the band-reconstruction due to the superlattice. | [
"Condensed Matter Physics",
"Fundamental Constituents of Matter"
]
|
10.1016/j.tecto.2012.06.022 | Mechanisms of margin inversion in the external Western Alps: Implications for crustal rheology | The kinematics of the collisional crustal wedge in the external Western Alps is discussed in the light of new cross sections of the whole external zone at the latitude of the Belledonne-Grandes Rousses-Oisans massifs (External Crystalline Massifs, ECM), as well as a detailed analysis of the deformation of their basement and cover. The cross sections were built from new field data and published geological maps, and were restored through time (Oligo-Miocene times) to unravel the successive stages of the Dauphinois margin contractional deformation. During Oligocene times, the Variscan basement was deformed essentially by greenschist facies Alpine distributed shear zones with no significant reactivation of the inherited Jurassic normal faults or the Variscan foliation. However, the inherited syn-rift basins localized the deformation characterized by a thick-skinned style and a cover disharmonically folded over basement shear zones, with no major décollement in between (shortening of 11. 5. km, 20%). Those early deformations progressively localized on the frontal crustal ramp and caused shortening in the folded belt (16. 5. km of shortening, 23%). A similar sequence of deformation has been inferred in other Alpine ECMs. This strongly suggests that the crust of Dauphinois proximal passive margin was thin enough, and its buoyancy low enough (as a result of the Liassic rifting), to experience significant tectonic burial during the Tertiary collision. As a consequence of a weakening by both the presence of inherited basins (and their weak syn-rift sedimentary rocks) and the P-T conditions (greenschist facies), the crust was shortened and the structural style was thick-skinned. | [
"Earth System Science"
]
|
216301 | A miniature bio-photonics companion diagnostics platform for reliable cancer diagnosis and treatment monitoring. | Current diagnostic options for cancer treatment monitoring rely on imaging techniques and cannot guarantee proper assessment of therapeutic response. This project aims to develop a disruptive Point of Care (PoC) device for cancer early diagnosis and treatment monitoring as a companion diagnostics tool. One of the scientific breakthroughs of this project is the development of a “cancer stem cells” detection platform by virtue of expression of the cancer stem cell-specific transcription factor TWIST1, which controls the expression of the bloodstream circulating biomarkers POSTN, PCOLCE and TGBI. Cancer stem cells represent the most aggressive/tumorigenic cell compartment within tumors.
BIOCDx will combine advanced concepts from the photonic, nano-biochemical, micro-fluidic and reader/packaging platforms aiming to overcome limitations related to detection reliability, sensitivity, specificity, compactness and cost issues. BIOCDx will rely on ultrasensitive, photonic elements based on an array of 8 asymmetric MZI waveguides fabricated by TriPlex technology on silicon nitride substrates and will achieve a 100 fold improvement –with respect to current technologies- of sensitivity (<10-8 RIU). BIOCDx will emlploy a smart concept of signal multiplexing for lowering the number of photodetectors required in multi-analyte detection and allowing for a substantial reduction of chip size. A sandwich assay, enhanced with nanoparticles, will be developed, based on the use of two antibodies per protein, to detect all three circulating proteins. This will enhance the limit of detection (LOD) close to femtomolar and the reliability. BIOCDx photonic, nano-biochemical, fluidics and packaging platforms will be integrated into a portable, desktop PoC device. Its validation in preclinical and clinical setting will be performed in three cancer types: breast cancer, hormone-independent prostate cancer and melanoma. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Systems and Communication Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1073/pnas.1003747107 | EphB-ephrin-B2 interactions are required for thymus migration during organogenesis | Thymus organogenesis requires coordinated interactions of multiple cell types, including neural crest (NC) cells, to orchestrate the formation, separation, and subsequent migration of the developing thymus from the third pharyngeal pouch to the thoracic cavity. The molecular mechanisms driving these processes are unclear; however, NC-derived mesenchyme has been shown to play an important role. Here, we show that, in the absence of ephrin-B2 expression on thymic NC-derived mesenchyme, the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analysis of individual NC-derived thymic mesenchymal cells shows that, in the absence of ephrin-B2, their motility is impaired as a result of defective EphB receptor signaling. This implies a NC-derived cell-specific role of EphB-ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis. | [
"Cell Biology, Development, Stem Cells and Regeneration",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1021/acsnano.5b04713 | Microfluidic diffusion analysis of the sizes and interactions of proteins under native solution conditions | Characterizing the sizes and interactions of macromolecules under native conditions is a challenging problem in many areas of molecular sciences, which fundamentally arises from the polydisperse nature of biomolecular mixtures. Here, we describe a microfluidic platform for diffusional sizing based on monitoring micron-scale mass transport simultaneously in space and time. We show that the global analysis of such combined space-time data enables the hydrodynamic radii of individual species within mixtures to be determined directly by deconvoluting average signals into the contributions from the individual species. We demonstrate that the ability to perform rapid noninvasive sizing allows this method to be used to characterize interactions between biomolecules under native conditions. We illustrate the potential of the technique by implementing a single-step quantitative immunoassay that operates on a time scale of seconds and detects specific interactions between biomolecules within complex mixtures. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
10.1088/0067-0049/208/2/17 | The Second Fermi Large Area Telescope Catalog Of Gamma Ray Pulsars | This catalog summarizes 117 high-confidence > 0. 1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data, through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions. | [
"Universe Sciences",
"Fundamental Constituents of Matter"
]
|
172056 | Paragone: vaccines for animal parasites | Helminth and ectoparasitic infections of ruminants and poultry have a huge impact on the biological efficiency of these vital food sources. Indiscriminate antiparasitic use has led to drug resistance across the globe. The main alternative to the dwindling supply of antiparasitics is vaccines. Here, in the PARAGONE project, findings from previous EU and other-funded projects on parasite vaccine development will be exploited to take a number of promising prototypes towards commercialisation. Partners from the Europe, China, Uruguay, SMEs and pharma, will directly move forward prototypes against the ruminant helminths Fasciola hepatica, Cooperia spp., Ostertagia ostertagi, Teladorsagia circumcincta and Haemonchus contortus and, the ectoparasitic mites, Psoroptes ovis (ruminants) and Dermanyssus gallinae (poultry). They will utilise novel adjuvants or delivery systems to maximise efficacy of some of the prototypes. Moreover, immunology studies will focus on pathogens that have previously proved problematic, often because they release immunosuppressive molecules that must be overcome for vaccines to work or because recombinant vaccines have failed to elicit protection observed with native prototypes. State-of-the-art technologies will be used to interrogate host/parasite interactions to define key signatures of protection that can be used to inform delivery systems that will enhance immunity, while other studies will define polymorphism in current vaccine candidates to ensure derived prototypes will be fit-for-purpose across geographic scales. Fundamental, is engagement of the scientists with pharma and other stakeholders (farmers, veterinarians, regulators) via many dissemination activities that will be used to obtain feedback on how the vaccines can be best deployed in the field. The output will be at least two prototypes to the point of uptake by pharma, government or philanthropic agencies, and a clear pathway to commercialisation for all prototypes studied. | [
"Immunity, Infection and Immunotherapy",
"Biotechnology and Biosystems Engineering",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1063/1.4927220 | Analysis Of The Correlation Dimension For Inertial Particles | We obtain an implicit equation for the correlation dimension which describes clustering of inertial particles in a complex flow onto a fractal measure. Our general equation involves a propagator of a nonlinear stochastic process in which the velocity gradient of the fluid appears as additive noise. When the long-time limit of the propagator is considered our equation reduces to an existing large-deviation formalism, from which it is difficult to extract concrete results. In the short-time limit, however, our equation reduces to a solvability condition on a partial differential equation. We show how this approach leads to a perturbative expansion of the correlation dimension, for which the coefficients can be obtained exactly and in principle to any order. We derive the perturbation series for the correlation dimension of inertial particles suspended in three-dimensional spatially smooth random flows with white-noise time correlations, obtaining the first 33 non-zero coefficients exactly. | [
"Mathematics",
"Condensed Matter Physics"
]
|
217989 | Reconstructing a dated tree of life using phylogenetic incongruence | With the advent of genome-scale sequencing, molecular phylogeny, which reconstructs gene trees from homologous sequences, has reached an impasse. Instead of answering open questions, new genomes have reignited old debates. The problem is clear, gene trees are not species trees, each is the unique result of series of evolutionary events. If, however, we model these differences in the context of a common species tree, we can access a wealth of information on genome evolution and the diversification of species that is not available to traditional methods. For example, as horizontal gene transfer (HGT) can only occur between coexisting species, HGTs provide information on the order of speciations. When HGT is rare, lineage sorting can generate incongruence between gene trees and the dating problem can be formulated in terms of biologically meaningful parameters (such as population size), that are informative on the rate of evolution and hence invaluable to molecular dating.
My first goal is to develop methods that systematically extract information on the pattern and timing of genomic evolution by explaining differences between gene trees. This will allow us to, for the first time, reconstruct a dated tree of life from genome-scale data. We will use parallel programming to maximise the number of genomes analysed.
My second goal is to apply these methods to open problems, e.g.: i) to resolve the timing of microbial evolution and its relationship to Earth history, where the extreme paucity of fossils limits the use of molecular dating methods, by using HGT events as “molecular fossils”; ii) to reconstruct rooted phylogenies from complete genomes and harness phylogenetic incongruence to answer long standing questions, such as the of diversification of animals or the position of eukaryotes among archaea; and iii) for eukaryotic groups such as Fungi, where evidence of significant amounts of HGT is emerging our methods will also allow the quantification of the extent of HGT. | [
"Integrative Biology: from Genes and Genomes to Systems",
"Environmental Biology, Ecology and Evolution",
"Computer Science and Informatics"
]
|
interreg_3353 | Institutional Capacity for Territorial Development | The targeted analysis will address the institutional factors explaining the efficiency of public institutions in designing and implementing successful territorial development strategies and policy in the framework of EU Cohesion Policy. The main objective of this targeted analysis is to develop a common methodology aiming at recognizing, assessing and enhance institutional efficiency. This methodology will also support the identification of technical assistance measures to be adopted at central and regional government levels in order to strengthen the administrative capacity for the implementation of Cohesion Policy. In this regard, the identification of successful experiences or methods seen as a benchmark for other regions in Europe, represent a relevant expected result of the analysis. The targeted analysis will mainly address selected territories of France and Italy. However, it will be extended to two additional case studies selected according to their relevance in relation to the goal of the targeted analysis (likely including one of the Member States having joined in 2004 or one of the current accessing countries). The identification of the two additional case studies will be decided during the implementation phase in cooperation between the TPG and the stakeholders. | [
"Human Mobility, Environment, and Space",
"Institutions, Governance and Legal Systems"
]
|
10.1016/j.zemedi.2013.02.002 | Grating-based X-ray phase contrast for biomedical imaging applications | In this review article we describe the development of grating-based X-ray phase-contrast imaging, with particular emphasis on potential biomedical applications of the technology. We review the basics of image formation in grating-based phase-contrast and dark-field radiography and present some exemplary multimodal radiography results obtained with laboratory X-ray sources. Furthermore, we discuss the theoretical concepts to extend grating-based multimodal radiography to quantitative transmission, phase-contrast, and dark-field scattering computed tomography. | [
"Physical and Analytical Chemical Sciences",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Materials Engineering"
]
|
10.3847/0004-637X/826/1/34 | Expanding Molecular Bubble Surrounding Tyco S Supernova Remnant Sn 1572 Observed With The Iram 30 M Telescope Evidence For A Single Degenerate Progenitor | Whether the progenitors of SNe Ia are single-degenerate or double-degenerate white dwarf (WD) systems is a highly debated topic. To address the origin of Tycho's Type Ia supernova remnant (SNR), SN 1572, we have carried out a (CO)-C-12 J = 2-1 mapping and a 3 mm line survey toward the remnant using the IRAM 30 m telescope. We show that Tycho is surrounded by a clumpy molecular bubble at a local standard of rest velocity of similar to 61 km s(-1), which expands at a speed of similar to 4. 5 km s(-1) and has a mass of similar to 220 M-circle dot (at the distance of 2. 5 kpc). Enhanced (CO)-C-12 J = 2-1 line emission relative to (CO)-C-12 J = 1-0 emission and possible line broadenings (in velocity range -64 to -60 km s(-1)) are found at the northeastern boundary of the SNR, where the shell is deformed and decelerated. These features, combined with the morphological correspondence between the expanding molecular bubble and Tycho, suggest that the SNR is associated with the bubble at the velocity range -66 to -57 km s(-1). The most plausible origin for the expanding bubble is the fast outflow (with velocity of hundreds km s(-1)) driven from the vicinity of a WD as it accreted matter from a nondegenerate companion star. The SNR has been expanding in the low-density wind-blown bubble, and the shock wave has just reached the molecular cavity wall. This is the first unambiguous detection of an expanding bubble driven by the progenitor of a Type Ia SNR, which constitutes evidence for a single-degenerate progenitor for this SN Ia. | [
"Universe Sciences",
"Physical and Analytical Chemical Sciences"
]
|
10.1021/acsnano.8b01387 | Transparent, Flexible Silicon Nanostructured Wire Networks with Seamless Junctions for High-Performance Photodetector Applications | Optically transparent photodetectors are crucial in next-generation optoelectronic applications including smart windows and transparent image sensors. Designing photodetectors with high transparency, photoresponsivity, and robust mechanical flexibility remains a significant challenge, as is managing the inevitable trade-off between high transparency and strong photoresponse. Here we report a scalable method to produce flexible crystalline Si nanostructured wire (NW) networks fabricated from silicon-on-insulator (SOI) with seamless junctions and highly responsive porous Si segments that combine to deliver exceptional performance. These networks show high transparency (~92% at 550 nm), broadband photodetection (350 to 950 nm) with excellent responsivity (25 A/W), optical response time (0. 58 ms), and mechanical flexibility (1000 cycles). Temperature-dependent photocurrent measurements indicate the presence of localized electronic states in the porous Si segments, which play a crucial role in light harvesting and photocarrier generation. The scalable low-cost approach based on SOI has the potential to deliver new classes of flexible optoelectronic devices, including next-generation photodetectors and solar cells. | [
"Condensed Matter Physics",
"Synthetic Chemistry and Materials",
"Materials Engineering",
"Systems and Communication Engineering"
]
|
10.1016/bs.aivir.2019.07.003 | Structural mass spectrometry goes viral | Over the last 20 years, mass spectrometry (MS), with its ability to analyze small sample amounts with high speed and sensitivity, has more and more entered the field of structural virology, aiming to investigate the structure and dynamics of viral proteins as close to their native environment as possible. The use of non-perturbing labels in hydrogen-deuterium exchange MS allows for the analysis of interactions between viral proteins and host cell factors as well as their dynamic responses to the environment. Cross-linking MS, on the other hand, can analyze interactions in viral protein complexes and identify virus-host interactions in cells. Native MS allows transferring viral proteins, complexes and capsids into the gas phase and has broken boundaries to overcome size limitations, so that now even the analysis of intact virions is possible. Different MS approaches not only inform about size, stability, interactions and dynamics of virus assemblies, but also bridge the gap to other biophysical techniques, providing valuable constraints for integrative structural modeling of viral complex assemblies that are often inaccessible by single technique approaches. In this review, recent advances are highlighted, clearly showing that structural MS approaches in virology are moving towards systems biology and ever more experiments are performed on cellular level. | [
"Physical and Analytical Chemical Sciences",
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
219573 | A low-cost disposable electrochemical biosensor for point of care (poc) hypolactasia diagnostic testing | LACTOPOC is a multidisciplinary research and training programme targeted to provide Dr. Macia-Gonzalez, an expert in electrochemical analytical platforms design, with new entrepreneurial and scientific skills on translation of innovative biosensor technology into Point of Care (POC) diagnostic devices.
LACTOPOC main scientific goal is to develop a low-cost and highly reproducible biosensor manufacturing platform technology for POC hypolactasia diagnostic testing. The project is based on the combination of two-well established analytical tools, i.e. paper-based microfluidics and electrochemistry, together with mass-manufacturing technologies for innovative design such wax and screen printing.
Hypolactasia is related to low levels or reduced activity of intestinal lactase, the enzyme responsible for the hydrolysis of lactose during its digestion. Undigested lactose after intake of dairy products is then accumulated in the intestine causing flatulence, abdominal pain and diarrhea in the individuals suffering from this malfunction. Despite it affects over half of the world population, its diagnosis remains challenging because associated symptoms are not specific and available methods for its diagnosis are unspecific and rely on trained staff and complex equipment.
LACTOPOC will bring forward the technology developed by OSASEN for determination of D-xylose in urine and venous blood samples based on an electrochemical biosensor lab-prototype into a robust POC device with high sensitivity and reproducibility. The device will be able to detect and quantify accurately minimum D-Xylose concentration levels in a simple drop of human capillary blood sample. This novel POC biosensor device will assist LacTEST®, a non-invasive diagnostic test based on the synthetic analog gaxilose recently developed by VenterPharma, to become the first promising POC diagnostic testing for hypolactasia available in the market, leveraging their impact on patients and health care providers. | [
"Physical and Analytical Chemical Sciences",
"Products and Processes Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1038/NMAT3260 | On The Molecular Origin Of Supercapacitance In Nanoporous Carbon Electrodes | Lightweight, low-cost supercapacitors with the capability of rapidly storing a large amount of electrical energy can contribute to meeting continuous energy demands and effectively levelling the cyclic nature of renewable energy sources1. The excellent electrochemical performance of supercapacitors is due to a reversible ion adsorption in porous carbon electrodes. Recently, it was demonstrated that ions from the electrolyte could enter sub nanometre pores, greatly increasing the capacitance2, 3, 4. However, the molecular mechanism of this enhancement remains poorly understood. Here we provide the first quantitative picture of the structure of an ionic liquid adsorbed inside realistically modelled microporous carbon electrodes. We show how the separation of the positive and negative ions occurs inside the porous disordered carbons, yielding much higher capacitance values (125 F g−1) than with simpler electrode geometries5. The proposed mechanism opens the door for the design of materials with improved energy storage capabilities. It also sheds new light on situations where ion adsorption in porous structures or membranes plays a role. | [
"Condensed Matter Physics",
"Physical and Analytical Chemical Sciences",
"Synthetic Chemistry and Materials"
]
|
10.1098/rsbl.2016.0961 | Increased food availability raises eviction rate in a cooperative breeding mammal | In group-living mammals, the eviction of subordinate females from breeding groups by dominants may serve to reduce feeding competition or to reduce breeding competition. Here, we combined both correlational and experimental approaches to investigate whether increases in food intake by dominant females reduces their tendency to evict subordinate females in wild meerkats (
Suricata suricatta
). We used 20 years of long-term data to examine the association between foraging success and eviction rate, and provisioned dominant females during the second half of their pregnancy, when they most commonly evict subordinates. We show that rather than reducing the tendency for dominants to evict subordinates, foraging success of dominant females is positively associated with the probability that pregnant dominant females will evict subordinate females and that experimental feeding increased their rates of eviction. Our results suggest that it is unlikely that the eviction of subordinate females serves to reduce feeding competition and that its principal function may be to reduce reproductive competition. The increase in eviction rates following experimental feeding also suggests that rather than feeding competition, energetic constraints may normally constrain eviction rates. | [
"Environmental Biology, Ecology and Evolution",
"Integrative Biology: from Genes and Genomes to Systems",
"Physiology in Health, Disease and Ageing"
]
|
W2050404753 | Modeling Challenges in the Synthetic Biology of Secondary Metabolism | The successful engineering of secondary metabolite production relies on the availability of detailed computational models of metabolism. In this brief review we discuss the types of models used for synthetic biology and their application for the engineering of metabolism. We then highlight some of the major modeling challenges, in particular the need to make informative model predictions based on incomplete and uncertain information. This issue is particularly pressing in the synthetic biology of secondary metabolism, due to the genetic diversity of microbial secondary metabolite producers, the difficulty of enzyme-kinetic characterization of the complex biosynthetic machinery, and the need for engineered pathways to function efficiently in heterologous hosts. We argue that an explicit quantitative consideration of the resulting uncertainty of metabolic models can lead to more informative predictions to guide the design of improved production hosts for bioactive secondary metabolites. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Biotechnology and Biosystems Engineering"
]
|
10.1038/nm.4420 | A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle | Over 40% of microRNAs (miRNAs) are located in introns of protein-coding genes, and many of these intronic miRNAs are co-regulated with their host genes1,2. In such cases of co-regulation, the products of host genes and their intronic miRNAs can cooperate to coordinately regulate biologically important pathways3,4. Therefore, we screened intronic miRNAs dysregulated in the livers of mouse models of obesity to identify previously uncharacterized protein-coding host genes that may contribute to the pathogenesis of obesityassociated insulin resistance and type 2 diabetes mellitus. Our approach revealed that expression of both the gene encoding ectodysplasin A (Eda), the causal gene in X-linked hypohidrotic ectodermal dysplasia (XLHED)5, and its intronic miRNA, miR-676, was increased in the livers of obese mice. Moreover, hepatic EDA expression is increased in obese human subjects and reduced upon weight loss, and its hepatic expression correlates with systemic insulin resistance. We also found that reducing miR-676 expression in db/db mice increases the expression of proteins involved in fatty acid oxidation and reduces the expression of inflammatory signaling components in the liver. Further, we found that Eda expression in mouse liver is controlled via PPAR and RXR, increases in circulation under conditions of obesity, and promotes JNK activation and inhibitory serine phosphorylation of IRS1 in skeletal muscle. In accordance with these findings, gain- and loss-of-function approaches reveal that liver-derived EDA regulates systemic glucose metabolism, suggesting that EDA is a hepatokine that can contribute to impaired skeletal muscle insulin sensitivity in obesity. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1051/0004-6361/201935469 | Impact Of Nonconvergence And Various Approximations Of The Partition Function On The Molecular Column Densities In The Interstellar Medium | We emphasize that the completeness of the partition function, that is, the use of a converged partition function at the typical temperature range of the survey, is very important to decrease the uncertainty on this quantity and thus to derive reliable interstellar molecular densities. In that context, we show how the use of different approximations for the rovibrational partition function together with some interpolation and/or extrapolation procedures may affect the estimate of the interstellar molecular column density. For that purpose, we apply the partition function calculations to astronomical observations performed with the IRAM-30m telescope towards the NGC7538-IRS1 source of two N-bearing molecules: isocyanic acid (HNCO, a quasilinear molecule) and methyl cyanide (CH$_3$CN, a symmetric top molecule). The case of methyl formate (HCOOCH$_3$), which is an asymmetric top O-bearing molecule containing an internal rotor is also discussed. Our analysis shows that the use of different partition function approximations leads to relative differences in the resulting column densities in the range 9 to 43\%. Thus, we expect this work to be relevant for surveys of sources with temperatures higher than 300~K and to observations in the infrared. | [
"Physical and Analytical Chemical Sciences",
"Universe Sciences"
]
|
TW 93128627 A | Logical partitioning in redundant systems | Provided are a method, system, and article of manufacture, wherein a plurality of processing nodes in a storage system are partitioned into a plurality of logical processing units, and wherein the plurality of logical processing units can respond to I/O requests from a host coupled to the storage system. At least two logical processing units are grouped, wherein data in a first storage coupled to a first logical processing unit of the least two logical processing units is mirrored by data in a second storage coupled to the second logical processing unit of the at least two logical processing units. In response to a failure of the first logical processing unit, an I/O request from the host is responded to via the second logical processing unit. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
10.1098/rsbl.2017.0660 | Mechanistic models versus machine learning, a fight worth fighting for the biological community? | Ninety per cent of the world's data have been generated in the last 5 years ( Machine learning: the power and promise of computers that learn by example . Report no. DES4702. Issued April 2017. Royal Society). A small fraction of these data is collected with the aim of validating specific hypotheses. These studies are led by the development of mechanistic models focused on the causality of input–output relationships. However, the vast majority is aimed at supporting statistical or correlation studies that bypass the need for causality and focus exclusively on prediction. Along these lines, there has been a vast increase in the use of machine learning models, in particular in the biomedical and clinical sciences, to try and keep pace with the rate of data generation. Recent successes now beg the question of whether mechanistic models are still relevant in this area. Said otherwise, why should we try to understand the mechanisms of disease progression when we can use machine learning tools to directly predict disease outcome? | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Integrative Biology: from Genes and Genomes to Systems",
"Computer Science and Informatics"
]
|
10.1117/12.2249978 | Lock In Thermography Approach For Imaging The Efficiency Of Light Emitters And Optical Coolers | Developing optical cooling technologies requires access to reliable efficiency measurement techniques and ability to detect spatial variations in the efficiency and light emission of the devices. We investigate the possibility to combine the calorimetric efficiency measurement principles with lock-in thermography (LIT) and conventional luminescence microscopy to enable spatially resolved measurement of the efficiency, current spreading and local device heating of double diode structures (DDS) serving as test vessels for developing thermophotonic cooling devices. Our approach enables spatially resolved characterization and localization of the losses of the double diode structures as well as other light emitting semiconductor devices. In particular, the approach may allow directly observing effects like current crowding and surface recombination on the light emission and heating of the DDS devices. | [
"Physical and Analytical Chemical Sciences",
"Condensed Matter Physics"
]
|
10.1016/j.neuron.2016.07.033 | Actin- and Myosin-Dependent Vesicle Loading of Presynaptic Docking Sites Prior to Exocytosis | Variance analysis of postsynaptic current amplitudes suggests the presence of distinct docking sites (also called release sites) where vesicles pause before exocytosis. Docked vesicles participate in the readily releasable pool (RRP), but the relation between docking site number and RRP size remains unclear. It is also unclear whether all vesicles of the RRP are equally release competent, and what cellular mechanisms underlie RRP renewal. We address here these questions at single glutamatergic synapses, counting released vesicles using deconvolution. We find a remarkably low variance of cumulative vesicle counts during action potential trains. This, combined with Monte Carlo simulations, indicates that vesicles transit through two successive states before exocytosis, so that the RRP is up to 2-fold higher than the docking site number. The transition to the second state has a very rapid rate constant, and is specifically inhibited by latrunculin B and blebbistatin, suggesting the involvement of actin and myosin. | [
"Neuroscience and Disorders of the Nervous System",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
interreg_3362 | Regional branch observatories of intelligent markets in Central Europe monitoring technology trends and market developments in the area of smart specializations | Common challenge faced by all PPs is a missing link between the Regional Innovation Strategies(RIS) monitoring and real needs of smart specialisations(SmartS) of end users. There is no methodical support on national level and no tools for benchmarking. Each region gathers data but in different structure,sometimes not having any monitoring institution.
Main objective of the projects is to fill in this gap and build a link between the RIS and end users.
This can be done by elaborating model for Regional Branch Observatories(RO),equipped with a set of monitoring and benchmarking tools, available to all RIS stakeholders and intelligent markets’ actors.
As the project will coincide with mid-term evaluation of RIS, PPs will elaborate policy recommendations for EU commission, based on international pilot projects and research results; a network of RO will enable national and EU authorities to monitor RIS implementation across EU. Based on SmartS in PPs regions specific technology areas were selected, for which tools and knowledge management services for RO will be elaborated -health, life science, ICT, future services, sustainable production technics and Industry 4.0. Project approach ensures defining needs of all RIS stakeholders, as representatives of target groups(TG) from each PP region will be involved in the process(participatory approach). Involvement of those TGs will ensure results elaborated cover all RIS markets in CE.
The RIS and SmartS topics were already tackled by several projects within Interreg frames and outside, however none of them was concentrated and dealt with monitoring. This missing part becomes a significant problem concerning the mid-term evaluation of RIS and need for changes in direction EU policy is heading. This steps can be done only within the frames of international actions. CE regions involved in this project cover 32% of EU member states,which gives significant probe that can be used as a benchmark for the entire EU. | [
"Individuals, Markets and Organisations",
"Institutions, Governance and Legal Systems",
"Computer Science and Informatics"
]
|
10.1016/j.matdes.2020.108742 | Homotypic targeting and drug delivery in glioblastoma cells through cell membrane-coated boron nitride nanotubes | Glioblastoma multiforme (GBM) is one of the most aggressive types of brain cancer, characterized by rapid progression, resistance to treatments, and low survival rates; the development of a targeted treatment for this disease is still today an unattained objective. Among the different strategies developed in the latest few years for the targeted delivery of nanotherapeutics, homotypic membrane-membrane recognition is one of the most promising and efficient. In this work, we present an innovative drug-loaded nanocarrier with improved targeting properties based on the homotypic recognition of GBM cells. The developed nanoplatform consists of boron nitride nanotubes (BNNTs) loaded with doxorubicin (Dox) and coated with cell membranes (CM) extracted from GBM cells (Dox-CM-BNNTs). We demonstrated as Dox-CM-BNNTs are able to specifically target and kill GBM cells in vitro, leaving unaffected healthy brain cells, upon successful crossing an in vitro blood-brain barrier model. The excellent targeting performances of the nanoplatform can be ascribed to the protein component of the membrane coating, and proteomic analysis of differently expressed membrane proteins present on the CM of GBM cells and of healthy astrocytes allowed the identification of potential candidates involved in the process of homotypic cancer cell recognition. | [
"Materials Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Synthetic Chemistry and Materials",
"Cell Biology, Development, Stem Cells and Regeneration"
]
|
US 2011/0045654 W | PRESERVATIVE FREE BIMATOPROST AND TIMOLOL SOLUTIONS | The present invention is directed to preservative-free solutions of bimatoprost and timolol for lowering intra-ocular pressure and treatment of glaucoma. | [
"Products and Processes Engineering",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1068/a130358p | Employment Insecurity and First-Time Homeownership: Evidence from Twenty-Two European Countries | Many young people in Europe face employment insecurity, a condition which will likely persist following the global economic downturn that started with the financial crisis of 2007–08. Previous research has shown that employment insecurity impedes the entry into homeownership. It is, however, less clear how this delayed entry into homeownership is filtered by contextual arrangements at the country level. Using longitudinal data from the EU Statistics on Income and Living Conditions (2007–11), we confirm prior findings on the negative effect of employment insecurity across European countries. We also find contextual variations. In more marketised housing provision systems in Northern and Western Europe, where mortgages are readily available to those in secure employment, the negative effect of employment insecurity (relative to having secure employment) on the transition into homeownership is accentuated. In more familialistic systems with strongly regulated labour markets in Southern Europe, the difference between young people in different employment situations is smaller, yet still significant. We find similar-sized differences between those in insecure and secure employment in the Baltic States, but not in the other Eastern and Central European countries, where housing shortages impede the entry into homeownership for young people across different employment positions. | [
"Human Mobility, Environment, and Space",
"Individuals, Markets and Organisations"
]
|
W2018521651 | Recurrent lentigo maligna melanoma commingling the tumour nests of a basal cell carcinoma | <h2>Summary</h2> There are various types and combinations of coexisting cutaneous neoplasms which have been documented in the past but are uncommon. In this report we describe a case of basal cell carcinoma (BCC) colonised by recurrent lentigo maligna melanoma. A review of the literature has established the coexistence of lentigo maligna and BCC in six cases. The unusual combination of melanoma and BCC poses a therapeutic and prognostic dilemma. BCC is known to have a favourable outcome whereas melanoma tends to behave in a more aggressive manner leading to a less favourable outcome. There are conflicting views as to whether these lesions should be treated as BCC's or lentigo maligna melanoma. Our case appears to be unique, in that it was a recurrent lentigo maligna melanoma which was colonising the BCC. We treated our patient with wide local excision and full thickness skin graft and will continue to observe him on an outpatient basis. There needs to be long term follow up of a larger number of patients for us to truly appreciate the biological significance of parasitism of BCC by lentigo maligna melanoma. | [
"Physiology in Health, Disease and Ageing",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1371/journal.ppat.1001166 | Phylodynamics and Human-mediated dispersal of a zoonotic virus | Understanding the role of humans in the dispersal of predominately animal pathogens is essential for their control. We used newly developed Bayesian phylogeographic methods to unravel the dynamics and determinants of the spread of dog rabies virus (RABV) in North Africa. Each of the countries studied exhibited largely disconnected spatial dynamics with major geopolitical boundaries acting as barriers to gene flow. Road distances proved to be better predictors of the movement of dog RABV than accessibility or raw geographical distance, with occasional long distance and rapid spread within each of these countries. Using simulations that bridge phylodynamics and spatial epidemiology, we demonstrate that the contemporary viral distribution extends beyond that expected for RABV transmission in African dog populations. These results are strongly supportive of human-mediated dispersal, and demonstrate how an integrated phylogeographic approach will turn viral genetic data into a powerful asset for characterizing, predicting, and potentially controlling the spatial spread of pathogens. | [
"Environmental Biology, Ecology and Evolution",
"Immunity, Infection and Immunotherapy",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
10.1039/c8sm00949j | Stress-dependent amplification of active forces in nonlinear elastic media | Forces generated by molecular motors and contractile cells can be dramatically amplified by the nonlinear elasticity of the surrounding medium. | [
"Condensed Matter Physics"
]
|
10.1016/j.celrep.2017.02.046 | Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate | The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3′-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3′-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport. Surprisingly, these proteins all bind capped RNAs without strong preferences for given transcripts, and their steady-state binding correlates poorly with their function. Despite this, PHAX and ZC3H18 compete for CBC binding and we demonstrate that this competitive binding is functionally relevant. We further show that CBC-containing complexes are short lived in vivo, and we therefore suggest that RNA fate involves the transient formation of mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions"
]
|
W1976024539 | Metabolically versatile large-genome prokaryotes | Although versatile microorganisms are critical in industrial applications where the ability to cope with change and carry out complex tasks is needed, very little is in fact known about the evolutionary and ecological meanings of versatility in prokaryotes. Testing the hypothesis that a large genome size is a prerequisite for versatility in prokaryotes, we found that putatively versatile prokaryotes are phylogenetically and ecologically diverse and indeed include many well known and commercially relevant versatile microorganisms. Despite individual differences in metabolic abilities, a common trait of large-genome prokaryotes appears that they have gained their large genomes as an evolutionary response to nutrient-scarce and/or variable environments. This insight seriously questions the ability of traditional microbiology methods to isolate versatile prokaryotes and casts doubt on the ecological relevance of knowledge based on the study of specialists. | [
"Environmental Biology, Ecology and Evolution",
"Biotechnology and Biosystems Engineering",
"Integrative Biology: from Genes and Genomes to Systems"
]
|
10.1002/anie.201412204 | A synthetic erectile optogenetic stimulator enabling blue-light-inducible penile erection | Precise spatiotemporal control of physiological processes by optogenetic devices inspired by synthetic biology may provide novel treatment opportunities for gene- and cell-based therapies. An erectile optogenetic stimulator (EROS), a synthetic designer guanylate cyclase producing a blue-light-inducible surge of the second messenger cyclic guanosine monophosphate (cGMP) in mammalian cells, enabled blue-light-dependent penile erection associated with occasional ejaculation after illumination of EROS-transfected corpus cavernosum in male rats. Photostimulated short-circuiting of complex psychological, neural, vascular, and endocrine factors to stimulate penile erection in the absence of sexual arousal may foster novel advances in the treatment of erectile dysfunction. | [
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Physiology in Health, Disease and Ageing",
"Biotechnology and Biosystems Engineering"
]
|
10.1145/2674005.2675014 | Midas Empowering 802 11Ac Networks With Multiple Input Distributed Antenna Systems | Next generation WLANs (802. 11ac) are undergoing a major shift in their communication paradigm with the introduction of multi-user MIMO (MU-MIMO), transitioning from single-user to multi-user communications. We argue that the conventional AP deployment model of co-located antennas as well as their PHY and MAC mechanisms are not designed to realize the complete potential of MU-MIMO. We propose to leverage distributed antenna systems (DAS) to empower next generation 802. 11ac networks. We highlight the multitude of benefits that DAS brings to MU-MIMO and 802. 11ac in general. However, several challenges arise in the process of realizing these benefits in practice, where avoiding client modifications and making only minimal software modifications to APs is important to enable rapid adoption. Towards addressing these challenges, we present the design and implementation of MIDAS, the Multiple-Input Distributed Antenna System. MIDAS couples a DAS deployment of AP antennas with a suite of novel yet standards-compatible mechanisms at the PHY and MAC layers that best leverage the DAS deployment to maximize 802. 11ac performance. Our WARP-based experimental evaluation demonstrates MIDAS's ability to significantly boost the performance of current 802. 11ac design, demonstrating throughput gains over 802. 11ac MU-MIMO for 100-200%, while remaining amenable to commercial adoption. | [
"Systems and Communication Engineering",
"Computer Science and Informatics"
]
|
233174 | Computations by Neurons and Populations in Visual Cortex | Neurons in primary visual cortex (area V1) receive feedforward inputs from thalamic afferents and lateral inputs from other cortical neurons. Little is known about how these components interact to determine the responses of a V1 neuron. One camp ascribes most responses to feedforward mechanisms. The other camp ascribes them mostly to lateral interactions. We propose that these two apparently opposed views can be simply reconciled in a single framework. We hypothesize that area V1 can operate both in a feedforward regime and in a lateral interaction regime, depending on the nature of the stimulus and on the cognitive task at hand, and that the transition from one regime to the other is governed by synaptic inhibition. We will test these hypotheses by recording from individual V1 neurons while monitoring the activity of nearby populations of cortical neurons via multiprobe electrodes. In Aim 1 we will relate the activity of V1 neurons to that of nearby populations. We will use simple measures of correlation and nonlinear models that predict individual spikes to measure how responses depend on a feedforward contribution (the receptive field ) and on a lateral contribution (the connection field ). We will test our first hypothesis, concerning the role of the stimulus in changing this dependence. In Aim 2 we will extend these results to a behaving animal. We will record from V1 of mice performing a 2-alternative forced-choice psychophysical task, and we will test our second hypothesis, concerning the role of the cognitive task in determining the operating regime of the cortex. In Aim 3 we will seek a biophysical interpretation of the functional mechanisms and effective connectivity revealed by the previous Aims. We will test our third hypothesis, concerning the role of synaptic inhibition. The tools involved will include intracellular recordings and optical stimulation in transgenic mice whose cortical neurons are sensitive to light. | [
"Neuroscience and Disorders of the Nervous System"
]
|
10.1186/s40478-019-0714-6 | Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models | Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments. In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors. SIGNIFICANCE: Delta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs. | [
"Prevention, Diagnosis and Treatment of Human Diseases",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Immunity, Infection and Immunotherapy",
"Neuroscience and Disorders of the Nervous System"
]
|
10.1038/srep43844 | OM-85 is an immunomodulator of interferon-β production and inflammasome activity | The inflammasome-IL-1 axis and type I interferons (IFNs) have been shown to exert protective effects upon respiratory tract infections. Conversely, IL-1 has also been implicated in inflammatory airway pathologies such as asthma and chronic obstructive pulmonary disease (COPD). OM-85 is a bacterial extract with proved efficacy against COPD and recurrent respiratory tract infections, a cause of co-morbidity in asthmatic patients. We therefore asked whether OM-85 affects the above-mentioned innate immune pathways. Here we show that OM-85 induced interferon-β through the Toll-like receptor adaptors Trif and MyD88 in bone marrow-derived dendritic cells. Moreover, it exerted a dual role on IL-1 production; on the one hand, it upregulated proIL-1β and proIL-1α levels in a MyD88-dependent manner without activating the inflammasome. On the other hand, it repressed IL-1β secretion induced by alum, a well-known NLRP3 activator. In vivo, OM-85 diminished the recruitment of inflammatory cells in response to peritoneal alum challenge. Our findings therefore suggest that OM-85 favors a protective primed state, while dampening inflammasome activation in specific conditions. Taken together, these data bring new insights into the mechanisms of OM-85 action on innate immune pathways and suggest potential explanations for its efficacy in the treatment of virus-induced airway diseases. | [
"Immunity, Infection and Immunotherapy",
"Molecules of Life: Biological Mechanisms, Structures and Functions",
"Prevention, Diagnosis and Treatment of Human Diseases"
]
|
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