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10.1093/nar/gkq801
Molecular basis of engineered meganuclease targeting of the endogenous human RAG1 locus
Homing endonucleases recognize long target DNA sequences generating an accurate double-strand break that promotes gene targeting through homologous recombination. We have modified the homodimeric I-CreI endonuclease through protein engineering to target a specific DNA sequence within the human RAG1 gene. Mutations in RAG1 produce severe combined immunodeficiency (SCID), a monogenic disease leading to defective immune response in the individuals, leaving them vulnerable to infectious diseases. The structures of two engineered heterodimeric variants and one single-chain variant of I-CreI, in complex with a 24-bp oligonucleotide of the human RAG1 gene sequence, show how the DNA binding is achieved through interactions in the major groove. In addition, the introduction of the G19S mutation in the neighborhood of the catalytic site lowers the reaction energy barrier for DNA cleavage without compromising DNA recognition. Gene-targeting experiments in human cell lines show that the designed single-chain molecule preserves its in vivo activity with higher specificity, further enhanced by the G19S mutation. This is the first time that an engineered meganuclease variant targets the human RAG1 locus by stimulating homologous recombination in human cell lines up to 265bp away from the cleavage site. Our analysis illustrates the key features for la carte procedure in protein-DNA recognition design, opening new possibilities for SCID patients whose illness can be treated ex vivo.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Immunity, Infection and Immunotherapy", "Integrative Biology: from Genes and Genomes to Systems", "Prevention, Diagnosis and Treatment of Human Diseases" ]
864877
Deep Earth Mantle Phase Transition Maps: Studied by Time-Resolved Experiments
Processes in Earth's lower mantle govern our planet's inner dynamics and control surface plate tectonics. As such, a quantitative understanding of the physical and chemical properties of the lower mantle is pivotal to model Earth’s dynamic evolution, including the long-term chemical interactions between mantle and atmosphere that are vital to the development of habitability on Earth, and possibly other planets. While seismic tomography is providing increasingly detailed three-dimensional maps of the lower mantle, the interpretation of tomographic models to elucidate key factors such as mantle geochemical heterogeneity or dynamic mantle flow processes has proven to be highly ambiguous. All evidence points to phase transitions being the missing link needed to converge to a consistent interpretation of seismic observations. The same phase transitions also play a key role in governing mantle dynamics. But even fundamental properties, such as the location of major phase transition boundaries in Earth’s mantle, are poorly constrained. This is because the parameter space (pressure-temperature-composition) is huge and experimental measurements at planetary interior conditions are extremely slow. DEEP-MAPS will employ a novel class of time-resolved high-pressure/-temperature experiments that reduce by several orders of magnitude the time for key experiments. This will allow DEEP-MAPS to map lower mantle phase transitions, their impact on physical properties and their seismic signature with practically continuous coverage in relevant pressure-temperature-composition-space. DEEP-MAPS will further probe the time-dependence of phase transitions, transforming our understanding of how to scale from laboratory measurements to geophysical processes. DEEP-MAPS will provide a step-change in our ability to interpret mantle seismic observables and to quantify the geodynamic impact of mantle phase transitions, ultimately leading to a holistic picture of Earth’s deep mantle.
[ "Condensed Matter Physics", "Earth System Science" ]
10.1101/676189
Tailoring Cryo Electron Microscopy Grids By Photo Micropatterning For In Cell Structural Studies
Abstract Spatially-controlled cell adhesion on electron microscopy (EM) supports remains a bottleneck in specimen preparation for cellular cryo-electron tomography. Here, we describe contactless and mask-free photo-micropatterning of EM grids for site-specific deposition of extracellular matrix-related proteins. We attained refined cell positioning for micromachining by cryo-focused ion beam milling. Complex patterns generated predictable intracellular organization, allowing direct correlation between cell architecture and in-cell 3D-structural characterization of the underlying molecular machinery.
[ "Materials Engineering", "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
2730710
Ofi, pool management at your fingertips!
In ensuring safe, hygienic swimming environment, spas and pools need to be frequently checked and adjusted to maintain optimum levels of pH, chlorine/bromine/salt and water hardness. As most pool/spa owners perform the checks manually and constantly using visual analysis colorimetry-based solutions, users do not always get accurate results, posing health and wellness risk when corrective chemicals are added based on inaccurate readings. Delays in water analysis leads to increased quantities of corrective chemical products (>20%), wall damages, continuously running filtration systems, all resulting in increased maintenance costs. There is need for a solution that can leverage the home automation and connected device trend to remotely control, monitor and maintain water quality with minimal direct visits to the pool and reduce annual maintenance cost. Asamgo, a passionate French company has developed Ofi, is an intelligent floating device which floats on the surface of the pool/spa analysing the pH, chlorine/bromine/salt, alkalinity and water hardness values of the water in real time via the electrochemical analysis method. These values are accurately returned on Smartphone App and are accompanied by advice on maintenance actions to be carried out if necessary. Our target customers are private pool and spa owners, pool professionals, pool maintenance distributors and retailers. Ofi eliminates the recurring manual water analysis tasks and will offer 20% reduction of amounts of chemicals required for ideal pool condition, real-time feedback on status of the pool and immediate notification when levels are not right, 99.99% accuracy on recommended remedy measures and reduced overall maintenance costs. In addition, maintenance products recommended by Ofi can be ordered through the Ofi App. Within a 4-year period, we expect to generate a cumulative revenue of €20.10-million, gross profit of €7.04-million while creating a total of 13 jobs.
[ "Products and Processes Engineering", "Systems and Communication Engineering", "Physical and Analytical Chemical Sciences", "Computer Science and Informatics" ]
10.1016/j.devcel.2017.08.002
YAP/TAZ Orchestrate VEGF Signaling during Developmental Angiogenesis
Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. However, the signal transduction pathways culminating in the biological consequences of VEGF signaling are only partially understood. Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial signal transducers to mediate VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium-specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality. Mechanistically, we show that VEGF activates YAP/TAZ via its effects on actin cytoskeleton and that activated YAP/TAZ induce a transcriptional program to further control cytoskeleton dynamics and thus establish a feedforward loop that ensures a proper angiogenic response. Lack of YAP/TAZ also results in altered cellular distribution of VEGFR2 due to trafficking defects from the Golgi apparatus to the plasma membrane. Altogether, our study identifies YAP/TAZ as central mediators of VEGF signaling and therefore as important regulators of angiogenesis. Wang et al. identify YAP/TAZ as essential co-transcription factors in endothelial cells during developmental angiogenesis. They describe that YAP/TAZ are activated by VEGF and that their activity is needed for transducing the VEGF signal into a specific transcriptional program, required for a full angiogenic response.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
2717441
Eu patient- centric clinical trial platform
EU-PEARL has the ambition of transforming the current approach of conducting single-compound clinical trials into the use of cross-company Integrated Research Platforms (IRPs), taking into consideration both patients’ interests and the opportunities from novel molecules for addressing medical needs. Patient-centric data and knowledge sharing have the potential to accelerate the development of new treatments and reduce the operational costs of clinical trials. EU-PEARL will improve clinical effectiveness, patients’ satisfaction and societal access to timely and affordable medicines and it will shape the clinical trials of the future. This will change the industry paradigm from competition to cooperation in four disease areas and provide the framework for designing IRPs in other disease areas. The main objectives of EU-PEARL are: (1) To create a reusable, accessible and sustainable modular IRP for the design and execution of patient-centric, cross- company IRP in any disease area with unmet needs; (2) To set up the open, dynamic, patient inclusive IRP governance structure that will manage the appropriate regulatory, ethical, legal, statistical and data utilisation requirements of the IRP; (3) To disseminate and exploit the EU-PEARL paradigm through the provision of the necessary common tools, procedures, expertise and operational skills working to the highest scientific, regulatory and ethical standards and best practices, developed jointly by public and industry partners in a consensus-based approach; and (4) To create trial-ready IRP networks in the four disease areas of Major Depressive Disorder (MDD), Tuberculosis (TB), Non-Alcoholic Steatohepatitis (NASH) and Neurofibromatosis (NF).
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Computer Science and Informatics", "Institutions, Governance and Legal Systems" ]
644574
Encountering diplomacy in early modern southeast asia
This research project is a study in global history. It explores how diplomatic practices and foreign relations were shaped in the pluralistic, multi-centric, open geography of maritime Southeast Asia during the seventeenth and eighteenth century. In this period, exchange between local polities and aspiring European colonial powers flourished. The project uses the rich history of negotiations and cross-cultural communication between local Southeast Asian polities and various actors from Europe to integrate practices of balancing power relations and local indigenous traditions into a nuanced global history of diplomacy. Although foreign relations are widely regarded as an important vector for cultural exchange, and while embassies have emerged as a favoured site for studying cultural encounters, little is known about the ways in which transregional interactions shaped the very principles and practices of diplomatic dealings over the course of this transformative period. The project will introduce the concept of the diplomatic encounter which allows to study relevant processes and practices in their own time and under consideration of their specific political culture. It compares different acts of negotiation including the foreign relations of insular Muslim chiefdoms, colonial rivalries, the diplomatic strategies of small city states and the impact of expanding empires in the region. Re-addressing early modern diplomatic encounters in South East Asia in diverse sources written in various languages will thus serve to overcome binaries in diplomatic history and ultimately contribute to a new narrative of diplomatic history as demanded by leading scholars in the field. The project will be hosted at the Centre for Concurrences in Colonial and Postcolonial Studies, a leading interdisciplinary research environment with an existing and steadily growing focus on Southeast Asia.
[ "The Study of the Human Past", "Institutions, Governance and Legal Systems" ]
W153135129
The Use of Cortical Heterologous Sheets for Sinus Lift Bone Grafting: A Modification of Tulasne's Technique with 7-Year Follow-up
In this article, the authors describe their experience with using cortical deantigenated equine bone sheets in sinus lift grafting procedures performed on 23 patients. The technique employed resembles that described by Tulasne but avoids the need for using harvested calvaria bone and introduces some additional operating variants. The use of heterologous cortical bone sheets effectively managed even large lacerations of the Schneiderian membrane and allowed for immediate stabilization of the heterologous bone granules. Average histomorphometric values for bone cores collected six months after grafting, at the time of implant placement, were: newly formed bone tissue 43.9±4.2%, residual bone substitute 7.4±1.4%, medullary spaces 48.7±4.0%. At seven year follow-up, clinical and radiographic examination indicated that the use of the bone sheets preserved the regenerated bone volume. In conclusion, the use of heterologous cortical bone sheets in association with granular bone graft material enabled long-term stabilization of the graft material and effective management of intra-surgical complications.
[ "Materials Engineering", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1109/ICSE.2009.5070527
Learning Operational Requirements From Goal Models
Goal-oriented methods have increasingly been recognised as an effective means for eliciting, elaborating, analysing and specifying software requirements. A key activity in these approaches is the elaboration of a correct and complete set of opertional requirements, in the form of pre- and trigger-conditions, that guarantee the system goals. Few existing approaches provide support for this crucial task and mainly rely on significant effort and expertise of the engineer. In this paper we propose a tool-based framework that combines model checking, inductive learning and scenarios for elaborating operational requirements from goal models. This is an iterative process that requires the engineer to identify positive and negative scenarios from counterexamples to the goals, generated using model checking, and to select operational requirements from suggestions computed by inductive learning.
[ "Computer Science and Informatics" ]
10.1051/0004-6361/201424326
Asteroseismic Inference On The Spin Orbit Misalignment And Stellar Parameters Of Hat P 7
Context. The measurement of obliquities ‐ the angle between the orbital and stellar rotation ‐ in star-planet systems is of great importance for understanding planet system formation and evolution. The bright and well-studied HAT-P-7 (Kepler-2) system is intriguing because several Rossiter-McLaughlin (RM) measurements found a high projected obliquity in this system, but it was not possible so far to determine whether the orbit is polar and/or retrograde. Aims. The goal of this study is to measure the stellar inclination and hereby the full 3D obliquity of the HAT-P-7 system instead of only the 2D projection as measured by the RM e ect. In addition, we provide an updated set of stellar parameters for the star. Methods. We used the full set of available observations from Kepler spanning Q0-Q17 to produce the power spectrum of HAT-P-7. We extracted oscillation-mode frequencies via an Markov chain Monte Carlo peak-bagging routine and used the results from this to estimate the stellar inclination angle. Combining this with the projected obliquity from RM and the inclination of the orbital plane allowed us to determine the stellar obliquity. Furthermore, we used asteroseismology to model the star from the extracted frequencies using two di erent approaches to the modelling, for which either the stellar evolution codes MESA or GARSTEC were adopted.
[ "Universe Sciences" ]
W1976557440
Metabonomic analysis of the toxic effects of TM208 in rat urine by HPLC-ESI-IT-TOF/MS
4-Methylpiperazine-1-carbodithiocacid-3-cyano-3,3-diphenylpropyl ester hydrochloride (TM208) was a potential antitumor new drug with many preliminary studies in pharmacokinetics and pharmacodynamics. This study aims to determine whether TM208 elicits toxic effects by metabonomics for the first time. Sprague Dawley (SD) rats were exposured to TM208 at a single therapeutic dose (100mg/kg/d) for 5 days, metabolites of urine samples from both control and TM208-treated groups were analyzed using high performance liquid chromatography-electrospray ionization source in combination with hybrid ion trap and high-resolution time-of-flight mass spectrometry (HPLC-ESI-IT-TOF/MS). Metabolites such as aminoadipic acid, creatine, gluconic acid, cis-aconitic acid, succinic acid and pipecolic acid which changed significantly, were identified as potential biomarkers. These results suggest that the changes in urinary metabolites of rats after exposure to TM208 were mainly related to energy metabolism and amino acid metabolism, which may be helpful to further understand the mechanism of TM208 toxicity in rats and a new drug development.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physical and Analytical Chemical Sciences", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1038/ncomms3023
Suppression of electron-vibron coupling in graphene nanoribbons contacted via a single atom
Graphene nanostructures, where quantum confinement opens an energy gap in the band structure, hold promise for future electronic devices. To realize the full potential of these materials, atomic-scale control over the contacts to graphene and the graphene nanostructure forming the active part of the device is required. The contacts should have a high transmission and yet not modify the electronic properties of the active region significantly to maintain the potentially exciting physics offered by the nanoscale honeycomb lattice. Here we show how contacting an atomically well-defined graphene nanoribbon to a metallic lead by a chemical bond via only one atom significantly influences the charge transport through the graphene nanoribbon but does not affect its electronic structure. Specifically, we find that creating well-defined contacts can suppress inelastic transport channels.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1167/17.1.14
Transsaccadic Perceptual Fusion
Transsaccadic perceptual fusion is the integration of pre- and postsaccadic images into a single percept aligned in spatial coordinates. Several early studies reported an absence of transsaccadic fusion between dissimilar patterns, effectively stopping research on this question for three decades. We have now corrected two problematic aspects of these earlier studies and find robust evidence for transsaccadic perceptual fusion. First, we used simple pre- and postsaccadic targets, (|, ) for which spatial alignment is not critical. Second, we reduced the contrast of the postsaccadic stimulus, so that it would not suppress fusion. Participants reported seeing a superposition of the pre- and postsaccadic targets on 67% of trials. Importantly, we obtained similar results when the two stimuli were presented without an intervening eye movement, suggesting the existence of a general fusion mechanism. Directional biases in the saccade condition suggest that remapping might be the mechanism realigning the pre- and postsaccadic locations. Remapping may thus not only predict where targets will be located after a saccade but may also guide content, predicting what targets will look like. However, the constraints on the appearance of the fused percept suggest that it plays, at best, a limited role in visual stability across saccades.
[ "Neuroscience and Disorders of the Nervous System" ]
Q4255875
APOYO A LA LIQUIDEZ PARA LAS MICROEMPRESAS AFECTADAS POR LA EMERGENCIA DE LA COVID
APOYO A LA LIQUIDEZ DE LAS MICROEMPRESAS Y LAS PEQUEÑAS EMPRESAS DE LOS SECTORES MINORISTA, DE SUMINISTRO Y DE SERVICIOS PERSONALES CUYA ACTIVIDAD HA SIDO SUSPENDIDA COMO CONSECUENCIA DEL DECRETO DEL PRIMER MINISTRO DE 11 DE MARZO DE 2020
[ "Individuals, Markets and Organisations", "Institutions, Governance and Legal Systems" ]
10.1038/NCLIMATE1595
Impact Of Climate Change On The Baltic Sea Ecosystem Over The Past 1 000 Years
Marked ecosystem changes in the Baltic Sea have been recorded in the sediments, but the reasons are not fully understood. Now an integrated study of high-resolution sediment records (of the past 1,000 years) in combination with an ecosystem modelling approach reveals that surface temperature changes strongly influence deepwater oxygenation. Climate change has a strong impact on ecosystem health, particularly in marginal seas1 such as the Baltic, for example causing the spreading of anoxic areas (oxygen-free areas, the so-called dead zones) through strong feedbacks. Marked ecosystem changes in the Baltic Sea have been recorded in the sedimentary archive, but the reasons are not fully understood2,3. Here we report an integrated study of high-resolution sediment records (past 1,000 years) in combination with an ecosystem modelling approach, providing new insights into the functioning of the Baltic Sea ecosystem under natural and human-influenced climatic changes. Between the Little Ice Age and the Modern Warm Period the surface water temperatures reconstructed using TEX86 palaeothermometry increased by ∼2 °C. Simultaneously, the anoxic areas in the Baltic Sea began to expand significantly as evident from the accumulation of laminated sediments. Ecosystem model simulations support our findings of widespread oxic areas during the Little Ice Age. Backed up by the modelling results that take into account anthropogenic-influenced nutrient load scenarios, our results provide evidence that surface temperature changes strongly influence deepwater oxygenation. This highlights the risk of a continued spreading of anoxic areas during scenarios of continued climate warming in the future.
[ "Earth System Science", "Environmental Biology, Ecology and Evolution" ]
260820
Drug addiction: molecular changes in reward and aversion circuits
Our affective and motivational state is important for our decisions, actions and quality of life. Many pathological conditions affect this state. For example, addictive drugs are hyperactivating the reward system and trigger a strong motivation for continued drug intake, whereas many somatic and psychiatric diseases lead to an aversive state, characterized by loss of motivation. I will study specific neural circuits and mechanisms underlying reward and aversion, and how pathological signaling in these systems can trigger relapse in drug addiction. Given the important role of the dopaminergic neurons in the midbrain for many aspects of reward signaling, I will study how synaptic plasticity in these cells, and in their target neurons in the striatum, contribute to relapse in drug seeking. I will also study the circuits underlying aversion. Little is known about these circuits, but my hypothesis is that an important component of aversion is signaled by a specific neuronal population in the brainstem parabrachial nucleus, projecting to the central amygdala. We will test this hypothesis and also determine how this aversion circuit contributes to the persistence of addiction and to relapse. To dissect this complicated system, I am developing new genetic methods for manipulating and visualizing specific functional circuits in the mouse brain. My unique combination of state-of-the-art competence in transgenics and cutting edge knowledge in the anatomy and functional organization of the circuits behind reward and aversion should allow me to decode these systems, linking discrete circuits to behavior. Collectively, the results will indicate how signals encoding aversion and reward are integrated to control addictive behavior and they may identify novel avenues for treatment of drug addiction as well as aversion-related symptoms affecting patients with chronic inflammatory conditions and cancer.
[ "Neuroscience and Disorders of the Nervous System", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1142/s0218271818420051
Neutron star mergers as sites of r-process nucleosynthesis and short gamma-ray bursts
Neutron star mergers have been long considered as promising sites of heavy [Formula: see text]-process nucleosynthesis. We overview the observational evidence supporting this scenario including: the total amount of [Formula: see text]-process elements in the galaxy, extreme metal-poor stars, geological radioactive elemental abundances, dwarf galaxies and short gamma-ray bursts (sGRBs). Recently, the advanced LIGO and Virgo observatories discovered a gravitational-wave signal of a neutron star merger, GW170817, as well as accompanying multi-wavelength electromagnetic (EM) counterparts. The ultra-violet, optical and near infrared (n/R) observations point to [Formula: see text]-process elements that have been synthesized in the merger ejecta. The rate and ejected mass inferred from GW170817 and the EM counterparts are consistent with other observations. We however, find that, within the simple one zone chemical evolution models (based on merger rates with reasonable delay time distributions as expected from evolutionary models, or from observations of sGRBs), it is difficult to reconcile the current observations of the Eu abundance history of galactic stars for [Fe/H] [Formula: see text]. This implies that to account for the role of mergers in the galactic chemical evolution, we need a galactic model with multiple populations that have different spatial distributions and/or varying formation rates.
[ "Universe Sciences", "Fundamental Constituents of Matter" ]
W2069651718
The Influence of the Heme Sixth Ligand on the Backbone Dynamics of an Endogenously Hexacoordinate Hemoglobin
The hemoglobin of the cyanobacterium Synechococcus sp. PCC 7002 (GlbN) protects the cell from reactive oxygen/nitrogen species.1 GlbN coordinates the heme group with two histidines in the absence of an exogenous ligand and undergoes an unusual post-translational attachment of the heme group to the H helix. GlbN is well behaved by NMR spectroscopic standards, making it an excellent target for structural and dynamic studies aimed at characterizing the differential lability of the axial histidines, the perturbations caused by the post-translational modification, and the effect of exogenous ligand binding. The structure of GlbN is largely unperturbed by the covalent heme-protein cross-link,2 but binding of diatomic ligands such as CO (to ferrous GlbN) and CN- (to ferric GlbN) induces the formation of a distal hydrogen bond network and causes a shift of the B and E helices. 15N relaxation measurements indicate that the differences in ps-ns dynamics between the proximal and distal sides of the heme cofactor are minimal and also independent of heme covalent attachment. Upon CO or CN- binding the us-ms timescale motions are enhanced in the B and E helices, suggesting that the preferential displacement of the distal histidine is due to the stability of the final bound state rather than an intrinsic bond strength difference. The implications of increased dynamics on the distal side of the pocket after ligand binding will be discussed in terms of ligand migration inside GlbN and related globins.1) Scott et al., Biochemistry, 2010, 49: 7000-7011.2) Pond et al., Biomolecular NMR Assignments, 2009, 3: 211-214.Supported by NSF grant MCB 0843439.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physical and Analytical Chemical Sciences" ]
10.1093/imrn/rnv018
Simultaneous dense and nondense orbits and the space of lattices
We show that the set of points nondense under the ×n-map on the circle and dense for the geodesic flow after we identify the circle with a periodic horospherical orbit of the modular surface has full Haudorff dimension. We also show the analogous result for toral automorphisms on the 2-torus and a diagonal flow. Our results can be interpreted in number-theoretic terms: the set of well-approximable numbers that are nondense under the ×n-map has full Hausdorff dimension. Similarly, the set of well-approximable 2-vectors that are nondense under a hyperbolic toral automorphism has full Hausdorff dimension. Our result for numbers is the counterpart to a classical result of Kaufmann.
[ "Mathematics" ]
10.1111/brv.12110
Moving forward on facilitation research: response to changing environments and effects on the diversity, functioning and evolution of plant communities
Once seen as anomalous, facilitative interactions among plants and their importance for community structure and functioning are now widely recognized. The growing body of modelling, descriptive and experimental studies on facilitation covers a wide variety of terrestrial and aquatic systems throughout the globe. However, the lack of a general body of theory linking facilitation among different types of organisms and biomes and their responses to environmental changes prevents further advances in our knowledge regarding the evolutionary and ecological implications of facilitation in plant communities. Moreover, insights gathered from alternative lines of inquiry may substantially improve our understanding of facilitation, but these have been largely neglected thus far. Despite over 15 years of research and debate on this topic, there is no consensus on the degree to which plant-plant interactions change predictably along environmental gradients (i. e. the stress-gradient hypothesis), and this hinders our ability to predict how plant-plant interactions may affect the response of plant communities to ongoing global environmental change. The existing controversies regarding the response of plant-plant interactions across environmental gradients can be reconciled when clearly considering and determining the species-specificity of the response, the functional or individual stress type, and the scale of interest (pairwise interactions or community-level response). Here, we introduce a theoretical framework to do this, supported by multiple lines of empirical evidence. We also discuss current gaps in our knowledge regarding how plant-plant interactions change along environmental gradients. These include the existence of thresholds in the amount of species-specific stress that a benefactor can alleviate, the linearity or non-linearity of the response of pairwise interactions across distance from the ecological optimum of the beneficiary, and the need to explore further how frequent interactions among multiple species are and how they change across different environments. We review the latest advances in these topics and provide new approaches to fill current gaps in our knowledge. We also apply our theoretical framework to advance our knowledge on the evolutionary aspects of plant facilitation, and the relative importance of facilitation, in comparison with other ecological processes, for maintaining ecosystem structure, functioning and dynamics. We build links between these topics and related fields, such as ecological restoration, woody encroachment, invasion ecology, ecological modelling and biodiversity-ecosystem-functioning relationships. By identifying commonalities and insights from alternative lines of research, we further advance our understanding of facilitation and provide testable hypotheses regarding the role of (positive) biotic interactions in the maintenance of biodiversity and the response of ecological communities to ongoing environmental changes.
[ "Environmental Biology, Ecology and Evolution", "Earth System Science" ]
10.1007/978-3-319-69904-2_26
Conceptual Modeling For Genomics Building An Integrated Repository Of Open Data
Many repositories of open data for genomics, collected by world-wide consortia, are important enablers of biological research; moreover, all experimental datasets leading to publications in genomics must be deposited to public repositories and made available to the research community. These datasets are typically used by biologists for validating or enriching their experiments; their content is documented by metadata. However, emphasis on data sharing is not matched by accuracy in data documentation; metadata are not standardized across the sources and often unstructured and incomplete.
[ "Integrative Biology: from Genes and Genomes to Systems", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Computer Science and Informatics" ]
US 0221518 W
87144, HUMAN AMINO ACID TRANSPORTER FAMILY MEMBER AND USES THEREFOR
The invention provides isolated nucleic acids molecules, designated 87144 nucleic acid molecules, which encode novel amino acid transporter family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 87144 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 87144 gene has been introduced or disrupted. The invention still further provides isolated 87144 proteins, fusion proteins, antigenic peptides and anti-87144 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Products and Processes Engineering", "Prevention, Diagnosis and Treatment of Human Diseases" ]
W584526140
Quantum information science and its contributions to mathematics : American Mathematical Society Short Course, January 3-4, 2009, Washington, DC
This volume is based on lectures delivered at the 2009 AMS Short Course on Quantum Computation and Quantum Information, held January 3-4, 2009, in Washington, D.C. Part I of this volume consists of two papers giving introductory surveys of many of the important topics in the newly emerging field of quantum computation and quantum information, i.e., quantum information science (QIS). The first paper discusses many of the fundamental concepts in QIS and ends with the curious and counter-intuitive phenomenon of entanglement concentration. The second gives an introductory survey of quantum error correction and fault tolerance, QIS's first line of defence against quantum decoherence. Part II consists of four papers illustrating how QIS research is currently contributing to the development of new research directions in mathematics. The first paper illustrates how differential geometry can be a fundamental research tool for the development of compilers for quantum computers. The second paper gives a survey of many of the connections between quantum topology and quantum computation. The last two papers give an overview of the new and emerging field of quantum knot theory, an interdisciplinary research field connecting quantum computation and knot theory. These two papers illustrate surprising connections with a number of other fields of mathematics. In the appendix, an introductory survey article is also provided for those readers unfamiliar with quantum mechanics.
[ "Mathematics", "Computer Science and Informatics" ]
978616
Exploring tribal representation across american indian-produced radio in us reservation and urban contexts
This comparative research into tribal radio representation identifies and analyses indigenous communication strategies in American Indian community radio to explore how community radio practices and structures can facilitate meaningful self-representation in contexts where indigenous groups are marginalised. Through this analysis, this research seeks to update understanding of ways in which indigenous radio stations avail of and deploy emergent material developments, including podcasting and streaming technologies alongside ‘low power’ broadcasting. Drawing on the inclusive principles of Participatory Action Research (Tacchi et al 2003), research findings will be discussed on-site with tribal communities to share examples of good practice. This collaborative approach will enable tribal members to avail of findings and to provide input into research outcomes in a reciprocal process. Proposed research outputs will span academic, public, and indigenous media contexts in order to widen the benefits of this research for media and sociology scholars, indigenous practitioners, and policymakers. The research focus on indigenous communication strategies is of direct value for EU cultural and social contexts, in which established indigenous communities continue to be significantly under-represented in much of Europe’s mainstream media.
[ "The Social World and Its Interactions", "Studies of Cultures and Arts", "Systems and Communication Engineering" ]
US 2023/0035972 W
DYNAMIC PACKET RE-ORDERING, DISCARDING, AND FLOW SWITCHING
A radio access network node transmits a packet discard indication to configure a user equipment with indications that the node may discard packets corresponding to an indicated flow or corresponding to a flow received via an indicated resource. The packet discard indication configures the user equipment not to send a negative acknowledgement that a packet was not received via an indicated flow upon receiving an out-of-sequence packet corresponding to the indicated flow. The packet discard indication may configure the user equipment to decode a packet discarded from a flow indicated as being discarding-enabled via an indicated resource of an alternative target flow that may have a different quality-of-service, latency, or reliability than the flow to which the discarded packet belongs. The node may offload transmission of a packet discarded from a discarding-enabled flow to a flow indicated as an alternative target flow designated for offloading in the packet discard indication.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
759655
Supercapacitive Polymer Electrodes for Directing Epithelial Repair
In this project we develop a new approach, using the conducting polymer poly (3,4-ethylene dioxythiophene) (PEDOT) to apply electrical fields (EFs) for guidance of cells. EFs are recognised as important guidance cues in the development and life cycle of human tissues. However, better tools are urgently needed to support experiments and applications. By developing supercapacitive PEDOT electrodes, able to support an ionic flow over extended time frames, we here target the most widely studied clinical application for EF stimulation, accelerated wound healing. Our technology facilitates the transfer from petri dish to device by offering an alternative driving process to metals. In addition, we establish a strategy where electrodes can be recharged in situ, by using intermediate periods of current flow in the reverse direction and below the threshold for triggering a biological response. Ionic flow driven by PEDOT electrodes can, in contrast to metals, be reversed with any small ion present in the electrolyte. The project will be driven in several steps: after proving the principle in scratch assays in vitro, we will proceed to three dimensional culture systems. The versatility of our concept will allow more complex wound healing models to be studied including human ex-vivo models. We will employ microfluidics to make high-throughput screening possible, thereby efficiently mapping EF parameters and especially the effects of sub-threshold stimulation. The ultimate goal at the end of the project is to transfer technology in the form of a polymer based wound-dressing for accelerating repair, the SPEEDER. In summary, we present a new concept which greatly facilitates EF stimulation in vitro and shows great promise for clinical use. Studies will better reproduce the biological situation, provide data essential for understanding this important effect, and point the way for how it can best be exploited for future applications.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Prevention, Diagnosis and Treatment of Human Diseases", "Materials Engineering" ]
10.1103/PhysRevB.94.245422
Interpenetrating graphene networks: Three-dimensional node-line semimetals with massive negative linear compressibilities
We investigated the stability and mechanical and electronic properties of 15 metastable mixed sp2-sp3 carbon allotropes in the family of interpenetrating graphene networks (IGNs) using density functional theory (DFT). IGN allotropes exhibit nonmonotonic bulk and linear compressibilities before their structures irreversibly transform into new configurations under large hydrostatic compression. The maximum bulk compressibilities vary widely between structures and range from 3. 6 to 306 TPa-1. We find all the IGN allotropes have negative linear compressibilities with maximum values varying from -0. 74 to -133TPa-1. The maximal negative linear compressibility of Z33 (-133TPa-1 at 3. 4 GPa) exceeds previously reported values at pressures higher than 1. 0 GPa. IGN allotropes can be classified as either armchair or zigzag type, and these two types of IGNs exhibit different electronic properties. Zigzag-type IGNs are node-line semimetals, while armchair-type IGNs are either semiconductors or node-loop or node-line semimetals. Experimental synthesis of these IGN allotropes might be realized since their formation enthalpies relative to graphite are only 0. 1-0. 5 eV/atom (that of C60 fullerene is about 0. 4 eV/atom), and energetically feasible binary compound pathways are possible.
[ "Condensed Matter Physics", "Materials Engineering" ]
10.1017/s1358246118000115
Lady Parts: The Metaphysics of Pregnancy
What is the metaphysical relationship between the fetus/embryo and the pregnant organism? In this paper I apply a substance metaphysics view developed by Barry Smith and Berit Brogaard to argue, on the basis of topological connectedness, that fetuses/embryos are Lady-Parts: part of the maternal organism up until birth. This leaves two options. Either mammalian organisms begin at birth, or we revise our conception of organisms such that mammalian organisms can be part of other mammals. The first option has some advantages: it is numerically neat; aligns with an intuitive picture of organisms as physically distinct individuals; and ties ‘coming into existence’ to a suitably recognisable and important event: birth. But it denies that the fetus survives birth, or that human organisms existed prior to their birth. The second option allows us to recognise that human organisms exist prior to and survive their birth, but at a cost: it leaves the question of when an organism comes into existence unanswered, and demands potentially far-reaching conceptual revision across a range of domains.
[ "Texts and Concepts" ]
10.1016/j.jaac.2019.03.006
A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment
Objective: Women exposed to childhood maltreatment (CM) are more likely to exhibit insensitive parenting, which may have consequences for their offspring's development. Variation in the oxytocin-receptor gene (OXTR) moderates risk of CM-associated long-term sequelae associated with mother−child attachment, although functionality of previously investigated single nucleotide polymorphisms (SNPs) remained elusive. Here, we investigated the role of OXTR rs237895, a brain tissue expression quantitative trait locus (eQTL), as a moderator of the relationship between CM and maternal behavior (MB) and the association between MB and offspring attachment security. Method: Of 110 women with information on rs237895 genotype (T-allele = 64, CC = 46), 107 had information on CM (CTQ) and 99 on standardized observer-based ratings of MB at 6 months postpartum (responsivity and detachment), which were used in principal component analysis to obtain a latent factor representing MB. Offspring (n = 86) attachment was evaluated at 12 months of age. Analyses predicting MB were adjusted for socioeconomic status, age, postpartum depression, and genotype-based ethnicity. Analyses predicting child attachment were adjusted for infant sex, socioeconomic status, and postpartum depression. Results: rs237895 significantly moderated the relationship between CM and MB (F1;66 = 7. 99, p < . 01), indicating that CM was associated with maternal insensitivity only in high−OXTR-expressing T-allele carriers but not in low−OXTR-expressing CC homozygotes. Moreover, maternal insensitivity predicted offspring insecure attachment (B = –0. 551; p < . 05). Conclusion: Women with a high OXTR expressing genotype are more susceptible to CM-related impairments in MB that, in turn, predict attachment security in their children, supporting the role of the OT system in the intergenerational transmission of risk associated with maternal CM.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1002/art.33411
Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: Relevance for recent optic nerve ischemia
Objective To assess local expression and plasma levels of pentraxin 3 (PTX3) in patients with giant cell arteritis (GCA). Methods Plasma and serum samples were obtained from 75 patients with GCA (20 of whom had experienced optic nerve ischemia in the previous 3 weeks and 24 of whom had experienced symptom onset in the previous 6 months and had no history of optic nerve ischemia) and 63 controls (35 age-matched healthy subjects, 15 patients with rheumatoid arthritis, and 13 patients with chronic stable angina). In 9 patients in whom GCA was recently diagnosed, circulating levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α (MIP-1α), CCL4/MIP-1β, CCL11/eotaxin, CXCL9/monokine induced by interferon-γ, CXCL10/interferon-γ-inducible 10-kd protein, tumor necrosis factor α (TNFα), interferon-γ, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor, and FasL were measured via a multiplexed cytometric assay. PTX3 and VEGF concentrations were assessed by enzyme-linked immunosorbent assay. PTX3 and CD68 expression were determined by immunohistochemistry and immunofluorescence on temporal artery samples. Results GCA patients with very recent optic nerve ischemia had significantly higher PTX3 and VEGF levels compared to other GCA patients and controls. GCA patients with a disease duration of <6 months had significantly higher PTX3 levels compared to other GCA patients and controls. Immunohistochemistry revealed selective PTX3 expression in the wall of inflamed arteries. Conclusion Our findings indicate that local expression of PTX3 is a feature of vascular inflammation in GCA; elevated circulating levels of PTX3 identify patients with very recent optic nerve ischemia or a recent diagnosis. Optic nerve ischemia is also associated with increased circulating VEGF levels.
[ "Physiology in Health, Disease and Ageing", "Immunity, Infection and Immunotherapy" ]
10.1152/jn.00536.2013
Activation properties of trigeminal motoneurons in participants with and without bruxism
In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e. g. , serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4. 6 ± 1. 5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (<20% of maximal), whereby the firing rate of higher threshold motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities such as eating, nonnutritive chewing, clenching, and yawning.
[ "Neuroscience and Disorders of the Nervous System", "Physiology in Health, Disease and Ageing" ]
10.1093/molbev/msw214
Transmission between archaic and modern human ancestors during the evolution of the oncogenic human papillomavirus 16
Every human suffers through life a number of papillomaviruses (PVs) infections, most of them asymptomatic. A notable exception are persistent infections by Human papillomavirus 16 (HPV16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. Oncogenic potential is not homogeneous among HPV16 lineages, and genetic variation within HPV16 exhibits some geographic structure. However, an in-depth analysis of the HPV16 evolutionary history was still wanting. We have analyzed extant HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. We show that codivergence with modern humans explains at most 30% of the present viral geographical distribution. The most explanatory scenario suggests that ancestral HPV16 already infected ancestral human populations and that viral lineages co-diverged with the hosts in parallel with the split between archaic Neanderthal-Denisovans and ancestral modern human populations, generating the ancestral HPV16A and HPV16BCD viral lineages, respectively. We propose that after out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. We hypothesize that differential coevolution of HPV16 lineages with different but closely related ancestral human populations and subsequent host-switch events in parallel with introgression of archaic alleles into the genomes of modern human ancestors may be largely responsible for the present-day differential prevalence and association with cancers for HPV16 variants.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Integrative Biology: from Genes and Genomes to Systems", "Immunity, Infection and Immunotherapy" ]
W2073045545
CPU/GPU computing for a multi-block structured grid based high-order flow solver on a large heterogeneous system
The high-order schemes have attracted more and more attention in computational fluid dynamics (CFD) simulations. As a kind of high-order schemes, weighted compact nonlinear schemes (WCNSs) have been widely applied in large eddy simulations, direct numerical simulations etc. However, due to the computational complexity, WCNSs require high-performance platforms. In recent years, the highly parallel graphics processing unit (GPU) is rapidly gaining maturity as a powerful engine for high performance computer. In this paper, we present a high-order double-precision solver of the three-dimensional, compressible viscous flow using multi-block structured grids on GPU clusters. The solver utilizes the high-order WCNS scheme for space discretization and Jacobi iteration method for time discretization. In order to utilize the computational capability of CPU and GPU for the solver, we present a workload balancing model for distributing workload among CPUs and GPUs. And we design two strategies to overlap computations with communications. The performance analyses show that the single-GPU solver achieves about 8× speed-ups relative to a serial computation on a CPU core. The performance results validate the workload distribution scheme. The strong and weak scaling analyses show that GPU clusters offer a significant advantage in performance.
[ "Computer Science and Informatics", "Products and Processes Engineering" ]
10.1002/2017WR021726
Pore Scale Hydrodynamics In A Progressively Bioclogged Three Dimensional Porous Medium 3 D Particle Tracking Experiments And Stochastic Transport Modeling
Biofilms are ubiquitous bacterial communities that grow in various porous media including soils, trickling, and sand filters. In these environments, they play a central role in services ranging from degradation of pollutants to water purification. Biofilms dynamically change the pore structure of the medium through selective clogging of pores, a process known as bioclogging. This affects how solutes are transported and spread through the porous matrix, but the temporal changes to transport behavior during bioclogging are not well understood. To address this uncertainty, we experimentally study the hydrodynamic changes of a transparent 3-D porous medium as it experiences progressive bioclogging. Statistical analyses of the system's hydrodynamics at four time points of bioclogging (0, 24, 36, and 48 h in the exponential growth phase) reveal exponential increases in both average and variance of the flow velocity, as well as its correlation length. Measurements for spreading, as mean-squared displacements, are found to be non-Fickian and more intensely superdiffusive with progressive bioclogging, indicating the formation of preferential flow pathways and stagnation zones. A gamma distribution describes well the Lagrangian velocity distributions and provides parameters that quantify changes to the flow, which evolves from a parallel pore arrangement under unclogged conditions, toward a more serial arrangement with increasing clogging. Exponentially evolving hydrodynamic metrics agree with an exponential bacterial growth phase and are used to parameterize a correlated continuous time random walk model with a stochastic velocity relaxation. The model accurately reproduces transport observations and can be used to resolve transport behavior at intermediate time points within the exponential growth phase considered.
[ "Earth System Science", "Physical and Analytical Chemical Sciences", "Products and Processes Engineering" ]
10.1002/zaac.201300489
Synthesis and characterization of an azobenzene-functionalized ethene-bridged PMO
The azobenzene-functionalized ethene-bridged periodic mesoporous organosilica (PMO) was synthesized in a three step process. After synthesizing the pure PMO the azobenzene switch was post synthetically grafted at the ethene bridge. The successful synthesis was verified by N2 sorption measurements, IR spectroscopy, elemental analysis, and solid state MAS-NMR spectroscopy. The switching process of the azobenzene was proven by UV/Vis measurements.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1146/annurev-cellbio-100818-125204
Developmental Cell Death in the Cerebral Cortex
In spite of the high metabolic cost of cellular production, the brain contains only a fraction of the neurons generated during embryonic development. In the rodent cerebral cortex, a first wave of programmed cell death surges at embryonic stages and affects primarily progenitor cells. A second, larger wave unfolds during early postnatal development and ultimately determines the final number of cortical neurons. Programmed cell death in the developing cortex is particularly dependent on neuronal activity and unfolds in a cell-specific manner with precise temporal control. Pyramidal cells and interneurons adjust their numbers in sync, which is likely crucial for the establishment of balanced networks of excitatory and inhibitory neurons. In contrast, several other neuronal populations are almost completely eliminated through apoptosis during the first two weeks of postnatal development, highlighting the importance of programmed cell death in sculpting the mature cerebral cortex.
[ "Neuroscience and Disorders of the Nervous System", "Cell Biology, Development, Stem Cells and Regeneration" ]
CA 2013050773 W
UNITIZED PRECAST GRILLAGE FOUNDATION AND METHOD FOR MANUFACTURING THE SAME
The present invention discloses a unitized precast grillage foundation for supporting a tower comprising: a plurality of anchoring elements defining a grid for resting on an underlying surface; a base connected on the grid, the base comprising at least a first footing and a second footing spaced apart and at least one connecting member between and connected to the at least first footing and the second footing; and a beam-column projecting upwardly from the base, and a method of making same. In a preferred embodiment, the tower is an electrical transmission tower.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1609/aaai.v34i05.6402
SensEmBERT: Context-Enhanced Sense Embeddings for Multilingual Word Sense Disambiguation
Contextual representations of words derived by neural language models have proven to effectively encode the subtle distinctions that might occur between different meanings of the same word. However, these representations are not tied to a semantic network, hence they leave the word meanings implicit and thereby neglect the information that can be derived from the knowledge base itself. In this paper, we propose SensEmBERT, a knowledge-based approach that brings together the expressive power of language modelling and the vast amount of knowledge contained in a semantic network to produce high-quality latent semantic representations of word meanings in multiple languages. Our vectors lie in a space comparable with that of contextualized word embeddings, thus allowing a word occurrence to be easily linked to its meaning by applying a simple nearest neighbour approach. We show that, whilst not relying on manual semantic annotations, SensEmBERT is able to either achieve or surpass state-of-the-art results attained by most of the supervised neural approaches on the English Word Sense Disambiguation task. When scaling to other languages, our representations prove to be equally effective as their English counterpart and outperform the existing state of the art on all the Word Sense Disambiguation multilingual datasets. The embeddings are released in five different languages at http://sensembert. org.
[ "Computer Science and Informatics" ]
10.1007/978-3-642-32512-0_6
What S The Frequency Kenneth Sublinear Fourier Sampling Off The Grid
We design a sublinear Fourier sampling algorithm for a case of sparse off-grid frequency recovery. These are signals with the form $$f(t) = \sum _{j=1}^k a_j \mathrm{e}^{i\omega _j t} + \int \nu (\omega )\mathrm{e}^{i\omega t}d\mu (\omega )$$f(t)=?j=1kajei?jt+??(?)ei?tdμ(? ); i. e. , exponential polynomials with a noise term. The frequencies $$\{\omega _j\}$${?j} satisfy $$\omega _j\in [\eta ,2\pi -\eta ]$$?j?[?,2?-?] and $$\min _{i\ne j} |\omega _i-\omega _j|\ge \eta $$mini?j|?i-?j|?? for some $$\eta > 0$$?>0. We design a sublinear time randomized algorithm which, for any $$\epsilon \in (0,\eta /k]$$∈? (0,?/k], which takes $$O(k\log k\log (1/\epsilon )(\log k+\log (\Vert a\Vert _1/\Vert \nu \Vert _1))$$O(klogklog(1/∈)(logk+log(?a?1/?? ?1)) samples of $$f(t)$$f(t) and runs in time proportional to number of samples, recovering $$\omega _j'\approx \omega _j$$?j?? ?j and $$a_j'\approx a_j$$aj? ?aj such that, with probability $$\varOmega (1)$$Ω(1), the approximation error satisfies $$|\omega _j'-\omega _j|\le \epsilon $$|?j?-?j|≤∈ and $$|a_j-a_j'|\le \Vert \nu \Vert _1/k$$|aj-aj?|≤?? ?1/k for all $$j$$j with $$|a_j|\ge \Vert \nu \Vert _1/k$$|aj|????1/k. We apply our model and algorithm to bearing estimation or source localization and discuss their implications for receiver array processing.
[ "Mathematics", "Computer Science and Informatics", "Systems and Communication Engineering" ]
320594
Tensor Decomposition for Data Analysis with Applications to Health and Environment
Multi-Way factor Analysis (MWA) is attracting growing interest in many disciplines of engineering, as described in this proposal. Because the applications are much more numerous than those that serve as focus for this project, the tools developed in the framework of the project will have major impact. MWA is probably the simplest extension of the well-known (linear) Factor Analysis. However, despite its extremely wide panel of applications and its apparently simple expression, it still, surprisingly, lacks theoretical background. The reason is that this identification problem disguises challenges of unexpected magnitude. In fact, several tensor problems still remain open for several decades, and the difficulties should not be overlooked. Yet, the lack of identifiability results (existence, uniqueness) prevents the design of efficient numerical algorithms. The first objective is to address these theoretical problems and develop appropriate identification algorithms. Multilinear models underlying MWA are shown to be closely related to tensor algebra and multivariate polynomials, so that tools can be borrowed from Algebraic Geometry, with the goal of developing theoretical solutions and numerical algorithms. The second objective is to apply these solutions to practical problems in various realms of application. In particular, it centers on creating modified models, better matched to analysis of health (e.g., EEG) or environmental data (e.g., water resources, microbial ecosystems), to analyzing their identifiability, and to developing corresponding identification algorithms. The final goal is to design a device able to detect and track suspect or toxic molecules in river or tap waters. This very challenging research proposal is positioned in close collaboration with specialists in the above-mentioned application fields, and is at the core of European population health.
[ "Mathematics", "Computer Science and Informatics", "Products and Processes Engineering", "Environmental Biology, Ecology and Evolution" ]
3742484
Origin and maintenance of biodiversity: an ecological, evolutionary and developmental theory of organisms’ interactions
Ecological interactions are the backbone of ecosystems and play an essential role in the availability of the services they provide. These interactions are to a large extent dictated by the body size of the interacting organisms. Efforts to understand the origin and maintenance of networks of interacting organisms have considered ecological and evolutionary processes in communities based on species-averaged body size. However, this species-centric approach neglects the often dramatic body size changes of organisms during their development. EcoEvoDevoNetwork will for the first time explore how evolutionary, ecological and developmental processes shape the emergence and maintenance of complex networks of interacting organisms, and will investigate how these processes mediate responses to environmental change. The result will open new vistas in complex eco-evolutionary networks and provide tools to assess and monitor the impacts of human activities on ecosystems. The research proposed here will build on recently developed ecological framework that synthesize size-structured models and trophic network models, and will extend it by incorporating evolutionary processes. This extended framework will for the first time explicitly account for processes at three different levels of biological organization: individual, population and community, in an ecological and evolutionary context. The applicant has a strong background in eco-evolutionary dynamics of size-structured populations, and will benefit from the expertise of the supervisor (Dr. C. Melián) in eco-evolutionary networks and statistical modeling during this project. The excellent supervision, infrastructure and facilities at the host institute will ensure the successful execution of this project and will provide a unique opportunity for the applicant to build a strong career in science.
[ "Environmental Biology, Ecology and Evolution", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1016/j.actamat.2020.10.050
In-situ synchrotron X-ray micro-diffraction investigation of ultra-low-strain deformation microstructure in laminated Ti-Al composites
An ultra-low-strain deformation microstructure was revealed for the first time non-destructively in the bulk interior of an annealed laminated Ti-Al composite—in the “fully recrystallized” Al layer—by a synchrotron-based micro-diffraction technique, namely differential aperture X-ray microscopy (DAXM), through real space mapping with a very high angular resolution (0. 01°). This ultra-low-strain deformation microstructure was found to result from the thermal stress, induced during cooling after annealing, due to the different coefficients of thermal expansion for the Ti and Al layers. The annealed sample was further tensile deformed to a strain of 1. 66% and followed by in situ DAXM and analyzed by various misorientation mapping methods. The results pointed to the important effects of the initial microstructure and the interface constraint, as well as the grain size and crystal orientation, on the plastic deformation. A gradient in dislocation density from the layer interface to the center was found in the Al layer of the annealed sample, and this gradient increased slightly during tensile deformation. The variation of the dislocation density was further discussed based on the activation and interaction of dislocations in grains of different sizes and orientations during plastic deformation. The findings of this study provided valuable insights in understanding the constraint effect of the laminated metal composite and the design of novel composite materials.
[ "Condensed Matter Physics", "Materials Engineering" ]
978863
Ultra-Lightweight concrete for 3d printing technologies
The construction industry does not follow the same enlightened path as other fields of science and has thus suffered a technology bypass, relying on centuries-old processes and procedures to manage complex modern projects. In conventional concrete construction projects, more than 60% of the total cost is spent on the formwork. One of the technologies which can revolutionize our perception and approach to construction, is 3D printing of concrete. 3D printing, also referred to as Additive Manufacturing (AM), is a technology which builds solid parts via a layer-by-layer process. Since in 3D printing, no formwork is required, and a short project time is required due to continuous work done by the printer, a dramatic reduction in the project cost and improvement of workers’ safety can be achieved. Up to date, much research has been conducted in the field of printing technique, while design of proper insulation of printed walls has gathered little attention. Although, this issue is highly important due to gradually tightening EU regulations. Therefore, proposed project is aiming to fill the gap in knowledge and introduce for the first-time insulating ultra-lightweight concrete (ULWC) material for AM. By proposed interdisciplinary methodology, based on the experimental and numerical methods, in micro- and macro-scales technology, a multi-scale tool enabling to produce advanced 3D printed wall systems. Multi-scale tool will allow to develop 3D models of ULWCs with optimized mechanical and insulating properties. Hence, limited amount of required field and labor works will be necessary, thus further decrement of the final concrete cost and waste production will be achieved. Through the interdisciplinary approach and establishing industrial cooperation, this project will contribute towards development and production of energy saving constructions in accordance with EU Energy Efficiency Strategy.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1016/j.coi.2014.07.002
The dissection of complex susceptibility to infectious disease: Bacterial, viral and parasitic infections
Infectious diseases are the result of the exposure of susceptible hosts to pathogenic microbes. Genetic factors are important determinants of host susceptibility and efforts are being made to establish the molecular identity of such genetic susceptibility variants by genome-wide association studies. Results obtained to date partly confirm already known genetic vulnerabilities, but also point to new and unexpected mechanisms of susceptibility that extend from classical innate and acquired immunity to weaknesses in constitutional resistance. These studies also revealed an overlap in genetic control between infectious disease and other common immune and inflammatory disorders.
[ "Immunity, Infection and Immunotherapy", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1039/C6CC07773K
Ruthenium Ii Catalyzed C H Functionalizations On Benzoic Acids With Aryl Alkenyl And Alkynyl Halides By Weak O Coordination
C–H arylations of weakly coordinating benzoic acids were achieved by versatile ruthenium(II) catalysis with ample substrate scope. Thus, user-friendly ruthenium(II) biscarboxylate complexes modified with tricyclohexylphosphine enabled C–H functionalizations with aryl electrophiles. The unique versatility of the ruthenium(II) catalysis manifold was reflected by facilitating effective C–H activations with aryl, alkenyl and alkynyl halides.
[ "Synthetic Chemistry and Materials", "Physical and Analytical Chemical Sciences" ]
984841
Punishment as communication: transgressors’ interpretation and understanding of punishment
Punishment is ubiquitous. We discipline children when they misbehave, and we demand even harsher sanctions for criminal offences. Punishment is thought to serve a communicative purpose: Through punishment, victims and third parties seek to send various “messages” to transgressors (e.g., condemning the wrongness of the act and imploring them to reform). But are these messages effectively delivered and understood by transgressors? And does the interpretation of a punitive message have the desired effects on the transgressor? To answer these questions, this research examines (a) the types of messages transgressors receive through punishment (why they think they are being punished), and (b) transgressors’ reactions to them (e.g., perceived fairness, experienced remorse). Further, it explores (c) the features of a punitive message that influences how the message is interpreted by transgressors. The research will be built on a theoretical framework that integrates knowledge from three distinct fields: legal philosophy, social psychology, and behavioural economics. The specific hypotheses deducted from this framework will be tested in controlled experimental lab studies as well as in a court setting. The insights from this research will be informative to all disciplines interested in criminal justice and punishment. First, this research will develop our theoretical understanding of punitive procedures and their effects. Second, it has important implications for how we should deliver punishment to enhance justice outcomes, whether in the context of formal legal proceedings or informal sanctions. The quality of the research will be strengthened by access to exceptional research facilities and expertise at the host university, and interdisciplinary collaboration with scholars both within the university and beyond. Further, the expertise and methodological training acquired through the fellowship will significantly develop the researcher’s capacities and profile.
[ "The Social World and Its Interactions", "Institutions, Governance and Legal Systems", "The Human Mind and Its Complexity" ]
10.1002/anie.201607825
Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles
The important role of vesicles in many aspects of cell function is well-recognized, but only recently have sophisticated imaging techniques begun to reveal their ubiquity in nature. While we further our understanding of the biological properties of vesicles and their physiological functions, increasingly elegant artificial vesicles are being developed for a wide range of technological applications and basic research. Herein, we examine the state of the art of biological and synthetic vesicles and place their biological features in the context of recent synthetic developments, thus providing a unique overview of these complex and rapidly developing fields. The challenges and opportunities associated with future biological and synthetic studies of vesicles are also presented.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Synthetic Chemistry and Materials", "Cell Biology, Development, Stem Cells and Regeneration" ]
10.1042/BJ20130241
In Vivo Characterization Of The Properties Of Sumo1 Specific Monobodies
Monobodies are small recombinant proteins designed to bind with high affinity to target proteins. Monobodies have been generated to mimic the SIM [SUMO (small ubiquitin-like modifier)-interacting motif] present in many SUMO target proteins, but their properties have not been determined in cells. In the present study we characterize the properties of two SUMO1-specific monobodies (hS1MB4 and hS1MB5) in HEK (human embyronic kidney)-293 and HeLa cells and examine their ability to purify SUMO substrates from cell lines and rat brain. Both hS1MB4 and hS1MB5 compared favourably with commercially available antibodies and were highly selective for binding to SUMO1 over SUMO2/3 in pull-down assays against endogenous and overexpressed SUMO and SUMOylated proteins. Monobodies expressed in HeLa cells displayed a nuclear and cytosolic distribution that overlaps with SUMO1. Expression of the monobodies effectively inhibited protein SUMOylation by SUMO1 and, surprisingly, by SUMO2/3, but were not cytotoxic for at least 36 h. We attribute the effects on SUMO2/3 to the role of SUMO1 in chain termination and/or monobody inhibition of the SUMO-conjugating E1 enzyme complex. Taken together, these data provide the first demonstration that monobodies represent useful new tools both to isolate SUMO conjugates and to probe cell SUMOylation pathways in vivo.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1039/c5mb00763a
Signalling to the nucleus under the control of light and small molecules
One major regulatory mechanism in cell signalling is the spatio-temporal control of the localization of signalling molecules. We synthetically designed an entire cell signalling pathway, which allows controlling the transport of signalling molecules from the plasma membrane to the nucleus, by using light and small molecules.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1371/journal.ppat.1000883
Quorum sensing inhibition selects for virulence and cooperation in pseudomonas aeruginosa
With the rising development of bacterial resistance the search for new medical treatments beyond conventional antimicrobials has become a key aim of public health research. Possible innovative strategies include the inhibition of bacterial virulence. However, consideration must be given to the evolutionary and environmental consequences of such new interventions. Virulence and cooperative social behaviour of the bacterium Pseudomonas aeruginosa rely on the quorum-sensing (QS) controlled production of extracellular products (public goods). Hence QS is an attractive target for anti-virulence interventions. During colonization, non-cooperating (and hence less virulent) P. aeruginosa QS-mutants, benefiting from public goods provided by wild type isolates, naturally increase in frequency providing a relative protection from invasive infection. We hypothesized that inhibition of QS-mediated gene expression removes this growth advantage and selection of less virulent QS-mutants, and maintains the predominance of more virulent QS-wild type bacteria. We addressed this possibility in a placebo-controlled trial investigating the anti-QS properties of azithromycin, a macrolide antibiotic devoid of bactericidal activity on P. aeruginosa, but interfering with QS, in intubated patients colonized by P. aeruginosa. In the absence of azithromycin, non-cooperating (and hence less virulent) lasR (QS)-mutants increased in frequency over time. Azithromycin significantly reduced QS-gene expression measured directly in tracheal aspirates. Concomitantly the advantage of lasR-mutants was lost and virulent wild-type isolates predominated during azithromycin treatment. We confirmed these results in vitro with fitness and invasion experiments. Azithromycin reduced growth rate of the wild-type, but not of the lasR-mutant. Furthermore, the lasR-mutant efficiently invaded wild-type populations in the absence, but not in the presence of azithromycin. These in vivo and in vitro results demonstrate that anti-virulence interventions based on QS-blockade diminish natural selection towards reduced virulence and therefore may increase the prevalence of more virulent genotypes in the Hospital environment. More generally, the impact of intervention on the evolution of virulence of pathogenic bacteria should be assessed.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
interreg_3888
VIA ALPINA DEVELOPMENT VENTURE - Together with local stakeholders, develop high-quality natural and cultural tourism and education offers basing on the Via Alpina network of hiking trails
VIADVENTURE is based on the results of the VIA ALPINA project, developed within Interreg IIIB Alpine Space from 2001 to 2004. This project has established the Via Alpina "product", a network of hiking trails throughout the Alps, complete with basic information documents, an on-line database and specific marking and information panels along the trails. Also, it produced an international Quality Guide dealing with all aspects of the tourism chain. The challenge is now to put the Via Alpina product into use in order to obtain concrete benefits in the Alpine regions. Due to the exceptional dimension of Via Alpina, a significant territorial animation initiative is necessary in order to inform and involve public and private stakeholders. It is necessary to focus in the next three years on working with such local partners to develop the communication and marketing and especially to create special offers basing on the local resources. Special attention will be given to the young public and to the integration of environmental education.
[ "Human Mobility, Environment, and Space", "Environmental Biology, Ecology and Evolution", "Earth System Science" ]
10.1111/pbi.12416
Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants
Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Biotechnology and Biosystems Engineering" ]
10.1016/j.redox.2020.101618
The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells
Fanconi Anemia (FA) is a disease characterized by bone marrow (BM) failure and aplastic anemia. In addition to a defective DNA repair system, other mechanisms are involved in its pathogenesis, such as defective mitochondrial metabolism, accumulation of lipids, and increment of oxidative stress production. To better understand the role of these metabolic alterations in the process of HSC maturation in FA, we evaluated several biochemical and cellular parameters on mononuclear cells isolated from the bone marrow of FA patients or healthy donors. To mimic the cellular residence in the BM niche or their exit from the BM niche to the bloodstream, cells have been grown in hypoxic or normoxic conditions, respectively. The data show that, in normoxic conditions, a switch from anaerobic to aerobic metabolism occurs both in healthy and in pathological samples. However, in FA cells this change is associated with altered oxidative phosphorylation, the increment of oxidative stress production, no activation of the endogenous antioxidant defenses and arrest in the G2M phase of the cell cycle. By contrast, FA cells grown in hypoxic conditions do not show cell cycle and metabolic alterations in comparison to the healthy control, maintaining both an anaerobic flux. The data reported herein suggests that the passage from the BM niche to the bloodstream represents a crucial point in the FA pathogenesis associated with mitochondrial dysfunction.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Physiology in Health, Disease and Ageing" ]
10.1016/j.wace.2020.100262
Factors affecting extreme rainfall events in the South Pacific
Extreme rainfall events in the South Pacific are widespread and affected by various factors on different time scales. We use daily rainfall data from 20 stations over the South Pacific to investigate the characteristics of extreme rainfall events from 1979 to 2018. For regional analysis, we group the stations into three clusters characterizing the western, the central, and the far eastern regions of the South Pacific Convergence Zone (SPCZ). Extreme rainfall events contribute to roughly 20% of the seasonal mean rainfall in all three clusters. Among all four factors considered, tropical cyclones (TCs) cause the highest increase in the probability (ΔpwesternSPCZ~286%, ΔpcentralSPCZ~84%, ΔpfareasternSPCZ~189%) of extreme rainfall events. The Madden-Julian Oscillation (MJO) is the second most important factor affecting the probability of extreme rainfall events, increasing it by 30–60% when the MJO is active over the western SPCZ in phases 5–6, over the central SPCZ in phases 6–7, and over the far eastern SPCZ in phases 8–1. The probability is reduced by the same order of magnitudes during the opposite dry phases of the MJO, i. e. , phases 1–3 for the western and central SPCZ, and 3–6 for far the eastern SPCZ region. The probability of extreme rainfall events increases during La-Niña (El-Niño) conditions to the southwest (southeast) of the mean SPCZ by 27% (31%); however, the impact of the El-Niño and Southern Oscillation (ENSO) along the SPCZ is not apparent. Dynamical analysis shows that the favorable conditions for generating extreme rainfall events are associated with northwesterly moisture transport and its convergence. The impact of TCs, MJO, and ENSO on rainfall extreme events can be partly understood considering this dynamical analysis. Extratropical Rossby waves can trigger tropical disturbances, but their impact on extreme rainfall events is generally less important than of the TCs, MJO, and ENSO.
[ "Earth System Science" ]
10.1016/j.euroecorev.2017.06.001
The importance of peers for compliance with norms of fair sharing
A burgeoning literature in economics has started examining the role of social norms in explaining economic behavior. Surprisingly, the vast majority of this literature has studied social norms in asocial decision settings, where individuals are observed to act in isolation from each other. In this paper we use a large-scale dictator game experiment (N = 850) to show that “peers” can have a profound influence on individuals’ perceptions of norms of fair sharing, which we elicit in an incentive compatible way. However, in contrast to these strong peer effects in social norms of fair sharing, we find limited evidence of the influence of norms and peers on actual sharing behavior. We discuss how these results can be explained by heterogeneity in normative views as well as in willingness to comply with norms.
[ "Individuals, Markets and Organisations", "The Social World and Its Interactions" ]
10.3390/ijms20020373
Expanding the Genetic Code for Site-Directed Spin-Labeling
Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy enables studies of the structure, dynamics, and interactions of proteins in the noncrystalline state. The scope and analytical value of SDSL–EPR experiments crucially depends on the employed labeling strategy, with key aspects being labeling chemoselectivity and biocompatibility, as well as stability and spectroscopic properties of the resulting label. The use of genetically encoded noncanonical amino acids (ncAA) is an emerging strategy for SDSL that holds great promise for providing excellent chemoselectivity and potential for experiments in complex biological environments such as living cells. We here give a focused overview of recent advancements in this field and discuss their potentials and challenges for advancing SDSL–EPR studies.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
172205
Bringing personalized knowledge to students in public schools through artificial intelligence in elearning
In the EU, private and public expenditure per full-time student rose from 5,674 to 6,900, i.e. by almost 22% from 2005 to 2010 whilst PISA results remain largely stable. In order to impact students’ learning curve, we need advanced learning tools, i.e. e-learning needs to be infused with AI: content creation tools, adaptive learning, collaborating learning, and Open Education Resource management. That is why we have created Icarus, an AI plugin system that can be installed on top of one of the most recognized free open source Dokeos e-learning platform. Icarus provides tools to students to frequent a learning path and to teachers to create one as a personalized and adaptive tutor with a series of modules. It will be available open source based on a freemium business model where we only charge for customization work. There is currently no open source AI e-learning application available at a freemium. The objective of a Phase II project will be to a) scale up the Icarus plugin system on top of the main open source e-learning platform additionally to Dokeos and to b) pilot Icarus in at least three public or private primary schools in two different EU countries. In Phase I, we will conduct a Feasibility Study and a Business Plan including the following objectives: feasibility study, partner search, market, business model, risk and IP assessment as well as draft a work plan for Phase II. The project Icarus responds to topic ICT-37-2015. As an innovative SME, we propose to scale-up our ICT product Icarus that will disrupt the market by being the first open source AI system for e-learning that can directly be used by all levels of educational institutions: This is going to have a measurable impact on education with students reaching higher scores in PISA evaluations and ultimately bringing better results as part of the future work force. The EC funding will allow us to grow our company significantly. We will invest in new staff to more than double our staff from 2015.
[ "Computer Science and Informatics", "The Social World and Its Interactions" ]
AT 0100151 W
CONCEALED WINDOW AND DOOR FRAME
The invention relates to a plastic, especially polyethylene, concealed frame, which can be directly set in concrete. The inventive frame comprises a base element (1) and a frame (3), said frame (3) being able to move to a certain extent in relation to the base element (1) before being definitively joined thereto (1) in order to offset tolerances. Preferably, a step (5) is provided in the lower side of the outer surface of the frame (3), which can be used as a traction edge when fitting full thermal insulation (6). Plastic screws (4) should be used to join the frame (3) to the base element (1).
[ "Products and Processes Engineering", "Materials Engineering" ]
10.1145/2187836.2187948
Opal Automated Form Understanding For The Deep Web
Forms are our gates to the web. They enable us to access the deep content of web sites. Automatic form understanding unlocks this content for applications ranging from crawlers to meta-search engines and is essential for improving usability and accessibility of the web. Form understanding has received surprisingly little attention other than as component in specific applications such as crawlers. No comprehensive approach to form understanding exists and previous works disagree even in the definition of the problem. In this paper, we present OPAL, the first comprehensive approach to form understanding. We identify form labeling and form interpretation as the two main tasks involved in form understanding. On both problems OPAL pushes the state of the art: For form labeling, it combines signals from the text, structure, and visual rendering of a web page, yielding robust characterisations of common design patterns. In extensive experiments on the ICQ and TEL-8 benchmarks and a set of 200 modern web forms OPAL outperforms previous approaches by a significant margin. For form interpretation, we introduce a template language to describe frequent form patterns. These two parts of OPAL combined yield form understanding with near perfect accuracy (> 98%).
[ "Computer Science and Informatics" ]
IB 2009005383 W
SINGLE-LENS EXTENDED DEPTH-OF-FIELD IMAGING SYSTEMS
An extended depth of field (EDOF) imaging system (10) is disclosed that has a corresponding extended depth of focus (EDOF'). The imaging system has an optical system (20) consisting of a single lens element (22) and an objectwise aperture stop (AS) arrange substantially at a zero-coma axial position. The single lens element is configured so that the optical system has a select amount of spherical aberration (SA) in the range 0.2? =SA = 2?, where ? is an imaging wavelength. The imaging system has an image sensor (30) for forming a digitized raw image (IM) of an object (OB). In applications, the raw image can be used directly. The imaging system also has an image processing unit (54) adapted to process the raw images to form contrast-enhanced images. The image processing includes forming an enhanced modulation transfer functions (MTF) using a gain function (G) applied to the "raw" MTF. Embodiments of the single lens element include at least one diffractive feature (23) to reduce chromatic aberration. Single lens elements with at least one aspheric surface (S1, S2 or S1 and S2) are also disclosed.
[ "Systems and Communication Engineering", "Physical and Analytical Chemical Sciences", "Materials Engineering" ]
10.1016/j.ffa.2018.12.002
Irreducible polynomials over F<inf>2<sup>r</sup></inf> with three prescribed coefficients
For any positive integers n≥3 and r≥1, we prove that the number of monic irreducible polynomials of degree n over F2r in which the coefficients of Tn−1, Tn−2 and Tn−3 are prescribed has period 24 as a function of n, after a suitable normalization. A similar result holds over F5r, with the period being 60. We also show that this is a phenomena unique to characteristics 2 and 5. The result is strongly related to the supersingularity of certain curves associated with cyclotomic function fields, and in particular it complements an equidistribution result of Katz.
[ "Mathematics" ]
10.1039/C7CC02997G
Supramolecular Functional Assemblies Dynamic Membrane Transporters And Peptide Nanotubular Composites
The fabrication of functional molecular devices constitutes one of the most important current challenges for chemical sciences. The complex processes accomplished by living systems continuously demand the assistance of non-covalent interactions between molecular building blocks. Additionally, these building blocks (proteins, membranes, nucleotides) are also constituted by self-assembled structures. Therefore, supramolecular chemistry is the discipline required to understand the properties of the minimal self-assembled building blocks of living systems and to develop new functional smart materials. In the first part of this feature article, we highlight selected examples of the preparation of supramolecular membrane transporters with special emphasis on the application of dynamic covalent bonds. In the second section of the paper we review recent breakthroughs in the preparation of peptide nanotube hybrids with functional applications. The development of these devices constitutes an exciting process from where we can learn how to understand and manipulate supramolecular functional assemblies.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials" ]
10.1016/j.microc.2015.11.024
Virtual reading of a large ancient handwritten science book
We present a fundamental development step of a new technique to read and digitize ancient handwritten documents. Chemical analysis by x-ray fluorescence and x-ray tomography enabled us to decipher words and drawings from inside a closed, 200-pages 18. th century handwritten book. The ink chemistry is essential: tomographic reading is feasible thanks to the iron present in ancient inks (iron gall) over one millennium-whereas carbon or organic inks do not provide sufficient x-ray contrast. The results presented are a key progress towards the ultimate goal of the technique: non-invasive reading of fragile and/or unopenable documents.
[ "Physical and Analytical Chemical Sciences", "The Study of the Human Past", "Computer Science and Informatics" ]
2728245
Sharing-Economy matching platform to revolutionize last-mile logistics
The rapid growth in e-commerce is changing the consumer behavior, increasing the logistic burden in last-mile delivery. From this fact are arisen two mayor problems. For one side, our logistic infrastructure will never be ready for the number of delivery-vehicles required to fulfill such demand. From the other, last-mile delivery entails the ≈53% of the transport costs, a figure that most of the SME cannot assume. Hence, an oligopolistic horizon of large companies like Amazon will come unless smart solutions will avoid it. Nimber is a decentralized delivery-company that is disrupting logistics in Norway. Our vision is to become the global leaders in the last-mile delivery sector by providing the market with a sustainable, efficient, CO2 minimal and convenient alternative to last-mile delivery for SME and individuals. In this regard,Nimber platform presently matches persons needing items delivered with the most optimal delivery solution: people going that way anyway. Thus, we operate for peer-to-peer deliveries (P2P). With SWIFTLY, we seek to hybridize our peer-to-peer model into the business-to-customer (B2C) or business-to-business (B2B) sectors. For such aim, we will offer two novel tools: a bundling algorithm which optimizes loads and deliveries per route to increase the profitability of the professional bringers' services and a pricing algorithm to offer the fairest pricing for both parties (bringer and sender) and speed up the time to close a deal. With this approach we solve the problems of rapidly-growing e-commerce by optimizing existing commuter pathways to deliver goods.
[ "Products and Processes Engineering", "Computer Science and Informatics" ]
W2006148285
Optimized Multisite Ventricular Pacing in Postoperative Single-Ventricle Patients
Ventricular dyssynchrony is associated with morbidity and mortality after palliation of a single ventricle. The authors hypothesized that resynchronization with optimized temporary multisite pacing postoperatively would be safe, feasible, and effective. Pacing was assessed in the intensive care unit within the first 24 h after surgery. Two unipolar atrial pacing leads and four bipolar ventricular pacing leads were placed at standardized sites intraoperatively. Pacing was optimized to maximize mean arterial pressure. The protocol tested 11 combinations of the 4 different ventricular lead sites, 6 atrioventricular delays (50-150 ms), and 14 intraventricular delays. Optimal pacing settings were thus determined and ultimately compared in four configurations: bipolar, unipolar, single-site atrioventricular pacing, and intrinsic rhythm. Each patient was his or her own control, and all pacing comparisons were implemented in random sequence. Single-ventricle palliation was performed for 17 children ages 0-21 years. Pacing increased mean arterial pressure (MAP) versus intrinsic rhythm, with the following configurations: bipolar multisite pacing increased MAP by 2.2 % (67.7 ± 2.4 to 69.2 ± 2.4 mmHg; p = 0.013) and unipolar multisite pacing increased MAP by 2.8 % (67.7 ± 2.4 to 69.6 ± 2.7 mmHg; p = 0.002). Atrioventricular single-site pacing increased MAP by 2.1 % (67.7 ± 2.4 to 69.1 ± 2.5 mmHg: p = 0.02, insignificant difference under Bonferroni correction). The echocardiographic fractional area change in nine patients increased significantly only with unipolar pacing (32 ± 3.1 to 36 ± 4.2 %; p = 0.02). No study-related adverse events occurred. Multisite pacing optimization is safe and feasible in the early postoperative period after single-ventricle palliation, with improvements in mean arterial pressure and fractional area shortening. Further study to evaluate clinical benefits is required.
[ "Physiology in Health, Disease and Ageing", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.15184/aqy.2018.257
Scales, weights and weight-regulated artefacts in Middle and Late Bronze Age Britain
The identification of weights and weight-regulated artefacts is of primary importance for confirming the existence of European Bronze Age value ratios and exchange systems. Until recently, however, no such Bronze Age artefacts had been identified in Britain. Here, statistical analysis identifies - for the first time - Middle and Late Bronze Age balance weights and weight-regulated gold objects from Britain, Ireland and Atlantic France. These finds allow for new interpretations concerning modes of exchange and their significance in Atlantic Europe, further underlining a Continental - and possibly Mediterranean - influence on Britain during the late second and early first millennia BC.
[ "The Study of the Human Past" ]
668640
The Enigma of the Hyksos
The Hyksos (Greek rendering of the Egyptian title “rulers of the foreign countries”) were a dynasty of foreign rulers of Egypt between c.1640 and 1530 BC. Some modern researchers, following the ancient historian Flavius Josephus (1st cent. AD) thought they were ancestors of the early Israelites, others suggested that their appearance should be tied to the Hurrian expansion to the Levant. Most scholars today think, according to the onomastic data, that they were western Semites. Their geographical origin in the Levant, their seizure of power and their role in history, remains, however, an enigma, as the period is poorly represented in texts. Nevertheless the Hyksos phenomenon has thus far mainly been studied by text-based Egyptology. In the last decades, however, excavations at T. el-Dab‘a, T. el-Rotaba, T. el Maskhuta and other places in the eastern Delta have produced an enormous wealth of new data such as urban settlements, palaces, tombs, temples, offering remains, besides enormous quantities of material culture and physical remains which can be attributed to the carriers of the Hyksos rule and their predecessors. These materials, left thus far largely aside in the historical discussion, can be utilised as first class historical sources. The envisaged investigations will be conducted in 8 interrelated research tracks, incorporating an array of archaeological, historical, theoretical and analytical sciences. The aim is to reveal in a holistic approach the origin, the dialogue with and the impact of western Asiatic people on culture of the host country and finally their heritage. They played a much greater role in the history of the Old World than envisaged and pushed Egypt into the focus of what happened in the Near East in the 2nd millennium BC. This innovative exploration of the Hyksos phenomenon has the potential to write a new chapter in the history of this salient region and offer a model.
[ "The Study of the Human Past" ]
10.1016/j.vibspec.2012.07.011
Micro ATR FTIR imaging of hanging drop protein crystallisation
Protein crystallisation is of great importance within structural proteomic projects where considerable time and effort is spent trying to obtain high resolution structural information from the X-ray diffraction of protein crystals. The crystallisation process is largely empirical due to a lack of understanding of crystallisation kinetics and it is often very challenging to obtain crystals of sufficient size and quality for X-ray analysis and data collection. This paper presents the use of micro attenuated total reflection (ATR) - Fourier Transform Infrared (FTIR) spectroscopic imaging as an analytical method for the measurement of the growth of protein crystals using the hanging drop approach. As well as allowing for the measurement of in situ growth of protein crystals, the high spatial resolution of this method allows the detection of micro-crystals. The use of this technique could be very advantageous for protein structural studies since it allows both detection of the growth of small protein crystals and provides chemical information as the crystals form.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1088/1742-6596/1065/21/212026
Combining Experiments For Linear Dynamic Network Identification In The Presence Of Nonlinearities
In many practical applications it might be desirable to excite only point at a time in an interconnection of multiple dynamic subsystems (e. g. large-scale system). Therefore multiple experiments need to be combined to successfully identify one or more subsystems in the network of subsystems. This papers illustrates how the identification of a linear subsystem of a dynamical network containing one or more nonlinear subsystems can result in biased estimates when multiple experiments are combined using the Best Linear Approximation (BLA) based approach.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.1109/TCOMM.2015.2456177
Reduced-Complexity Soft-Decision Multiple-Symbol Differential Sphere Detection
Unlike a generic PSK/QAM detector, which may visit a constellation diagram only once, a depth-first Sphere Decoder (SD) has to re-visit the same constellation diagram multiple times. Therefore, in order to prevent the SD from repeating the detection operations, the Schnorr-Euchner search strategy of Schnorr and Euchner may be invoked for optimizing the nodes' search-order, where the ideal case is for the SD to visit the constellation nodes in a zigzag fashion. However, when the hard-decision Multiple-Symbol Differential Sphere Detection (MSDSD) of Lampe et al. is invoked for using multiple receive antennas N-R\ge 1, the Schnorr-Euchner search strategy has to visit and sort all the M\textrm{PSK} constellation points. A similar situation is encountered for the soft-decision MSDSD of Pauli et al. , when the a priori LLRs gleaned from the channel decoder are taken into account. In order to tackle these open problems, in this paper, we propose a correlation process for the hard-decision MSDSD of Lampe et al. and a reduced-complexity design for the soft-decision MSDSD of Pauli et al. , so that the Schnorr-Euchner search strategy always opts for visiting the M{PSK} constellation points in a zigzag fashion. Our simulation results demonstrate that a substantial complexity reduction is achieved by our reduced-complexity design without imposing any performance loss. Explicitly, up to 88. 7% complexity reduction is attained for MSDSD (N-w=4) aided D16PSK. This complexity reduction is quite substantial, especially when the MSDSD is invoked several times during turbo detection. Furthermore, in order to offer an improved solution and a comprehensive study for the soft-decision MSDSD, we also propose to modify the output of the SD to harmonize its operation with the near-optimum Approx-Log-MAP. Then the important subject of coherent versus noncoherent is discussed in the context of coded systems, which suggests that MSDSD aided DPSK is an eminently suitable candidate for turbo detection assisted coded systems operating at high Doppler frequencies.
[ "Systems and Communication Engineering", "Computer Science and Informatics" ]
10.15252/embj.201593534
Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm
Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects de novo targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of de novo DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.
[ "Integrative Biology: from Genes and Genomes to Systems", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W2323913645
Relative Valuation
In this paper we studied the sectoral behavior of Indian capital market through relative valuation for a period over a period of 21 years. The period covered under the study is from 1990–2010. The study has been done both for a total period (1990–2010) and three sub-periods, viz. 1990–96, 1997–2003, 2004–10. The research finds that price multiple distributions tend to be non-normal prior to 2003. On post-2003 basis these sample distributions are approximately normal, thereby implying that mean and standard deviations are relevant descriptive statistic measures in the Indian context, for a more recent period. The study also finds that we cannot judge all the sectors by classifying them with single high or low price multiples. Different sectors tend to have different high and low multiples which stand true both for total period as well as for sub-periods.
[ "Individuals, Markets and Organisations" ]
US 21159780 A
Glass ribbon float tank with a pyrometer assembly having a heated viewing tube and method of use
A viewing tube extension for an infrared radiation pyrometer includes a tube having a heater therein. The heater has a passageway so that the pyrometer sights a glass ribbon moving through a forming chamber of a flat glass making apparatus. Vapors from the heating chamber moving into the tube are maintained above their dew point as a purge gas moves the vapors out of the tube.
[ "Materials Engineering", "Products and Processes Engineering" ]
US 2015/0024664 W
USE OF MICROPARTICLE ADDITIVES TO SIMULTANEOUSLY ENABLE ARTIFACT-FREE IMAGE REGISTRATION, AUTO-FOCUSING, AND CHROMATIC ABERRATION CORRECTION IN MICROSCOPY
High-contrast, high-density cell-sized microparticles (120) are introduced into a cell (llO)-containing solution prior to the solution being spread onto a planar substrate (100) for imaging. The microparticles facilitate both the process of imager autofocusing and the subsequent registration of multiple images taken of regions of the substrate. The microparticles can further facilitate the correction of chromatic aberration.
[ "Physical and Analytical Chemical Sciences", "Systems and Communication Engineering" ]
10.1111/1365-2745.12504
Evidence For Arrested Succession In A Liana Infested Amazonian Forest
1. Empirical evidence and modelling both suggest that global changes may lead to an increased dominance of lianas and thus to an increased prevalence of liana-infested forest formations in tropical forests. The implications for tropical forest structure and the carbon cycle remain poorly understood. 2. We studied the ecological processes underpinning the structure and dynamics of a liana-infested forest in French Guiana, using a combination of long-term surveys (tree, liana, seedling and litterfall), soil chemical analyses and remote-sensing approaches (LiDAR and Landsat). 3. At stand scale and for adult trees, the liana-infested forest had higher growth, recruitment and mortality rates than the neighbouring high-canopy forest. Both total seedling density and tree seedling recruitment were lower in the liana-infested forest. Stand scale above-ground biomass of the liana-infested forest was 58% lower than in the high-canopy forest. 4. Above-ground net primary productivity (ANPP) was comparable in the liana-infested and highcanopy forests. However, due to more abundant leaf production, the relative contribution of fast turnover carbon pools to ANPP was larger in the liana-infested forest and the carbon residence time was half that of the high-canopy forest. 5. Although soils of the liana-infested forest were richer in nutrients, soil elemental ratios suggest that liana-infested forest and high-canopy forest soils both derive from the same geological substrate. The higher nutrient concentration in the liana-infested forest may therefore be the result of a release of nutrients from vegetation after a forest blowdown. 6. Using small-footprint LiDAR campaigns, we show that the overall extent of the liana-infested forest has remained stable from 2007 to 2012 but about 10% of the forest area changed in forest cover type. Landsat optical imagery confirms the liana-infested forest presence in the landscape for at least 25 years. 7. Synthesis. Because persistently high rates of liana infestation are maintained by the fast dynamics of the liana-infested forest, liana-infested forests here appear to be the result of an arrested tropical forest succession. If the prevalence of such arrested succession forests were to increase in the future, this would have important implications for the carbon sink potential of Amazonian forests.
[ "Environmental Biology, Ecology and Evolution", "Earth System Science" ]
EP 2006010357 W
IMPROVED METHOD FOR PRODUCING WASHING OR CLEANING AGENTS
The invention relates to a method for producing washing or cleaning agent granulates, adapted to produce, at low pressure and with high throughput rates, granulates that have a narrow particle distribution. According to said method, a slurry comprising washing or cleaning-active ingredients is atomized through a hollow cone nozzle which has an entry orifice, an atomizing orifice and a swirl chamber connecting the entry orifice and the atomizing orifice, the swirl chamber having a spiraling design. The invention also relates to corresponding hollow cone nozzles.
[ "Products and Processes Engineering", "Materials Engineering" ]
10.7717/peerj.5944
Differences in persistence between dogs and wolves in an unsolvable task in the absence of humans
Despite being closely related, dogs perform worse than wolves in independent problem-solving tasks. These differences in problem-solving performance have been attributed to dogs’ greater reliance on humans, who are usually present when problem-solving tasks are presented. However, more fundamental motivational factors or behavioural traits such as persistence, motor diversity and neophobia may also be responsible for differences in task performance. Hence, to better understand what drives the differences between dogs’ and wolves’ problem-solving performance, it is essential to test them in the absence of humans. Here, we tested equally raised and kept dogs and wolves with two unsolvable tasks, a commonly used paradigm to study problem-solving behaviour in these species. Differently from previous studies, we ensured no humans were present in the testing situation. We also ensured that the task was unsolvable from the start, which eliminated the possibility that specific manipulative behaviours were reinforced. This allowed us to measure both persistence and motor diversity more accurately. In line with previous studies, we found wolves to be more persistent than dogs. We also found motor diversity to be linked to persistence and persistence to be linked to contact latency. Finally, subjects were consistent in their performance between the two tasks. These results suggest that fundamental differences in motivation to interact with objects drive the differences in the performance of dogs and wolves in problem-solving tasks. Since correlates of problem-solving success, that is persistence, neophobia, and motor diversity are influenced by a species’ ecology, our results support the socioecological hypothesis, which postulates that the different ecological niches of the two species (dogs have evolved to primarily be scavengers and thrive on and around human refuse, while wolves have evolved to primarily be group hunters and have a low hunting success rate) have, at least partly, shaped their behaviours.
[ "Environmental Biology, Ecology and Evolution", "The Human Mind and Its Complexity" ]
10.1242/jcs.115808
The α2Na+/K+-ATPase is critical for skeletal and heart muscle function in zebrafish
The Na+/K+-ATPase generates ion gradients across the plasma membrane, essential for multiple cellular functions. In mammals, four different Na+/K+-ATPase α-subunit isoforms are associated with characteristic cell-type expression profiles and kinetics. We found the zebrafish α2Na+/K+-ATPase associated with striated muscles and that α2Na+/K+-ATPase knockdown causes a significant depolarization of the resting membrane potential in slow-twitch fibers of skeletal muscles. Abrupt mechanosensory responses were observed in α2Na+/K+-ATPase deficient embryos, possibly linked to a postsynaptic defect. The α2Na+/K+-ATPase deficiency reduced the heart rate and caused a loss of left-right asymmetry in the heart tube. Similar phenotypes observed by knockdown of the Na+/Ca2+ exchanger indicated a role for the interplay between these two proteins on the observed phenotypes. Furthermore, proteomics identified up- and down-regulation of specific phenotype-related proteins, such as parvalbumin, CaM, GFAP and multiple kinases, thus highlighting a potential proteome change associated with the dynamics of α2Na+/K+-ATPase. Taken together, our findings display that zebrafish α2Na+/K+-ATPase is important for skeletal and heart muscle functions.
[ "Cell Biology, Development, Stem Cells and Regeneration", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
W1974708874
Tryptophan-scanning mutagenesis of the ligand binding pocket in Thermotoga maritima arginine-binding protein
The Thermotoga maritima arginine binding protein (TmArgBP) is a member of the periplasmic binding protein superfamily. As a highly thermostable protein, TmArgBP has been investigated for the potential to serve as a protein scaffold for the development of fluorescent protein biosensors. To establish a relationship between structural dynamics and ligand binding capabilities, we constructed single tryptophan mutants to probe the arginine binding pocket. Trp residues placed around the binding pocket reveal a strong dependence on fluorescence emission of the protein with arginine for all but one of the mutants. Using these data, we calculated dissociation constants of 1.9-3.3 μM for arginine. Stern-Volmer quenching analysis demonstrated that the protein undergoes a large conformational change upon ligand binding, which is a common feature of this protein superfamily. While still active at room temperature, time-resolved intensity and anisotropy decay data suggest that the protein exists as a highly rigid structure under these conditions. Interestingly, TmArgBP exists as a dimer at room temperature in both the presence and absence of arginine, as determined by asymmetric flow field flow fractionation (AF4) and supported by native gel-electrophoresis and time-resolved anisotropy. Our data on dynamics and stability will contribute to our understanding of hyperthermophilic proteins and their potential biotechnological applications.
[ "Physical and Analytical Chemical Sciences", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1007/s10892-017-9246-0
This is a Tricky Situation: Situationism and Reasons-Responsiveness
Situations are powerful: the evidence from experimental social psychology suggests that agents are hugely influenced by the situations they find themselves in, often without their knowing it (this, roughly-speaking, is the thesis of situationism). In our paper, we evaluate how situational factors affect our reasons-responsiveness, as conceived of by John Fischer and Mark Ravizza, and, through this, how they also affect moral responsibility. We argue that the situationist experiments suggest that situational factors impair, among other things, our moderate reasons-responsiveness, which is plausibly required for moral responsibility. However, even though we argue that situational factors lower the degree of our reasons-responsiveness, we propose that agents remain moderately reasons-responsive to the degree required for moral responsibility. Nonetheless, those (adversely) affected by situational factors are arguably less morally responsible than those who are not subject to similar situational factors. We further evaluate an understanding of reasons-responsiveness (developed by Manuel Vargas in the light of situationist data) which relativizes reasons-responsiveness to agents’ circumstances. We argue that the situationist data do not warrant this kind of divergence from Fischer’s and Ravizza’s account. We conclude by discussing what situationist experiments tell us about our relationship to non-reasons.
[ "Texts and Concepts", "The Human Mind and Its Complexity" ]
10.1371/journal.pone.0194179
Niosomes, an alternative for liposomal delivery
Niosomes are used in studies for drug delivery or gene transfer. However, their physical properties and features relative to liposomes are not well documented. To characterize and more rationally optimize niosome formulations, the properties of these vesicle systems are compared to those of liposomes composed of phosphatidylcholine and phosphatidyletha-nolamine lipids plus cholesterol. Niosomes are highly stable and only slightly more leaky than liposomes as assayed by calcein leakage; the permeability for ions (KCl) is higher than that of liposomes. Contrary to liposomes, the size of niosomes decreases substantially upon freezing in liquid nitrogen and subsequent thawing, as shown by cryo-EM and dynamic light scattering. The packing of niosomal membranes was determined by laurdan fluorescence and is slightly lower than that of liposomes. We did not succeed in the functional reconstitution of the L-arginine/L-ornithine antiporter ArcD2 in niosomes, which we attribute to the non-ionic nature of the surfactants. The antimicrobial peptides alamethicin and melittin act similarly on niosomes and liposomes composed of unsaturated components, whereas both niosomes and liposomes are unaffected when saturated amphiphiles are used. In conclusion, in terms of stability and permeability for drug-size molecules niosomes are comparable to liposomes and they may offer an excellent, inexpensive alternative for delivery purposes.
[ "Physical and Analytical Chemical Sciences", "Synthetic Chemistry and Materials", "Materials Engineering" ]
W2009148965
Theory of the spin Hall effect, and its inverse, in a ferromagnetic metal near the Curie temperature
We give a theory of the inverse spin Hall effect (ISHE) in ferromagnetic metals based on skew scattering via collective spin fluctuations. This extends Kondo's theory of the anomalous Hall effect (AHE) to include short-range spin-spin correlations. We find a relation between the ISHE and the four-spin correlations near the Curie temperature TC. Such four-spin correlations do not contribute to the AHE, which relates to the three-spin correlations. Thus our theory shows an essential difference between the AHE and ISHE, providing an essential complement to Kondo's classic theory of the AHE in metals. We note the relation to skew-scattering mechanisms based on impurity scattering. Our theory can be compared to recent experimental results byWei et al. [Nat. Commun. 3, 1058 (2012)] for the ISHE in ferromagnetic alloys.
[ "Condensed Matter Physics" ]
743077
Thermal Magnetic Resonance: A New Instrument to Define the Role of Temperature in Biological Systems and Disease for Diagnosis and Therapy
Temperature is a physical parameter with diverse biological implications and crucial clinical relevance. With an ever increasing interest in thermal applications, non-invasive in vivo methods to modulate temperature and characterize subsequent effects are imperative. Magnetic resonance (MR) is a mainstay of diagnosis but lacks inherent means for focal thermal modulation. Ultrahigh field (UHF) MR employs higher radio frequencies (RF) than conventional MR and has unique potential to provide focal temperature manipulation and high resolution imaging (ThermalMR). Our simulations show that we can adapt an UHF- MR device to generate heat in highly focused regions of tissue by using high-density RF transmitter arrays. This new instrument will provide a revolutionary method for precise in vivo temperature manipulations. To establish high-fidelity thermal dosimetry, we will investigate pioneering strategies that exploit electrical and heat transfer tissue properties. For thermal dosage control, novel methods of MR thermometry will be developed. The capacity of ThermalMR for thermal intervention will be demonstrated in model systems. Its efficacy for drug release will be explored using new thermo-responsive nanocarriers loaded with fluorinated probes, exquisitely quantifiable with 19F MR. The applicability and safety of ThermalMR will be demonstrated in animal models followed by a feasibility study in healthy subjects. To link thermal responses of MR contrasts with molecular signatures, gene expression profiling will be performed. The aim is to understand the thermal properties of healthy and pathological tissues and explore the use of temperature modulation as a therapeutic tool. ThermalMR will eradicate the main barriers to the study and use of temperature - a critical dimension of life that is of intense clinical interest, but so far very poorly understood. This approach opens an entirely new research field of thermal phenotyping: where physics, biology and medicine meet.
[ "Prevention, Diagnosis and Treatment of Human Diseases", "Physical and Analytical Chemical Sciences", "Systems and Communication Engineering", "Molecules of Life: Biological Mechanisms, Structures and Functions" ]
10.1002/adfm.201103034
Co-implantation of carbon and protons: An integrated silicon device technology compatible method to generate the lasing G-center
The optically active carbon related G-center is attracting great interest because of evidence that it can provide lasing in silicon. Here a technique to form the G-center in silicon is reported. The carbon G-center is generated by implantation of carbon followed by proton irradiation. Photoluminescence measurements confirm the controlled formation of high levels of the G-center that, importantly, completely dominates the emission spectrum. Unlike previous methods of introducing the G-center the current approach significantly is truly fully compatible with standard silicon ULSI (ultralarge scale integration) technology.
[ "Condensed Matter Physics", "Materials Engineering", "Synthetic Chemistry and Materials" ]
883476
Early childhood education elearning framework, leveraging novel technology for a whole new way of learning music.
Scientific research proves that early music education, specifically by children ages 0 to 5, is a powerful tool for attaining children’s full intellectual, social and creative potential. Numerous research studies show indisputable evidence that learning music at an early age speeds the development of speech and reading skills, leading to improved comprehension. Musically trained children develop to their full potential, in contrast to the outdated, normative learning models. The early childhood educational paradigm has not experienced changes in decades. Current model is qualitative, teacher-centred and universal. On top of that, formal early childhood education suffers many challenges, including budget cuts, very low attendance in ECE by children and inadequate music qualifications of early childhood educators. Today, professional early childhood music education is purchased by parents in the form of private music classes, or one-off music performances. The burden is on the parents to take up private tuition, and the high costs of private, stationary lessons is a major barrier. Pomelody is the world’s first and only, eLearning framework for comprehensive music education for infants, toddlers and pre-schoolers, which we describe as analogous to a combination of Netflix and Spotify. Pomelody combines our eLearning web application, with assisted learning software tools to track, analyse and enhance children’s learning processes, increasing learning impact and the final performance. Pomelody is a direct response to the “gap” between research and practice on early childhood music education, and fills a significant market gap within the edTech and eLearning segments. Pomelody partakes in the rise of a next giant market opportunity, where according to forecast the global eLearning market for kids is poised to grow over the next decade to reach $325 billion by 2025.
[ "Computer Science and Informatics", "The Social World and Its Interactions" ]
10.1051/0004-6361/200913483
The Agn Fraction Of Submm Selected Galaxies And Contributions To The Submm Mm Wave Extragalactic Background Light
We present a comparison of the SCUBA Half Degree Extragalactic Survey (SHADES) at 450, 850 and 1100 microns with deep guaranteed time 15 microns AKARI FU-HYU survey data and Spitzer guaranteed time data at 3. 6-24 microns in the Lockman Hole East. The AKARI data was analysed using bespoke software based in part on the drizzling and minimum-variance matched filtering developed for SHADES, and was cross calibrated against Infrared Space Observatory (ISO) fluxes. Our stacking analyses find AKARI 15um galaxies with >~200 microJy contribute >10% of the 450 micron background, but only 0. 3.
[ "Universe Sciences" ]
948601
STOrylines of futuRe extreMes
Future climate projections show a strengthening of the hydrological cycle with more droughts and floods expected. This means a higher likelihood of cascading drought-to-flood disasters such as the Millennium Drought – Brisbane flooding in Australia or the California drought – Oroville spillway collapse in the US. Current research and management treat floods and droughts as independent, which leads to large underestimations of their future risk. Droughts allow ample time for impacts and adaptation, which influence hazard, exposure, and vulnerability of a subsequent flood. There are anecdotal examples of these events, but research is needed on the underlying interactions between hydrology and society. In the PerfectSTORM project (‘STOrylines of futuRe extreMes’), I propose to study drought-to-flood events to provide the understanding needed to prevent major disasters in the future. The innovative approach that I will develop is based on a combination of qualitative and quantitative storylines of past and future drought-to-flood risk in case studies and extrapolation of this rich case study information to the global scale. Qualitative storylines will be collected with narrative interviews and mental simulation workshops and will be edited and analysed. Quantitative storylines will be developed from timeseries of hydrological and social data that will be analysed and modelled. These storylines will then be combined in an iterative way using innovative data visualisation. A range of global datasets will be analysed to find global types and hotspots of drought-to-flood events and a global future 3D possibility space will be developed using socio-hydrological modelling. Positive pathways for future management of drought-to-flood events in different parts of the world will then be explored. The PerfectSTORM project will provide in-depth understanding of the hydrosocial feedbacks and dynamic vulnerability of cascading hazards.
[ "Earth System Science", "Human Mobility, Environment, and Space" ]
713780
Photonic Terahertz Signal Analyzers
Spectrum analysis and vector network analysis are enabling technologies for component development throughout the microwave and millimeter wave band. Due to the lack of affordable electronics for frequencies above 100 GHz, vector network analyzers (VNAs) have to use frequency extenders to reach into the THz frequency band (100 GHz-10 THz). The bandwidth of frequency extended electronic systems is restricted to about 50%. Several extender setups have to be used for larger spans, requiring realignment and tedious recalibration. Further, extenders become increasingly expensive the higher the THz frequency and are, therefore, barley used. Electronic spectrum analyzers face similar problems as VNAs. Only a few examples of highly expensive photonic, pulsed frequency comb-based systems have been demonstrated. Affordable, large bandwidth commercial THz metrology tools are missing so far. This proposal aims for the development of photonic THz characterization tools based on telecom-wavelength compatible photomixing technology to satisfy this need: 1.) Photonic vector network analysers (PVNAs) with extreme frequency coverage will be realized by two approaches: a) A planar, on-chip, and broadband dielectric waveguide topology with integrated photomixers for the realization of a continuous-wave (CW) two-port PVNA, covering at least 100 GHz to 1.1 THz in a single setup. b) A pulsed, free space photonic two-port VNA for frequency extension towards 5 THz. 2.) CW photonic THz spectrum analyzers (PSAs) with a frequency coverage of at least 50 GHz -1.1 THz and a simple extension towards 2.7 THz. This system will be realized both free space and on-chip by using a photonic sweep oscillator that is mixed with the signal to be investigated and down-converted by a room-temperature operating THz detector. These systems will provide a solid basis for THz component development. The long term goal beyond this proposal is a competence center for THz device engineering.
[ "Physical and Analytical Chemical Sciences", "Systems and Communication Engineering" ]
223412
Advanced integrated supervisory and wind turbine control for optimal operation of large wind power plants
Cost of energy (COE) is the most important single factor in deployment of renewables in the energy system. Reduction of COE is, among other things, directly related to operational control of Wind Power Plants (WPP) as a whole and the individual wind turbines (WT) within them. In the Total Control project the COE reduction will be pursued by developing and validating advanced integrated WPP/WT control schemes, where all essential interactions between the WPP WT’s are accounted for including both production and load aspects. Optimal WPP control is traditionally formulated as a one-parameter optimization problem focusing on the WPP production only. However, ultimately the optimal WPP performance should result from a multi objective optimization problem, where the optimal economic performance of a WPP is pursued over the WPP life time, conditioned on external grid demands. This is what Total Control is about. The suggested integrated WPP/WT control approach seeks the optimal economical WPP revenue – i.e. the optimal economic balance between WPP power production and WPP operational costs. This is done by developing hierarchically coupled WPP and WT control schemes conditioned on a set of superior grid operator demands. In the WPP control design phase information is only fed from the WPP controller to the individual WT controllers, whereas in on-line operational control available WT and WPP flow field information will be assimilated into the WPP control for optimal system performance. Furthermore, the WPP controller will also make use of current market information (e.g. energy price, demand for ancillary services etc.) as well as information about the state of individual turbines (e.g. current operational state, maintenance requirements and component lifetime consumption) to allow COE objectives to be optimised dynamically.
[ "Products and Processes Engineering", "Systems and Communication Engineering" ]
2718632
Vegetable ozone therapy crops sanitized naturally from seed to feed
Crop pests and disease have serious consequences for agriculture, in terms of economic losses and wastefulness of resources. In addition, according to the FAO, transboundary plant pests and diseases – growing in the last years because of globalization, trade and climate change, as well as reduced resilience in production systems due to decades of agricultural intensification - affect food crops, threatening food security. Agriculture is to be safe, healthy and sustainable, so it is essential to have healthy crops; they play a role in producing sufficient quantities of healthy foods and contribute to the quality of life.OXIR is an innovative technology for spraying aqueous ozone (O3) for disease control and sanitation of greenhouse crops, taking advantage of the powerful oxidation-based (hence non-selective) anti-pathogen action of ozone. OXIR offers two configurations adaptable to users’ needs a fixed and a mobile prototype, that will allow European farmers saving €6.000,00/ha/year due to reductions in chemicals and labour. Currently, existing solutions to fight crop pests and diseases include synthetic chemical pesticides – posing serious environmental concerns - and bio-pesticides – that are not strongly effective, as their pest spectrum is narrow. Compared to these solutions, OXIR is highly efficient against fungi and bacteria (85-99% removal) and viruses (90-99%); costs-effective: OXIR treatment saves working time (1 min. treatment; 20 min. safety interval) compared to biopesticides and chemicals; environmentally sustainable: OXIR is IPM compatible, sustainable, and does not leave polluting residues. The goal of the Phase 2 project is to upgrade OXIR from its current preproduction state to market readiness and develop the first commercial product.
[ "Products and Processes Engineering", "Biotechnology and Biosystems Engineering", "Environmental Biology, Ecology and Evolution" ]
170934
Learning from failure in a collaborative entrepreneurship network
The LIFE project is about collaborative learning from failure in entrepreneurship and collaborative actions to bring entrepreneurship forward. Although cultural diversity is one of Europe’s biggest assets, this also creates severe obstacles for entrepreneurs to scale their efforts at the pan-European level. The distributed markets, language barriers and decentralized policy leads to: lack of access to talent & relevant expertise, to sufficient financing and to adequate facilities & networks. Hinged on a yearly Failing Forward conference, the project will - map out all the relevant stakeholders and programs in each of the partnering areas in a systematic way, making this available to all web entrepreneurs across Europe in one centralized platform, - identify, share and discuss best practices & success stories This yearly pan-European conference in Brussels will be complemented with local spin-off events in the partner regions, to - generate and grow awareness that failure is an inherent part of the process of entrepreneurship and innovation; - share and celebrate the success stories that were built on incremental learning; - open up the existing startup support programs to web entrepreneurs from all over Europe
[ "The Social World and Its Interactions", "Individuals, Markets and Organisations" ]
10.1073/pnas.1220345110
Rotavirus mRNAS are released by transcript-specific channels in the double-layered viral capsid
Rotaviruses are the single most common cause of fatal and severe childhood diarrheal illness worldwide (>125 million cases annually). Rotavirus shares structural and functional features with many viruses, such as the presence of segmented double-stranded RNA genomes selectively and tightly packed with a conserved number of transcription complexes in icosahedral capsids. Nascent transcripts exit the capsid through 12 channels, but it is unknown whether these channels specialize in specific transcripts or simply act as general exit conduits; a detailed description of this process is needed for understanding viral replication and genomic organization. To this end, we developed a single molecule assay for capturing and identifying transcripts extruded from transcriptionally active viral particles. Our findings support a model in which each channel specializes in extruding transcripts of a specific segment that in turn is linked to a single transcription complex. Our approach can be extended to study other viruses and transcription systems.
[ "Molecules of Life: Biological Mechanisms, Structures and Functions", "Immunity, Infection and Immunotherapy" ]
W28828025
Adult house mouse (Mus musculus) ultrasonic calls: hormonal and pheromonal regulation
Abstract An adult male house mouse typically begins calling at ultrasonic frequencies when presented with either a female mouse or her odors. Although direct experimental evidence has been difficult to obtain, ethological, genetic, endocrine, neurological, sound-spectrographic and perceptual findings all indirectly support male calling conveying important information to the female during sexual encounters. Since male calls correlate with the male's immediate sexual arousal and are also attractive to the female, these calls could help coordinate aspects of a mating bout. As might be expected of a reproductive behavior, male calling is hormonally and pheromonally regulated, similarly to other aspects of male reproductive physiology and behavior. Evidence is reviewed that androgen exerts a permissive activational effect during adulthood through its actions in the same brain area (the medial preoptic area) that regulates male-typical copulatory behavior. This activational effect also accounts for the sex difference in mouse calling. Evidence is also reviewed that male calling is pheromonally elicited by chemosignals in female urine.
[ "Physiology in Health, Disease and Ageing", "Neuroscience and Disorders of the Nervous System", "Environmental Biology, Ecology and Evolution" ]
10.1002/pssb.201200155
Effect of gap modes on graphene and multilayer graphene in tip-enhanced Raman spectroscopy
The experimental system formed by an electrochemically etched Au tip and an Au substrate is studied in a tip-enhanced Raman spectroscopy (TERS) setup with side illumination. A resonant optical cavity is created allowing the interaction between localized surface plasmons (LSPs) from the tip and surface plasmon polaritons (SPPs) from the substrate, the so called 'gap modes'. We investigate the interaction between multilayer graphene and gap modes as well as localized emission of defects and inner unknown molecules enhanced by this coupling. The effect of this intense localized electromagnetic field is also studied on monolayer graphene deposited on SiO2. Graphical representation of TERS on graphene.
[ "Physical and Analytical Chemical Sciences", "Condensed Matter Physics" ]
10.1073/pnas.1616392114
Ancient X chromosomes reveal contrasting sex bias in Neolithic and Bronze Age Eurasian migrations
Dramatic events in human prehistory, such as the spread of agriculture to Europe from Anatolia and the late Neolithic/Bronze Age migration from the Pontic-Caspian Steppe, can be investigated using patterns of genetic variation among the people who lived in those times. In particular, studies of differing female and male demographic histories on the basis of ancient genomes can provide information about complexities of social structures and cultural interactions in prehistoric populations. We use a mechanistic admixture model to compare the sex-specifically–inherited X chromosome with the autosomes in 20 early Neolithic and 16 late Neolithic/Bronze Age human remains. Contrary to previous hypotheses suggested by the patrilocality of many agricultural populations, we find no evidence of sex-biased admixture during the migration that spread farming across Europe during the early Neolithic. For later migrations from the Pontic Steppe during the late Neolithic/Bronze Age, however, we estimate a dramatic male bias, with approximately five to 14 migrating males for every migrating female. We find evidence of ongoing, primarily male, migration from the steppe to central Europe over a period of multiple generations, with a level of sex bias that excludes a pulse migration during a single generation. The contrasting patterns of sex-specific migration during these two migrations suggest a view of differing cultural histories in which the Neolithic transition was driven by mass migration of both males and females in roughly equal numbers, perhaps whole families, whereas the later Bronze Age migration and cultural shift were instead driven by male migration, potentially connected to new technology and conquest.
[ "The Study of the Human Past", "Integrative Biology: from Genes and Genomes to Systems" ]
10.1016/j.jet.2014.09.002
Liquid bundles
Parties in financial markets, industries, compensation design or politics may negotiate on either a piecemeal or a bundled basis. Little is known about the desirability of bundling when values are common and/or information endogenous. The paper shows that bundling encourages information-equalizing investments, thereby facilitating trade. It accordingly revisits and qualifies existing knowledge on security design.
[ "Individuals, Markets and Organisations" ]
10.1136/gutjnl-2018-317065
Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets
ObjectiveHepatitis D virus (HDV) is a circular RNA virus coinfecting hepatocytes with hepatitis B virus. Chronic hepatitis D results in severe liver disease and an increased risk of liver cancer. Efficient therapeutic approaches against HDV are absent. DesignHere, we combined an RNAi loss-of-function and small molecule screen to uncover host-dependency factors for HDV infection. ResultsFunctional screening unravelled the hypoxia-inducible factor (HIF)-signalling and insulin-resistance pathways, RNA polymerase II, glycosaminoglycan biosynthesis and the pyrimidine metabolism as virus-hepatocyte dependency networks. Validation studies in primary human hepatocytes identified the carbamoyl-phosphatesynthetase 2, aspartate transcarbamylase and dihydroorotase (CAD) enzyme and estrogen receptor alpha (encoded by ESR1) as key host factors for HDV life cycle. Mechanistic studies revealed that the two host factors are required for viral replication. Inhibition studies using N-(phosphonoacetyl)-L-aspartic acid and fulvestrant, specific CAD and ESR1 inhibitors, respectively, uncovered their impact as antiviral targets. ConclusionThe discovery of HDV host-dependency factors elucidates the pathogenesis of viral disease biology and opens therapeutic strategies for HDV cure.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1038/leu.2017.137
MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation
Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a-/- dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected DCs ameliorated disease. Mechanistically, lack of miR-146a enhanced JAK2-STAT1 pathway activity, which led to higher expression of class II-transactivator (CIITA) and consecutively increased MHCII-levels on DCs. Inhibition of JAK1/2 or CIITA knockdown in DCs prevented miR-146a-/- DC-induced GVHD exacerbation. Consistent with our findings in mice, patients with the miR-146a polymorphism rs2910164 in hematopoietic cells displayed higher MHCII levels on monocytes, which could be targeted by JAK1/2 inhibition. Our findings indicate that the miR-146a polymorphism rs2910164 identifies patients at high risk for GVHD before allo-HCT. Functionally we show that miR-146a acts as a central regulator of recipient-type DC activation during GVHD by dampening the pro-inflammatory JAK-STAT/CIITA/MHCII axis, which provides a scientific rationale for early JAK1/2 inhibition in selected patients.
[ "Immunity, Infection and Immunotherapy", "Molecules of Life: Biological Mechanisms, Structures and Functions", "Prevention, Diagnosis and Treatment of Human Diseases" ]
10.1016/j.epsl.2012.09.051
Gas emissions due to magma-sediment interactions during flood magmatism at the Siberian Traps: Gas dispersion and environmental consequences
We estimate the fluxes of extremely reduced gas emissions produced during the emplacement of the Siberian Traps large igneous province, due to magma intrusion in the coaliferous sediments of the Tunguska Basin. Using the results of a companion paper (Iacono-Marziano et al. , accepted for publication), and a recent work about low temperature interaction between magma and organic matter (Svensen et al. , 2009), we calculate CO-CH4-dominated gas emission rates of 7×1015-2×1016g/yr for a single magmatic/volcanic event. These fluxes are 7-20 times higher than those calculated for purely magmatic gas emissions, in the absence of interaction with organic matter-rich sediments. We investigate, by means of atmospheric modelling employing present geography of Siberia, the short and mid-term dispersion of these gas emissions into the atmosphere. The lateral propagation of CO and CH4 leads to an important perturbation of the atmosphere chemistry, consisting in a strong reduction of the radical OH concentration. As a consequence, both CO and CH4 lifetimes in the lower atmosphere are enhanced by a factor of at least 3, at the continental scale, as a consequence of 30 days of magmatic activity. The short-term effect of the injection of carbon monoxide and methane into the atmosphere is therefore to increase the residence times of these two species and, in turn, their capacity of geographic expansion. The estimated CO and CH4 volume mixing ratios (i. e. the number of molecules of CO or CH4 per cm3, divided by the total number of molecules per cm3) in the low atmosphere are 2-5ppmv at the continental scale and locally higher than 50ppmv. The dimension of the area affected by these high volume mixing ratios decreases in the presence of a lava flow accompanying magma intrusion at depth. Complementary calculations for a 10-yr duration of the magmatic activity suggest (i) an increase in the mean CH4 volume mixing ratio of the whole atmosphere up to values 3-15 times higher than the current one, and (ii) recovery times of 100yr to bring back the atmospheric volume mixing ratio of CH4 to the pre-magmatic value. Thermogenic methane emissions from the Siberian Traps have already been proposed to crucially contribute to end Permian-Early Triassic global warming and to the negative carbon isotopic shift observed globally in both marine and terrestrial sediments. Our results corroborate these hypotheses and suggest that concurrent high temperature CO emissions also played a key role by contributing to increase (i) the radiative forcing of methane and therefore in its global warming potential, and (ii) the input of isotopically light carbon into the atmosphere that generated the isotopic excursion. We also speculate a poisoning effect of high carbon monoxide concentrations on end-Permian fauna, at a local scale.
[ "Earth System Science", "Physical and Analytical Chemical Sciences" ]
225379
Rethinking the health experience and active lifestyles of chinese students
Rethinking the Health Experience and Active Lifestyles of Chinese Students Rising immigration rates into the European Union (EU) has brought increased cultural and linguistic diversity, but also increasing levels of inequalities and the associated challenges of their alleviation. The promotion of physical activity as part of a healthy lifestyle, particularly for the young, is an important part of the European policy to address health inequalities. Minority ethnic youth are amongst those groups with the lowest levels of physical activity, and are identified as a ‘risk’ group in ‘problem-orientated’, ‘deficit’ (and Western) approaches. Chinese youth is a specific group within this physically inactive category, and yet have rarely been the focus of research or policy initiatives. Although described by teachers as ‘model minorities’ - hardworking high achievers - in physical education, health and physical activity (PEHPA), little is known about Chinese youth’s physical activity involvement, or what might represent best practice in PEHPA promotion for this group. Using innovative, participatory methodologies, this research will map the influences on Chinese youth’s needs, meanings, and experiences in PEHPA, create strength-based, new knowledge that goes beyond existing ‘deficit’ approaches to inform strategies to promote their health and physical activity, and develop best practice guidelines for schools and communities. The training through research will be within the Diversity, Equity and Inclusion (DEI) research centre at Leeds Beckett University, one of the largest groupings of internationally renowned experts in the field, with supervision from the Centre head whose research programme provides an ideal match to the training requirements of the proposed research. The training will specifically extend the applicant’s theoretical expertise in contemporary theorising of ethnicity, race, intersectionality and inclusion/promotion; develop expertise in innovative research
[ "The Social World and Its Interactions", "Human Mobility, Environment, and Space", "Prevention, Diagnosis and Treatment of Human Diseases" ]