Section Extension from Hyperbolic Geometry of Punctured Disk and Holomorphic Family of Flat Bundles

The construction of sections of bundles with prescribed jet values plays a fundamental role in problems of algebraic and complex geometry. When the jet values are prescribed on a positive dimensional subvariety, it is handled by theorems of Ohsawa-Takegoshi type which give extension of line bundle valued square-integrable top-degree holomorphic forms from the fiber at the origin of a family of complex manifolds over the open unit 1-disk when the curvature of the metric of line bundle is semipositive. We prove here an extension result when the curvature of the line bundle is only semipositive on each fiber with negativity on the total space assumed bounded from below and the connection of the metric locally bounded, if a square-integrable extension is known to be possible over a double point at the origin. It is a Hensel-lemma-type result analogous to Artin's application of the generalized implicit function theorem to the theory of obstruction in deformation theory. The motivation is the need in the abundance conjecture to construct pluricanonical sections from flatly twisted pluricanonical sections. We also give here a new approach to the original theorem of Ohsawa-Takegoshi by using the hyperbolic geometry of the punctured open unit 1-disk to reduce the original theorem of Ohsawa-Takegoshi to a simple application of the standard method of constructing holomorphic functions by solving the d-bar equation with cut-off functions and additional blowup weight functions

SSMap: A new UniProt-PDB mapping resource for the curation of structural-related information in the UniProt/Swiss-Prot Knowledgebase

<p>Abstract</p> <p>Background</p> <p>Sequences and structures provide valuable complementary information on protein features and functions. However, it is not always straightforward for users to gather information concurrently from the sequence and structure levels. The UniProt knowledgebase (UniProtKB) strives to help users on this undertaking by providing complete cross-references to Protein Data Bank (PDB) as well as coherent feature annotation using available structural information. In this study, SSMap – a new UniProt-PDB residue-residue level mapping – was generated. The primary objective of this mapping is not only to facilitate the two tasks mentioned above, but also to palliate a number of shortcomings of existent mappings. SSMap is the first isoform sequence-specific mapping resource and is up-to-date for UniProtKB annotation tasks. The method employed by SSMap differs from the other mapping resources in that it stresses on the correct reconstruction of the PDB sequence from structures, and on the correct attribution of a UniProtKB entry to each PDB chain by using a series of post-processing steps.</p> <p>Results</p> <p>SSMap was compared to other existing mapping resources in terms of the correctness of the attribution of PDB chains to UniProtKB entries, and of the quality of the pairwise alignments supporting the residue-residue mapping. It was found that SSMap shared about 80% of the mappings with other mapping sources. New and alternative mappings proposed by SSMap were mostly good as assessed by manual verification of data subsets. As for local pairwise alignments, it was shown that major discrepancies (both in terms of alignment lengths and boundaries), when present, were often due to differences in methodologies used for the mappings.</p> <p>Conclusion</p> <p>SSMap provides an independent, good quality UniProt-PDB mapping. The systematic comparison conducted in this study allows the further identification of general problems in UniProt-PDB mappings so that both the coverage and the quality of the mappings can be systematically improved for the benefit of the scientific community. SSMap mapping is currently used to provide PDB cross-references in UniProtKB.</p

Macrophage depletion blocks congenital SARM1-dependent neuropathy

Axon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified 2 rare NMNAT2 missense variants in 2 brothers afflicted with a progressive neuropathy syndrome. The polymorphisms resulted in amino acid substitutions V98M and R232Q, which reduced NMNAT2 NAD+-synthetase activity. We generated a mouse model to mirror the human syndrome and found that Nmnat2V98M/R232Q compound-heterozygous CRISPR mice survived to adulthood but developed progressive motor dysfunction, peripheral axon loss, and macrophage infiltration. These disease phenotypes were all SARM1-dependent. Remarkably, macrophage depletion therapy blocked and reversed neuropathic phenotypes in Nmnat2V98M/R232Q mice, identifying a SARM1-dependent neuroimmune mechanism as a key driver of disease pathogenesis. These findings demonstrate that SARM1 induced inflammatory neuropathy and highlight the potential of immune therapy as a treatment for this rare syndrome and other neurodegenerative conditions associated with NMNAT2 loss and SARM1 activation

Confucius computer: a philosophical digital agent for intergenerational philosophical play

Confucianism is commonly defined as “... a system of philosophical, ethical and political thought based on the teachings of Confucius,” which originated through the teachings of Confucius during the sixth-century BCE. It is a way of life or a philosophy of human nature that considers human relationships as the foundation of the society. Confucius teachings had highly influenced the development of several cultures in Asia, making Confucianism an intangible cultural heritage. In this paper, we are re-acquainting users with an intangible heritage that is part of their everyday, by developing a system that permits experiencing Confucius teachings virtually and interactively. The system can measure philosophical intent of the human and generate meaningful philosophical answers. It is also aimed for intergenerational sharing of Confucius heritage through a simple interactive process with the virtual sage making the experience enjoyable and entertaining. Previous research in natural language processing (NLP) mainly focused on the understanding and delivering of human natural language accurately. In this research, we explored how to apply NLP to model the knowledge and teachings of Confucius, through the natural conversation between human and computer. This virtual Confucius, a chat agent that generates outputs based on Confucius teachings, using a series of algorithms and techniques to improve the matching accuracy between user input and computer output, introduces a novel way of interacting with intangible cultures. Our user evaluation results revealed that there is a positive correlation between relevance and enjoyment, finding their experiences interacting with virtual Confucius very encouraging. Adults who participated in experiencing the virtual Confucius together with their children believed that this system has the potential to improve intergenerational interactions through shared play

Lending Crowdfunding : Principles and Market Development

publishedVersio

Dye molecules in electrolytes: new approach for suppression of dye-desorption in dye-sensitized solar cells

The widespread commercialization of dye-sensitized solar cells remains limited because of the poor long-term stability. We report on the influence of dye-molecules added in liquid electrolyte on long-term stability of dye-sensitized solar cells. Dye-desorption from the TiO2 surface during long-term cycling is one of the decisive factors that degrade photocurrent densities of devices which in turn determine the efficiencies of the devices. For the first time, desorption of dye from the TiO2 surface could be suppressed by controlling thermodynamic equilibrium; by addition of dye molecules in the electrolyte. The dye molecules in the electrolyte can suppress the driving forces for the adsorbed dye molecules to be desorbed from TiO2 nanoparticles. As a result, highly enhanced device stabilities were achieved due to the reduction of dye-desorption although there was a little decrease in the initial efficiencies.open4

Efficacy of Metreleptin in Obese Patients With Type 2 Diabetes: Cellular and Molecular Pathways Underlying Leptin Tolerance

Objective: Metreleptin has been efficacious in improving metabolic control in patients with lipodystrophy, but its efficacy has not been tested in obese patients with type 2 diabetes. Research Design and Methods: We studied the role of leptin in regulating the endocrine adaptation to long-term caloric deprivation and weight loss in obese diabetic subjects over 16 weeks in the context of a double-blinded, placebo–controlled, randomized trial. We then performed detailed interventional and mechanistic signaling studies in humans in vivo, ex vivo, and in vitro. Results: In obese patients with diabetes, metreleptin administration for 16 weeks did not alter body weight or circulating inflammatory markers but reduced HbA$_{1c}$ marginally (8.01 $\pm$ 0.93–7.96 $\pm$ 1.12, P = 0.03). Total leptin, leptin-binding protein, and antileptin antibody levels increased, limiting free leptin availability and resulting in circulating free leptin levels of $\sim$50 ng/mL. Consistent with clinical observations, all metreleptin signaling pathways studied in human adipose tissue and peripheral blood mononuclear cells were saturable at $\sim$50 ng/mL, with no major differences in timing or magnitude of leptin-activated STAT3 phosphorylation in tissues from male versus female or obese versus lean humans in vivo, ex vivo, or in vitro. We also observed for the first time that endoplasmic reticulum (ER) stress in human primary adipocytes inhibits leptin signaling. Conclusions: In obese patients with diabetes, metreleptin administration did not alter body weight or circulating inflammatory markers but reduced HbA$_{1c}$ marginally. ER stress and the saturable nature of leptin signaling pathways play a key role in the development of leptin tolerance in obese patients with diabetes

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

A review of high impact weather for aviation meteorology

This review paper summarizes current knowledge available for aviation operations related to meteorology and provides suggestions for necessary improvements in the measurement and prediction of weather-related parameters, new physical methods for numerical weather predictions (NWP), and next-generation integrated systems. Severe weather can disrupt aviation operations on the ground or in-flight. The most important parameters related to aviation meteorology are wind and turbulence, fog visibility, aerosol/ash loading, ceiling, rain and snow amount and rates, icing, ice microphysical parameters, convection and precipitation intensity, microbursts, hail, and lightning. Measurements of these parameters are functions of sensor response times and measurement thresholds in extreme weather conditions. In addition to these, airport environments can also play an important role leading to intensification of extreme weather conditions or high impact weather events, e.g., anthropogenic ice fog. To observe meteorological parameters, new remote sensing platforms, namely wind LIDAR, sodars, radars, and geostationary satellites, and in situ instruments at the surface and in the atmosphere, as well as aircraft and Unmanned Aerial Vehicles mounted sensors, are becoming more common. At smaller time and space scales (e.g., < 1 km), meteorological forecasts from NWP models need to be continuously improved for accurate physical parameterizations. Aviation weather forecasts also need to be developed to provide detailed information that represents both deterministic and statistical approaches. In this review, we present available resources and issues for aviation meteorology and evaluate them for required improvements related to measurements, nowcasting, forecasting, and climate change, and emphasize future challenges