Fredholm factorization of Wiener-Hopf scalar and matrix kernels

A general theory to factorize the Wiener-Hopf (W-H) kernel using Fredholm Integral Equations (FIE) of the second kind is presented. This technique, hereafter called Fredholm factorization, factorizes the W-H kernel using simple numerical quadrature. W-H kernels can be either of scalar form or of matrix form with arbitrary dimensions. The kernel spectrum can be continuous (with branch points), discrete (with poles), or mixed (with branch points and poles). In order to validate the proposed method, rational matrix kernels in particular are studied since they admit exact closed form factorization. In the appendix a new analytical method to factorize rational matrix kernels is also described. The Fredholm factorization is discussed in detail, supplying several numerical tests. Physical aspects are also illustrated in the framework of scattering problems: in particular, diffraction problems. Mathematical proofs are reported in the pape

The Expectation Monad in Quantum Foundations

The expectation monad is introduced abstractly via two composable adjunctions, but concretely captures measures. It turns out to sit in between known monads: on the one hand the distribution and ultrafilter monad, and on the other hand the continuation monad. This expectation monad is used in two probabilistic analogues of fundamental results of Manes and Gelfand for the ultrafilter monad: algebras of the expectation monad are convex compact Hausdorff spaces, and are dually equivalent to so-called Banach effect algebras. These structures capture states and effects in quantum foundations, and also the duality between them. Moreover, the approach leads to a new re-formulation of Gleason's theorem, expressing that effects on a Hilbert space are free effect modules on projections, obtained via tensoring with the unit interval.Comment: In Proceedings QPL 2011, arXiv:1210.029

Thermocapillary actuation of liquid flow on chemically patterned surfaces

We have investigated the thermocapillary flow of a Newtonian liquid on hydrophilic microstripes which are lithographically defined on a hydrophobic surface. The speed of the microstreams is studied as a function of the stripe width w, the applied thermal gradient |dT/dx| and the liquid volume V deposited on a connecting reservoir pad. Numerical solutions of the flow speed as a function of downstream position show excellent agreement with experiment. The only adjustable parameter is the inlet film height, which is controlled by the ratio of the reservoir pressure to the shear stress applied to the liquid stream. In the limiting cases where this ratio is either much smaller or much larger than unity, the rivulet speed shows a power law dependency on w, |dT/dx| and V. In this study we demonstrate that thermocapillary driven flow on chemically patterned surfaces can provide an elegant and tunable method for the transport of ultrasmall liquid volumes in emerging microfluidic technologies

Bridging the Mid-Infrared-to-Telecom Gap with Silicon Nanophotonic Spectral Translation

Expanding far beyond traditional applications in optical interconnects at telecommunications wavelengths, the silicon nanophotonic integrated circuit platform has recently proven its merits for working with mid-infrared (mid-IR) optical signals in the 2-8 {\mu}m range. Mid-IR integrated optical systems are capable of addressing applications including industrial process and environmental monitoring, threat detection, medical diagnostics, and free-space communication. Rapid progress has led to the demonstration of various silicon components designed for the on-chip processing of mid-IR signals, including waveguides, vertical grating couplers, microcavities, and electrooptic modulators. Even so, a notable obstacle to the continued advancement of chip-scale systems is imposed by the narrow-bandgap semiconductors, such as InSb and HgCdTe, traditionally used to convert mid-IR photons to electrical currents. The cryogenic or multi-stage thermo-electric cooling required to suppress dark current noise, exponentially dependent upon the ratio Eg/kT, can limit the development of small, low-power, and low-cost integrated optical systems for the mid-IR. However, if the mid-IR optical signal could be spectrally translated to shorter wavelengths, for example within the near-infrared telecom band, photodetectors using wider bandgap semiconductors such as InGaAs or Ge could be used to eliminate prohibitive cooling requirements. Moreover, telecom band detectors typically perform with higher detectivity and faster response times when compared with their mid-IR counterparts. Here we address these challenges with a silicon-integrated approach to spectral translation, by employing efficient four-wave mixing (FWM) and large optical parametric gain in silicon nanophotonic wires

Clade, Country and Region-specific HIV-1 Vaccines: Are they necessary?

Today, scientists are often encouraged to custom-design vaccines based on a particular country or clade. Here, we review the scientific literature and then suggest that the overwhelming endeavor to produce a unique vaccine for every world region or virus subtype may not be necessary

mRNA vaccine mitigates SARS-CoV-2 infections and COVID-19

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in December of 2019 and is responsible for millions of infections and deaths across the globe. Vaccination against SARS-CoV-2 has proven effective to contain the spread of the virus and reduce disease. The production and distribution of these vaccines occurred at a remarkable pace, largely through the employment of the novel mRNA platform. However, interruptions in supply chain and high demand for clinical grade reagents have impeded the manufacture and distribution of mRNA vaccines at a time when accelerated vaccine deployment is crucial. Furthermore, the emergence of SARS-CoV-2 variants across the globe continues to threaten the efficacy of vaccines encoding the ancestral virus spike protein. Here, we report results from preclinical studies on mRNA vaccines developed using a proprietary mRNA production process developed by GreenLight Biosciences. Two mRNA vaccines encoding the full-length, nonstabilized SARS-CoV-2 spike protein, GLB-COV2-042 and GLB-COV2-043, containing uridine and pseudouridine, respectively, were evaluated in rodents for their immunogenicity and protection from SARS-CoV-2 challenge with the ancestral strain and the Alpha (B.1.1.7) and Beta (B.1.351) variants. In mice and hamsters, both vaccines induced robust spike-specific binding and neutralizing antibodies, and in mice, vaccines induced significant T cell responses with a clear Th1 bias. In hamsters, both vaccines conferred significant protection following challenge with SARS-CoV-2 as assessed by weight loss, viral load, and virus replication in the lungs and nasopharynx. These results support the development of GLB-COV2-042 and GLB-COV2-043 for clinical use

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Large-Scale Genome-Wide Meta-Analysis of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture for Different Diagnosis Criteria

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation