Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo

This work was supported by funding from The NIHR Academic Clinical Fellowship scheme and a Wellcome Trust Clinical Research Training fellowship (107389/Z/15/Z) awarded to USG; a Wellcome Trust Senior Investigator award (101848/Z/ 13/Z) to MKM and a Barts and The London Charity award (No. 723/1795) to PTFK

TRAIL regulatory receptors constrain human hepatic stellate cell apoptosis

This work was funded by UCLH NIHR BRC (sample collection), Wellcome Trust Investigator award (MKM) and Clinical Research Training Fellowship (USG); Medical Research Council grant (MKM) and Clinician Scientist Fellowship (DP); EASL fellowship (IO); National Health and Medical Research Council Australia (KPS)

Development of Large Bandgap Materials Using Reactive Growth in Al-SI Eutectic for Optical and RF Applications

Carbon was utilized as reactive element to modify the microstructure using forced mixing during crystallization of the Al-Si alloy by rotation and stirring. We nucleated the material on SiC substrates while the Al-Si melt was rotated with a speed of 30rpm in a graphite crucible. Several experiments were performed and parameters such as time of mixing, soaking temperature, rotation rate of the substrate and rate of cooling during the solidification was changed. We observed dendrite and cell morphologies during the solidification of rotating melt. The microstructure was characterized by optical microscopy and SEM-EDX and compositional spectroscopy. The effect of carbon impurities was studied on the solidifying microstructure. When we used the longer soak time of the melt in presence of carbon impurities we observed the destruction of dendritic morphology and the formation of cellular and colony structures. Similar approach has been used for Ga2O3, a novel large bandgap material also

Development of a strontium optical lattice clock for the SOC mission on the ISS

The ESA mission "Space Optical Clock" project aims at operating an optical lattice clock on the ISS in approximately 2023. The scientific goals of the mission are to perform tests of fundamental physics, to enable space-assisted relativistic geodesy and to intercompare optical clocks on the ground using microwave and optical links. The performance goal of the space clock is less than $1 \times 10^{-17}$ uncertainty and $1 \times 10^{-15} {\tau}^{-1/2}$ instability. Within an EU-FP7-funded project, a strontium optical lattice clock demonstrator has been developed. Goal performances are instability below $1 \times 10^{-15} {\tau}^{-1/2}$ and fractional inaccuracy $5 \times 10^{-17}$. For the design of the clock, techniques and approaches suitable for later space application are used, such as modular design, diode lasers, low power consumption subunits, and compact dimensions. The Sr clock apparatus is fully operational, and the clock transition in $^{88}$Sr was observed with linewidth as small as 9 Hz.Comment: 12 pages, 8 figures, SPIE Photonics Europe 201

A modified deep learning weather prediction using cubed sphere for global precipitation

Deep learning (DL), a potent technology to develop Digital Twin (DT), for weather prediction using cubed spheres (DLWP-CS) was recently proposed to facilitate data-driven simulations of global weather fields. DLWP-CS is a temporal mapping algorithm wherein time-stepping is performed through U-NET. Although DLWP-CS has shown impressive results for fields, such as temperature and geopotential height, this technique is complicated and computationally challenging for a complex, non-linear field, such as precipitation, which depends on other prognostic environmental co-variables. To address this challenge, we modify the DLWP-CS and call our technique “modified DLWP-CS” (MDLWP-CS). In this study, we transform the architecture from a temporal to a spatio-temporal mapping (multivariate setup), wherein precursor(s) of precipitation can be used as input. As a proof of concept, as a first simple case, a 2-m surface air temperature is used to predict precipitation using MDLWP-CS. The model is trained using hourly ERA-5 reanalysis and the resulting experimental findings are compared to two benchmark models, viz, the linear regression and an operational numerical weather prediction model, which is the Global Forecast System (GFS). The fidelity of MDLWP-CS is much better compared to linear regression and the results are equivalent to GFS output in terms of daily precipitation prediction with 1 day lag. These results provide an encouraging framework for an efficient DT that can facilitate speedy, high fidelity precipitation predictions.</jats:p

Development of a strontium optical lattice clock for the SOC mission on the ISS

Ultra-precise optical clocks in space will allow new studies in fundamental physics and astronomy. Within an European Space Agency (ESA) program, the Space Optical Clocks (SOC) project aims to install and to operate an optical lattice clock on the International Space Station (ISS) towards the end of this decade. It would be a natural follow-on to the ACES mission, improving its performance by at least one order of magnitude. The payload is planned to include an optical lattice clock, as well as a frequency comb, a microwave link, and an optical link for comparisons of the ISS clock with ground clocks located in several countries and continents. Within the EU-FP7-SPACE-2010-1 project no. 263500, during the years 2011-2015 a compact, modular and robust strontium lattice optical clock demonstrator has been developed. Goal performance is a fractional frequency instability below 1x10^{-15}, tau^{-1/2} and a fractional inaccuracy below 5x10^{-17}. Here we describe the current status of the apparatus' development, including the laser subsystems. Robust preparation of cold {88}^Sr atoms in a second stage magneto-optical trap (MOT) is achieved.Comment: 27 Pages, 15 figures, Comptes Rendus Physique 201

Immune system-wide Mendelian randomization and triangulation analyses support autoimmunity as a modifiable component in dementia-causing diseases

Immune system and blood–brain barrier dysfunction are implicated in the development of Alzheimer’s and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood–brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-β, tau and α-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer’s disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49–0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases

Policy of foreign direct investment liberalisation in India: implications for retail sector

This study has analysed the impact of liberalisation of Indian economy and FDI policy on the retail sector since its implementation in the 1990s. It also further analyses sub-categories by investigating its impact on the unorganised retail sector and the flow of FDI in single-brand retail and multi-brand retail sectors. A comprehensive and critical review of the existing evidence on the subject was carried out, and descriptive statistical analysis of data from 1991 to 2013 was performed which leads to conclude that the policy of FDI liberalisation has proved to provide diversification and sustainable development to the Indian economy and specifically retail sector which is considered to be one of the significant pillars of economy. Furthermore, for continuous growth of the economy, it seems vital to encourage more investment in other sectors by liberalising the restrictive policies

Estimating Dementia Risk Using Multifactorial Prediction Models

IMPORTANCE: The clinical value of current multifactorial algorithms for individualized assessment of dementia risk remains unclear. OBJECTIVE: To evaluate the clinical value associated with 4 widely used dementia risk scores in estimating 10-year dementia risk. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based UK Biobank cohort study assessed 4 dementia risk scores at baseline (2006-2010) and ascertained incident dementia during the following 10 years. Replication with a 20-year follow-up was based on the British Whitehall II study. For both analyses, participants who had no dementia at baseline, had complete data on at least 1 dementia risk score, and were linked to electronic health records from hospitalizations or mortality were included. Data analysis was conducted from July 5, 2022, to April 20, 2023. EXPOSURES: Four existing dementia risk scores: the Cardiovascular Risk Factors, Aging and Dementia (CAIDE)-Clinical score, the CAIDE-APOE-supplemented score, the Brief Dementia Screening Indicator (BDSI), and the Australian National University Alzheimer Disease Risk Index (ANU-ADRI). MAIN OUTCOMES AND MEASURES: Dementia was ascertained from linked electronic health records. To evaluate how well each score predicted the 10-year risk of dementia, concordance (C) statistics, detection rate, false-positive rate, and the ratio of true to false positives were calculated for each risk score and for a model including age alone. RESULTS: Of 465 929 UK Biobank participants without dementia at baseline (mean [SD] age, 56.5 [8.1] years; range, 38-73 years; 252 778 [54.3%] female participants), 3421 were diagnosed with dementia at follow-up (7.5 per 10 000 person-years). If the threshold for a positive test result was calibrated to achieve a 5% false-positive rate, all 4 risk scores detected 9% to 16% of incident dementia and therefore missed 84% to 91% (failure rate). The corresponding failure rate was 84% for a model that included age only. For a positive test result calibrated to detect at least half of future incident dementia, the ratio of true to false positives ranged between 1 to 66 (for CAIDE-APOE-supplemented) and 1 to 116 (for ANU-ADRI). For age alone, the ratio was 1 to 43. The C statistic was 0.66 (95% CI, 0.65-0.67) for the CAIDE clinical version, 0.73 (95% CI, 0.72-0.73) for the CAIDE-APOE-supplemented, 0.68 (95% CI, 0.67-0.69) for BDSI, 0.59 (95% CI, 0.58-0.60) for ANU-ADRI, and 0.79 (95% CI, 0.79-0.80) for age alone. Similar C statistics were seen for 20-year dementia risk in the Whitehall II study cohort, which included 4865 participants (mean [SD] age, 54.9 [5.9] years; 1342 [27.6%] female participants). In a subgroup analysis of same-aged participants aged 65 (±1) years, discriminatory capacity of risk scores was low (C statistics between 0.52 and 0.60). CONCLUSIONS AND RELEVANCE: In these cohort studies, individualized assessments of dementia risk using existing risk prediction scores had high error rates. These findings suggest that the scores were of limited value in targeting people for dementia prevention. Further research is needed to develop more accurate algorithms for estimation of dementia risk

The Space Optical Clocks Project: Development of high-performance transportable and breadboard optical clocks and advanced subsystems

The use of ultra-precise optical clocks in space ("master clocks") will allow for a range of new applications in the fields of fundamental physics (tests of Einstein's theory of General Relativity, time and frequency metrology by means of the comparison of distant terrestrial clocks), geophysics (mapping of the gravitational potential of Earth), and astronomy (providing local oscillators for radio ranging and interferometry in space). Within the ELIPS-3 program of ESA, the "Space Optical Clocks" (SOC) project aims to install and to operate an optical lattice clock on the ISS towards the end of this decade, as a natural follow-on to the ACES mission, improving its performance by at least one order of magnitude. The payload is planned to include an optical lattice clock, as well as a frequency comb, a microwave link, and an optical link for comparisons of the ISS clock with ground clocks located in several countries and continents. Undertaking a necessary step towards optical clocks in space, the EU-FP7-SPACE-2010-1 project no. 263500 (SOC2) (2011-2015) aims at two "engineering confidence", accurate transportable lattice optical clock demonstrators having relative frequency instability below 1\times10^-15 at 1 s integration time and relative inaccuracy below 5\times10^-17. This goal performance is about 2 and 1 orders better in instability and inaccuracy, respectively, than today's best transportable clocks. The devices will be based on trapped neutral ytterbium and strontium atoms. One device will be a breadboard. The two systems will be validated in laboratory environments and their performance will be established by comparison with laboratory optical clocks and primary frequency standards. In this paper we present the project and the results achieved during the first year.Comment: Contribution to European Frequency and Time Forum 2012, Gothenburg, Swede