The Repository Chemotion: Infrastructure for Sustainable Research in Chemistry

We describe the development of a repository for chemistry research data (called Chemotion) that provides solutions for current challenges to store research data in a feasible manner, allowing the conservation of domain‐specific information in a machine‐readable format. A main advantage of the repository Chemotion is the comprehensive functionality, offering options to collect, prepare and reuse data with discipline specific methods and data processing tools. For selected analytical data, automated procedures are implemented to facilitate the curation of the data. Chemotion provides functions for a feasible data publishing process including automated Digital Object Identifier (DOI) generation and workflows for peer reviewing of the submissions, including embargo settings. The described developments were used to establish a research‐data infrastructure to build a new community‐driven repository as a comprehensive alternative to commercial databases

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p < 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

All-electrical detection of the spin-charge conversion in nanodevices based on SrTiO3 two-dimensional electron gases

The Magnetoelectric Spin-Orbit (MESO) technology aims to bring logic into memory by combining a ferromagnet with a magnetoelectric (ME) element for information writing, and a spin-orbit (SO) element for information read-out through spin-charge conversion. Among candidate SO materials to achieve a large MESO output signal, oxide Rashba two-dimensional electron gases (2DEGs) have shown very large spin-charge conversion efficiencies, albeit mostly in spin-pumping experiments. Here, we report all-electrical spin-injection and spin-charge conversion experiments in nanoscale devices harnessing the inverse Edelstein effect of SrTiO3 2DEGs. We have designed, patterned and fabricated nanodevices in which a spin current injected from a cobalt layer into the 2DEG is converted into a charge current. We optimized the spin-charge conversion signal by applying back-gate voltages, and studied its temperature evolution. We further disentangled the inverse Edelstein contribution from spurious effects such as the planar Hall effect, the anomalous Hall effect or the anisotropic magnetoresistance. The combination of non-volatility and high energy efficiency of these devices could potentially lead to new technology paradigms for beyond-CMOS computing architectures

Genetic algorithm-based optimization of pulse sequences.

Funder: Cambridge Commonwealth, European and International Trust; Id: http://dx.doi.org/10.13039/501100003343PURPOSE: The performance of pulse sequences in vivo can be limited by fast relaxation rates, magnetic field inhomogeneity, and nonuniform spin excitation. We describe here a method for pulse sequence optimization that uses a stochastic numerical solver that in principle is capable of finding a global optimum. The method provides a simple framework for incorporating any constraint and implementing arbitrarily complex cost functions. Efficient methods for simulating spin dynamics and incorporating frequency selectivity are also described. METHODS: Optimized pulse sequences for polarization transfer between protons and X-nuclei and excitation pulses that eliminate J-coupling modulation were evaluated experimentally using a surface coil on phantoms, and also the detection of hyperpolarized [2-13 C]lactate in vivo in the case of J-coupling modulation-free excitation. RESULTS: The optimized polarization transfer pulses improved the SNR by ~50% with a more than twofold reduction in the B1 field, and J-coupling modulation-free excitation was achieved with a more than threefold reduction in pulse length. CONCLUSION: This process could be used to optimize any pulse when there is a need to improve the uniformity and frequency selectivity of excitation as well as to design new pulses to steer the spin system to any desired achievable state

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

New factors for protein transport identified by a genome-wide CRISPRi screen in mammalian cells

Protein and membrane trafficking pathways are critical for cell and tissue homeostasis. Traditional genetic and biochemical approaches have shed light on basic principles underlying these processes. However, the list of factors required for secretory pathway function remains incomplete, and mechanisms involved in their adaptation poorly understood. Here, we present a powerful strategy based on a pooled genome-wide CRISPRi screen that allowed the identification of new factors involved in protein transport. Two newly identified factors, TTC17 and CCDC157, localized along the secretory pathway and were found to interact with resident proteins of ER-Golgi membranes. In addition, we uncovered that upon TTC17 knockdown, the polarized organization of Golgi cisternae was altered, creating glycosylation defects, and that CCDC157 is an important factor for the fusion of transport carriers to Golgi membranes. In conclusion, our work identified and characterized new actors in the mechanisms of protein transport and secretion, and opens stimulating perspectives for the use of our platform in physiological and pathological contexts.Includes Wellcome Trust, MRC and H202

Burden of Stroke in Europe:An Analysis of the Global Burden of Disease Study Findings From 2010 to 2019

BACKGROUND:While most European Regions perform well in global comparisons, large discrepancies within stroke epidemiological parameters exist across Europe. The objective of this analysis was to evaluate the stroke burden across European regions and countries in 2019 and its difference to 2010.METHODS:The GBD 2019 analytical tools were used to evaluate regional and country-specific estimates of incidence, prevalence, deaths, and disability-adjusted life years of stroke for the European Region as defined by the World Health Organization, with its 53 member countries (EU-53) and for European Union as defined in 2019, with its 28 member countries (EU-28), between 2010 and 2019. Results were analyzed at a regional, subregional, and country level.RESULTS:In EU-53, the absolute number of incident and prevalent strokes increased by 2% (uncertainty interval [UI], 0%–4%), from 1 767 280 to 1 802 559 new cases, and by 4% (UI, 3%–5%) between 2010 and 2019, respectively. In EU-28, the absolute number of prevalent strokes and stroke-related deaths increased by 4% (UI, 2%–5%) and by 6% (UI, 1%–10%), respectively. All-stroke age-standardized mortality rates, however, decreased by 18% (UI, −22% to −14%), from 82 to 67 per 100 000 people in the EU-53, and by 15% (UI, −18% to −11%), from 49.3 to 42.0 per 100 000 people in EU-28. Despite most countries presenting reductions in age-adjusted incidence, prevalence, mortality, and disability-adjusted life year rates, these rates remained 1.4×, 1.2×, 1.6×, and 1.7× higher in EU-53 in comparison to the EU-28.CONCLUSIONS:EU-53 showed a 2% increase in incident strokes, while they remained stable in EU-28. Age-standardized rates were consistently lower for all-stroke burden parameters in EU-28 in comparison to EU-53, and huge discrepancies in incidence, prevalence, mortality, and disability-adjusted life-year rates were observed between individual countries.<br/

Isolation and Characterization of Novel Murine Epiphysis Derived Mesenchymal Stem Cells

BACKGROUND: While bone marrow (BM) is a rich source of mesenchymal stem cells (MSCs), previous studies have shown that MSCs derived from mouse BM (BMMSCs) were difficult to manipulate as compared to MSCs derived from other species. The objective of this study was to find an alternative murine MSCs source that could provide sufficient MSCs. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we described a novel type of MSCs that migrates directly from the mouse epiphysis in culture. Epiphysis-derived MSCs (EMSCs) could be extensively expanded in plastic adherent culture, and they had a greater ability for clonogenic formation and cell proliferation than BMMSCs. Under specific induction conditions, EMSCs demonstrated multipotency through their ability to differentiate into adipocytes, osteocytes and chondrocytes. Immunophenotypic analysis demonstrated that EMSCs were positive for CD29, CD44, CD73, CD105, CD166, Sca-1 and SSEA-4, while negative for CD11b, CD31, CD34 and CD45. Notably, EMSCs did not express major histocompatibility complex class I (MHC I) or MHC II under our culture system. EMSCs also successfully suppressed the proliferation of splenocytes triggered by concanavalin A (Con A) or allogeneic splenocytes, and decreased the expression of IL-1, IL-6 and TNF-α in Con A-stimulated splenocytes suggesting their anti-inflammatory properties. Moreover, EMSCs enhanced fracture repair, ameliorated necrosis in ischemic skin flap, and improved blood perfusion in hindlimb ischemia in the in vivo experiments. CONCLUSIONS/SIGNIFICANCES: These results indicate that EMSCs, a new type of MSCs established by our simple isolation method, are a preferable alternative for mice MSCs due to their better growth and differentiation potentialities