Atomic-scale combination of germanium-zinc nanofibers for structural and electrochemical evolution

Alloys are recently receiving considerable attention in the community of rechargeable batteries as possible alternatives to carbonaceous negative electrodes; however, challenges remain for the practical utilization of these materials. Herein, we report the synthesis of germanium-zinc alloy nanofibers through electrospinning and a subsequent calcination step. Evidenced by in situ transmission electron microscopy and electrochemical impedance spectroscopy characterizations, this one-dimensional design possesses unique structures. Both germanium and zinc atoms are homogenously distributed allowing for outstanding electronic conductivity and high available capacity for lithium storage. The as-prepared materials present high rate capability (capacity of similar to 50% at 20 C compared to that at 0.2 C-rate) and cycle retention (73% at 3.0 C-rate) with a retaining capacity of 546 mAh g(-1) even after 1000 cycles. When assembled in a full cell, high energy density can be maintained during 400 cycles, which indicates that the current material has the potential to be used in a large-scale energy storage system

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

mTOR independent regulation of macroautophagy by Leucine Rich Repeat Kinase 2 via Beclin-1

Leucine rich repeat kinase 2 is a complex enzyme with both kinase and GTPase activities, closely linked to the pathogenesis of several human disorders including Parkinson’s disease, Crohn’s disease, leprosy and cancer. LRRK2 has been implicated in numerous cellular processes; however its physiological function remains unclear. Recent reports suggest that LRRK2 can act to regulate the cellular catabolic process of macroautophagy, although the precise mechanism whereby this occurs has not been identi ed. To investigate the signalling events through which LRRK2 acts to in uence macroautophagy, the mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) and Beclin-1/phosphatidylinositol 3-kinase (PI3K) pathways were evaluated in astrocytic cell models in the presence and absence of LRRK2 kinase inhibitors. Chemical inhibition of LRRK2 kinase activity resulted in the stimulation of macroautophagy in a non-canonical fashion, independent of mTOR and ULK1, but dependent upon the activation of Beclin 1-containing class III PI3-kinase

Stability of Piceatannol in Dulbecco's Modified Eagle's Medium by In Situ UPLC-MS/MS Analysis

Piceatannol is a stilbenoid, which has shown bioactivities in various cell culture models. However, its stability in cell culture medium is not clear. Here, UPLC-MS/MS was applied in situ to analyze the degradation products of piceatannol in Dulbecco's Modified Eagle's Medium (DMEM) and cell culture to investigate the compound's stability in DMEM. During the incubation with cell culture medium (at 4 and 37 °C), several piceatannol derivatives, such as an oxidation product ( m/z 243.06), a reduction product ( m/z 247.09), dimers ( m/z 485.12 and 487.14) and trimers ( m/z 727.18) were detected, which demonstrated the instability of piceatannol in cell culture conditions. To confirm if the new products during the incubation were generated due to the instability of piceatannol, ascorbic acid was added. The presence of ascorbic acid could significantly slow the degradation rate of piceatannol and the generation of piceatannol derivatives, which proved that the new products were generated by the degradation of piceatannol and indicated that the instability of piceatannol might be related to its antioxidant activity

Phylogenomic analysis of a global collection of Escherichia coli ST38: evidence of interspecies and environmental transmission?

We performed a comprehensive phylogenomic analysis of 925 extraintestinal pathogenic Escherichia coli (ExPEC) ST38 genomes from 38 countries and diverse hosts and sources. The phylogeny resolved two broad clades: A (593 strains; 91% human) and B (332 isolates; 42% human), each with distinct ST38 clusters linked to the carriage of specific bla CTX-M alleles, often in association with other antibiotic resistance genes, class 1 integrons and specific plasmid replicon types. Co-carriage of fyuA and irp2 virulence genes, a reliable proxy for carriage of the Yersinia high-pathogenicity island, featured in 580 (62.7%) genomes. ST38 lineages carrying combinations of ExPEC and intestinal pathogenic Escherichia coli virulence factors were also identified. The F plasmid replicon was identified in 536 (58%) genomes, and 112 of these (21%) carry cjrABC-senB, a virulence operon frequently identified in pandemic ExPEC sequence types. Most (108; 96.4%) cjrABC-senB+ ST38 isolates were from human and other sources, except food animals, and were associated with F5:A-:B10 (41 isolates), F1:A2:B20 (20 isolates), and F24:A-:B1 (15 isolates) F replicon types. ST38 genomes that were inferred to carry a ColV-F virulence plasmid (69; 7.4%) were mostly from human (12; 17.4%), avian (26; 37.7%), or poultry (10; 6.9%) sources. We identified multiple examples of putative inter-host and host-environment transmission events, where genomes differed by <35 SNPs. This work emphasizes the importance of adopting a One Health approach for phylogenomic studies that seek to improve understanding of antimicrobial resistance and pathogen evolution. IMPORTANCE Extraintestinal pathogenic Escherichia coli (ExPEC) sequence type (ST) 38 is one of the top 10 human pandemic lineages. Although a major cause of urinary tract and blood stream infections, ST38 has been poorly characterized from a global phylogenomic perspective. A comprehensive genome-scale analysis of 925 ST38 isolate genomes identified two broad ancestral clades and linkage of discrete ST38 clusters with specific bla CTX-M variants. In addition, the clades and clusters carry important virulence genes, with diverse but poorly characterized plasmids. Numerous putative interhost and environment transmission events were identified here by the presence of ST38 clones (defined as isolates with ≤35 SNPs) within humans, companion animals, food sources, urban birds, wildlife, and the environment. A small cluster of international ST38 clones from diverse sources, likely representing progenitors of a hospital outbreak that occurred in Brisbane, Australia, in 2017, was also identified. Our study emphasizes the importance of characterizing isolate genomes derived from nonhuman sources and geographical locations, without any selection bias

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

A Unifying Framework for Evaluating the Predictive Power of Genetic Variants Based on the Level of Heritability Explained

An increasing number of genetic variants have been identified for many complex diseases. However, it is controversial whether risk prediction based on genomic profiles will be useful clinically. Appropriate statistical measures to evaluate the performance of genetic risk prediction models are required. Previous studies have mainly focused on the use of the area under the receiver operating characteristic (ROC) curve, or AUC, to judge the predictive value of genetic tests. However, AUC has its limitations and should be complemented by other measures. In this study, we develop a novel unifying statistical framework that connects a large variety of predictive indices together. We showed that, given the overall disease probability and the level of variance in total liability (or heritability) explained by the genetic variants, we can estimate analytically a large variety of prediction metrics, for example the AUC, the mean risk difference between cases and non-cases, the net reclassification improvement (ability to reclassify people into high- and low-risk categories), the proportion of cases explained by a specific percentile of population at the highest risk, the variance of predicted risks, and the risk at any percentile. We also demonstrate how to construct graphs to visualize the performance of risk models, such as the ROC curve, the density of risks, and the predictiveness curve (disease risk plotted against risk percentile). The results from simulations match very well with our theoretical estimates. Finally we apply the methodology to nine complex diseases, evaluating the predictive power of genetic tests based on known susceptibility variants for each trait

Psychiatric disorders in individuals born very preterm / very low-birth weight: An individual participant data (IPD) meta-analysis

Background: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants. / Methods: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight 2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555). / Findings: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups. / Interpretation: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders in individuals born VP/VLBW. / Funding: Australia's National Health & Medical Research Council; CAPES (Coordenação de Aperfeiçoamento de Pessoal deNível Superior) - International Cooperation General Program; Canadian Institutes of Health Research Team Grant; National Council for Scientific and Technological Development (CNPq); Academy of Finland; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; European Union's Horizon 2020 research and innovation programme: Project RECAP-Preterm; European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL); Neurologic Foundation of New Zealand; MRC programme grant; Health Research Council of New Zealand; National Institutes of Health, USA; The Research Council of Norway; Joint Research Committee between St. Olavs Hospital and Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU); Liaison Committee between Central Norway Regional Health Authority and NTNU

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

BACKGROUND/AIMS: Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model. METHODS: A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model. RESULTS: PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (-0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum alpha-fetoprotein (&gt;100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF. CONCLUSIONS: Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF