Superconductivity enhanced conductance fluctuations in few layer graphene nanoribbons

We investigate the mesoscopic disorder induced rms conductance variance $\delta G$ in a few layer graphene nanoribbon (FGNR) contacted by two superconducting (S) Ti/Al contacts. By sweeping the back-gate voltage, we observe pronounced conductance fluctuations superimposed on a linear background of the two terminal conductance G. The linear gate-voltage induced response can be modeled by a set of inter-layer and intra-layer capacitances. $\delta G$ depends on temperature T and source-drain voltage $V_{sd}$. $\delta G$ increases with decreasing T and $|V_{sd}|$. When lowering $|V_{sd}|$, a pronounced cross-over at a voltage corresponding to the superconducting energy gap $\Delta$ is observed. For |V_{sd}|\ltequiv \Delta the fluctuations are markedly enhanced. Expressed in the conductance variance $G_{GS}$ of one graphene-superconducutor (G-S) interface, values of 0.58 e^2/h are obtained at the base temperature of 230 mK. The conductance variance in the sub-gap region are larger by up to a factor of 1.4-1.8 compared to the normal state. The observed strong enhancement is due to phase coherent charge transfer caused by Andreev reflection at the nanoribbon-superconductor interface.Comment: 15 pages, 5 figure

Application of shotgun metagenomics sequencing and targeted sequence capture to detect circulating porcine viruses in the Dutch-German border region

Porcine viruses have been emerging in recent decades, threatening animal and human health, as well as economic stability for pig farmers worldwide. Next-generation sequencing (NGS) can detect and characterize known and unknown viruses but has limited sensitivity when an unbiased approach, such as shotgun metagenomics sequencing, is used. To increase the sensitivity of NGS for the detection of viruses, we applied and evaluated a broad viral targeted sequence capture (TSC) panel and compared it to an unbiased shotgun metagenomic approach. A cohort of 36 pooled porcine nasal swab and blood serum samples collected from both sides of the Dutch-German border region were evaluated. Overall, we detected 46 different viral species using TSC, compared to 40 viral species with a shotgun metagenomics approach. Furthermore, we performed phylogenetic analysis on recovered influenza A virus (FLUAV) genomes from Germany and revealed a close similarity to a zoonotic influenza strain previously detected in the Netherlands. Although TSC introduced coverage bias within the detected viruses, it improved sensitivity, genome sequence depth and contig length. In-depth characterization of the swine virome, coupled with developing new enrichment techniques, can play a crucial role in the surveillance of circulating porcine viruses and emerging zoonotic pathogens

Surface temperature lapse rates over complex terrain : lessons from the Cascade Mountains

The typically sparse distribution of weather stations in mountainous terrain inadequately resolves temperature variability. Accordingly, high‐resolution gridding of climate data (for applications such as hydrological modeling) often relies on assumptions such as a constant surface temperature lapse rate (i.e., decrease of surface temperature with altitude) of 6.5°C km⁻¹. Using an example of the Cascade Mountains, we describe the temporal and spatial variability of the surface temperature lapse rate, combining data from: (1) COOP stations, (2) nearby radiosonde launches, (3) a temporary dense network of sensors, (4) forecasts from the MM5 regional model, and (5) PRISM geo‐statistical analyses. On the windward side of the range, the various data sources reveal annual mean lapse rates of 3.9–5.2°C km⁻¹, substantially smaller than the often‐assumed 6.5°C km⁻¹. The data sets show similar seasonal and diurnal variability, with lapse rates smallest (2.5–3.5°C km⁻¹) in late‐summer minimum temperatures, and largest (6.5–7.5°C km⁻¹) in spring maximum temperatures. Geographic (windward versus lee side) differences in lapse rates are found to be substantial. Using a simple runoff model, we show the appreciable implications of these results for hydrological modeling

First detection of porcine respirovirus 1 in Germany and the Netherlands

Porcine respirovirus 1, also referred to as porcine parainfluenza virus 1 (PPIV-1), was first detected in deceased pigs from Hong Kong in 2013. It has since then been found in the USA, Chile and most recently in Hungary. Information on the pathogenicity and global spread is sparse. However, it has been speculated to play a role in the porcine respiratory disease complex. To investigate the porcine virome, we screened 53 pig samples from 26 farms within the Dutch-German border region using shotgun metagenomics sequencing (SMg). After detecting PPIV-1 in five farms through SMg, a real-time reverse transcriptase PCR (RT-qPCR) assay was designed, which not only confirmed the presence of the virus in 1 of the 5 farms but found an additional 6 positive farms. Phylogenetic analysis found the closest match to be the first detected PPIV-1 strain in Hong Kong. The Dutch-German region represents a significant area of pig farming within Europe and could provide important information on the characterization and circulation of porcine viruses, such as PPIV-1. With its recent detection in Hungary, these findings suggest widespread circulation of PPIV-1 in Central Europe, highlighting the need for further research on persistence, pathogenicity and transmission in Europe

Assessment of Viral Targeted Sequence Capture Using Nanopore Sequencing Directly from Clinical Samples

Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative

The inter-relationship between depressed mood, functional decline and disability over a 10-year observational period within the Longitudinal Urban Cohort Ageing Study (LUCAS)

Background: The WHO defines 'healthy ageing' as 'the process of developing and maintaining the functional ability'. Late-life depression and frailty compromise well-being and independence of older people. To date, there exists little research on the interaction of the dynamic processes of frailty and depression and only a few studies were longitudinal. Conclusions about the direction of effects remained uncertain. Methods: Data were obtained from each of the last six biyearly waves (2007-2017) of the Longitudinal Urban Cohort Ageing Study (LUCAS) in Hamburg, Germany, a prospective observational cohort study of manifold aspects of ageing. Screening of predictor and event variables: depressed mood: one question from the 5-item Mental Health Inventory Screening Test; frailty: LUCAS Functional Ability Index, status 'frail'; disability: one question on need for human help with basic activities of daily living. Kaplan-Meier curves and Cox's proportional hazards regression were used for time-to-event analyses with shifting baseline. Results: Sample size in 2007 was 2012, average age 76.2 years; ±6.5. Main results were as follows: (1) depression significantly increased the hazard of subsequent frailty (HR=1.581; 95% CI 1.257 to 1.988; p<0.001); (2) frailty significantly increased the hazard of subsequent depression (HR=2.324; 95% CI 1.703 to 3.172; p<0.001); (3) depression significantly increased the hazard of subsequent disability (HR=2.589; 95% CI 1.885 to 3.557; p<0.001) and (4) disability did not significantly increase the hazard of subsequent depression (HR=1.540; 95% CI 0.917 to 2.579; p=0.102). Conclusion: Our results suggest an interdependence of the processes of depression and frailty/disability rather than unidirectional dependencies. These observable processes may be representative of underlying unobservable profound life changes. Obviously, there is a need for early screening to initiate appropriate interventions

Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients

Background: Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose. Objective: The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS. Design: This was designed as a retrospective, multicenter study. Setting: Thirteen University hospitals were studied. Patients: We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3). Measurements: Measurements included biochemical parameters of activity of CS: mean serum cortisol “day-curve” (CDC) (target 150–300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC). Results: A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 μg/dL] vs 348.6 nmol/L [12.6 μg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 μg/dL] vs 491.1 nmol/L [17.8 μg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 μg/24 h] vs 452.6 nmol/24 h [164 μg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 μg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 μg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible. Conclusions: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS