Beyond Nanopore Sequencing in Space: Identifying the Unknown

Astronaut Kate Rubins sequenced DNA on the International Space Station (ISS) for the first time in August 2016 (Figure 1A). A 2D sequencing library containing an equal mixture of lambda bacteriophage, Escherichia coli, and Mus musculus was prepared on the ground with a SQK_MAP006 kit and sent to the ISS frozen and loaded into R7.3 flow cells. After a total of 9 on-orbit sequencing runs over 6 months, it was determined that there was no decrease in sequencing performance on-orbit compared to ground controls (1). A total of ~280,000 and ~130,000 reads generated on-orbit and on the ground, respectively, identified 90% of reads that were attributed to 30% lambda bacteriophage, 30% Escherichia coli, and 30% M. musculus (Figure 1B). Extensive bioinformatics analysis determined comparable 2D and 1D read accuracies between flight and ground runs (Figure 1C), and data collected from the ISS were able to construct directed assemblies of E.coli and lambda genomes at 100% and M. musculus mitochondrial genome at 96.7%. These findings validate sequencing as a viable option for potential on-orbit applications such as environmental microbial monitoring and disease diagnosis. Current microbial monitoring of the ISS applies culture-based techniques that provide colony forming unit (CFU) data for air, water, and surface samples. The identity of the cultured microorganisms in unknown until sample return and ground-based analysis, a process that can take up to 60 days. For sequencing to benefit ISS applications, spaceflight-compatible sample preparation techniques are required. Subsequent to the testing of the MinION on-orbit, a sample-to-sequence method was developed using miniPCR and basic pipetting, which was only recently proven to be effective in microgravity. The work presented here details the in- flight sample preparation process and the first application of DNA sequencing on the ISS to identify unknown ISS-derived microorganisms

Atomically Thin Resonant Tunnel Diodes built from Synthetic van der Waals Heterostructures

Vertical integration of two-dimensional van der Waals materials is predicted to lead to novel electronic and optical properties not found in the constituent layers. Here, we present the direct synthesis of two unique, atomically thin, multi-junction heterostructures by combining graphene with the monolayer transition-metal dichalocogenides: MoS2, MoSe2, and WSe2.The realization of MoS2-WSe2-Graphene and WSe2-MoSe2-Graphene heterostructures leads toresonant tunneling in an atomically thin stack with spectrally narrow room temperature negative differential resistance characteristics

Defining County-Level Terrestrial Rabies Freedom Using the US National Rabies Surveillance System: Surveillance Data Analysis

Background: Rabies is a deadly zoonotic disease with nearly 100% fatality rate. In the United States, rabies virus persists in wildlife reservoirs, with occasional spillover into humans and domestic animals. The distribution of reservoir hosts in US counties plays an important role in public health decision-making, including the recommendation of lifesaving postexposure prophylaxis upon suspected rabies exposures. Furthermore, in surveillance data, it is difficult to discern whether counties have no cases reported because rabies was not present or because counties have an unreported rabies presence. These epizootics are monitored by the National Rabies Surveillance System (NRSS), to which approximately 130 state public health, agriculture, and academic laboratories report animal rabies testing statistics. Historically, the NRSS classifies US counties as free from terrestrial rabies if, over the previous 5 years, they and any adjacent counties did not report any rabies cases and they tested ≥15 reservoir animals or 30 domestic animals. Objective: This study aimed to describe and evaluate the historical NRSS rabies-free county definition, review possibilities for improving this definition, and develop a model to achieve more precise estimates of the probability of terrestrial rabies freedom and the number of reported county-level terrestrial rabies cases. Methods: Data submitted to the NRSS by state and territorial public health departments and the US Department of Agriculture Wildlife Services were analyzed to evaluate the historical rabies-free definition. A zero-inflated negative binomial model created county-level predictions of the probability of rabies freedom and the expected number of rabies cases reported. Data analyzed were from all animals submitted for laboratory diagnosis of rabies in the United States from 1995 to 2020 in skunk and raccoon reservoir territories, excluding bats and bat variants. Results: We analyzed data from 14,642 and 30,120 county-years in the raccoon and skunk reservoir territories, respectively. Only 0.85% (9/1065) raccoon county-years and 0.79% (27/3411) skunk county-years that met the historical rabies-free criteria reported a case in the following year (99.2% negative predictive value for each), of which 2 were attributed to unreported bat variants. County-level model predictions displayed excellent discrimination for detecting zero cases and good estimates of reported cases in the following year. Counties classified as rabies free rarely (36/4476, 0.8%) detected cases in the following year. Conclusions: This study concludes that the historical rabies freedom definition is a reasonable approach for identifying counties that are truly free from terrestrial raccoon and skunk rabies virus transmission. Gradations of risk can be measured using the rabies prediction model presented in this study. However, even counties with a high probability of rabies freedom should maintain rabies testing capacity, as there are numerous examples of translocations of rabies-infected animals that can cause major changes in the epidemiology of rabies

The Effect of Glucagon-Like Peptide-2 Receptor Agonists on Colonic Anastomotic Wound Healing

Background. Glucagon-like peptide 2 (GLP-2) is an intestinal specific trophic hormone, with therapeutic potential; the effects on intestinal healing are unknown. We used a rat model of colonic healing, under normoxic, and stress (hypoxic) conditions to examine the effect of GLP-2 on intestinal healing. Methods. Following colonic transection and reanastomosis, animals were randomized to one of six groups (n = 8/group): controls, native GLP-2, long-acting GLP-2 (GLP-2- MIMETIBODY, GLP-2-MMB), animals were housed under normoxic or hypoxic (11%  O2) conditions. Animals were studied five days post-operation for anastomotic strength and wound characteristics. Results. Anastomotic bursting pressure was unchanged by GLP-2 or GLP-2-MMB in normoxic or hypoxic animals; both treatments increased crypt cell proliferation. Wound IL-1β increased with GLP-2; IFNγ with GLP-2 and GLP-2-MMB. IL-10 and TGF-β were decreased; Type I collagen mRNA expression increased in hypoxic animals while Type III collagen was reduced with both GLP-2 agonists. GLP-2 MMB, but not native GLP-2 increased TIMP 1-3 mRNA levels in hypoxia. Conclusions. The effects on CCP, cytokines and wound healing were similar for both GLP-2 agonists under normoxic and hypoxic conditions; anastomotic strength was not affected. This suggests that GLP-2 (or agonists) could be safely used peri-operatively; direct studies will be required

Tumour characteristics and survival in familial breast cancer prospectively diagnosed by annual mammography

Women from breast cancer families without a demonstrable BRCA1/2 mutation were subjected to annual mammography from age 30 years onwards. One-hundred and ninety-eight patients were diagnosed prospectively with invasive breast cancer and followed for a total of 1513 years. Overall 10-year survival was 88 %. Together with our previous report that women in such kindreds had about twice the population risk of breast cancer, the combined conclusion was that the overall chances of developing breast cancer causing death within 10 years before 50 years of age was 1 % or less when subjected to annual mammography and current treatment. These are empirical prospective observations which may be used for genetic counselling. The majority (160/194 = 84 %) of patients had ER+ and/or low grade tumours with 92 % 10-year survival. One minor group of the patients had ER- tumours, another small group had high grade tumours with nodal spread, both groups were associated with worse prognosis, but the two groups were not mutually associated

Clinicians’ perspectives and experiences of providing cervical ripening at home or in-hospital in the United Kingdom

Acknowledgements We are grateful to those who gave their time for interviews and focus groups despite the severe workload pressures and ongoing COVID-19 pandemic. CHOICE is funded by the National Institute of Healthcare Research Health Technology and Assessment (NIHR HTA) NIHR 127569. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of the National Institute of Healthcare Research or the Department of Health and Social Care.Peer reviewedPublisher PD

Pattern scaling the parameters of a Markov-Chain gamma-distribution daily precipitation generator

General circulation models (GCMs) are the most sophisticated tools at our disposal for studying future climates, but there are limitations to overcome. These include resolutions that may be too coarse for impact assessments, limited or zero availability of some policy-relevant scenarios, and limited time-series length for assessing the risk of extreme events. We illustrate how these limitations can be addressed by combining a stochastic precipitation generator (SPG) with pattern scaling (PS) of its key parameters. Computationally inexpensive, SPG parameters can be perturbed to generate time-series representative of weather under a future climate with high spatial and temporal resolution. If the SPG parameter perturbations are derived directly from GCM simulations projections can only be made for scenarios already simulated by the GCM. Instead, we obtain the parameter perturbations using PS, facilitating emulation of scenarios not necessarily explicitly simulated by the GCM, and where we scale perturbations approximately linearly with global temperature change. PS is commonly applied to estimate perturbations in the mean of climate variables, but rarely to higher-order parameters as we demonstrate here. We apply PS for the first time, globally, to the parameters of a daily, first-order Markov-chain gamma-distribution SPG using output from the IPSL-CM6A-LR GCM to perturb an SPG fitted to observed data from two stations in diverse climates (Santarém, Brazil and Reykjavik, Iceland) to illustrate this novel approach. We produce time series corresponding to a range of GWLs and demonstrate the capability of the combined SPG-PS approach to study local-scale, future daily precipitation characteristics, climate and subsequent risk of extreme weather events

Beyond Nanopore Sequencing in Space: Identifying the Unknown

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