Lipidomics of human umbilical cord serum : identification of unique sterol sulfates

Aim: There are currently limited lipidomics data for human umbilical cord blood. Therefore, the lipidomes of cord sera from six newborns and sera from six nonpregnant females were compared. Materials & methods: Sera lipidomics analyses were conducted using a high-resolution mass spectrometry analytical platform. Results: Cord serum contained a diverse array of glycerophospholipids, albeit generally at lower concentrations than monitored in adult serum. The unexpected observations were that cord serum contained several neurosteroid sulfates and bile acid sulfates that were not detectable in adult serum. Conclusion: Our data are the first to demonstrate that cord serum contains bile acid sulfates that are synthesized early in the hydroxylase, neutral and acidic pathways of primary bile acid biosynthesis and support previous publications of cord blood perfluoralkyl toxins in newborns. Lay abstract: Umbilical cord blood offers the potential to increase our understanding of fetal development during pregnancy and during development after delivery. Our studies of complex sterols in umbilical cord blood (bile acid sulfates) suggest that with further studies these may be useful biomarkers of abnormal fetal liver development.Peer reviewe

Brazing development and interfacial metallurgy study of tungsten and copper joints with eutectic gold copper brazing alloy

Current proposals for the divertor component of a thermonuclear fusion reactor include tungsten and copper as potentially suitable materials. This paper presents the procedures developed for the successful brazing of tungsten to oxygen free high conductivity (OFHC) copper using a fusion appropriate gold based brazing alloy, Orobraze 890 (Au80Cu20). The objectives were to develop preparation techniques and brazing procedures in order to produce a repeatable, defect free butt joint for tungsten to copper. Multiple brazing methods were utilised and brazing parameters altered to achieve the best joint possible. Successful and unsuccessful brazed specimens were sectioned and analysed using optical and scanning electron microscopy, EDX analysis and ultrasonic evaluation. It has been determined that brazing with Au80Cu20 has the potential to be a suitable joining method for a tungsten to copper joint

Spatio-temporal methods for estimating subsurface ocean thermal response to tropical cyclones

Tropical cyclones (TCs), driven by heat exchange between the air and sea, pose a substantial risk to many communities around the world. Accurate characterization of the subsurface ocean thermal response to TC passage is crucial for accurate TC intensity forecasts and for an understanding of the role that TCs play in the global climate system. However, that characterization is complicated by the high-noise ocean environment, correlations inherent in spatio-temporal data, relative scarcity of in situ observations, and the entanglement of the TC-induced signal with seasonal signals. We present a general methodological framework that addresses these difficulties, integrating existing techniques in seasonal mean field estimation, Gaussian process modeling, and nonparametric regression into a functional ANOVA model. Importantly, we improve upon past work by properly handling seasonality, providing rigorous uncertainty quantification, and treating time as a continuous variable, rather than producing estimates that are binned in time. This functional ANOVA model is estimated using in situ subsurface temperature profiles from the Argo fleet of autonomous floats through a multi-step procedure, which (1) characterizes the upper ocean seasonal shift during the TC season; (2) models the variability in the temperature observations; (3) fits a thin plate spline using the variability estimates to account for heteroskedasticity and correlation between the observations. This spline fit reveals the ocean thermal response to TC passage. Through this framework, we obtain new scientific insights into the interaction between TCs and the ocean on a global scale, including a three-dimensional characterization of the near-surface and subsurface cooling along the TC storm track and the mixing-induced subsurface warming on the track's right side.Comment: 33 pages, 14 figures; supplement and code at https://github.com/huisaddison/tc-ocean-method

Making alternative fuel vehicles work: Storage through absorption on Missouri corn cob

Abstract only availableThe USA's current demand for petroleum leads to many problems (many being global concerns as well): a dependence on foreign nations for our energy, an increase in pollution/global warming, and high gas prices. Each of those is the source of many more problems that will become worse if not addressed: Foreign dependence results in oil-effected politics and economic foreign dependence. Pollution and global warming result in an increase in the destruction of natural habitats due to changing climates, skin damage/cancer due to sun exposure, and natural disasters such as hurricanes and tornadoes that depend on higher temperatures. Along with gas prices increasing, so will the prices of goods and services as the cost of energy to produce them increases. My research with the Alliance for Collaborative Research in Alternative Fuel Technology addresses these issues by overcoming many of the hurdles that make current alternative fuels impractical. We have produced porous activated carbons that store high capacities of methane (natural gas) through physisorption for use in vehicle tanks. In optimizing storage capacity, we have studied production methods that vary the pore size distributions, surface areas, and densities of our carbons. We have found that the optimal pore size for methane is 1.1 nanometers and that it is best to maximize surface area and density. Our current best performers store 115-119 grams of methane per liter of carbon at ambient temperature and 34 bar, compared to the DOE target of 118 g/L. Our research is now expanding to include hydrogen storage.Alliance for Collaborative Research in Alternative Fuel Technolog

MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial.

PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC

Full genome comparison and characterization of avian H10 viruses with different pathogenicity in Mink (Mustela vison) reveals genetic and functional differences in the non-structural gene

<p>Abstract</p> <p>Background</p> <p>The unique property of some avian H10 viruses, particularly the ability to cause severe disease in mink without prior adaptation, enabled our study. Coupled with previous experimental data and genetic characterization here we tried to investigate the possible influence of different genes on the virulence of these H10 avian influenza viruses in mink.</p> <p>Results</p> <p>Phylogenetic analysis revealed a close relationship between the viruses studied. Our study also showed that there are no genetic differences in receptor specificity or the cleavability of the haemagglutinin proteins of these viruses regardless of whether they are of low or high pathogenicity in mink.</p> <p>In poly I:C stimulated mink lung cells the NS1 protein of influenza A virus showing high pathogenicity in mink down regulated the type I interferon promoter activity to a greater extent than the NS1 protein of the virus showing low pathogenicity in mink.</p> <p>Conclusions</p> <p>Differences in pathogenicity and virulence in mink between these strains could be related to clear amino acid differences in the non structural 1 (NS1) protein. The NS gene of mink/84 appears to have contributed to the virulence of the virus in mink by helping the virus evade the innate immune responses.</p

Dedicated plug based closure for large bore access –The MARVEL prospective registry

Objectives: To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers. Background: The MANTA is a novel plug-based devic

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe