Passive Heat Therapy in Sedentary Humans Increases Skeletal Muscle Capillarisation and eNOS Content but Not Mitochondrial Density or GLUT4 Content.

Passive heat therapy (PHT) has been proposed as an alternative intervention to traditional moderate intensity continous training (MICT) in individuals who are unable or unwilling to exercise. This study aimed to make the first comparison of the effect of PHT and MICT on 1) skeletal muscle capillarisation and endothelial specific eNOS content and 2) mitochondrial density, GLUT4 and IMTG content. Twenty young sedentary males (21±1years, BMI 25±1kg.m-2) were allocated to either 6 weeks of PHT (n=10; 40-50min at 40°C in a heat chamber, 3x/wk) or MICT (n=10; time matched cycling at ~65% VO2peak). Muscle biopsies were taken from the vastus lateralis muscle pre- and post-training. Immunofluorescence microscopy was used to assess changes in skeletal muscle mitochondrial density, GLUT4 and IMTG content, capillarisation and endothelial specific eNOS content. VO2peak and whole body insulin sensitivity were also assessed. PHT and MICT both increased capillary density and capillary-fibre perimeter exchange index (P<0.05), and endothelial specific eNOS content (P<0.05). However, unlike MICT (P<0.05) PHT did not increase mitochondrial density (P=0.443), GLUT4 (P=0.217) or IMTG content (P=0.957). Both intervention improved aerobic capacity and whole body insulin sensitivity (P<0.05). 6 weeks PHT in young sedentary males increases skeletal muscle capillarisation and eNOS content to a similar extent as MICT, however, unlike MICT PHT does not affect skeletal muscle mitochondrial density, GLUT4 or IMTG content

N-[(2-Chloro-3-quinol­yl)meth­yl]-4-fluoro­aniline

In the title compound, C16H12ClFN2, the dihedral angle between the quinoline ring system and the flourophenyl ring is 86.70 (4)°. In the crystal, mol­ecules are linked into chains along the a axis by N—H⋯N hydrogen bonds. In addition, C—H⋯π inter­actions involving the two benzene rings are observed

PG&E WaveConnect Program Final Report

The PG&E WaveConnect project was intended to demonstrate the technical and economic viability of wave power in the open ocean adjacent to PG&E's service territory. WaveConnect was conceived as a multi-stage development process leading to long-term megawatt-scale wave power production. The first-stage tasks consisted of site selection, permitting, pilot plant design, and assessment of technology and commercial readiness. The second stage would have included development of infrastructure, undersea cabling, and deployment of wave energy conversion devices (WECs). In the third stage, the most promising WEC devices would have been deployed in larger quantities and connected to the grid. This report documents the findings of Stage One. Site Selection: After studying the wave energy potential, grid interconnection and other project infrastructure along the California coast, PG&E selected two sites: one near Eureka, called the Humboldt WaveConnect (HWC) project, and another near Vandenberg Air Force Base, called the Central Coast WaveConnect project (CCWC). Permitting: FERC issued PG&E preliminary permits for HWC in 2008 and for CCWC in 2010. PG&E chose to use FERC's Pilot Project Licensing Process, which was intended to streamline licensing to allow relatively quick and easy installation, operation, and environmental testing for pilot projects. Permitting, however, proved to be complicated, time-consuming and expensive, mainly because of the uncertain impacts of WEC devices. PG&E learned that even under the PPLP the project would still require a full analysis under CEQA, including an EIR, as well as Monitoring and Adaptive Management Programs and other requirements that had significant cost and scheduling implications. A majority of efforts were expended on permitting activities. Pilot Plant Design: PG&E prepared a conceptual design for a 5-MW pilot test facility at the Humboldt site, which consisted of an off-shore deployment area where WECs of different designs and from different device manufacturers could be tested. PG&E was to provide permitting, subsea cables, and on-shore facilities necessary to connect WaveConnect to an existing PG&E substation, while the WEC manufacturers would provide, operate and maintain their devices during the test period. Technology and Commercial Readiness: PG&E issued a Request for Information to the wave power industry to assess the technical and commercial capabilities of WEC manufacturers. Sixteen manufacturers responded, representing the four best-known and most mature designs. PG&E found that WECs are early-stage devices with evolving designs and little real-world operating experience. These characteristics made environmental impacts difficult to assess, which complicated permitting efforts. It also made a megawatt-scale demonstration project difficult to support because early stage WECs are costly and have limited track records for performance and reliability. Results: PG&E withdrew its FERC DPLA for HWC in November 2010 and surrendered its preliminary permit for CCWC in May 2011, effectively discontinuing the project for the following combination of reasons: Permitting issues were much more challenging than originally anticipated. Stage One project funding of 6 million proved insufficient to complete the necessary development and permitting work. During Stage One development, PG&E determined that permitting costs would be 2 million to $5 million greater than originally budgeted. The cost of developing a five-year, 5-MW pilot project at Humboldt Bay is much greater than the$15 million to 20 million originally estimated. Even assuming that vendors provide WEC devices at no cost to the utility, which was the proposed strategy with WaveConnect, PG&E concluded that a pilot project comparable to HWC would cost approximately 47 million. If WEC devices were purchased for such a project, its total cost would be on the order of $90 million. It is unclear when or if wave power will become competitive with renewable energy alternatives. Significant additional investment in design, testing and demonstration will be needed to improve designs and reduce costs. Using a vendor-provided installed cost goal of$2500/kW for mature WECs in five to 10 years, PG&E concluded that their LCOE would be in the range of $175-$250/MWh, which is not competitive with current or near-term renewable alternatives such as wind or solar photovoltaics. Although PG&E discontinued the project and no WEC devices were deployed, WaveConnect advanced PG&E's understanding of the technological, engineering, permitting, environmental, economic, stakeholder, and related issues involved in undertaking any wave power project now or in the future. As WEC technologies mature, and regulatory and permitting agencies grow more familiar with their environmental impacts, PG&E believes that wave power will merit further evaluation, demonstration and deployment

A Real-World Observational Study Evaluating the Probability of Glycemic Control with Basal Insulin or Glucagon-Like Peptide-1 Receptor Agonist in Japanese Patients with Type 2 Diabetes.

Introduction:The effectiveness of basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in providing glycemic control in patients with type 2 diabetes (T2D) in Japanese routine practice is not well known. This real-world observational study evaluated the probability of achieving glycemic control in Japanese patients with T2D uncontrolled by oral antidiabetic drugs (OADs) who initiated BI or GLP-1 RA therapy.Methods:Patients with T2D aged ≥ 18 years initiating BI or GLP-1 RA therapy following treatment with OADs were selected from real-world data (RWD) retrieved from a large electronic medical record database in Japan, using data from 01 January 2010 to 30 June 2019. Patients were required to have glycated hemoglobin (HbA1c) ≥ 7% within 90 days prior to the first prescription of BI or GLP-1 RA. The probability of reaching first HbA1c < 7% was assessed over a 24-month period in cohorts of patients who initiated BI (n = 3477) or GLP-1 RA (n = 780) and in subcohorts by number of OADs at baseline (1, 2, or ≥ 3), HbA1c at baseline (≥ 7 to < 8%, ≥ 8 to < 9%, or ≥ 9%), and age (< 65 or ≥ 65 years).Results:Mean (standard deviation) baseline HbA1c was 9.4% (1.8%) and 8.8% (1.4%) in patients initiating BI or GLP-1 RA therapy, respectively. The cumulative probability of achieving glycemic control was 50.1% with BI and 60.3% with GLP-1 RA therapy, respectively, at 12 months, and 60.8% and 66.6%, respectively, at 24 months. Quarterly (3-month intervals) conditional probabilities of achieving glycemic control decreased over time and were < 10% after 12 months. Patients with more OADs or higher HbA1c at baseline had a lower probability of achieving glycemic control.Conclusion:Among Japanese patients with T2D who initiated BI or GLP-1 RA therapy after treatment with OADs, the probability of reaching first glycemic control diminished over time. Further therapy intensification is warranted in patients who do not achieve glycemic control within 6-12 months with BI or GLP-1 RA, particularly those with high HbA1c or taking multiple OADs

Observation of the nonlinear Hall effect under time reversal symmetric conditions

The electrical Hall effect is the production of a transverse voltage under an out-of-plane magnetic field. Historically, studies of the Hall effect have led to major breakthroughs including the discoveries of Berry curvature and the topological Chern invariants. In magnets, the internal magnetization allows Hall conductivity in the absence of external magnetic field. This anomalous Hall effect (AHE) has become an important tool to study quantum magnets. In nonmagnetic materials without external magnetic fields, the electrical Hall effect is rarely explored because of the constraint by time-reversal symmetry. However, strictly speaking, only the Hall effect in the linear response regime, i.e., the Hall voltage linearly proportional to the external electric field, identically vanishes due to time-reversal symmetry. The Hall effect in the nonlinear response regime, on the other hand, may not be subject to such symmetry constraints. Here, we report the observation of the nonlinear Hall effect (NLHE) in the electrical transport of the nonmagnetic 2D quantum material, bilayer WTe2. Specifically, flowing an electrical current in bilayer WTe2 leads to a nonlinear Hall voltage in the absence of magnetic field. The NLHE exhibits unusual properties sharply distinct from the AHE in metals: The NLHE shows a quadratic I-V characteristic; It strongly dominates the nonlinear longitudinal response, leading to a Hall angle of about 90 degree. We further show that the NLHE directly measures the "dipole moment" of the Berry curvature, which arises from layer-polarized Dirac fermions in bilayer WTe2. Our results demonstrate a new Hall effect and provide a powerful methodology to detect Berry curvature in a wide range of nonmagnetic quantum materials in an energy-resolved way

2,6-Dide­oxy-2,6-imino-l-glycero-d-ido-heptitol

The title mol­ecule, C7H15NO5, the major product from selective enzymatic oxidation followed by hydrogeno­lysis of the corresponding azido­heptitol, was found by X-ray crystallography to exisit in a chair conformation with three axial hydroxyl groups. One of the hydroxymethyl groups is disordered over two sets of sites in a 0.590 (3):0.410 (3) ratio. In the crystal, O—H⋯O, O—H⋯(O,O), O—H⋯N and N—H⋯O hydrogen bonding occurs

Tissue-Specific Gene Delivery via Nanoparticle Coating

Author Manuscript: 2010 August 1.The use of biomaterials for gene delivery can potentially avoid many of the safety concerns with viral gene delivery. However, the efficacy of polymeric gene delivery methods is low, particularly in vivo. One significant concern is that the interior and exterior composition of polymeric gene delivery nanoparticles are often coupled, with a single polymer backbone governing all functions from biophysical properties of the polymer/DNA particle to DNA condensation and release. In this work we develop electrostatically adsorbed poly(glutamic acid)-based peptide coatings to alter the exterior composition of a core gene delivery particle and thereby affect tissue-specificity of gene delivery function in vivo. We find that with all coating formulations tested, the coatings reduce potential toxicity associated with uncoated cationic gene delivery nanoparticles following systemic injection. Particles coated with a low 2.5:1 peptide:DNA weight ratio (w/w) form large 2 μ sized particles in the presence of serum that can facilitate specific gene delivery to the liver. The same particles coated at a higher 20:1 w/w form small 200 nm particles in the presence of serum that can facilitate specific gene delivery to the spleen and bone marrow. Thus, variations in nanoparticle peptide coating density can alter the tissue-specificity of gene delivery in vivo.National Institutes of Health (U.S.) (BRP: 1R01CA124427-01)National Institutes of Health (U.S.) (EB 000244)National Institutes of Health (U.S.) (U54 CA119349-01)David & Lucile Packard Foundation (Fellowship 1999-1453A