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Emerging biomarkers and intervention targets for immune-modulation of atherosclerosis - A review of the experimental evidence.

The role of inflammation in atherosclerosis and plaque vulnerability is well recognized. However, it is only during recent years it has become evident that this inflammation is modulated by immune responses against plaque antigens such as oxidized LDL. Interestingly, both protective and pathogenic immune responses exist and experimental data from animal studies suggest that modulation of these imm

Comparability : Manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14-15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. T

Echocardiographic consequences of smoking status in middle-aged subjects

Background: Smoking is known to have many short- and long-term cardiovascular effects. Cardiac index (CI), which is cardiac output indexed to body surface area, is considered to be a valid measure of cardiac performance. We investigated whether there were any differences in CI or other echocardiographic variables between never smokers, ex-smokers, and current smokers in a cardiopulmonary healthy p

Pharmacokinetic Evaluation of Once-Weekly and Once-Monthly Buprenorphine Subcutaneous Injection Depots (CAM2038) Versus Intravenous and Sublingual Buprenorphine in Healthy Volunteers Under Naltrexone Blockade : An Open-Label Phase 1 Study

Introduction: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal® injection depot technology. These two drug products are being developed for opioid dependence treatment, with a target for once-weekly and once-monthly SC dosing. The rationale for developing two products with different dosing frequencies is that tr

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer : Extended Analysis of the Phase 3 PREVAIL Study

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final

Slow-light-based optical frequency shifter

We demonstrate experimentally and theoretically a controllable way of shifting the frequency of an optical pulse by using a combination of spectral hole burning, slow light effect, and linear Stark effect in a rare-earth-ion-doped crystal. We claim that the solid angle of acceptance of a frequency shift structure can be close to 2π, which means that the frequency shifter could work not only for op

Road Safety Management – The need for a systematic approach

In order to achieve significant improvements in road safety at the national level, there is a need for a systematic approach to road safety management with clear responsibilities and accountability. In this paper – after a review of the literature on guidelines, recommendations and research findings – twelve essential elements of such a systematic approach are pointed out, and corresponding releva

Correlating structure and electronic band-edge properties in organolead halide perovskites nanoparticles

After having emerged as primary contenders in the race for highly efficient optoelectronics materials, organolead halide perovskites (OHLP) are now being investigated in the nanoscale regime as promising building blocks with unique properties. For example, unlike their bulk counterpart, quantum dots of OHLP are brightly luminescent, owing to large exciton binding energies that cannot be rationaliz

Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits : the GLACIER Study

Background:Recent cross-sectional genome-wide scans have reported associations of 97 independent loci with body mass index (BMI). In 3541 middle-aged adult participants from the GLACIER Study, we tested whether these loci are associated with 10-year changes in BMI and other cardiometabolic traits (fasting and 2-h glucose, triglycerides, total cholesterol, and systolic and diastolic blood pressures

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

Aims/hypothesis: Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart−/− mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affe

Comparative Proteomic Analysis of Extracellular Vesicles Isolated by Acoustic Trapping or Differential Centrifugation

Extracellular vesicles (ECVs), including microparticles and exosomes, are submicrometer membrane vesicles released by diverse cell types upon activation or stress. Circulating ECVs are potential reservoirs of disease biomarkers, and the complexity of these vesicles is significantly lower compared to their source, blood plasma, which makes ECV-based biomarker studies more promising. Proteomic profi

Tapasin facilitation of MHC-I separates closely related allomorphs, is strongly influenced by peptide length and depends on stability

Only a small fraction of the peptides inside a cell are eventually presented by HLA-I on the cell surface. The presented peptides have HLA-I allomorph-specific motifs and length restrictions. Tapasin influences HLA-I antigen presentation both qualitatively and quantitatively to different degrees depending on both peptide sequence and HLA-I allomorph. The tapasin-dependence in cellular context has

In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions

The maintenance of H3K9 and DNA methylation at imprinting control regions (ICRs) during early embryogenesis is key to the regulation of imprinted genes. Here, we reveal that ZFP57, its cofactor KAP1, and associated effectors bind selectively to the H3K9me3-bearing, DNA-methylated allele of ICRs in ES cells. KAP1 deletion induces a loss of heterochromatin marks at ICRs, whereas deleting ZFP57 or DN

Acceptorless dehydrogenation of 4-methylpiperidine by supported pincer-ligated iridium catalysts in continuous flow

Finding alternative and sustainable ways to produce, store and convert energy is key for reducing fossil fuel-based CO2 emissions. In this transformation, hydrogen for energy storage and hydrogen-powered fuel cells for energy conversion can play important roles. However, storage of hydrogen itself is difficult and the concept of reversible liquid organic hydrogen carriers (LOHCs) has been proposed

Sex and gender in infection and immunity : addressing the bottlenecks from basic science to public health and clinical applications

Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of

Chemical Limits on X-ray Nanobeam Studies in Water

Operando X-ray studies of chemical reactions have gained increasing interest lately, fueled by the emergence of a new generation of powerful focused X-ray sources. Although it is well known that ionizing radiation causes damage to samples via radical chemistry, this effect is often overlooked in studies of working devices or catalysts where intense focused beams are used as nanoscale probes. Here,