Improvements in the CHERS system for DT experiments on TFTR

Improvements in the charge exchange recombination spectroscopy (CHERS) system have resulted in accurate measurements of T{sub i} and V{sub {phi}} profiles during DT experiments. These include moving the spectrometer detector array and electronics farther away from the tokamak to a low neutron flux location. This relocation has also improved access to all components of the system. Also, a nonplasma-viewing calibration fiber system was added to monitor the change in fiber transmission due to the high flux DT neutrons. Narrowband filtered light transmitted through the calibration fiber is now used as a reference for the VO measurement. At the highest neutron flux of {approximately} 2.5 {times} 10{sup 18} neutrons/see (fusion power {approximately} 6.2 MW) a modest 5% decrease in fiber transmission was observed. Corrections for transmission loss are made and T{sub i} (r,t) and absolute V{sub phi} (r,t) profiles are automatically calculated within four minutes of every shot

Predicting evolution and visualizing high-dimensional fitness landscapes

The tempo and mode of an adaptive process is strongly determined by the structure of the fitness landscape that underlies it. In order to be able to predict evolutionary outcomes (even on the short term), we must know more about the nature of realistic fitness landscapes than we do today. For example, in order to know whether evolution is predominantly taking paths that move upwards in fitness and along neutral ridges, or else entails a significant number of valley crossings, we need to be able to visualize these landscapes: we must determine whether there are peaks in the landscape, where these peaks are located with respect to one another, and whether evolutionary paths can connect them. This is a difficult task because genetic fitness landscapes (as opposed to those based on traits) are high-dimensional, and tools for visualizing such landscapes are lacking. In this contribution, we focus on the predictability of evolution on rugged genetic fitness landscapes, and determine that peaks in such landscapes are highly clustered: high peaks are predominantly close to other high peaks. As a consequence, the valleys separating such peaks are shallow and narrow, such that evolutionary trajectories towards the highest peak in the landscape can be achieved via a series of valley crossingsComment: 12 pages, 7 figures. To appear in "Recent Advances in the Theory and Application of Fitness Landscapes" (A. Engelbrecht and H. Richter, eds.). Springer Series in Emergence, Complexity, and Computation, 201

Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials

Improved Measurement of the dˉ/uˉ\bar d / \bar u Asymmetry in the Nucleon Sea

Measurements of the ratio of Drell-Yan yields from an 800 \rm{GeV/c} proton beam incident on liquid hydrogen and deuterium targets are reported. Approximately 360,000 Drell-Yan muon pairs remained after all cuts on the data. From these data, the ratio of anti-down ($\bar{d}$) to anti-up ($\bar{u}$) quark distributions in the proton sea is determined over a wide range in Bjorken-$x$. These results confirm previous measurements by E866 and extend them to lower $x$. From these data, $(\bar{d}-\bar{u})$ and $\int(\bar{d}-\bar{u})dx$ are evaluated for $0.015<x<0.35$. These results are compared with parameterizations of various parton distribution functions, models and experimental results from NA51, NMC, and HERMES.Comment: 17 pages, 15 figure

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele