COBRA-WC pretest predictions and post-test analysis of the FOTA temperature distribution during FFTF natural-circulation transients

The natural circulation tests of the Fast Flux Test Facility (FFTF) demonstrated a safe and stable transition from forced convection to natural convection and showed that natural convection may adequately remove decay heat from the reactor core. The COBRA-WC computer code was developed by the Pacific Northwest laboratory (PNL) to account for buoyancy-induced coolant flow redistribution and interassembly heat transfer, effects that become important in mitigating temperature gradients and reducing reactor core temperatures when coolant flow rate in the core is low. This report presents work sponsored by the US Department of Energy (DOE) with the objective of checking the validity of COBRA-WC during the first 220 seconds (sec) of the FFTF natural-circulation (plant-startup) tests using recorded data from two instrumented Fuel Open Test Assemblies (FOTAs). Comparison of COBRA-WC predictions of the FOTA data is a part of the final confirmation of the COBRA-WC methodology for core natural-convection analysis

Elevated HbA1c levels and the accumulation of differentiated T cells in CMV+ individuals

Aims/hypothesis Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals. Methods A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. Results Among CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p \u3c 0.01) and EMRA (B = 2.90, p \u3c 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p \u3c 0.05) after applying similar adjustments. No associations were observed in CMV− individuals. Conclusions/interpretation The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users

High-Resolution Radio Imaging of Gravitational Lensing Candidates in the 1 Jansky BL Lac Sample

While BL Lacertae objects are widely believed to be highly beamed, low-luminosity radio galaxies, many radio-selected BL Lacs have extended radio power levels and optical emission lines that are too luminous to be low-luminosity radio galaxies. Also, Stocke & Rector discovered an excess of MgII absorption systems along BL Lac sightlines compared to quasars, suggesting that gravitational lensing may be another means of creating the BL Lac phenomenon in some cases. We present a search for gravitationally-lensed BL Lacs with deep, high-resolution, two-frequency VLA radio maps of seven lensing candidates from the 1 Jansky BL Lac sample. We find that none of these objects are resolved into an Einstein ring like B 0218+357, nor do any show multiple images of the core. All of the lensing candidates that were resolved show a flat-spectrum core and very unusual, steep-spectrum extended morphology that is incompatible with a multiply lensed system. Thus, while these observations do not rule out microlensing, no macrolensing is observed.Comment: Accepted, A

XMM-Newton observations of the BL Lac MS0205.7+3509: a dense, low-metallicity absorber

The high-frequency-peaked BL Lac, MS0205.7+3509 was observed twice with XMM-Newton. Both X-ray spectra are synchrotron-dominated, with mean 0.2--10keV fluxes of 2.80+/-0.01 and 3.34+/-0.02 E-12 erg/cm^2/s. The X-ray spectra are well fit by a power-law with absorption above the Galactic value, however no absorption edges are detected, implying a low metallicity absorber (Z_\sun = 0.04(+0.03)(-0.01)) or an absorber with redshift above one (best-fit z=2.1 for an absorber with solar abundances). In either case the absorbing column density must be ~9E21 cm^-2. A new optical spectrum is presented, with a MgII absorption doublet detected at z=0.351, but no other significant features. The optical spectrum shows little reddening, implying a low dust to gas ratio in the absorber. MS0205.7+3509 must therefore be viewed through a high column density, low-metallicity gas cloud, probably at z=0.351 and associated with the galaxy that has been shown to be within ~2" of the BL Lac.Comment: 5 pages, 4 figures, accepted for publication in A&

Exercise and Omega-3 Polyunsaturated Fatty Acid Supplementation for the Treatment of Hepatic Steatosis in Hyperphagic OLETF Rats

Background and Aims. This study examined if exercise and omega-3 fatty acid (n3PUFA) supplementation is an effective treatment for hepatic steatosis in obese, hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods. Male OLETF rats were divided into 4 groups (n=8/group): (1) remained sedentary (SED), (2) access to running wheels; (EX) (3) a diet supplemented with 3% of energy from fish oil (n3PUFA-SED); and (4) n3PUFA supplementation plus EX (n3PUFA+EX). The 8 week treatments began at 13 weeks, when hepatic steatosis is present in OLETF-SED rats. Results. EX alone lowered hepatic triglyceride (TAG) while, in contrast, n3PUFAs failed to lower hepatic TAG and blunted the ability of EX to decrease hepatic TAG levels in n3PUFAs+EX. Insulin sensitivity was improved in EX animals, to a lesser extent in n3PUFA+EX rats, and did not differ between n3PUFA-SED and SED rats. Only the EX group displayed higher complete hepatic fatty acid oxidation (FAO) to CO2 and carnitine palmitoyl transferase-1 activity. EX also lowered hepatic fatty acid synthase protein while both EX and n3PUFA+EX decreased stearoyl CoA desaturase-1 protein. Conclusions. Exercise lowers hepatic steatosis through increased complete hepatic FAO, insulin sensitivity, and reduced expression of de novo fatty acid synthesis proteins while n3PUFAs had no effect

e-Science and biological pathway semantics

<p>Abstract</p> <p>Background</p> <p>The development of e-Science presents a major set of opportunities and challenges for the future progress of biological and life scientific research. Major new tools are required and corresponding demands are placed on the high-throughput data generated and used in these processes. Nowhere is the demand greater than in the semantic integration of these data. Semantic Web tools and technologies afford the chance to achieve this semantic integration. Since pathway knowledge is central to much of the scientific research today it is a good test-bed for semantic integration. Within the context of biological pathways, the BioPAX initiative, part of a broader movement towards the standardization and integration of life science databases, forms a necessary prerequisite for its successful application of e-Science in health care and life science research. This paper examines whether BioPAX, an effort to overcome the barrier of disparate and heterogeneous pathway data sources, addresses the needs of e-Science.</p> <p>Results</p> <p>We demonstrate how BioPAX pathway data can be used to ask and answer some useful biological questions. We find that BioPAX comes close to meeting a broad range of e-Science needs, but certain semantic weaknesses mean that these goals are missed. We make a series of recommendations for re-modeling some aspects of BioPAX to better meet these needs.</p> <p>Conclusion</p> <p>Once these semantic weaknesses are addressed, it will be possible to integrate pathway information in a manner that would be useful in e-Science.</p

The Sedentary Multi-Frequency Survey. I. Statistical Identification and Cosmological Properties of HBL BL Lacs

We have assembled a multi-frequency database by cross-correlating the NVSS catalog of radio sources with the RASSBSC list of soft X-ray sources, obtaining optical magnitude estimates from the Palomar and UK Schmidt surveys as provided by the APM and COSMOS on-line services. By exploiting the nearly unique broad-band properties of High-Energy Peaked (HBL) BL Lacs we have statistically identified a sample of 218 objects that is expected to include about 85% of BL Lacs and that is therefore several times larger than all other published samples of HBLs. Using a subset (155 objects) that is radio flux limited and statistically well-defined we have derived the \vovm distribution and the LogN-LogS of extreme HBLs (fx/fr >= 3E-10 erg/cm2/s/Jansky) down to 3.5 mJy. We find that the LogN-LogS flattens around 20 mJy and that = 0.42 +/- 0.02. This extends to the radio band earlier results, based on much smaller X-ray selected samples, about the anomalous cosmological observational properties of HBL BL Lacs. A comparison with the expected radio LogN-LogS of all BL Lacs (based on a beaming model) shows that extreme HBLs make up roughly 2% of the BL Lac population, independently of radio flux. This result, together with the flatness of the radio logN-logS at low fluxes, is in contrast with the predictions of a recent model which assumes an anti-correlation between peak frequency and bolometric luminosity. The extreme fx/fr flux ratios and high X-ray fluxes of these BL Lacs makes them good candidate TeV sources, some of the brighter (and closer) ones possibly detectable with the current generation of Cerenkov telescopes.Comment: 11 pages, LaTeX, 6 ps figures. Accepted for publication in MNRA

Translational Approach to Examine the Importance of Aerobic Fitness on Nonalcoholic Fatty Liver Disease [abstract]

Comparative Medicine - OneHealth and Comparative Medicine Poster Session.Low cardiorespiratory fitness, independent of physical activity levels, is the best predictor of early mortality and is linked to type 2 diabetes and CVD. In the absence of exercise training, it is believed that genetic inheritance accounts for up to 70% of the variation in intrinsic aerobic fitness. Recent cross-sectional reports in humans also have linked low aerobic fitness with nonalcoholic fatty liver disease (NAFLD). NAFLD, fatty liver not due to alcohol consumption, encompasses a gamut of liver maladaptations and is a primary cause of chronic liver disease and liver-related morbidity and mortality. NAFLD occurs in ~30% of US adults, 75-100% of obese and extremely obese individuals, and is considered the hepatic component of the metabolic syndrome. Despite the recent observations in humans between low fitness and NAFLD, there is a paucity of mechanistic information detailing this link. In order to address this important clinical problem, we have developed an interdisciplinary team across multiple institutions and fields of study and have taken a translational approach, employing both novel whole animal model studies and isolated primary hepatocyte cell culture experiments, to gain mechanistic insight into the human observational studies. We have utilized a novel rat model in which rats are artificially selected over several generations for high and low intrinsic endurance capacity, resulting in high capacity runners (HCR) with high aerobic fitness and low capacity runners (LCR) with significantly lower aerobic fitness (Science, 307:418-20, 2005). These rats display contrasting phenotypes without the influence of exercise training, making them an excellent model to mechanistically assess the role of aerobic fitness on NAFLD. Utilizing this model, we have provided the first mechanistic evidence that the LCR rats have reduced hepatic mitochondrial content and oxidative capacity, increased hepatic de novo lipogenic profiles, and develop hepatic steatosis with progression to greater fibrosis and apoptosis compared to the HCR rats. The LCR rats also are unable to maintain systemic insulin sensitivity following exposure to high-fat feeding. However, since it is impossible to completely eliminate the influence of peripheral factors on liver metabolism, we have subsequently isolated primary hepatocytes from HCR and LCR rats. We have observed a similar phenotype in the primary hepatocytes from LCR animals, with significant reductions in fatty acid oxidation and the inability to maintain insulin signaling in response to lipid exposure compared with HCR hepatocytes. These findings have important clinical implications, as low aerobic fitness due to physical inactivity and/or genetic inheritability may lead to increased susceptibility to NAFLD, and suggest that the clinical measurement of aerobic fitness may serve as a valuable prognostic tool. We are currently conducting a human clinical trial to assess the efficacy of exercise in improving aerobic fitness and reducing NAFLD, and because exercise is the proven method to increase aerobic fitness, it should remain the cornerstone therapy for fatty liver disease