The conversion of white adipose to the highly thermogenic beige adipose tissue has been proposed as a potential strategy to counter the unfavorable consequences of obesity. Three regulators of this ...conversion have recently emerged but information regarding their control is limited, and contradictory. We present two studies examining the control of these regulators. Study 1: In 10 young men, the plasma concentrations of irisin and fibroblast growth factor 21 (FGF21) were determined prior to and during activation of the sympathetic nervous system via hypoxic gas breathing (FIO2 = 0.11). The measurements were performed twice, once with and once without prior/concurrent sympathetic inhibition via transdermal clonidine administration. FGF21 was unaffected by basal sympathetic inhibition (338±113 vs. 295±80 pg/mL; P = 0.43; mean±SE), but was increased during hypoxia mediated sympathetic activation (368±135); this response was abrogated (P = 0.035) with clonidine (269±93). Irisin was unaffected by sympathetic inhibition and/or hypoxia (P>0.21). Study 2: The plasma concentration of irisin and FGF21, and the skeletal muscle protein content of fibronectin type III domain containing 5 (FNDC5) was determined in 19 young adults prior to and following three weeks of sprint interval training (SIT). SIT decreased FGF21 (338±78 vs. 251±36; P = 0.046) but did not affect FNDC5 (P = 0.79). Irisin was decreased in males (127±18 vs. 90±23 ng/mL; P = 0.045) and increased in females (139±14 vs. 170±18). Collectively, these data suggest a potential regulatory role of acute sympathetic activation pertaining to the browning of white adipose; further, there appears to be a sexual dimorphic response of irisin to SIT.
A primary goal of molecular ecology is to understand the influence of abiotic factors on the spatial distribution of genetic variation. Features including altitudinal clines, topography and landscape ...characteristics affect the proportion of suitable habitat, influence dispersal patterns, and ultimately structure genetic differentiation among populations. We studied the effects of altitude and topography on genetic variation of long-toed salamanders (Ambystoma macrodactylum), a geographically widespread amphibian species throughout northwestern North America. We focused on 10 low altitude sites (< 1200 m) and 11 high-altitude sites in northwestern Montana and determined multilocus genotypes for 549 individuals using seven microsatellite loci. We tested four hypotheses: (1) gene flow is limited between high- and low-altitude sites; and, (2) gene flow is limited among high-altitude sites due to harsh habitat and extreme topographical relief between sites; (3) low-altitude sites exhibit higher among-site gene flow due to frequent flooding events and low altitudinal relief; and (4) there is a negative correlation between altitude and genetic variation. Overall FST values were moderate (0.08611; P < 0.001). Pairwise FST estimates between high and low populations and a population graphing method supported the hypothesis that low-altitude and high-altitude sites, taken together, are genetically differentiated from each other. Also as predicted, gene flow is more prominent among low-altitude sites than high-altitude sites; low-altitude sites had a significantly lower FST (0.03995; P < 0.001) than high altitude sites (FST = 0.10271; P < 0.001). Use of Bayesian analysis of population structure (BAPS) resulted in delineation of 10 genetic groups, two among low-altitude populations and eight among high-altitude populations. In addition, within high altitude populations, basin-level genetic structuring was apparent. A nonequilibrium algorithm for detecting current migration rates supported these population distinctions. Finally, we also found a significant negative correlation between genetic diversity and altitude. These results are consistent with the hypothesis that topography and altitudinal gradients shape the spatial distribution of genetic variation in a species with a broad geographical range and diverse life history. Our study sheds light on which key factors limit dispersal and ultimately species' distributions.
On-detector digital electronics in high-energy physics (HEP) experiments is increasingly being implemented by means of static random access memory (SRAM)-based field programmable gate arrays (FPGAs), ...due to their reconfigurability, fast data processing, and transfer. Radiation-induced single-event upsets (SEUs) in the configuration hinder the correct operation, since they may alter the programmed routing paths and logic functions. In most data acquisition systems, data from clustered front-end modules are aggregated by a single board, which then transmits data to off-detector electronics for acquisition and triggering. In this work, we present a novel scrubber capable of correcting radiation-induced upsets in the configuration of SRAM-based FPGAs by majority voting across clustered modules. We designed it for the Aerogel Ring Imaging CHerenkov (ARICH) counter of the Belle II experiment at the KEK Laboratory, Tsukuba, Japan. We discuss the architecture of the system and its implementation in a Virtex-5 FPGA, in the aggregator board, for correcting the configuration of up to six Spartan-6 LX45 FPGAs, on pertaining front-end modules. We discuss results from neutron irradiation tests at the TRIGA reactor of the Jožef Stefan Institute, Ljubljana, Slovenia, which show that our solution corrects an average of 6.2 k upsets in each target FPGA before the failure of the scrubber. Moreover, with respect to the Xilinx soft error mitigation (SEM) controller, our design improved the mean time before failure of data readout by 30%.
Thermostability and residual enzymatic activity at 50°C and pH 4.8 of endoglucanase present in the (hemi) cellulolytic complexes produced by A. niger after cultivation under SSF using different types ...of pretreated sugarcane bagasse (SEB, SEBw, and LHWB).
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•Novel cost-effective bioprocesses for cellulolytic enzymes production are needed.•Cultivation conditions should be accompanied by characterization of the thermostability.•Phenolic compounds released after biomass pretreatment restricted fungal growth.•Improved enzyme production requires the removal of inhibitors from the pretreated biomass.•Cellulases produced under SSF were less prone to deactivation by phenolics.
High productivity and enzyme stability are desirable characteristics of bioprocesses for production of the (hemi) cellulolytic enzymes needed for biomass conversion. This paper reports a comparative study of different cultivation systems, investigating production efficiency and the thermostability of the (hemi) cellulolytic enzymatic cocktails. A selected strain of Aspergillus niger was cultivated using a novel sequential fermentation (SF) technique as well as the conventional submerged (SmF) and solid-state fermentation (SSF) methods. Enzyme production and thermostability were evaluated considering the effects of pretreatment (using steam-explosion and liquid hot water) of the sugarcane bagasse used as carbon source and inducer. For endoglucanase and xylanase enzymes, cultivation under SSF favored production when using washed steam-exploded bagasse and liquid hot water-pretreated bagasse as the solid substrates. However, removal of inhibitors from the pretreated biomass employed in the cultivation media was necessary, because the presence of phenolic compounds restricted fungal growth. It was concluded that the cultivation conditions should be conducted in conjunction with characterization of the thermostability of the enzymes, due to the inverse relation that can exist between these two process criteria. The findings revealed that endoglucanase and β-glucosidase produced under SSF were less prone to deactivation by the phenolics in the medium. The residual activities of such enzymes after 24h of incubation at 50°C were between 80 and 100%, indicating that they are highly thermostable. The results emphasize the potential of SSF for the production of (hemi) cellulolytic enzymes that are more stable.
Purpose
Patients with secondary adrenal insufficiency (SAI) have an increased morbidity and an impaired health-related quality of life (HRQoL), which seems to primarily depend on the sub-optimal ...replacement of hypoadrenalism with standard glucocorticoid (GC) therapy, and on the inadequate correction of other associated pituitary deficiencies. A dual-release hydrocortisone (DR-HC) formulation has shown to exert positive effects on morbidity and HRQoL, mainly in patients with primary adrenal insufficiency. We assessed the variations of anthropometric and metabolic parameters and HRQoL in patients with SAI after switching from cortisone acetate (CA) or hydrocortisone (HC) to DR-HC.
Methods
Twenty-one patients (17 M, 4 F) treated with CA (
n
= 16; 25 mg/day twice a day) or HC (
n
= 5; 20 mg/day three times a day), were evaluated for waist circumference, BMI, fasting glucose, HbA1c, insulin, HOMA-IR index, serum lipids, electrolytes, blood pressure and HRQoL at baseline, at 3, 6 and 12 months after switching from CA/HC to DR-HC.
Results
The study showed a significant reduction of waist circumference and BMI (
p
= 0.04, for both), after 3 and 6months of DR-HC treatment, respectively. No significant changes were observed for fasting glucose, insulin, HOMA-IR index, HbA1c, total cholesterol, triglycerides, LDL cholesterol, electrolytes, and blood pressure. However, HDL cholesterol significantly decreased (
p
= 0.003). An improvement of AddiQoL total score was observed during DR-HC treatment (
p
= 0.01), mainly for the category “emotions”. No predictors resulted for these changes.
Conclusion
DR-HC treatment provides some benefits in patients with SAI, reducing central adiposity and improving HRQoL; however, worsening of HDL cholesterol is observed during treatment with DR-HC.
The 100-year global warming potential (GWP) is the primary metric used to compare the climate impacts of emissions of different greenhouse gases (GHGs). The GWP relies on radiative forcing rather ...than damages, assumes constant future concentrations, and integrates over a timescale of 100 years without discounting; these choices lead to a metric that is transparent and simple to calculate, but have also been criticized. In this paper, we take a quantitative approach to evaluating the choice of time horizon, accounting for many of these complicating factors. By calculating an equivalent GWP timescale based on discounted damages resulting from CH
and CO
pulses, we show that a 100-year timescale is consistent with a discount rate of 3.3% (interquartile range of 2.7% to 4.1% in a sensitivity analysis). This range of discount rates is consistent with those often considered for climate impact analyses. With increasing discount rates, equivalent timescales decrease. We recognize the limitations of evaluating metrics by relying only on climate impact equivalencies without consideration of the economic and political implications of metric implementation.
The Level-1 barrel trigger of the ATLAS experiment is based on the resistive plate chambers (RPCs) detectors. The on-detector trigger electronics identifies muons with specific values of transverse ...momentum, by using coincidences between different layers of detectors. Trigger data are then transferred from on-detector to off-detector trigger electronics boards. Data are processed by a complex system, which combines trigger data from the barrel and the end-cap regions and provide the combined muon candidate to the central trigger processor (CTP). The system has been performing well for almost a decade. However, in order to cope with continuously increasing large hadron collider luminosity and more demanding requirements on trigger efficiency and performance, various upgrades for the full-trigger system were already deployed and others are foreseen in the next years. Most of the trigger upgrades are based on the state-of-the-art technologies and allow designing more complex trigger menus, increasing processing power and data transfer bandwidth in order to send more trigger candidates, to perform topological selections, and to support new physics studies. In this paper, we describe the design of the first prototype of the barrel interface board, designed around a Xilinx field-programmable gate array, which transfers RPC trigger data to the CTP system; the board supports the optical transmission of trigger data with fixed latency and new trigger algorithms. We discuss the design strategies, the hardware implementation, and the results of the first functional and integration tests.
The influence of medium composition and culture conditions on Streptococcus pneumoniae serotype 23F cultivation was investigated in order to develop an industrial method for polysaccharide (PS) ...production. Acid-hydrolyzed casein (AHC) and dialyzed enzymatically hydrolyzed soybean meal (EHS) were investigated as nitrogen sources, and the vitamin solution of Hoeprich's medium and dialyzed yeast extract as vitamin sources. The influence of initial glucose concentration was also evaluated. In flask experiments, the best nitrogen source for PS production was AHC; EHS yielded small amounts of PS without interfering with bacterial growth. Dialyzed yeast extract provided an approximately 2-fold increase in PS production when compared to Hoeprich's vitamin solution. In a 5-l bioreactor, it was observed that the pneumococcus did not grow under aerobic conditions, CO₂did not increase PS yield, glucose was inhibitory above 30 g l–¹, and the main glucose catabolism product was lactate, which had an inhibitory effect on cell growth. When anaerobic cultivation was performed under N₂flow using the optimized medium, 240 mg l–¹of soluble PS was obtained, which represents a 3-fold increase in yield as compared to that described in the published patent Yavordios and Cousin (1983) European Patent 0 071515 A1. Application of these results would considerably simplify upstream and downstream processes for PS production.
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