An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway

PURPOSE: To determine the effects of 28 d of creatine supplementation during training on body composition, strength, sprint performance, and hematological profiles. METHODS: In a double-blind and randomized manner, 25 NCAA division IA football players were matched-paired and assigned to supplement their diet for 28 d during resistance/agility training (8 h x wk[-1]) with a Phosphagen HP (Experimental and Applied Sciences, Golden, CO) placebo (P) containing 99 g x d(-1) of glucose, 3 g x d(-1) of taurine, 1.1 g x d(-1) of disodium phosphate, and 1.2 g x d(-1) of potassium phosphate (P) or Phosphagen HP containing the P with 15.75 g x d(-1) of HPCE pure creatine monohydrate (HP). Before and after supplementation, fasting blood samples were obtained; total body weight, total body water, and body composition were determined; subjects performed a maximal repetition test on the isotonic bench press, squat, and power clean; and subjects performed a cycle ergometer sprint test (12 x 6-s sprints with 30-s rest recovery). RESULTS: Hematological parameters remained within normal clinical limits for active individuals with no side effects reported. Total body weight significantly increased (P < 0.05) in the HP group (P 0.85 +/- 2.2; HP 2.42 +/- 1.4 kg) while no differences were observed in the percentage of total body water. DEXA scanned body mass (P 0.77 +/- 1.8; HP 2.22 +/- 1.5 kg) and fat/bone-free mass (P 1.33 +/- 1.1; HP 2.43 +/- 1.4 kg) were significantly increased in the HP group. Gains in bench press lifting volume (P -5 +/- 134; HP 225 +/- 246 kg), the sum of bench press, squat, and power clean lifting volume (P 1,105 +/- 429; HP 1,558 +/- 645 kg), and total work performed during the first five 6-s sprints was significantly greater in the HP group. CONCLUSION: The addition of creatine to the glucose/taurine/electrolyte supplement promoted greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance during intense resistance/agility training.     

Thrombolytic therapy in Missouri hospital emergency departments: compliance with the National Heart Attack Alert Program guidelines

Adhesive interactions between leukocytes and endothelium are required for subsequent leukocyte extravasation toward inflammatory sites. Understanding the possible kinetic expression of vascular cell adhesion molecule-1 (VCAM-1) in the middle ear cavity during an inflammatory cascade in vivo may be important for clarifying local immunological responses in otitis media. Two inflammatory models were produced in the rat and involved acute middle ear mucosal and cutaneous inflammation induced after inoculation or intradermal injection of lipopolysaccharide (LPS). After intravenous injection of both 125I-labeled anti-VCAM-1 and 131I-labeled control monoclonal antibody (mAb), the kinetic expression of VCAM-1 in the middle ear and skin was assessed by local radionuclide uptake. The biodistribution of an 125I-labeled anti-VCAM-1 mAb as a potential detector of focal inflammation was examined in normal rats. Both inflammatory lesions were characterized by early and sustained (up to 24 h) expression of VCAM-1, with maximal expression at 4 h after LPS stimulation. The kinetics of VCAM-1 expression was similar among the middle ear mucosa or skin specimens studied and different stimulation methods. A similar biodistribution and clearance of radioactivity between 125I-labeled anti-VCAM-1 mAb and 131I- or 99mTc-labeled control mAb were observed. The present result suggest that functional VCAM-1 induced by LPS is expressed in both middle ear tissue and skin lesions and may play a role in the initial stage of inflammatory response produced. Although VCAM-1 upregulation is a very early event in the inflammatory cascade, 125I-labeled anti-VCAM-1 mAb may be useful for the early detection of focal inflammation in the middle ear.     

Saturation intensity and time response of InGaAs-InGaP MQW opticalmodulators

We report modulation saturation and time response measurements on InGaAs-InGaP MQW modulators. The measurements yield a saturation intensity of (3.7±0.1) kW/cm² for a 0-10 V swing and switching times between 10 and 90 ns, depending on the bias voltage and incident light intensity. The observed dependence indicates that field screening due to carrier build-up is the dominant physical mechanism determining both the speed and the saturation intensity. This conclusion is supported by results of theoretical calculations     

Object-oriented specification of a bandwidth management system for ATM-based virtual private networks

This paper describes the specification of a bandwidth management system for ATM-based virtual private networks (vpn). Such a system allows a vpn customer to dynamically modify the bandwidth allocated to vpn connections. The analysis process focuses on the service management information model and interfaces required to provide that service to the customer. The specification work is performed according to a second generation object-oriented development method called Fusion. The vpn service and management architectures as well as the different actors involved are also described in detail.     

Distributed constraint optimization with MULBS: A case study on collaborative meeting scheduling

This paper introduces MULBS, a new DCOP (distributed constraint optimization problem) algorithm and also presents a DCOP formulation for scheduling of distributed meetings in collaborative environments. Scheduling in CSCWD can be seen as a DCOP where variables represent time slots and values are resources of a production system (machines, raw-materials, hardware components, etc.) or management system (meetings, project tasks, human resources, money, etc). Therefore, a DCOP algorithm must find a set of variable assignments that maximize an objective function taking constraints into account. However, it is well known that such problems are NP-complete and that more research must be done to obtain feasible and reliable computational approaches. Thus, DCOP emerges as a very promising technique: the search space is decomposed into smaller spaces and agents solve local problems, collaborating in order to achieve a global solution. We show with empirical experiments that MULBS outperforms some of the state-of-the-art algorithms for DCOP, guaranteeing high quality solutions using less computational resources for the distributed meeting scheduling task.     

Ethanol, immunomodulation and cancer

Several major physiological changes or disease states occur more frequently in alcohol abusers or prolonged high users. These include: cancer, immunosuppression, and nutritional deficiencies. They interact with potential enhancement of cancer growth or survival. Clearly alcohol abuse yielding cirrhosis is associated with immunosuppression of cellular immune functions. Severe, prolonged ethanol consumption frequently is associated with one or more nutrient deficiency. Such deficiencies are more common when there are other major problems such as liver or pancreas damage and in prolonged alcohol abusers should influence the host defenses against pathogens and tumors. The amount and frequency of nutritional and immunological deficiencies with "binge" or less severe alcohol abuse is less clear, but animal studies suggest they are frequently present. Clearly, nutrient deficiencies are common in alcohol abusers and could play significant roles in ethanol associated problems including immunosuppression. Data summarized suggest that immunosuppression caused by nutritional deficiencies and/or direct effects of ethanol and its' metabolites on lymphoid cells is a potential component of cancer in alcohol abusers. However the frequent occurrence of nutritional deficiencies, immunosuppression, and certain cancers in severe, prolonged ethanol abusers is an association, not proven cause and effect.     

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

The effect of increasing application rate of granular calcium ammonium nitrate on net nitrification in a laboratory study of grassland soils

Soil incubation studies were undertaken in controlled environment cabinets at 15°C to investigate the effect of increasing application rates of calcium ammonium nitrate (CAN) on net nitrification in two grassland soils. Granular CAN was applied to the surface of freshly collected, moist soil, at a rate equivalent to 0, 100, 200, 400, 800 and 1600µg NH ₄ ⁺ -N and NO ₃ ^- -N per gram of oven dry soil. In half the treatments finely ground CaCO₃ was incorporated into the moist soil to raise the starting pH. Changes in soil mineral N and pH were measured at weekly intervals up to six-weeks. The most probable number (MPN) technique was used to enumerate the NH ₄ ⁺ -N and NO ₂ ^- -N oxidizers at the beginning and end of the incubation.At low rates of CAN application there was considerable NH ₄ ⁺ -N oxidation to NO ₃ ^- -N during the incubation of both soils. Lime stimulated this N transformation. At high application rates (i.e. 800 and 1600 ppm) there was little change in NH ₄ ⁺ -N or NO ₃ ^- -N on either soil during the 6 week incubation, in the presence or absence of lime. The rate of NO ₃ ^- -N produced peaked at 5.6 and 3.8 mg NO ₃ ^- -N kg^–1 d^–1 on soil 1 and 2 respectively, in the presence of lime. Above a level of 400 ppm CAN (equivalent to 38 kg N ha^–1) the rate of NO ₃ ^- -N produced decreased. The higher rate of net nitrification in soil 1 compared with soil 2 was probably due to a higher number of nitrifying bacteria. Although high rates of CAN decreased the nitrifying activity of both soils there was little difference between treatments in the actual numbers of NH ₄ ⁺ -N and NO ₂ ^- -N oxidizers determined by the MPN technique.The results showed that the rate of granular CAN applied to the soil surface can influence the local activity of nitrifying bacteria and subsequent N transformations. At application rates of CAN generally used agriculturally for grass production, it is likely that net nitrification of the NH ₄ ⁺ -N in the fertilizer granule will be inhibited.     

Characterisation and behaviour of Ti/TiO2/noble metal anodes

The morphology, composition and the electrical and electrochemical behaviour of the anodic microporous layer, prepared by the galvanostatic anodisation of Ti after sparking, followed by galvanostatic deposition of Pt or Ir have been investigated. These electrodes are proposed to function as dimensionally stable anodes (DSAs). For Ti/TiO₂/Pt electrodes, Pt is deposited within some of the micropores of the oxide film. In contrast, for Ti/TiO₂/Ir, the metal is deposited preferentially on the top surface. This difference is thought to result from the position of the metal deposition potential with respect to the flat band potential of n-TiO₂. Optical imaging of both types of DSA suggests that only a few sites on the surface are responsible for electron exchange at the DSA-electrolyte interface. C-AFM measurements of Ti/TiO₂/Pt samples subjected to long-term anodic polarisation, suggest that the Ti-noble metal contact is progressively insulated by thickening of the TiO₂ barrier layer, promoting passivation of the DSA. For Ir coated anodes, catalytic activity is directly related to the presence of Ir and to the stability of the catalytic oxide layer. Under Cu electrowinning conditions, the electrochemically formed hydrated Ir oxide was found to be catalytically less stable, than the iridium oxide film subjected to a heat treatment.     

Investigation of bio-ethanol steam reforming over cobalt-based catalysts

The catalytic performance of cobalt catalysts supported on γ-Al₂O₃, TiO₂, ZrO₂ were studied for bio-ethanol steam reforming (BESR) reaction. The supported catalysts (10 wt%Co) were prepared by impregnation and characterized through Thermogravimetric analysis (TGA), H₂ chemisorption, laser Raman Spectroscopy, Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS), and temperature-programmed reaction (TPRxn). The metallic cobalt sites were found to correlate with the BESR reaction activity. The reaction and H₂ chemisorption showed that ZrO₂ supported catalyst showed the best dispersion and best catalytic activity. Over the 10% Co/ZrO₂ catalyst, using a H₂O:EtOH:inert molar ratio of 10:1:75 and a GHSV = 5000 h⁻¹, 100% ethanol conversion and a yield of 5.5 mol H₂/mol EtOH were obtained at 550 °C and atmospheric pressure.