309 research outputs found

    NOD2/CARD 15 gene mutations in patients with Familial Mediterranean Fever

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    Microelectromagnetic ferrofluid-based actuator

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    Computer simulations were used to investigate the performance of a microscale ferrofluid-based magnetic actuator developed for liquid dispensing in microfluidic channels. The actuation was based on the movement of a ferrofluid plug in a magnetic field gradient generated by on-chip effectively infinite parallel conductors. The movement, positioning, and retaining of ferrofluid plugs with different lengths at various locations along a microfluidic channel were investigated for two cases. In case (a), the magnetic field gradient was generated by a single conductor; when the ferrofluid reached its equilibrium position, the current was switched off and the nearest neighbor conductor was energized. A similar, consecutive on/off current switching was performed for case (b), where a set of conductors was energized simultaneously

    Electronic Structure of Lanthanum Hydrides with Switchable Optical Properties

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    Recent dramatic changes in the optical properties of LaH_{2+x} and YH_{2+x} films discovered by Huiberts et al. suggest their electronic structure is described best by a local model. Electron correlation is important in H^- -centers and in explaining the transparent insulating behavior of LaH_3. The metal-insulator transition at x0.8x\sim 0.8 takes place in a band of highly localized states centered on the HH-vacancies in the LaH_3 structure.Comment: plain tex, 3 figure

    Electrical transport in amorphous semiconducting AlMgB14 films

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    The electrical transport properties of semiconducting AlMgB14films deposited at room temperature and 573K are reported in this letter. The as-deposited films are amorphous, and they exhibit high n-type electrical conductivity, which is believed to stem from the conduction electrons donated by Al, Mg, and/or Fe impurities in these films. The film deposited at 573K is less conductive than the room-temperature-deposited film. This is attributed to the nature of donor or trap states in the band gap related to the different deposition temperatures

    Theory for Metal Hydrides with Switchable Optical Properties

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    Recently it has been discovered that lanthanum, yttrium, and other metal hydride films show dramatic changes in the optical properties at the metal-insulator transition. Such changes on a high energy scale suggest the electronic structure is best described by a local model based on negatively charged hydrogen (H^-) ions. We develop a many-body theory for the strong correlation in a H^- ion lattice. The metal hydride is described by a large UU-limit of an Anderson lattice model. We use lanthanum hydride as a prototype of these compounds, and find LaH3_3 is an insulator with a substantial gap consistent with experiments. It may be viewed either as a Kondo insulator or a band insulator due to strong electron correlation. A H vacancy state in LaH3_3 is found to be highly localized due to the strong bonding between the electron orbitals of hydrogen and metal atoms. Unlike the impurity states in the usual semiconductors, there is only weak internal optical transitions within the vacancy. The metal-insulator transition takes place in a band of these vacancy states.Comment: 18 pages, 16 figures and 6 tables. Submitted to PR

    Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

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    Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusions Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic models with strong repressors

    Bone growth during rapamycin therapy in young rats

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    <p>Abstract</p> <p>Background</p> <p>Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties.</p> <p>Methods</p> <p>Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I) were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption.</p> <p>Results</p> <p>At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by <it>histone-4 </it>and <it>mammalian target of rapamycin </it>(<it>mTOR</it>) expression. A reduction in <it>parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) </it>and an increase in <it>Indian hedgehog </it>(<it>Ihh</it>) expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the <it>receptor activator of nuclear factor kappa β ligand </it>(<it>RANKL</it>) and <it>vascular endothelial growth factor </it>(<it>VEGF</it>) expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks.</p> <p>Conclusion</p> <p>When given to young rats, 2 weeks of rapamycin significantly decreased endochondral bone growth. No catch-up growth was demonstrated at the end of 4 weeks, although markers of chondrocyte proliferation and differentiation improved. Clinical studies need to be done to evaluate these changes in growing children.</p

    Numerical solution of a pursuit-evasion differential game involving two spacecraft in low earth orbit

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    This paper considers a spacecraft pursuit-evasion problem taking place in low earth orbit. The problem is formulated as a zero-sum differential game in which there are two players, a pursuing spacecraft that attempts to minimize a payoff, and an evading spacecraft that attempts to maximize the same payoff. We introduce two associated optimal control problems and show that a saddle point for the differential game exists if and only if the two optimal control problems have the same optimal value. Then, on the basis of this result, we propose two computational methods for determining a saddle point solution: a semi-direct control parameterization method (SDCP method), which is based on a piecewise-constant control approximation scheme, and a hybrid method, which combines the new SDCP method with the multiple shooting method. Simulation results show that the proposed SDCP and hybrid methodsare superior to the semi-direct collocation nonlinear programming method (SDCNLP method), which is widely used to solve pursuit-evasion problems in the aerospace field
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