Structural and functional conservation of key domains in InsP3 and ryanodine receptors

Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6??) and without (3.0??) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore.     

Energy Management System Design and Testing for Smart Buildings Under Uncertain Generation (Wind/Photovoltaic) and Demand

This study provides details of the energy management architecture used in the Goldwind microgrid test bed. A complete mathematical model, including all constraints and objectives, for microgrid operational management is first described using a modified prediction interval scheme. Forecasting results are then achieved every 10 min using the modified fuzzy prediction interval model, which is trained by particle swarm optimization.A scenario set is also generated using an unserved power profile and coverage grades of forecasting to compare the feasibility of the proposed method with that of the deterministic approach. The worst case operating points are achieved by the scenario with the maximum transaction cost. In summary, selection of the maximum transaction operating point from all the scenarios provides a cushion against uncertainties in renewable generation and load demand.     

Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease.

Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex. The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M(r) 350K). The length of the CAG/polyglutamine repeat is inversely correlated with the age of disease onset. The molecular pathways mediating the neuropathology of Huntington's disease are poorly understood. Transgenic mice expressing exon 1 of the human huntingtin gene with an expanded CAG/polyglutamine repeat develop a progressive syndrome with many of the characteristics of human Huntington's disease. Here we demonstrate evidence of caspase-1 activation in the brains of mice and humans with the disease. In this transgenic mouse model of Huntington's disease, expression of a dominant-negative caspase-1 mutant extends survival and delays the appearance of neuronal inclusions, neurotransmitter receptor alterations and onset of symptoms, indicating that caspase-1 is important in the pathogenesis of the disease. In addition, we demonstrate that intracerebroventricular administration of a caspase inhibitor delays disease progression and mortality in the mouse model of Huntington's disease.     

Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.

Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Abeta42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-beta may be effective in preventing and treating Alzheimer's disease.     

Computationally efficient locality-aware interconnection topology for multi-processor system-on-chip (MP-SoC)

This paper evaluates the Triplet Based Architecture, TriBA – a new idea in chip multiprocessor architectures and a class of Direct Interconnection Network (DIN). TriBA consists of a 2D grid of small, programmable processing units, each physically connected to its three neighbors so that advantageous features of group locality can be fully and efficiently utilized. Any communication model can be well characterized by locality properties and, any topology has its intrinsic, structural, locality characteristics. We propose a new criterion in performance evaluation that is based on the concept of locality in an interconnection network, the “lower layer complete connect”. Our proposed criterion depicts how completely a processing node is connected to all its neighbors. TriBA is compared with 2D Mesh and Binary Tree as static interconnection network. The comparison / evaluation is enumerated from three orthogonal view points, viz., computational speed, physical layout and cost. Our analysis concludes that TriBA is computationally efficient interconnection strategy that exploits group locality in processing nodes.     

Microstructure and properties of nano-TiN modified Ti（C,N）-based cermets fabricated by powder injection molding and die pressing

Powder injection molding （PIM） and die pressing were employed to fabricate nano-TiN modified Ti（C,N）- based cermets. The shrinkage behavior, microstructure, porosity, and mechanical properties of the samples with and without nano-TiN addition fabricated by PIM and die pressing were analyzed. It is demonstrated that for either PIM or die pressing, the porosities are obviously reduced, the mechanical properties are significantly improved after adding nano-TiN, and the hard particles are refined; the rim phase thickness obviously becomes thinner, and the number of dimples in fracture also increases. Compared the samples fabricated by die pressing, it is difficult for PIM to obtain dense Ti（C,N）-based cermets. Due to the too much existence of pores and isolated carbon, the mechanical properties of the sintered samples by PIM are inferior to those of the sintered ones by die pressing.     

Structural and optical properties of Cr doped ZnO crystalline thin films deposited by reactive electron beam evaporation technique

ZnO and Cr-doped ZnO thin films are grown on to glass substrates using reactive electron beam(e-beam) evaporation technique.Variation of structural,morphological,and optical properties with Cr doping is investigated.X-ray diffraction(XRD) studies show that the films are polycrystalline in nature with single phase.Energy dispersive spectroscopy(EDS) results demonstrate that Cr ions are substitutionally incorporated into ZnO.Atomic force microscopy(AFM) reveals that the films present a compact surface and root mean squared(RMS) roughness increased with Cr contents.The optical band gap energy Eg of the films has been determined using Transmission data by spectrophotometer and ellipsometry.The band gap energy found to be decreased with increasing Cr doping concentration.The optical constants(refractive index,extinction coefficient) are calculated using ellipsometry and found to increase with Cr doping concentration.     

Climate change impacts on crop yield,crop water productivity and food security-A review

This paper provides a comprehensive review of literature related to the assessment of climate change impacts on crop productivity using climate,water and crop yield models.The existing studies present that climate change models with higher spatial resolution can be a way forward for future climate projections.Meanwhile,stochastic projections of more than one climate model are necessary for providing insights into model uncertainties as well as to develop risk management strategies.It is projected that water availability will increase in some parts of the world,which will have its own effect on water use efficiency and water allocation.Crop production can increase if irrigated areas are expanded or irrigation is intensified,but these may increase the rate of environmental degradation.Since climate change impacts on soil water balance will lead to changes of soil evaporation and plant transpiration,consequently,the crop growth period may shorten in the future impacting on water productivity.Crop yields affected by climate change are projected to be different in various areas,in some areas crop yields will increase,and for other areas it will decrease depending on the latitude of the area and irrigation application.Existing modelling results show that an increase in precipitation will increase crop yield,and what is more,crop yield is more sensitive to the precipitation than temperature.If water availability is reduced in the future,soils of high water holding capacity will be better to reduce the impact of drought while maintaining crop yield.With the temperature increasing and precipitation fluctuations,water availability and crop production are likely to decrease in the future.If the irrigated areas are expanded,the total crop production will increase;however,food and environmental quality may degrade.