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The molecular chaperone Hsp90 supports the functional activity of specific substrate proteins (clients). For client processing, the Hsp90 dimer undergoes a series of ATP-driven conformational rearrangements. Flexible linkers connecting the three domains of Hsp90 are crucial to enable dynamic arrangements. The long charged linker connecting the N-terminal (NTD) and middle (MD) domains exhibits additional functions in vitro and in vivo. The structural basis for these functions remains unclear. Here, we characterize the conformation and dynamics of the linker and NTD−MD domain interactions by NMR spectroscopy. Our results reveal two regions in the linker that are dynamic and exhibit secondary structure conformation. We show that these regions mediate transient interactions with strand β8 of the NTD. As a consequence, this strand detaches and exposes a hydrophobic surface patch, which enables binding to the p53 client. We propose that the charged linker plays an important regulatory role by coupling the Hsp90 NTD−MD arrangement with the accessibility of a client binding site on the NTD.  相似文献   
94.
The quantity control of hazardous waste in Israel relies primarily on the Environmental Services Company (ESC) reports. With limited management tools, the Ministry of Environmental Protection (MoEP) has no applicable methodology to confirm or monitor the actual amounts of hazardous waste produced by various industrial sectors. The main goal of this research was to develop a method for estimating the amounts of hazardous waste produced by various sectors. In order to achieve this goal, sector-specific indicators were tested on three hazardous waste producing sectors in the Haifa Metropolis: petroleum refineries, dry cleaners, and public hospitals. The findings reveal poor practice of hazardous waste management in the dry cleaning sector and in the public hospitals sector. Large discrepancies were found in the dry cleaning sector, between the quantities of hazardous waste reported and the corresponding indicator estimates. Furthermore, a lack of documentation on hospitals' pharmaceutical and chemical waste production volume was observed. Only in the case of petroleum refineries, the reported amount was consistent with the estimate.  相似文献   
95.
Abstract

We pose the problem of estimating the width of the upper layer of a two-stratum medium using data from reflectance measurements made at the interface separating the medium from its surroundings. The lower stratum is assumed to be infinite. In this analysis both the scattering and the absorption coefficients are allowed to differ, but are assumed to be known. We also suggest a simple way to include effects of noise into the analysis.  相似文献   
96.
Particulate and THM Precursor Removal with Ferric Chloride   总被引:1,自引:0,他引:1  
Pilot-scale experiments were performed to investigate the effectiveness of enhanced coagulation in removing particles and trihalomethane (THM) precursors from two surface source waters: California State Project water and Colorado River water. The removal of suspended particles and natural organic matter at various ferric chloride doses and coagulation pHs was assessed through source water and filter effluent measurements of turbidity, particle count, UV254, TOC, and THM formation potential. Overall, it was found that optimal removal of particles and THM precursors by enhanced coagulation with ferric chloride is obtained at high coagulant doses (>16 mg∕L) and low pH conditions. Generally, turbidity removal is more efficient and head loss is more moderate at ambient pH compared with pH 5.5. Additionally, filter effluent particle counts were found to be consistent with residual turbidity data. The removal of THM precursors by enhanced coagulation is significantly enhanced at pH 5.5 compared with ambient pH. The reduction in THM formation potential is consistent with the trends observed for the THM precursor removal data (i.e., UV254 and TOC data). Furthermore, specific UV absorbance was used to estimate the proportion of humic substances in the raw waters. Enhanced coagulation was found to be less effective for the source water with the lower specific UV absorbance.  相似文献   
97.
    
The rapid clearance of drugs from human cells is carried out by MRP1 and other proteins of the ABC transporter superfamily. Selective mutations carried out by DeGorter indicated that replacement of Y324 by phenylalanine (but not by tryptophan or alanine) enhances the capacity of the protein to extrude various drugs. In this study we investigate the effect of mutation on the structure of the isolated transmembrane domain of MRP1 through molecular dynamics simulations of the protein embedded in a POPC membrane. The simulations reveal a persistent tendency of the translocation path to experience a partial constriction, losing ∼50 % of the water inside the conducting path. While the Wt, Y324W and Y324A transporters all experienced the same constriction, the Y324F transporter, the one having a higher clearance rate than the Wt, retains a fully open configuration. The structure of the Y324F mutant reveals an alternate set of stabilizing interactions that force a kink in transmembrane helix 6, which keeps the protein in a fully open outward-facing configuration thus providing a molecular-level account for the higher activity of the mutant. The ability of the simulations to corroborate the experimental observations implies that the homology model of MRP1 is a proper representation of the internal interactions between the residues in the protein, and can be used as a reliable model for studying the human multidrug resistance function of the MRP1 protein.  相似文献   
98.
The Gibbs free energy of mixing dissipated when fresh river water flows into the sea can be harnessed for sustainable power generation. Pressure retarded osmosis (PRO) is one of the methods proposed to generate power from natural salinity gradients. In this study, we carry out a thermodynamic and energy efficiency analysis of PRO work extraction. First, we present a reversible thermodynamic model for PRO and verify that the theoretical maximum extractable work in a reversible PRO process is identical to the Gibbs free energy of mixing. Work extraction in an irreversible constant-pressure PRO process is then examined. We derive an expression for the maximum extractable work in a constant-pressure PRO process and show that it is less than the ideal work (i.e., Gibbs free energy of mixing) due to inefficiencies intrinsic to the process. These inherent inefficiencies are attributed to (i) frictional losses required to overcome hydraulic resistance and drive water permeation and (ii) unutilized energy due to the discontinuation of water permeation when the osmotic pressure difference becomes equal to the applied hydraulic pressure. The highest extractable work in constant-pressure PRO with a seawater draw solution and river water feed solution is 0.75 kWh/m(3) while the free energy of mixing is 0.81 kWh/m(3)-a thermodynamic extraction efficiency of 91.1%. Our analysis further reveals that the operational objective to achieve high power density in a practical PRO process is inconsistent with the goal of maximum energy extraction. This study demonstrates thermodynamic and energetic approaches for PRO and offers insights on actual energy accessible for utilization in PRO power generation through salinity gradients.  相似文献   
99.
Environmental impacts due to engineered nanomaterials arise both from releases of the nanomaterials themselves as well as from their synthesis. In this work, we employ the USEtox model to quantify and compare aquatic ecotoxicity impacts over the life cycle of carbon nanotubes (CNTs). USEtox is an integrated multimedia fate, transport, and toxicity model covering large classes of organic and inorganic substances. This work evaluates the impacts of non-CNT emissions from three methods of synthesis (arc ablation, CVD, and HiPco), and compares these to the modeled ecotoxicity of CNTs released to the environment. Parameters for evaluating CNT ecotoxicity are bounded by a highly conservative "worst case" scenario and a "realistic" scenario that draws from existing literature on CNT fate, transport, and ecotoxicity. The results indicate that the ecotoxicity impacts of nanomaterial production processes are roughly equivalent to the ecotoxicity of CNT releases under the unrealistic worst case scenario, while exceeding the results of the realistic scenario by 3 orders of magnitude. Ecotoxicity from production processes is dominated by emissions of metals from electricity generation. Uncertainty exists for both production and release stages, and is modeled using a combination of Monte Carlo simulation and scenario analysis. The results of this analysis underscore the contributions of existing work on CNT fate and transport, as well as the importance of life cycle considerations in allocating time and resources toward research on mitigating the impacts of novel materials.  相似文献   
100.
A novel forward (direct) osmosis (FO) desalination process is presented. The process uses an ammonium bicarbonate draw solution to extract water from a saline feed water across a semi-permeable polymeric membrane. Very large osmotic pressures generated by the highly soluble ammonium bicarbonate draw solution yield high water fluxes and can result in very high feed water recoveries. Upon moderate heating, ammonium bicarbonate decomposes into ammonia and carbon dioxide gases that can be separated and recycled as draw solutes, leaving the fresh product water. Experiments with a laboratory-scale FO unit utilizing a flat sheet cellulose tri-acetate membrane demonstrated high product water flux and relatively high salt rejection. The results further revealed that reverse osmosis (RO) membranes are not suitable for the FO process because of relatively low product water fluxes attributed to severe internal concentration polarization in the porous support and fabric layers of the RO membrane.  相似文献   
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