Whither or wither microbicides?

After disappointing results from all efficacy trials conducted to date, the field of microbicides research now faces substantial challenges. Poor coordination among interested parties and the choice of nonvalidated scientific targets for phase III studies have hampered progress and created mistrust about the use of microbicides as a method to prevent HIV-1 sexual transmission. Although new promising strategies are available, there will need to be serious reappraisals of how decisions are made to advance the next generations of candidates into clinical trials, and the use of appropriate animal models in this process will be critical.     

基于RBF网络的联合收获机脱粒滚筒恒速控制

对联合收获机行走、收割、脱粒系统进行分析,提出了系统数学模型的基本形式.针对该模型的高阶次、非线性和难以准确获得具体参数等问题,将模型差分方程的基本形式分解为与控制信号无关和有关的2个部分,利用RBF神经网络技术分别对2个部分进行在线辨识,控制器根据辨识结果进行控制,构建了自适应控制.利用该系统进行了不同条件下的仿真和试验,试验证明利用RBF网络可快速有效地拟合被控对象.当对象参数发生变化时,系统可实现跟踪适应,达到较好的控制效果.     

采摘机器人视觉伺服控制系统设计

分析了采摘机器人目标位置与机器人关节角度之间的运动学关系,给出了两者之间的坐标变换公式.根据伺服控制特点,在机器人伺服控制中引入模糊PID控制方法,利用模糊控制策略在线自适应整定PID参数,提高了控制系统的动、静态性能.仿真和实验结果验证了设计的合理性和有效性.     

Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis

Lysosomal storage diseases (LSDs) are a group of heterogeneous disorders caused by defects in lysosomal enzymes or transporters, resulting in accumulation of undegraded macromolecules or metabolites. Macrophage numbers are expanded in several LSDs, leading to histiocytosis of unknown pathophysiology. Here, we found that mice lacking the equilibrative nucleoside transporter 3 (ENT3) developed a spontaneous and progressive macrophage-dominated histiocytosis. In the absence of ENT3, defective apoptotic cell clearance led to lysosomal nucleoside buildup, elevated intralysosomal pH, and altered macrophage function. The macrophage accumulation was partly due to increased macrophage colony-stimulating factor and receptor expression and signaling secondary to the lysosomal defects. These studies suggest a cellular and molecular basis for the development of histiocytosis in several human syndromes associated with ENT3 mutations and potentially other LSDs.     

Export-mediated assembly of mycobacterial glycoproteins parallels eukaryotic pathways

Protein O-mannosylation is an essential and evolutionarily conserved post-translational modification among eukaryotes. This form of protein modification is also described in Mycobacterium tuberculosis; however, the mechanism of mannoprotein assembly remains unclear. Evaluation of differentially translocated chimeric proteins and mass spectrometry to monitor glycosylation demonstrated that specific translocation processes were required for protein O-mannosylation in M. tuberculosis. Additionally, Rv1002c, a M. tuberculosis membrane protein homolog of eukaryotic protein mannosyltransferases, was shown to catalyze the initial step of protein mannosylation. Thus, the process of protein mannosylation is conserved between M. tuberculosis and eukaryotic organisms.     

Converting ceria polyhedral nanoparticles into single-crystal nanospheres

Ceria nanoparticles are one of the key abrasive materials for chemical-mechanical planarization of advanced integrated circuits. However, ceria nanoparticles synthesized by existing techniques are irregularly faceted, and they scratch the silicon wafers and increase defect concentrations. We developed an approach for large-scale synthesis of single-crystal ceria nanospheres that can reduce the polishing defects by 80% and increase the silica removal rate by 50%, facilitating precise and reliable mass-manufacturing of chips for nanoelectronics. We doped the ceria system with titanium, using flame temperatures that facilitate crystallization of the ceria yet retain the titania in a molten state. In conjunction with molecular dynamics simulation, we show that under these conditions, the inner ceria core evolves in a single-crystal spherical shape without faceting, because throughout the crystallization it is completely encapsulated by a molten 1- to 2-nanometer shell of titania that, in liquid state, minimizes the surface energy. The principle demonstrated here could be applied to other oxide systems.     

Effect of immunosuppressive doses of cyclosporine on pancreatic beta cell function in pigs

OBJECTIVE: To evaluate whether immunosuppressive doses of cyclosporine (CsA) have an adverse effect on the liver, kidney, and pancreatic beta cells of pigs. ANIMALS: 8 juvenile 8-week-old Landrace X Large White crossbred pigs. PROCEDURE: CsA (100 to 140 mg/kg) was administered orally to euglycemic pigs to reach whole blood trough concentrations of approximately 1500 ng/mL. To determine pancreatic beta cell function, plasma C-peptide and insulin concentrations were measured in response to i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Effects on liver and kidney were determined by monitoring serum measurements of liver function and serum creatinine concentrations, respectively. RESULTS: Plasma concentrations of C-peptide were significantly lower in euglycemic CsA-treated pigs, compared with control pigs, following i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Furthermore, the glucose clearance rate was decreased in euglycemic CsA-treated pigs, compared with control pigs. Serum creatinine concentrations and 4 of 7 serum measurements of liver function were not adversely affected by CsA administration. Serum concentrations of bilirubin and albumin were significantly increased, and serum alanine aminotransferase activity was significantly decreased in CsA-treated pigs, compared with control pigs. Histologic evaluation of liver and kidney sections revealed no pathologic findings in CsA-treated or control pigs. CONCLUSIONS AND CLINICAL RELEVANCE: In our study, immunosuppressive doses of CsA caused an impairment of porcine pancreatic beta cell function, but did not have toxic effects on the kidney. However, on the basis of changes in serum bilirubin and albumin concentrations and alanine aminotransferase activity, subclinical toxic effects on the liver did occur when immunosuppressive doses of CsA were administered.     

Auxin Modulates Gibberellin-Induced Effects on Growth,Yield, and Raw Product Recovery for Frozen Processing in Potato (<Emphasis Type="Italic">Solanum tuberosum</Emphasis> L.)

Tuber shape phenotype is an important determinant of raw product (≥7.6-cm-long French fries) recovery for frozen processing. Tuber length-to-width (L/W) ratios ≥1.8 translate to maximum yield of raw product; however, some cultivars produce tubers with much lower L/W ratios. While gibberellin (GA) can be used to elongate tubers, it also decreases tuber size and can thereby attenuate raw product recovery. We investigated the utility of GA and naphthaleneacetic acid (NAA) combination treatments for modifying tuber set, size, and shape to increase yield of raw product from ‘Payette Russet’ and ‘Alturas’; two late-season frozen-processing cultivars that often produce tubers with undesirably low L/W ratios. Models describing L/W ratio and fry yield by tuber size class were developed to translate total U.S. No. 1 tuber yields (>113 g) into yield of raw product. Increases in the L/W ratios of 113–284-g tubers had a greater effect on recovery of French fries (% fresh wt) than for tubers >284 g. Undersize (<113 g) and oversize (>340 g) tubers yielded 0 and 96% fries, respectively, regardless of L/W ratio. GA applied as a seed treatment effectively hastened emergence and altered tuber shape by increasing the L/W ratios of ‘Alturas’ and ‘Payette Russet’ tubers, enhancing total fry yield for the 113–340-g tubers by 24–46%, depending on concentration and application technique (dip, spray, in-furrow). However, GA also decreased apical dominance and shifted tuber size distribution away from >284-g tubers toward higher yields of <170-g tubers, erasing the gains in fry yield when all size classes (>113 g) were considered. When combined with GA, NAA maintained apical dominance, attenuated the shift in tuber size distribution, had no effect on the GA-induced increase in tuber L/W ratio, and only partly moderated the GA-induced stimulation of plant emergence. Raw product yield from ‘Payette Russet’ increased 12–39% in spray application trials by using NAA to confine the effect of GA to tuber shape and limit the loss of U.S. No. 1 tubers to undersize. Increases in tuber L/W ratio with GA/NAA seed treatments translated to increased yield of fries only when the relative concentrations were adjusted to minimize loss of >284-g tubers and gain in undersize tubers, as dictated by cultivar sensitivity to GA. ‘Alturas’ was less sensitive to GA than ‘Payette Russet’ for shifts in tuber size distribution but not shape, resulting in 17% increase in raw product with GA alone in pre-plant seed spray application studies. GA/NAA combination treatments provide an effective approach to manipulate tuber size distribution and enhance the yield of raw product for frozen processing in cultivars with a rounder tuber shape phenotype.