In situ reduction of charge noise in GaAs/AlGaAs Schottky-gated devices

We show that an insulated electrostatic gate can be used to strongly suppress ubiquitous background charge noise in Schottky-gated GaAs/AlGaAs devices. Via a 2-D self-consistent simulation of the conduction band profile we show that this observation can be explained by reduced leakage of electrons from the Schottky gates into the semiconductor through the Schottky barrier, consistent with the effect of "bias cooling". Upon noise reduction, the noise power spectrum generally changes from Lorentzian to $1/f$ type. By comparing wafers with different Al content, we exclude that DX centers play a dominant role in the charge noise.Comment: 4 pages, 3 figure

Quark and Nucleon Self-Energy in Dense Matter

In a recent work we introduced a nonlocal version of the Nambu--Jona-Lasinio(NJL) model that was designed to generate a quark self-energy in Euclidean space that was similar to that obtained in lattice simulations of QCD. In the present work we carry out related calculations in Minkowski space, so that we can study the effects of the significant vector and axial-vector interactions that appear in extended NJL models and which play an important role in the study of the $\rho$, $\omega$ and $a_1$ mesons. We study the modification of the quark self-energy in the presence of matter and find that our model reproduces the behavior of the quark condensate predicted by the model-independent relation $_{\rho} = <\bar qq>_0(1-\sigma_N\rho_N/f_{\pi}^2m_{\pi}^2 +...)$, where $\sigma_N$ is the pion-nucleon sigma term and $\rho_N$ is the density of nuclear matter. (Since we do not include a model of confinement, our study is restricted to the analysis of quark matter. We provide some discussion of the modification of the above formula for quark matter.) The inclusion of a quark current mass leads to a second-order phase transition for the restoration of chiral symmetry. That restoration is about 80% at twice nuclear matter density for the model considered in this work. We also find that the part of the quark self-energy that is explicitly dependent upon density has a strong negative Lorentz-scalar term and a strong positive Lorentz-vector term, which is analogous to the self-energy found for the nucleon in nuclear matter when one makes use of the Dirac equation for the nucleon. In this work we calculate the nucleon self -energy in nuclear matter using our model of the quark self-energy and obtain satisfactory results.Comment: 19 pages, 8 figures, 2 tables, revte

Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus, a New Twist on ATP Formation.

UnlabelledSyntrophus aciditrophicus is a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation by S.&nbsp;aciditrophicus However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome of S.&nbsp;aciditrophicus leaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show that S.&nbsp;aciditrophicus uses AMP-forming, acetyl-CoA synthetase (Acs1) for ATP synthesis from acetyl-CoA. acs1 mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, of S.&nbsp;aciditrophicus grown in pure culture and coculture. Cell extracts of S.&nbsp;aciditrophicus had low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified from S.&nbsp;aciditrophicus and recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) in S.&nbsp;aciditrophicus cells support the operation of Acs1 in the acetate-forming direction. Thus, S.&nbsp;aciditrophicus has a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase.ImportanceBacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA. Syntrophus aciditrophicus apparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as its genome does not have homologs to the genes for phosphate acetyltransferase and acetate kinase. Here, we show that S.&nbsp;aciditrophicus uses an alternative approach, an AMP-forming, acetyl-CoA synthetase, to make ATP from acetyl-CoA. AMP-forming, acetyl-CoA synthetases were previously thought to function only in the activation of acetate to acetyl-CoA

Isolation of Bacteriocin-producing Staphylococcus spp. Strains from Human Skin Wounds, Soft Tissue Infections and Bovine Mastitis

A collection of 206 Staphylococcus spp. isolates was investigated for their ability to produce compounds exhibiting antistaphylococcal activity. This group included Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus xylosus strains recovered from bovine mastitis (n = 158) and human skin wounds and soft tissues infections (n = 48). Production of substances with antimicrobial activity was observed in six strains. Five of them were recovered from bovine mastitis, and one was isolated from the infected human skin wound. Three of the six antimicrobials produced by the different strains showed substantial loss of antimicrobial activity upon treatment with proteolytic enzymes, which suggests their peptidic structure. Additional studies have shown that one of the putative bacteriocins was efficiently secreted to the liquid medium, facilitating its large-scale production and isolation. The peptide produced by the M2B strain exhibited promising activity; however, against narrow spectrum of Staphylococcus spp. clinical and animal isolates. Growth inhibition was observed only in the case of 13 (including nine S. aureus, three S. xylosus and one S. epidermidis strains) out of 206 strains tested. Important advantage of the produced agent was its high thermal stability. Fifteen minutes of incubation at 90°C did not affect its antimicrobial potential. The highest efficiency of production of the agent was demonstrated in TSB medium after 24 hours at 37°C. The researches revealed that ability to production of bacteriocin among staphylococci is not very common. Only one (S. xylosus strain assigned as M2B) out of 206 strains tested produced satisfactory amounts of antistaphylococcal bacteriocin. In spite of that, we would encourage other researchers for investigation of their collections of Staphylococcus spp. isolates towards selection strains producing antimicrobial agents

A correlation of air-coupled ultrasonic and thermal diffusivity data for CFCC materials

An air-coupled (non contact) through-transmission ultrasonic investigation has been conducted on 2D multiple ply Nicalon{trademark} SiC fiber/SiNC CFCC panels as a function of number of processing cycles. Corresponding thermal diffusivity imaging was also conducted. The results of the air-coupled ultrasonic investigation correlated with thermal property variations determined via infrared methods. Areas of delaminations were detected and effects of processing cycles were also detected

Ischaemic preconditioning improves proteasomal activity and increases the degradation of δPKC during reperfusion

The response of the myocardium to an ischaemic insult is regulated by two highly homologous protein kinase C (PKC) isozymes, delta and epsilon PKC. Here, we determined the spatial and temporal relationships between these two isozymes in the context of ischaemia/reperfusion (I/R) and ischaemic preconditioning (IPC) to better understand their roles in cardioprotection. Using an ex vivo rat model of myocardial infarction, we found that short bouts of ischaemia and reperfusion prior to the prolonged ischaemic event (IPC) diminished delta PKC translocation by 3.8-fold and increased epsilon PKC accumulation at mitochondria by 16-fold during reperfusion. In addition, total cellular levels of delta PKC decreased by 60 +/- 2.7% in response to IPC, whereas the levels of epsilon PKC did not significantly change. Prolonged ischaemia induced a 48 +/- 11% decline in the ATP-dependent proteasomal activity and increased the accumulation of misfolded proteins during reperfusion by 192 +/- 32%; both of these events were completely prevented by IPC. Pharmacological inhibition of the proteasome or selective inhibition of epsilon PKC during IPC restored delta PKC levels at the mitochondria while decreasing epsilon PKC levels, resulting in a loss of IPC-induced protection from I/R. Importantly, increased myocardial injury was the result, in part, of restoring a delta PKC-mediated I/R pro-apoptotic phenotype by decreasing pro-survival signalling and increasing cytochrome c release into the cytosol. Taken together, our findings indicate that IPC prevents I/R injury at reperfusion by protecting ATP-dependent 26S proteasomal function. This decreases the accumulation of the pro-apoptotic kinase, delta PKC, at cardiac mitochondria, resulting in the accumulation of the pro-survival kinase, epsilon PKC.NIH[AA11147]Oklahoma Center for Advancement of Science and Technology[HR05-171S

Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy

Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy

Method-dependent epidemiological cutoff values (ECVs) for detection of triazole resistance in Candida and Aspergillus species for the SYO colorimetric broth and Etest agar diffusion methods

Although the Sensitrite Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method-agent-dependent): 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex (SC), 157 C. (Meyerozyma) guilliermondii, 676 C. krusei (Pichia kudriavzevii), 298 C (Clavispora) lusitaniae, 911 and 3,691 C. parapsilosissensu stricto (SS) and C. parapsilosisSC, respectively, 36 C. metapsilosis, 110 C. orthopsilosis, 1,854 C. tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A. flavus, 130 A. nidulans, 233 A. niger, and 302 A. terreus complexes. SYO/Etest MICs for 282 confirmed non-WT isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2, CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast spp., and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for ECV definition were pooled and we proposed SYO ECVs for S. cerevisiae, 9 yeast and 3 Aspergillus species, and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 \ub5g/ml for C. albicans and the Etest itraconazole ECV of 2 \ub5g/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as overall, the SYO appears to perform better for susceptibility testing of yeast spp. and the Etest for Aspergillus spp. Further evaluations should be conducted with more Candida mutants

Modelling the Role of the Hsp70/Hsp90 System in the Maintenance of Protein Homeostasis

Neurodegeneration is an age-related disorder which is characterised by the accumulation of aggregated protein and neuronal cell death. There are many different neurodegenerative diseases which are classified according to the specific proteins involved and the regions of the brain which are affected. Despite individual differences, there are common mechanisms at the sub-cellular level leading to loss of protein homeostasis. The two central systems in protein homeostasis are the chaperone system, which promotes correct protein folding, and the cellular proteolytic system, which degrades misfolded or damaged proteins. Since these systems and their interactions are very complex, we use mathematical modelling to aid understanding of the processes involved. The model developed in this study focuses on the role of Hsp70 (IPR00103) and Hsp90 (IPR001404) chaperones in preventing both protein aggregation and cell death. Simulations were performed under three different conditions: no stress; transient stress due to an increase in reactive oxygen species; and high stress due to sustained increases in reactive oxygen species. The model predicts that protein homeostasis can be maintained during short periods of stress. However, under long periods of stress, the chaperone system becomes overwhelmed and the probability of cell death pathways being activated increases. Simulations were also run in which cell death mediated by the JNK (P45983) and p38 (Q16539) pathways was inhibited. The model predicts that inhibiting either or both of these pathways may delay cell death but does not stop the aggregation process and that eventually cells die due to aggregated protein inhibiting proteasomal function. This problem can be overcome if the sequestration of aggregated protein into inclusion bodies is enhanced. This model predicts responses to reactive oxygen species-mediated stress that are consistent with currently available experimental data. The model can be used to assess specific interventions to reduce cell death due to impaired protein homeostasis

Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving

Synthetic chemists have devoted tremendous effort towards the production of precision synthetic polymers with defined sequences and specific functions. However, the creation of a general technology that enables precise control over monomer sequence, with efficient isolation of the target polymers, is highly challenging. Here, we report a robust strategy for the production of sequence-defined synthetic polymers through a combination of liquid-phase synthesis and selective molecular sieving. The polymer is assembled in solution with real-time monitoring to ensure couplings proceed to completion, on a three-armed star-shaped macromolecule to maximize efficiency during the molecular sieving process. This approach is applied to the construction of sequence-defined polyethers, with side-arms at precisely defined locations that can undergo site-selective modification after polymerization. Using this versatile strategy, we have introduced structural and functional diversity into sequence-defined polyethers, unlocking their potential for real-life applications in nanotechnology, healthcare and information storage