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41.
42.
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects over 6 million people worldwide. Development of new drugs to treat this disease remains a priority since those currently available have variable efficacy and frequent adverse effects, especially during the long regimens required for treating the chronic stage of the disease. T. cruzi modulates the host cell-metabolism to accommodate the cell cytosol into a favorable growth environment and acquire nutrients for its multiplication. In this study we evaluated the specific anti-T. cruzi activity of nine bio-energetic modulator compounds. Notably, we identified that 17-DMAG, which targets the ATP-binding site of heat shock protein 90 (Hsp90), has a very high (sub-micromolar range) selective inhibition of the parasite growth. This inhibitory effect was also highly potent (IC50 = 0.27 μmol L−1) against the amastigote intracellular replicative stage of the parasite. Moreover, molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. Evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting the difficulties encountered when going from in vitro assays onto preclinical drug developmental stages.  相似文献   
43.
The establishment of the gut microbiota poses implications for short and long-term health. Bifidobacterium is an important taxon in early life, being one of the most abundant genera in the infant intestinal microbiota and carrying out key functions for maintaining host-homeostasis. Recent metagenomic studies have shown that different factors, such as gestational age, delivery mode, or feeding habits, affect the gut microbiota establishment at high phylogenetic levels. However, their impact on the specific bifidobacterial populations is not yet well understood. Here we studied the impact of these factors on the different Bifidobacterium species and subspecies at both the quantitative and qualitative levels. Fecal samples were taken from 85 neonates at 2, 10, 30, 90 days of life, and the relative proportions of the different bifidobacterial populations were assessed by 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing. Absolute levels of the main species were determined by q-PCR. Our results showed that the bifidobacterial population establishment is affected by gestational age, delivery mode, and infant feeding, as it is evidenced by qualitative and quantitative changes. These data underline the need for understanding the impact of perinatal factors on the gut microbiota also at low taxonomic levels, especially in the case of relevant microbial populations such as Bifidobacterium. The data obtained provide indications for the selection of the species best suited for the development of bifidobacteria-based products for different groups of neonates and will help to develop rational strategies for favoring a healthy early microbiota development when this process is challenged.  相似文献   
44.
Alloy K41X has been proposed as interconnect material for high temperature vapor electrolysis (HTVE) devices. This chromia forming alloy (alloy K41X) was oxidized at 800 °C in a thermobalance in oxidizing (synthetic air) and reducing (Ar–1 %H2–9 %H2O) environments for 250 h. The evolution of the contact resistance was evaluated using a dedicated device under the same conditions. There were higher oxidation kinetics rate in air than in Ar–1 %H2–9 %H2O but surprisingly, the corresponding area specific resistance (ASR) values were 20 times higher in Ar–1 %H2–9 %H2O mixture than in air. Additional tests and analyses (exposure in Ar–D2–H2O environment, GD-OES and SIMS analyses) clearly showed that the higher ASR value can be attributed to the presence of hydrogen in the oxide scale when exposed in Ar–H2–H2O mixture. In situ changes of atmosphere during ASR measurement showed the rapid kinetics for hydrogen desorption.  相似文献   
45.
46.
Micropollutants as pharmaceutical active compounds (PhACs), residuals of personal care products or endocrine disrupting chemicals are of increasing interest in water pollution control. In this context the removal efficiencies of sewage treatment plants (STPs) are of importance, as their effluents are important point sources for the release of those substances into the aquatic environment. Activated sludge based wastewater treatment is the worldwide prevalently used treatment technique. In conventional plants the separation of treated wastewater and sludge occurs via sedimentation. A new development is the application of membrane technology for this separation step. The studies focus on the influence of the solids retention time (SRT) on the removal efficiency, as the SRT is the most important parameter in the design of STPs. A conventional activated sludge plant (CASP) and a membrane bioreactor (MBR) were operated at different SRTs. The substances selected are the antiepileptic carbamazepine, the analgesics diclofenac and ibuprofen, the lipid regulator bezafibrate, the polycyclic musks tonalide and galaxolide and the contraceptive 17alpha-ethinylestradiole. No significant differences in the removal efficiency were detected. Due to the absence of suspended solids in the MBR effluent, substances with high adsorption potential could be retained to slightly higher amounts.  相似文献   
47.
Stereoscopic Particle Image Velocimetry measurements investigating the effect of vortex generators (VGs) on the flow near stall were carried out in a purpose‐built wind tunnel for airfoil investigations on a DU 91‐W2‐250 profile. Measurements were conducted at Re = 0.9?106, corresponding to free stream velocity U = 15 m s?1. The objective was to investigate the flow structures induced by the vortex generators and study their separation controlling behavior on the airfoil. The uncontrolled flow (no VGs) displayed unsteady behavior with separation as observed from large streamwise velocity variations. The corresponding controlled flow (with VGs) showed the same unsteadiness, where the appearance of the vortex structures alternated with a much less separated or even attached boundary layer as also seen in the measured airfoil data: CL = 1.56, CD = 0.116 with VGs and CL = 1.16, CD = 0.135 without. On average, the controlled flow left an attached flow as opposed to the uncontrolled one. Mixing close to the wall, transferring high momentum fluid into the near wall region, was observed, and the hypothesis of variations in the streamwise velocity component in the boundary layer was supported by a Snapshot Proper Orthogonal Decomposition analysis. This analysis also revealed some of the dynamics of the induced vortices. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   
48.
In this paper, the synthesis, design, and implementation of a programmable phase shifter circuit for sinusoidal signals is presented. The proposed circuit, built-up herein with operational amplifiers (OPAMPs), high precision resistors and low voltage switches, consists of a digitally controlled amplitude attenuator in combination with a single-tone orthogonalizer. Experimental results agree with theoretical background: the attained phase range was 252° in 256 steps with a median step of 0.9°. The inaccuracy of the circuit was determined to be of 0.03 %. Contrary to other OPAMP approaches for sinusoidal signals reported in the literature and based on a first-order all-pass filter structure, the approximation suggested in this work is based on a different concept. The achieved results demonstrate the functionality of the system for the case of a sinusoidal signal with frequency of 1 kHz. Notwithstanding, the proposed architecture can be extended to operate at higher frequencies by using different building blocks with larger bandwidth. Furthermore, it can be extended as well to work out with other periodic input waveforms, like triangular shapes or square waves, with the use of an appropriate orthogonalizer.  相似文献   
49.
Bibliometric maps have the potential to become useful tools for science policy issues. The complexity of the structures, however, makes it often very difficult to interpret the results. In this study, we present a case study in which we use the bibliometric mapping results to address a high level science policy issue of research efficiency. By revealing the results in an alternative way, we increased the utility of bibliometric mapping within the science policy context. Moreover, by including additional information to the entities in the landscape, we provide useful input for the research potential.  相似文献   
50.
Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of alcohol use outcomes were examined in 278 individuals diagnosed with a current schizophrenia-spectrum or bipolar disorder and an alcohol use disorder (AUD). At 6-months follow-up, 144 of 228 available participants (63%) had good clinical outcomes. The results of structural equation modeling indicated that type of pretreatment residential setting was directly related to treatment, with participants who lived in supervised settings (41%) reporting significantly more days of treatment (β = .34, p  相似文献   
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