Long-Term Exposure to High Altitude Affects Voluntary Spatial Attention at Early and Late Processing Stages

The neurocognitive basis of the effect of long-term high altitude exposure on voluntary attention is unclear. Using event related potentials, the high altitude group (people born in low altitude but who had lived at high altitude for 3 years) and the low altitude group (living in low altitude only) were investigated using a voluntary spatial attention discrimination task under high and low perceptual load conditions. The high altitude group responded slower than the low altitude group, while bilateral N1 activity was found only in the high altitude group. The P3 amplitude was smaller in the high altitude compared to the low altitude group only under high perceptual load. These results suggest that long-term exposure to high altitudes causes hemispheric compensation during discrimination processes at early processing stages and reduces attentional resources at late processing stages. In addition, the effect of altitude during the late stage is affected by perceptual load

Alterations in Phospholipid Catabolism in Mycobacterium Tuberculosis LysX Mutant

Mycobacterium tuberculosis lysX mutant, defective for production of lysinylated phosphatidylglycerol, is sensitive to cationic antimicrobial peptides, is not proficient for proliferation in mice lungs, and exhibits altered membrane potential (Maloney et al., 2009). In the present study we show that a lysX complement strain expressing lysX from inducible tet promoter is proficient in restoring lysX phenotypes, confirming that the observed phenotypes are specific to lysX. To evaluate the correlation between changes in membrane potential and lysX activity, we visualized regions of cardiolipin (CL), one of the abundant phospholipids of mycobacteria, by staining with fluorescent dye 10-N-nonyl acridine orange and found that CL is localized as bright spots at septal regions and poles of actively dividing cells, but not in stationary phase cells. lysX mutants were elongated and showed more numerous and brighter CL staining at both mid cell and quarter cell septa, compared with wild type, indicating a defect in the cell division process. Evaluation of 14C-acetic acid incorporation into major phospholipids such as CL, phosphatidylethanolamine (PE), phosphatidylinositol (PI), and their degradation between lysX mutant and its parent revealed differences in the turnover of PE and PI. Our results favor a hypothesis that alterations in phospholipid metabolism could be contributing to changes in membrane potential, hence the observed phenotype of lysX mutant

Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming

SummaryObtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2−/−/γc−/− mice and secrete more than 300 μg/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications

The Impact of Mouse Passaging of Mycobacterium tuberculosis Strains prior to Virulence Testing in the Mouse and Guinea Pig Aerosol Models

It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in the mouse or guinea pig aerosol models.By testing three M. tuberculosis H37Rv samples, one deletion mutant, and one recent clinical isolate for survival by the quantitative organ CFU counting method in mouse or guinea pig aerosol or intravenous infection models, we could discern no increase in bacterial fitness as a result of passaging of M. tuberculosis strains in mice prior to quantitative virulence testing in two animal models. Surface lipid expression as assessed by neutral red staining and thin-layer chromatography for PDIM analysis also failed to identify virulence correlates.These results indicate that animal passaging of M. tuberculosis strains prior to quantitative virulence testing in mouse or guinea pig models does not enhance or restore potency to strains that may have lost virulence due to in vitro passaging. It is critical to verify virulence of parental strains before genetic manipulations are undertaken and comparisons are made

Successful Shortening of Tuberculosis Treatment Using Adjuvant Host-Directed Therapy with FDA-Approved Phosphodiesterase Inhibitors in the Mouse Model

Global control of tuberculosis (TB), an infectious disease that claims nearly 2 million lives annually, is hindered by the long duration of chemotherapy required for curative treatment. Lack of adherence to this intense treatment regimen leads to poor patient outcomes, development of new or additional drug resistance, and continued spread of M.tb. within communities. Hence, shortening the duration of TB therapy could increase drug adherence and cure in TB patients. Here, we report that addition of the United Stated Food and Drug Administration-approved phosphodiesterase inhibitors (PDE-Is) cilostazol and sildenafil to the standard TB treatment regimen reduces tissue pathology, leads to faster bacterial clearance and shortens the time to lung sterilization by one month, compared to standard treatment alone, in a murine model of TB. Our data suggest that these PDE-Is could be repurposed for use as adjunctive drugs to shorten TB treatment in humans

Numerical Analysis and Design of Thermal Management System for Lithium Ion Battery Pack Using Thermoelectric Coolers

A new design of thermal management system for lithium ion battery pack using thermoelectric coolers (TECs) is proposed. Firstly, the 3D thermal model of a high power lithium ion battery and the TEC is elaborated. Then the model is calibrated with experiment results. Finally, the calibrated model is applied to investigate the performance of a thermal management system for a lithium ion battery pack. The results show that battery thermal management system (BTMS) with TEC can cool the battery in very high ambient temperature. It can also keep a more uniform temperature distribution in the battery pack than common BTMS, which will extend the life of the battery pack and may save the expensive battery equalization system

Study of Working Medium Performance by Acoustic Emission in EDM Machining of Ti6Al4V

In electrical discharge machining (EDM), the working medium plays an important role in the material removal process. Lots of methods have been utilized to study this process, but a widely accepted explanation about this process has not been yet accomplished. In this study, the acoustic emission (AE) sensor was fixed on EDM machine to study the material removal process by observing the expansion and contraction process of gas bubble surrounding the discharge plasma. The machining performance in different working mediums was studied for Ti-6Al-4V machining in air, kerosene, and water-based emulsion. Discharge in different working mediums would result in different material removal rates and surface quality. The difference of AE wave frequency domain distribution for discharge in different working mediums was studied. It was observed that the frequency of acoustic emission wave generated by discharge in different working mediums would be different. The characteristic difference of single AE wave generated by discharge in air, kerosene, and water-based emulsion was compared. It was found that the duration time and peak amplitude of acoustic emission wave generated by discharge in different working mediums were different, and the acoustic emission wave generated by discharge in water-based emulsion would last longer and get higher peak amplitude compared to discharge in air and kerosene. The significant difference of AE wave generated by discharge in water-based emulsion from that in kerosene was found. Based on the acoustic emission wave observation, the special characteristic of the material removal process for discharge in water-based emulsion was found

BOLD signal change and contrast reversing frequency: an event-related fMRI study in human primary visual cortex.

It is believed that human primary visual cortex (V1) increases activity with increasing temporal frequency of a visual stimulus. Two kinds of visual stimulus were used in the previous studies, one is patterned-flash stimulus with a fixed onset period and an increasing average luminance with the increase of temporal frequency, the other is contrast reversing flickering checkerboard or grating with a constant average luminance across different temporal frequencies. That hemodynamic responses change as a function of reversal frequency of contrast reversing checkerboard is at odds with neurophysiological studies in animals and neuroimaging studies in humans. In the present study, we addressed the relationship between reversal frequency of contrast reversing checkerboard and hemodynamic response in human V1 using an event-related experimental paradigm and found that the transient characteristics of blood oxygenation level dependent response in human V1 depended very little on the reversal frequency of a contrast reversing checkerboard

Comparison and Summary of Two Methods for Determination of Kinematic Viscosity of Organic Heat Carriers in Different Laboratories

In China, capillary viscometer method is often used to test the kinematic viscosity of organic heat carriers. This method is manually tested and requires cleaning with acetone or petroleum ether, which is easy to cause environmental pollution. In this study, capillary viscometer method and stabinger viscometer method were used to test samples and compare the results. Through data analysis, it was proved that stabinger viscometer method has the advantages of high efficiency, green and environmental protection, and can be applied to accurately determine the kinematic viscosity of organic heat carriers