Neuroprotective Effects of Ischemic Preconditioning on Global Brain Ischemia through Up-Regulation of Acid-Sensing Ion Channel 2a

Transient forebrain or global ischemia induces cell death in vulnerable CA1 pyramidal neurons. A brief period of ischemia, i.e., ischemic preconditioning, affords CA1 neurons robust protection against a subsequent, more prolonged ischemic challenge. Using the four-vessel occlusion model, we established an ischemic preconditioning model in which rodents were subjected to 3 min of sublethal ischemia 48 h before a 15 min lethal ischemia. We showed that preconditioning attenuated the ischemia-induced neural cell death and DNA fragmentation in the hippocampal CA1 region. RT-PCR and western blot analysis showed that preconditioning prior to an ischemic insult significantly increased ASIC 2a mRNA and protein expression in comparison to the ischemic insult alone (p < 0.01). These findings implicate a new role of ASIC 2a on endogenous neuroprotection from ischemic insult

The development of high field magnets utilizing Bi-2212 wind &amp; react insert coils

Wind &amp; react Bi-2212 inserts have been manufactured and tested inside a wide-bore NbTi-Nb3Sn magnet providing a background field up to 20T at 4.2K. A pair of six-layer concentric coils both achieved critical currents of 350 A (JE = 200 A/mm2) in a 20T background field. A thicker 14-layer insert made from 119m of round wire had a critical quench current IQ of 287A (JE = 162 A/mm2) at the same field and contributed to a combined central field of 22.5 T. This is a record for a fully superconducting magnet at 4.2 K. The 14-layer coil, equipped with an external protective shunt, was used for an extensive series of quench measurements and endured &gt;150 quenches without damage. Minimum quench energies were found to be in the range of 200-500mJ in background fields of 15-20T when the coil carried 70-95% of its critical quench current

The Case-Only Test for Gene-Environment Interaction is Not Uniformly Powerful: An Empirical Example: Gene-Environment Interaction

The case-only test has been proposed as a more powerful approach to detect gene-environment (G×E) interactions. This approach assumes that the genetic and environmental factors are independent. While it is well known that Type I error rate will increase if this assumption is violated, it is less widely appreciated that gene-environment correlation can also lead to power loss. We illustrate this phenomenon by comparing the performance of the case-only test to other approaches to detect G×E interactions in a genome-wide association study of esophageal squamous carcinoma (ESCC) in Chinese populations. Some of these approaches do not use information on the correlation between exposure and genotype (standard logistic regression), while others seek to use this information in a robust fashion to boost power without increasing Type I error (two-step, empirical Bayes and cocktail methods). G×E interactions were identified involving drinking status and two regions containing genes in the alcohol metabolism pathway, 4q23 and 12q24. Although the case-only test yielded the most significant tests of G×E interaction in the 4q23 region, the case-only test failed to identify significant interactions in the 12q24 region which were readily identified using other approaches. The low power of the case-only test in the 12q24 region is likely due to the strong inverse association between the SNPs in this region and drinking status. This example underscores the need to consider multiple approaches to detect gene-environment interactions, as different tests are more or less sensitive to different alternative hypotheses and violations of the gene-environment independence assumption

Involvement of Glutamate Transporter-1 in Neuroprotection against Global Brain Ischemia-Reperfusion Injury Induced by Postconditioning in Rats

Ischemic postconditioning refers to several transient reperfusion and ischemia cycles after an ischemic event and before a long duration of reperfusion. The procedure produces neuroprotective effects. The mechanisms underlying these neuroprotective effects are poorly understood. In this study, we found that most neurons in the CA1 region died after 10 minutes of ischemia and is followed by 72 hours of reperfusion. However, brain ischemic postconditioning (six cycles of 10 s/10 s reperfusion/re-occlusion) significantly reduced neuronal death. Significant up-regulation of Glutamate transporter-1 was found after 3, 6, 24, 72 hours of reperfusion. The present study showed that ischemic postconditioning decreases cell death and that upregulation of GLT-1 expression may play an important role on this effect

Subgroup Economic Analysis for Glioblastoma in a Health Resource-Limited Setting

BACKGROUND: The aim of this research was to evaluate the economic outcomes of radiotherapy (RT), temozolomide (TMZ) and nitrosourea (NT) strategies for glioblastoma patients with different prognostic factors. METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was developed to track monthly patient transitions. Transition probabilities and utilities were derived primarily from published reports. Costs were estimated from the perspective of the Chinese healthcare system. The survival data with different prognostic factors were simulated using Weibull survival models. Costs over a 5-year period and quality-adjusted life years (QALYs) were estimated. Probabilistic sensitivity and one-way analyses were performed. The baseline analysis in the overall cohort showed that the TMZ strategy increased the cost and QALY relative to the RT strategy by $25,328.4 and 0.29, respectively; and the TMZ strategy increased the cost and QALY relative to the NT strategy by$23,906.5 and 0.25, respectively. Therefore, the incremental cost effectiveness ratio (ICER) per additional QALY of the TMZ strategy, relative to the RT strategy and the NT strategy, amounts to $87,940.6 and$94,968.3, respectively. Subgroups with more favorable prognostic factors achieved more health benefits with improved ICERs. Probabilistic sensitivity analyses confirmed that the TMZ strategy was not cost-effective. In general, the results were most sensitive to the cost of TMZ, which indicates that better outcomes could be achieved by decreasing the cost of TMZ. CONCLUSIONS/SIGNIFICANCE: In health resource-limited settings, TMZ is not a cost-effective option for glioblastoma patients. Selecting patients with more favorable prognostic factors increases the likelihood of cost-effectiveness

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

Analysis of the Long-Term Characteristics of BDS On-Orbit Satellite Atomic Clock: Since BDS-3 Was Officially Commissioned

Satellite atomic clocks are the key elements for position, navigation, and timing services of the Global navigation satellite system (GNSS); it is necessary to research the characteristics of BDS-3 on-orbit satellite atomic clocks for their further optimization. In this study, clock offset data with a duration of 620 days since BDS-3 was officially commissioned were applied to long-term characteristic analysis. To begin with, the precision clock offset data of Deutsches geoforschungs zentrum (GFZ) processed by a MAD-based method were used as reliable test data. Herein, the working principle and main characteristics of satellite atomic clocks are analyzed and discussed, and thus, a comprehensive long-term characteristic analysis scheme is designed. On this basis, the performance indicators—mainly including physical parameters, periodic characteristics, frequency drift rate, frequency accuracy, frequency stability—were calculated and analyzed respectively, revealing the long-term characteristics of the BDS in orbit satellite atomic clocks during the test period. The results of experimental data testify that the performance of BDS-3 satellite atomic clocks is significantly superior to that of BDS-2, especially in terms of drift rate and frequency stability, and the performance of passive hydrogen maser (PHM) is generally superior to that of rubidium atomic frequency standards (RAFS). Within about half a year since BDS-3 was officially commissioned, the frequency stability of BDS-3 satellite atomic clock gradually improved and then reached the order of 10−15, reflecting the effectiveness of system maintenance and inter-satellite link. Furthermore, some novel conclusions are drawn, such as the long-term period term of the fitting residual and drift rate, which may be caused by the earth’s revolution

Improving the electrochemical properties of SSZ electrolyte-supported solid oxide fuel cells

Electrolyte-supported solid oxide fuel cells (NiO-1Ce10ScZr vertical bar 1Ce10ScZr vertical bar LSM-1Ce10ScZr) were prepared in this study. The effects of cosintering temperatures of cathode and anode with electrolyte and the additions of metal oxide (Bi2O3 and CeO2) in the anode on the microstructures and electrochemical properties were investigated. The carbon deposition behaviors of the anode with added CeO2 were also evaluated. Results indicated that the maximum power density (P-max) initially increased from 0.28 W/cm(2) (1150 degrees C) to 0.35 W/cm(2) (1250 degrees C), and then decreased to 0.33 W/cm(2) (1300 degrees C) with the increase in co-sintering temperature from 1150 degrees C to 1300 degrees C. The variation tendency of P-max was attributed to a complex combination of the bond strength increase of the interfaces and the densification of the electrodes with the increase of the co-sintering temperature. Adding proper CeO2 in the anode effectively improved the electrochemical properties of the ZrO2 doped with Sc2O3 electrolyte-supported single cells. This phenomenon could be related to the increase of the dimension of three-phase boundary. The P-max of the SSZ electrolyte-supported single cell with the anode mixed with 1.0 wt% CeO2 could reach 0.42 W/cm(2). The mixture of 1.0 wt% CeO2 in the anode could also effectively suppress the carbon deposition of CH4 on the anode surface. (C) 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved