Ultrathin gate-oxide breakdown-reversibility at low voltage

Solid-insulator breakdown always leads to a permanent conduction path that is irreversible. This is a built-in assumption in all gate-oxide breakdown reliability measurement and lifetime projection. This assumption is not valid when the gate-oxide thickness is less than 2 nm and the operation voltage is 1 V or less. The authors examine the impact of reversible breakdown using breakdown data from 12 000 devices stressed by plasma charging damage. The data support the notion that when the surge current is limited at breakdown, the breakdown event may not leave any mark such as a permanent conduction path. The implication is that the commonly used accelerated-stress test, such as time dependent dielectric breakdown (TDDB), may be underestimating the actual gate-oxide lifetime by as much as a million folds.     

An in vivo model for elucidation of the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced insulin resistance: evidence for differential regulation of insulin signaling by TNF-alpha

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce insulin resistance in cultured cells as well as in animal models. The aim of this study was to map the in vivo mechanism whereby TNF-alpha contributes to the pathogenesis of impaired insulin signaling, using obese and lean Zucker rats in which TNF-alpha activity was inhibited through adenovirus-mediated gene transfer. We employed a replication-incompetent adenovirus-5 (Ad5) vector to endogenously express a TNF inhibitor (TNFi) gene, which encodes a chimeric protein consisting of the extracellular domain of the human 55-kDa TNF receptor joined to a mouse IgG heavy chain. Control animals consisted of rats infected with the same titer of adenovirus carrying the lac-z complementary DNA, encoding for beta-galactosidase. There was a significant reduction in plasma insulin and free fatty acid levels in TNFi obese rats 2 days following Ad5 administration. The peripheral insulin sensitivity index was 50% greater, whereas hepatic glucose output was completely suppressed during hyperinsulinemic glucose clamps in TNFi obese animals, with no differences observed between the two lean groups. The improvement in peripheral and hepatic sensitivity to insulin seen in the obese animals was independent of insulin receptor (IR) number and insulin binding affinity for IR. However, TNF-alpha neutralization led to a 2.5-fold increase in tyrosine phosphorylation of IR in skeletal muscle, whereas this was unchanged in liver. There was also a 4-fold increase in particulate protein tyrosine phosphatase activity of skeletal muscle in TNFi obese animals vs. beta-galactosidase controls, whereas protein tyrosine phosphatase activity in liver was unchanged. These results suggest that TNF-alpha is a mediator of insulin resistance in obesity and may modulate IR signaling in skeletal muscle and liver through different pathways. TNF-alpha may affect insulin action in the liver either at sites distal to the IR or indirectly, possibly because of increased provision of gluconeogenic substrates or altered counterregulation. In addition, the Ad5-mediated gene delivery system employed here provides an in vivo model that is efficient and economical for exploring mechanisms involved in TNF-alpha-induced insulin resistance in various genetic models of obesity-linked diabetes.     

Increased activation of protein kinase A type I contributes to the T cell deficiency in common variable immunodeficiency

The molecular mechanisms underlying the T cell dysfunction often present in common variable immunodeficiency (CVI) are not established. cAMP-dependent protein kinase A type I (PKAI) is an important inhibitor of T cell proliferation after Ag stimulation. We therefore investigated the possibility that activation of PKAI may be involved in the development of T cell dysfunction in CVI. An exogenously added PKAI-selective antagonist (Rp-8-Br-cAMPS) induced a significant increase in anti-CD3-stimulated PBMC proliferation in 20 CVI patients compared with no effect in 15 controls. Purified T cells from 7 CVI patients with strictly defined T cell deficiency had elevated endogenous cAMP levels compared with controls. Treatment of T cells from these CVI patients with Rp-8-bromo-cAMP-phosphorothioate markedly improved anti-CD3-stimulated proliferation (up to 3.7-fold), particularly in CD4+ lymphocytes, reaching proliferation levels comparable to control values. No effect of cAMP antagonist on T cell proliferation was seen in controls. In these CVI patients, cAMP antagonist also increased IL-2 production in anti-CD3-stimulated T cells. However, exogenously added IL-2 at concentrations comparable to the achieved increase in IL-2 levels after addition of cAMP antagonist had no effect on T cell proliferation. Furthermore, the stimulatory effects of exogenously added IL-2 at higher concentrations and cAMP antagonist on T cell proliferation were additive. Our findings indicate that increased PKAI activation may be an important molecular basis for the T cell defect in CVI and suggest that the cAMP/PKAI system may be a potential molecular target for immunomodulating therapy in these patients.     

Anticonvulsants and congenital malformations

Earlier studies indicated that the prevalence of congenital anomalies is greater in infants of epileptic mothers treated with anticonvulsants than in infants of mothers without epilepsy. We carried out a study of women in the General Practice Research Database who delivered liveborn infants between January 1988 and March 1993 and who were exposed to an anticonvulsant drug during the first trimester of pregnancy, and women with epilepsy not treated with anticonvulsants during pregnancy. We matched two nonexposed women without epilepsy to each exposed woman for age at delivery, date of baby's birth, and general practice. Two hundred ninety-seven women treated for epilepsy had 10 liveborn infants with major anomalies (3.4%) compared with 6 of the 594 nonexposed women (1.0%, RR = 3.3, 95% CI 1.2-9.2). We conclude that the infants of women with epilepsy who are treated with an anticonvulsant during the first trimester of pregnancy have an increased risk of major congenital anomalies.     

AIDS education in Tanzania: promoting risk reduction among primary school children

OBJECTIVES: The purpose of this study was to test the effects of an education program in Tanzania designed to reduce children's risk of human immunodeficiency virus (HIV) infection and to improve their tolerance of and care for people with acquired immunodeficiency syndrome (AIDS). METHODS: A randomized controlled community trial including baseline and 12-month follow-up surveys was employed. Public primary schools in the Arusha and Kilimanjaro regions of Tanzania were stratified according to location and randomly assigned to intervention (n = 6) or comparison (n = 12) conditions. Of the 1063 sixth-grade students (average age: 13.6 years) who participated at baseline, 814 participated in the follow-up survey. RESULTS: At follow-up, statistically significant effects favoring the intervention group were observed for exposure to AIDS information and communication, AIDS knowledge, attitudes toward people with AIDS, and subjective norms and behavioral intentions toward having sexual intercourse. A consistent positive but nonsignificant trend was seen for attitudes toward having sexual intercourse and for initiation of sexual intercourse during the previous year (7% vs 17%). CONCLUSIONS: It is feasible and effective to train local teachers and health workers to provide HIV/AIDS education to Tanzanian primary school children.     

发展我军舰载无源干扰装备的几点设想

介绍了我军舰载无源干扰装备的现状,分析了现有装备的不足,并对改进方法进行了初步探讨,提出用来对付精确制导武器的电子战必须从单一的对抗措施发展到同时使用多种对抗措施,从单舰的对抗措施发展到编队间协同对抗措施。     

HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid

High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg—33% (20/60) and wild-type (WT)—7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.     

Coapplication of Magnesium Supplementation and Vibration Modulate Macrophage Polarization to Attenuate Sarcopenic Muscle Atrophy through PI3K/Akt/mTOR Signaling Pathway

Sarcopenia is an age-related geriatric syndrome characterized by the gradual loss of muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to be beneficial to structural and functional outcomes of skeletal muscles, while magnesium (Mg) is a cofactor associated with better indices of skeletal muscle mass and strength. We hypothesized that LMHFV, Mg and their combinations could suppress inflammation and sarcopenic atrophy, promote myogenesis via PI3k/Akt/mTOR pathway in senescence-accelerated mouse P8 (SAMP8) mice and C2C12 myoblasts. Results showed that Mg treatment and LMHFV could significantly decrease inflammatory expression (C/EBPα and LYVE1) and modulate a CD206-positive M2 macrophage population at month four. Mg treatment also showed significant inhibitory effects on FOXO3, MuRF1 and MAFbx mRNA expression. Coapplication showed a synergistic effect on suppression of type I fiber atrophy, with significantly higher IGF-1, MyoD, MyoG mRNA (p < 0.05) and pAkt protein expression (p < 0.0001) during sarcopenia. In vitro inhibition of PI3K/Akt and mTOR abolished the enhancement effects on myotube formation and inhibited MRF mRNA and p85, Akt, pAkt and mTOR protein expressions. The present study demonstrated that the PI3K/Akt/mTOR pathway is the predominant regulatory mechanism through which LMHFV and Mg enhanced muscle regeneration and suppressed atrogene upregulation.     

Lexical and conceptual processing in Chinese-English bilinguals: further evidence for asymmetry

According to the asymmetry model of bilingual representation (Kroll & Stewart, 1994), the first language (L1) lexicon is closely tied to an underlying conceptual memory, whereas second language (L2) items are mostly associated with their L1 equivalents. An outcome of this architecture is that L1-to-L2, or forward, translation must be mediated by the conceptual memory, whereas L2-to-L1 (backward) translation takes a direct lexical path. Some predictions derived from this hypothetical structure were tested in the present study, which took into account, through analysis of covariance, variations in response production time, concept retrieval time, and some other characteristics associated with the individual test items. Proficient Chinese-English bilinguals were tested on delayed production (Balota & Chumbley, 1985), picture naming, word translation, and category matching. The expected asymmetrical pattern of translation latencies (i.e., forward > backward) was demonstrated, although it could be statistically explained by the item characteristic of familiarity; matching an L1 item to a category name was faster than matching an L2 item, suggesting relatively strong L1 conceptual links. The present results are best accommodated by a form of asymmetry that allows for nondominant L2-concept linkage, the use of which is conditional upon the familiarity of the test item to the bilingual.