Варізонна технологія формування структур швидкодіючих GaAs – транзисторів як основи сучасних ВІС

Reducing the size of silicon devices is accompanied by an increase in the effective rate of electrons,  decrease transit time and the transition to a ballistic work.Power consumption is reduced too. Formation of large integrated circuits structures onSi-homotransition reduces their frequency range and performance.Nowadaysproposed several new types of devices and technologies forming of large integrated circuits structures that based on high speeds and mobility of electrons in GaAs, and  small size structures.These include, for example, the heterostructure field-effect transistors on a segmented doping, bipolar transistors with wide-emitter, transistor with soulful base, vertical ballistic transistors, devices with flat-doped barriers and hot electron transistors as element base of modern high-speed large integrated circuits.In this article we consider graded-gap technology formatting as bipolar and field-effect transistors, which are the basis of modern high-speedof large integrated circuits structures.Зменшення розмірів кремнієвих приладів супровуджується збільшенням ефективної швидкості електронів, зменшенням їх пролітного часу і переходом до балістичного режиму роботи. Одночасно, як наслідок, із зменшенням розмірів знижується і споживана потужність. Формування структур ВІС на Si-гомопереході зменшує їх частотний діапазон та швидкодію. Сучасними світовими розробниками було запропоновано декілька нових типів приладів і технологій формування їх структур, які використовують переваги високих значень швидкості і рухливості електронів в GaAs, а також використання малих розмірів структур. До них відносяться, наприклад, польові транзистори на гетероструктурах із сегментованим легуванням (СЛПТ), біполярні транзистори (БГТ) із широкозонним емітером, транзистором з проникливою базою , вертикальні балістичні транзистори, прилади з плоско-легованими бар'єрами і транзистори на гарячих електронах, як елементної бази сучасних сучасних швидкодіючих ВІС. В даній статті ми зупинимось варізонної технології формування структур як біполяних, так і польових транзисторів, які стануть основою сучасних швидкодіючих ВІС

Insulin receptor isoform variations in prostate cancer cells

� 2016 Perks, Zielinska, Wang, Jarrett, Frankow, Ladomery, Bahl, Rhodes, Oxley and Holly. Men who develop prostate cancer (PCa) increasingly have one of the co-morbidities associated with a Western lifestyle that are characterized by hyperinsulinemia, hyperglycemia and increased expression of insulin-like growth factors-I (IGF-I) and IGF-II. Each have been associated with poor prognosis and more aggressive cancers that exhibit increased metabolism and increased glucose uptake. The insulin receptor (IR) has two splice isoforms IR-A and IR-B: IR-A has a higher affinity for IGF-II comparable to that for insulin, whereas the IR-B isoform predominantly just binds to insulin. In this study, we assessed alterations in the IR-A and IR-B isoform ratio and associated changes in cell proliferation and migration of PCa cell lines following exposure to altered concentrations of glucose and treatment with IGF-II and insulin. We observed that where IR-B predominated insulin had a greater effect on migration than IGF-II and IGF-II was more effective when IR-A was the main isoform. With regard to proliferation IGF-II was more effective than insulin regardless of which isoform was dominant. We assessed the abundance of the IR isoforms both in vivo and in vitro and observed that the majority of the tissue samples and cell lines expressed more IR-A than IR-B. Alterations in the isoforms in response to changes in their hormonal milieu could have a profound impact on how malignant cells behave and play a role in promoting carcinogenesis. A greater understanding of the mechanisms underlying changes in alternative splicing of the IR may provide additional targets for future cancer therapies

The Unfolded Protein Response in Amelogenesis and Enamel Pathologies

During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other “professional” secretory cells, ameloblasts employ the unfolded protein response (UPR) to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum)/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI) and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed

The effect Akt2 deletion on tumor development in Pten+/− mice

The serine/threonine kinase Akt is frequently activated in human cancers and is considered an attractive therapeutic target. However, the relative contributions of the different Akt isoforms to tumorigenesis, and the effect of their deficiencies on cancer development are not well understood. We had previously shown that Akt1 deficiency is sufficient to markedly reduce the incidence of tumors in Pten+/− mice. Particularly, Akt1 deficiency inhibits endometrial carcinoma and prostate neoplasia in Pten+/− mice. Here, we analyzed the effect of Akt2 deficiency on the incidence of tumors in Pten+/− mice. Relative to Akt1, Akt2 deficiency had little-to-no effect on the incidence of prostate neoplasia, endometrial carcinoma, intestinal polyps and adrenal lesions in Pten+/− mice. However, Akt2 deficiency significantly decreased the incidence of thyroid tumors in Pten+/−, which correlates with the relatively high level of Akt2 expression in the thyroid. Thus, unlike Akt1 deletion, Akt2 deletion is not sufficient to markedly inhibit tumorigenesis in Pten+/− mice in most tested tissues. The relatively small effect of Akt2 deletion on the inhibition of tumorigenesis in Pten+/− mice could be explained, in part, by an insufficient decrease in total Akt activity, due to the relatively lower Akt2 versus Akt1 expression, and relatively high blood insulin levels in Pten+/−Akt2−/− mice. The relatively high blood insulin levels in Pten+/−Akt2−/− mice may elevate the activity of Akt1, and possibly Akt3, thus, limiting the reduction of total Akt activity and preventing this activity from dropping to a threshold level required to inhibit tumorigenesis

Oncogene Activation Induces Metabolic Transformation Resulting in Insulin-Independence in Human Breast Cancer Cells

Normal breast epithelial cells require insulin and EGF for growth in serum-free media. We previously demonstrated that over expression of breast cancer oncogenes transforms MCF10A cells to an insulin-independent phenotype. Additionally, most breast cancer cell lines are insulin-independent for growth. In this study, we investigated the mechanism by which oncogene over expression transforms MCF10A cells to an insulin-independent phenotype. Analysis of the effects of various concentrations of insulin and/or IGF-I on proliferation of MCF10A cells demonstrated that some of the effects of insulin were independent from those of IGF-I, suggesting that oncogene over expression drives a true insulin-independent proliferative phenotype. To test this hypothesis, we examined metabolic functions of insulin signaling in insulin-dependent and insulin-independent cells. HER2 over expression in MCF10A cells resulted in glucose uptake in the absence of insulin at a rate equal to insulin-induced glucose uptake in non-transduced cells. We found that a diverse set of oncogenes induced the same result. To gain insight into how HER2 oncogene signaling affected increased insulin-independent glucose uptake we compared HER2-regulated gene expression signatures in MCF10A and HER2 over expressing MCF10A cells by differential analysis of time series gene expression data from cells treated with a HER2 inhibitor. This analysis identified genes specifically regulated by the HER2 oncogene, including VAMP8 and PHGDH, which have known functions in glucose uptake and processing of glycolytic intermediates, respectively. Moreover, these genes specifically implicated in HER2 oncogene-driven transformation are commonly altered in human breast cancer cells. These results highlight the diversity of oncogene effects on cell regulatory pathways and the importance of oncogene-driven metabolic transformation in breast cancer

The association between adult attained height and sitting height with mortality in the European prospective investigation into cancer and nutrition (EPIC)

Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1=1.11, 95%CI=1.00-1.24; women: HRQ5 vs. Q1=1.17, 95%CI=1.07-1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1=0.63, 95%CI=0.56-0.71; women: HRQ5 vs. Q1=0.81, 95%CI=0.70-0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1=0.64, 95%CI=0.55-0.75; women: HRQ5 vs. Q1=0.60, 95%CI=0.49-0.74) and respiratory disease mortality (men: HRQ5 vs. Q1=0.45, 95%CI=0.28-0.71; women: HRQ5 vs. Q1=0.60, 95%CI=0.40-0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality