SOT-MRAM 300mm integration for low power and ultrafast embedded memories

We demonstrate for the first time full-scale integration of top-pinned perpendicular MTJ on 300 mm wafer using CMOS-compatible processes for spin-orbit torque (SOT)-MRAM architectures. We show that 62 nm devices with a W-based SOT underlayer have very large endurance (> 5x10^10), sub-ns switching time of 210 ps, and operate with power as low as 300 pJ.Comment: presented at VLSI2018 session C8-

Population pharmacokinetics of daptomycin in critically ill patients with various degrees of renal impairment

Objectives The objective of this study was to characterize the pharmacokinetics of unbound and total concentrations of daptomycin in infected ICU patients with various degrees of renal impairment. From these results, the probability of attaining antimicrobial efficacy and the risks of toxicity were assessed. Methods Twenty-four ICU patients with various renal functions and requiring treatment of complicated skin and soft-tissue infections, bacteraemia, or endocarditis with daptomycin were recruited. Daptomycin (Cubicin®) at 10 mg/kg was administered every 24 h for patients with creatinine clearance (CLCR) ≥30 mL/min and every 48 h for patients with CLCR <30 mL/min. Total and unbound plasma concentrations and urine concentrations of daptomycin were analysed simultaneously following a population pharmacokinetic approach. Simulations were conducted to estimate the probability of attaining efficacy (unbound AUCu/MIC >40 or >80) or toxicity (Cmin >24.3 mg/L) targets. Results Exposure to unbound daptomycin increased when the renal function decreased, thus increasing the probability of reaching the efficacy targets, but also the risk of toxicity. Modifications of the unbound fraction (fu) of daptomycin did not affect the pharmacokinetics of unbound daptomycin, but did affect the pharmacokinetics of total daptomycin. Conclusions Daptomycin at 10 mg/kg q24h allowed efficacy pharmacokinetic/pharmacodynamic targets for ICU patients with CLCR ≥30 mL/min to be reached. For patients with CLCR <30 mL/min, halving the rate of drug administration, i.e. 10 mg/kg q48h, was sufficient to reach these targets. No adverse events were observed, but the toxicity of the 10 mg/kg q24h dosing regimen should be further assessed, particularly for patients with altered renal function

Bioreactors as engineering support to treat cardiac muscle and vascular disease

Cardiovascular disease is the leading cause of morbidity and mortality in the Western World. The inability of fully differentiated, load-bearing cardiovascular tissues to in vivo regenerate and the limitations of the current treatment therapies greatly motivate the efforts of cardiovascular tissue engineering to become an effective clinical strategy for injured heart and vessels. For the effective production of organized and functional cardiovascular engineered constructs in vitro, a suitable dynamic environment is essential, and can be achieved and maintained within bioreactors. Bioreactors are technological devices that, while monitoring and controlling the culture environment and stimulating the construct, attempt to mimic the physiological milieu. In this study, a review of the current state of the art of bioreactor solutions for cardiovascular tissue engineering is presented, with emphasis on bioreactors and biophysical stimuli adopted for investigating the mechanisms influencing cardiovascular tissue development, and for eventually generating suitable cardiovascular tissue replacements

Rationales, design and recruitment for the Elfe longitudinal study

Background Many factors act simultaneously in childhood to influence health status, life chances and well being, including pre-birth influences, the environmental pollutants of early life, health status but also the social influences of family and school. A cohort study is needed to disentangle these influences and explore attribution. Methods Elfe will be a nationally representative cohort of 20 000 children followed from birth to adulthood using a multidisciplinary approach. The cohort will be based on the INSEE Permanent Demographic Panel (EDP) established using census data and civil records. The sample size has been defined in order to match the representativeness criteria and to obtain some prevalence estimation, but also to address the research area of low exposure/rare effects. The cohort will be based on repeated surveys by face to face or phone interview (at birth and each year) as well as medical interview (at 2 years) and examination (at 6 years). Furthermore, biological samples will be taken at birth to evaluate the foetal exposition to toxic substances, environmental sensors will be placed in the child's homes. Pilot studies have been initiated in 2007 (500 children) with an overall acceptance rate of 55% and are currently under progress, the 2-year survey being carried out in October this year. Discussion The longitudinal study will provide a unique source of data to analyse the development of children in their environment, to study the various factors interacting throughout the life course up to adulthood and to determine the impact of childhood experience on the individual's physical, psychological, social and professional development

Accumulation of Polychlorinated Biphenyls in Adipocytes: Selective Targeting to Lipid Droplets and Role of Caveolin-1

Background : Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that preferentially accumulate in lipid-rich tissues of contaminated organisms. Although the adipose tissue constitutes a major intern reservoir of PCBs and recent epidemiological studies associate PCBs to the development of obesity and its related disorders, little is known about the mechanisms involved in their uptake by the adipose tissue and their intracellular localization in fat cells

Modulation of cancer cell growth and progression by Caveolin-1 in the tumor microenvironment

Caveolin-1 (Cav-1), a major structural component of cell membrane caveolae, is involved in a variety of intracellular signaling pathways as well as transmembrane transport. Cav-1, as a scaffolding protein, modulates signal transduction associated with cell cycle progression, cellular senescence, cell proliferation and death, lipid homeostasis, etc. Cav-1 is also thought to regulate the expression or activity of oncoproteins, such as Src family kinases, H-Ras, protein kinase C, epidermal growth factor, extracellular signal-regulated kinase, and endothelial nitric oxide synthase. Because of its frequent overexpression or mutation in various tumor tissues and cancer cell lines, Cav-1 has been speculated to play a role as an oncoprotein in cancer development and progression. In contrast, Cav-1 may also function as a tumor suppressor, depending on the type of cancer cells and/or surrounding -stromal cells in the tumor microenvironment as well as the stage of tumors.

Caveolin-1 overexpression is an early event in the progression of papillary carcinoma of the thyroid

Caveolin-1 is a major structural component of caveolae, which are plasma membrane microdomains implicated in the regulation of intracellular signalling pathways. Previous in vitro and in vivo studies on the function of caveolin-1 in carcinoma showed controversial results, indicating that the physiological role of caveolin-1 varies according to the origin of carcinoma. In this study, we investigated caveolin-1 expression in thyroid neoplasms by means of immunohistochemistry using a rabbit polyclonal antibody against caveolin-1. Normal follicular cells did not express caveolin-1. In papillary carcinoma, caveolin-1 expression was observed in high incidence, and especially in microcancer (less than 1.0 cm in diameter), caveolin-1 was positive in all cases except one. In undifferentiated (anaplastic) carcinoma, its incidence was significantly reduced. On the other hand, all cases of follicular carcinoma and adenoma were classified as negative for caveolin-1. These results suggest that caveolin-1 may play a role predominantly in the early phase of papillary carcinoma, whereas it has little influence on follicular tumours

Estrogen Receptor Alpha Is Expressed in Mesenteric Mesothelial Cells and Is Internalized in Caveolae upon Freund's Adjuvant Treatment

Transformation of epithelial cells into connective tissue cells (epithelial-mesenchymal transition, EMT) is a complex mechanism involved in tumor metastasis, and in normal embryogenesis, while type II EMT is mainly associated with inflammatory events and tissue regenaration. In this study we examined type II EMT at the ultrastructural and molecular level during the inflammatory process induced by Freund's adjuvant treatment in rat mesenteric mesothelial cells. We found that upon the inflammatory stimulus mesothelial cells lost contact with the basal lamina and with each other, and were transformed into spindle-shaped cells. These morphological changes were accompanied by release of interleukins IL-1alpha, -1beta and IL-6 and by secretion of transforming growth factor beta (TGF-beta) into the peritoneal cavity. Mesothelial cells also expressed estrogen receptor alpha (ER-alpha) as shown by immunolabeling at the light and electron microscopical levels, as well as by quantitative RT-PCR. The mRNA level of ER-alpha showed an inverse correlation with the secretion of TGF-beta. At the cellular and subcellular levels ER-alpha was colocalized with the coat protein caveolin-1 and was found in the plasma membrane of mesothelial cells, in caveolae close to multivesicular bodies (MVBs) or in the membrane of these organelles, suggesting that ER-alpha is internalized via caveola-mediated endocytosis during inflammation. We found asymmetric, thickened, electron dense areas on the limiting membrane of MVBs (MVB plaques) indicating that these sites may serve as platforms for collecting and organizing regulatory proteins. Our morphological observations and biochemical data can contribute to form a potential model whereby ER-alpha and its caveola-mediated endocytosis might play role in TGF-beta induced type II EMT in vivo