Receptor-Specific Mechanisms Regulate Phosphorylation of AKT at Ser473: Role of RICTOR in β1 Integrin-Mediated Cell Survival

A tight control over AKT/PKB activation is essential for cells, and they realise this in part by regulating the phosphorylation of Ser473 in the “hydrophobic motif” of the AKT carboxy-terminal region. The RICTOR-mTOR complex (TORC2) is a major kinase for AKT Ser473 phosphorylation after stimulation by several growth factors, in a reaction proposed to require p21-activated kinase (PAK) as a scaffold. However, other kinases may catalyse this reaction in stimuli-specific manners. Here we characterised the requirement of RICTOR, ILK, and PAK for AKT Ser473 phosphorylation downstream of selected family members of integrins, G protein-coupled receptors, and tyrosine-kinase receptors and analysed the importance of this phosphorylation site for adhesion-mediated survival. siRNA-mediated knockdown in HeLa and MCF7 cells showed that RICTOR-mTOR was required for phosphorylation of AKT Ser473, and for efficient phosphorylation of the downstream AKT targets FOXO1 Thr24 and BAD Ser136, in response to β1 integrin-stimulation. ILK and PAK1/2 were dispensable for these reactions. RICTOR knockdown increased the number of apoptotic MCF7 cells on β1 integrin ligands up to 2-fold after 24 h in serum-free conditions. β1 integrin-stimulation induced phosphorylation of both AKT1 and AKT2 but markedly preferred AKT2. RICTOR-mTOR was required also for LPA-induced AKT Ser473 phosphorylation in MCF7 cells, but, interestingly, not in HeLa cells. PAK was needed for the AKT Ser473 phosphorylation in response to LPA and PDGF, but not to EGF. These results demonstrate that different receptors utilise different enzyme complexes to phosphorylate AKT at Ser473, and that AKT Ser473 phosphorylation significantly contributes to β1 integrin-mediated anchorage-dependent survival of cells

Physics-based model of planar-gate IGBT Including MOS side two-dimensional effects

An existing physics-based insulated gate bipolar transistor (IGBT) model, which has been proven accurate for both inductive turn-off and inductive turn-on simulations, is modified to account for planar-gate IGBT 2-D effects at the MOS end of the drift region. The modification is based on a steady-state solution of carrier distribution in the JFET region of the IGBT. The accuracy of this solution is verified through a set of finite element simulations. The improved accuracy of the modified model in terms of on-state forward drop and voltage tail at turn-on is verified through comparison with experimental results

Physical modeling of fast p-i-n diodes with carrier lifetime zoning, part II : Parameter extraction

In this paper, a parameter extraction procedure for high-voltage diodes with local lifetime control is proposed. It is designed for use with the physics-based diode model described in Part I, which is capable of simulating diodes with local lifetime control. The parameter extraction procedure described requires a forward characteristic and a reverse recovery measurement. The parameter extraction procedure is illustrated using finite-element simulations. The physics-based model using the parameters extracted is then compared with experimental results

Physical modeling of fast p-i-n diodes with carrier lifetime zoning, part I : Device model

This paper presents the development and implementation of a physics-based diode model which can simulate aspects of high-voltage diodes such as snappy recovery during punch-through and the modified carrier density profile due to local lifetime control. It uses a Fourier series solution for the ambipolar diffusion equation in the lightly doped base region. The model is compared with finite-element device simulations. A parameter extraction procedure for the diode with lifetime control is proposed in Part II

Modeling of IGBT resistive and inductive turn-on behavior

Although insulated-gate bipolar-transistor (IGBT) turn-on losses can be comparable to turn-off losses, IGBT turn-on has not been as thoroughly studied in the literature. In the present work IGBT turn on under resistive and inductive load conditions is studied in detail through experiments, finite element simulations, and circuit simulations using physics-based semiconductor models. Under resistive load conditions, it is critical to accurately model the conductivity-modulation phenomenon. Under clamped inductive load conditions at turn-on there is strong interaction between the IGBT and the freewheeling diode undergoing reverse recovery. Physics-based IGBT and diode models are used that have been proved accurate in the simulation of IGBT turn-off

Modeling of MOS-Side carrier injection in trench-gate IGBTs

A compact trench-gate insulated-gate bipolar transistor model that captures MOS-side carrier injection is developed. The model retains the simplicity of a 1-D solution to the ambipolar diffusion equation, but at the same time, captures the MOS-side carrier injection and its effects on steady-state carrier distribution in the drift region and on switching waveforms

National prevalence survey in Brazil to evaluate the quality of microbiology laboratories: the importance of defining priorities to allocate limited resources

This report describes a survey of microbiology laboratories (n = 467) serving Brazilian hospitals with = 10 intensive care beds and/or involved in the government health care adverse event reporting system. Coordinators were interviewed and laboratories classified as follows: Level 0 (no minimal functioning conditions-85.4% of laboratories); Level 1 (minimal functioning conditions but inadequate execution of basic routine-6.7%); Level 2 (minimal functioning conditions and adequate execution of basic routine but no adequate procedures for quality control-5.8%); Level 3 (minimal functioning conditions, adequate execution of basic routine, and adequate procedures for quality control, but no direct communication with the infection control department-0.9%); Level 4 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, and direct communication with infection control, but no available advanced resources-none); and Level 5 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, direct communication with infection control, and available advanced resources-0.9%). Twelve laboratories did not perform Ziehl-Neelsen staining; 271 did not have safety cabinets; and >30% without safety cabinets had automated systems. Low quality was associated with serving hospitals not participating in government adverse-event program; private hospitals; nonteaching hospitals; and those outside state capitals. Results may reflect what occurs in many other countries where defining priorities is important due to limited resources.331737