Novel Approach to Design Ultra Wideband Microwave Amplifiers: Normalized Gain Function Method

In this work, we propose a novel approach called as “Normalized Gain Function (NGF) method” to design low/medium power single stage ultra wide band microwave amplifiers based on linear S parameters of the active device. Normalized Gain Function TNGF is defined as the ratio of T and |S21|^2, desired shape or frequency response of the gain function of the amplifier to be designed and the shape of the transistor forward gain function, respectively. Synthesis of input/output matching networks (IMN/OMN) of the amplifier requires mathematically generated target gain functions to be tracked in two different nonlinear optimization processes. In this manner, NGF not only facilitates a mathematical base to share the amplifier gain function into such two distinct target gain functions, but also allows their precise computation in terms of TNGF=T/|S21|^2 at the very beginning of the design. The particular amplifier presented as the design example operates over 800-5200 MHz to target GSM, UMTS, Wi-Fi and WiMAX applications. An SRFT (Simplified Real Frequency Technique) based design example supported by simulations in MWO (MicroWave Office from AWR Corporation) is given using a 1400mW pHEMT transistor, TGF2021-01 from TriQuint Semiconductor

Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.P50 GM067041 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHSPublished versio

Gain of function mutants: Ion channels and G protein-coupled receptors

Many ion channels and receptors display striking phenotypes for gain-of-function mutations but milder phenotypes for null mutations. Gain of molecular function can have several mechanistic bases: selectivity changes, gating changes including constitutive activation and slowed inactivation, elimination of a subunit that enhances inactivation, decreased drug sensitivity, changes in regulation or trafficking of the channel, or induction of apoptosis. Decreased firing frequency can occur via increased function of K+ or Cl- channels. Channel mutants also cause gain-of-function syndromes at the cellular and circuit level; of these syndromes, the cardiac long-QT syndromes are explained in a more straightforward way than are the epilepsies. G protein-coupled receptors are also affected by activating mutations

STAT3 gain-of-function syndrome

STAT3 gain-of-function (GOF) syndrome is a multi-organ primary immune regulatory disorder characterized by early onset autoimmunity. Patients present early in life, most commonly with lymphoproliferation, autoimmune cytopenias, and growth delay. However, disease is often progressive and can encompass a wide range of clinical manifestations such as: enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, and rarely neurologic disease, vasculopathy, and malignancy. Treatment of the autoimmune and immune dysregulatory features of STAT3-GOF patients relies heavily on immunosuppression and is often challenging and fraught with complications including severe infections. Defects in the T cell compartment leading to effector T cell accumulation and decreased T regulatory cells may contribute to autoimmunity. While T cell exhaustion and apoptosis defects likely contribute to the lymphoproliferative phenotype, no conclusive correlations are yet established. Here we review the known mechanistic and clinical characteristics of this heterogenous PIRD

Parameter-Dependent Lyapunov Functions for Linear Systems With Constant Uncertainties

Robust stability of linear time-invariant systems with respect to structured uncertainties is considered. The small gain condition is sufficient to prove robust stability and scalings are typically used to reduce the conservatism of this condition. It is known that if the small gain condition is satisfied with constant scalings then there is a single quadratic Lyapunov function which proves robust stability with respect to all allowable time-varying perturbations. In this technical note we show that if the small gain condition is satisfied with frequency-varying scalings then an explicit parameter dependent Lyapunov function can be constructed to prove robust stability with respect to constant uncertainties. This Lyapunov function has a rational quadratic dependence on the uncertainties

Study of gain variation as a function of physical parameters of GEM foil

The ALICE experiment at LHC has planned to upgrade the TPC by replacing the MWPC with GEM based detecting elements to restrict the IBF to a tolerable value. However the variation of the gain as a function of physical parameters of industrially produced large size GEM foils is needed to be studied as a part of the QA procedure for the detector. The size of the electron avalanche and consequently the gain for GEM based detectors depend on the electric field distribution inside the holes. Geometry of a hole plays an important role in defining the electric field inside it. In this work we have studied the variation of the gain as a function of the hole diameters using Garfield++ simulation package.Comment: 2 pages, 4 figures, Proceedings of 13th. Pisa Meeting on Advanced Detectors (May 24 - 30, 2015

pax1-1 partially suppresses gain-of-function mutations in Arabidopsis AXR3/IAA17

Background: The plant hormone auxin exerts many of its effects on growth and development by controlling transcription of downstream genes. The Arabidopsis gene AXR3/IAA17 encodes a member of the Aux/IAA family of auxin responsive transcriptional repressors. Semi-dominant mutations in AXR3 result in an increased amplitude of auxin responses due to hyperstabilisation of the encoded protein. The aim of this study was to identify novel genes involved in auxin signal transduction by screening for second site mutations that modify the axr3-1 gain-of-function phenotype. Results: We present the isolation of the partial suppressor of axr3-1 (pax1-1) mutant, which partially suppresses almost every aspect of the axr3-1 phenotype, and that of the weaker axr3-3 allele. axr3-1 protein turnover does not appear to be altered by pax1-1. However, expression of an AXR3:: GUS reporter is reduced in a pax1-1 background, suggesting that PAX1 positively regulates AXR3 transcription. The pax1-1 mutation also affects the phenotypes conferred by stabilising mutations in other Aux/IAA proteins; however, the interactions are more complex than with axr3-1. Conclusion: We propose that PAX1 influences auxin response via its effects on AXR3 expression and that it regulates other Aux/IAAs secondarily