Evolutionary trends in Transmit/Receive Module for Active Phased Array Radars

Worldwide, defense technologies are rapidly evolving and are currently aiming at integrating diverse functionalities like Radar, Electronic Warfare, Communications, etc., on a singular miniaturized platform. Hence, it cannot be denied that the advancements in modern Active Phased Array Radar technologies assume a critical role towards the achievement of this goal. A typical Active Phased Array Radar comprises of an Active Antenna Array Unit (AAAU) consisting of a large number of radiating elements, Transmit/Receive (T/R) Modules with other associated RF and digital circuitry and power electronics.  This paper presents mainly the developments in Transmit/Receive (T/R) Module technology, which assimilates various stages of the technological evolution - past, current and futuristic. It discusses how these technologies contribute towards the improvement of efficiency, miniaturization and reliability without compromising its performance parameters

Endothelial Cell Surface Expressed Chemotaxis and Apoptosis Regulator (ECSCR) Regulates Lipolysis in White Adipocytes via the PTEN/AKT Signaling Pathway.

Elevated plasma triglycerides are associated with increased susceptibility to heart disease and stroke, but the mechanisms behind this relationship are unclear. A clearer understanding of gene products which influence plasma triglycerides might help identify new therapeutic targets for these diseases. The Endothelial Cell Surface expressed Chemotaxis and apoptosis Regulator (ECSCR) was initially studied as an endothelial cell marker, but has recently been identified in white adipocytes, the primary storage cell type for triglycerides. Here we confirm ECSCR expression in white adipocytes and show that Ecscr knockout mice show elevated fasting plasma triglycerides. At a cellular level, cultured 3T3-L1 adipocytes silenced for Ecscr show a blunted Akt phosphorylation response. Additionally we show that the phosphatase and tensin homology containing (PTEN) lipid phosphatase association with ECSCR is increased by insulin stimulation. These data suggest a scenario by which ECSCR contributes to control of white adipocyte lipolysis. In this scenario, white adipocytes lacking Ecscr display elevated PTEN activity, thereby reducing AKT activation and impairing insulin-mediated suppression of lipolysis. Collectively, these results suggest that ECSCR plays a critical function in regulating lipolysis in white adipose tissue

Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse Model

Fractalkine receptor 1 (CX3CR1) mediates macrophage infiltration and accumulation, causing venous neointimal hyperplasia (VNH)/venous stenosis (VS) in arteriovenous fistula (AVF). The effect of blocking CX3CR1 using an anti-human variable VHH molecule (hCX3CR1 VHH, BI 655088) on VNH/VS was determined using a humanized mouse in which the human ( ) gene was knocked in (KI). Whole-transcriptomic RNA sequencing with bioinformatics analysis was used on human stenotic AVF samples, C57BL/6J, KI mice with AVF and CKD, and in experiments to identify the pathways involved in preventing VNH/VS formation after hCX3CR1 VHH administration. Accumulation of CX3CR1 and CD68 was significantly increased in stenotic human AVFs. In C57BL/6J mice with AVF, there was increased , and gene expression, and increased immunostaining of CX3CR1 and CD68. In hCX3CR1-KI mice treated with hCX3CR1 VHH molecule (KI-A), compared with vehicle controls (KI-V), there was increased lumen vessel area and patency, and decreased neointima in the AVF outflow veins. RNA-seq analysis identified TNF- and NF- B as potential targets of CX3CR1 inhibition. In KI-A-treated vessels compared with KI-V, there was decreased gene expression of , , and ; with reduction of , NF- B, and ; decreased M1, Ly6C, smooth muscle cells, fibroblast-activated protein, fibronectin, and proliferation; and increased TUNEL and M2 staining. In cell culture, monocytes stimulated with PMA and treated with hCX3CR1 VHH had decreased , , proliferation, and migration. CX3CR1 blockade reduces VNH/VS formation by decreasing proinflammatory cues

Insulin stimulation increases association between ECSCR C-terminus and PTEN in 293T cell overexpression system.

<p><b>A.</b> 293T cells were co-transfected with FLAG-tagged PTEN and either full-length or cytoplasmic truncated ECSCR and subjected to anti-FLAG immune precipitation. Full-length, but not truncated, ECSCR co-immune precipitates with PTEN. <b>B.</b> Insulin stimulation increases ECSCR-PTEN association. <b>C.</b> PI3K inhibitor LY294002 but not by PKA inhibitor cAMPS-Rp blocks ECSCR-PTEN association. Blots are representative of three independent experiments. <b>D</b>. Model for ECSCR influence on insulin inhibition of HSL in white adipocytes. ECSCR interaction with PTEN is predicted to inhibit its activity, allowing increased insulin activation of the PI3K-AKT axis. <i>Dashed lines</i> represent indirect interactions.</p

Tissue expression of ECSCR protein in mouse and human white adipocytes.

<p><b>A.</b> Anti-ECSCR western blot of adult male mouse tissues. Results are representative of lysates from three independent animals. WAT, epididymal white adipose tissue. Tub, tubulin loading control. <b>B.</b> ECSCR protein in cultured 3T3-L1 cells during differentiation to adipocytes. ECSCR protein is compared to reference lipid droplet marker perilipin, with GAPDH as loading control. <b>C.</b> Fractionation of freshly resected human white adipose tissue into mature adipocytes (buoyant fraction) and stromal vascular fraction (SVF). ECSCR is prominent on lipid-bearing, buoyant white adipocytes. SVF antigen CD34 is detected only in the pelleted fraction. <b>D.</b> Confocal micrographs of human muscle and WAT tissue sections stained with UEA-1 lectin (Red) to show vasculature and, anti-ECSCR antiserum (Green). Top: Skeletal muscle. ECSCR is present on the capillaries and on an unidentified resident cell type. Striated muscle fibers are negative for ECSCR. Bottom: White adipose tissue. Adipocyte profiles, immune reactive for ECSCR but negative for UEA lectin, are indicated with (*).</p

<i>Ecscr</i> silenced 3T3-L1 adipocytes and <i>ex vivo</i> differentiated <i>Ecscr</i>^-/- adipocyte cells show reduced Akt phosphorylation.

<p><b>A-C.</b> 3T3-L1 pre-adipocytes were transduced with lentiviral control shRNA or <i>Ecscr</i>-targeting shRNA and allowed to differentiate after puromycin selection. Adipocytes were then stimulated with insulin or isoproterenol and analyzed for lipolysis pathways (<b>A and B</b>), and glycerol release (<b>C</b>). Results are presented as mean +/- SEM of three independent experiments. Similar results were obtained with a second, independent, <i>Ecscr</i> targeting shRNA (not shown). <b>D and E.</b> Stromal vascular fraction cells obtained from wild-type (left) or <i>Ecscr</i>^-/- mice (right) were differentiated into mature adipocytes, stimulated as indicated, then analyzed for lipolysis relevant phospho-epitopes. <b>D.</b> Ex-vivo adipocytes from <i>Ecscr</i>^-/-mice show deficient insulin-dependent AKT activation. <b>E.</b> Densitometry quantitation of pAKT (s473) blots (mean +/- SEM of three independent experiments. For panels <b>B,C</b> and <b>E, *, p<0.05, **, p<0.01, Student’s T-test.</b></p