Analogue and digital linear modulation techniques for mobile satellite

The choice of modulation format for a mobile satellite service is complex. The subjective performance is summarized of candidate schemes and voice coder technologies. It is shown that good performance can be achieved with both analogue and digital voice systems, although the analogue system gives superior performance in fading. The results highlight the need for flexibility in the choice of signaling format. Linear transceiver technology capable of using many forms of narrowband modulation is described

Increased response to morphine in mice lacking protein kinase C epsilon

The protein kinase C (PKC) family of serine–threonine kinases has been implicated in behavioral responses to opiates, but little is known about the individual PKC isozymes involved. Here, we show that mice lacking PKCε have increased sensitivity to the rewarding effects of morphine, revealed as the expression of place preference and intravenous self-administration at very low doses of morphine that do not evoke place preference or self-administration in wild-type mice. The PKCε null mice also show prolonged maintenance of morphine place preference in response to repeated testing when compared with wild-type mice. The supraspinal analgesic effects of morphine are enhanced in PKCε null mice, and the development of tolerance to the spinal analgesic effects of morphine is delayed. The density of μ-opioid receptors and their coupling to G-proteins are normal. These studies identify PKCε as a key regulator of opiate sensitivity in mice

Full-Array Noise Performance of Deployment-Grade SuperSpec mm-Wave On-Chip Spectrometers

SuperSpec is an on-chip filter bank spectrometer designed for wideband moderate-resolution spectroscopy at millimeter wavelengths, employing TiN kinetic inductance detectors. SuperSpec technology will enable large-format spectroscopic integral field units suitable for high-redshift line intensity mapping and multi-object spectrographs. In previous results, we have demonstrated noise performance in individual detectors suitable for photon noise-limited ground-based observations at excellent mm-wave sites. In these proceedings, we present the noise performance of a full R∼275 spectrometer measured using deployment-ready RF hardware and software. We report typical noise equivalent powers through the full device of ∼3×10⁻¹⁶ W Hz^(−1/2) at expected sky loadings, which are photon noise dominated. Based on these results, we plan to deploy a six-spectrometer demonstration instrument to the Large Millimeter Telescope in early 2020

SuperSpec: development towards a full-scale filter bank

SuperSpec is a new spectrometer-on-a-chip technology for submm/mm-wave spectroscopy. SuperSpec stands out from other direct-detection submm spectrometer technologies in that the detectors are coupled to a series of resonant filters along a single microwave feedline instead of using dispersive optics. SuperSpec makes use of kinetic inductance detectors (KIDs) to detect radiation in this filter bank. The small profile of this design makes SuperSpec a natural choice to produce a multi-object spectrometer for tomographic mapping or galaxy redshift surveys. We have recently fabricated a device that is a 50 channel subset of a full 280 channel filter bank, which would cover the 190 - 310 GHz range at R = 275. Analysis of the data from this device informs us of the potential design modifications to enable a high-yield background-limited SuperSpec spectrometer. The results indicate that this subset filter bank can scale up to a full filter bank with only a few collisions in readout space and less than 20% variation in responsivity for the detectors. Additionally, the characterization of this and other prototype devices suggests that the noise performance is limited by generation-recombination noise. Finally, we find that the detectors are sufficiently sensitive for ground-based spectroscopy at R = 100, appropriate for tomographic mapping experiments. Further modifications are required to reach the background limit for R = 400, ideal for spectroscopy of individual galaxies

Assessment of intimate partner violence by child welfare services

The purpose of this study was to describe policy and practice with respect to the assessment of intimate partner violence in a sample of child welfare agencies located throughout the United States and to examine the relationship of contextual characteristics and assessment practices. Telephone interviews were conducted with key informants from child welfare agencies. A snowball interviewing strategy was used to identify the best informant in each agency. Almost all of the participating agencies conducted some assessment of intimate partner violence, with most reporting that the majority of screening or assessment occurred during investigation of referrals. However, only 43.1% reported that all of the families referred to the child welfare system were assessed for intimate partner violence, and 52.8% indicated they had a written policy pertaining to screening and assessment of the problem. There was little relationship between county or agency characteristics and assessment practices. Additional research is needed to determine factors that influence assessment practices and to identify strategies to support and extend efforts to identify intimate partner violence and provide appropriate services for families in the child welfare system

Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy, which is responsible for therapy-refractory AML relapse

Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor

Considerable evidence has associated the expression of matrix metalloproteinases (MMPs) with the degradation of cartilage and bone in chronic conditions such as arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of MMP inhibitors with appropriate pharmacological properties. We have identified butanediamide, N4- hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S- (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and stability to permit evaluation in an experimental model of chronic destructive arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia associated with osteoclasia, severe bone and cartilage destruction, and ectopic new bone growth are well developed by 3 wk after adjuvant injection. Rats were injected with Freund's adjuvant on day 0. GI168 was was administered systemically from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12, and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological and histological ankle joint evaluation on day 22 revealed a profound dose related inhibition of bone and cartilage destruction in treated rats relative to rats receiving vehicle alone. A significant reduction in edema, pannus formation, periosteal new bone growth and the numbers of adherent marrow osteoclasts was also noted. However, no significant decrease in polymorphonuclear and mononuclear leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen. This unique profile of antiarthritic activity indicates that GI168 is osteo- and chondro-protective, and it supports a direct role for MMP in cartilage and bone damage and pannus formation in adjuvant- induced arthritis

Full-array noise performance of deployment-grade SuperSpec mm-wave on-chip spectrometers

SuperSpec is an on-chip filter bank spectrometer designed for wideband moderate-resolution spectroscopy at millimeter wavelengths, employing TiN kinetic inductance detectors. SuperSpec technology will enable large-format spectroscopic integral field units suitable for high-redshift line intensity mapping and multi-object spectrographs. In previous results, we have demonstrated noise performance in individual detectors suitable for photon noise-limited ground-based observations at excellent mm-wave sites. In these proceedings, we present the noise performance of a full R∼275 R∼275 spectrometer measured using deployment-ready RF hardware and software. We report typical noise equivalent powers through the full device of ∼3× 10 −16 ∼3×10−16 W Hz −1/2 W Hz−1/2 at expected sky loadings, which are photon noise dominated. Based on these results, we plan to deploy a six-spectrometer demonstration instrument to the Large Millimeter Telescope in early 2020