Experimental evaluation of an advanced Space Shuttle main engine hot-gas manifold design concept

This study, using an extensively modified, full-scale space shuttle main engine (SSME) hot-gas manifold (HGM), established a detailed aerodynamic data base to support development of an advanced, three-dimensional, fluid-dynamic analysis computer model. In addition, the advanced SSME hot-gas manifold design used in this study demonstrated improved flow environment (uniformity) in the fuel side turbine exit and transfer duct exit regions. Major modifications were incorporated in the full-scale HGM flow test article model using two large transfer ducts on the fuel turbine side of the HGM in place of the three small transfer ducts in the present design. Other model features included an increases in the flow areas downstream of the 180-degree turn and in the fishbowl regions

Optimization of stochastic control processes with respect to probability on entering a target manifold

Optimization of stochastic control processes with respect to probability of entering target manifold in specific time interva

Background light measurements at the DUMAND site

Ambient light intensities at the DUMAND site, west of the island of Hawaii were measured around the one photoelectron level. Throughout the water column between 1,500m and 4,700m, a substantial amount of stimulateable bioluminescence is observed with a ship suspended detector. But non-stimulated bioluminescence level is comparable, or less than, K sup 40 background, when measured with a bottom tethered detector typical of a DUMAND optical module

READOUT ASIC FOR 3D POSITION-SENSITIVE DETECTORS.

We describe an application specific integrated circuit (ASIC) for 3D position-sensitive detectors. It was optimized for pixelated CZT sensors, and it measures, corresponding to an ionizing event, the energy and timing of signals from 121 anodes and one cathode. Each channel provides low-noise charge amplification, high-order shaping, along with peak- and timing-detection. The cathode's timing can be measured in three different ways: the first is based on multiple thresholds on the charge amplifier's voltage output; the second uses the threshold crossing of a fast-shaped signal; and the third measures the peak amplitude and timing from a bipolar shaper. With its power of 2 mW per channel the ASIC measures, on a CZT sensor Connected and biased, charges up to 100 fC with an electronic resolution better than 200 e{sup -} rms. Our preliminary spectral measurements applying a simple cathode/mode ratio correction demonstrated a single-pixel resolution of 4.8 keV (0.72 %) at 662 keV, with the electronics and leakage current contributing in total with 2.1 keV

MINERvA neutrino detector response measured with test beam data

The MINERvA collaboration operated a scaled-down replica of the solid scintillator tracking and sampling calorimeter regions of the MINERvA detector in a hadron test beam at the Fermilab Test Beam Facility. This article reports measurements with samples of protons, pions, and electrons from 0.35 to 2.0 GeV/c momentum. The calorimetric response to protons, pions, and electrons are obtained from these data. A measurement of the parameter in Birks' law and an estimate of the tracking efficiency are extracted from the proton sample. Overall the data are well described by a Geant4-based Monte Carlo simulation of the detector and particle interactions with agreements better than 4%, though some features of the data are not precisely modeled. These measurements are used to tune the MINERvA detector simulation and evaluate systematic uncertainties in support of the MINERvA neutrino cross section measurement program.Comment: as accepted by NIM

1D Frustrated Ferromagnetic Model with Added Dzyaloshinskii-Moriya Interaction

The one-dimensional (1D) isotropic frustrated ferromagnetic spin-1/2 model is considered. Classical and quantum effects of adding a Dzyaloshinskii-Moriya (DM) interaction on the ground state of the system is studied using the analytical cluster method and numerical Lanczos technique. Cluster method results, show that the classical ground state magnetic phase diagram consists of only one single phase: "chiral". The quantum corrections are determined by means of the Lanczos method and a rich quantum phase diagram including the gapless Luttinger liquid, the gapped chiral and dimer orders is obtained. Moreover, next nearest neighbors will be entangled by increasing DM interaction and for open chains, end-spins are entangled which shows the long distance entanglement (LDE) feature that can be controlled by DM interaction.Comment: 8 pages, 9 figure

HIV latency is reversed by ACSS2-driven histone crotonylation

Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2). This reprogrammed the local chromatin at the HIV LTR through increased histone acetylation and reduced histone methylation. Pharmacologic inhibition or siRNA knockdown of ACSS2 diminished histone crotonylation-induced HIV replication and reactivation. ACSS2 induction was highly synergistic in combination with either a protein kinase C agonist (PEP005) or a histone deacetylase inhibitor (vorinostat) in reactivating latent HIV. In the SIV-infected nonhuman primate model of AIDS, the expression of ACSS2 was significantly induced in intestinal mucosa in vivo, which correlated with altered fatty acid metabolism. Our study links the HIV/SIV infection-induced fatty acid enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a novel epigenetic regulator for HIV transcription that can be targeted for HIV eradication

Detecting ancient codispersals and host shifts by double dating of host and parasite phylogenies: Application in proctophyllodid feather mites associated with passerine birds

Inferring cophylogeographic events requires matching the timing of these events on both host and symbiont (e.g., parasites) phylogenies because divergences of hosts and their symbionts may not temporally coincide, and host switches may occur. We investigate a large radiation of birds (Passeriformes) and their permanent symbionts, the proctophyllodid feather mites (117 species from 116 bird species; six genes, 11,468 nt aligned) using two time‐calibration strategies for mites: fossils only and host phylogeography only. Out of 10 putative cophylogeographic events 4 agree in timing for both symbiont and host events being synchronous co‐origins or codispersals; three were based on host shifts, but agree in timing being very close to the origin of modern hosts; two disagree; and one large basal mite split was seemingly independent from host phylogeography. Among these events was an ancient (21–25.3 Mya), synchronous codispersal from the Old World leading to the origin and diversifications of New World emberizoid passerids and their mites, the thraupis + quadratus species groups of Proctophyllodes. Our framework offers a more robust detection of host and symbiont cophylogeographic events (as compared to host‐symbiont reconciliation analysis and using host phylogeography for time‐calibration) and provides independent data for testing alternative hypotheses on timing of host diversification and dispersal.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/1/evo13309-sup-0003-figureS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/2/evo13309.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/3/evo13309-sup-0006-figureS6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/4/evo13309_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/5/evo13309-sup-0009-figureS9.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/6/evo13309-sup-0005-figureS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/7/evo13309-sup-0004-figureS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/8/evo13309-sup-0002-figureS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138927/9/evo13309-sup-0008-figureS8.pd

PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.

OBJECTIVE: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225-240