Microwave Power Transmission System Studies. Volume 1: Executive Summary

A study of microwave power generation, transmission, reception and control was conducted as a part of a program to demonstrate the feasibility of power transmission from geosynchronous orbit. A summary is presented of results concerning design approaches, estimated costs (ROM), critical technology, associated ground and orbital test programs with emphasis on dc to rf conversion, transmitting antenna, phase control, mechanical systems, flight operations, ground power receiving-rectifying antenna with systems analysis, and evaluation. Recommendations for early further in-depth studies complementing the technology program are included

Microwave power transmission system studies. Volume 2: Introduction, organization, environmental and spaceborne systems analyses

Introduction, organization, analyses, conclusions, and recommendations for each of the spaceborne subsystems are presented. Environmental effects - propagation analyses are presented with appendices covering radio wave diffraction by random ionospheric irregularities, self-focusing plasma instabilities and ohmic heating of the D-region. Analyses of dc to rf conversion subsystems and system considerations for both the amplitron and the klystron are included with appendices for the klystron covering cavity circuit calculations, output power of the solenoid-focused klystron, thermal control system, and confined flow focusing of a relativistic beam. The photovoltaic power source characteristics are discussed as they apply to interfacing with the power distribution flow paths, magnetic field interaction, dc to rf converter protection, power distribution including estimates for the power budget, weights, and costs. Analyses for the transmitting antenna consider the aperture illumination and size, with associated efficiencies and ground power distributions. Analyses of subarray types and dimensions, attitude error, flatness, phase error, subarray layout, frequency tolerance, attenuation, waveguide dimensional tolerances, mechanical including thermal considerations are included. Implications associated with transportation, assembly and packaging, attitude control and alignment are discussed. The phase front control subsystem, including both ground based pilot signal driven adaptive and ground command approaches with their associated phase errors, are analyzed

Submesoscale hotspots of productivity and respiration : insights from high-resolution oxygen and fluorescence sections

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 130 (2017): 1-11, doi:10.1016/j.dsr.2017.10.005.Modeling studies have shown that mesoscale and submesoscale processes can stimulate phytoplankton productivity and export production. Here, we present observations from an undulating, towed Video Plankton Recorder (VPR-II) in the tropical Atlantic. The VPR-II collected profiles of oxygen, fluorescence, temperature and salinity in the upper 140 m of the water column at a spatial resolution of 1 m in the vertical and <2 km in the horizontal. The data reveal remarkable "hotspots", i.e. locations 5 to 10 km wide which have elevated fluorescence and decreased oxygen, both of which are likely the result of intense submesoscale upwelling. Based on estimates of source water, estimated from identical temperature and salinity surfaces, hotspots are more often areas of net respiration than areas of net production — although the inferred changes in oxygen are subject to uncertainty in the determination of the source of the upwelled waters since the true source water may not have been sampled. We discuss the spatial distribution of these hotspots and present a conceptual model outlining their possible generation and decline. Simultaneous measurements of O2/Ar in the mixed layer from a shipboard mass spectrometer provide estimates of rates of surface net community production. We find that the subsurface biological hotspots are often expressed as an increase in mixed layer rates of net community production. Overall, the large number of these hotspots support the growing evidence that submesoscale processes are important drivers in upper ocean biological production.Funding for this work came from the National Science Foundation (R.H.R.S. and D.J.M) (OCE-0925284, OCE-1048897, and OCE- 1029676) and the National Aeronautics and Space Administration (D.J.M.) (NNX08AL71G and NNX13AE47G)

National trends in hospital, long-term care and outpatient Acinetobacter baumannii resistance rates

Introduction: Acinetobacter baumannii is a top-priority pathogen of the World Health Organization (WHO) and the Centers for Disease Control (CDC) due to antibiotic resistance. Gap Statement: Trends in A. baumannii resistance rates that include community isolates are unknown. Aim: Identify trends in A. baumannii resistance rates across the Veterans Affairs (VA) Healthcare System, including isolates from patients treated in hospitals, long-term care facilities and outpatient clinics nationally. Methodology: We included A. baumannii clinical cultures collected from VA patients from 2010 to 2018. Cultures were categorized by location: VA medical centers (VAMCs), long-term care (LTC) units [community living centers (CLCs)], or outpatient. We assessed carbapenem resistance, multidrug resistance (MDR) and extensive drug resistance (XDR). Time trends were assessed with Joinpoint regression. Results: We identified 19 376 A. baumannii cultures (53% VAMCs, 4% CLCs, 43% outpatient). Respiratory cultures were the most common source of carbapenem-resistant (43 %), multidrug-resistant (49 %) and extensively drug-resistant (21 %) isolates. Over the study period, the number of A. baumannii cultures decreased significantly in VAMCs (11.9% per year). In 2018, carbapenem resistance was seen in 28% of VAMC isolates and 36% of CLC isolates, but only 6% of outpatient isolates, while MDR was found in 31% of VAMC isolates and 36% of CLC isolates, but only 8 % of outpatient isolates. Carbapenem-resistant, multidrug-resistant and extensively drug-resistant A. baumannii isolates decreased significantly in VAMCs and outpatient clinics over time (VAMCs: by 4.9, 7.2 and 6.9%; outpatient: by 11.3, 10.5 and 10.2% per year). Resistant phenotypes remained stable in CLCs. Conclusion: In the VA nationally, the prevalence of A. baumannii is decreasing, as is resistance. Carbapenem-resistant and multidrug-resistant A. baumannii remain common in VAMCs and CLCs. The focus of infection control and antimicrobial stewardship efforts to prevent transmission of resistant A. baumannii should be in hospital and LTC settings

JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor

The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy (PML) in immunosuppressed and immunomodulated patients. Initial infection with JCPyV is common and the virus establishes a long-term persistent infection in the urogenital system of 50-70% of the human population worldwide. A major gap in the field is that we do not know how the virus traffics from the periphery to the brain to cause disease. Our recent discovery that human choroid plexus epithelial cells are fully susceptible to virus infection together with reports of JCPyV infection of choroid plexus in vivo has led us to hypothesize that the choroid plexus plays a fundamental role in this process. The choroid plexus is known to relay information between the blood and the brain by the release of extracellular vesicles. This is particularly important because human macroglia (oligodendrocytes and astrocytes), the major targets of virus infection in the central nervous system (CNS), do not express the known attachment receptors for the virus and do not bind virus in human tissue sections. In this report we show that JCPyV infected choroid plexus epithelial cells produce extracellular vesicles that contain JCPyV and readily transmit the infection to human glial cells. Transmission of the virus by extracellular vesicles is independent of the known virus attachment receptors and is not neutralized by antisera directed at the virus. We also show that extracellular vesicles containing virus are taken into target glial cells by both clathrin dependent endocytosis and macropinocytosis. Our data support the hypothesis that the choroid plexus plays a fundamental role in the dissemination of virus to brain parenchyma

Defective myogenesis in the absence of the muscle-specific lysine methyltransferase SMYD1

AbstractThe SMYD (SET and MYND domain) family of lysine methyltransferases harbor a unique structure in which the methyltransferase (SET) domain is intervened by a zinc finger protein–protein interaction MYND domain. SMYD proteins methylate both histone and non-histone substrates and participate in diverse biological processes including transcriptional regulation, DNA repair, proliferation and apoptosis. Smyd1 is unique among the five family members in that it is specifically expressed in striated muscles. Smyd1 is critical for development of the right ventricle in mice. In zebrafish, Smyd1 is necessary for sarcomerogenesis in fast-twitch muscles. Smyd1 is expressed in the skeletal muscle lineage throughout myogenesis and in mature myofibers, shuttling from nucleus to cytosol during myoblast differentiation. Because of this expression pattern, we hypothesized that Smyd1 plays multiple roles at different stages of myogenesis. To determine the role of Smyd1 in mammalian myogenesis, we conditionally eliminated Smyd1 from the skeletal muscle lineage at the myoblast stage using Myf5cre. Deletion of Smyd1 impaired myoblast differentiation, resulted in fewer myofibers and decreased expression of muscle-specific genes. Muscular defects were temporally restricted to the second wave of myogenesis. Thus, in addition to the previously described functions for Smyd1 in heart development and skeletal muscle sarcomerogenesis, these results point to a novel role for Smyd1 in myoblast differentiation

Persistent molecular disease in adult patients with AML evaluated with whole-exome and targeted error-corrected DNA sequencing

PURPOSE: Persistent molecular disease (PMD) after induction chemotherapy predicts relapse in AML. In this study, we used whole-exome sequencing (WES) and targeted error-corrected sequencing to assess the frequency and mutational patterns of PMD in 30 patients with AML. MATERIALS AND METHODS: The study cohort included 30 patients with adult AML younger than 65 years who were uniformly treated with standard induction chemotherapy. Tumor/normal WES was performed for all patients at presentation. PMD analysis was evaluated in bone marrow samples obtained during clinicopathologic remission using repeat WES and analysis of patient-specific mutations and error-corrected sequencing of 40 recurrently mutated AML genes (MyeloSeq). RESULTS: WES for patient-specific mutations detected PMD in 63% of patients (19/30) using a minimum variant allele fraction (VAF) of 2.5%. In comparison, MyeloSeq identified persistent mutations above 0.1% VAF in 77% of patients (23/30). PMD was usually present at relatively high levels (\u3e2.5% VAFs), such that WES and MyeloSeq agreed for 73% of patients despite differences in detection limits. Mutations in CONCLUSION: PMD and clonal hematopoiesis are both common in patients with AML in first remission. These findings demonstrate the importance of baseline testing for accurate interpretation of mutation-based tumor monitoring assays for patients with AML and highlight the need for clinical trials to determine whether these complex mutation patterns correlate with clinical outcomes in AML

Biogenesis of JC Polyomavirus Associated Extracellular Vesicles

JC polyomavirus (JCPyV) is a small, non-enveloped virus that persists in the kidney in about half the adult population. In severely immune-compromised individuals JCPyV causes the neurodegenerative disease progressive multifocal leukoencephalopathy (PML) in the brain. JCPyV has been shown to infect cells by both direct and indirect mechanisms, the latter involving extracellular vesicle (EV) mediated infection. While direct mechanisms of infection are well studied indirect EV mediated mechanisms are poorly understood. Using a combination of chemical and genetic approaches we show that several overlapping intracellular pathways are responsible for the biogenesis of virus containing EV. Here we show that targeting neutral sphingomyelinase 2 (nSMase2) with the drug cambinol decreased the spread of JCPyV over several viral life cycles. Genetic depletion of nSMase2 by either shRNA or CRISPR/Cas9 reduced EV-mediated infection. Individual knockdown of seven ESCRT-related proteins including HGS, ALIX, TSG101, VPS25, VPS20, CHMP4A, and VPS4A did not significantly reduce JCPyV associated EV (JCPyV(+) EV) infectivity, whereas knockdown of the tetraspanins CD9 and CD81 or trafficking and/or secretory autophagy-related proteins RAB8A, RAB27A, and GRASP65 all significantly reduced the spread of JCPyV and decreased EV-mediated infection. These findings point to a role for exosomes and secretory autophagosomes in the biogenesis of JCPyV associated EVs with specific roles for nSMase2, CD9, CD81, RAB8A, RAB27A, and GRASP65 proteins

The effects of anatabine on non-invasive indicators of muscle damage: a randomized, double-blind, placebo-controlled, crossover study

Background: Anatabine (ANA), a minor tobacco alkaloid found in the Solanaceae family of plants, may exhibit anti-inflammatory activity, which may be useful to aid in recovery from exercise-induced muscle damage. The purpose of this study, therefore, was to examine the effects of ANA supplementation on the recovery of isometric strength and selected non-invasive indicators of muscle damage. Methods: A double-blinded, placebo-controlled, crossover design was used to study eighteen men (mean ± SD age = 22.2 ± 3.1 yrs; body mass = 80.3 ± 15.7 kg) who participated in two randomly-ordered conditions separated by a washout period. The ANA condition consisted of consuming 6–12 mg anatabine per day for 10 days, while testing took place during days 7–10. The placebo (PLA) condition was identical except that the PLA supplement contained no ANA. Maximal voluntary isometric peak torque (PT) of the forearm flexors, arm circumference, hanging joint angle, and subjective pain ratings were measured before (PRE), immediately after (POST), and 24, 48, and 72 h after six sets of 10 maximal, eccentric isokinetic forearm flexion muscle actions. Resting heart rate and blood pressure were measured at PRE and 72 h in each condition. Results: For PT, hanging joint angle, arm circumference, and subjective pain ratings, there were no condition x time (p \u3e 0.05) interactions, there were no main effects for condition (p \u3e 0.05), but there were main effects for time (p \u3c 0.001). There were no condition x time (p \u3e 0.05) interactions and no main effects for condition (p \u3e 0.05) or time (p \u3e 0.05) for blood pressure or resting heart rate. Conclusions: ANA supplementation had no effect on the recovery of muscle strength, hanging joint angle, arm swelling, or subjective pain ratings after a bout of maximal eccentric exercise in the forearm flexors. Therefore, ANA may not be beneficial for those seeking to improve recovery from heavy eccentric exercise. Future studies should examine the effects of ANA on the pro-inflammatory cytokine responses to exercise-induced muscle damage and the chronic low-grade inflammation observed in obese and elderly individuals