Magnetospheric and solar wind dependences of coupled fast-mode resonances outside the plasmasphere

We investigate the magnetospheric and solar wind factors that control the occurrence probabilities, locations, and frequencies of standing Alfvén waves excited via coupled fast-mode resonances (cFMRs) in the outer magnetosphere's dawn and dusk sectors. The variation of these cFMR properties with the observed magnetospheric plasma density profiles and inputs to the semiempirically modeled magnetic field from the numerical cFMR calculations of Archer et al. (2015) are studied. The probability of cFMR occurrence increases with distance between the magnetopause and the Alfvén speed's local maximum. The latter's location depends on magnetospheric activity: during high activity it is situated slightly outside the plasmapause, whereas at low activity it is found at much larger radial distances. The frequencies of cFMR are proportional to the Alfvén speed near the magnetopause, which is affected by both density and magnetic field variations. The location of the excited resonance, however, depends on the relative steepness of the Alfvén speed radial profile. The steeper this is, the closer the resonance is to the outer boundary and vice versa. The variation of the density profiles with solar wind conditions and activity is also shown

Frequency variability of standing Alfven waves excited by fast mode resonances in the outer magnetosphere

NASA. Grant Number: NAS5-0209

Mechanisms involved in acquisition of bla<inf>NDM</inf> genes by IncA/C<inf>2</inf> and IncFII<inf>Y</inf> plasmids

Copyright © 2016, American Society for Microbiology. All Rights Reserved. blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

Impact of asymmetries on fuel performance in inertial confinement fusion

Low-mode asymmetries prevent effective compression, confinement, and heating of the fuel in inertial confinement fusion (ICF) implosions, and their control is essential to achieving ignition. Ion temperatures (Tion) in ICF experiments are inferred from the broadening of primary neutron spectra. Directional motion (flow) of the fuel at burn also impacts broadening and will lead to artificially inflated "Tion" values. Flow due to low-mode asymmetries is expected to give rise to line-of-sight variations in measured Tion. We report on intentionally asymmetrically driven experiments at the OMEGA laser facility designed to test the ability to accurately predict and measure line-of-sight differences in apparent Tion due to low-mode asymmetry-seeded flows. Contrasted to chimera and xrage simulations, the measurements demonstrate how all asymmetry seeds have to be considered to fully capture the flow field in an implosion. In particular, flow induced by the stalk that holds the target is found to interfere with the seeded asymmetry. A substantial stalk-seeded asymmetry in the areal density of the implosion is also observed

Soft X‐ray and ENA Imaging of the Earth’s Dayside Magnetosphere

The LEXI and SMILE missions will provide soft X‐ray images of the Earth's magnetosheath and cusps after their anticipated launch in 2023 and 2024, respectively. The IBEX mission showed the potential of an Energetic Neutral Atom (ENA) instrument to image dayside magnetosheath and cusps, albeit over the long hours required to raster an image with a single pixel imager. Thus, it is timely to discuss the two imaging techniques and relevant science topics. We simulate soft X‐ray and low‐ENA images that might be observed by a virtual spacecraft during two interesting solar wind scenarios: a southward turning of the interplanetary magnetic field and a sudden enhancement of the solar wind dynamic pressure. We employ the OpenGGCM global magnetohydrodynamics model and a simple exospheric neutral density model for these calculations. Both the magnetosheath and the cusps generate strong soft X‐rays and ENA signals that can be used to extract the locations and motions of the bow shock and magnetopause. Magnetopause erosion corresponds closely to the enhancement of dayside reconnection rate obtained from the OpenGGCM model, indicating that images can be used to understand global‐scale magnetopause reconnection. When dayside imagers are installed with high‐ENA inner‐magnetosphere and FUV/UV aurora imagers, we can trace the solar wind energy flow from the bow shock to the magnetosphere and then to the ionosphere in a self‐standing manner without relying upon other observatories. Soft X‐ray and/or ENA imagers can also unveil the dayside exosphere density structure and its response to space weather

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets

BACKGROUND: Targeting persistent tubercule bacilli has become an important challenge in the development of anti-tuberculous drugs. As the glyoxylate bypass is essential for persistent bacilli, interference with it holds the potential for designing new antibacterial drugs. We have developed kinetic models of the tricarboxylic acid cycle and glyoxylate bypass in Escherichia coli and Mycobacterium tuberculosis, and studied the effects of inhibition of various enzymes in the M. tuberculosis model. RESULTS: We used E. coli to validate the pathway-modeling protocol and showed that changes in metabolic flux can be estimated from gene expression data. The M. tuberculosis model reproduced the observation that deletion of one of the two isocitrate lyase genes has little effect on bacterial growth in macrophages, but deletion of both genes leads to the elimination of the bacilli from the lungs. It also substantiated the inhibition of isocitrate lyases by 3-nitropropionate. On the basis of our simulation studies, we propose that: (i) fractional inactivation of both isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 is required for a flux through the glyoxylate bypass in persistent mycobacteria; and (ii) increasing the amount of active isocitrate dehydrogenases can stop the flux through the glyoxylate bypass, so the kinase that inactivates isocitrate dehydrogenase 1 and/or the proposed inactivator of isocitrate dehydrogenase 2 is a potential target for drugs against persistent mycobacteria. In addition, competitive inhibition of isocitrate lyases along with a reduction in the inactivation of isocitrate dehydrogenases appears to be a feasible strategy for targeting persistent mycobacteria. CONCLUSION: We used kinetic modeling of biochemical pathways to assess various potential anti-tuberculous drug targets that interfere with the glyoxylate bypass flux, and indicated the type of inhibition needed to eliminate the pathogen. The advantage of such an approach to the assessment of drug targets is that it facilitates the study of systemic effect(s) of the modulation of the target enzyme(s) in the cellular environment

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

The effectiveness of health coaching, home blood pressure monitoring, and home-titration in controlling hypertension among low-income patients: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Despite the many antihypertensive medications available, two-thirds of patients with hypertension do not achieve blood pressure control. This is thought to be due to a combination of poor patient education, poor medication adherence, and "clinical inertia." The present trial evaluates an intervention consisting of health coaching, home blood pressure monitoring, and home medication titration as a method to address these three causes of poor hypertension control.</p> <p>Methods/Design</p> <p>The randomized controlled trial will include 300 patients with poorly controlled hypertension. Participants will be recruited from a primary care clinic in a teaching hospital that primarily serves low-income populations.</p> <p>An intervention group of 150 participants will receive health coaching, home blood pressure monitoring, and home-titration of antihypertensive medications during 6 months. The control group (n = 150) will receive health coaching plus home blood pressure monitoring for the same duration. A passive control group will receive usual care. Blood pressure measurements will take place at baseline, and after 6 and 12 months. The primary outcome will be change in systolic blood pressure after 6 and 12 months. Secondary outcomes measured will be change in diastolic blood pressure, adverse events, and patient and provider satisfaction.</p> <p>Discussion</p> <p>The present study is designed to assess whether the 3-pronged approach of health coaching, home blood pressure monitoring, and home medication titration can successfully improve blood pressure, and if so, whether this effect persists beyond the period of the intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT01013857</p