A Device for Noninvasive Assessment of Vascular Impairment Risk in the Lower Extremity

The repeatability and resolution of the clinical gold standard of vascular assessment, the ankle-brachial index (ABI), was compared to that of a new device that dynamically assesses tissue perfusion during external loading utilizing laser Doppler flowmetry. Eight subjects of varying levels of vascular impairment were tested in successive weeks using two different sites on the subject\u27s posterior calf. These new measures included the perfusion decrease as well as the unloading delay during cyclic loading. Some new dynamic tissue perfusion measures demonstrated comparable levels of reproducibility with the ABI (e.g., 10%-20%). Only the unloading delay showed potentially enhanced resolution over ABI measures. The perfusion decrease showed little resolution, and the remaining parameters exhibited too great variability (25%-90%). The unloading delay associated with the reperfusion response during cyclic loading displayed the greatest combination of reproducibility and differentiation between subject groups of varying levels of vascular impairment. The preliminary results of this pilot study were also used to estimate sample sizes necessary to detect possible significant (

Regulation of adenylyl cyclase by membrane potential

Mammalian adenylyl cyclases possess 12 transmembrane-spanning domains and bear a superficial resemblance to certain classes of ion channels. Some evidence suggests that bacterial and sea urchin sperm adenylyl cyclases can be regulated by membrane depolarization. In the present study, we explored the effect of altering membrane potential on the adenylyl cyclase activity of cerebellar granule cells with acute potassium depolarization. A biphasic stimulatory and then inhibitory response is evoked by progressive increases in the extracellular [K]:[Na] ratio in the absence of extracellular Ca2+. This effect does not mimic the linear increase in membrane potential elicited under the same conditions. Instead it appears as though membrane depolarization opens L-type (nimodipine-sensitive) Ca2+ channels, allowing the entry of Na+, which directly stimulates adenylyl cyclase activity. Gramicidin, which generates pores that are permeable to monovalent cations, and concurrently eliminates the membrane potential, permits a similar stimulation by extracellularly applied Na+. Although the results indicate no direct sensitivity of cerebellar granule cell adenylyl cyclase to membrane potential, they do demonstrate that, as a result of membrane depolarization, the influx of Na+, as well as Ca2+, will elevate cAMP levels

Intrauterine growth restriction increases fetal hepatic gluconeogenic capacity and reduces messenger ribonucleic acid translation initiation and nutrient sensing in fetal liver and skeletal muscle.

Expression of key metabolic genes and proteins involved in mRNA translation, energy sensing, and glucose metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR). PI-IUGR fetuses weighed 55% less; had reduced oxygen, glucose, isoleucine, insulin, and IGF-I levels; and had 40% reduction in net branched chain amino acid uptake. In PI-IUGR skeletal muscle, levels of insulin receptor were increased 80%, whereas phosphoinositide-3 kinase (p85) and protein kinase B (AKT2) were reduced by 40%. Expression of eukaryotic initiation factor-4e was reduced 45% in liver, suggesting a unique mechanism limiting translation initiation in PI-IUGR liver. There was either no change (AMP activated kinase, mammalian target of rapamycin) or a paradoxical decrease (protein phosphatase 2A, eukaryotic initiation factor-2 alpha) in activation of major energy and cell stress sensors in PI-IUGR liver and skeletal muscle. A 13- to 20-fold increase in phosphoenolpyruvate carboxykinase and glucose 6 phosphatase mRNA expression in the PI-IUGR liver was-associated with a 3-fold increase in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha mRNA and increased phosphorylation of cAMP response element binding protein. Thus PI-IUGR is-associated with reduced branched chain amino acid uptake and growth factors, yet up-regulation of proximal insulin signaling and a marked increase in the gluconeogenic pathway. Lack of activation of several energy and stress sensors in fetal liver and skeletal muscle, despite hypoxia and low energy status, suggests a novel strategy for survival in the PI-IUGR fetus but with potential maladaptive consequences for reduced nutrient sensing and insulin sensitivity in postnatal life

A Dynamical (e,2e) Investigation of the Structurally Related Cyclic Ethers Tetrahydrofuran, Tetrahydropyran, and 1,4-Dioxane

Triple differential cross section measurements for the electron-impact ionization of the highest occupied molecular orbitals of tetrahydropyran and 1,4-dioxane are presented. For each molecule, experimental measurements were performed using the (e,2e) technique in asymmetric coplanar kinematics with an incident electron energy of 250 eV and an ejected electron energy of 20 eV. With the scattered electrons being detected at -5°, the angular distributions of the ejected electrons in the binary and recoil regions were observed. These measurements are compared with calculations performed within the molecular 3-body distorted wave model. Here, reasonable agreement was observed between the theoretical model and the experimental measurements. These measurements are compared with results from a recent study on tetrahydrofuran [D. B. Jones, J. D. Builth-Williams, S. M. Bellm, L. Chiari, C. G. Ning, H. Chaluvadi, B. Lohmann, O. Ingolfsson, D. Madison, and M. J. Brunger, Chem. Phys. Lett. 572, 32 (2013)] in order to evaluate the influence of structure on the dynamics of the ionization process across this series of cyclic ethers

Dynamical (e,2e) Investigations of Structurally Related Cyclic Ethers

Experimental and theoretical cross sections are presented for electron-impact ionization of a series of cyclic ethers

Predictors of tropical cyclone-induced urban tree failure: an international scoping review

Background: Trees are critical components of rural and urban ecosystems throughout the world. While they have adapted to the historic conditions of their native environments, climate change, urbanization, and human-assisted range expansion may test the storm resiliency of many tree species. Objective: In this global multilingual scoping review, we investigate a range of intrinsic (i.e., tree characteristics) and external (i.e., environmental and management) factors which have been used to predict tree failure during tropical cyclones. Design: We searched online databases and journals in English, Chinese, French, Japanese, Portuguese, and Spanish to find peer-reviewed papers and dissertations. We retained papers that used ground-based methods to study tree damage following a tropical cyclone and conducted a statistical analysis of factors that influence tree resistance to damage. From each paper we extracted details of study methods, and the relationships between damage and predictors. Results: Our efforts generated 65 peer-reviewed papers and dissertations that met our final criteria for inclusion (i.e., data on the relative proportion of trees failed/intact as assessed no more than a year after the storm event). Of these papers 37 independent variables were assessed to predict tree failure. Research in both urban and rural settings tends to be concentrated in regions frequently impacted by tropical cyclones. Characteristics of species such as wood density have been studied in rural environments and are also relevant predictors for tree failure in urban trees. Environmental characteristics unique to urban settings such as planting areas surrounded by pavement need further research. Several urban studies demonstrate that risk assessment methods can predict tree failure during a storm. Conclusion: Results can be used by future storm researchers to identify both predictors may warrant inclusion in their models as well as predictors which have yet to be tested. Results can also inform planning and activities that can mitigate tropical cyclone damage to the urban forest

Open superstring field theory I: gauge fixing, ghost structure, and propagator

The WZW form of open superstring field theory has linearized gauge invariances associated with the BRST operator Q and the zero mode η [subscript 0] of the picture minus-one fermionic superconformal ghost. We discuss gauge fixing of the free theory in a simple class of gauges using the Faddeev-Popov method. We find that the world-sheet ghost number of ghost and antighost string fields ranges over all integers, except one, and at any fixed ghost number, only a finite number of picture numbers appear. We calculate the propagators in a variety of gauges and determine the field-antifield content and the free master action in the Batalin-Vilkovisky formalism. Unlike the case of bosonic string field theory, the resulting master action is not simply related to the original gauge-invariant action by relaxing the constraint on the ghost and picture numbers.United States. Dept. of Energy (Cooperative rRsearch Agreement DE-FG02-05ER41360.

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Genomic epidemiology of syphilis in England: a population-based study.

BACKGROUND: Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum subspecies pallidum. Since 2012, syphilis rates have risen dramatically in many high-income countries, including England. Although this increase in syphilis prevalence is known to be associated with high-risk sexual activity in gay, bisexual, and other men who have sex with men (GBMSM), cases are rising in heterosexual men and women. The transmission dynamics within and between sexual networks of GBMSM and heterosexual people are not well understood. We aimed to investigate if whole genome sequencing could be used to supplement or enhance epidemiological insights around syphilis transmission. METHODS: We linked national patient demographic, geospatial, and behavioural metadata to whole T pallidum genome sequences previously generated from patient samples collected from across England between Jan 1, 2012, and Oct 31, 2018, and performed detailed phylogenomic analyses. FINDINGS: Of 497 English samples submitted for sequencing, we recovered 240 genomes (198 from the UK Health Security Agency reference laboratory and 42 from other laboratories). Three duplicate samples (same patient and collection date) were included in the main phylogenies, but removed from further analyses of English populations, leaving 237 genomes. 220 (92·8%) of 237 samples were from men, nine (3·8%) were from women, and eight (3·4%) were of unknown gender. Samples were mostly from London (n=118 [49·8%]), followed by southeast England (n=29 [12·2%]), northeast England (n=24 [10·1%]), and southwest England (n=15 [6·3%]). 180 (76·0%) of 237 genomes came from GBMSM, compared with 25 (10·5%) from those identifying as men who have sex with women, 15 (6·3%) from men with unrecorded sexual orientation, nine (3·8%) from those identifying as women who have sex with men, and eight (3·4%) from people of unknown gender and sexual orientation. Phylogenomic analysis and clustering revealed two dominant T pallidum sublineages in England. Sublineage 1 was found throughout England and across all patient groups, whereas sublineage 14 occurred predominantly in GBMSM older than 34 years and was absent from samples sequenced from the north of England. These different spatiotemporal trends, linked to demography or behaviour in the dominant sublineages, suggest they represent different sexual networks. By focusing on different regions of England we were able to distinguish a local heterosexual transmission cluster from a background of transmission in GBMSM. INTERPRETATION: These findings show that, despite extremely close genetic relationships between T pallidum genomes globally, genomics can still be used to identify putative transmission clusters for epidemiological follow-up. This could be of value for deconvoluting putative outbreaks and for informing public health interventions. FUNDING: Wellcome funding to the Sanger Institute, UK Research and Innovation, National Institute for Health and Care Research, European and Developing Countries Clinical Trials Partnership, and UK Health Security Agency