Energetic Submesoscales Maintain Strong Mixed Layer Stratification during an Autumn Storm

Atmospheric storms are an important driver of changes in upper-ocean stratification and small-scale (1-100 m) turbulence. Yet, the modifying effects of submesoscale (0.1-10 km) motions in the ocean mixed layer on stratification and small-scale turbulence during a storm are not well understood. Here, we use large-eddy simulations to study the coupled response of submesocales and small-scale turbulence to the passage of an idealized autumn storm, with a wind stress representative of a storm observed in the North Atlantic above the Porcupine Abyssal Plain. Due to a relatively shallow mixed layer and a strong down-front wind, existing scaling theory predicts that submesoscales should be unable to re-stratify the mixed layer during the storm. In contrast, our simulations reveal a persistent and strong mean stratification in the mixed layer both during and after the storm. In addition, we find that the mean dissipation rate remains elevated throughout the mixed layer during the storm, despite the strong mean stratification. These results are attributed to strong spatial variability in stratification and small-scale turbulence at the submesoscale and have important implications for sampling and modeling submesoscales and their effects on stratification and turbulence in the upper-ocean.DBW was supported by the National Science Foundation via an NSF Postdoctoral Fellowship (1421125) and an NSF Polar Programs Grant (1501993). JRT was supported by the Natural Environment Research Council via Award NE/J010472/1

Reconstitution of T cell receptor signaling in ZAP-70-deficient cells by retroviral transduction of the ZAP-70 gene.

A variant of severe combined immunodeficiency syndrome (SCID) with a selective inability to produce CD8 single positive T cells and a signal transduction defect in peripheral CD4+ cells has recently been shown to be the result of mutations in the ZAP-70 gene. T cell receptor (TCR) signaling requires the association of the ZAP-70 protein tyrosine kinase with the TCR complex. Human T cell leukemia virus type I-transformed CD4+ T cell lines were established from ZAP-70-deficient patients and normal controls. ZAP-70 was expressed and appropriately phosphorylated in normal T cell lines after TCR engagement, but was not detected in T cell lines from ZAP-70-deficient patients. To determine whether signaling could be reconstituted, wild-type ZAP-70 was introduced into deficient cells with a ZAP-70 retroviral vector. High titer producer clones expressing ZAP-70 were generated in the Gibbon ape leukemia virus packaging line PG13. After transduction, ZAP-70 was detected at levels equivalent to those observed in normal cells, and was appropriately phosphorylated on tyrosine after receptor engagement. The kinase activity of ZAP-70 in the reconstituted cells was also appropriately upregulated by receptor aggregation. Moreover, normal and transduced cells, but not ZAP-70-deficient cells, were able to mobilize calcium after receptor ligation, indicating that proximal TCR signaling was reconstituted. These results indicate that this form of SCID may be corrected by gene therapy

Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA

Death, dying and informatics: misrepresenting religion on MedLine

BACKGROUND: The globalization of medical science carries for doctors worldwide a correlative duty to deepen their understanding of patients' cultural contexts and religious backgrounds, in order to satisfy each as a unique individual. To become better informed, practitioners may turn to MedLine, but it is unclear whether the information found there is an accurate representation of culture and religion. To test MedLine's representation of this field, we chose the topic of death and dying in the three major monotheistic religions. METHODS: We searched MedLine using PubMed in order to retrieve and thematically analyze full-length scholarly journal papers or case reports dealing with religious traditions and end-of-life care. Our search consisted of a string of words that included the most common denominations of the three religions, the standard heading terms used by the National Reference Center for Bioethics Literature (NRCBL), and the Medical Subject Headings (MeSH) used by the National Library of Medicine. Eligible articles were limited to English-language papers with an abstract. RESULTS: We found that while a bibliographic search in MedLine on this topic produced instant results and some valuable literature, the aggregate reflected a selection bias. American writers were over-represented given the global prevalence of these religious traditions. Denominationally affiliated authors predominated in representing the Christian traditions. The Islamic tradition was under-represented. CONCLUSION: MedLine's capability to identify the most current, reliable and accurate information about purely scientific topics should not be assumed to be the same case when considering the interface of religion, culture and end-of-life care

Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation

Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called “ClimGen”. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

New Experimental Limits on Macroscopic Forces Below 100 Microns

Results of an experimental search for new macroscopic forces with Yukawa range between 5 and 500 microns are presented. The experiment uses 1 kHz mechanical oscillators as test masses with a stiff conducting shield between them to suppress backgrounds. No signal is observed above the instrumental thermal noise after 22 hours of integration time. These results provide the strongest limits to date between 10 and 100 microns, improve on previous limits by as much as three orders of magnitude, and rule out half of the remaining parameter space for predictions of string-inspired models with low-energy supersymmetry breaking. New forces of four times gravitational strength or greater are excluded at the 95% confidence level for interaction ranges between 200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction

Considering the influence of coronary motion on artery-specific biomechanics using fluid-structure interaction simulation

The endothelium in the coronary arteries is subject to wall shear stress and vessel wall strain, which influences the biology of the arterial wall. This study presents vessel-specific fluid-structure interaction (FSI) models of three coronary arteries, using directly measured experimental geometries and boundary conditions. FSI models are used to provide a more physiologically complete representation of vessel biomechanics, and have been extended to include coronary bending to investigate its effect on shear and strain. FSI both without- and with-bending resulted in significant changes in all computed shear stress metrics compared to CFD (p = 0.0001). Inclusion of bending within the FSI model produced highly significant changes in Time Averaged Wall Shear Stress (TAWSS) + 9.8% LAD, + 8.8% LCx, - 2.0% RCA; Oscillatory Shear Index (OSI) + 208% LAD, 0% LCx, + 2600% RCA; and transverse wall Shear Stress (tSS) + 180% LAD, + 150% LCx and + 200% RCA (all p < 0.0001). Vessel wall strain was homogenous in all directions without-bending but became highly anisotropic under bending. Changes in median cyclic strain magnitude were seen for all three vessels in every direction. Changes shown in the magnitude and distribution of shear stress and wall strain suggest that bending should be considered on a vessel-specific basis in analyses of coronary artery biomechanics

Imaging Coulomb Islands in a Quantum Hall Interferometer

In the Quantum Hall regime, near integer filling factors, electrons should only be transmitted through spatially-separated edge states. However, in mesoscopic systems, electronic transmission turns out to be more complex, giving rise to a large spectrum of magnetoresistance oscillations. To explain these observations, recent models put forward that, as edge states come close to each other, electrons can hop between counterpropagating edge channels, or tunnel through Coulomb islands. Here, we use scanning gate microscopy to demonstrate the presence of quantum Hall Coulomb islands, and reveal the spatial structure of transport inside a quantum Hall interferometer. Electron islands locations are found by modulating the tunneling between edge states and confined electron orbits. Tuning the magnetic field, we unveil a continuous evolution of active electron islands. This allows to decrypt the complexity of high magnetic field magnetoresistance oscillations, and opens the way to further local scale manipulations of quantum Hall localized states