Structure retrieval at atomic resolution in the presence of multiple scattering of the electron probe

The projected electrostatic potential of a thick crystal is reconstructed at atomic-resolution from experimental scanning transmission electron microscopy data recorded using a new generation fast- readout electron camera. This practical and deterministic inversion of the equations encapsulating multiple scattering that were written down by Bethe in 1928 removes the restriction of established methods to ultrathin ($\lesssim 50$ {\AA}) samples. Instruments already coming on-line can overcome the remaining resolution-limiting effects in this method due to finite probe-forming aperture size, spatial incoherence and residual lens aberrations.Comment: 6 pages, 3 figure

Effect of Statins on Functional Expression of Membrane Transporters in L6 Rat Skeletal Muscle Cells

Statins reduce LDL-cholesterol and the risk of atherosclerosis. They are generally safe, although statin-induced myopathy is relatively common. Membrane transporters play a crucial role in determining statin side effects. Little is known regarding the interaction of drug transporters in muscle cells with statins. Study aims: The present study aimed to determine the effect of statins on functional expression of monocarboxylate transporters (MCTs) and multidrug resistance-associated proteins (MRPs) in L6 rat skeletal myotube cells. Methods: Relative gene expression at mRNA level was confirmed by RT2 ProfilerTM Rat Drug Transporter PCR array. The uptake of 3H-labelled DL-lactate (1 μCi/ml) was measured to functionally expressed MCT function. The inhibition of [3H]-DL-lactate uptake was assessed in the presence or absence of statins and compared to that of the MCT inhibitors, phloretin and CHC. Transporter-mediated dye efflux was used as functional assay for the MRP efflux transporters. Results: In L6 rat skeletal myotubes, relatively high mRNA expression level was observed for Mct1and Mrp1for uptake and efflux transporters, respectively. The [3H]-DL-lactate uptake was shown to be a concentration-, pH-dependent and Na+-independent manner with Michaelis-Menten constant (Km) value of 16.17 ± 2.4 mM vs 15.63 ± 3.0 mM in the presence and absence of Na+, respectively. The maximum velocity of substrate binding (Vmax) of the DL-lactate uptake inhibition by lipophilic statins; simvastatin and atorvastatin, were in the same order as phloretin and CHC, while no significant inhibitory magnitude with hydrophilic statins; pravastatin and rosuvastatin. However, the L6 rat skeletal myotubes did not exhibit lactate efflux function. Among four of statins used, only simvastatin showed an affinity inhibition of MRP function in L6 cells. Conclusions: This study has shown that lipophilic statins significantly inhibit functional expression of MCTs, even though they have not shown relatively high inhibition impact on MRPs

UK export performance research - review and implications

Previous research on export performance has been criticized for being a mosaic of autonomous endeavours and for a lack of theoretical development. Building upon extant models of export performance, and a review and analysis of research on export performance in the UK for the period 1990-2005, an integrated model of export performance is developed and theoretical explanations of export performance are put forward. It is suggested that a multi-theory approach to explaining export performance is viable. Management and policy implications for the UK emerging from the review and synthesis of the literature and the integrated model are discussed

Reconstructing the Scattering Matrix from Scanning Electron Diffraction Measurements Alone

Three-dimensional phase contrast imaging of multiply-scattering samples in X-ray and electron microscopy is extremely challenging, due to small numerical apertures, the unavailability of wavefront shaping optics, and the highly nonlinear inversion required from intensity-only measurements. In this work, we present a new algorithm using the scattering matrix formalism to solve the scattering from a non-crystalline medium from scanning diffraction measurements, and recover the illumination aberrations. Our method will enable 3D imaging and materials characterization at high resolution for a wide range of materials

The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study.

BACKGROUND:Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. RESULTS:In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > - 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5-67.0) years and admission APACHE II score of 21.0 (16.0-32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p < 10-5). CONCLUSIONS:In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM

Effective actions with fixed points, (error in derivation of coefficient corrected)

The specific form of the constant term in the asymptotic expansion of the heat-kernel on an axially-symmetric space with a codimension two fixed-point set of conical singularities is used to determine the associated conformal change of the effective action in four dimensions. Another derivation of the relevant coefficient is presented.Comment: 10p,uses JyTeX,MUTP/94/1

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

A first--order irreversible thermodynamic approach to a simple energy converter

Several authors have shown that dissipative thermal cycle models based on Finite-Time Thermodynamics exhibit loop-shaped curves of power output versus efficiency, such as it occurs with actual dissipative thermal engines. Within the context of First-Order Irreversible Thermodynamics (FOIT), in this work we show that for an energy converter consisting of two coupled fluxes it is also possible to find loop-shaped curves of both power output and the so-called ecological function against efficiency. In a previous work Stucki [J.W. Stucki, Eur. J. Biochem. vol. 109, 269 (1980)] used a FOIT-approach to describe the modes of thermodynamic performance of oxidative phosphorylation involved in ATP-synthesis within mithochondrias. In that work the author did not use the mentioned loop-shaped curves and he proposed that oxidative phosphorylation operates in a steady state simultaneously at minimum entropy production and maximum efficiency, by means of a conductance matching condition between extreme states of zero and infinite conductances respectively. In the present work we show that all Stucki's results about the oxidative phosphorylation energetics can be obtained without the so-called conductance matching condition. On the other hand, we also show that the minimum entropy production state implies both null power output and efficiency and therefore this state is not fulfilled by the oxidative phosphorylation performance. Our results suggest that actual efficiency values of oxidative phosphorylation performance are better described by a mode of operation consisting in the simultaneous maximization of the so-called ecological function and the efficiency.Comment: 20 pages, 7 figures, submitted to Phys. Rev.