Observation of Parity Nonconservation in Møller Scattering

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A_(PV) = [-175 ± 30(stat)± 20(syst)] X 10^(-9). This first direct observation of parity nonconservation in Møller scattering leads to a measurement of the electron’s weak charge at low energy Q^e_W = -0:053 ± 0:011. This is consistent with the standard model expectation at the current level of precision: sin^2θ_W = (M_Z)_(MS) = 0:2293 ± 0:0024(stat) ± 0:0016(syst) ± 0:0006(theory)

Development and evaluation of an interactive multimedia clinical skills teaching program designed for the pediatric clerkship.

Background and Purpose: The physical examination section of a multimedia program developed to teach infant history and physical examination skills was evaluated. Methods: 71 students participated: one group viewed only the physical examination section (PX), one the history section (HX), one none of the program (CX). Physical examination skills were assessed by direct observation of medical students performing an abdominal exam and scored using a checklist at baseline, immediately after intervention and at the end of the pediatric clerkship. Results were analyzed using ANOVA with repeated measures. Results: Baseline scores were: PX 2.5; HX 2.8. The PX group scored significantly higher immediately post intervention at 6.8 compared to the HX group 3.1. At the end of the clerkship significant differences between the groups remained. Final group mean scores were: PX 5.5, HX 4.4 and CX 2.7. Conclusion: The program improved examination skills with attenuation over 6 weeks

Electrostatic Solar Sail: A Propellantless Propulsion Concept for an Interstellar Probe Mission

The propulsion of an electrostatic solar sail (E Sail) is obtained by extracting momentum from the solar wind through electrostatic repulsion of the positively charged solar wind ions (see Figure 1). The positively charged solar wind protons are deflected by the electric field created around the tethers.This electric field grows in diameter as the spacecraft moves away from the Sun, therefore the E Sail effective area grows. The growth of the E-Sail effective area allows the propulsive force to decrease as 1/r up to distances of 20 AU as it moves away from the Sun, unlike solar sail propulsion whose thrust decreases as 1/r 2 but only to distances of 5AU. This propulsive force is created without using propellant and, therefore, E-sail avoids both the mass and complexity of chemical rockets (that require large amounts of propellant, propellant storage tanks, plumbing, valves, and insulation)

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

A High-Quality Genome-Scale Model for Rhodococcus opacus Metabolism

Rhodococcus opacus is a bacterium that has a high tolerance to aromatic compounds and can produce significant amounts of triacylglycerol (TAG). Here, we present iGR1773, the first genome-scale model (GSM) of R. opacus PD630 metabolism based on its genomic sequence and associated data. The model includes 1773 genes, 3025 reactions, and 1956 metabolites, was developed in a reproducible manner using CarveMe, and was evaluated through Metabolic Model tests (MEMOTE). We combine the model with two Constraint-Based Reconstruction and Analysis (COBRA) methods that use transcriptomics data to predict growth rates and fluxes: E-Flux2 and SPOT (Simplified Pearson Correlation with Transcriptomic data). Growth rates are best predicted by E-Flux2. Flux profiles are more accurately predicted by E-Flux2 than flux balance analysis (FBA) and parsimonious FBA (pFBA), when compared to 44 central carbon fluxes measured by 13C-Metabolic Flux Analysis (13C-MFA). Under glucose-fed conditions, E-Flux2 presents an R2 value of 0.54, while predictions based on pFBA had an inferior R2 of 0.28. We attribute this improved performance to the extra activity information provided by the transcriptomics data. For phenol-fed metabolism, in which the substrate first enters the TCA cycle, E-Flux2’s flux predictions display a high R2 of 0.96 while pFBA showed an R2 of 0.93. We also show that glucose metabolism and phenol metabolism function with similar relative ATP maintenance costs. These findings demonstrate that iGR1773 can help the metabolic engineering community predict aromatic substrate utilization patterns and perform computational strain design

The Cold Big-Bang Cosmology as a Counter-example to Several Anthropic Arguments

A general Friedmann big-bang cosmology can be specified by fixing a half-dozen cosmological parameters such as the photon-to-baryon ratio Eta, the cosmological constant Lambda, the curvature scale R, and the amplitude Q of (assumed scale-invariant) primordial density fluctuations. There is currently no established theory as to why these parameters take the particular values we deduce from observations. This has led to proposed `anthropic' explanations for the observed value of each parameter, as the only value capable of generating a universe that can host intelligent life. In this paper, I explicitly show that the requirement that the universe generates sun-like stars with planets does not fix these parameters, by developing a class of cosmologies (based on the classical `cold big-bang' model) in which some or all of the cosmological parameters differ by orders of magnitude from the values they assume in the standard hot big-bang cosmology, without precluding in any obvious way the existence of intelligent life. I also give a careful discussion of the structure and context of anthropic arguments in cosmology, and point out some implications of the cold big-bang model's existence for anthropic arguments concerning specific parameters.Comment: 13 PRD-style pages, 2 postscript figures. Reference 26 corrected. Accepted to Phys. Rev.

Quantitative assessment of barriers to the clinical development and adoption of cellular therapies:A pilot study

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community

Trans-cerebral HCO3- and PCO2 exchange during acute respiratory acidosis and exercise-induced metabolic acidosis in humans

This study investigated trans-cerebral internal jugular venous-arterial bicarbonate ([HCO(3)(−)]) and carbon dioxide tension (PCO(2)) exchange utilizing two separate interventions to induce acidosis: 1) acute respiratory acidosis via elevations in arterial PCO(2) (PaCO(2)) (n = 39); and 2) metabolic acidosis via incremental cycling exercise to exhaustion (n = 24). During respiratory acidosis, arterial [HCO(3)(−)] increased by 0.15 ± 0.05 mmol ⋅ l(−1) per mmHg elevation in PaCO(2) across a wide physiological range (35 to 60 mmHg PaCO(2); P < 0.001). The narrowing of the venous-arterial [HCO(3)(−)] and PCO(2) differences with respiratory acidosis were both related to the hypercapnia-induced elevations in cerebral blood flow (CBF) (both P < 0.001; subset n = 27); thus, trans-cerebral [HCO(3)(−)] exchange (CBF × venous-arterial [HCO(3)(−)] difference) was reduced indicating a shift from net release toward net uptake of [HCO(3)(−)] (P = 0.004). Arterial [HCO(3)(−)] was reduced by −0.48 ± 0.15 mmol ⋅ l(−1) per nmol ⋅ l(−1) increase in arterial [H(+)] with exercise-induced acidosis (P < 0.001). There was no relationship between the venous-arterial [HCO(3)(−)] difference and arterial [H(+)] with exercise-induced acidosis or CBF; therefore, trans-cerebral [HCO(3)(−)] exchange was unaltered throughout exercise when indexed against arterial [H(+)] or pH (P = 0.933 and P = 0.896, respectively). These results indicate that increases and decreases in systemic [HCO(3)(−)] – during acute respiratory/exercise-induced metabolic acidosis, respectively – differentially affect cerebrovascular acid-base balance (via trans-cerebral [HCO(3)(−)] exchange)