Recycled Pulsars Discovered at High Radio Frequency

We present the timing parameters of nine pulsars discovered in a survey of intermediate Galactic latitudes at 1400 MHz with the Parkes radio telescope. Eight of these pulsars possess small pulse periods and period derivatives thought to be indicative of ``recycling''. Six of the pulsars are in circular binary systems, including two with relatively massive white dwarf companions. We discuss the implications of these new systems for theories of binary formation and evolution. One long-period pulsar (J1410-7404) has a moderately weak magnetic field and an exceedingly narrow average pulse profile, similar to other recycled pulsars.Comment: 9 pages, 4 figures. Accepted for publication in Ap

Quantitation of selective autophagic protein aggregate degradation in vitro and in vivo using luciferase reporters

The analysis of autophagy in cells and tissue has principally been performed via qualitative measures. These assays identify autophagosomes or measure the conversion of LC3I to LC3II. However, qualitative assays fail to quantitate the degradation of an autophagic substrate and therefore only indirectly measure an intact autophagic system. “Autophagic flux” can be measured using long-lived proteins that are degraded via autophagy. We developed a quantifiable luciferase reporter assay that measures the degradation of a long-lived polyglutamine protein aggregate, polyQ80-luciferase. Using this reporter, the induction of autophagy via starvation or rapamycin in cells preferentially decreases polyQ80-luciferase when compared with a non-aggregating polyQ19-luciferase after four hours of treatment. This response was both time- and concentration-dependent, prevented by autophagy inhibitors and absent in ATG5 knockout cells. We adapted this assay to living animals by electroporating polyQ19-luciferase and polyQ80-luciferase expression constructs into the right and left tibialis anterior (TA) muscles of mice, respectively. The change in the ratio of polyQ80-luciferase to polyQ19-luciferase signal before and after autophagic stimulation or inhibition was quantified via in vivo bioluminescent imaging. Following two days of starvation or treatment with intraperitoneal rapamycin, there was a ~35% reduction in the ratio of polyQ80:polyQ19-luciferase activity, consistent with the selective autophagic degradation of polyQ80 protein. This autophagic response in skeletal muscle in vivo was abrogated by co-treatment with chloroquine and in ATG16L1 hypomorphic mice. Our study demonstrates a method to quantify the autophagic flux of an expanded polyglutamine via luciferase reporters in vitro and in vivo

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the development of the Adams ARED module including its capabilities, limitations, and assumptions. Preliminary results, validation activities, and a practical application of the module to inform the relative effect of the flywheels on exercise will be discussed

Research and education in management of large-scale technical programs

A research effort is reported which was conducted by NASA in conjunction with Drexel University, and which was aimed at an improved understanding of large scale systems technology and management

Animal intrusion studies for protective barriers: Status report for FY 1988

The objective of the Biointrusion Control Task is to provide technical support to Westinghouse Hanford Company's Protective Barrier Development Program for evaluating and predicting potential impacts of animal burrowing on long-term barrier performance. This document reviews the major accomplishments for FY 1988, which is the initial year of the work. The scope of work includes a literature review, field studies, and modeling to assess burrowing impacts as they may contribute to increased infiltration of surface water through barriers, increased quantities of soil available for erosion because of surface soil disturbance, and direct physical transport of contaminants to the surface. 68 refs., 8 figs., 5 tabs

Crossing the phantom divide with Ricci-like holographic dark energy

We study a holographic model for the dark energy considered recently in the literature which postulates an energy density $\rho \sim R$, where $R$ is the Ricci scalar curvature. We obtain a cosmological scenario that comes from considering two non-interacting fluids along a reasonable Ansatz for the cosmic coincidence parameter. We adjust the involved parameters in the model according to the observational data and we show that the equation of state for the dark energy experience a cross through the -1 barrier. In addition, we find a disagreement in these parameters with respect to an approach from a scalar field theory.Comment: Match with accepted version by EPJ

From the zero-field metal-insulator transition in two dimensions to the quantum Hall transition: a percolation-effective-medium theory

Effective-medium theory is applied to the percolation description of the metal-insulator transition in two dimensions with emphasis on the continuous connection between the zero-magnetic-field transition and the quantum Hall transition. In this model the system consists of puddles connected via saddle points, and there is loss of quantum coherence inside the puddles. The effective conductance of the network is calculated using appropriate integration over the distribution of conductances, leading to a determination of the magnetic field dependence of the critical density. Excellent quantitative agreement is obtained with the experimental data, which allows an estimate of the puddle physical parameters

QUARTERLY PROGRESS REPORT JANUARY, FEBRUARY, MARCH, 1968 REACTOR FUELS AND MATERIALS DEVELOPMENT PROGRAMS FOR FUELS AND MATERIALS BRANCH OF USAEC DIVISION OF REACTOR DEVELOPMENT AND TECHNOLOGY

Progress is reported in these areas: nuclear graphite; fuel development for gas-cooled reactors; HTGR graphite studies; nuclear ceramics; fast-reactor nitrides research; non-destructive testing; metallic fuels; basic swelling studies; ATR gas and water loop operation and maintenance; reactor fuels and materials; fast reactor dosimetry and damage analysis; and irradiation damage to reactor metals

Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase.

Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases. This inhibitor is orally bioavailable, and it increases liver IR phosphorylation in vivo and reverses high-fat diet-induced diabetes. Our findings suggest that LMPTP is a key promoter of insulin resistance and that LMPTP inhibitors would be beneficial for treating type 2 diabetes

A Deficiency in the Autophagy Gene Atg16L1 Enhances Resistance to Enteric Bacterial Infection

SummaryPolymorphisms in the essential autophagy gene Atg16L1 have been linked with susceptibility to Crohn’s disease, a major type of inflammatory bowel disease (IBD). Although the inability to control intestinal bacteria is thought to underlie IBD, the role of Atg16L1 during extracellular intestinal bacterial infections has not been sufficiently examined and compared to the function of other IBD susceptibility genes, such as Nod2, which encodes a cytosolic bacterial sensor. We find that Atg16L1 mutant mice are resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. An Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, but this hyperimmune phenotype and its protective effects are lost in Atg16L1/Nod2 double-mutant mice. These results reveal an immunosuppressive function of Atg16L1 and suggest that gene variants affecting the autophagy pathway may have been evolutionarily maintained to protect against certain life-threatening infections