Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation

The goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with the hypothesis that a number of negative regulators of mTORC1 will be engaged during a supraphysiological model of hypertrophy. To achieve this, mTORC1- IRS-1/2 signaling, BiP/CHOP/IRE1, and AMPK activation were determined in rat plantaris muscle following synergist ablation (SA). SA resulted in significant increases in muscle mass of 4% per day throughout the 21 days of the experiment. The expression of the insulin-like growth factors (IGF) were high throughout the 21st day of overload. However, IGF signaling was limited, since IRS-1 and -2 were undetectable in the overloaded muscle from day 3 to day 9. The decreases in IRS-1/2 protein were paralleled by increases in GRB10 Ser501/503 and S6K1 Thr389 phosphorylation, two mTORC1 targets that can destabilize IRS proteins. PKB Ser473 phosphorylation was higher from 3– 6 days, and this was associated with increased TSC2 Thr939 phosphorylation. The phosphorylation of TSC2 Thr1345 (an AMPK site) was also elevated, whereas phosphorylation at the other PKB site, Thr1462, was unchanged at 6 days. In agreement with the phosphorylation of Thr1345, SA led to activation of AMPK1 during the initial growth phase, lasting the first 9 days before returning to baseline by day 12. The UPR markers CHOP and BiP were elevated over the first 12 days following ablation, whereas IRE1 levels decreased. These data suggest that during supraphysiological muscle loading at least three potential molecular brakes engage to downregulate mTORC1. m

Toward a descriptive model of solar particles in the heliosphere

During a workshop on the interplanetary charged particle environment held in 1987, a descriptive model of solar particles in the heliosphere was assembled. This model includes the fluence, composition, energy spectra, and spatial and temporal variations of solar particles both within and beyong 1 AU. The ability to predict solar particle fluences was also discussed. Suggestions for specific studies designed to improve the basic model were also made

Phobos: Low Velocity Impacts

Marss inner moon, Phobos, is located deep in the planets gravity well and orbits far below the planets synchronous orbit. Images of the surface of Phobos, in particular from Viking Orbiter 1, MGS, MRO, and MEX, reveal a rich collisional history, including freshlooking impact craters and subdued older ones, very large impact structures (compared to the size of Phobos), such as Stickney, and much smaller ones. Sources of impactors colliding with Phobos include a priori: A) Impactors from outside the martian system (asteroids, comets, and fragments thereof); B) Impactors from Mars itself (ejecta from large impacts on Mars); and C) Impactors from Mars orbit, including impact ejecta launched from Deimos and ejecta launched from, and reintercepted by, Phobos. In addition to individual craters on Phobos, the networks of grooves on this moon have also been attributed in part or in whole to impactors from some of these sources, particularly B. We report the preliminary results of a systematic survey of the distribution, morphology, albedo, and color characteristics of fresh impact craters and associated ejecta deposits on Phobos. Considering that the different potential impactor sources listed above are expected to display distinct dominant compositions and different characteristic impact velocity regimes, we identify specific craters on Phobos that are more likely the result of low velocity impacts by impactors derived from Mars orbit than from any alternative sources. Our finding supports the hypothesis that the spectrally Redder Unit on Phobos may be a superficial veneer of accreted ejecta from Deimos, and that Phoboss bulk might be distinct in composition from Deimos

Topological Phase Diagram of a Two-Subband Electron System

We present a phase diagram for a two-dimensional electron system with two populated subbands. Using a gated GaAs/AlGaAs single quantum well, we have mapped out the phases of various quantum Hall states in the density-magnetic filed plane. The experimental phase diagram shows a very different topology from the conventional Landau fan diagram. We find regions of negative differential Hall resistance which are interpreted as preliminary evidence of the long sought reentrant quantum Hall transitions. We discuss the origins of the anomalous topology and the negative differential Hall resistance in terms of the Landau level and subband mixing.Comment: 4 pages, 4 figure

Hypercomplex quantum mechanics

The fundamental axioms of the quantum theory do not explicitly identify the algebraic structure of the linear space for which orthogonal subspaces correspond to the propositions (equivalence classes of physical questions). The projective geometry of the weakly modular orthocomplemented lattice of propositions may be imbedded in a complex Hilbert space; this is the structure which has traditionally been used. This paper reviews some work which has been devoted to generalizing the target space of this imbedding to Hilbert modules of a more general type. In particular, detailed discussion is given of the simplest generalization of the complex Hilbert space, that of the quaternion Hilbert module.Comment: Plain Tex, 11 page

Predictors of failed attendances in a multi-specialty outpatient centre using electronic databases.

BACKGROUND: Failure to keep outpatient medical appointments results in inefficiencies and costs. The objective of this study is to show the factors in an existing electronic database that affect failed appointments and to develop a predictive probability model to increase the effectiveness of interventions. METHODS: A retrospective study was conducted on outpatient clinic attendances at Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly sampled for analysis. The outcome measure was failed outpatient appointments according to each patient's latest appointment. RESULTS: Failures comprised of 21% of all appointments and 39% when using the patients' latest appointment. Using odds ratios from the mutliple logistic regression analysis, age group (0.75 to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for Malays, 1.61 for Indians compared to Chinese), days from scheduling to appointment (2.38 for more than 21 days compared to less than 7 days), previous failed appointments (1.79 for more than 60% failures and 4.38 for no previous appointments, compared with less than 20% failures), provision of cell phone number (0.10 for providing numbers compared to otherwise) and distance from hospital (1.14 for more than 14 km compared to less than 6 km) were significantly associated with failed appointments. The predicted probability model's diagnostic accuracy to predict failures is more than 80%. CONCLUSION: A few key variables have shown to adequately account for and predict failed appointments using existing electronic databases. These can be used to develop integrative technological solutions in the outpatient clinic

Fluorinated benzalkylsilane molecular rectifiers

We report on the synthesis and electrical properties of nine new alkylated silane self-assembled monolayers (SAMs) – (EtO)3Si(CH2)nN = CHPhX where n = 3 or 11 and X = 4-CF[subscript 3], 3,5-CF[subscript 3], 3-F-4-CF[subscript 3], 4-F, or 2,3,4,5,6-F, and explore their rectification behavior in relation to their molecular structure. The electrical properties of the films were examined in a metal/insulator/metal configuration, with a highly-doped silicon bottom contact and a eutectic gallium-indium liquid metal (EGaIn) top contact. The junctions exhibit high yields (>90%), a remarkable resistance to bias stress, and current rectification ratios (R) between 20 and 200 depending on the structure, degree of order, and internal dipole of each molecule. We found that the rectification ratio correlates positively with the strength of the molecular dipole moment and it is reduced with increasing molecular length.National Science Foundation (U.S.) (Award ECCS 1254757)Wake Forest University (Pilot Research Grant

Thermal tides in the Martian middle atmosphere as seen by the Mars Climate Sounder

The first systematic observations of the middle atmosphere of Mars (35–80km) with the Mars Climate Sounder (MCS) show dramatic patterns of diurnal thermal variation, evident in retrievals of temperature and water ice opacity. At the time of writing, the data set of MCS limb retrievals is sufficient for spectral analysis within a limited range of latitudes and seasons. This analysis shows that these thermal variations are almost exclusively associated with a diurnal thermal tide. Using a Martian general circulation model to extend our analysis, we show that the diurnal thermal tide dominates these patterns for all latitudes and all seasons

HOx observations over West Africa during AMMA: impact of isoprene and NOx

Aircraft OH and HO2 measurements made over West Africa during the AMMA field campaign in summer 2006 have been investigated using a box model constrained to observations of long-lived species and physical parameters. "Good" agreement was found for HO2 (modelled to observed gradient of 1.23 ± 0.11). However, the model significantly overpredicts OH concentrations. The reasons for this are not clear, but may reflect instrumental instabilities affecting the OH measurements. Within the model, HOx concentrations in West Africa are controlled by relatively simple photochemistry, with production dominated by ozone photolysis and reaction of O(1D) with water vapour, and loss processes dominated by HO2 + HO2 and HO2 + RO2. Isoprene chemistry was found to influence forested regions. In contrast to several recent field studies in very low NOx and high isoprene environments, we do not observe any dependence of model success for HO2 on isoprene and attribute this to efficient recycling of HOx through RO2 + NO reactions under the moderate NOx concentrations (5–300 ppt NO in the boundary layer, median 76 ppt) encountered during AMMA. This suggests that some of the problems with understanding the impact of isoprene on atmospheric composition may be limited to the extreme low range of NOx concentrations

Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes