Pck1 Gene Silencing in the Liver Improves Glycemia Control, Insulin Sensitivity, and Dyslipidemia in db/db Mice

OBJECTIVE—Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C; encoded by Pck1) catalyzes the first committed step in gluconeogenesis. Extensive evidence demonstrates a direct correlation between PEPCK-C activity and glycemia control. Therefore, we aimed to evaluate the metabolic impact and their underlying mechanisms of knocking down hepatic PEPCK-C in a type 2 diabetic model

Calculation of the vibrational frequencies of carbon clusters and fullerenes with empirical potentials

Vibrational frequencies for carbon clusters, fullerenes and nanotubes evaluated using empirical carbon-carbon potentials are presented. For linear and cyclic clusters, frequencies evaluated with the reactive empirical bond order (REBO) potential provide the closest agreement with experiment. The mean absolute deviation (MAD) between experiment and the calculated harmonic frequencies is 79 cm−1 for the bending modes and 76 cm−1 for the stretching modes. The effects of anharmonicity are included via second order vibrational perturbation theory and tend to increase the frequency of the bending modes while the stretching modes have negative shifts in the region of 20 - 60 cm−1, with larger shifts for the higher frequency modes. This results in MADs for the bending and stretching modes of 84 cm−1 and 58 cm−1, respectively. For the fullerene molecule C60, the high frequency modes are predicted to have harmonic frequencies that are significantly higher than experiment, and this is not corrected by accounting for anharmonicity. This overestimation of experimental observed frequencies is also evident in the calculated frequencies of the G band in nanotubes. This suggests that the REBO potential is not optimal for these larger systems and it is shown that adjustment of the parameters within the potential leads to closer agreement with experiment, particularly if higher and lower frequency modes are considered separately

Spitzer Space Telescope observations of the Carina Nebula: The steady march of feedback-driven star formation

We report the first results of imaging the Carina Nebula with Spitzer/IRAC, providing a catalog of point sources and YSOs based on SED fits. We discuss several aspects of the extended emission, including dust pillars that result when a clumpy molecular cloud is shredded by massive star feedback. There are few "extended green objects" (EGOs) normally taken as signposts of outflow activity, and none of the HH jets detected optically are seen as EGOs. A population of "extended red objects" tends to be found around OB stars, some with clear bow-shocks. These are dusty shocks where stellar winds collide with flows off nearby clouds. Finally, the relative distributions of O stars and subclusters of YSOs as compared to dust pillars shows that while some YSOs are located within pillars, many more stars and YSOs reside just outside pillar heads. We suggest that pillars are transient phenomena, part of a continuous outwardly propagating wave of star formation driven by massive star feedback. As pillars are destroyed, they leave newly formed stars in their wake, which are then subsumed into the young OB association. Altogether, the current generation of YSOs shows no strong deviation from a normal IMF. The number of YSOs suggests a roughly constant star-formation rate over the past 3Myr, implying that star formation in pillars constitutes an important mechanism to construct unbound OB associations. Accelerated pillars may give birth to O-type stars that, after several Myr, could appear to have formed in isolation.Comment: 25 pages, 15 figures, MNRAS accepte

MICE: The muon ionization cooling experiment. Step I: First measurement of emittance with particle physics detectors

Copyright @ 2011 APSThe Muon Ionization Cooling Experiment (MICE) is a strategic R&D project intended to demonstrate the only practical solution to providing high brilliance beams necessary for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (RAL) in the United Kingdom. It comprises a dedicated beamline to generate a range of input muon emittances and momenta, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance of the incoming beam will be measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in Liquid Hydrogen (LH2) absorbers to RF cavity acceleration. A second spectrometer, identical to the first, and a second muon identification system will measure the outgoing emittance. In the 2010 run at RAL the muon beamline and most detectors were fully commissioned and a first measurement of the emittance of the muon beam with particle physics (time-of-flight) detectors was performed. The analysis of these data was recently completed and is discussed in this paper. Future steps for MICE, where beam emittance and emittance reduction (cooling) are to be measured with greater accuracy, are also presented.This work was supported by NSF grant PHY-0842798

Development and pilot testing of a decision aid for surrogates of patients with prolonged mechanical ventilation*

Shared decision making is inadequate in intensive care units (ICUs). Decision aids can improve decision making quality, though their role in an ICU setting is unclear. We aimed to develop and pilot test a decision aid for shared decision makers of patients undergoing prolonged mechanical ventilation

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study

Background: Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic β-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that char- acterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial charac- terization of an atypical new biomarker that detects these early conditions with just one measurement. Methods: Water T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exqui- sitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. Results: Plasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflamma- tion, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. Conclusions: Water T2 detects a constellation of early abnormalities associated with metabolic syndrome, provid- ing a global view of an individual’s metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Zebrafish Kidney Phagocytes Utilize Macropinocytosis and Ca2+-Dependent Endocytic Mechanisms

Background: The innate immune response constitutes the first line of defense against invading pathogens and consists of a variety of immune defense mechanisms including active endocytosis by macrophages and granulocytes. Endocytosis can be used as a reliable measure of selective and non-selective mechanisms of antigen uptake in the early phase of an immune response. Numerous assays have been developed to measure this response in a variety of mammalian and fish species. The small size of the zebrafish has prevented the large-scale collection of monocytes/macrophages and granulocytes for these endocytic assays. Methodology/Principal Findings: Pooled zebrafish kidney hematopoietic tissues were used as a source of phagocytic cells for flow-cytometry based endocytic assays. FITC-Dextran, Lucifer Yellow and FITC-Edwardsiella ictaluri were used to evaluate selective and non-selective mechanisms of uptake in zebrafish phagocytes. Conclusions/Significance: Zebrafish kidney phagocytes characterized as monocytes/macrophages, neutrophils and lymphocytes utilize macropinocytosis and Ca 2+-dependant endocytosis mechanisms of antigen uptake. These cells do not appear to utilize a mannose receptor. Heat-killed Edwardsiella ictaluri induces cytoskeletal interactions for internalization in zebrafish kidney monocytes/macrophages and granulocytes. The proposed method is easy to implement and should prove especially useful in immunological, toxicological and epidemiological research