Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing

It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.Fil: Cakir, Isin. Brown University; Estados UnidosFil: Cyr, Nicole E.. Brown University; Estados UnidosFil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Litvinov, Bogdan Patedakis. Brown University; Estados UnidosFil: Romero, Amparo. Brown University; Estados UnidosFil: Stuart, Ronald C.. Brown University; Estados UnidosFil: Nillni, Eduardo A.. Brown University; Estados Unido

Time Variations in Elemental Abundances in Solar Energetic Particle Events

The Solar Isotope Spectrometer (SIS) on-board the Advanced Composition Explorer has a large collection power and high telemetry rate, making it possible to study elemental abundances in large solar energetic particle (SEP) events as a function of time. Results have now been obtained for more than 25 such events. Understanding the causes of these variations is key to obtaining reliable solar elemental abundances and to understanding solar acceleration processes. Such variations have been previously attributed to two models: (1) a mixture of an initial impulsive phase having enhanced heavy element abundances with a longer gradual phase with coronal abundances and (2) rigidity dependent escape from CME-driven shocks through plasma waves generated by wave-particle interactions. In this second model the injected abundances are assumed to be coronal. Both these models can be expected to depend upon solar longitude since impulsive events are associated with flares at longitudes well-connected magnetically to the observer, and shock properties and connection of the observer to the shock are also longitude dependent. We present results on temporal variations from event to event and within events and show that they appear to have a longitude dependence. We show that the events which have been well-explained by model (2) tend to be near central meridian or the west limb. In addition, we show that there are events with little time variation and heavy element enhancements similar to those of impulsive events. These events seem to be better explained by model (1) with only an impulsive phase

Monolithic Multigrid for Magnetohydrodynamics

The magnetohydrodynamics (MHD) equations model a wide range of plasma physics applications and are characterized by a nonlinear system of partial differential equations that strongly couples a charged fluid with the evolution of electromagnetic fields. After discretization and linearization, the resulting system of equations is generally difficult to solve due to the coupling between variables, and the heterogeneous coefficients induced by the linearization process. In this paper, we investigate multigrid preconditioners for this system based on specialized relaxation schemes that properly address the system structure and coupling. Three extensions of Vanka relaxation are proposed and applied to problems with up to 170 million degrees of freedom and fluid and magnetic Reynolds numbers up to 400 for stationary problems and up to 20,000 for time-dependent problems

A comparison of spectral element and finite difference methods using statically refined nonconforming grids for the MHD island coalescence instability problem

A recently developed spectral-element adaptive refinement incompressible magnetohydrodynamic (MHD) code [Rosenberg, Fournier, Fischer, Pouquet, J. Comp. Phys. 215, 59-80 (2006)] is applied to simulate the problem of MHD island coalescence instability (MICI) in two dimensions. MICI is a fundamental MHD process that can produce sharp current layers and subsequent reconnection and heating in a high-Lundquist number plasma such as the solar corona [Ng and Bhattacharjee, Phys. Plasmas, 5, 4028 (1998)]. Due to the formation of thin current layers, it is highly desirable to use adaptively or statically refined grids to resolve them, and to maintain accuracy at the same time. The output of the spectral-element static adaptive refinement simulations are compared with simulations using a finite difference method on the same refinement grids, and both methods are compared to pseudo-spectral simulations with uniform grids as baselines. It is shown that with the statically refined grids roughly scaling linearly with effective resolution, spectral element runs can maintain accuracy significantly higher than that of the finite difference runs, in some cases achieving close to full spectral accuracy.Comment: 19 pages, 17 figures, submitted to Astrophys. J. Supp

Pseudogap phase of cuprate superconductors confined by Fermi surface topology

The properties of cuprate high-temperature superconductors are largely shaped by competing phases whose nature is often a mystery. Chiefly among them is the pseudogap phase, which sets in at a doping $p^*$ that is material-dependent. What determines $p^*$ is currently an open question. Here we show that the pseudogap cannot open on an electron-like Fermi surface, and can only exist below the doping $p_{FS}$ at which the large Fermi surface goes from hole-like to electron-like, so that $p^*$ $\leq$ $p_{FS}$. We derive this result from high-magnetic-field transport measurements in La$_{1.6-x}$Nd$_{0.4}$Sr$_x$CuO$_4$ under pressure, which reveal a large and unexpected shift of $p^*$ with pressure, driven by a corresponding shift in $p_{FS}$. This necessary condition for pseudogap formation, imposed by details of the Fermi surface, is a strong constraint for theories of the pseudogap phase. Our finding that $p^*$ can be tuned with a modest pressure opens a new route for experimental studies of the pseudogap.Comment: 15 pages, 5 figures, 7 supplemental figure

Dark energy with gravitational lens time delays

Strong lensing gravitational time delays are a powerful and cost effective probe of dark energy. Recent studies have shown that a single lens can provide a distance measurement with 6-7 % accuracy (including random and systematic uncertainties), provided sufficient data are available to determine the time delay and reconstruct the gravitational potential of the deflector. Gravitational-time delays are a low redshift (z~0-2) probe and thus allow one to break degeneracies in the interpretation of data from higher-redshift probes like the cosmic microwave background in terms of the dark energy equation of state. Current studies are limited by the size of the sample of known lensed quasars, but this situation is about to change. Even in this decade, wide field imaging surveys are likely to discover thousands of lensed quasars, enabling the targeted study of ~100 of these systems and resulting in substantial gains in the dark energy figure of merit. In the next decade, a further order of magnitude improvement will be possible with the 10000 systems expected to be detected and measured with LSST and Euclid. To fully exploit these gains, we identify three priorities. First, support for the development of software required for the analysis of the data. Second, in this decade, small robotic telescopes (1-4m in diameter) dedicated to monitoring of lensed quasars will transform the field by delivering accurate time delays for ~100 systems. Third, in the 2020's, LSST will deliver 1000's of time delays; the bottleneck will instead be the aquisition and analysis of high resolution imaging follow-up. Thus, the top priority for the next decade is to support fast high resolution imaging capabilities, such as those enabled by the James Webb Space Telescope and next generation adaptive optics systems on large ground based telescopes.Comment: White paper submitted to SNOWMASS201

An absence of equipoise: Examining surgeons\u27 decision talk during encounters with women considering breast cancer surgery

Shared decision-making is recommended for decisions with multiple reasonable options, yet clinicians often subtly or explicitly guide choices. Using purposive sampling, we performed a secondary analysis of 142 audio-recorded encounters between 13 surgeons and women eligible for breast-conserving surgery with radiation or mastectomy. We trained 9 surgeons in shared decision-making and provided them one of two conversation aids; 4 surgeons practiced as usual. Based on a published taxonomy of treatment recommendations (pronouncements, suggestions, proposals, offers, assertions), we examined how surgeons framed choices with patients. Many surgeons made assertions providing information and advice (usual care 71% vs. intervention 66%; p = 0.54). Some made strong pronouncements (usual care 51% vs. intervention 36%; p = .09). Few made proposals and offers, leaving the door open for deliberation (proposals usual care 21% vs. intervention 26%; p = 0.51; offers usual care 40% vs. intervention 40%; p = 0.98). Surgeons were significantly more likely to describe options as comparable when using a conversation aid, mentioning this in all intervention group encounters (usual care 64% vs. intervention 100%; p\u3c0.001). Conversation aids can facilitate offers of comparable options, but other conversational actions can inhibit aspects of shared decision-making