Corticosterone Regulates Both Naturally Occurring and Cocaine‐Induced Dopamine Signaling by Selectively Decreasing Dopamine Uptake

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine\u27s effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine

BOSS-LDG: A Novel Computational Framework that Brings Together Blue Waters, Open Science Grid, Shifter and the LIGO Data Grid to Accelerate Gravitational Wave Discovery

We present a novel computational framework that connects Blue Waters, the NSF-supported, leadership-class supercomputer operated by NCSA, to the Laser Interferometer Gravitational-Wave Observatory (LIGO) Data Grid via Open Science Grid technology. To enable this computational infrastructure, we configured, for the first time, a LIGO Data Grid Tier-1 Center that can submit heterogeneous LIGO workflows using Open Science Grid facilities. In order to enable a seamless connection between the LIGO Data Grid and Blue Waters via Open Science Grid, we utilize Shifter to containerize LIGO's workflow software. This work represents the first time Open Science Grid, Shifter, and Blue Waters are unified to tackle a scientific problem and, in particular, it is the first time a framework of this nature is used in the context of large scale gravitational wave data analysis. This new framework has been used in the last several weeks of LIGO's second discovery campaign to run the most computationally demanding gravitational wave search workflows on Blue Waters, and accelerate discovery in the emergent field of gravitational wave astrophysics. We discuss the implications of this novel framework for a wider ecosystem of Higher Performance Computing users.Comment: 10 pages, 10 figures. Accepted as a Full Research Paper to the 13th IEEE International Conference on eScienc

Contrasting effects of sleep fragmentation and angiotensin-II treatment upon pro-inflammatory responses of mice

Disordered sleep promotes inflammation in brain and peripheral tissues, but the mechanisms that regulate these responses are poorly understood. One hypothesis is that activation of the sympathetic nervous system (SNS) from sleep loss elevates blood pressure to promote vascular sheer stress leading to inflammation. As catecholamines produced from SNS activation can directly regulate inflammation, we pharmacologically altered blood pressure using an alternative approach-manipulation of the renin-angiotensin system (RAS). Male C57BL6/J mice were treated with angiotensin or captopril to elevate and reduce blood pressure, respectively and then exposed to 24-h of sleep fragmentation (SF) or allowed to sleep (control). Pro- and anti-inflammatory cytokine gene expression and as endothelial adhesion gene expression as well as serum glucocorticoids (corticosterone) were measured. RAS manipulation elevated cytokines and endothelial adhesion expression in heart and aorta while SF increased cytokine expression in peripheral tissues, but not brain. However, there were interactive effects of angiotensin-II and SF upon cytokine gene expression in hippocampus and hypothalamus, but not prefrontal cortex. SF, but not RAS manipulation, elevated serum corticosterone concentration. These findings highlight the contrasting effects of RAS manipulation and SF, implying that inflammation from SF is acting on different pathways that are largely independent of RAS manipulation

Asymmetric Supernovae from Magneto-Centrifugal Jets

Strong toroidal magnetic fields generated in stellar collapse can generate magneto-centrifugal jets in analogy to those found in simulations of black hole accretion and explain why all core collapse supernovae are found to be substantially asymmetric and predominantly bi-polar. We describe two phases: the initial LeBlanc-Wilson jet and a subsequent protopulsar or toroidal jet that propagates at about the core escape velocity. The jets will produce bow shocks that tend to expel matter, including iron and silicon, into equatorial tori, accounting for observations of the element distribution in Cas A. A magnetic ``switch'' mechanism may apply in instances of low density and large magnetic field with subsequent increase in the speed and collimation of the toroidal jet, depositing relatively little momentum. The result could be enough infall to form a black hole with a third, highly relativistic jet that could catch up to the protopulsar jet after it has emerged from the star. The interaction of these two jets could generate internal shocks and explain the presence of iron lines in the afterglow. Recent estimates that typical gamma-ray burst energy is about 3x10^50 erg imply either a very low efficiency for conversion of rotation into jets, or a rather rapid turnoff of the jet process even though the black hole still rotates rapidly. Magnetars and ``hypernovae'' might arise in an intermediate parameter regime of energetic jets that yield larger magnetic fields and provide more energy than the routine case, but that are not so tightly collimated that they yield failed supernova. (slightly abridged)Comment: AASTeX, 29 pages, 2 postscript figures, accepted by ApJ, November 20, 200

Wave Function of a Brane-like Universe

Within the mini-superspace model, brane-like cosmology means performing the variation with respect to the embedding (Minkowski) time $\tau$ before fixing the cosmic (Einstein) time $t$. The departure from Einstein limit is parameterized by the 'energy' conjugate to $\tau$, and characterized by a classically disconnected Embryonic epoch. In contrast with canonical quantum gravity, the wave-function of the brane-like Universe is (i) $\tau$-dependent, and (ii) vanishes at the Big Bang. Hartle-Hawking and Linde proposals dictate discrete 'energy' levels, whereas Vilenkin proposal resembles $\alpha$-particle disintegration.Comment: Revtex, 4 twocolumn pages, 3 eps figures (accepted for publication in Class. Quan. Grav.

X-ray \u3cem\u3eSwift\u3c/em\u3e Observations of SN 2018cow

Supernova (SN) 2018cow is an optical transient detected in the galaxy CGCG 137–068. It has been classified as a SN due to various characteristics in its optical spectra. The transient is also a bright X-ray source. We present results of the analysis of ∼ 62 ks of X-ray observations taken with the Neil Gehrels Swift Observatory over 27 days. We found a variable behavior in the 0 . 3 − 10 keV X-ray light curve of SN 2018cow, with variability timescales of days. The observed X-ray variability could be due to the interaction between the SN ejecta and a non-uniform circum-stellar medium, perhaps related to previous mass ejections from a luminous-blue-variable-like progenitor

A Liquid Model Analogue for Black Hole Thermodynamics

We are able to characterize a 2--dimensional classical fluid sharing some of the same thermodynamic state functions as the Schwarzschild black hole. This phenomenological correspondence between black holes and fluids is established by means of the model liquid's pair-correlation function and the two-body atomic interaction potential. These latter two functions are calculated exactly in terms of the black hole internal (quasilocal) energy and the isothermal compressibility. We find the existence of a ``screening" like effect for the components of the liquid.Comment: 20 pages and 6 Encapsulated PostScript figure

Development and Evolution of a Statewide Outpatient Consultation Service: Leveraging Telemedicine to Improve Access to Specialty Care

Despite a robust health care system in the United States, many Americans experience health care disparities as a result of poor access to medical care. Academic medicine plays an important role in addressing health care disparities by providing primary and specialty care for the poor and uninsured. In South Carolina, 43 of its 46 counties are designated as fully or partially Medically Underserved Areas (MUAs), defined as areas with a shortage of medical providers, high infant mortality, and either high elderly population or high poverty rates. To address these health care disparities, an academic medical center in South Carolina created a hub-and-spoke specialty care model using telemedicine in partnership with primary care providers across community settings. Initial private foundation grant funding enabled the development and dissemination of technology to provide remote teleconsultations by physicians at the academic medical center (hub) to patients in their primary care offices (spoke). This model, now supported by recurring state funding and professional billing, provides much-needed services, including psychiatry, nutrition counseling, and various surgical and medical subspecialties, to rural and underserved populations in the state. This manuscript provides a narrative review of the development of this statewide telemedicine service, with an emphasis on identification of stakeholders, technology issues, barriers to implementation, and future directions