Generic Isolated Horizons and their Applications

Boundary conditions defining a generic isolated horizon are introduced. They generalize the notion available in the existing literature by allowing the horizon to have distortion and angular momentum. Space-times containing a black hole, itself in equilibrium but possibly surrounded by radiation, satisfy these conditions. In spite of this generality, the conditions have rich consequences. They lead to a framework, somewhat analogous to null infinity, for extracting physical information, but now in the \textit{strong} field regions. The framework also generalizes the zeroth and first laws of black hole mechanics to more realistic situations and sheds new light on the `origin' of the first law. Finally, it provides a point of departure for black hole entropy calculations in non-perturbative quantum gravity.Comment: 4 pages, RevTeX. Minor typos were corrected and the fact that, in contrast to Ref [4], isolated horizons are now allowed to have distortion and rotation was clarifie

\u3cem\u3eDe Novo\u3c/em\u3e [PSI\u3csup\u3e+\u3c/sup\u3e] Prion Formation Involves Multiple Pathways to Form Infectious Oligomers

Prion and other neurodegenerative diseases are associated with misfolded protein assemblies called amyloid. Research has begun to uncover common mechanisms underlying transmission of amyloids, yet how amyloids form in vivo is still unclear. Here, we take advantage of the yeast prion, [PSI +], to uncover the early steps of amyloid formation in vivo. [PSI +] is the prion form of the Sup35 protein. While [PSI +] formation is quite rare, the prion can be greatly induced by overexpression of the prion domain of the Sup35 protein. This de novo induction of [PSI +] shows the appearance of fluorescent cytoplasmic rings when the prion domain is fused with GFP. Our current work shows that de novoinduction is more complex than previously thought. Using 4D live cell imaging, we observed that fluorescent structures are formed by four different pathways to yield [PSI +] cells. Biochemical analysis of de novo induced cultures indicates that newly formed SDS resistant oligomers change in size over time and lysates made from de novo induced cultures are able to convert [psi −] cells to [PSI +] cells. Taken together, our findings suggest that newly formed prion oligomers are infectious

“Dirty Factory Town” or “A Good City?”: Neoliberalism and the Cultural Politics of Rust Belt Urban Revitalization.

On July 4, 1984, AutoWorld opened in Flint, Michigan. A curious combination of Disney-style theme park and historical museum, the $80 million dollar urban revitalization project was also an attempt by a “Rust Belt” city to transform its image and economy following the devastating deindustrialization of the late 1970s and early 1980s. AutoWorld closed its doors less than a year after opening due to lack of visitors, unable to succeed in its mission. Through analysis of the development and execution of this project, as well as contemporary culturally based urban revitalization projects throughout the “Rust Belt” including Cleveland’s Rock and Roll Hall of Fame, Youngstown’s Historical Center of Labor and Industry, and Baltimore’s Harborplace development, this dissertation investigates the complex cultural, political, and economic strategies undertaken by former industrial urban centers in the wake of deindustrialization and during the emergence of neoliberalism in the 1970s and 80s. In these urban revitalization sites, we can see the economic and cultural logics of neoliberalism intersecting on the ground as cities struggled over the terms of their image and their place in a “post-industrial,” post-New Deal America, and such sites are thus crucial for understanding the complex interactions of capital, culture, and urban politics both in their own historical moment and our own. In chapters focusing on the roots of the neoliberal turn, the development and implications of the “Rust Belt” image in the national imagination, the roles of organized labor and its representation in these cultural projects, and the various institutional identities that these projects took on, this study illuminates the ways that “Rust Belt” cities negotiated the economic, moral and cultural dimensions of the neoliberal turn of the late 1970s and 1980s, and how that framework has guided those cities since.PHDAmerican CultureUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/100045/1/swis_1.pd

Local variations in spatial synchrony of influenza epidemics

Background: Understanding the mechanism of influenza spread across multiple geographic scales is not complete. While the mechanism of dissemination across regions and states of the United States has been described, understanding the determinants of dissemination between counties has not been elucidated. The paucity of high resolution spatial-temporal influenza incidence data to evaluate disease structure is often not available. Methodology and Findings: We report on the underlying relationship between the spread of influenza and human movement between counties of one state. Significant synchrony in the timing of epidemics exists across the entire state and decay with distance (regional correlation = 62%). Synchrony as a function of population size display evidence of hierarchical spread with more synchronized epidemics occurring among the most populated counties. A gravity model describing movement between two populations is a stronger predictor of influenza spread than adult movement to and from workplaces suggesting that non-routine and leisure travel drive local epidemics. Conclusions: These findings highlight the complex nature of influenza spread across multiple geographic scales. © 2012 Stark et al

The Effects of Insurance Status on Pediatric Traumatic Brain Injury Outcomes: A Literature Review

Objective: To review the literature that describes the effects of insurance status on traumatic brain injury (TBI) outcomes among pediatric patients to understand how policies related to access to health insurance changes TBI outcomes. Method: This review was conducted using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA). A search of OVID Medline was conducted in May of 2016 for all years for peer-reviewed articles that included keywords related to “brain injuries” and “insurance status”. Articles were included if authors conducted a separate analysis of children aged 0 to 18. Articles were excluded if the TBI was the result of abuse. Results: After screening for inclusion and exclusion criteria, a total of 12 articles were analyzed. Discussion/Summary: The findings of this review indicate that insurance status has a significant effect on the health outcomes of pediatric patients who experience TBI, with insured children having lower mortality rates than those with insurance from the government or uninsured. In addition, those insured from the government had a survival benefit when compared to those without insurance. We found evidence that insurance status plays a role in long term outcomes such as rates of placement into rehabilitation facilities and level of disability

Hydrogen Balmer Line Broadening in Solar and Stellar Flares

The broadening of the hydrogen lines during flares is thought to result from increased charge (electron, proton) density in the flare chromosphere. However, disagreements between theory and modeling prescriptions have precluded an accurate diagnostic of the degree of ionization and compression resulting from flare heating in the chromosphere. To resolve this issue, we have incorporated the unified theory of electric pressure broadening of the hydrogen lines into the non-LTE radiative transfer code RH. This broadening prescription produces a much more realistic spectrum of the quiescent, A0 star Vega compared to the analytic approximations used as a damping parameter in the Voigt profiles. We test recent radiative-hydrodynamic (RHD) simulations of the atmospheric response to high nonthermal electron beam fluxes with the new broadening prescription and find that the Balmer lines are over-broadened at the densest times in the simulations. Adding many simultaneously heated and cooling model loops as a "multithread" model improves the agreement with the observations. We revisit the three-component phenomenological flare model of the YZ CMi Megaflare using recent and new RHD models. The evolution of the broadening, line flux ratios, and continuum flux ratios are well-reproduced by a multithread model with high-flux nonthermal electron beam heating, an extended decay phase model, and a "hot spot" atmosphere heated by an ultrarelativistic electron beam with reasonable filling factors: 0.1%, 1%, and 0.1% of the visible stellar hemisphere, respectively. The new modeling motivates future work to understand the origin of the extended gradual phase emission.Comment: 31 pages, 13 figures, 2 tables, accepted for publication in the Astrophysical Journa

AlGaInN laser diode technology for GHz high-speed visible light communication through plastic optical fiber and water

AlGaInN ridge waveguide laser diodes are fabricated to achieve single-mode operation with optical powers up to 100 mW at ∼420  nm∼420  nm for visible free-space, underwater, and plastic optical fiber communication. We report high-frequency operation of AlGaInN laser diodes with data transmission up to 2.5 GHz for free-space and underwater communication and up to 1.38 GHz through 10 m of plastic optical fiber

Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse

<p>Abstract</p> <p>Background</p> <p>Alzheimer's Disease (AD) is the most common of the conformational neurodegenerative disorders characterized by the conversion of a normal biological protein into a β-sheet-rich pathological isoform. In AD the normal soluble Aβ (sAβ) forms oligomers and fibrils which assemble into neuritic plaques. The most toxic form of Aβ is thought to be oligomeric. A recent study reveals the cellular prion protein, PrP^C, to be a receptor for Aβ oligomers. Aβ oligomers suppress LTP signal in murine hippocampal slices but activity remains when pretreated with the PrP monoclonal anti-PrP antibody, 6D11. We hypothesized that targeting of PrP^Cto prevent Aβ oligomer-related cognitive deficits is a potentially novel therapeutic approach. APP/PS1 transgenic mice aged 8 months were intraperitoneally (i.p.) injected with 1 mg 6D11 for 5 days/week for 2 weeks. Two wild-type control groups were given either the same 6D11 injections or vehicle solution. Additional groups of APP/PS1 transgenic mice were given either i.p. injections of vehicle solution or the same dose of mouse IgG over the same period. The mice were then subjected to cognitive behavioral testing using a radial arm maze, over a period of 10 days. At the conclusion of behavioral testing, animals were sacrificed and brain tissue was analyzed biochemically or immunohistochemically for the levels of amyloid plaques, PrP^C, synaptophysin, Aβ40/42 and Aβ oligomers.</p> <p>Results</p> <p>Behavioral testing showed a marked decrease in errors in 6D11 treated APP/PS1 Tg mice compared with the non-6D11 treated Tg groups (p < 0.0001). 6D11 treated APP/PS1 Tg mice behaved the same as wild-type controls indicating a recovery in cognitive learning, even after this short term 6D11 treatment. Brain tissue analysis from both treated and vehicle treated APP/PS1 groups indicate no significant differences in amyloid plaque burden, Aβ40/42, PrP^Cor Aβ oligomer levels. 6D11 treated APP/PS1 Tg mice had significantly greater synaptophysin immunoreactivity in the dentate gyrus molecular layer of the hippocampus compared to vehicle treated APP/PS1 Tg mice (p < 0.05).</p> <p>Conclusions</p> <p>Even short term treatment with monoclonal antibodies such as 6D11 or other compounds which block the binding of Aβ oligomers to PrP^Ccan be used to treat cognitive deficits in aged AD transgenic mice.</p

Carbonic anhydrase inhibition selectively prevents amyloid b neurovascular mitochondrial toxicity

Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer’s disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid b (Ab)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Ab, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Ab, without affecting metabolic function. ATZ was effective at concentrations 10 times lower than MTZ. Both MTZ and ATZ prevented mitochondrial membrane depolarization and H2O2 generation, with no effects on intracellular pH or ATP production. Importantly, the drugs did not primarily affect calcium homeostasis. This work suggests a new role for carbonic anhydrases (CAs) in the Ab-induced mitochondrial toxicity associated with AD and cerebral amyloid angiopathy (CAA), and paves the way to AD clinical trials for CAIs, FDA-approved drugs with a well-known profile of brain delivery