Ricci-flat Metrics with U(1) Action and the Dirichlet Boundary-value Problem in Riemannian Quantum Gravity and Isoperimetric Inequalities

The Dirichlet boundary-value problem and isoperimetric inequalities for positive definite regular solutions of the vacuum Einstein equations are studied in arbitrary dimensions for the class of metrics with boundaries admitting a U(1) action. We show that in the case of non-trivial bundles Taub-Bolt infillings are double-valued whereas Taub-Nut and Eguchi-Hanson infillings are unique. In the case of trivial bundles, there are two Schwarzschild infillings in arbitrary dimensions. The condition of whether a particular type of filling in is possible can be expressed as a limitation on squashing through a functional dependence on dimension in each case. The case of the Eguchi-Hanson metric is solved in arbitrary dimension. The Taub-Nut and the Taub-Bolt are solved in four dimensions and methods for arbitrary dimension are delineated. For the case of Schwarzschild, analytic formulae for the two infilling black hole masses in arbitrary dimension have been obtained. This should facilitate the study of black hole dynamics/thermodynamics in higher dimensions. We found that all infilling solutions are convex. Thus convexity of the boundary does not guarantee uniqueness of the infilling. Isoperimetric inequalities involving the volume of the boundary and the volume of the infilling solutions are then investigated. In particular, the analogues of Minkowski's celebrated inequality in flat space are found and discussed providing insight into the geometric nature of these Ricci-flat spaces.Comment: 40 pages, 3 figure

In vivo biodistribution and physiologically based pharmacokinetic modeling of inhaled fresh and aged cerium oxide nanoparticles in rats

Abstract Background Cerium oxide (CeO2) nanoparticles used as a diesel fuel additive can be emitted into the ambient air leading to human inhalation. Although biological studies have shown CeO2 nanoparticles can cause adverse health effects, the extent of the biodistribution of CeO2 nanoparticles through inhalation has not been well characterized. Furthermore, freshly emitted CeO2 nanoparticles can undergo an aging process by interaction with other ambient airborne pollutants that may influence the biodistribution after inhalation. Therefore, understanding the pharmacokinetic of newly-generated and atmospherically-aged CeO2 nanoparticles is needed to assess the risks to human health. Methods A novel experimental system was designed to integrate the generation, aging, and inhalation exposure of Sprague Dawley rats to combustion-generated CeO2 nanoparticles (25 and 90 nm bimodal distribution). Aging was done in a chamber representing typical ambient urban air conditions with UV lights. Following a single 4-hour nose-only exposure to freshly emitted or aged CeO2 for 15 min, 24 h, and 7 days, ICP-MS detection of Ce in the blood, lungs, gastrointestinal tract, liver, spleen, kidneys, heart, brain, olfactory bulb, urine, and feces were analyzed with a mass balance approach to gain an overarching understanding of the distribution. A physiologically based pharmacokinetic (PBPK) model that includes mucociliary clearance, phagocytosis, and entry into the systemic circulation by alveolar wall penetration was developed to predict the biodistribution kinetic of the inhaled CeO2 nanoparticles. Results Cerium was predominantly recovered in the lungs and feces, with extrapulmonary organs contributing less than 4 % to the recovery rate at 24 h post exposure. No significant differences in biodistribution patterns were found between fresh and aged CeO2 nanoparticles. The PBPK model predicted the biodistribution well and identified phagocytizing cells in the pulmonary region accountable for most of the nanoparticles not eliminated by feces. Conclusions The biodistribution of fresh and aged CeO2 nanoparticles followed the same patterns, with the highest amounts recovered in the feces and lungs. The slow decrease of nanoparticle concentrations in the lungs can be explained by clearance to the gastrointestinal tract and then to the feces. The PBPK model successfully predicted the kinetic of CeO2 nanoparticles in various organs measured in this study and suggested most of the nanoparticles were captured by phagocytizing cells.http://deepblue.lib.umich.edu/bitstream/2027.42/134633/1/12989_2016_Article_156.pd

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

3-D Inlet Shock-Boundary Layer Interactions - PIV Database for the Second SBLI Workshop

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97090/1/AIAA2012-3214.pd

DISTRIBUTION AND PROPERTIES OF CDP-DIGLYCERIDE:INOSITOL TRANSFERASE FROM BRAIN 1

CDP-diglyceride is converted to phosphatidyl inositol by several particulate subcellular fractions of guinea pig brain, with highest specific activity in the microsomal fraction. Optimal conditions with respect to pH, metal ion concentration, and substrate concentrations have been determined. The reaction was stimulated by the addition of bovine serum albumin and by Tween 80. Of several dl-CDP-diglycerides synthesized and used as substrates in a spectrophoto-metric assay for the enzyme, dl-CDP-didecanoin was the most active. The enzyme showed a high selectivity for myo-inositol. Of a number of compounds tested, only scyllo -inosose and epi -inosose served as substrates. Three inositol isomers and three myo -inositol monophosphates inhibited the reaction slightly. The most potent inhibitor found was galactinol, a myo -inositol galactoside.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66197/1/j.1471-4159.1969.tb06850.x.pd

Weather effects on the patterns of people's everyday activities: a study using GPS traces of mobile phone users

This study explores the effects that the weather has on people's everyday activity patterns. Temperature, rainfall, and wind speed were used as weather parameters. People's daily activity patterns were inferred, such as place visited, the time this took place, the duration of the visit, based on the GPS location traces of their mobile phones overlaid upon Yellow Pages information. Our analysis of 31,855 mobile phone users allowed us to infer that people were more likely to stay longer at eateries or food outlets, and (to a lesser degree) at retail or shopping areas when the weather is very cold or when conditions are calm (non-windy). When compared to people's regular activity patterns, certain weather conditions affected people's movements and activities noticeably at different times of the day. On cold days, people's activities were found to be more diverse especially after 10AM, showing greatest variations between 2PM and 6PM. A similar trend is observed between 10AM and midnight on rainy days, with people's activities found to be most diverse on days with heaviest rainfalls or on days when the wind speed was stronger than 4 km/h, especially between 10AM–1AM. Finally, we observed that different geographical areas of a large metropolis were impacted differently by the weather. Using data of urban infrastructure to characterize areas, we found strong correlations between weather conditions upon people's accessibility to trains. This study sheds new light on the influence of weather conditions on human behavior, in particular the choice of daily activities and how mobile phone data can be used to investigate the influence of environmental factors on urban dynamics

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

GenTAC registry report: Gender differences among individuals with genetically triggered thoracic aortic aneurysm and dissection

Previous data suggest women are at increased risk of death from aortic dissection. Therefore, we analyzed data from the GenTAC registry, the NIH‐sponsored program that collects information about individuals with genetically triggered thoracic aortic aneurysms and cardiovascular conditions. We performed cross‐sectional analyses in adults with Marfan syndrome (MFS), familial thoracic aortic aneurysm or dissection (FTAAD), bicuspid aortic valve (BAV) with thoracic aortic aneurysm or dissection, and subjects under 50 years of age with thoracic aortic aneurysm or dissection (TAAD <50 years). Women comprised 32% of 1,449 subjects and were 21% of subjects with BAV, 34% with FTAAD, 22% with TAAD <50 years, and 47% with MFS. Thoracic aortic dissections occurred with equal gender frequency yet women with BAV had more extensive dissections. Aortic size was smaller in women but was similar after controlling for BSA. Age at operation for aortic valve dysfunction, aneurysm or dissection did not differ by gender. Multivariate analysis (adjusting for age, BSA, hypertension, study site, diabetes, and subgroup diagnoses) showed that women had fewer total aortic surgeries (OR = 0.65, P  < 0.01) and were less likely to receive angiotensin converting enzyme inhibitors (ACEi; OR = 0.68, P  < 0.05). As in BAV, other genetically triggered aortic diseases such as FTAAD and TAAD <50 are more common in males. In women, decreased prevalence of aortic operations and less treatment with ACEi may be due to their smaller absolute aortic diameters. Longitudinal studies are needed to determine if women are at higher risk for adverse events. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97193/1/35836_ftp.pd

Mitochondrial Substrate-Level Phosphorylation as Energy Source for Glioblastoma: Review and Hypothesis

Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers. Ultrastructural and biochemical evidence shows that GBM cells exhibit mitochondrial abnormalities incompatible with energy production through oxidative phosphorylation (OxPhos). Under such conditions, the mitochondrial F0-F1 ATP synthase operates in reverse at the expense of ATP hydrolysis to maintain a moderate membrane potential. Moreover, expression of the dimeric M2 isoform of pyruvate kinase in GBM results in diminished ATP output, precluding a significant ATP production from glycolysis. If ATP synthesis through both glycolysis and OxPhos was impeded, then where would GBM cells obtain high-energy phosphates for growth and invasion? Literature is reviewed suggesting that the succinate-CoA ligase reaction in the tricarboxylic acid cycle can substantiate sufficient ATP through mitochondrial substrate-level phosphorylation (mSLP) to maintain GBM growth when OxPhos is impaired. Production of high-energy phosphates would be supported by glutaminolysis-a hallmark of GBM metabolism-through the sequential conversion of glutamine -> glutamate -> alpha-ketoglutarate -> succinyl CoA -> succinate. Equally important, provision of ATP through mSLP would maintain the adenine nucleotide translocase in forward mode, thus preventing the reverse-operating F0-F1 ATP synthase from depleting cytosolic ATP reserves. Because glucose and glutamine are the primary fuels driving the rapid growth of GBM and most tumors for that matter, simultaneous restriction of these two substrates or inhibition of mSLP should diminish cancer viability, growth, and invasion