A slice of AdS_5 as the large N limit of Seiberg duality

A slice of AdS_5 is used to provide a 5D gravitational description of 4D strongly-coupled Seiberg dual gauge theories. An (electric) SU(N) gauge theory in the conformal window at large N is described by the 5D bulk, while its weakly coupled (magnetic) dual is confined to the IR brane. This framework can be used to construct an N = 1 MSSM on the IR brane, reminiscent of the original Randall-Sundrum model. In addition, we use our framework to study strongly-coupled scenarios of supersymmetry breaking mediated by gauge forces. This leads to a unified scenario that connects the extra-ordinary gauge mediation limit to the gaugino mediation limit in warped space.Comment: 47 Pages, axodraw4j.st

Exposure to Environmental Tobacco Smoke and Cognitive Abilities among U.S. Children and Adolescents

We used the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994, to investigate the relationship between environmental tobacco smoke (ETS) exposure and cognitive abilities among U.S. children and adolescents 6–16 years of age. Serum cotinine was used as a biomarker of ETS exposure. Children were included in the sample if their serum cotinine levels were ≤15 ng/mL, a level consistent with ETS exposure, and if they denied using any tobacco products in the previous 5 days. Cognitive and academic abilities were assessed using the reading and math subtests of the Wide Range Achievement Test–Revised and the block design and digit span subtests of the Wechsler Intelligence Scale for Children–III. Analyses were conducted using SUDAAN software. Of the 5,365 6- to 16-year-olds included in NHANES III, 4,399 (82%) were included in this analysis. The geometric mean serum cotinine level was 0.23 ng/mL (range, 0.035–15 ng/mL); 80% of subjects had levels < 1 ng/mL. After adjustment for sex, race, region, poverty, parent education and marital status, ferritin, and blood lead concentration, there was a significant inverse relationship between serum cotinine and scores on reading (β= −2.69, p = 0.001), math (β= −1.93, p = 0.01), and block design (β= −0.55, p < 0.001) but not digit span (β= −0.08, p = 0.52). The estimated ETS-associated decrement in cognitive test scores was greater at lower cotinine levels. A log-linear analysis was selected as the best fit to characterize the increased slope in cognitive deficits at lower levels of exposure. These data, which indicate an inverse association between ETS exposure and cognitive deficits among children even at extremely low levels of exposure, support policy to further restrict children’s exposure

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Independent Recruitment of a Flavin-Dependent Monooxygenase for Safe Accumulation of Sequestered Pyrrolizidine Alkaloids in Grasshoppers and Moths

Several insect lineages have developed diverse strategies to sequester toxic pyrrolizidine alkaloids from food-plants for their own defense. Here, we show that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the holometabolous butterflies, an almost identical strategy evolved independently for safe accumulation of pyrrolizidine alkaloids. This strategy involves a pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to their respective N-oxide, enabling the insects to avoid high concentrations of toxic pyrrolizidine alkaloids in the hemolymph. We have identified a pyrrolizidine alkaloid N-oxygenase, which is a flavin-dependent monooxygenase, of the grasshopper Zonocerus variegatus. After heterologous expression in E. coli, this enzyme shows high specificity for pyrrolizidine alkaloids of various structural types and for the tropane alkaloid atropine as substrates, a property that has been described previously for a pyrrolizidine alkaloid N-oxygenase of the arctiid moth Grammia geneura. Phylogenetic analyses of insect flavin-dependent monooxygenase sequences suggest that independent gene duplication events preceded the establishment of this specific enzyme in the lineages of the grasshoppers and of arctiid moths. Two further flavin-dependent monooxygenase sequences have been identified from Z. variegatus sharing amino acid identities of approximately 78% to the pyrrolizidine alkaloid N-oxygenase. After heterologous expression, both enzymes are also able to catalyze the N-oxygenation of pyrrolizidine alkaloids, albeit with a 400-fold lower specific activity. With respect to the high sequence identity between the three Z. variegatus sequences this ability to N-oxygenize pyrrolizidine alkaloids is interpreted as a relict of a former bifunctional ancestor gene of which one of the gene copies optimized this activity for the specific adaptation to pyrrolizidine alkaloid containing food plants

Simultaneous bilateral hip replacement reveals superior outcome and fewer complications than two-stage procedures: a prospective study including 1819 patients and 5801 follow-ups from a total joint replacement registry

<p>Abstract</p> <p>Background</p> <p>Total joint replacements represent a considerable part of day-to-day orthopaedic routine and a substantial proportion of patients undergoing unilateral total hip arthroplasty require a contralateral treatment after the first operation. This report compares complications and functional outcome of simultaneous versus early and delayed two-stage bilateral THA over a five-year follow-up period.</p> <p>Methods</p> <p>The study is a post hoc analysis of prospectively collected data in the framework of the European IDES hip registry. The database query resulted in 1819 patients with 5801 follow-ups treated with bilateral THA between 1965 and 2002. According to the timing of the two operations the sample was divided into three groups: I) 247 patients with simultaneous bilateral THA, II) 737 patients with two-stage bilateral THA within six months, III) 835 patients with two-stage bilateral THA between six months and five years.</p> <p>Results</p> <p>Whereas postoperative hip pain and flexion did not differ between the groups, the best walking capacity was observed in group I and the worst in group III. The rate of intraoperative complications in the first group was comparable to that of the second. The frequency of postoperative local and systemic complication in group I was the lowest of the three groups. The highest rate of complications was observed in group III.</p> <p>Conclusions</p> <p>From the point of view of possible intra- and postoperative complications, one-stage bilateral THA is equally safe or safer than two-stage interventions. Additionally, from an outcome perspective the one-stage procedure can be considered to be advantageous.</p

Gestational Weight Gain and Body Mass Index in Children: Results from Three German Cohort Studies

Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring's body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear. We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring's mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5-6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status. In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m(2) of 'real' BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers. Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers

Swelling-Activated Ca2+ Channels Trigger Ca2+ Signals in Merkel Cells

Merkel cell-neurite complexes are highly sensitive touch receptors comprising epidermal Merkel cells and sensory afferents. Based on morphological and molecular studies, Merkel cells are proposed to be mechanosensory cells that signal afferents via neurotransmission; however, functional studies testing this hypothesis in intact skin have produced conflicting results. To test this model in a simplified system, we asked whether purified Merkel cells are directly activated by mechanical stimulation. Cell shape was manipulated with anisotonic solution changes and responses were monitored by Ca2+ imaging with fura-2. We found that hypotonic-induced cell swelling, but not hypertonic solutions, triggered cytoplasmic Ca2+ transients. Several lines of evidence indicate that these signals arise from swelling-activated Ca2+-permeable ion channels. First, transients were reversibly abolished by chelating extracellular Ca2+, demonstrating a requirement for Ca2+ influx across the plasma membrane. Second, Ca2+ transients were initially observed near the plasma membrane in cytoplasmic processes. Third, voltage-activated Ca2+ channel (VACC) antagonists reduced transients by half, suggesting that swelling-activated channels depolarize plasma membranes to activate VACCs. Finally, emptying internal Ca2+ stores attenuated transients by 80%, suggesting Ca2+ release from stores augments swelling-activated Ca2+ signals. To identify candidate mechanotransduction channels, we used RT-PCR to amplify ion-channel transcripts whose pharmacological profiles matched those of hypotonic-evoked Ca2+ signals in Merkel cells. We found 11 amplicons, including PKD1, PKD2, and TRPC1, channels previously implicated in mechanotransduction in other cells. Collectively, these results directly demonstrate that Merkel cells are activated by hypotonic-evoked swelling, identify cellular signaling mechanisms that mediate these responses, and support the hypothesis that Merkel cells contribute to touch reception in the Merkel cell-neurite complex