Towards multi-scale dynamics on the baryonic branch of Klebanov-Strassler

We construct explicitly a new class of backgrounds in type-IIB supergravity which generalize the baryonic branch of Klebanov-Strassler. We apply a solution-generating technique that, starting from a large class of solutions of the wrapped-D5 system, yields the new solutions, and then proceed to study in detail their properties, both in the IR and in the UV. We propose a simple intuitive field theory interpretation of the rotation procedure and of the meaning of our new solutions within the Papadopoulos-Tseytlin ansatz, in particular in relation to the duality cascade in the Klebanov-Strassler solution. The presence in the field theory of different VEVs for operators of dimensions 2, 3 and 6 suggests that this is an important step towards the construction of the string dual of a genuinely multi-scale (strongly coupled) dynamical model.Comment: 37 pages, 7 figures. References added, version to appear in JHE

Comparison of Population-Based Association Study Methods Correcting for Population Stratification

Population stratification can cause spurious associations in population–based association studies. Several statistical methods have been proposed to reduce the impact of population stratification on population–based association studies. We simulated a set of stratified populations based on the real haplotype data from the HapMap ENCODE project, and compared the relative power, type I error rates, accuracy and positive prediction value of four prevailing population–based association study methods: traditional case-control tests, structured association (SA), genomic control (GC) and principal components analysis (PCA) under various population stratification levels. Additionally, we evaluated the effects of sample sizes and frequencies of disease susceptible allele on the performance of the four analytical methods in the presence of population stratification. We found that the performance of PCA was very stable under various scenarios. Our comparison results suggest that SA and PCA have comparable performance, if sufficient ancestral informative markers are used in SA analysis. GC appeared to be strongly conservative in significantly stratified populations. It may be better to apply GC in the stratified populations with low stratification level. Our study intends to provide a practical guideline for researchers to select proper study methods and make appropriate inference of the results in population-based association studies

Serum 25-Hydroxyvitamin D and Risk of Lung Cancer in Male Smokers: A Nested Case-Control Study

A role for vitamin D in cancer risk reduction has been hypothesized, but few data exist for lung cancer. We investigated the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25(OH)D], and lung cancer risk in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers.Lung cancer cases (n = 500) were randomly selected based on month of blood collection, and 500 controls were matched to them based on age and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate-adjusted conditional logistic regression. To account for seasonal variation in 25(OH)D concentrations, season-specific and season-standardized quintiles of 25(OH)D were examined, and models were also stratified on season of blood collection (darker season = November-April and sunnier season = May-October). Pre-determined, clinically-defined cutpoints for 25(OH)D and 25(OH)D as a continuous measure were also examined.Overall, 25(OH)D was not associated with lung cancer. Risks were 1.08 (95% CI 0.67-1.75) and 0.83 (95% CI 0.53-1.31) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.91 (95% CI 0.48-1.72) for the ≥75 vs. <25 nmol/L clinical categories. Inverse associations were, however, suggested for subjects with blood collections from November-April, with ORs of 0.77 (95% CI 0.41-1.45, p-trend = 0.05) and 0.65 (95% CI 0.37-1.14, p-trend = 0.07) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.61 (95% CI 0.24-1.52, p-trend = 0.01) for ≥75 vs. <25 nmol/L. We also found 11% lower risk for a 10 nmol/L increase in 25(OH)D in the darker season based on the continuous measure (OR = 0.89, 95% CI 0.81-0.98, p = 0.02).In this prospective study of male smokers, circulating 25(OH)D was not associated with lung cancer risk overall, although inverse associations were suggested among those whose blood was drawn during darker months

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises

Cohort differences in disease and disability in the young-old: findings from the MRC Cognitive Function and Ageing Study (MRC-CFAS)

© 2007 Jagger et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Metastatic progression due to development or enrichment of therapy-resistant tumor cells is eventually lethal. Molecular characterization of such chemotherapy resistant tumor cell clones may identify markers responsible for malignant progression and potential targets for new treatment. Here, in a case of stage IV adenocarcinoma of the gastroesophageal junction, we report the successful genome wide analysis using array comparative genomic hybridization (CGH) of DNA from only fourteen tumor cells using a bead-based single cell selection method from a bone metastasis progressing during chemotherapy.</p> <p>Case presentation</p> <p>In a case of metastatic adenocarcinoma of the gastroesophageal junction, the progression of bone metastasis was observed during a chemotherapy regimen of epirubicin, oxaliplatin and capecitabine, whereas lung-, liver and lymph node metastases as well as the primary tumor were regressing. A bone marrow aspirate sampled at the site of progressing metastasis in the right iliac bone was performed, and single cell molecular analysis using array-CGH of Epithelial Specific Antigen (ESA)-positive metastatic cells, and revealed two distinct regions of amplification, 12p12.1 and 17q12-q21.2 amplicons, containing the KRAS (12p) and ERBB2 (HER2/NEU) (17q) oncogenes. Further intrapatient tumor heterogeneity of these highlighted gene copy number changes was analyzed by fluorescence in situ hybridization (FISH) in all available primary and metastatic tumor biopsies, and ErbB2 protein expression was investigated by immunohistochemistry.</p> <p>ERBB2 was heterogeneously amplified by FISH analysis in the primary tumor, as well as liver and bone metastasis, but homogenously amplified in biopsy specimens from a progressing bone metastasis after three initial cycles of chemotherapy, indicating a possible enrichment of erbB2 positive tumor cells in the progressing bone marrow metastasis during chemotherapy. A similar amplification profile was detected for wild-type KRAS, although more heterogeneously expressed in the bone metastasis progressing on chemotherapy. Correspondingly, the erbB2 protein was found heterogeneously expressed by immunohistochemical staining of the primary tumor of the gastroesophageal junction, while negative in liver and bone metastases, but after three initial cycles of palliative chemotherapy with epirubicin, oxaliplatin and capecetabine, the representative bone metastasis stained strongly positive for erbB2.</p> <p>Conclusion</p> <p>Global analysis of genetic aberrations, as illustrated by performing array-CGH analysis on genomic DNA from only a few selected tumor cells of interest sampled from a progressing bone metastasis, can identify relevant therapeutic targets and genetic aberrations involved in malignant progression, thus emphasizing the importance and feasibility of this powerful tool on the road to more personalized cancer therapies in the future.</p

Policy challenges for the pediatric rheumatology workforce: Part I. Education and economics

For children with rheumatic conditions, the available pediatric rheumatology workforce mitigates their access to care. While the subspecialty experiences steady growth, a critical workforce shortage constrains access. This three-part review proposes both national and international interim policy solutions for the multiple causes of the existing unacceptable shortfall. Part I explores the impact of current educational deficits and economic obstacles which constrain appropriate access to care. Proposed policy solutions follow each identified barrier

Shape similarity, better than semantic membership, accounts for the structure of visual object representations in a population of monkey inferotemporal neurons

The anterior inferotemporal cortex (IT) is the highest stage along the hierarchy of visual areas that, in primates, processes visual objects. Although several lines of evidence suggest that IT primarily represents visual shape information, some recent studies have argued that neuronal ensembles in IT code the semantic membership of visual objects (i.e., represent conceptual classes such as animate and inanimate objects). In this study, we investigated to what extent semantic, rather than purely visual information, is represented in IT by performing a multivariate analysis of IT responses to a set of visual objects. By relying on a variety of machine-learning approaches (including a cutting-edge clustering algorithm that has been recently developed in the domain of statistical physics), we found that, in most instances, IT representation of visual objects is accounted for by their similarity at the level of shape or, more surprisingly, low-level visual properties. Only in a few cases we observed IT representations of semantic classes that were not explainable by the visual similarity of their members. Overall, these findings reassert the primary function of IT as a conveyor of explicit visual shape information, and reveal that low-level visual properties are represented in IT to a greater extent than previously appreciated. In addition, our work demonstrates how combining a variety of state-of-the-art multivariate approaches, and carefully estimating the contribution of shape similarity to the representation of object categories, can substantially advance our understanding of neuronal coding of visual objects in cortex

G12/13 Signaling Pathways Substitute for Integrin αIIbβ3-Signaling for Thromboxane Generation in Platelets

We have previously shown that ADP-induced TXA(2) generation requires signaling from αIIbβ3 integrin in platelets. Here we observed that, unlike ADP, protease-activated receptor (PAR)-mediated TXA(2) generation occurs independently of αIIbβ3. PAR agonists, but not ADP, activate G(12/13) signaling pathways. Hence, we evaluated the role of these pathways in TXA(2) generation.Inhibition of ADP-induced thromboxane generation by fibrinogen receptor antagonist SC57101 was rescued by co-stimulation of G(12/13) pathways with YFLLRNP. This observation suggested an existence of a common signaling effector downstream of integrins and G(12/13) pathways. Hence, we evaluated role of three potential tyrosine kinases; c-Src, Syk and FAK (Focal Adhesion Kinase) that are known to be activated by integrins. c-Src and Syk kinase did not play a role in ADP-induced functional responses in platelets. Selective activation of G(12/13) pathways resulted in the activation of FAK, in the absence of integrin signaling. Interestingly, αIIbβ3-mediated FAK activation occurred in a Src family kinase (SFK)-independent manner whereas G(12/13) pathway caused FAK activation in a SFK and RhoA-dependent manner. A FAK selective inhibitor TAE-226, blocked TXA(2) generation. However, in comparison to WT mice, Pf4-Cre/Fak-Floxed mice did not show any difference in platelet TXA(2) generation.Therefore, we conclude that differential activation of FAK occurs downstream of Integrins and G(12/13) pathways. However, the common effector molecule, possibly a tyrosine kinase downstream of integrins and G(12/13) pathways contributing to TXA(2) generation in platelets remains elusive