The Hydrodynamics of M-Theory

We consider the low energy limit of a stack of N M-branes at finite temperature. In this limit, the M-branes are well described, via the AdS/CFT correspondence, in terms of classical solutions to the eleven dimensional supergravity equations of motion. We calculate Minkowski space two-point functions on these M-branes in the long-distance, low-frequency limit, i.e. the hydrodynamic limit, using the prescription of Son and Starinets [hep-th/0205051]. From these Green's functions for the R-currents and for components of the stress-energy tensor, we extract two kinds of diffusion constant and a viscosity. The N dependence of these physical quantities may help lead to a better understanding of M-branes.Comment: 1+19 pages, references added, section 5 clarified, eq. (72) correcte

Gene expression patterns that predict sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer cell lines and human lung tumors

BACKGROUND: Increased focus surrounds identifying patients with advanced non-small cell lung cancer (NSCLC) who will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). EGFR mutation, gene copy number, coexpression of ErbB proteins and ligands, and epithelial to mesenchymal transition markers all correlate with EGFR TKI sensitivity, and while prediction of sensitivity using any one of the markers does identify responders, individual markers do not encompass all potential responders due to high levels of inter-patient and inter-tumor variability. We hypothesized that a multivariate predictor of EGFR TKI sensitivity based on gene expression data would offer a clinically useful method of accounting for the increased variability inherent in predicting response to EGFR TKI and for elucidation of mechanisms of aberrant EGFR signalling. Furthermore, we anticipated that this methodology would result in improved predictions compared to single parameters alone both in vitro and in vivo. RESULTS: Gene expression data derived from cell lines that demonstrate differential sensitivity to EGFR TKI, such as erlotinib, were used to generate models for a priori prediction of response. The gene expression signature of EGFR TKI sensitivity displays significant biological relevance in lung cancer biology in that pertinent signalling molecules and downstream effector molecules are present in the signature. Diagonal linear discriminant analysis using this gene signature was highly effective in classifying out-of-sample cancer cell lines by sensitivity to EGFR inhibition, and was more accurate than classifying by mutational status alone. Using the same predictor, we classified human lung adenocarcinomas and captured the majority of tumors with high levels of EGFR activation as well as those harbouring activating mutations in the kinase domain. We have demonstrated that predictive models of EGFR TKI sensitivity can classify both out-of-sample cell lines and lung adenocarcinomas. CONCLUSION: These data suggest that multivariate predictors of response to EGFR TKI have potential for clinical use and likely provide a robust and accurate predictor of EGFR TKI sensitivity that is not achieved with single biomarkers or clinical characteristics in non-small cell lung cancers

The role of discharge variability in determining alluvial stratigraphy

We illustrate the potential for using physics-based modeling to link alluvial stratigraphy to large river morphology and dynamics. Model simulations, validated using ground penetrating radar data from the Río Paraná, Argentina, demonstrate a strong relationship between bar-scale set thickness and channel depth, which applies across a wide range of river patterns and bar types. We show that hydrologic regime, indexed by discharge variability and flood duration, exerts a first-order influence on morphodynamics and hence bar set thickness, and that planform morphology alone may be a misleading variable for interpreting deposits. Indeed, our results illustrate that rivers evolving under contrasting hydrologic regimes may have very similar morphology, yet be characterized by marked differences in stratigraphy. This realization represents an important limitation on the application of established theory that links river topography to alluvial deposits, and highlights the need to obtain field evidence of discharge variability when developing paleoenvironmental reconstructions. Model simulations demonstrate the potential for deriving such evidence using metrics of paleocurrent variance

Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes

Objective— The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. Approach and Results— We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. Conclusions— We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels

Stationary Configurations Imply Shift Symmetry: No Bondi Accretion for Quintessence / k-Essence

In this paper we show that, for general scalar fields, stationary configurations are possible for shift symmetric theories only. This symmetry with respect to constant translations in field space should either be manifest in the original field variables or reveal itself after an appropriate field redefinition. In particular this result implies that neither k-Essence nor Quintessence can have exact steady state / Bondi accretion onto Black Holes. We also discuss the role of field redefinitions in k-Essence theories. Here we study the transformation properties of observables and other variables in k-Essence and emphasize which of them are covariant under field redefinitions. Finally we find that stationary field configurations are necessarily linear in Killing time, provided that shift symmetry is realized in terms of these field variables.Comment: 8 page

Gender Differences in Leg Stiffness and Stiffness Recruitment Strategy During Two-Legged Hopping

The authors compared leg stiffness (KVERT), muscle activation, and joint movement patterns between 11 men and 10 women during hopping. Physically active and healthy men and women performed continuous 2-legged hopping at their preferred rate and at 3.0 Hz. Compared with men, women demonstrated decreased KVERT; however, after the authors normalized for body mass, gender differences in KVERT were eliminated. In comparison with men, women also demonstrated increased quadriceps and soleus activity, as well as greater quadriceps-to-hamstrings coactivation ratios. There were no significant gender differences for joint movement patterns (p > .05). The relationship between the observed gender differences in muscle recruitment and the increased risk of anterior cruciate ligament injury in women requires further study

The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin

AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3) and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1). Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD) and schizophrenia (SZ); yet its localization and function in neurons have not been described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic spines, and synapses, colocalizing preferentially with markers of early and recycling endosomes. Functional studies reveal overexpression and down-regulation of AGAP1 affects both neuronal endosomal trafficking and dendritic spine morphology, supporting a role for AGAP1 in the recycling endosomal trafficking involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1 expression to mutations in the DTNBP1 gene, which is associated with neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are selectively reduced in the null allele of the mouse orthologue of DTNBP1. We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function

Enteral Feeding with Human Milk Decreases Time to Discharge in Infants following Gastroschisis Repair

We reviewed a multi-institutional database to assess the effect of enteral feeding with human milk on duration from initiation of feeds to discharge after gastroschisis repair

Patients’ Perspectives, Experiences, and Concerns With Perianal Fistulae:Insights From Online Targeted-Disease Forums

Background: Perianal fistulae can undermine physical, emotional, and social well-being in patients with Crohn’s disease and are challenging to manage. Social media offers a rich opportunity to gain an in-depth understanding of the impact of perianal fistulae on patients’ daily lives outside of controlled environments. In this study, we conducted social media analytics to examine patients’ experiences with perianal fistulae and assessed the impact of perianal fistulae on patients’ behavior and overall well-being. Methods: We used a mixed-method approach to examine 119 986 publicly available posts collected from 10 Crohn’s disease forums in the United States between January 01, 2010 and January 01, 2020. Discussions related to Crohn’s perianal fistulae were retrieved. We randomly selected 700 posts and qualitatively analyzed them using an inductive thematic approach. We then applied a latent Dirichlet allocation probabilistic topic model to explore themes in an unsupervised manner on the collection of 119 986 posts. Results: In the qualitative analysis, 5 major themes were identified: (1) burden of perianal fistula; (2) challenges associated with treatment; (3) online information seeking and sharing; (4) patient experiences with treatments; and (5) patients’ apprehension about treatments. In the quantitative analysis, the percentages of posts related to the major themes were (1) 20%, (2) 29%, (3) 66%, and (4) 28%, while the topic model did not identify theme 5. Conclusions: Social media reveals a dynamic range of themes governing patients’ perspectives and experiences with Crohn’s perianal fistulae. In addition to the biopsychosocial burden, patients frequently express dissatisfaction with current treatments and often struggle to navigate among available management options.</p

Importance of transient resonances in extreme-mass-ratio inspirals

The inspiral of stellar-mass compact objects, like neutron stars or stellar-mass black holes, into supermassive black holes provides a wealth of information about the strong gravitational-field regime via the emission of gravitational waves. In order to detect and analyse these signals, accurate waveform templates which include the effects of the compact object's gravitational self-force are required. For computational efficiency, adiabatic templates are often used. These accurately reproduce orbit-averaged trajectories arising from the first-order self-force, but neglect other effects, such as transient resonances, where the radial and poloidal fundamental frequencies become commensurate. During such resonances the flux of gravitational waves can be diminished or enhanced, leading to a shift in the compact object's trajectory and the phase of the waveform. We present an evolution scheme for studying the effects of transient resonances and apply this to an astrophysically motivated population. We find that a large proportion of systems encounter a low-order resonance in the later stages of inspiral; however, the resulting effect on signal-to-noise recovery is small as a consequence of the low eccentricity of the inspirals. Neglecting the effects of transient resonances leads to a loss of 4% of detectable signals.Comment: 24 pages, 12 figures, 2 appendices; changes to match published versio