Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRβ.

Mechanisms underlying the development of idiopathic dilated cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor-β (ESRRβ), a member of the nuclear receptor family of transcription factors, as highly expressed in murine hearts and other highly oxidative striated muscle beds. Mice bearing cardiac-specific deletion of ESRRβ (MHC-ERRB KO) develop DCM and sudden death at ~10 mo of age. Isolated adult cardiomyocytes from the MHC-ERRB KO mice showed an increase in calcium sensitivity and impaired cardiomyocyte contractility, which preceded echocardiographic cardiac remodeling and dysfunction by several months. Histological analyses of myocardial biopsies from patients with various cardiomyopathies revealed that ESRRβ protein is absent from the nucleus of cardiomyocytes from patients with DCM but not other forms of cardiomyopathy (ischemic, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy). Taken together these observations suggest that ESRRβ is a critical component in the onset of DCM by affecting contractility and calcium balance.NEW & NOTEWORTHY Estrogen-related receptor-β (ESRRβ) is highly expressed in the heart and cardiac-specific deletion results in the development of a dilated cardiomyopathy (DCM). ESRRβ is mislocalized in human myocardium samples with DCM, suggesting a possible role for ESRRβ in the pathogenesis of DCM in humans

Modeling and simulation of nanofluid transport via elastic sheets

The field of nanofluidics research has spanned over the past decade with a variety of promising applications. We investigate the ``laminar boundary layer flow’’ of a Newtonian nanofluid past a moving extendable/contractable horizontal plate with surface velocity and thermal slip effects. The passively controlled nanofluid model (PCM) is considered. Such models are physically more realistic as compared to the “actively controlled models” (ACM). Using Lie symmetry group method, the governing equations are reduced by a set of highly coupled nonlinear ODE’s with thermo-solutal coupled boundary conditions. The reduced equations are solved numerically by a generalized collocation method. The influences of the emerging parameters on the local skin friction factor and the local Nusselt number are depicted numerically. The skin friction is decreased as the thermo-phoresis and buoyancy ratio parameters are decreased. The heat transfer rates reduce with thermophoresis and buoyancy ratio parameters. Velocity slip also leads to a rise in wall temperature gradient. This study is relevant to near-wall flows in nanofluid fuel cells, nano-materials processing et

Quasi-normal frequencies: Key analytic results

The study of exact quasi-normal modes [QNMs], and their associated quasi-normal frequencies [QNFs], has had a long and convoluted history - replete with many rediscoveries of previously known results. In this article we shall collect and survey a number of known analytic results, and develop several new analytic results - specifically we shall provide several new QNF results and estimates, in a form amenable for comparison with the extant literature. Apart from their intrinsic interest, these exact and approximate results serve as a backdrop and a consistency check on ongoing efforts to find general model-independent estimates for QNFs, and general model-independent bounds on transmission probabilities. Our calculations also provide yet another physics application of the Lambert W function. These ideas have relevance to fields as diverse as black hole physics, (where they are related to the damped oscillations of astrophysical black holes, to greybody factors for the Hawking radiation, and to more speculative state-counting models for the Bekenstein entropy), to quantum field theory (where they are related to Casimir energies in unbounded systems), through to condensed matter physics, (where one may literally be interested in an electron tunelling through a physical barrier).Comment: V1: 29 pages; V2: Reformatted, 31 pages. Title changed to reflect major additions and revisions. Now describes exact QNFs for the double-delta potential in terms of the Lambert W function. V3: Minor edits for clarity. Four references added. No physics changes. Still 31 page

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

PGB pair production at LHC and ILC as a probe of the topcolor-assisted technicolor models

The topcolor-assisted technicolor (TC2) model predicts some light pseudo goldstone bosons (PGBs), which may be accessible at the LHC or ILC. In this work we study the pair productions of the charged or neutral PGBs at the LHC and ILC. For the productions at the LHC we consider the processes proceeding through gluon-gluon fusion and quark-antiquark annihilation, while for the productions at the ILC we consider both the electron-positron collision and the photon-photon collision. We find that in a large part of parameter space the production cross sections at both colliders can be quite large compared with the low standard model backgrounds. Therefore, in future experiments these productions may be detectable and allow for probing TC2 model.Comment: 26 pages, 16 figures. slight changes in the text; notations for curves changed; references adde

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Group-based memory rehabilitation for people with multiple sclerosis: subgroup analysis of the ReMiND trial

Background/Aim: Memory problems are frequently reported in people with multiple sclerosis (MS). These can be debilitating and affect individuals and their families. This sub-group analysis focused on the effectiveness of memory rehabilitation in patients with MS. Methods: Data were extracted from a single blind randomised controlled trial, the ReMiND trial, which also included participants with traumatic brain injury and stroke. Participants were randomly allocated to compensation or restitution treatment programmes, or a self-help control. The programmes were manual-based and comprised two individual and ten group sessions. Outcome measures included assessments of memory, mood and activities of daily living. A total of 39 patients with MS participated in this study (ten males (26%), 29 females (74%); mean±SD age: 48.3±10.8 years). Results: Comparison of groups showed no significant effect of treatment on memory, but there were significant differences between compensation and restitution on self-report symptoms of emotional distress at both 5- (p=0.04) and 7-month (p=0.05) follow-up sessions. The compensation group showed less distress than the restitution group. Conclusions: Individuals with MS who received compensation memory rehabilitation reported significantly less emotional distress than those who received restitution. Further research is needed to explore why self-reported memory problems did not differ between groups

Semi-analytic results for quasi-normal frequencies

The last decade has seen considerable interest in the quasi-normal frequencies [QNFs] of black holes (and even wormholes), both asymptotically flat and with cosmological horizons. There is wide agreement that the QNFs are often of the form omega_n = (offset) + i n (gap), though some authors have encountered situations where this behaviour seems to fail. To get a better understanding of the general situation we consider a semi-analytic model based on a piecewise Eckart (Poeschl-Teller) potential, allowing for different heights and different rates of exponential falloff in the two asymptotic directions. This model is sufficiently general to capture and display key features of the black hole QNFs while simultaneously being analytically tractable, at least for asymptotically large imaginary parts of the QNFs. We shall derive an appropriate "quantization condition" for the asymptotic QNFs, and extract as much analytic information as possible. In particular, we shall explicitly verify that the (offset)+ i n (gap) behaviour is common but not universal, with this behaviour failing unless the ratio of rates of exponential falloff on the two sides of the potential is a rational number. (This is "common but not universal" in the sense that the rational numbers are dense in the reals.) We argue that this behaviour is likely to persist for black holes with cosmological horizons.Comment: V1: 28 pages, no figures. V2: 3 references added, no physics changes. V3: 29 pages, 9 references added, no physics changes; V4: reformatted, now 27 pages. Some clarifications, comparison with results obtained by monodromy techniques. This version accepted for publication in JHEP. V5: Minor typos fixed. Compatible with published versio

Coverage, Continuity and Visual Cortical Architecture

The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure

Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes

The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte transcriptional regulation.Singapore. Agency for Science, Technology and Research (National Science Scholarship )Massachusetts Institute of Technology (Eugene Bell Career Development Chair)National Science Foundation (U.S.) (Award No. DBI-0821391)Pfizer Inc