On the p,qp,q-binomial distribution and the Ising model

A completely new approach to the Ising model in 1 to 5 dimensions is developed. We employ $p,q$-binomial coefficients, a generalisation of the binomial coefficients, to describe the magnetisation distributions of the Ising model. For the complete graph this distribution corresponds exactly to the limit case $p=q$. We take our investigation to the simple $d$-dimensional lattices for $d=1,2,3,4,5$ and fit $p,q$-binomial distributions to our data, some of which are exact but most are sampled. For $d=1$ and $d=5$ the magnetisation distributions are remarkably well-fitted by $p,q$-binomial distributions. For $d=4$ we are only slightly less successful, while for $d=2,3$ we see some deviations (with exceptions!) between the $p,q$-binomial and the Ising distribution. We begin the paper by giving results on the behaviour of the $p,q$-distribution and its moment growth exponents given a certain parameterization of $p,q$. Since the moment exponents are known for the Ising model (or at least approximately for $d=3$) we can predict how $p,q$ should behave and compare this to our measured $p,q$. The results speak in favour of the $p,q$-binomial distribution's correctness regarding their general behaviour in comparison to the Ising model. The full extent to which they correctly model the Ising distribution is not settled though.Comment: 51 pages, 23 figures, submitted to PRB on Oct 23 200

IL-17A induces Pendrin expression and chloride-bicarbonate exchange in human bronchial epithelial cells

The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to a number of inflammatory diseases. Using microarray analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as a potential mediator of this effect. These data were verified by real-time, quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and immunofluorescence, we confirmed that Pendrin protein expression is increased in IL-17 treated HBE cells and that it is primarily localized to the mucosal surface of the cells. Functional studies using live-cell fluorescence to measure intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE cells treated with short interfering RNA against Pendrin showed substantially reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of IL-17A-dependent epithelial changes and that Pendrin may therefore be a therapeutic target in IL-17A-dependent lung disease. © 2014 Adams et al

Accelerated Global and Local Brain Aging Differentiate Cognitively Impaired From Cognitively Spared Patients With Schizophrenia

BACKGROUND: Accelerated aging has been proposed as a mechanism underlying the clinical and cognitive presentation of schizophrenia. The current study extends the field by examining both global and regional patterns of brain aging in schizophrenia, as inferred from brain structural data, and their association with cognitive and psychotic symptoms. METHODS: Global and local brain-age-gap-estimates (G-brainAGE and L-brainAGE) were computed using a U-Net Model from T(1)-weighted structural neuroimaging data from 84 patients (aged 16–35 years) with early-stage schizophrenia (illness duration <5 years) and 1,169 healthy individuals (aged 16–37 years). Multidomain cognitive data from the patient sample were submitted to Heterogeneity through Discriminative Analysis (HYDRA) to identify cognitive clusters. RESULTS: HYDRA classified patients into a cognitively impaired cluster (n = 69) and a cognitively spared cluster (n = 15). Compared to healthy individuals, G-brainAGE was significantly higher in the cognitively impaired cluster (+11.08 years) who also showed widespread elevation in L-brainAGE, with the highest deviance observed in frontal and temporal regions. The cognitively spared cluster showed a moderate increase in G-brainAGE (+8.94 years), and higher L-brainAGE localized in the anterior cingulate cortex. Psychotic symptom severity in both clusters showed a positive but non-significant association with G-brainAGE. DISCUSSION: Accelerated aging in schizophrenia can be detected at the early disease stages and appears more closely associated with cognitive dysfunction rather than clinical symptoms. Future studies replicating our findings in multi-site cohorts with larger numbers of participants are warranted

Mechanical Systems with Symmetry, Variational Principles, and Integration Algorithms

This paper studies variational principles for mechanical systems with symmetry and their applications to integration algorithms. We recall some general features of how to reduce variational principles in the presence of a symmetry group along with general features of integration algorithms for mechanical systems. Then we describe some integration algorithms based directly on variational principles using a discretization technique of Veselov. The general idea for these variational integrators is to directly discretize Hamilton’s principle rather than the equations of motion in a way that preserves the original systems invariants, notably the symplectic form and, via a discrete version of Noether’s theorem, the momentum map. The resulting mechanical integrators are second-order accurate, implicit, symplectic-momentum algorithms. We apply these integrators to the rigid body and the double spherical pendulum to show that the techniques are competitive with existing integrators

Role of Sirtuins in Modulating Neurodegeneration of the Enteric Nervous System and Central Nervous System.

Neurodegeneration of the central and enteric nervous systems is a common feature of aging and aging-related diseases, and is accelerated in individuals with metabolic dysfunction including obesity and diabetes. The molecular mechanisms of neurodegeneration in both the CNS and ENS are overlapping. Sirtuins are an important family of histone deacetylases that are important for genome stability, cellular response to stress, and nutrient and hormone sensing. They are activated by calorie restriction (CR) and by the coenzyme, nicotinamide adenine dinucleotide (NAD+). Sirtuins, specifically the nuclear SIRT1 and mitochondrial SIRT3, have been shown to have predominantly neuroprotective roles in the CNS while the cytoplasmic sirtuin, SIRT2 is largely associated with neurodegeneration. A systematic study of sirtuins in the ENS and their effect on enteric neuronal growth and survival has not been conducted. Recent studies, however, also link sirtuins with important hormones such as leptin, ghrelin, melatonin, and serotonin which influence many important processes including satiety, mood, circadian rhythm, and gut homeostasis. In this review, we address emerging roles of sirtuins in modulating the metabolic challenges from aging, obesity, and diabetes that lead to neurodegeneration in the ENS and CNS. We also highlight a novel role for sirtuins along the microbiota-gut-brain axis in modulating neurodegeneration

Double-peaked Narrow-Line Signatures of Dual Supermassive Black Holes in Galaxy Merger Simulations

We present a first attempt to model the narrow-line (NL) region of active galactic nuclei (AGN) in hydrodynamic simulations of galaxy mergers, using a novel physical prescription. This model is used to determine the origin of double-peaked NL (dNL) AGN in merging galaxies and their connection to supermassive black hole (SMBH) pairs, motivated by recent observations of such objects. We find that dNL AGN induced by the relative motion of SMBH pairs are a generic but short-lived feature of gaseous major mergers. dNL AGN should often be observed in late-stage mergers, during the kpc-scale phase of SMBH inspiral or soon after the SMBH merger. However, even within the kpc-scale phase, only a minority of dNL AGN are directly induced by SMBH motion; their lifetimes are typically a few Myr. Most double peaks arise from gas kinematics near the SMBH, although prior to the SMBH merger up to 80% of all dNL profiles may be influenced by SMBH motion via altered peak ratios or velocity offsets. The total lifetimes of dNL AGN depend strongly on viewing angle and on properties of the merging galaxies. Also, in a typical merger, at least 10-40% of the double peaks induced by SMBH motion have small projected separations, 0.1-1 kpc, such that dual peaks of stellar surface brightness are not easily resolved. Diffuse tidal features can indicate late-stage galaxy mergers, although they do not distinguish SMBH pairs from merged SMBHs. We show that dNL profiles with peak velocity splittings > 500 km s^-1 or with measurable overall velocity shifts are often associated with SMBH pairs. Our results support the notion that selection of dNL AGN is a promising method for identifying dual SMBH candidates, but demonstrate the critical importance of high-resolution, multi-wavelength follow-up observations, and the use of multiple lines of evidence, for confirming the dual nature of candidate SMBH pairs. (Abridged)Comment: 24 pages, 9 figures. Moderate revisions; accepted to MNRA