Statistical Inference for Valued-Edge Networks: Generalized Exponential Random Graph Models

Across the sciences, the statistical analysis of networks is central to the production of knowledge on relational phenomena. Because of their ability to model the structural generation of networks, exponential random graph models are a ubiquitous means of analysis. However, they are limited by an inability to model networks with valued edges. We solve this problem by introducing a class of generalized exponential random graph models capable of modeling networks whose edges are valued, thus greatly expanding the scope of networks applied researchers can subject to statistical analysis

Formation of unique nanocrystalline Cu-In-Se bulk pn homojunctions for opto-electronic devices

Semiconductor pn junctions, integrated in optoelectronic devices require high quality crystals, made by expensive, technically difficult processes. Bulk heterojunction (BHJ) structures offer practical alternatives to circumvent the cost, flexibility and scale-up challenges of crystalline planar pn junctions. Fabrication methods for the current organic or inorganic BHJ structures invariably create interface mismatch and low doping issues. To overcome such issues, we devised an innovative approach, founded on novel inorganic material system that ensued from single-step electrodeposited copper-indium-selenide compounds. Surface analytical microscopies and spectroscopies reveal unusual phenomena, electro-optical properties and quantum effects. They support the formation of highly-ordered, sharp, abrupt 3-dimensional nanoscale pn BHJs that facilitate efficient charge carrier separation and transport, and essentially perform the same functions as crystalline planar pn junctions. This approach offers a low-cost processing platform to create nanocrystalline films, with the attributes necessary for efficient BHJ operation. It allows roll-to-roll processing of flexible devices in simple thin-film form factor.Partial funding for this work is provided by customers of Xcel Energy through a grant from the Renewable Development Fund. The authors gratefully acknowledge sample preparation, analytical contributions and useful discussions with Sharmila Menezes and Yan Li (InterPhases Solar); Senli Guo (Brucker Nano); Terrence McGuckin (Ephemeron Labs); and Nassim Rahimi (HORIBA Scientific). A. Samantilleke acknowledges Prof. L. M. Peter (Bath University, UK) for introducing EER technique

GBR 12909 administration as a mouse model of bipolar disorder mania: mimicking quantitative assessment of manic behavior

Mania is a core feature of bipolar disorder (BD) that traditionally is assessed using rating scales. Studies using a new human behavioral pattern monitor (BPM) recently demonstrated that manic BD patients exhibit a specific profile of behavior that differs from schizophrenia and is characterized by increased motor activity, increased specific exploration, and perseverative locomotor patterns as assessed by spatial d. It was hypothesized that disrupting dopaminergic homeostasis by inhibiting dopamine transporter (DAT) function would produce a BD mania-like phenotype in mice as assessed by the mouse BPM. We compared the spontaneous locomotor and exploratory behavior of C57BL/6J mice treated with the catecholamine transporter inhibitor amphetamine or the selective DAT inhibitor GBR 12909 in the mouse BPM. We also assessed the duration of the effect of GBR 12909 by testing mice in the BPM for 3 h and its potential strain dependency by testing 129/SvJ mice. Amphetamine produced hyperactivity and increased perseverative patterns of locomotion as reflected in reduced spatial d values but reduced exploratory activity in contrast to the increased exploration observed in BD patients. GBR 12909 increased activity and reduced spatial d in combination with increased exploratory behavior, irrespective of inbred strain. These effects persisted for at least 3 h. Thus, selectively inhibiting the DAT produced a long-lasting cross-strain behavioral profile in mice that was consistent with that observed in manic BD patients. These findings support the use of selective DAT inhibition in animal models of the impaired dopaminergic homeostasis putatively involved in the pathophysiology of BD mania

Use of dietary supplements in Olympic athletes is decreasing: a follow-up study between 2002 and 2009

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the frequency of use of dietary supplements (DS) among large sample of elite Finnish athletes and to describe possible changes in dietary supplement use between the years 2002 and 2009.</p> <p>Methods</p> <p>A prospective follow-up study was conducted on Olympic athletes. The first survey was conducted on Olympic athletes in 2002 (N = 446) and the follow-up study was conducted between May 2008 and June 2009 (N = 372).</p> <p>Results</p> <p>In 2002, a total of 81% of the athletes used dietary supplements (a mean of 3.37 ± 3.06 DS per user) and in 2009, a total of 73% of the athletes (a mean of 2.60 ± 2.69 per DS user) used them. After adjusting for age-, sex- and sport type, the OR (95% confidence interval, CI) for use of any dietary supplement was significantly less in 2009 as compared with 2002 results (OR, 0.62; 95% CI, 0.43-0.90). Decrease in DS use was observed in all supplement subgroups (vitamins, minerals, nutritional supplements). Athletes in speed and power events and endurance events reported use of any dietary supplement significantly more often than team sport athletes both in 2002 and 2009. In year 2009, the frequency of all dietary supplement use increased when athlete's age increased and the increase was significant in older age groups: of the athletes under 21 years 63%, 21-24 years 83% and over 24 years 90% consumed nutritional supplements.</p> <p>Conclusions</p> <p>Based in our study, there seems to be a lowering trend of dietary supplement use among elite Finnish athletes although differences between sport subgroups and age groups are considerable.</p

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Many-particle Brownian and Langevin Dynamics Simulations with the Brownmove package

<p>Abstract</p> <p>Background</p> <p>Brownian Dynamics (BD) is a coarse-grained implicit-solvent simulation method that is routinely used to investigate binary protein association dynamics, but due to its efficiency in handling large simulation volumes and particle numbers it is well suited to also describe many-protein scenarios as they often occur in biological cells.</p> <p>Results</p> <p>Here we introduce our "brownmove" simulation package which was designed to handle many-particle problems with varying particle numbers and allows for a very flexible definition of rigid and flexible protein and polymer models. Both a Brownian and a Langevin dynamics (LD) propagation scheme can be used and hydrodynamic interactions are treated efficiently with our recently introduced TEA-HI ansatz [Geyer, Winter, JCP 130 (2009) 114905]. With simulations of constrained polymers and flexible models of spherical proteins we demonstrate that it is crucial to include hydrodynamics when multi-bead models are used in BD or LD simulations. Only then both the translational and the rotational diffusion coefficients and the timescales of the internal dynamics can be reproduced correctly. In the third example project we show how constant density boundary conditions [Geyer et al, JCP 120 (2004) 4573] can be used to set up a non-equilibrium simulation of diffusional transport across an array of fixed obstacles. Finally, we demonstrate how the agglomeration dynamics of multiple particles with attractive patches can be analysed conveniently with the help of a dynamic interaction network.</p> <p>Conclusions</p> <p>Combining BD and LD propagation, fast hydrodynamics, a flexible protein model, and interfaces for "open" simulation settings, our freely available "brownmove" simulation package constitutes a new platform for coarse-grained many-particle simulations of biologically relevant diffusion and transport processes.</p

Nef Alleles from All Major HIV-1 Clades Activate Src-Family Kinases and Enhance HIV-1 Replication in an Inhibitor-Sensitive Manner

The HIV-1 accessory factor Nef is essential for high-titer viral replication and AIDS progression. Nef function requires interaction with many host cell proteins, including specific members of the Src kinase family. Here we explored whether Src-family kinase activation is a conserved property of Nef alleles from a wide range of primary HIV-1 isolates and their sensitivity to selective pharmacological inhibitors. Representative Nef proteins from the major HIV-1 subtypes A1, A2, B, C, F1, F2, G, H, J and K strongly activated Hck and Lyn as well as c-Src to a lesser extent, demonstrating for the first time that Src-family kinase activation is a highly conserved property of primary M-group HIV-1 Nef isolates. Recently, we identified 4-amino substituted diphenylfuropyrimidines (DFPs) that selectively inhibit Nef-dependent activation of Src-family kinases as well as HIV replication. To determine whether DFP compounds exhibit broad-spectrum Nef-dependent antiretroviral activity against HIV-1, we first constructed chimeric forms of the HIV-1 strain NL4-3 expressing each of the primary Nef alleles. The infectivity and replication of these Nef chimeras was indistinguishable from that of wild-type virus in two distinct cell lines (U87MG astroglial cells and CEM-T4 lymphoblasts). Importantly, the 4-aminopropanol and 4-aminobutanol derivatives of DFP potently inhibited the replication of all chimeric forms of HIV-1 in both U87MG and CEM-T4 cells in a Nef-dependent manner. The antiretroviral effects of these compounds correlated with inhibition of Nef-dependent activation of endogenous Src-family kinases in the HIV-infected cells. Our results demonstrate that the activation of Hck, Lyn and c-Src by Nef is highly conserved among all major clades of HIV-1 and that selective targeting of this pathway uniformly inhibits HIV-1 replication

Overexpression of Reelin Prevents the Manifestation of Behavioral Phenotypes Related to Schizophrenia and Bipolar Disorder

Despite the impact of schizophrenia and mood disorders, which in extreme cases can lead to death, recent decades have brought little progress in the development of new treatments. Recent studies have shown that Reelin, an extracellular protein that is critical for neuronal development, is reduced in schizophrenia and bipolar disorder patients. However, data on a causal or protective role of Reelin in psychiatric diseases is scarce. In order to study the direct influence of Reelin's levels on behavior, we subjected two mouse lines, in which Reelin levels are either reduced (Reelin heterozygous mice) or increased (Reelin overexpressing mice), to a battery of behavioral tests: open-field, black–white box, novelty-suppressed-feeding, forced-swim-test, chronic corticosterone treatment followed by forced-swim-test, cocaine sensitization and pre-pulse inhibition (PPI) deficits induced by N-methyl--aspartate (NMDA) antagonists. These tests were designed to model some aspects of psychiatric disorders such as schizophrenia, mood, and anxiety disorders. We found no differences between Reeler heterozygous mice and their wild-type littermates. However, Reelin overexpression in the mouse forebrain reduced the time spent floating in the forced-swim-test in mice subjected to chronic corticosterone treatment, reduced behavioral sensitization to cocaine, and reduced PPI deficits induced by a NMDA antagonist. In addition, we demonstrate that while stress increased NMDA NR2B-mediated synaptic transmission, known to be implicated in depression, Reelin overexpression significantly reduced it. Together, these results point to the Reelin signaling pathway as a relevant drug target for the treatment of a range of psychiatric disorders