Accurate first-principle equation of state for the One-Component Plasma

Accurate "first-principle" expressions for the excess free energy $F_{ex}$ and internal energy $U_{ex}$ of the classical one-component plasma (OCP) are obtained. We use the Hubbard-Schofield transformation that maps the OCP Hamiltonian onto the Ising-like Hamiltonian, with coefficients expressed in terms of equilibrium correlation functions of a reference system. We use the ideal gas as a reference system for which all the correlation functions are known. Explicit calculations are performed with the high-order terms in the Ising-like Hamiltonian omitted. For small values of the plasma parameter $\Gamma$ the Debye-Huckel result for $F_{ex}$ and $U_{ex}$ is recovered. For large $\Gamma$ these depend linearly on $\Gamma$ in accordance with the Monte Carlo findings for the OCP. The MC data for the internal energy are reproduced fairly well by the obtained analytical expression.Comment: 15 pages, 2 figures, to appear in Contrib. Plasma Phys., v.38 N4, (1998

The 'not-so-strange' body in the mirror: : A principal components analysis of direct and mirror self-observation

This document is the Accepted Manuscript version of the following article: Paul M. Jenkinson, and Catherine Preston, ‘The “not-so-strange” body in the mirror: A principal components analysis of direct and mirror self-observation’, Consciousness and Cognition, Vol. 48, pp. 262-272, first published online 4 January 2017, doi: http://dx.doi.org/10.1016/j.concog.2016.12.007 This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.In this study we adopted a psychometric approach to examine how the body is subjectively experienced in a mirror. One hundred and twenty-four healthy participants viewed their body for five minutes directly or via a mirror, and then completed a 20-item questionnaire designed to capture subjective experiences of the body. PCA revealed a two-component structure for both direct and mirror conditions, comprising body evaluations (and alienation) and unusual feelings and perceptions. The relationship between these components and pre-existing tendencies for appearance anxiety, body dysmorphic-type beliefs, dissociative symptomatology, self-objectification and delusion ideation further supported the similarity between direct and mirror conditions; however, the occurrence of strange experiences like those reported to occur during prolonged face viewing was not confirmed. These results suggest that, despite obvious differences in visual feedback, observing the body via a mirror (as an outside observer) is subjectively equivalent to observing the body directly (from our own viewpoint).Peer reviewedFinal Accepted Versio

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents

The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt

Neuronal Plasticity and Multisensory Integration in Filial Imprinting

Many organisms sample their environment through multiple sensory systems and the integration of multisensory information enhances learning. However, the mechanisms underlying multisensory memory formation and their similarity to unisensory mechanisms remain unclear. Filial imprinting is one example in which experience is multisensory, and the mechanisms of unisensory neuronal plasticity are well established. We investigated the storage of audiovisual information through experience by comparing the activity of neurons in the intermediate and medial mesopallium of imprinted and naïve domestic chicks (Gallus gallus domesticus) in response to an audiovisual imprinting stimulus and novel object and their auditory and visual components. We find that imprinting enhanced the mean response magnitude of neurons to unisensory but not multisensory stimuli. Furthermore, imprinting enhanced responses to incongruent audiovisual stimuli comprised of mismatched auditory and visual components. Our results suggest that the effects of imprinting on the unisensory and multisensory responsiveness of IMM neurons differ and that IMM neurons may function to detect unexpected deviations from the audiovisual imprinting stimulus

A database application for pre-processing, storage and comparison of mass spectra derived from patients and controls.

BACKGROUND: Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest. RESULTS: A new database application is presented, to detect and identify significantly differentially expressed peptides in peptide profiles obtained from body fluids of patient and control groups. The presented modular software is capable of central storage of mass spectra and results in fast analysis. The software architecture consists of 4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database, which contains all metadata, such as experiment numbers and sample codes, 3) a FTP (File Transport Protocol) server to store all raw mass spectrometry files and processed data, and 4) the software package R, which is used for modular statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test. Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that peptide-profiles of two patient groups 1) breast cancer patients with leptomeningeal metastases and 2) prostate cancer patients in end stage disease can be distinguished from those of control groups. CONCLUSION: The database application is capable to distinguish patient Matrix Assisted Laser Desorption Ionization (MALDI-TOF) peptide profiles from control groups using large size datasets. The modular architecture of the application makes it possible to adapt the application to handle also large sized data from MS/MS- and Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry experiments. It is expected that the higher resolution and mass accuracy of the FT-ICR mass spectrometry prevents the clustering of peaks of different peptides and allows the identification of differentially expressed proteins from the peptide profiles

Systematic generation of in vivo G protein-coupled receptor mutants in the rat

G-protein-coupled receptors (GPCRs) constitute a large family of cell surface receptors that are involved in a wide range of physiological and pathological processes, and are targets for many therapeutic interventions. However, genetic models in the rat, one of the most widely used model organisms in physiological and pharmacological research, are largely lacking. Here, we applied N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis to generate an in vivo GPCR mutant collection in the rat. A pre-selected panel of 250 human GPCR homologs was screened for mutations in 813 rats, resulting in the identification of 131 non-synonymous mutations. From these, seven novel potential rat gene knockouts were established as well as 45 lines carrying missense mutations in various genes associated with or involved in human diseases. We provide extensive in silico modeling results of the missense mutations and show experimental data, suggesting loss-of-function phenotypes for several models, including Mc4r and Lpar1. Taken together, the approach used resulted not only in a set of novel gene knockouts, but also in allelic series of more subtle amino acid variants, similar as commonly observed in human disease. The mutants presented here may greatly benefit studies to understand specific GPCR function and support the development of novel therapeutic strategies

Targeting of a Chlamydial Protease Impedes Intracellular Bacterial Growth

Chlamydiae are obligate intracellular bacteria that propagate in a cytosolic vacuole. Recent work has shown that growth of Chlamydia induces the fragmentation of the Golgi apparatus (GA) into ministacks, which facilitates the acquisition of host lipids into the growing inclusion. GA fragmentation results from infection-associated cleavage of the integral GA protein, golgin-84. Golgin-84-cleavage, GA fragmentation and growth of Chlamydia trachomatis can be blocked by the peptide inhibitor WEHD-fmk. Here we identify the bacterial protease chlamydial protease-like activity factor (CPAF) as the factor mediating cleavage of golgin-84 and as the target of WEHD-fmk-inhibition. WEHD-fmk blocked cleavage of golgin-84 as well as cleavage of known CPAF targets during infection with C. trachomatis and C. pneumoniae. The same effect was seen when active CPAF was expressed in non-infected cells and in a cell-free system. Ectopic expression of active CPAF in non-infected cells was sufficient for GA fragmentation. GA fragmentation required the small GTPases Rab6 and Rab11 downstream of CPAF-activity. These results define CPAF as the first protein that is essential for replication of Chlamydia. We suggest that this role makes CPAF a potential anti-infective therapeutic target

Cost-effectiveness of collaborative care for chronically ill patients with comorbid depressive disorder in the general hospital setting, a randomised controlled trial

Background. Depressive disorder is one of the most common disorders, and is highly prevalent in chronically ill patients. The presence of comorbid depression has a negative influence on quality of life, health care costs, self-care, morbidity, and mortality. Early diagnosis and well-organized treatment of depression has a positive influence on these aspects. Earlier research in the USA has reported good results with regard to the treatment of depression with a collaborative care approach and an antidepressant algorithm. In the UK 'Problem Solving Treatment' has proved to be feasible. However, in the general hospital setting this approach has not yet been evaluated. Methods/Design. CC: DIM (Collaborative Care: Depression Initiative in the Medical setting) is a two-armed randomised controlled trial with randomisation at patient level. The aim of the trial is to evaluate the treatment of depressive disorder in general hospitals in the Netherlands based on a collaborative care framework, including contracting, 'Problem Solving Treatment', antidepressant algorithm, and manual-guided self-help. 126 outpatients with diabetes mellitus, chronic obstructive pulmonary disease, or cardiovascular diseases will be randomised to either the intervention group or the control group. Patients will be included if they have been diagnosed with moderate to severe depression, based on the DSM-IV criteria in a two-step screening method. The intervention group will receive treatment based on the collaborative care approach; the control group will receive 'care as usual'. Baseline and follow-up measurements (after 3, 6, 9, and 12 months) will be performed by means of questionnaires. The primary outcome measure is severity of depressive symptoms, as measured with the PHQ-9. The secondary outcome measure is the cost-effectiveness of these treatments according to the TiC-P, the EuroQol and the SF-36. Discussion. Earlier research has indicated that depressive disorder is a chronic, mostly recurrent illness, which tends to cluster with physical comorbidity. Even though the treatment of depressive disorder based on the guidelines for depression is proven effective, these guidelines are often insufficiently adhered to. Collaborative care and 'Problem Solving Treatment' will be specifically tailored to patients with depressive disorders and evaluated in a general hospital setting in the Netherlands