Statistical modelling of transcript profiles of differentially regulated genes

Background: The vast quantities of gene expression profiling data produced in microarray studies, and the more precise quantitative PCR, are often not statistically analysed to their full potential. Previous studies have summarised gene expression profiles using simple descriptive statistics, basic analysis of variance (ANOVA) and the clustering of genes based on simple models fitted to their expression profiles over time. We report the novel application of statistical non-linear regression modelling techniques to describe the shapes of expression profiles for the fungus Agaricus bisporus, quantified by PCR, and for E. coli and Rattus norvegicus, using microarray technology. The use of parametric non-linear regression models provides a more precise description of expression profiles, reducing the "noise" of the raw data to produce a clear "signal" given by the fitted curve, and describing each profile with a small number of biologically interpretable parameters. This approach then allows the direct comparison and clustering of the shapes of response patterns between genes and potentially enables a greater exploration and interpretation of the biological processes driving gene expression. Results: Quantitative reverse transcriptase PCR-derived time-course data of genes were modelled. "Splitline" or "broken-stick" regression identified the initial time of gene up-regulation, enabling the classification of genes into those with primary and secondary responses. Five-day profiles were modelled using the biologically-oriented, critical exponential curve, y(t) = A + (B + Ct)Rt + ε. This non-linear regression approach allowed the expression patterns for different genes to be compared in terms of curve shape, time of maximal transcript level and the decline and asymptotic response levels. Three distinct regulatory patterns were identified for the five genes studied. Applying the regression modelling approach to microarray-derived time course data allowed 11% of the Escherichia coli features to be fitted by an exponential function, and 25% of the Rattus norvegicus features could be described by the critical exponential model, all with statistical significance of p < 0.05. Conclusion: The statistical non-linear regression approaches presented in this study provide detailed biologically oriented descriptions of individual gene expression profiles, using biologically variable data to generate a set of defining parameters. These approaches have application to the modelling and greater interpretation of profiles obtained across a wide range of platforms, such as microarrays. Through careful choice of appropriate model forms, such statistical regression approaches allow an improved comparison of gene expression profiles, and may provide an approach for the greater understanding of common regulatory mechanisms between genes

Perceptions of human attractiveness comprising face and voice cues

In human mate choice, sexually dimorphic faces and voices comprise hormone-mediated cues that purportedly develop as an indicator of mate quality or the ability to compete with same-sex rivals. If preferences for faces communicate the same biologically relevant information as do voices, then ratings of these cues should correlate. Sixty participants (30 male and 30 female) rated a series of opposite-sex faces, voices, and faces together with voices for attractiveness in a repeated measures computer-based experiment. The effects of face and voice attractiveness on face-voice compound stimuli were analyzed using a multilevel model. Faces contributed proportionally more than voices to ratings of face-voice compound attractiveness. Faces and voices positively and independently contributed to the attractiveness of male compound stimuli although there was no significant correlation between their rated attractiveness. A positive interaction and correlation between attractiveness was shown for faces and voices in relation to the attractiveness of female compound stimuli. Rather than providing a better estimate of a single characteristic, male faces and voices may instead communicate independent information that, in turn, provides a female with a better assessment of overall mate quality. Conversely, female faces and voices together provide males with a more accurate assessment of a single dimension of mate quality

Speed of inhibition predicts teacher-rated medication response in boys with attention deficit hyperactivity disorder

Item does not contain fulltextThis study aimed at investigating whether one of the key deficits in Attention Deficit Hyperactivity Disorder (ADHD), slow response inhibition, predicted the response to methylphenidate (MPH) treatment. In order to address this issue, we used Stop Signal Reaction Times (SSRTs) measured at baseline in 20 medication-nave boys with ADHD as predictor, and parent and teacher ratings that were collected during a double-blind, placebo-controlled titration trial of MPH in the same group as outcome measures. Parent and teacher ratings were collected on primary scales, measuring ADHD symptoms, and secondary scales, measuring oppositional and disruptive behaviour. Placebo response and ADHD/Oppositional Defiant Disorder symptom severity at baseline were controlled for in the analyses. The SSRT did not predict the MPH response as measured by parent ratings, but it did predict the MPH response as measured by teacher ratings. This effect was specific for the ADHD scales. The slower SSRTs were, the less children benefited from MPH. Moreover, children with longer SSRTs needed higher doses of MPH for optimal symptom relief than children with shorter SSRTs. These findings have implications for clinicians who face the decision of which MPH dose to prescribe.18 p

Design of master and slave modules on battery management system for electric vehicles

Nowadays, electric vehicle usage and the use of LiFePO4 batteries in electric vehicles gradually increase. However, there are important features to be considered to use these batteries safely and efficiently. Incorrect use of these batteries can lead to burning, explosion or shortening of the life of batteries. In this paper, a Battery Management System (BMS) for lithium based batteries is designed that operates more efficiently and communicates with UART between master and slave modules and can communicate via CAN protocol with external devices. Micro controller based control and protection equipment is designed that help to measure and monitor the voltage, temperature and current values of the batteries. They protect the battery cells from the conditions such as over charge, over discharge, high current, high temperature. BMS balances battery cell voltages during charging process with passive cell voltage balancing. In addition to the main controller module in the BMS, slave controller modules have been added to provide high resolution voltage and temperature tracking. A modular BMS has been devised which can be used in groups of batteries of different voltage values thanks to electrically isolated slave control modules

Response execution and inhibitionin children with AD/HD and other disruptive disorders: the role of behavioural activation.

Item does not contain fulltextThis study was aimed at (a) replicating findings of slow and variable response execution and slow response inhibition in Attention Deficit/Hyperactivity Disorder (AD/HD), (b) investigating whether these deficits are specifically related to AD/HD or may also be observed in Oppositional Defiant Disorder (ODD), and children comorbid for AD/HD+ODD, and (c) examining the role of activation level in task performance of children with AD/HD. To meet these aims, the stop paradigm was administered at three levels of activation, using a slow, medium, and fast presentation rate of stimuli, to 4 groups of children: 24 AD/HD children, 21 children with ODD, 27 children with comorbid AD/HD+ODD, and 41 normal controls. As hypothesized, children with AD/HD exhibited a slow response execution process with considerable variability in the speed of responding compared to normal controls. Slow response execution was also observed in the comorbid AD/HD+ODD group but not in the pure ODD group. Larger variability in the speed of responding was common to all disruptive groups compared with controls. In contrast to our hypothesis, no group differences emerged for inhibitory functioning. Finally, the slow event rate condition caused a further deterioration in the speed of the response execution process in both the AD/HD group and ODD group

Response Inhibition in Children With DSM-IV Subtypes of AD/HD and Related Disruptive Disorders: The Role of Reward

Item does not contain fulltextThe current study had four aims: (a) to replicate previous findings of slow response inhibition in Attention Deficit/Hyperactivity Disorder (AD/HD), (b) to explore whether poor response inhibition in children with AD/HD is a core problem or rather a result of an underlying problem related to reward, (c) to investigate the specificity of poor response inhibition and the role of reward in relation to AD/HD, and (d) to study whether findings would be different for three subtypes of AD/HD. In order to address these issues, a stop paradigm was administered under a reward condition and under a nonreward condition to an AD/HD group (n = 24), an Oppositional Defiant Disorder (ODD)/Conduct Disorder (CD) group (n = 21), a comorbid AD/HD + ODD/CD group (n = 27), and a normal control (NC) group (n = 41). Firstly, contrary to prediction, none of the Disruptive Behavior Disorder (DBD) groups differed from the NC group with respect to the speed of the inhibition process. Secondly, it was shown that children with AD/HD and children with comorbid AD/HD + ODD/CD, but not children with ODD/CD alone, slowed down more dramatically in the reward condition than normal controls. This finding was interpreted as a strategy to increase the chance of being rewarded in children with AD/HD and children with comorbid AD/HD + ODD/CD, but not in children with pure ODD/CD. Finally, analysis of AD/HD subtypes did not change the main findings of this study

Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery

Objectives: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. Design: A prospective randomized clinical trial. Setting: University hospital. Participants: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Interventions: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Measurements and Main Results: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor a; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (P = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. Conclusions: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery

Auger mediated quantum sticking of positrons to surfaces: Evidence for single step transition from a scattering state to a surface image potential bound state

We present the observation of an efficient mechanism for positron sticking to surfaces termed here Auger mediated quantum sticking. In this process the energy associated with the positrons transition from an unbound scattering state to a bound image potential state is coupled to a valence electron which can then have sufficient energy to leave the surface. Compelling evidence for this mechanism is found in a narrow secondary electron peak observed at incident positron kinetic energies well below the electron work function.Comment: 4 pages, 4 figure

The impact of specific language impairment on working memory in children with ADHD combined type

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 812- to 1212-year-old children diagnosed with ADHD-C. A group of ADHD-C with SLI was compared to a group of ADHD-C without SLI, and a group of normal children, matched on age and nonverbal intelligence. The results show that ADHD-C children with SLI scored significantly lower than those without SLI and normal children, on verbal working memory measures only. Both ADHD groups performed normally on spatial working memory measures. It is concluded that working memory deficits are not a specific characteristic of ADHD but are associated with language impairments. The importance of screening for language disorders in studies of neuropsychological functioning in children with ADHD is emphasized

Ca 2+ signalling in urethral interstitial cells of Cajal

Interstitial cells of Cajal (ICC) in the urethra have been proposed as specialized pacemakers that are involved in the generation of urethral tone and therefore the maintenance of urinary continence. Recent studies on freshly dispersed ICC from the urethra of rabbits have demonstrated that pacemaker activity in urethra ICC is characterized by spontaneous transient depolarizations (STDs) under current clamp and spontaneous transient inward currents (STICs) under voltage clamp. When these events were simultaneously recorded with changes in intracellular Ca 2+ (using a Nipkow spinning disk confocal microscope) they were found to be associated with global Ca 2+ oscillations. In this short review we will consider some of these recent findings regarding the contribution of intracellular Ca 2+ stores and Ca 2+ influx to the generation of pacemaker activity in urethral ICC with particular emphasis on the contribution of reverse Na + /Ca 2+ exchange (NCX)