2,770 research outputs found
Regulatory control and the costs and benefits of biochemical noise
Experiments in recent years have vividly demonstrated that gene expression
can be highly stochastic. How protein concentration fluctuations affect the
growth rate of a population of cells, is, however, a wide open question. We
present a mathematical model that makes it possible to quantify the effect of
protein concentration fluctuations on the growth rate of a population of
genetically identical cells. The model predicts that the population's growth
rate depends on how the growth rate of a single cell varies with protein
concentration, the variance of the protein concentration fluctuations, and the
correlation time of these fluctuations. The model also predicts that when the
average concentration of a protein is close to the value that maximizes the
growth rate, fluctuations in its concentration always reduce the growth rate.
However, when the average protein concentration deviates sufficiently from the
optimal level, fluctuations can enhance the growth rate of the population, even
when the growth rate of a cell depends linearly on the protein concentration.
The model also shows that the ensemble or population average of a quantity,
such as the average protein expression level or its variance, is in general not
equal to its time average as obtained from tracing a single cell and its
descendants. We apply our model to perform a cost-benefit analysis of gene
regulatory control. Our analysis predicts that the optimal expression level of
a gene regulatory protein is determined by the trade-off between the cost of
synthesizing the regulatory protein and the benefit of minimizing the
fluctuations in the expression of its target gene. We discuss possible
experiments that could test our predictions.Comment: Revised manuscript;35 pages, 4 figures, REVTeX4; to appear in PLoS
Computational Biolog
Mining and analysis of audiology data to find significant factors associated with tinnitus masker
Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments.
Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques.
Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus.
Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic.
Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient.
Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence.
Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the
choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained
Long-term reductions in tinnitus severity
BACKGROUND: This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. METHODS: Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Oregon Health & Science University Tinnitus Clinic. All patients were then evaluated and treated within a comprehensive tinnitus management program. Follow-up questionnaires were mailed to the same 300 patients 6 to 36 months after their initial tinnitus clinic appointment. RESULTS: One hundred ninety patients (133 males, 57 females; mean age 57 years) returned follow-up questionnaires 6 to 36 months (mean = 22 months) after their initial tinnitus clinic appointment. This group of patients exhibited significant long-term reductions in self-rated tinnitus loudness, Tinnitus Severity Index scores, tinnitus-related anxiety and prevalence of current depression. Patients who improved their sleep patterns or Beck Depression Inventory scores exhibited greater reductions of tinnitus severity scores than patients who continued to experience insomnia and depression at follow-up. CONCLUSIONS: Individualized tinnitus management programs that were designed for each patient contributed to overall reductions in tinnitus severity exhibited on follow-up questionnaires. Identification and treatment of patients experiencing anxiety, insomnia or depression are vital components of an effective tinnitus management program. Utilization of acoustic therapy also contributed to improvements exhibited by these patients
Defecting or not defecting: how to "read" human behavior during cooperative games by EEG measurements
Understanding the neural mechanisms responsible for human social interactions
is difficult, since the brain activities of two or more individuals have to be
examined simultaneously and correlated with the observed social patterns. We
introduce the concept of hyper-brain network, a connectivity pattern
representing at once the information flow among the cortical regions of a
single brain as well as the relations among the areas of two distinct brains.
Graph analysis of hyper-brain networks constructed from the EEG scanning of 26
couples of individuals playing the Iterated Prisoner's Dilemma reveals the
possibility to predict non-cooperative interactions during the decision-making
phase. The hyper-brain networks of two-defector couples have significantly less
inter-brain links and overall higher modularity - i.e. the tendency to form two
separate subgraphs - than couples playing cooperative or tit-for-tat
strategies. The decision to defect can be "read" in advance by evaluating the
changes of connectivity pattern in the hyper-brain network
Robust Detection of Hierarchical Communities from Escherichia coli Gene Expression Data
Determining the functional structure of biological networks is a central goal
of systems biology. One approach is to analyze gene expression data to infer a
network of gene interactions on the basis of their correlated responses to
environmental and genetic perturbations. The inferred network can then be
analyzed to identify functional communities. However, commonly used algorithms
can yield unreliable results due to experimental noise, algorithmic
stochasticity, and the influence of arbitrarily chosen parameter values.
Furthermore, the results obtained typically provide only a simplistic view of
the network partitioned into disjoint communities and provide no information of
the relationship between communities. Here, we present methods to robustly
detect coregulated and functionally enriched gene communities and demonstrate
their application and validity for Escherichia coli gene expression data.
Applying a recently developed community detection algorithm to the network of
interactions identified with the context likelihood of relatedness (CLR)
method, we show that a hierarchy of network communities can be identified.
These communities significantly enrich for gene ontology (GO) terms, consistent
with them representing biologically meaningful groups. Further, analysis of the
most significantly enriched communities identified several candidate new
regulatory interactions. The robustness of our methods is demonstrated by
showing that a core set of functional communities is reliably found when
artificial noise, modeling experimental noise, is added to the data. We find
that noise mainly acts conservatively, increasing the relatedness required for
a network link to be reliably assigned and decreasing the size of the core
communities, rather than causing association of genes into new communities.Comment: Due to appear in PLoS Computational Biology. Supplementary Figure S1
was not uploaded but is available by contacting the author. 27 pages, 5
figures, 15 supplementary file
The role of input noise in transcriptional regulation
Even under constant external conditions, the expression levels of genes
fluctuate. Much emphasis has been placed on the components of this noise that
are due to randomness in transcription and translation; here we analyze the
role of noise associated with the inputs to transcriptional regulation, the
random arrival and binding of transcription factors to their target sites along
the genome. This noise sets a fundamental physical limit to the reliability of
genetic control, and has clear signatures, but we show that these are easily
obscured by experimental limitations and even by conventional methods for
plotting the variance vs. mean expression level. We argue that simple, global
models of noise dominated by transcription and translation are inconsistent
with the embedding of gene expression in a network of regulatory interactions.
Analysis of recent experiments on transcriptional control in the early
Drosophila embryo shows that these results are quantitatively consistent with
the predicted signatures of input noise, and we discuss the experiments needed
to test the importance of input noise more generally.Comment: 11 pages, 5 figures minor correction
Non-L\'evy mobility patterns of Mexican Me'Phaa peasants searching for fuelwood
We measured mobility patterns that describe walking trajectories of
individual Me'Phaa peasants searching and collecting fuelwood in the forests of
"La Monta\~na de Guerrero" in Mexico. These one-day excursions typically follow
a mixed pattern of nearly-constant steps when individuals displace from their
homes towards potential collecting sites and a mixed pattern of steps of
different lengths when actually searching for fallen wood in the forest.
Displacements in the searching phase seem not to be compatible with L\'evy
flights described by power-laws with optimal scaling exponents. These findings
however can be interpreted in the light of deterministic searching on heavily
degraded landscapes where the interaction of the individuals with their scarce
environment produces alternative searching strategies than the expected L\'evy
flights. These results have important implications for future management and
restoration of degraded forests and the improvement of the ecological services
they may provide to their inhabitants.Comment: 15 pages, 4 figures. First version submitted to Human Ecology. The
final publication will be available at http://www.springerlink.co
Body image, body dissatisfaction and weight status in south asian children: a cross-sectional study
Background
Childhood obesity is a continuing problem in the UK and South Asian children represent a group that are particularly vulnerable to its health consequences. The relationship between body dissatisfaction and obesity is well documented in older children and adults, but is less clear in young children, particularly South Asians. A better understanding of this relationship in young South Asian children will inform the design and delivery of obesity intervention programmes. The aim of this study is to describe body image size perception and dissatisfaction, and their relationship to weight status in primary school aged UK South Asian children.
Methods
Objective measures of height and weight were undertaken on 574 predominantly South Asian children aged 5-7 (296 boys and 278 girls). BMI z-scores, and weight status (underweight, healthy weight, overweight or obese) were calculated based on the UK 1990 BMI reference charts. Figure rating scales were used to assess perceived body image size (asking children to identify their perceived body size) and dissatisfaction (difference between perceived current and ideal body size). The relationship between these and weight status were examined using multivariate analyses.
Results
Perceived body image size was positively associated with weight status (partial regression coefficient for overweight/obese vs. non-overweight/obese was 0.63 (95% CI 0.26-0.99) and for BMI z-score was 0.21 (95% CI 0.10-0.31), adjusted for sex, age and ethnicity). Body dissatisfaction was also associated with weight status, with overweight and obese children more likely to select thinner ideal body size than healthy weight children (adjusted partial regression coefficient for overweight/obese vs. non-overweight/obese was 1.47 (95% CI 0.99-1.96) and for BMI z-score was 0.54 (95% CI 0.40-0.67)).
Conclusions
Awareness of body image size and increasing body dissatisfaction with higher weight status is established at a young age in this population. This needs to be considered when designing interventions to reduce obesity in young children, in terms of both benefits and harms
Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70
Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis
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