A conceptual and computational framework for modelling and understanding the non-equilibrium gene regulatory networks of mouse embryonic stem cells

The capacity of pluripotent embryonic stem cells to differentiate into any cell type in the body makes them invaluable in the field of regenerative medicine. However, because of the complexity of both the core pluripotency network and the process of cell fate computation it is not yet possible to control the fate of stem cells. We present a theoretical model of stem cell fate computation that is based on Halley and Winkler's Branching Process Theory (BPT) and on Greaves et al.'s agent-based computer simulation derived from that theoretical model. BPT abstracts the complex production and action of a Transcription Factor (TF) into a single critical branching process that may dissipate, maintain, or become supercritical. Here we take the single TF model and extend it to multiple interacting TFs, and build an agent-based simulation of multiple TFs to investigate the dynamics of such coupled systems. We have developed the simulation and the theoretical model together, in an iterative manner, with the aim of obtaining a deeper understanding of stem cell fate computation, in order to influence experimental efforts, which may in turn influence the outcome of cellular differentiation. The model used is an example of self-organization and could be more widely applicable to the modelling of other complex systems. The simulation based on this model, though currently limited in scope in terms of the biology it represents, supports the utility of the Halley and Winkler branching process model in describing the behaviour of stem cell gene regulatory networks. Our simulation demonstrates three key features: (i) the existence of a critical value of the branching process parameter, dependent on the details of the cistrome in question; (ii) the ability of an active cistrome to "ignite" an otherwise fully dissipated cistrome, and drive it to criticality; (iii) how coupling cistromes together can reduce their critical branching parameter values needed to drive them to criticality.This work was performed as part of the CellBranch project, funded by the UK’s Biotechnology and Biological Sciences Research Council (BBSRC, http://www.bbsrc.ac.uk/), project reference BB/L018705/1. Grant holder: SS

Organizational innovation in the multinational enterprise: internalization theory and business history

This article engages in a methodological experiment by using historical evidence to challenge a common misperception about internalization theory. The theory has often been criticized for maintaining that it assumes a hierarchically organized MNE based on knowledge flowing from the home country. This is not an accurate description of how global firms operate in recent decades, but this article shows it has never been true historically. Using longitudinal data on individual firms from the nineteenth century onwards, it reveals evidence of how entrepreneurs and firms with multinational activity faced with market imperfections changed the design of their headquarters and their organizational structures

Home on the Range: Factors Explaining Partial Migration of African Buffalo in a Tropical Environment

Partial migration (when only some individuals in a population undertake seasonal migrations) is common in many species and geographical contexts. Despite the development of modern statistical methods for analyzing partial migration, there have been no studies on what influences partial migration in tropical environments. We present research on factors affecting partial migration in African buffalo (Syncerus caffer) in northeastern Namibia. Our dataset is derived from 32 satellite tracking collars, spans 4 years and contains over 35,000 locations. We used remotely sensed data to quantify various factors that buffalo experience in the dry season when making decisions on whether and how far to migrate, including potential man-made and natural barriers, as well as spatial and temporal heterogeneity in environmental conditions. Using an information-theoretic, non-linear regression approach, our analyses showed that buffalo in this area can be divided into 4 migratory classes: migrants, non-migrants, dispersers, and a new class that we call “expanders”. Multimodel inference from least-squares regressions of wet season movements showed that environmental conditions (rainfall, fires, woodland cover, vegetation biomass), distance to the nearest barrier (river, fence, cultivated area) and social factors (age, size of herd at capture) were all important in explaining variation in migratory behaviour. The relative contributions of these variables to partial migration have not previously been assessed for ungulates in the tropics. Understanding the factors driving migratory decisions of wildlife will lead to better-informed conservation and land-use decisions in this area

The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors - results of a prospective study

<p>Abstract</p> <p>Background</p> <p>Few data exist on survival or health-related quality of life (QOL) related to herbal remedy use among long-term breast cancer survivors. The objective of this report is to examine whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors.</p> <p>Methods</p> <p>In 1999-2000, we collected the information of herbal remedy use and QOL during a telephone interview with 371 Los Angeles Non-Hispanic/Hispanic white women who had survived more than 10 years after breast cancer diagnosis. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. Patients were followed for mortality from the baseline interview through 2007. 299 surviving patients completed a second telephone interview on QOL in 2002-2004. We used multivariable Cox proportional hazards methods to estimate relative risks (RR) and 95% confidence intervals (CI) for mortality and applied multivariable linear regression models to compare average SF-36 change scores (follow-up - baseline) between herbal remedy users and non-users.</p> <p>Results</p> <p>Fifty-nine percent of participants were herbal remedy users at baseline. The most commonly used herbal remedies were echinacea, herbal teas, and ginko biloba. Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause (44 deaths, RR = 1.28, 95% CI = 0.62-2.64) and breast cancer (33 deaths, RR = 1.78, 95% CI = 0.72-4.40) mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey (<it>P </it>= 0.16), but herbal remedy users' physical component summary scores decreased more than those of non-users (-5.7 vs. -3.2, <it>P </it>= 0.02).</p> <p>Conclusions</p> <p>Our data provide some evidence that herbal remedy use is associated with poorer survival and a poorer physical component score for health-related QOL among women who have survived breast cancer for at least 10 years. These conclusions are based on exploratory analyses of data from a prospective study using two-sided statistical tests with no correction for multiple testing and are limited by few deaths for mortality analysis and lack of information on when herbal remedy use was initiated or duration of or reasons for use.</p

Prevalence and risk factors for internet gaming disorder

Objectives: To estimate the prevalence of internet gaming disorder (IGD) and associated risk factors in a sample of secondary and postsecondary students from a public federal institution of higher education (Instituto Federal de Educação, Ciência e Tecnologia) in Southern Brazil. Methods: The study included a sociodemographic questionnaire, the Beck Depression Inventory (BDI), Self-Report Questionnaire (SRQ-20), Pittsburgh Sleep Quality Index (PSQI-BR), the Mini-Social Phobia Inventory (Mini-SPIN), and the Game Addiction Scale (GAS). Finally, IGD was measured with the Brazilian version of the Internet Gaming Disorder Scale-Short-Form (IGDS9-SF), which has been psychometrically validated in this population. Results: Overall, 38.2% (n=212) of the sample exhibited IGD symptoms, with 18.2% (n=101) being classed as at-risk gamers. Regression analysis found IGD to be associated with male gender, severe depressive symptoms, poor sleep quality, increased time spent gaming, and total free time spent gaming (p < 0.001). Conclusions: The prevalence of IGD in this sample was relatively high, and associated risk factors found were similar to those previously reported in the literature. Further studies investigating the epidemiology of IGD in Brazilian samples are warranted to better understand treatment needs and inform preventive measures in this population

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

Prevalence and associated factors of Internet gaming disorder among community dwelling adults in Macao, China

Objectives: To estimate the prevalence of internet gaming disorder (IGD) and associated risk factors in a sample of secondary and postsecondary students from a public federal institution of higher education (Instituto Federal de Educação, Ciência e Tecnologia) in Southern Brazil. Methods: The study included a sociodemographic questionnaire, the Beck Depression Inventory (BDI), Self-Report Questionnaire (SRQ-20), Pittsburgh Sleep Quality Index (PSQI-BR), the Mini-Social Phobia Inventory (Mini-SPIN), and the Game Addiction Scale (GAS). Finally, IGD was measured with the Brazilian version of the Internet Gaming Disorder Scale-Short-Form (IGDS9-SF), which has been psychometrically validated in this population. Results: Overall, 38.2% (n=212) of the sample exhibited IGD symptoms, with 18.2% (n=101) being classed as at-risk gamers. Regression analysis found IGD to be associated with male gender, severe depressive symptoms, poor sleep quality, increased time spent gaming, and total free time spent gaming (p Conclusions: The prevalence of IGD in this sample was relatively high, and associated risk factors found were similar to those previously reported in the literature. Further studies investigating the epidemiology of IGD in Brazilian samples are warranted to better understand treatment needs and inform preventive measures in this population.</p

Instrument effects on stress jump measurements

Stress jumps occur in fluids that possess a viscous contribution to their total stress. On cessation of shear, such a fluid will show an instantaneous loss of stress, while some of the stress will remain and subsequently decay in some manner, either exponential or otherwise. The results in this paper show that filtering, present in most rheometers, will eliminate the stress jump and not allow its measurement. The torque head inertia for a spring-type torque measuring system is found to greatly influence the measurements and a stress jump is not seen. In fact, the material's true stress relaxation behaviour is far from that measured. The force rebalance torque measuring system is found to accurately measure stress jumps