Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

Heterogeneous Response to a Quorum-Sensing Signal in the Luminescence of Individual Vibrio fischeri

The marine bacterium Vibrio fischeri regulates its bioluminescence through a quorum sensing mechanism: the bacterium releases diffusible small molecules (autoinducers) that accumulate in the environment as the population density increases. This accumulation of autoinducer (AI) eventually activates transcriptional regulators for bioluminescence as well as host colonization behaviors. Although V.fischeri quorum sensing has been extensively characterized in bulk populations, far less is known about how it performs at the level of the individual cell, where biochemical noise is likely to limit the precision of luminescence regulation. We have measured the time-dependence and AI-dependence of light production by individual V.fischeri cells that are immobilized in a perfusion chamber and supplied with a defined concentration of exogenous AI. We use low-light level microscopy to record and quantify the photon emission from the cells over periods of several hours as they respond to the introduction of AI. We observe an extremely heterogeneous response to the AI signal. Individual cells differ widely in the onset time for their luminescence and in their resulting brightness, even in the presence of high AI concentrations that saturate the light output from a bulk population. The observed heterogeneity shows that although a given concentration of quorum signal may determine the average light output from a population of cells, it provides far weaker control over the luminescence output of each individual cell

Macro-level Modeling of the Response of C. elegans Reproduction to Chronic Heat Stress

A major goal of systems biology is to understand how organism-level behavior arises from a myriad of molecular interactions. Often this involves complex sets of rules describing interactions among a large number of components. As an alternative, we have developed a simple, macro-level model to describe how chronic temperature stress affects reproduction in C. elegans. Our approach uses fundamental engineering principles, together with a limited set of experimentally derived facts, and provides quantitatively accurate predictions of performance under a range of physiologically relevant conditions. We generated detailed time-resolved experimental data to evaluate the ability of our model to describe the dynamics of C. elegans reproduction. We find considerable heterogeneity in responses of individual animals to heat stress, which can be understood as modulation of a few processes and may represent a strategy for coping with the ever-changing environment. Our experimental results and model provide quantitative insight into the breakdown of a robust biological system under stress and suggest, surprisingly, that the behavior of complex biological systems may be determined by a small number of key components

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Clinical features of human influenza A (H5N1) infection in Vietnam: 2004-2006.

BACKGROUND: The first cases of avian influenza A (H5N1) in humans in Vietnam were detected in early 2004, and Vietnam has reported the second highest number of cases globally. METHODS: We obtained retrospective clinical data through review of medical records for laboratory confirmed cases of influenza A (H5N1) infection diagnosed in Vietnam from January 2004 through December 2006. Standard data was abstracted regarding clinical and laboratory features, treatment, and outcome. RESULTS: Data were obtained for 67 (72%) of 93 cases diagnosed in Vietnam over the study period. Patients presented to the hospital after a median duration of illness of 6 days with fever (75%), cough (89%), and dyspnea (81%). Diarrhea and mucosal bleeding at presentation were more common in fatal than in nonfatal cases. Common findings were bilateral pulmonary infiltrates on chest radiograph (72%), lymphopenia (73%), and increased serum transaminase levels (aspartate aminotransferase, 69%; alanine aminotransferase, 61%). Twenty-six patients died (case fatality rate, 39%; 95% confidence interval, 27%-51%) and the most reliable predictor of a fatal outcome was the presence of both neutropenia and raised alanine aminotransferase level at admission, which correctly predicted 91% of deaths and 82% of survivals. The risk of death was higher among persons aged < or =16 years, compared with older persons (P < .001), and the risk of death was higher among patients who did not receive oseltamivir treatment (P = .048). The benefit of oseltamivir treatment remained after controlling for potential confounding by 1 measure of severity (odds ratio, 0.15; 95% confidence interval, 0.026-0.893; P = .034). CONCLUSION: In cases of infection with Influenza A (H5N1), the presence of both neutropenia and raised serum transaminase levels predicts a poor outcome. Oseltamivir treatment shows benefit, but treatment with corticosteroids is associated with an increased risk of death

Elderly care in daily living in rural Vietnam : Need and its socioeconomic determinants

Background The proportion of older people is increasing rapidly in Vietnam. The majority of the elderly live in rural areas. Their health status is generally improving but this is less pronounced among the most vulnerable groups. The movement of young people for employment and the impact of other socioeconomic changes leave more elderly on their own and with less family support. This study aims to assess the daily care needs and their socioeconomic determinants among older people in a rural setting. Methods In 2007, people aged 60 years and older, living in 2,240 households, were randomly selected from the FilaBavi Demographic Surveillance System (DSS). They were interviewed using structured questionnaires to assess needed support in activities of daily living (ADLs). Individuals were interviewed about the presence of chronic illnesses that had been diagnosed by a physician. Participant socioeconomic characteristics were extracted from the FilaBavi repeat census. The repeat census used a repeat of the same survey methods and questions as the original FilaBavi DSS. Distributions of study participants by socioeconomic group, supports needed, levels of support received, types of caregivers, and the ADL index were described. Multivariate analyses were performed to identify socioeconomic determinants of the ADL index. Results The majority of older people do not need of support for each specific ADL item. Dependence in instrumental or intellectual ADLs was more common than for basic ADLs. People who need total help were less common than those who need some help in most ADLs. Over three-fifths of those who need help receive enough support in all ADL dimensions. Children and grandchildren are the main caregivers. Age group, sex, educational level, marital status, household membership, working status, household size, living arrangement, residential area, household wealth, poverty status, and chronic illnesses were determinants of daily care needs in old age. Conclusions Although majority of older people who needed help received enough support in daily care, the need of care is more demanded in disadvantaged groups. Future community-based, long-term elderly care should focus on instrumental and intellectual ADLs among the general population of older people, and on basic ADLs among those with chronic illnesses. Socioeconomic determinants of care needs should be addressed in future interventions

Health-related quality of life, and its determinants, among older people in rural Vietnam

Background The proportion of people in Vietnam aged 60 and above has increased rapidly in recent decades. However, there is a lack of evidence, particularly in rural settings, on their health-related quality of life (HRQoL) within the context of socioeconomic changes and health-sector reform in the country. This study assesses the level and determinants of HRQoL in a rural district in order to provide evidence for designing and implementing appropriate health policies. Methods In 2007, 2,873 people aged 60+ living in 2,240 households randomly selected from the FilaBavi demographic surveillance site (DSS) were interviewed using a generic EQ-5D questionnaire to assess their HRQoL. Socioeconomic characteristics of the people and their households were extracted from the DSS's re-census that year, and the EQ-5D index was calculated based on the time trade-off tariff. Multilevel-multivariate linear regression analysis was performed to measure the affect of socioeconomic factors on HRQoL. Results The EQ-5D index at old age was found to be 0.876 (95%CI: 0.870-0.882). Age between 60-69 or 70-79 years, position as household head, working until old age, literacy, and belonging to better wealth quintiles are determinants of higher HRQoL. Ageing has a primary influence on the deterioration of HRQoL at older ages, mainly due to reduction in physical rather than mental functions. Educational disparity in HRQoL is low, and exists mostly between basic and higher levels of education. Being a household head and working at old age are advantageous for attaining better quality of life in physical rather than psychological terms. Economic conditions affect HRQoL through sensory rather than physical utilities. Long-term living conditions more likely affect HRQoL than short-term economic conditions. Conclusions HRQoL at old age is at a high level, and varies substantially according to socioeconomic factors. Its determinants should be addressed in social and health policies designed to improve health of older people, especially among the most vulnerable groups.Aging and Living conditions ProgramVietnam-Sweden Collaborative Program in Health, SIDA/Sare