Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Attitude toward contraception and abortion among Curaçao women. Ineffective contraception due to limited sexual education?

Background In Curaçao is a high incidence of unintended pregnancies and induced abortions. Most of the induced abortions in Curaçao are on request of the woman and performed by general practitioners. In Curaçao, induced abortion is strictly prohibited, but since 1999 there has been a policy of connivance. We present data on the relevance of economic and socio-cultural factors for the high abortion-rates and the ineffective use of contraception. Methods Structured interviews to investigate knowledge and attitudes toward sexuality, contraception and abortion and reasons for ineffective use of contraceptives among women, visiting general practitioners. Results Of 158 women, 146 (92%) participated and 82% reported that their education on sexuality and about contraception was of good quality. However 'knowledge of reliable contraceptive methods' appeared to be - in almost 50% of the cases - false information, misjudgements or erroneous views on the chance of getting pregnant using coitus interruptus and about the reliability and health effects of oral contraceptive pills. Almost half of the interviewed women had incorrect or no knowledge about reliability of condom use and IUD. 42% of the respondents risked by their behavior an unplanned pregnancy. Most respondents considered abortion as an emergency procedure, not as contraception. Almost two third experienced emotional, physical or social problems after the abortion. Conclusions Respondents had a negative attitude toward reliable contraceptives due to socio-cultural determined ideas about health consequences and limited sexual education. Main economic factors were costs of contraceptive methods, because most health insurances in Curaçao do not cover contraceptives. To improve the effective use of reliable contraceptives, more adequate information should be given, targeting the wrong beliefs and false information. The government should encourage health insurance companies to reimburse contraceptives. Furthermore, improvement of counseling during the abortion procedure is important

CADASIL in Arabs: clinical and genetic findings

<p>Abstract</p> <p>Background</p> <p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in <it>NOTCH3 </it>epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs.</p> <p>Methods</p> <p>We studied three families from Saudi Arabia (Family A), Kuwait (Family B) and Yemen (Family C) with 19 individuals affected by CADASIL.</p> <p>Results</p> <p>The mean age of onset was 31 ± 6 and the clinical presentation included stroke in 68%, subcortical dementia in 17% and asymptomatic leukoariosis detected by MRI in 15%. Migraine and depression were frequently associated, 38% and 68% respectively. The mean age of death was 56 ± 11. All <it>NOTCH3 </it>exons were screened for mutations, which revealed the presence of previously reported mutations c.406C>T (p.Arg110>Cys) in two families (family A&B) and c.475C>T (p.Arg133>Cys) mutation in family C.</p> <p>Conclusion</p> <p>CADASIL occurs in Arabs, with clinical phenotype and genotype similar to that in other ethnic groups.</p

Predicting multiplex subcellular localization of proteins using protein-protein interaction network: a comparative study

<p>Abstract</p> <p>Background</p> <p>Proteins that interact in vivo tend to reside within the same or "adjacent" subcellular compartments. This observation provides opportunities to reveal protein subcellular localization in the context of the protein-protein interaction (PPI) network. However, so far, only a few efforts based on heuristic rules have been made in this regard.</p> <p>Results</p> <p>We systematically and quantitatively validate the hypothesis that proteins physically interacting with each other probably share at least one common subcellular localization. With the result, for the first time, four graph-based semi-supervised learning algorithms, Majority, <it>χ</it>²-score, GenMultiCut and FunFlow originally proposed for protein function prediction, are introduced to assign "multiplex localization" to proteins. We analyze these approaches by performing a large-scale cross validation on a <it>Saccharomyces cerevisiae </it>proteome compiled from BioGRID and comparing their predictions for 22 protein subcellular localizations. Furthermore, we build an ensemble classifier to associate 529 unlabeled and 137 ambiguously-annotated proteins with subcellular localizations, most of which have been verified in the previous experimental studies.</p> <p>Conclusions</p> <p>Physical interaction of proteins has actually provided an essential clue for their co-localization. Compared to the local approaches, the global algorithms consistently achieve a superior performance.</p

Immunohistochemical, morphological and ultrastructural resemblance between dendritic cells and folliculo-stellate cells in normal human and rat anterior pituitaries

Immunolabeling of cryo-sections of human anterior pituitaries obtained at autopsy, and of cryo-sections of freshly prepared rat anterior pituitaries, with a panel of monoclonal antibodies against markers of the monocyte/dendritic cell/macrophage lineage, reveals in both species a characteristic pattern of immunopositive cells, among which many cells with dendritic phenotype are found. Cells characterized by marker expression of MHC-class II determinants and a dendritic morphology are present in both human and rat anterior pituitary. Markers characteristic of dendritic cells such as the L25 antigen and the OX62 antigen were present in anterior pituitaries from human and rat respectively. The population of MHC-class II expressing dendritic cells of the rat anterior pituitary is compared at the ultrastructural level with the folliculo-stellate cell population, which cell type has been previously characterized by its distinctive ultrastructure and immunopositivity for the S100 protein. Using immune-electron microscopy of rat anterior pituitaries fixed with periodate-lysine-paraformaldehyde, we were able to distinguish non-granulated cells expressing MHC-class II determinants, whereas no MHC-class II expression was found in the granulated endocrine cells. Using double immunolabeling of cryo-sections of these rat AP with 25 nm and 15 nm gold labels, we demonstrated an overlap between the populations of MHC-class II-expressing and S100 protein-expressing cells. Furthermore, MHC-class II-expressing and S100-positive cells showed ultrastructural characteristics that have been previously ascribed to folliculo-stellate cells. At the light microscopical level in the rat AP, a proportion of 10 to 20% of the S100-positive cells was found immunopositive for the MHC-class II marker OX6. In the hu

Bio-Repository of DNA in stroke (BRAINS): A study protocol

<p>Abstract</p> <p>Background</p> <p>Stroke is one of the commonest causes of mortality in the world and anticipated to be an increasing burden to the developing world. Stroke has a genetic basis and identifying those genes may not only help us define the mechanisms that cause stroke but also identify novel therapeutic targets. However, large scale highly phenotyped DNA repositories are required in order for this to be achieved.</p> <p>Methods</p> <p>The proposed Bio-Repository of DNA in Stroke (BRAINS) will recruit all subtypes of stroke as well as controls from two different continents, Europe and Asia. Subjects recruited from the UK will include stroke patients of European ancestry as well as British South Asians. Stroke subjects from South Asia will be recruited from India and Sri Lanka. South Asian cases will also have control subjects recruited.</p> <p>Discussion</p> <p>We describe a study protocol to establish a large and highly characterized stroke biobank in those of European and South Asian descent. With different ethnic populations being recruited, BRAINS has the ability to compare and contrast genetic risk factors between those of differing ancestral descent as well as those who migrate into different environments.</p

Gender differences in health and health care utilisation in various ethnic groups in the Netherlands: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>To determine gender differences in health and health care utilisation within and between various ethnic groups in the Netherlands.</p> <p>Methods</p> <p>Data from the second Dutch National Survey of General Practice (2000–2002) were used. A total of 7,789 persons from the indigenous population and 1,512 persons from the four largest migrant groups in the Netherlands – Morocco, Netherlands Antilles, Turkey and Surinam – aged 18 years and older were interviewed. Self-reported health outcomes studied were general health status and the presence of acute (past 14 days) and chronic conditions (past 12 months). And self-reported utilisation of the following health care services was analysed: having contacted a general practitioner (past 2 months), a medical specialist, physiotherapist or ambulatory mental health service (past 12 months), hospitalisation (past 12 months) and use of medication (past 14 days). Gender differences in these outcomes were examined within and between the ethnic groups, using logistic regression analyses.</p> <p>Results</p> <p>In general, women showed poorer health than men; the largest differences were found for the Turkish respondents, followed by Moroccans, and Surinamese. Furthermore, women from Morocco and the Netherlands Antilles more often contacted a general practitioner than men from these countries. Women from Turkey were more hospitalised than Turkish men. Women from Morocco more often contacted ambulatory mental health care than men from this country, and women with an indigenous background more often used over the counter medication than men with an indigenous background.</p> <p>Conclusion</p> <p>In general the self-reported health of women is worse compared to that of men, although the size of the gender differences may vary according to the particular health outcome and among the ethnic groups. This information might be helpful to develop policy to improve the health status of specific groups according to gender and ethnicity. In addition, in some ethnic groups, and for some types of health care services, the use by women is higher compared to that by men. More research is needed to explain these differences.</p

Inequities in under-five child malnutrition in South Africa

OBJECTIVES: To assess and quantify the magnitude of inequalities in under-five child malnutrition, particularly those ascribable to socio-economic status and to consider the policy implications of these findings. METHODS: Data on 3765 under-five children were derived from the Living Standards and Development Survey. Household income, proxied by per capita household expenditure, was used as the main indicator of socio-economic status. Socio-economic inequality in malnutrition (stunting, underweight and wasting) was measured using the illness concentration index. The concentration index was calculated for the whole sample, as well as for different population groups, areas of residence (rural, urban and metropolitan) and for each province. RESULTS: Stunting was found to be the most prevalent form of malnutrition in South Africa. Consistent with expectation, the rate of stunting is observed to be the highest in the Eastern Cape and the Northern Province – provinces with the highest concentration of poverty. There are considerable pro-rich inequalities in the distribution of stunting and underweight. However, wasting does not manifest gradients related to socio-economic position. Among White children, no inequities are observed in all three forms of malnutrition. The highest pro-rich inequalities in stunting and underweight are found among Coloured children and metropolitan areas. There is a tendency for high pro-rich concentration indices in those provinces with relatively lower rates of stunting and underweight (Gauteng and the Western Cape). CONCLUSION: There are significant differences in under-five child malnutrition (stunting and underweight) that favour the richest of society. These are unnecessary, avoidable and unjust. It is demonstrated that addressing such socio-economic gradients in ill-health, which perpetuate inequalities in the future adult population requires a sound evidence base. Reliance on global averages alone can be misleading. Thus there is a need for evaluating policies not only in terms of improvements in averages, but also improvements in distribution. Furthermore, addressing problems of stunting and underweight, which are found to be responsive to improvements in household income status, requires initiatives that transcend the medical arena

Automated Builder and Database of Protein/Membrane Complexes for Molecular Dynamics Simulations

Molecular dynamics simulations of membrane proteins have provided deeper insights into their functions and interactions with surrounding environments at the atomic level. However, compared to solvation of globular proteins, building a realistic protein/membrane complex is still challenging and requires considerable experience with simulation software. Membrane Builder in the CHARMM-GUI website (http://www.charmm-gui.org) helps users to build such a complex system using a web browser with a graphical user interface. Through a generalized and automated building process including system size determination as well as generation of lipid bilayer, pore water, bulk water, and ions, a realistic membrane system with virtually any kinds and shapes of membrane proteins can be generated in 5 minutes to 2 hours depending on the system size. Default values that were elaborated and tested extensively are given in each step to provide reasonable options and starting points for both non-expert and expert users. The efficacy of Membrane Builder is illustrated by its applications to 12 transmembrane and 3 interfacial membrane proteins, whose fully equilibrated systems with three different types of lipid molecules (DMPC, DPPC, and POPC) and two types of system shapes (rectangular and hexagonal) are freely available on the CHARMM-GUI website. One of the most significant advantages of using the web environment is that, if a problem is found, users can go back and re-generate the whole system again before quitting the browser. Therefore, Membrane Builder provides the intuitive and easy way to build and simulate the biologically important membrane system

A Multicellular Model of Intestinal Crypt Buckling and Fission

Crypt fission is an in vivo tissue deformation process that is involved in both intestinal homeostasis and colorectal tumourigenesis. Despite its importance, the mechanics underlying crypt fission are currently poorly understood. Recent experimental development of organoids, organ-like buds cultured from crypt stem cells in vitro, has shown promise in shedding light on crypt fission. Drawing inspiration from observations of organoid growth and fission in vivo, we develop a computational model of a deformable epithelial tissue layer. Results from in silico experiments show the stiffness of cells and the proportions of cell subpopulations affect the nature of deformation in the epithelial layer. In particular, we find that increasing the proportion of stiffer cells in the layer increases the likelihood of crypt fission occurring. This is in agreement with and helps explain recent experimental work