Nerve growth factor nonresponsive pheochromocytoma cells: altered internalization results in signaling dysfunction.

Variant rat pheochromocytoma (PC12) cells which fail to respond to nerve growth factor (NGF) (PC12nnr5) (Green, S. H., R. E. Rydel, J. L. Connoly, and L. A. Greene. 1986. J. Cell Biol. 102:830-843) bind NGF at both high and low affinity sites. Although still undefined at the molecular level, these have been referred to as type I (high) and type II (low) receptors. They are apparently composed of two membrane-bound proteins, p75 and the protooncogene trk, both of which bind NGF, and apparently contribute singularly or in concert to the two observed affinities, and to the promotion of the NGF effects. In native PC12 cells, only the high affinity receptors are apparently capable of mediating internalization and degradation. PC12nnr5 cells also display type I binding, but the subsequent internalization is not the same fashion as in the parental cell line, nor is it subjected to lysosomal degradation. Rather it is initially sequestered during the first 15 min, and is eventually released intact into the medium. In contrast, EGF is bound, internalized, and degraded by PC12nnr5 cells, albeit less efficiently than in the parent cells. These observations argue that the defect(s) preventing the PC12nnr5 variants from responding to NGF prevents competent internalization, which in the case of NGF, may be required for the full expression of activity. The absence of trk, as one alteration in PC12nnr5 cells (Loeb, D. M., J. Maragos, D. Martin-Zanca, M. V. Chao, L. F. Parada, and L. A. Greene. 1991. Cell. 66:961-966), is consistent with this conclusion

Structure, (governance) and health: An unsolicited response

Background: In a recently published article, it was suggested that governance was the significant structural factor affecting the epidemiology of HIV. This suggestion was made notwithstanding the observed weak correlation between governance and HIV prevalence (r = .2). Unfortunately, the paper raised but left unexamined the potentially more important questions about the relationship between the broader health of populations and structural factors such as the national economy and physical infrastructure. Methods: Utilizing substantially the same data sources as the original article, the relationship between population health (healthy life expectancy) and three structural factors (access to improved water, GDP per capita, and governance) were examined in each of 176 countries. Results: Governance was found to be significantly correlated with population health, as were GDP per capita, and access to improved water. They were also found to be significantly correlated with each other. Conclusion: The findings are discussed with reference to the growing interest in structural factors as an explanation for population health outcomes, and the relatively weak relationship between governance and HIV prevalence

Variational Principles for Stochastic Soliton Dynamics

We develop a variational method of deriving stochastic partial differential equations whose solutions follow the flow of a stochastic vector field. As an example in one spatial dimension we numerically simulate singular solutions (peakons) of the stochastically perturbed Camassa-Holm (CH) equation derived using this method. These numerical simulations show that peakon soliton solutions of the stochastically perturbed CH equation persist and provide an interesting laboratory for investigating the sensitivity and accuracy of adding stochasticity to finite dimensional solutions of stochastic partial differential equations (SPDE). In particular, some choices of stochastic perturbations of the peakon dynamics by Wiener noise (canonical Hamiltonian stochastic deformations, or CH-SD) allow peakons to interpenetrate and exchange order on the real line in overtaking collisions, although this behaviour does not occur for other choices of stochastic perturbations which preserve the Euler-Poincar\'e structure of the CH equation (parametric stochastic deformations, or P-SD), and it also does not occur for peakon solutions of the unperturbed deterministic CH equation. The discussion raises issues about the science of stochastic deformations of finite-dimensional approximations of evolutionary PDE and the sensitivity of the resulting solutions to the choices made in stochastic modelling.Comment: 21 pages, 15 figures -- 2nd versio

HIV, Stigma, and Rates of Infection: A Rumour without Evidence

The modern concept of a social stigma comes from the work of American sociologist Erving Goffman, who described it as a response to a deeply discrediting attribute that devalues the person [1]. In the medical literature, stigma is almost inevitably written about in terms of adverse social sequelae of a disease—such as leprosy, tuberculosis, epilepsy, schizophrenia, or filariasis [2–6]—or a physical characteristic or functional loss, such as obesity, deafness, or paraplegia [7–9]. The consequences of stigma range from moderate opprobrium at one end of the spectrum to death [10]

Multisymplectic formulation of fluid dynamics using the inverse map

We construct multisymplectic formulations of fluid dynamics using the inverse of the Lagrangian path map. This inverse map, the ‘back-to-labels’ map, gives the initial Lagrangian label of the fluid particle that currently occupies each Eulerian position. Explicitly enforcing the condition that the fluid particles carry their labels with the flow in Hamilton's principle leads to our multisymplectic formulation. We use the multisymplectic one-form to obtain conservation laws for energy, momentum and an infinite set of conservation laws arising from the particle relabelling symmetry and leading to Kelvin's circulation theorem. We discuss how multisymplectic numerical integrators naturally arise in this approach.</p

Socioeconomic inequalities in access to health care: Examining the case of Burkina Faso

Copyright @ 2011 Johns Hopkins University PressThe past decade has recorded remarkable interest in socioeconomic inequalities in health care. A multivariate analysis of the World Health Survey data for Burkina Faso was conducted using STATA. This included questions on household economic factors, perceived need, and access to health care. Poverty was defined using Principal Components Analysis. There was no significant difference in perceived need on the basis of poverty or gender. The less poor accessed health care more than the poor, but this difference was significant only among males. Respondents who lived in urban areas accessed health care more than those in rural areas, but this difference was significant only among females. We argue that health care financing arrangements affect self-reported need and access to health care. Even when they perceive need, the poor do not access care, probably because of cost, exacerbated by non-availability of readily accessible health care facilities

Students' everyday problems: a systematic qualitative analysis

The growing acceptance ofqualitative research promises to minimise the perceived gap between counselling practitioner and counselling researcher, but brings with it the challenge offinding methods for dealing systematically, yet respectfully, with textual data. This article presents just such a method. Seventy-five students provided brief descriptions of the everyday problems of their university careers. A random sample of these first hand accounts was then sorted by 30 further students. Hierarchical cluster analysis and multidimensional scaling procedures were used to construct a categorical and dimensional framework within which the original first hand accounts are explored in more detail

Precise service level agreements

SLAng is an XML language for defining service level agreements, the part of a contract between the client and provider of an Internet service that describes the quality attributes that the service is required to possess. We define the semantics of SLAng precisely by modelling the syntax of the language in UML, then embedding the language model in an environmental model that describes the structure and behaviour of services. The presence of SLAng elements imposes behavioural constraints on service elements, and the precise definition of these constraints using OCL constitutes the semantic description of the language. We use the semantics to define a notion of SLA compatibility, and an extension to UML that enables the modelling of service situations as a precursor to analysis, implementation and provisioning activities