An orthonormalization procedure for multivariable function approximation

Where a function of several variables is given numerically in tabular form, an orthonormalization technique allows an approximation of the numerical data to be determined in a convenient functional form. In this technique, the speed and accuracy of coefficient computation are much improved

Primitive Divisors in Arithmetic Dynamics

Let F(z) be a rational function in Q(z) of degree at least 2 with F(0) = 0 and such that F does not vanish to order d at 0. Let b be a rational number having infinite orbit under iteration of F, and write F^n(b) = A_n/B_n as a fraction in lowest terms. We prove that for all but finitely many n > 0, the numerator A_n has a primitive divisor, i.e., there is a prime p such that p divides A_n and p does not divide A_i for all i < n. More generally, we prove an analogous result when F is defined over a number field and 0 is a periodic point for F.Comment: Version 2 is substantial revision. The proof of the main theorem has been simplified and strengthened. (16 pages

Rapid, solid-phase based automated analysis of chromatin structure and transcription factor occupancy in living eukaryotic cells

Transcription factors, chromatin components and chromatin modification activities are involved in many diseases including cancer. However, the means by which alterations in these factors influence the epigenotype of specific cell types is poorly understood. One problem that limits progress is that regulatory regions of eukaryotic genes sometimes extend over large regions of DNA. To improve chromatin structure–function analysis over such large regions, we have developed an automated, relatively simple procedure that uses magnetic beads and a capillary sequencer for ligation-mediated-PCR (LM-PCR). We show that the procedure can be used for the rapid examination of chromatin fine-structure, nucleosome positioning as well as changes in transcription factor binding-site occupancy during cellular differentiation

Weight changes following lower limb arthroplasty : a prospective observational study

The aim of this study was to assess patterns of weight loss/gain following total hip or knee joint replacement. Four hundred and fifty primary lower limb arthroplasty patients, where the current surgery was the last limiting factor to improved mobility, were selected. Over a one year period 212 gained weight (mean 5.03kg), 92 remained static, and 146 lost weight. The median change was a weight gain of 0.50Kg (p=0.002). All patients had a significant improvement in Oxford outcome scores. Hip arthroplasty patients were statistically more likely to gain weight than knee arthroplasty patients. A successful arthroplasty, restoring a patient's mobility, does not necessarily lead to subsequent weight loss. The majority of patients put on weight with an overall net weight gain. No adverse effect on functional outcome was noted

Blue light regenerates functional visual pigments in mammals through a retinyl-phospholipid intermediate.

The light absorbing chromophore in opsin visual pigments is the protonated Schiff base of 11-cis-retinaldehyde (11cRAL). Absorption of a photon isomerizes 11cRAL to all-trans-retinaldehyde (atRAL), briefly activating the pigment before it dissociates. Light sensitivity is restored when apo-opsin combines with another 11cRAL to form a new visual pigment. Conversion of atRAL to 11cRAL is carried out by enzyme pathways in neighboring cells. Here we show that blue (450-nm) light converts atRAL specifically to 11cRAL through a retinyl-phospholipid intermediate in photoreceptor membranes. The quantum efficiency of this photoconversion is similar to rhodopsin. Photoreceptor membranes synthesize 11cRAL chromophore faster under blue light than in darkness. Live mice regenerate rhodopsin more rapidly in blue light. Finally, whole retinas and isolated cone cells show increased photosensitivity following exposure to blue light. These results indicate that light contributes to visual-pigment renewal in mammalian rods and cones through a non-enzymatic process involving retinyl-phospholipids.It is currently thought that visual pigments in vertebrate photoreceptors are regenerated exclusively through enzymatic cycles. Here the authors show that mammalian photoreceptors also regenerate opsin pigments in light through photoisomerization of N-ret-PE (N-retinylidene-phosphatidylethanolamine

Proteomic analysis of skin invasion by blood fluke larvae.

BackgroundDuring invasion of human skin by schistosome blood fluke larvae (cercariae), a multicellular organism breaches the epidermis, basement membrane, and dermal barriers of skin. To better understand the pathobiology of this initial event in schistosome infection, a proteome analysis of human skin was carried out following invasion by cercariae of Schistosoma mansoni.Methodology and resultsHuman skin samples were exposed to cercariae for one-half hour to two hours. Controls were exposed to water used to collect cercariae in an identical manner, and punctured to simulate cercarial tunnels. Fluid from both control and experimental samples was analyzed by LC/MS/MS using a linear ion trap in "triple play" mode. The coexistence of proteins released by cercariae and host skin proteins from epidermis and basement membrane confirmed that cercarial tunnels in skin were sampled. Among the abundant proteins secreted by cercariae was the cercarial protease that has been implicated in degradation of host proteins, secreted proteins proposed to mediate immune invasion by larvae, and proteins implicated in protection of parasites against oxidative stress. Components of the schistosome surface tegument, previously identified with immune serum, were also released. Both lysis and apoptosis of epidermal cells took place during cercarial invasion of the epidermis. Components of lysed epidermal cells, including desmosome proteins which link cells in the stratum granulosum and stratum spinosum, were identified. While macrophage-derived proteins were present, no mast cell or lymphocyte cytokines were identified. There were, however, abundant immunoglobulins, complement factors, and serine protease inhibitors in skin. Control skin samples incubated with water for the same period as experimental samples ensured that invasion-related proteins and host protein fragments were not due to nonspecific degeneration of the skin samples.ConclusionsThis analysis identified secreted proteins from invasive larvae that are released during invasion of human skin. Analysis of specific host proteins in skin invaded by cercariae served to highlight both the histolytic events facilitating cercarial invasion, and the host defenses that attempt to arrest or retard invasion. Proteins abundant in psoriatic skin or UV and heat-stressed skin were not abundant in skin invaded by cercariae, suggesting that results did not reflect general stress in the surgically removed skin specimen. Abundant immunoglobulins, complement factors, and serine protease inhibitors in skin form a biochemical barrier that complements the structural barrier of the epidermis, basement membrane, and dermis. The fragmentation of some of these host proteins suggests that breaching of host defenses by cercariae includes specific degradation of immunoglobulins and complement, and either degradation of, or overwhelming the host protease inhibitor repertoire

Addressing the social determinants of health: A case study from the Mitanin (Community Health Worker) programme in India

The Mitanin Programme, a government community health worker (CHW) programme, was started in Chhattisgarh State of India in 2002. The CHWs (Mitanins) have consistently adopted roles that go beyond health programme- specific interventions to embrace community mobilization and action on local priorities. The aim of this research was to document how and why the Mitanins have been able to act on the social determinants of health, describing the catalysts and processes involved and the enabling programmatic and organiza- tional factors. A qualitative comparative case study of successful action by Mitanin was conducted in two ‘blocks’, purposefully selected as positive exemplars in two districts of Chhattisgarh. One case focused on malnutrition and the other on gender-based violence. Data collection involved 17 in-depth interviews and 10 group interviews with the full range of stakeholders in both blocks, including community members and programme team. Thematic analysis was done using a broad conceptual framework that was further refined. Action on social determinants involved raising awareness on rights, mobilizing women’s collectives, revitalizing local political structures and social action targeting both the community and government service providers. Through these processes, the Mitanins developed identities as agents of change and advocates for the community, both with respect to local cultural and gender norms and in ensuring accountability of service providers. The factors underpinning successful action on social determinants were identified as the significance of the original intent and vision of the programme, and how this was carried through into all aspects of programme design, the role of the Mitanins and their identification with village women, ongoing training and support, and the relative autonomy of the programme. Although the results are not narrowly generalizable and do not necessarily represent the situation of the Mitanin Programme as a whole, the explanatory framework may provide general lessons for programmes in similar contexts.Web of Scienc

Probability Models for Degree Distributions of Protein Interaction Networks

The degree distribution of many biological and technological networks has been described as a power-law distribution. While the degree distribution does not capture all aspects of a network, it has often been suggested that its functional form contains important clues as to underlying evolutionary processes that have shaped the network. Generally, the functional form for the degree distribution has been determined in an ad-hoc fashion, with clear power-law like behaviour often only extending over a limited range of connectivities. Here we apply formal model selection techniques to decide which probability distribution best describes the degree distributions of protein interaction networks. Contrary to previous studies this well defined approach suggests that the degree distribution of many molecular networks is often better described by distributions other than the popular power-law distribution. This, in turn, suggests that simple, if elegant, models may not necessarily help in the quantitative understanding of complex biological processes.