Modeled structure of the whole regulator G-protein signaling-2

There is an increasing interest towards the mechanism by which regulators of G-protein signaling regulate signals of G-protein-coupled receptors. RGS2 is a regulator of Gq protein signaling (RGS), the N-terminal region of which is known to contain determinants for G protein-coupled receptor recognition, but its structure is still unknown. To understand the molecular basis for this recognition, the three-dimensional model of RGS2, including N-terminal region and RGS box, was modeled. For this, RGS4 box structure and data from circular dichroism study of RGS2 N-terminal region were used. Then, membrane-targeting activity of the RGS2 amphipathic helix contained in the N-terminal region was investigated. Furthermore, in cellulo study provided first evidence that an internal sequence within the N-terminal region of RGS2 is involved in RGS2 regulation of cholecystokinin receptor-2 signal. RGS2 modeled structure can now serve to study molecular recognition of RGS2 by signaling molecules. © 2006 Elsevier Inc. All rights reserved.

Simulation of whole building coupled hygrothermal-airflow transfer in different climates

The coupled heat, air and moisture transfer between building envelopes and indoor air is complicated, and has a significant influence on the indoor environment and the energy performance of buildings. In the paper, a model for predicting coupled multi-zone hygrothermal-airflow transfer is presented. Both heat and moisture transfer in the building envelope and multi-zone indoor airflow are simultaneously considered; their interactions are modeled. The coupled system model is implemented into Matlab–Simulink, and is validated by using a series of testing tools and experiments. The new program is applied to investigate the moisture transfer effect on indoor air humidity and building energy consumption in different climates (hot-humid, temperate and hot-dry climates). The results show that not accounting for hygrothermal effects in modeling will result in overestimation of energy costs for hot and humid climate situations and possible over sizing of plant leading to inefficient operation.

Part-whole relations between food webs and the validity of local food-web descriptions

This work analyzes the relationship between large food webs describing potential feeding relations between species and smaller sub-webs thereof describing relations actually realized in local communities of various sizes. Special attention is given to the relationships between patterns of phylogenetic correlations encountered in large webs and sub-webs. Based on the current theory of food-web topology as implemented in the matching model, it is shown that food webs are scale invariant in the following sense: given a large web described by the model, a smaller, randomly sampled sub-web thereof is described by the model as well. A stochastic analysis of model steady states reveals that such a change in scale goes along with a re-normalization of model parameters. Explicit formulae for the renormalized parameters are derived. Thus, the topology of food webs at all scales follows the same patterns, and these can be revealed by data and models referring to the local scale alone. As a by-product of the theory, a fast algorithm is derived which yields sample food webs from the exact steady state of the matching model for a high-dimensional trophic niche space in finite time. (C) 2008 Elsevier B.V. All rights reserved.

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis.

Objective To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. Methods Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the “gold standard measure,” chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. Results The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. Conclusion We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.

Para-inflammation-mediated retinal recruitment of bone marrow-derived myeloid cells following whole-body irradiation is CCL2 dependent

Previous studies have shown that following whole-body irradiation bone marrow (BM)-derived cells can migrate into the central nervous system, including the retina, to give rise to microglia-like cells. The detailed mechanism, however, remains elusive. We show in this study that a single-dose whole-body ?-ray irradiation (8 Gy) induced subclinical damage (i.e., DNA damage) in the neuronal retina, which is accompanied by a low-grade chronic inflammation, para-inflammation, characterized by upregulated expression of chemokines (CCL2, CXCL12, and CX3CL1) and complement components (C4 and CFH), and microglial activation. The upregulation of chemokines CCL2 and CXCL12 and complement C4 lasted for more than 160 days, whereas the expression of CX3CL1 and CFH was upregulated for 2 weeks. Both resident microglia and BM-derived phagocytes displayed mild activation in the neuronal retina following irradiation. When BM cells from CX3CR1gfp/+ mice or CX3CR1gfp/gfp mice were transplanted to wild-type C57BL/6 mice, more than 90% of resident CD11b+ cells were replaced by donor-derived GFP+ cells after 6 months. However, when transplanting CX3CR1gfp/+ BM cells into CCL2-deficient mice, only 20% of retinal CD11b+ cells were replaced by donor-derived cells at 6 month. Our results suggest that the neuronal retina suffers from a chronic stress following whole-body irradiation, and a para-inflammatory response is initiated, presumably to rectify the insults and maintain homeostasis. The recruitment of BM-derived myeloid cells is a part of the para-inflammatory response and is CCL2 but not CX3CL1 dependent. © 2012 Wiley Periodicals, Inc.

Detection of streptomycin residues in whole milk using an optical immunobiosensor

The development of an assay for the detection of streptomycin residues in pasteurized whole milk using an optical biosensor (Biacore) is reported. Streptomycin-adipic hydrazide coupled to bovine thyroglobulin was used to produce a sheep polyclonal antibody. The antibody displayed excellent cross-reactivity with dihydrostreptomycin (106%). There was no significant cross-reaction with other aminoglycosides or common antibiotics. Streptomycin was also immobilized onto a CM5 sensor chip to provide a stable, reusable surface. The developed assay permitted the direct analysis of whole milk samples (similar to3.5% fat) without prior centrifugation and defatting. Results were available in 5 min. The limit of detection of the assay was determined as 4.1 ng/mL, well below the European maximum residue limit (MRL) of 200 ng/mL. Repeatability (or coefficient of variation) between runs was determined as 3.5% (100 ng/mL; 0.5 x MRL), 5.7% (200 ng/mL; MRL), and 7.6% (400 ng/mL; 2 x MRL).

Managing Cultural Diversity in Healthcare Partnerships: The Case of LIFT

Purpose: The National Health Service (NHS) Local Improvement Finance Trust (LIFT) programme was launched in 2001 as an innovative public-private partnership to address the historical under-investment in local primary care facilities in England. The organisations from the public and private sector that comprise a local LIFT partnership each have their own distinctive norms of behaviour and acceptable working practices - ultimately different organisational cultures. The purpose of this article is to assess the role of organisational culture in facilitating (or impeding) LIFT partnerships and to contribute to an understanding of how cultural diversity in public-private partnerships is managed at the local level. Design/methodology/approach: The approach taken was qualitative case studies, with data gathering comprising interviews and a review of background documentation in three LIFT companies purposefully sampled to represent a range of background factors. Elite interviews were also conducted with senior policy makers responsible for implementing LIFT policy at the national level. Findings: Interpreting the data against a conceptual framework designed to assess approaches to managing strategic alliances, the authors identified a number of key differences in the values, working practices and cultures in public and private organisations that influenced the quality of joint working. On the whole, however, partners in the three LIFT companies appeared to be working well together, with neither side dominating the development of strategy. Differences in culture were being managed and accommodated as partnerships matured. Research limitations/implications: As LIFT develops and becomes the primary source of investment for managing, developing and channelling funding into regenerating the primary care infrastructure, further longitudinal work might examine how ongoing partnerships are working, and how changes in the cultures of public and private partners impact upon wider relationships within local health economies and shape the delivery of patient care. Originality/value: To the authors' knowledge this is the first study of the role of culture in mediating LIFT partnerships and the findings add to the evidence on public-private partnerships in the NHS