Utilization and Application of Business Computing Systems in Corporate Real Estate

This study reports on the utilization of business computing systems by corporate real estate executives. A survey was undertaken to examine four issues: types of property data collected, MIS report generation, hardware/software usage, and decision models and experts employed. NACORE members were surveyed and reported extensive usage of well-known business computing systems (e.g., transaction processing and management information systems), while newer systems (e.g., decision support and expert systems) are just beginning to be introduced into corporate real estate. Empirical analysis revealed differences among industries in the types of reports and property financial data that are maintained.

Production of glycoprotein vaccines in Escherichia coli

<p>Abstract</p> <p>Background</p> <p>Conjugate vaccines in which polysaccharide antigens are covalently linked to carrier proteins belong to the most effective and safest vaccines against bacterial pathogens. State-of-the art production of conjugate vaccines using chemical methods is a laborious, multi-step process. <it>In vivo </it>enzymatic coupling using the general glycosylation pathway of <it>Campylobacter jejuni </it>in recombinant <it>Escherichia coli </it>has been suggested as a simpler method for producing conjugate vaccines. In this study we describe the <it>in vivo </it>biosynthesis of two novel conjugate vaccine candidates against <it>Shigella dysenteriae </it>type 1, an important bacterial pathogen causing severe gastro-intestinal disease states mainly in developing countries.</p> <p>Results</p> <p>Two different periplasmic carrier proteins, AcrA from <it>C. jejuni </it>and a toxoid form of <it>Pseudomonas aeruginosa </it>exotoxin were glycosylated with <it>Shigella </it>O antigens in <it>E. coli</it>. Starting from shake flask cultivation in standard complex medium a lab-scale fed-batch process was developed for glycoconjugate production. It was found that efficiency of glycosylation but not carrier protein expression was highly susceptible to the physiological state at induction. After induction glycoconjugates generally appeared later than unglycosylated carrier protein, suggesting that glycosylation was the rate-limiting step for synthesis of conjugate vaccines in <it>E. coli</it>. Glycoconjugate synthesis, in particular expression of oligosaccharyltransferase PglB, strongly inhibited growth of <it>E. coli </it>cells after induction, making it necessary to separate biomass growth and recombinant protein expression phases. With a simple pulse and linear feed strategy and the use of semi-defined glycerol medium, volumetric glycoconjugate yield was increased 30 to 50-fold.</p> <p>Conclusions</p> <p>The presented data demonstrate that glycosylated proteins can be produced in recombinant <it>E. coli </it>at a larger scale. The described methodologies constitute an important step towards cost-effective <it>in vivo </it>production of conjugate vaccines, which in future may be used for combating severe infectious diseases, particularly in developing countries.</p

PTPN22 polymorphisms may indicate a role for this gene in atopic dermatitis in West Highland white terriers

Canine atopic dermatitis is an allergic inflammatory skin disease common in West Highland white terriers. A genome-wide association study for atopic dermatitis in a population of West Highland white terriers identified a 1.3 Mb area of association on CFA17 containing canine protein tyrosine phosphatase non-receptor type 22 (lymphoid) PTPN22. This gene is a potential candidate gene for canine atopic dermatitis as it encodes a lymphoid-specific signalling mediator that regulates T-cell and possibly B-cell activity.Sequencing of PTPN22 in three atopic and three non-atopic West Highland white terriers identified 18 polymorphisms, including five genetic variants with a bioinformatically predicted functional effect. An intronic polymorphic repeat sequence variant was excluded as the cause of the genome-wide association study peak signal, by large-scale genotyping in 72 West Highland white terriers (gene-dropping simulation method, P = 0.01).This study identified 18 genetic variants in PTPN22 that might be associated with atopic dermatitis in West Highland white terriers. This preliminary data may direct further study on the role of PTPN22 in this disease. Large scale genotyping and complementary genomic and proteomic assays would be required to assess this possibility

Methods of analysis for survival outcomes with time-updated mediators, with application to longitudinal disease registry data.

Mediation analysis is a useful tool to illuminate the mechanisms through which an exposure affects an outcome but statistical challenges exist with time-to-event outcomes and longitudinal observational data. Natural direct and indirect effects cannot be identified when there are exposure-induced confounders of the mediator-outcome relationship. Previous measurements of a repeatedly-measured mediator may themselves confound the relationship between the mediator and the outcome. To overcome these obstacles, two recent methods have been proposed, one based on path-specific effects and one based on an additive hazards model and the concept of exposure splitting. We investigate these techniques, focusing on their application to observational datasets. We apply both methods to an analysis of the UK Cystic Fibrosis Registry dataset to identify how much of the relationship between onset of cystic fibrosis-related diabetes and subsequent survival acts through pulmonary function. Statistical properties of the methods are investigated using simulation. Both methods produce unbiased estimates of indirect and direct effects in scenarios consistent with their stated assumptions but, if the data are measured infrequently, estimates may be biased. Findings are used to highlight considerations in the interpretation of the observational data analysis

Dynamic survival prediction combining landmarking with a machine learning ensemble: Methodology and empirical comparison

Dynamic prediction models provide predicted survival probabilities that can be updated over time for an individual as new measurements become available. Two techniques for dynamic survival prediction with longitudinal data dominate the statistical literature: joint modelling and landmarking. There is substantial interest in the use of machine learning methods for prediction; however, their use in the context of dynamic survival prediction has been limited. We show how landmarking can be combined with a machine learning ensemble—the Super Learner. The ensemble combines predictions from different machine learning and statistical algorithms with the goal of achieving improved performance. The proposed approach exploits discrete time survival analysis techniques to enable the use of machine learning algorithms for binary outcomes. We discuss practical and statistical considerations involved in implementing the ensemble. The methods are illustrated and compared using longitudinal data from the UK Cystic Fibrosis Registry. Standard landmarking and the landmark Super Learner approach resulted in similar cross-validated predictive performance, in this case, outperforming joint modelling

Mediation of the total effect of cystic fibrosis‐related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study

Abstract: Aim: To investigate whether the effect of cystic fibrosis‐related diabetes (CFRD) on the composite outcome of mortality or transplant could act through lung function, pulmonary exacerbations and/or nutritional status. Methods: A retrospective cohort of adult cystic fibrosis (CF) patients who had not been diagnosed with CFRD were identified from the UK Cystic Fibrosis Registry (n = 2750). Rate of death or transplant was compared between patients who did and did not develop CFRD (with insulin use) during follow‐up using Poisson regression, separately by sex. Causal mediation methods were used to investigate whether lung function, pulmonary exacerbations and nutritional status lie on the causal pathway between insulin‐treated CFRD and mortality/transplant. Results: At all ages, the mortality/transplant rate was higher in both men and women diagnosed with CFRD. Pulmonary exacerbations were the strongest mediator of the effect of CFRD on mortality/transplant, with an estimated 15% [95% CI: 7%, 28%] of the effect at 2 years post‐CFRD diagnosis attributed to exacerbations, growing to 24% [95% CI: 9%, 46%] at 4 years post‐diagnosis. Neither lung function nor nutritional status were found to be significant mediators of this effect. Estimates were similar but with wider confidence intervals in a cohort that additionally included people with CFRD but not using insulin. Conclusion: There is evidence that pulmonary exacerbations mediate the effect of CFRD on mortality but, as they are estimated to mediate less than one‐quarter of the total effect, the mechanism through which CFRD influences survival may involve other factors

CARMA3 Is a Critical Mediator of G Protein-Coupled Receptor and Receptor Tyrosine Kinase-Driven Solid Tumor Pathogenesis

The CARMA–Bcl10–MALT1 (CBM) signalosome is an intracellular protein complex composed of a CARMA scaffolding protein, the Bcl10 linker protein, and the MALT1 protease. This complex was first recognized because the genes encoding its components are targeted by mutation and chromosomal translocation in lymphoid malignancy. We now know that the CBM signalosome plays a critical role in normal lymphocyte function by mediating antigen receptor-dependent activation of the pro-inflammatory, pro-survival NF-κB transcription factor, and that deregulation of this signaling complex promotes B-cell lymphomagenesis. More recently, we and others have demonstrated that a CBM signalosome also operates in cells outside of the immune system, including in several solid tumors. While CARMA1 (also referred to as CARD11) is expressed primarily within lymphoid tissues, the related scaffolding protein, CARMA3 (CARD10), is more widely expressed and participates in a CARMA3-containing CBM complex in a variety of cell types. The CARMA3-containing CBM complex operates downstream of specific G protein-coupled receptors (GPCRs) and/or growth factor receptor tyrosine kinases (RTKs). Since inappropriate expression and activation of GPCRs and/or RTKs underlies the pathogenesis of several solid tumors, there is now great interest in elucidating the contribution of CARMA3-mediated cellular signaling in these malignancies. Here, we summarize the key discoveries leading to our current understanding of the role of CARMA3 in solid tumor biology and highlight the current gaps in our knowledge

Impact of Experience Corps® Participation on Children’s Academic Achievement and School Behavior

This article reports on the impact of the Experience Corps® (EC) Baltimore program, an intergenerational, school-based program aimed at improving academic achievement and reducing disruptive school behavior in urban, elementary school students in Kindergarten through third grade (K-3). Teams of adult volunteers aged 60 and older were placed in public schools, serving 15 h or more per week, to perform meaningful and important roles to improve the educational outcomes of children and the health and well-being of volunteers. Findings indicate no significant impact of the EC program on standardized reading or mathematical achievement test scores among children in grades 1–3 exposed to the program. K-1st grade students in EC schools had fewer principal office referrals compared to K-1st grade students in matched control schools during their second year in the EC program; second graders in EC schools had fewer suspensions and expulsions than second graders in non-EC schools during their first year in the EC program. In general, both boys and girls appeared to benefit from the EC program in school behavior. The results suggest that a volunteer engagement program for older adults can be modestly effective for improving selective aspects of classroom behavior among elementary school students in under-resourced, urban schools, but there were no significant improvements in academic achievement. More work is needed to identify individual- and school-level factors that may help account for these results

Disaster Risk Reduction, Climate Change Adaptation and Human Security: A Commissioned Report for the Norwegian Ministry of Foreign Affairs by the Global Environmental Change and Human Security (GECHS) Project

The Norwegian Nobel Committee awarded the 2007 Nobel Peace Prize to the Intergovernmental Panel on Climate Change and Al Gore, in an effort to ‘contribute to a sharper focus on the processes and decisions that appear to be necessary to protect the world’s future climate and thereby to reduce the threat to the security of mankind’. In the wake of the 2007 award, the relationship between climate change and security has surfaced as a key concern among national governments and international institutions