Addressing Food Production Planning and Control Issues through Information Visualisation: An Agile Development

Food manufacturers have a compelling requirement to address their information management needs in relation to the management of variation in their supply chain and subsequent production processes. However, many organisational information systems are not explicitly designed to address variation and uncertainty. The action research project outlined in this paper addresses a gap in the information management literature by showing how visualisation of information aided the efficacy of perishable goods production in a small food manufacturer. A user-centred, agile approach enabled the design and implementation of an integrated, dynamic visual production management system. Underpinned by a new manufacturing strategy, this system provided an information bridge between members of the organisation and in so doing facilitated improved communication and decision making across the company. The outcome of this action research project significantly enhanced the business performance. It is argued that the increased awareness of the actions and needs of others in the factory supported the enhanced efficacy in the production

Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets

Multidrug binding and transport by the ATP binding cassette transporter ABCG2 is a factor in the clinical resistance to chemotherapy in leukaemia, and a contributory factor to the pharmacokinetic profiles of many other prescribed drugs. Despite its importance, the structural basis of multidrug transport, i.e. the ability to transport multiple distinct chemicals, has remained elusive. Previous research has shown that at least two residues positioned towards the cytoplasmic end of transmembrane helix 3 (TM3) of the transporter play a role in drug transport. We hypothesised that other residues, either in the longitudinal span of TM3, or a perpendicular slice through the intracellular end of other TM helices would also contribute to drug binding and transport by ABCG2. Single point mutant isoforms of ABCG2 were made at approximately 30 positions and were analysed for effects on protein expression, localisation (western blotting, confocal microscopy) and function (flow cytometry) in a mammalian stable cell line expression system. Our data were interpreted in terms of recent structural data on the ABCG protein subfamily and enabled us to propose a surface binding site for the drug mitoxantrone as well as a second, buried site for the same drug. Further mutational analysis of residues that spatially separate these two sites prompt us to suggest a molecular and structural pathway for mitoxantrone binding by ABCG2

CONTINUOUS AND DISCRETE BAROCLINIC MODES IN CONTINUOUSLY VARYING STRATIFICATION

We study the behavior of baroclinic modes in a continuously stratified fluid and theirdiscrete representation in a layer model. The modes are shown to rapidly approach simple sinusoidalbehavior under a Charney-coordinate transform. We propose a corresponding grid scheme to near-optimally preserve the oscillating structure in the discrete modes. The discrete modal representationand analysis are relevant for quasi-geostrophic models and are also shown to apply to the primitiveequations using a common discretization scheme.</p

The multidrug transporter ABCG2: still more questions than answers

ABCG2 is one of at least three human ATP binding cassette (ABC) transporters which can facilitate the export from cells of a wide range of chemically unrelated drug molecules. This capacity for multidrug transport is not only a confounding factor in chemotherapy, but is also one of the more perplexing phenomena in transporter biochemistry. Since its discovery in the last decade of the 20th century much has been revealed about ABCG2's localization, physiological function and its broad substrate range. There have also been many investigations of its structure and molecular mechanism. In this mini review article we take a Rumsfeldian approach to ABCG2 and essentially ask what we do know about this transporter, and what we will need to know about this transporter if we wish to use modulation of ABCG2 activity as a therapeutic approach

Bicarbonate and dichloroacetate: Evaluating pH altering therapies in a mouse model for metastatic breast cancer

BACKGROUND:The glycolytic nature of malignant tumors contributes to high levels of extracellular acidity in the tumor microenvironment. Tumor acidity is a driving force in invasion and metastases. Recently, it has been shown that buffering of extracellular acidity through systemic administration of oral bicarbonate can inhibit the spread of metastases in a mouse model for metastatic breast cancer. While these findings are compelling, recent assessments into the use of oral bicarbonate as a cancer intervention reveal limitations.METHODS:We posited that safety and efficacy of bicarbonate could be enhanced by dichloroacetate (DCA), a drug that selectively targets tumor cells and reduces extracellular acidity through inhibition of glycolysis. Using our mouse model for metastatic breast cancer (MDA-MB-231), we designed an interventional survival study where tumor bearing mice received bicarbonate, DCA, or DCA-bicarbonate (DB) therapies chronically.RESULTS:Dichloroacetate alone or in combination with bicarbonate did not increase systemic alkalosis in mice. Survival was longest in mice administered bicarbonate-based therapies. Primary tumor re-occurrence after surgeries is associated with survival rates. Although DB therapy did not significantly enhance oral bicarbonate, we did observe reduced pulmonary lesion diameters in this cohort. The DCA monotherapy was not effective in reducing tumor size or metastases or improving survival time. We provide in vitro evidence to suggest this outcome may be a function of hypoxia in the tumor microenvironment.CONCLUSIONS:DB combination therapy did not appear to enhance the effect of chronic oral bicarbonate. The anti-tumor effect of DCA may be dependent on the cancer model. Our studies suggest DCA efficacy is unpredictable as a cancer therapy and further studies are necessary to determine the role of this agent in the tumor microenvironment.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Use of communities of practice in business and health care sectors: A systematic review

<p>Abstract</p> <p>Background</p> <p>Since being identified as a concept for understanding knowledge sharing, management, and creation, communities of practice (CoPs) have become increasingly popular within the health sector. The CoP concept has been used in the business sector for over 20 years, but the use of CoPs in the health sector has been limited in comparison.</p> <p>Objectives</p> <p>First, we examined how CoPs were defined and used in these two sectors. Second, we evaluated the evidence of effectiveness on the health sector CoPs for improving the uptake of best practices and mentoring new practitioners.</p> <p>Methods</p> <p>We conducted a search of electronic databases in the business, health, and education sectors, and a hand search of key journals for primary studies on CoP groups. Our research synthesis for the first objective focused on three areas: the authors' interpretations of the CoP concept, the key characteristics of CoP groups, and the common elements of CoP groups. To examine the evidence on the effectiveness of CoPs in the health sector, we identified articles that evaluated CoPs for improving health professional performance, health care organizational performance, professional mentoring, and/or patient outcome; and used experimental, quasi-experimental, or observational designs.</p> <p>Results</p> <p>The structure of CoP groups varied greatly, ranging from voluntary informal networks to work-supported formal education sessions, and from apprentice training to multidisciplinary, multi-site project teams. Four characteristics were identified from CoP groups: social interaction among members, knowledge sharing, knowledge creation, and identity building; however, these were not consistently present in all CoPs. There was also a lack of clarity in the responsibilities of CoP facilitators and how power dynamics should be handled within a CoP group. We did not find any paper in the health sector that met the eligibility criteria for the quantitative analysis, and so the effectiveness of CoP in this sector remained unclear.</p> <p>Conclusion</p> <p>There is no dominant trend in how the CoP concept is operationalized in the business and health sectors; hence, it is challenging to define the parameters of CoP groups. This may be one of the reasons for the lack of studies on the effectiveness of CoPs in the health sector. In order to improve the usefulness of the CoP concept in the development of groups and teams, further research will be needed to clarify the extent to which the four characteristics of CoPs are present in the mature and emergent groups, the expectations of facilitators and other participants, and the power relationship within CoPs.</p

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Binding and functional properties of natural anti-T cell receptor antibodies in patients with rheumatoid arthritis

Natural autoantibodies specific for the T cell receptor (TCR) are present in all human sera. Differences in titer, epitope specificity, and isotype depend on physiological condition, viral infections, or the presence of autoimmune diseases. Individuals with rheumatoid arthritis (RA) make significantly higher titers of IgM isotype autoantibodies demonstrating major reactivity for the CDR1 region of the Vβ TCR. To establish a more intimate understanding of the role of these antibodies in the immune system we generated B cell hetero-hybridomas secreting monoclonal IgM autoantibodies from the synovial tissue and peripheral blood of RA patients. We report molecular and partial functional characterization of seven IgM anti-TCR monoclonal antibodies (mAbs). These autoantibodies were selected on a recombinant TCR and peptide epitopes and bind JURKAT human T cell lines and a subset of CD3⁺ human peripheral blood mononuclear cells (PBMCs) in flow cytometry experiments. The V regions of these antibodies were generally identical to germline sequences in both the heavy and the light chains and the heavy-chain CDR3 segments did not correspond to known antibody sequence. Three of these anti-TCR mAbs, OR2, ORS, and Syn 2H-11, demonstrated an antigen specific binding property defined as epitope recognition promiscuity. The molecules did not act as rheumatoid factors. These same mAbs bound to subsets of murine T cells and TCR peptide epitopes. The autoantibodies did not induce apoptosis in vitro, but prevented IL-2 production by antigen-specific T cells. These findings describe a unique group of immunoregulatory antibodies and represent a foundation for further investigations and their eventual use as therapeutic agents in human disease

Examining the relationship between diet-induced acidosis and cancer

Increased cancer risk is associated with select dietary factors. Dietary lifestyles can alter systemic acid-base balance over time. Acidogenic diets, which are typically high in animal protein and salt and low in fruits and vegetables, can lead to a sub-clinical or low-grade state of metabolic acidosis. The relationship between diet and cancer risk prompts questions about the role of acidosis in the initiation and progression of cancer. Cancer is triggered by genetic and epigenetic perturbations in the normal cell, but it has become clear that microenvironmental and systemic factors exert modifying effects on cancer cell development. While there are no studies showing a direct link between diet-induced acidosis and cancer, acid-base disequilibrium has been shown to modulate molecular activity including adrenal glucocorticoid, insulin growth factor (IGF-1), and adipocyte cytokine signaling, dysregulated cellular metabolism, and osteoclast activation, which may serve as intermediary or downstream effectors of carcinogenesis or tumor promotion. In short, diet-induced acidosis may influence molecular activities at the cellular level that promote carcinogenesis or tumor progression. This review defines the relationship between dietary lifestyle and acid-base balance and discusses the potential consequences of diet-induced acidosis and cancer occurrence or progression.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]