Illuminance and luminance distributions of a prototype ambient illumination system for Space Station Freedom

Preliminary results of research conducted in the late 1970's indicate that perceptual qualities of an enclosure can be influenced by the distribution of illumination within the enclosure. Subjective impressions such as spaciousness, perceptual clarity, and relaxation or tenseness, among others, appear to be related to different combinations of surface luminance. A prototype indirect ambient illumination system was developed which will allow crew members to alter surface luminance distributions within an enclosed module, thus modifying perceptual cues to match crew preferences. A traditional lensed direct lighting system was compared to the prototype utilizing the full-scale mockup of Space Station Freedom developed by Marshall Space Flight Center. The direct lensed system was installed in the habitation module with the indirect prototype deployed in the U.S. laboratory module. Analysis centered on the illuminance and luminance distributions resultant from these systems and the implications of various luminaire spacing options. All test configurations were evaluated for compliance with NASA Standard 3000, Man-System Integration Standards

Cardio-metabolic risk factors and prehypertension in persons without diabetes, hypertension, and cardiovascular disease

10.1186/1471-2458-13-730BMC Public Health131

Bridging health technology assessment (HTA) with multicriteria decision analyses (MCDA): field testing of the EVIDEM framework for coverage decisions by a public payer in Canada

<p>Abstract</p> <p>Background</p> <p>Consistent healthcare decisionmaking requires systematic consideration of decision criteria and evidence available to inform them. This can be tackled by combining multicriteria decision analysis (MCDA) and Health Technology Assessment (HTA). The objective of this study was to field-test a decision support framework (EVIDEM), explore its utility to a drug advisory committee and test its reliability over time.</p> <p>Methods</p> <p>Tramadol for chronic non-cancer pain was selected by the health plan as a case study relevant to their context. Based on extensive literature review, a by-criterion HTA report was developed to provide synthesized evidence for each criterion of the framework (14 criteria for the MCDA Core Model and 6 qualitative criteria for the Contextual Tool). During workshop sessions, committee members tested the framework in three steps by assigning: 1) weights to each criterion of the MCDA Core Model representing individual perspective; 2) scores for tramadol for each criterion of the MCDA Core Model using synthesized data; and 3) qualitative impacts of criteria of the Contextual Tool on the appraisal. Utility and reliability of the approach were explored through discussion, survey and test-retest. Agreement between test and retest data was analyzed by calculating intra-rater correlation coefficients (ICCs) for weights, scores and MCDA value estimates.</p> <p>Results</p> <p>The framework was found useful by the drug advisory committee in supporting systematic consideration of a broad range of criteria to promote a consistent approach to appraising healthcare interventions. Directly integrated in the framework as a "by-criterion" HTA report, synthesized evidence for each criterion facilitated its consideration, although this was sometimes limited by lack of relevant data. Test-retest analysis showed fair to good consistency of weights, scores and MCDA value estimates at the individual level (ICC ranging from 0.676 to 0.698), thus lending some support for the reliability of the approach. Overall, committee members endorsed the inclusion of most framework criteria and revealed important areas of discussion, clarification and adaptation of the framework to the needs of the committee.</p> <p>Conclusions</p> <p>By promoting systematic consideration of all decision criteria and the underlying evidence, the framework allows a consistent approach to appraising healthcare interventions. Further testing and validation are needed to advance MCDA approaches in healthcare decisionmaking.</p

Dissecting the transcriptional networks underlying breast cancer: NR4A1 reduces the migration of normal and breast cancer cell lines

Introduction: Breast cancer currently accounts for more than one-quarter of all female cancers and, despite the great progress in treatment observed in the past few years, the need for identification of new gene targets that can be used for diagnosis, prognosis and therapy is evident. A previous study identified the transcription factor NR4A1 as a gene upregulated in primary breast cancer compared with normal tissue by microarray analysis and sequencing technologies. The purpose of the study was to identify the role of NR4A1 in normal mammary epithelial and breast cancer cell biology.Methods: NR4A1 expression in breast tumours was assessed by semiquantitative and real-time PCR using RNA from normal and tumour samples or breast cancer cell lines. Immunohistochemistry on tissue microarrays was performed to check NR4A1 protein expression in breast tumours. MCF-10A and 226L normal mammary epithelial cells as well as the tumour lines PMC42, ZR-75-1 and MDA-MB-231 were transduced with full-length NR4A1, and the ability of NR4A1-overexpressing cells to migrate was tested using scratch wound or transwell migration assays. Proliferation was measured using the MTT and BrdU assays, while apoptosis was determined by the Annexin V assay. The ability of the cells to adhere to extracellular matrix was tested by adhesion assays and integrin cell surface expression was measured by flow cytometry. Activation of the FAK as well as ERK1/2 and PI3K pathways was checked by western blotting.Results: Breast tissue microarray analysis showed NR4A1 expression in primary tumours, which was reduced in higher grade and metastatic tumours. Ectopic expression of NR4A1 in MCF-10A, 226L, PMC42 and ZR-75-1 cells led to reduced ability of the cells to migrate, while no differences were observed in their proliferation and apoptotic index. NR4A1 expression altered the ability of the MCF-10A cells to adhere to the extracellular matrix and affected cell surface expression of integrins.Conclusions: NR4A1 acts as an antimigratory factor in two normal mammary epithelial and two breast cancer cell lines tested. It is therefore possible that NR4A1 acts as an antimigratory factor in breast tumours, and further studies should be conducted to understand the mechanisms involved

Pooled extracellular receptor-ligand interaction screening using CRISPR activation.

Extracellular interactions between cell surface receptors are necessary for signaling and adhesion but identifying them remains technically challenging. We describe a cell-based genome-wide approach employing CRISPR activation to identify receptors for a defined ligand. We show receptors for high-affinity antibodies and low-affinity ligands can be unambiguously identified when used in pools or as individual binding probes. We apply this technique to identify ligands for the adhesion G-protein-coupled receptors and show that the Nogo myelin-associated inhibitory proteins are ligands for ADGRB1. This method will enable extracellular receptor-ligand identification on a genome-wide scale

NR4A orphan nuclear receptor family members, NR4A2 and NR4A3, regulate neutrophil number and survival.

Neutrophil lifespan is plastic and highly responsive to factors that regulate cellular survival. Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signaling, which positively regulates neutrophil survival. The aim of this study was to define transcriptional responses to PKA activation and to delineate the roles of these factors in neutrophil function and survival. In human neutrophil gene array studies, we show that PKA activation upregulates a significant number of apoptosis related genes, the most highly regulated of these being NR4A2 and NR4A3 Direct PKA activation by the site-selective PKA agonist pair N6/8-AHA and treatment with endogenous activators of PKA, including adenosine and PGE2, results in a profound delay of neutrophil apoptosis and concomitant upregulation of NR4A2/3 in a PKA dependent manner. NR4A3 expression is also increased at sites of neutrophilic inflammation in a human model of intradermal inflammation. PKA activation also promotes survival of murine neutrophil progenitor cells, and siRNA to NR4A2 decreases neutrophil production in this model. Antisense knockdown of NR4A2 and NR4A3 homologues in zebrafish larvae significantly reduces absolute neutrophil number without affecting cellular migration. In summary, we show that NR4A2 and NR4A3 are components of a downstream transcriptional response to PKA activation in the neutrophil, and that they positively regulate neutrophil survival and homeostasis

Controls on Water Use for Thermoelectric Generation: Case Study Texas, U.S.

Large-scale U.S. dependence on thermoelectric (steam electric) generation requiring water for cooling underscores the need to understand controls on this water use. The study objective was to quantify water consumption and withdrawal for thermoelectric generation, identifying controls, using Texas as a case study. Water consumption for thermoelectricity in Texas in 2010 totaled ∼0.43 million acre feet (maf; 0.53 km³), accounting for ∼4% of total state water consumption. High water withdrawals (26.2 maf, 32.3 km³) mostly reflect circulation between ponds and power plants, with only two-thirds of this water required for cooling. Controls on water consumption include (1) generator technology/thermal efficiency and (2) cooling system, resulting in statewide consumption intensity for natural gas combined cycle generators with mostly cooling towers (0.19 gal/kWh) being 63% lower than that of traditional coal, nuclear, or natural gas steam turbine generators with mostly cooling ponds (0.52 gal/kWh). The primary control on water withdrawals is cooling system, with ∼2 orders of magnitude lower withdrawals for cooling towers relative to once-through ponds statewide. Increases in natural gas combined cycle plants with cooling towers in response to high production of low-cost natural gas has greatly reduced water demand for thermoelectric cooling since 2000