612 research outputs found

    Strategies for household energy conservation

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    The energy consumed by households for space heating and cooling, water heating, cooking and running appliances is a major component of national final energy use. Along with private transport, it is the only energy use (and corresponding greenhouse gas emissions) directly under householders’ control. Accordingly, many researchers have examined ways of reducing household energy use, using either monetary or non-monetary measures. We find that although case studies suggest only a limited role for energy pricing, our comparative study of domestic energy use by different nations suggests otherwise. Energy researchers have also examined various social science approaches, but again their effectiveness in case studies is limited. We argue, however, that householders, taking their cue from political leaders, do not presently take climate change very seriously. This attitude could well change over the next decade or so, and with it the scope for non-monetary approaches to energy and thus carbon reductions

    A STAT3-inhibitory hairpin decoy oligodeoxynucleotide discriminates between STAT1 and STAT3 and induces death in a human colon carcinoma cell line

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    <p>Abstract</p> <p>Background</p> <p>The Signal Transducer and Activator of Transcription 3 (STAT3) is activated in tumor cells, and STAT3-inhibitors are able to induce the death of those cells. Decoy oligodeoxynucleotides (dODNs), which bind to the DNA Binding Domain (DBD) of STAT3, are efficient inhibitors. However, they also inhibit STAT1, whose activity is essential not only to resistance to pathogens, but also to cell growth inhibition and programmed cell death processes. The aim of this study was to design STAT3-specific dODNs which do not affect STAT1-mediated processes.</p> <p>Results</p> <p>New dODNs with a hairpin (hpdODNs) were designed. Modifications were introduced, based on the comparison of STAT3- and STAT1-DBD interactions with DNA using 3D structural analyses. The designed hpdODNs were tested for their ability to inhibit STAT3 but not STAT1 by determining: i) cell death in the active STAT3-dependent SW480 colon carcinoma cell line, ii) absence of inhibition of interferon (IFN) γ-dependent cell death, iii) expression of STAT1 targets, and iv) nuclear location of STAT3 and STAT1. One hpdODN was found to efficiently induce the death of SW480 cells without interfering with IFNγ-activated STAT1. This hpdODN was found in a complex with STAT3 but not with STAT1 using an original in-cell pull-down assay; this hpdODN also did not inhibit IFNγ-induced STAT1 phosphorylation, nor did it inhibit the expression of the STAT1-target IRF1. Furthermore, it prevented the nuclear transfer of STAT3 but not that of IFNγ-activated STAT1.</p> <p>Conclusions</p> <p>Comparative analyses at the atomic level revealed slight differences in STAT3 and STAT1 DBDs' interaction with their DNA target. These were sufficient to design a new discriminating hpdODN that inhibits STAT3 and not STAT1, thereby inducing tumor cell death without interfering with STAT1-dependent processes. Preferential interaction with STAT3 depends on oligodeoxynucleotide sequence modifications but might also result from DNA shape changes, known to modulate protein/DNA interactions. The finding of a STAT3-specific hpdODN establishes the first rational basis for designing STAT3 DBD-specific inhibitors.</p

    Development of a Modular Biosensor System for Rapid Pathogen Detection

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    Progress in the field of pathogen detection relies on at least one of the following three qualities: selectivity, speed, and cost-effectiveness. Here, we demonstrate a proof of concept for an optical biosensing system for the detection of the opportunistic human pathogen Pseudomonas aeruginosa while addressing the abovementioned traits through a modular design. The biosensor detects pathogen-specific quorum sensing molecules and generates a fluorescence signal via an intracellular amplifier. Using a tailored measurement device built from low-cost components, the image analysis software detected the presence of P. aeruginosa in 42 min of incubation. Due to its modular design, individual components can be optimized or modified to specifically detect a variety of different pathogens. This biosensor system represents a successful integration of synthetic biology with software and hardware engineering

    ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment.

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    TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy) ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G) in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment

    Emotional reactions to involuntary psychiatric hospitalization and stigma-related stress among people with mental illness

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    Compulsory admission to psychiatric inpatient treatment can be experienced as disempowering and stigmatizing by people with serious mental illness. However, quantitative studies of stigma-related emotional and cognitive reactions to involuntary hospitalization and their impact on people with mental illness are scarce. Among 186 individuals with serious mental illness and a history of recent involuntary hospitalization, shame and self-contempt as emotional reactions to involuntary hospitalization, the cognitive appraisal of stigma as a stressor, self-stigma, empowerment as well as quality of life and self-esteem were assessed by self-report. Psychiatric symptoms were rated by the Brief Psychiatric Rating Scale. In multiple linear regressions, more self-stigma was predicted independently by higher levels of shame, self-contempt and stigma stress. A greater sense of empowerment was related to lower levels of stigma stress and self-contempt. These findings remained significant after controlling for psychiatric symptoms, diagnosis, age, gender and the number of lifetime involuntary hospitalizations. Increased self-stigma and reduced empowerment in turn predicted poorer quality of life and reduced self-esteem. The negative effect of emotional reactions and stigma stress on quality of life and self-esteem was largely mediated by increased self-stigma and reduced empowerment. Shame and self-contempt as reactions to involuntary hospitalization as well as stigma stress may lead to self-stigma, reduced empowerment and poor quality of life. Emotional and cognitive reactions to coercion may determine its impact more than the quantity of coercive experiences. Interventions to reduce the negative effects of compulsory admissions should address emotional reactions and stigma as a stressor

    Data Assimilation Enhancements to Air Force Weathers Land Information System

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    The United States Air Force (USAF) has a proud and storied tradition of enabling significant advancements in the area of characterizing and modeling land state information. 557th Weather Wing (557 WW; DoDs Executive Agent for Land Information) provides routine geospatial intelligence information to warfighters, planners, and decision makers at all echelons and services of the U.S. military, government and intelligence community. 557 WW and its predecessors have been home to the DoDs only operational regional and global land data analysis systems since January 1958. As a trusted partner since 2005, Air Force Weather (AFW) has relied on the Hydrological Sciences Laboratory at NASA/GSFC to lead the interagency scientific collaboration known as the Land Information System (LIS). LIS is an advanced software framework for high performance land surface modeling and data assimilation of geospatial intelligence (GEOINT) information
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