612 research outputs found
A Mathematical Model of Tau Protein Hyperphosphorylation: The Effects of Kinase Inhibitors as a Theoretical Alzheimer\u27s Disease Therapy
Strategies for household energy conservation
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
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A scalable bubble-free membrane aerator for biosurfactant production
The bioeconomy is a paramount pillar in the mitigation of greenhouse gas emissions and climate change. Still, the industrialization of bioprocesses is limited by economical and technical obstacles. The synthesis of biosurfactants as advanced substitutes for crude-oil-based surfactants is often restrained by excessive foaming. We present the synergistic combination of simulations and experiments towards a reactor design of a submerged membrane module for the efficient bubble-free aeration of bioreactors. A digital twin of the combined bioreactor and membrane aeration module was created and the membrane arrangement was optimized in computational fluid dynamics studies with respect to fluid mixing. The optimized design was prototyped and tested in whole-cell biocatalysis to produce rhamnolipid biosurfactants from sugars. Without any foam formation, the new design enables a considerable higher space-time yield compared to previous studies with membrane modules. The design approach of this study is of generic nature beyond rhamnolipid production
A STAT3-inhibitory hairpin decoy oligodeoxynucleotide discriminates between STAT1 and STAT3 and induces death in a human colon carcinoma cell line
<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
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Petrology and Geochemistry of Boninite Series Volcanic Rocks,Chichi-jima, Bonin Islands, Japan
An Eocene submarine boninite series volcanic center isexposed on the island of Chichi-jima, Bonin Islands, Japan. Five rocktypes, boninite, bronzite andesite, dacite, quartz dacite, and rhyolite,were distinguished within the boninite volcanic sequence on the basis ofpetrographic and geochemical observations. Boninite lavas contain highmagnesium, nickel, and chromium contentsindicative of primitive melts,but have high silica contents relative to other mantle-derived magmas.All boninite series lavas contain very low incompatible elementconcentrations, and concentrations of high-field strength elements inprimitive boninite lavas are less than half of those found in depletedmid-ocean ridge basalts. Abundances of large-ion lithophile elements arerelatively high in boninite series lavas, similar to the enrichmentsobserved in many island arc lavas. Trends for both major and traceelement data suggest that the more evolved lavas of the boninite magmaseries were derived primarily through high-level fractionalcrystallization of boninite. Textural features, such as resorption andglomeroporphyrocrysts, and reverse chemical zonations suggest that magmamixing contributed to the development of the quartz dacitelavas
Development of a Modular Biosensor System for Rapid Pathogen Detection
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 42Â 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.
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
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
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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Perspectives in melanoma: meeting report from the Melanoma Bridge (December 5th-7th, 2019, Naples, Italy).
The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including sequential or combination treatment are being tested. Approaches to overcome resistance and to potentiate the immune response are being developed. Increasing evidence emerges that tissue and blood-based biomarkers can predict the response to a therapy. The latest findings in melanoma research, including insights into the tumor microenvironment and new biomarkers, improved understanding of tumor immune response and resistance, novel approaches for combination strategies and the role of neoadjuvant and adjuvant therapy, were the focus of discussions at the Melanoma Bridge meeting (5-7 December, 2019, Naples, Italy), which are summarized in this report
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