224 research outputs found

    Wastewater as a Heat Source for Individual Residence Heating: A Techno-economic Feasibility Study in the Brussels Capital Region

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    A large part of the thermal energy in buildings is lost through the drain and ends up as warm wastewater in the sewer system. The installation of heat exchangers in the sewer system enables a rise of the source temperature of heat pumps, increasing their coefficient of performance. To investigate the potential of such a technique in the Brussels Capital Region, a test facility named MYRTES has been installed in the sewer network, the starting point of this facility being to have one heat recovery system per residence. To estimate the heat recovery rate, potentially available in the Brussels Capital Region, the data from this test facility have been used as inputs and validation for a predictive model, considering both the heat recovery and its financial and environmental implications. Simulations show a minimum heating power of the heat pump of 6.3 kW, at a hot water temperature of 45 °C. A maximum of 35% of the buildings in the Brussels Capital Region are eligible for the use of such a system. At current tariffs, the levelized cost of energy for these systems, is lower than for traditional air heat pumps, but is higher than for gas boiler systems. The total equivalent warming impact, however, is estimated to be around 49% lower than for gas boiler systems and around 13% lower than for air heat pumps. In conclusion, heating through these types of systems is more expensive than gas boiler systems, but with increased consumption the competitiveness of these systems improves

    Experimental and CFD investigation of cavitation phenomenon in the distributor of a Banki-Michell Turbine

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    Cavitation is a physical phenomenon that often occurs in hydraulic machines such as pumps, valves, and turbines. Although the Banki-Michell turbine has been used for a long time in small hydropower, no study related to this phenomenon of cavitation in the injector of this turbine has been done. In this study, we will present the results of a numerical study carried out in the nozzle of a Banki-Michell turbine. The numerical solution of the Navier Stokes cavitation equations of the Banki-Michell turbine injector was carried out considering a 2D geometry of the injector-rotor assembly. The simulation results showed that the cavitation phenomenon appears when the water flow area in the nozzle becomes less than 50%. Furthermore, the results also showed that the occurrence of this cavitation phenomenon in the injector is more likely at higher operating heads. The results of an experimental study of the geometry of the injector showed that the height of the water passage section varies linearly with the degree of opening of the stator valve

    The epidemiology of major incidents in the Western Cape Province, South Africa

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    Background. Major incidents put pressure on any health system. There are currently no studies describing the epidemiology of major incidents in South Africa (SA). The lack of data makes planning for major incidents and exercising of major incident plans difficult.Objective. To describe the epidemiology of major incidents in the Western Cape Province, SA.Methods. A retrospective analysis of the Western Cape Major Incident database was conducted for the period 1 December 2008 - 30 June 2014. Variables collected related to patient demographics and incident details. Summary statistics were used to describe all variables.Results. Seven hundred and seventy-seven major incidents were reviewed (median n=11 per month). Most major incidents occurred in the City of Cape Town (57.8%, n=449), but the Central Karoo district had the highest incidence (11.97/10 000 population). Transport-related incidents occurred most frequently (94.0%, n=730). Minibus taxis were involved in 312 major incidents (40.2%). There was no significant difference between times of day when incidents occurred. A total of 8 732 patients were injured (median n=8 per incident); ten incidents involved 50 or more victims. Most patients were adults (80.0%, n=6 986) and male (51.0%, n=4 455). Of 8 440 patients, 630 (7.5%) were severely injured. More than half of the patients sustained minor injuries (54.6%, n=4 605).Conclusion. Major incidents occurred more often than would have been expected compared with other countries, with road traffic crashes the biggest contributor. A national database will provide a better perspective of the burden of major incidents

    Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia.

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    N6-methyladenosine (m6A) is an abundant internal RNA modification1,2 that is catalysed predominantly by the METTL3-METTL14 methyltransferase complex3,4. The m6A methyltransferase METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but the potential of therapeutic applications targeting this enzyme remains unknown5-7. Here we present the identification and characterization of STM2457, a highly potent and selective first-in-class catalytic inhibitor of METTL3, and a crystal structure of STM2457 in complex with METTL3-METTL14. Treatment of tumours with STM2457 leads to reduced AML growth and an increase in differentiation and apoptosis. These cellular effects are accompanied by selective reduction of m6A levels on known leukaemogenic mRNAs and a decrease in their expression consistent with a translational defect. We demonstrate that pharmacological inhibition of METTL3 in vivo leads to impaired engraftment and prolonged survival in various mouse models of AML, specifically targeting key stem cell subpopulations of AML. Collectively, these results reveal the inhibition of METTL3 as a potential therapeutic strategy against AML, and provide proof of concept that the targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy

    Into the unknown: expression profiling without genome sequence information in CHO by next generation sequencing

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    The arrival of next-generation sequencing (NGS) technologies has led to novel opportunities for expression profiling and genome analysis by utilizing vast amounts of short read sequence data. Here, we demonstrate that expression profiling in organisms lacking any genome or transcriptome sequence information is feasible by combining Illumina’s mRNA-seq technology with a novel bioinformatics pipeline that integrates assembled and annotated Chinese hamster ovary (CHO) sequences with information derived from related organisms. We applied this pipeline to the analysis of CHO cells which were chosen as a model system owing to its relevance in the production of therapeutic proteins. Specifically, we analysed CHO cells undergoing butyrate treatment which is known to affect cell cycle regulation and to increase the specific productivity of recombinant proteins. By this means, we identified sequences for >13 000 CHO genes which added sequence information of ∼5000 novel genes to the CHO model. More than 6000 transcript sequences are predicted to be complete, as they covered >95% of the corresponding mouse orthologs. Detailed analysis of selected biological functions such as DNA replication and cell cycle control, demonstrated the potential of NGS expression profiling in organisms without extended genome sequence to improve both data quantity and quality

    Glucagon-like peptide-1 and its class B G protein-coupled receptors: A long march to therapeutic successes

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    Theglucagon-likepeptide (GLP)-1receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secretedfromthreemajor tissues inhumans,enteroendocrine L cells in the distal intestine, a cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a twodomain-binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidicGLP-1R agonists have been hampered, small-moleculemodulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders

    Climate and species affect fine root production with long-term fertilization in acidic tussock tundra near Toolik Lake, Alaska

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    Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Oecologia 153 (2007): 643-652, doi:10.1007/s00442-007-0753-8.Long-term fertilization of acidic tussock tundra has led to changes in plant species composition, increases in aboveground production and biomass and substantial losses of soil organic carbon (SOC). Root litter is an important input to SOC pools, though little is known about fine root demography in tussock tundra. In this study, we examined the response of fine root production and live standing fine root biomass to short- and long-term fertilization, as changes in fine root demography may contribute to observed declines in SOC. Live standing fine root biomass increased with long-term fertilization, while fine root production declined, reflecting replacement of the annual fine root system of Eriophorum vaginatum, with the long-lived fine roots of Betula nana. Fine root production increased in fertilized plots during an unusually warm growing season, but remained unchanged in control plots, consistent with observations that B. nana shows a positive response to climate warming. Calculations based on a few simple assumptions suggest changes in fine root demography with long-term fertilization and species replacement could account for between 20 and 39% of observed declines in SOC stocks.This project was supported by National Science Foundation research grants 9810222, 9911681, 0221606 and 0528748

    A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine.

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    Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels. In this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed. Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa. Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits

    Veterans walk to beat back pain: study rationale, design and protocol of a randomized trial of a pedometer-based Internet mediated intervention for patients with chronic low back pain

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    <p>Abstract</p> <p>Background</p> <p>Chronic back pain is a significant problem worldwide and may be especially prevalent among patients receiving care in the U.S. Department of Veterans Affairs healthcare system. Back pain affects adults at all ages and is associated with disability, lost workplace productivity, functional limitations and social isolation. Exercise is one of the most effective strategies for managing chronic back pain. Yet, there are few clinical programs that use low cost approaches to help patients with chronic back pain initiate and maintain an exercise program.</p> <p>Methods/Design</p> <p>We describe the design and rationale of a randomized controlled trial to assess the efficacy of a pedometer-based Internet mediated intervention for patients with chronic back pain. The intervention uses an enhanced pedometer, website and e-community to assist these patients with initiating and maintaining a regular walking program with the primary aim of reducing pain-related disability and functional interference. The study specific aims are: 1) To determine whether a pedometer-based Internet-mediated intervention reduces pain-related functional interference among patients with chronic back pain in the short term and over a 12-month timeframe. 2) To assess the effect of the intervention on walking (measured by step counts), quality of life, pain intensity, pain related fear and self-efficacy for exercise. 3) To identify factors associated with a sustained increase in walking over a 12-month timeframe among patients randomized to the intervention.</p> <p>Discussion</p> <p>Exercise is an integral part of managing chronic back pain but to be effective requires that patients actively participate in the management process. This intervention is designed to increase activity levels, improve functional status and make exercise programs more accessible for a broad range of patients with chronic back pain.</p> <p>Trial Registration Number</p> <p>NCT00694018</p
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