367 research outputs found

    Catalog of selected heavy duty transport energy management models

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    A catalog of energy management models for heavy duty transport systems powered by diesel engines is presented. The catalog results from a literature survey, supplemented by telephone interviews and mailed questionnaires to discover the major computer models currently used in the transportation industry in the following categories: heavy duty transport systems, which consist of highway (vehicle simulation), marine (ship simulation), rail (locomotive simulation), and pipeline (pumping station simulation); and heavy duty diesel engines, which involve models that match the intake/exhaust system to the engine, fuel efficiency, emissions, combustion chamber shape, fuel injection system, heat transfer, intake/exhaust system, operating performance, and waste heat utilization devices, i.e., turbocharger, bottoming cycle

    Prevalence and characterization of methicillin-resistant Staphylococcus aureus among healthy children in a city of Argentina

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    Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a major global problem. Healthy carriers of S. aureus strains have an important role in the dissemination of this bacterium. The aim of this study was to estimate the prevalence of S. aureus and methicillin-resistant S. aureus (MRSA) carriage among healthy children in a city of Buenos Aires province, Argentina, and to determine the potential risk factors for its acquisition. We also described the molecular features of MRSA strains circulating in this population. S. aureus carriage was investigated in all children attending the last year of kindergarten during the 2008 school- year period. Household contacts of MRSA carriers were also screened. Of 316 healthy children, 98 (31.0%) carried S. aureus, including 14 MRSA carriers (4.4%) and 84 methicillin susceptible S. aureus (MSSA) carriers (26.6%). All MRSA isolates carried the SCCmec type IV cassette. Eight of the fourteen isolates were closely related to the clone responsible for most severe community- acquired MRSA infections caused in our country (CAA: PFGE A, SCCmec IV, spa t311, ST5). Two subtypes (A1 and A2) were distinguished in this group by PFGE. Both had agr type II and presented the same virulence determinants, except for PVL coding genes and sea that were only harbored by subtype A1. Our results, based on the analysis of MRSA isolates recovered in the screening of healthy children, provide evidence of a community reservoir of the major CA-MRSA clone described in Argentina.Fil: Gardella, N.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica; ArgentinaFil: Murzicato, S.. Hospital Municipal de San Antonio de Areco; ArgentinaFil: Di Gregorio, Sabrina Noelia. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay; ArgentinaFil: Cuirolo, Arabela Ximena. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay; ArgentinaFil: Desse, J.. Hospital Paroissien; ArgentinaFil: Crudo, F.. Hospital Municipal de San Antonio de Areco; ArgentinaFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay; ArgentinaFil: Mollerach, Marta Eugenia. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay; Argentin

    Characteristics of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) Strains Isolated from Skin and Soft-Tissue Infections in Uruguay

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    We analyzed 90 nonduplicates community-associated methicillin-resistant S. aureus (CA-MRSA) strains isolated from skin and soft-tissue infections. All strains were mecA positive. Twenty-four of the 90 strains showed inducible macrolide-lincosamide-streptogramin B resistance. All strains produced α-toxin; 96% and 100% of them displayed positive results for lukS-F and cna genes, respectively. Eigthy-five strains expressed capsular polysaccharide serotype 8. Six different pulsotypes were discriminated by pulsed-field gel electrophoresis (PFGE) and three predominant groups of CA-MRSA strains (1, 2, and 4) were identified, in agreement with phenotypic and genotypic characteristics. Strains of group 1 (pulsotype A, CP8+, and Panton-Valentine leukocidin (PVL)+) were the most frequently recovered and exhibited a PFGE band pattern identical to other CA-MRSA strains previously isolated in Uruguay and Brazil. Three years after the first local CA-MRSA report, these strains are still producing skin and soft-tissue infections demonstrating the stability over time of this community-associated emerging pathogen

    Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome

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    Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall1. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFb pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity3. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes4,5. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFb signaling represent a new treatment strategy

    Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

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    Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required

    Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics? †

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    Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable

    The milieu of accountability of early companies in the Qing Dynasty: evidence from the ShĂ nghai-based print media.

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    This study looks at evidence from the ShĂ nghǎi (Shanghai)-based print media of the accountability of early Chinese companies from the middle period of the QÄ«ng (Qing) Dynasty when the Opium War broke out in 1840 until the imperial monarchy's overthrow in the revolution of 1911. The QÄ«ng Dynasty is known for its technical accounting stagnation. Yet, an examination of the ShĂ nghǎi-based print media shows the existence of a strong sense of public reporting by early companies of the QÄ«ng Dynasty. The findings of this study indicate that the print media displayed a rich milieu of accountability of these early companies by incorporating components of Western and Chinese benchmarks of accountability expressed in commercial metrics and key financial ratios

    The phenotypic and genotypic spectrum of individuals with mono- or biallelic ANK3 variants

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    ANK3 encodes ankyrin-G, a protein involved in neuronal development and signaling. Alternative splicing gives rise to three ankyrin-G isoforms comprising different domains with distinct expression patterns. Mono- or biallelic ANK3 variants are associated with non-specific syndromic intellectual disability in 14 individuals (seven with monoallelic and seven with biallelic variants). In this study, we describe the clinical features of 13 additional individuals and review the data on a total of 27 individuals (16 individuals with monoallelic and 11 with biallelic ANK3 variants) and demonstrate that the phenotype for biallelic variants is more severe. The phenotypic features include language delay (92%), autism spectrum disorder (76%), intellectual disability (78%), hypotonia (65%), motor delay (68%), attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) (57%), sleep disturbances (50%), aggressivity/self-injury (37.5%), and epilepsy (35%). A notable phenotypic difference was presence of ataxia in three individuals with biallelic variants, but in none of the individuals with monoallelic variants. While the majority of the monoallelic variants are predicted to result in a truncated protein, biallelic variants are almost exclusively missense. Moreover, mono- and biallelic variants appear to be localized differently across the three different ankyrin-G isoforms, suggesting isoform-specific pathological mechanisms.</p

    Mesenchymal-epithelial signalling in tumour microenvironment: role of high-mobility group Box 1.

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    Glucose deprivation, hypoxia and acidosis are characteristic features of the central core of most solid tumours. Myofibroblasts are stromal cells present in many such solid tumours, including those of the colon, and are known to be involved in all stages of tumour progression. HMGB1 is a nuclear protein with an important role in nucleosome stabilisation and gene transcription; it is also released from immune cells and is involved in the inflammatory process. We report that the microenvironmental condition of glucose deprivation is responsible for the active release of HMGB1 from various types of cancer cell lines (HT-29, MCF-7 and A549) under normoxic conditions. Recombinant HMGB1 (10 ng/ml) triggered proliferation in myofibroblast cells via activation of PI3K and MEK1/2. Conditioned medium collected from glucose-deprived HT-29 colon cancer cells stimulated the migration and invasion of colonic myofibroblasts, and these processes were significantly inhibited by immunoneutralising antibodies to HMGB1, RAGE and TLR4, together with specific inhibitors of PI3K and MEK1/2. Our data suggest that HMGB1 released from cancer cells under glucose deprivation is involved in stimulating colonic myofibroblast migration and invasion and that this occurs through the activation of RAGE and TLR4, resulting in the activation of the MAPK and PI3K signalling pathways. Thus, HMGB1 might be released by cancer cells in areas of low glucose in solid tumours with the resulting activation of myofibroblasts and is a potential therapeutic target to inhibit solid tumour growth
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