529 research outputs found

    Modeling the Effects of Late Cycle Oxygen Enrichment on Diesel Engine Combustion and Emissions

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    A multidimensional simulation of Auxiliary Gas Injection (AGI) for late cycle oxygen enrichment was exercised to assess the merits of AGI for reducing the emissions of soot from heavy duty diesel engines while not adversely affecting the NO{sub x} emissions of the engine. Here, AGI is the controlled enhancement of mixing within the diesel engine combustion chamber by high speed jets of air or another gas. The engine simulated was a Caterpillar 3401 engine. For a particular operating condition of this engine, the simulated soot emissions of the engine were reduced by 80% while not significantly affecting the engine-out NO{sub x} emissions compared to the engine operating without AGI. The effects of AGI duration, timing, and orientation are studied to confirm the window of opportunity for realizing lower engine-out soot while not increasing engine out NO{sub x} through controlled enhancement of in-cylinder mixing. These studies have shown that this window occurs during the late combustion cycle, from 20 to 60 crank angle degrees after top-dead-center. During this time, the combustion chamber temperatures are sufficiently high that soot oxidation increases in response in increased mixing, but the temperature is low enough that NO{sub x} reactions are quenched. The effect of the oxygen composition of the injected air is studied for the range of compositions between 21% and 30% oxygen by volume. This is the range of oxygen enrichment that is practical to produce from an air separation membrane. Simulations showed that this level of oxygen enrichment is insufficient to provide an additional benefit by either increasing the level of soot oxidation or prolonging the window of opportunity for increasing soot oxidation through enhanced mixing

    Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype.

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    This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataracts and abnormal electroretinograms are novel features of SMA-LED2

    BET inhibition as a single or combined therapeutic approach in primary paediatric B-precursor acute lymphoblastic leukaemia

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    Paediatric B-precursor ALL is a highly curable disease, however, treatment resistance in some patients and the long-term toxic effects of current therapies pose the need for more targeted therapeutic approaches. We addressed the cytotoxic effect of JQ1, a highly selective inhibitor against the transcriptional regulators, bromodomain and extra-terminal (BET) family of proteins, in paediatric ALL. We showed a potent in vitro cytotoxic response of a panel of primary ALL to JQ1, independent of their prognostic features but dependent on high MYC expression and coupled with transcriptional downregulation of multiple pro-survival pathways. In agreement with earlier studies, JQ1 induced cell cycle arrest. Here we show that BET inhibition also reduced c-Myc protein stability and suppressed progression of DNA replication forks in ALL cells. Consistent with c-Myc depletion and downregulation of pro-survival pathways JQ1 sensitised primary ALL samples to the classic ALL therapeutic agent dexamethasone. Finally, we demonstrated that JQ1 reduces ALL growth in ALL xenograft models, both as a single agent and in combination with dexamethasone. We conclude that targeting BET proteins should be considered as a new therapeutic strategy for the treatment of paediatric ALL and particularly those cases that exhibit suboptimal responses to standard treatment

    A homotopy approach to the feedback stabilization of linear systems

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76174/1/AIAA-20236-533.pd

    An integrated analysis and comparison of serum, saliva and sebum for COVID-19 metabolomics.

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    The majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range of patient pathologies. Here, correlations between serum metabolites, salivary metabolites and sebum lipids are studied for the first time. 83 COVID-19 positive and negative hospitalised participants provided blood serum alongside saliva and sebum samples for analysis by liquid chromatography mass spectrometry. Widespread alterations to serum-sebum lipid relationships were observed in COVID-19 positive participants versus negative controls. There was also a marked correlation between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate in the COVID-19 positive cohort. The biofluids analysed herein were also compared in terms of their ability to differentiate COVID-19 positive participants from controls; serum performed best by multivariate analysis (sensitivity and specificity of 0.97), with the dominant changes in triglyceride and bile acid levels, concordant with other studies identifying dyslipidemia as a hallmark of COVID-19 infection. Sebum performed well (sensitivity 0.92; specificity 0.84), with saliva performing worst (sensitivity 0.78; specificity 0.83). These findings show that alterations to skin lipid profiles coincide with dyslipidaemia in serum. The work also signposts the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions

    The impact of diabetes on multiple avoidable admissions: a cross-sectional study

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    Background Multiple admissions for ambulatory care sensitive conditions (ACSC) are responsible for an important proportion of health care expenditures. Diabetes is one of the conditions consensually classified as an ACSC being considered a major public health concern. The aim of this study was to analyse the impact of diabetes on the occurrence of multiple admissions for ACSC. Methods We analysed inpatient data of all public Portuguese NHS hospitals from 2013 to 2015 on multiple admissions for ACSC among adults aged 18 or older. Multiple ACSC users were identified if they had two or more admissions for any ACSC during the period of analysis. Two logistic regression models were computed. A baseline model where a logistic regression was performed to assess the association between multiple admissions and the presence of diabetes, adjusting for age and sex. A full model to test if diabetes had no constant association with multiple admissions by any ACSC across age groups. Results Among 301,334 ACSC admissions, 144,209 (47.9%) were classified as multiple admissions and from those, 59,436 had diabetes diagnosis, which corresponded to 23,692 patients. Patients with diabetes were 1.49 times (p < 0,001) more likely to be admitted multiple times for any ACSC than patients without diabetes. Younger adults with diabetes (18–39 years old) were more likely to become multiple users. Conclusion Diabetes increases the risk of multiple admissions for ACSC, especially in younger adults. Diabetes presence is associated with a higher resource utilization, which highlights the need for the implementation of adequate management of chronic diseases policies.NOVASaudeinfo:eu-repo/semantics/publishedVersio

    Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

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    The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of α-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy

    Identifying and mapping chemical bonding within phenolic resin using Secondary Electron Hyperspectral Imaging

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    The distributions of methylene and ether bridges have been shown to impact the mechanical properties of phenolic resin. This work demonstrates the ability of the novel SEM based technique, Secondary Electron Hyperspectral Imaging (SEHI), to characterise and map methylene and ether bridges within phenolic resin at the nanoscale
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