2,880 research outputs found

    Analytical and experimental study of two concentric cylinders coupled by a fluid gap

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    From a structural point of view a liquid coolant type nuclear reactor consists of a heavy steel vessel containing the core and related mechanical components and filled with a hot fluid. This vessel is protected from the severe environment of the core by a shielding structure, the thermal liner, which is usually a relatively thin steel cylinder concentric with the reactor vessel and separated from it by a gap filled with the coolant fluid. This arrangement leads to a potential vibration problem if the fundamental frequency, or one of the higher natural vibration frequencies, of this liner system is close to the frequency of some vibration source present in the reactor vessel. The shell rigidly clamped at its base and free at the top was investigated since it is a better description of the conditions encountered in typical reactor designs

    Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells

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    Obesity and type 2 diabetes lead to dramatically increased risks of atherosclerosis and CHD. Multiple mechanisms converge to promote atherosclerosis by increasing endothelial oxidative stress and up-regulating expression of pro-inflammatory molecules. Microvesicles (MV) are small ( < 1 μm) circulating particles that transport proteins and genetic material, through which they are able to mediate cell–cell communication and influence gene expression. Since MV are increased in plasma of obese, insulin-resistant and diabetic individuals, who often exhibit chronic vascular inflammation, and long-term feeding of a high-fat diet (HFD) to rats is a well-described model of obesity and insulin resistance, we hypothesised that this may be a useful model to study the impact of MV on endothelial inflammation. The number and cellular origin of MV from HFD-fed obese rats were characterised by flow cytometry. Total MV were significantly increased after feeding HFD compared to feeding chow (P< 0·001), with significantly elevated numbers of MV derived from leucocyte, endothelial and platelet compartments (P< 0·01 for each cell type). MV were isolated from plasma and their ability to induce reactive oxygen species (ROS) formation and vascular cell adhesion molecule (VCAM)-1 expression was measured in primary rat cardiac endothelial cells in vitro. MV from HFD-fed rats induced significant ROS (P< 0·001) and VCAM-1 expression (P= 0·0275), indicative of a pro-inflammatory MV phenotype in this model of obesity. These findings confirm that this is a useful model to further study the mechanisms by which diet can influence MV release and subsequent effects on cardio-metabolic health

    Characterization of a Reductively-Activated Elimination Pathway Relevant to the Biological Chemistry of the Kinamycins and Lomaiviticins

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    The lomaiviticins (1 and 2) and kinamycins (3–5) are bacterial metabolites with potent antimicrobial and antiproliferative activities. Herein we establish that 1–5 are capable of generating electrophilic acylfulvene intermediates (6) under mildly reducing conditions. These acylfulvenes 6 are formed by a multistep process comprising two-electron reduction and loss of dinitrogen to form an ortho-quinone methide, followed by elimination. Based on these studies, the structure of the product formed from 1 in DNA-cleavage assays is proposed (26). We also show that the bis(hydroxynaphthoquinone) substructures of the lomaiviticins activate the metabolites toward reduction. Finally, based on COMPARE and time-dependent cell response profiling analyses, we show that kinamycin C (4) and the monomeric lomaiviticin aglycon (24) operate by a mechanism of action that is distinct from simple diazofluorenes, such as 23

    Rumen fluke in Irish sheep: prevalence, risk factors and molecular identification of two paramphistome species

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    peer-reviewedBackground Rumen flukes are trematode parasites found globally; in tropical and sub-tropical climates, infection can result in paramphistomosis, which can have a deleterious impact on livestock. In Europe, rumen fluke is not regarded as a clinically significant parasite, recently however, the prevalence of rumen fluke has sharply increased and several outbreaks of clinical paramphistomosis have been reported. Gaining a better understanding of rumen fluke transmission and identification of risk factors is crucial to improve the control of this parasitic disease. In this regard, a national prevalence study of rumen fluke infection and an investigation of associated risk factors were conducted in Irish sheep flocks between November 2014 and January 2015. In addition, a molecular identification of the rumen fluke species present in Ireland was carried out using an isolation method of individual eggs from faecal material coupled with a PCR. After the DNA extraction of 54 individual eggs, the nuclear fragment ITS-2 was amplified and sequenced using the same primers. Results An apparent herd prevalence of 77.3 % was determined. Several risk factors were identified including type of pasture grazed, regional variation, and sharing of the paddocks with other livestock species. A novel relationship between the Suffolk breed and higher FEC was reported for the first time. The predominant rumen fluke species found was C. daubneyi. Nevertheless, P. leydeni was unexpectedly identified infecting sheep in Ireland for the first time. Conclusions An exceptionally high prevalence of rumen fluke among Irish sheep flocks has been highlighted in this study and a more thorough investigation is necessary to analyse its economic impact. The isolation of individual eggs coupled with the PCR technique used here has proven a reliable tool for discrimination of Paramphistomum spp. This technique may facilitate forthcoming studies of the effects of paramphistomosis on livestock production. The most noteworthy finding was the identification of P. leydeni affecting sheep in Ireland, however further studies are required to clarify its implications. Also, a significant relationship between Suffolk breed and a heavier infection was found, which can be used as a starting point for future research on control strategies of rumen fluke infection.This study was funded by Irish Department of Agriculture, Food and the Marine research stimulus funding; project reference 13/ S/405

    Mediation and Judicial Review: An empirical research study

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    The aim of this research is to establish an independent evidence base for identifying the value and the limits of mediation as an alternative to, or used alongside, judicial review. It has been devised in response to claims made by government and mediation providers that mediation can lead to savings in costs as well as in court time, and provide remedies and solutions to disputes that cannot be offered by the court. These claims will be considered in the specifi c context of judicial review, which not only has an important constitutional function, but, compared to other forms of civil litigation, offers flexibility, low costs and speed

    Determinants of health, health behaviours and demographic profile of patients attending an Australian university student-led osteopathy clinic.

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    BackgroundProfiles of health professions practice can inform pre-professional education, provide evidence to assist with interprofessional practice, and inform policy development. An understanding of the profile of patients seeking osteopathy care is emerging. Current research suggests that musculoskeletal presentations predominate with approximately one-third of patients presenting with co-morbid diseases. There is little data on these presentations in Australian osteopathy practice. This study aimed to describe the patient demographics, clinical presentations, health behaviours and determinants of health, including health literacy, of those attending for care at an Australian student-led osteopathy clinic.MethodsA convenience sample design was utilised where consecutive patients presenting for their initial consultation were invited to complete a health information questionnaire during 2016-2017. The questionnaire explored a range of health behaviours and the patient's health status. Data from the clinical records were also extracted to establish the presenting complaint, duration of the complaint and pertinent demographics. Descriptive statistics were generated for each variable.ResultsData were available for 1617 patients presenting for their initial consultation. The mean age of patients was 33.7 (±13.1) years with 55% (n = 887) identifying as female. Acute presentations predominated (n = 840, 52%), with presentations affecting the spine being the most common (57.8%). Most patients rated their health status as good to very good (75%). Approximately 7.5% of patients were identified as having low health literacy and 55.9% were currently suffering from one or more co-morbid presentations.ConclusionsThe demographic profile and presenting complaints of patients presenting to a student-led osteopathy clinic are largely consistent with other Australian private practice profiles. The current work also identified co-morbid presentations, and positive and negative health behaviours. Osteopaths may play a role in the management of, or referral for, these presentations where health behaviours require change, or management of co-morbid conditions is beyond the scope of practice. The increasing volume of patient profile literature globally suggests that osteopaths can play a substantial role in the management of musculoskeletal complaints. Further, osteopathy may play a role in screening determinants of health, and engage in multidisciplinary care to ensure those patients with co-morbid conditions or adverse health behaviours are managed appropriately

    Nitrosourea-misonidazole combination chemotherapy: effect on KHT sarcomas, marrow stem cells and gut.

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    C3H/HeJ mice bearing i.m. transplanted KHT sarcomas were treated with varying doses of either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin; CHLZ) as single agents or in combination with 1 mg/g of the chemical radiosensitizer, misonidazole (MISO). Using an in vivo-in vitro tumour-excision assay, the administration of MISO simultaneously with or 3 h after low doses of BCNU (less than 20 mg/kg) was found to give a dose-modification factor (DMF) of approximately 1.65 relative to BCNU alone. At higher doses of BCNU, there was less enhancement of cell kill. The DMF for tumour growth delay was likewise dependent on BCNU dose, continuously decreasing with increasing BCNU dose. In contrast, the anti-tumour activity of CHLZ, assessed by both clonogenic cell survival and tumour-growth delay, was not significantly enhanced by the addition of MISO. The enhancement of gastrointestinal toxicity and haematotoxicity by BCNU-MISO combinations was assessed by LD50/7 and CFU-S assays, respectively. MISO enhanced BCNU marrow toxicity by a factor of 1.2-1.3, whilst gut toxicity was enhanced by a factor of approximately 1.2
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