The interval mapping method is widely used for the genetic mapping of quantitative trait loci (QTLs), though true resolution of quantitative variation into QTLs is hampered with this method. ...Separation of QTLs is troublesome, because single-QTL is models are fitted. Further, genotype-by-environment interaction, which is of great importance in many quantitative traits, can only be approached by separately analyzing the data collected in multiple environments. Here, for the first time a novel analytic approach (MQM mapping) is demonstrated that accommodates both the mapping of multiple QTLs and genotype-by-environment interaction. MQM mapping is compared to interval mapping in the mapping of QTLs for flowering time in Arabidopsis thaliana under various photoperiod and vernalization conditions.
Summary
Aim To investigate the potential of rosiglitazone, a highly potent agonist at the nuclear peroxisome proliferator activated receptor‐γ (PPAR‐γ), to prevent the development of diabetes in the ...Zucker diabetic fatty (ZDF) rat or to ameliorate the condition at a later stage of the disease.
Methods Rosiglitazone (10 μmol/kg body weight daily) was given via the diet to ZDF rats from aged 6 weeks, before the onset of hyperglycaemia (Prevention group), or from aged 21 weeks after hyperglycaemia and proteinuria were established (Intervention group). Untreated ZDF rats and age‐matched Zucker lean rats (ZL) served as controls and the experiment was terminated when the animals were aged 28 weeks.
Results Whilst the combined ZDF control and Intervention groups were already hyperglycaemic (14.6 ± 1.6 vs. ZL 5.7 ± 0.1 mmol/l, mean ± s.e.m.; p < 0.05), glycosuric and polydipsic at aged 11 weeks, and thereafter had a declining plasma insulin concentration, rosiglitazone Prevention treatment maintained normoglycaemia even at aged 27 weeks (3.7 ± 0.3 mmol/l vs. ZL 3.0 ± 0.3 mmol/l; NS). Intervention treatment at aged 21 weeks, however, failed to ameliorate the diabetes. These functional data were supported by determinations of pancreatic insulin content (μg/mg tissue as follows: ZL, 43.1 ± 3.9; ZDF control (28 weeks) + ZDF Intervention control (21 weeks), 6.0 ± 0.8; Prevention, 63.6 ± 15.8; Intervention, 6.2 ± 0.9) and by morphological, immunohistochemical and electron microscopical examination of pancreata at the end of the study. Thus, islets from rosiglitazone Prevention rats were similar to ZL rats, whereas ZDF controls and Intervention rats exhibited islets depleted of insulin, with a disorganized architecture and an ultrastructure indicative of work hypertrophy. ZDF control rats and Intervention rats, though not rosiglitazone Prevention rats, also exhibited marked proteinuria, indicative of renal glomerular damage.
Conclusions Our results demonstrate that in ZDF rats, rosiglitazone prevents the progression from insulin resistance to overt diabetes. These data provide a rationale for investigating whether treatment with rosiglitazone of patients with early signs of perturbed glucose metabolism (e.g. impaired fasting glucose (IGT)) may prevent the progression to type 2 diabetes and its associated complications.
Machine learning n/γ discrimination in CLYC scintillators Doucet, E.; Brown, T.; Chowdhury, P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2020, Letnik:
954, Številka:
C
Journal Article
Recenzirano
Two machine learning techniques, one supervised (Artificial Neural Network) and the other unsupervised (k-means++) have been applied to the task of n/γ discrimination in 7Li-enriched CLYC detectors, ...and compared to traditional charge-comparison methods. The results show that a very basic artificial neural network can provide very good discrimination in the energy range investigated, and the k-means++ algorithm is capable of separating neutrons and gamma-rays in CLYC scintillators as well as suggesting reasonable window parameters for charge comparison methods.
The novel cationic flocculant, poly(lactic acid) choline iodide ester methacrylate (poly(PLA4ChMA)), has been shown to provide improved flocculation of 5.0 wt.% mature fine tailings (MFT) diluted in ...deionized water compared to commercial anionic polymers, with continued dewatering of the sediment occurring as the polymer undergoes partial hydrolytic degradation. However, the elevated dosages (10,000 ppm) required would make the polymer costly to implement on an industrial scale. With this motivation, the impact of MFT loading and the use of process water is explored while comparing the settling performance of poly(PLA4ChMA) to available commercial alternatives such as anionic FLOPAM A3338. Improved consolidation of 5.0 wt.% MFT diluted with process water could be achieved at reduced dosages (500 ppm) with poly(PLA4ChMA). However, the final compaction levels after polymer degradation were similar to those achieved with the nondegradable commercial flocculants. Flocculation-filtration experiments with undiluted MFT are also conducted to compare the performance of the polymers. Significantly faster rates of water release were observed with the cationic flocculants compared to FLOPAM A3338, but no improvement in the overall tailings compaction was found either before or after poly(PLA4ChMA) degradation. Thus, the improved dewatering observed with poly(PLA4ChMA) in dilute MFT suspensions does not extend to conditions that would be encountered in the field.
Background:
Extensor pollicis longus (EPL) rupture and tenosynovitis of the third dorsal compartment is often described in association with a history of rheumatoid arthritis or in the setting of a ...distal radius fracture. However, the literature suggests multiple other potential factors that may lead to a seemingly spontaneous rupture.
Methods:
We performed a systematic review following guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search consisted of headings and keywords related to tendon injuries, tendinopathy, hand surgery, tendon transfer, and injections, as published in reports and studies. Citations were screened by title and abstract against predetermined inclusion and exclusion criteria by 2 independent reviewers, with a third reviewer resolving discrepancies. To be eligible, articles had to meet the following inclusion criterion: describe cases of spontaneous EPL rupture or tenosynovitis of the third dorsal compartment. The exclusion criterion was any history of distal radius fracture or rheumatoid arthritis.
Results:
We identified 29 articles that met the inclusion criterion.
Conclusions:
A myriad of prodromal events or predisposing factors ultimately led to EPL rupture or tenosynovitis of the third compartment. Methods of reconstruction described included primary repair, tendon grafting, and tendon transfer techniques; all with generally good outcomes. These results highlight the inherent fragility of this tendon and support the historical recommendation for early release of the EPL tendon in the setting of tenosynovitis of the third dorsal compartment.
Orexins are novel appetite-stimulating peptides expressed in the lateral hypothalamic area (LHA), and their expression is stimulated by hypoglycemia in fasted rats. We investigated activation of ...orexin and other neurons during insulin-induced hypoglycemia using the immediate early gene product Fos. Insulin (50 U/kg) lowered plasma glucose by >50% after 5 h and stimulated feeding sixfold compared with saline-injected controls. Hypoglycemic rats allowed to feed and normoglycemic controls both showed sparse Fos-positive (Fos+) neurons in the LHA and the paraventricular nucleus (PVN) and arcuate nucleus (ARC) and showed none in the nucleus of the solitary tract (NTS), which relays visceral feeding signals to the LHA. In the LHA, total numbers of Fos+ neurons were comparable in fed hypoglycemic and control groups (60 +/- 6 vs. 52 +/- 4 cells/mm2, P > 0.05), as were Fos+ neurons immunoreactive for orexin (1.4 +/- 0.4 vs. 0.6 +/- 0.4 cells/mm2, P > 0.05). By contrast, hypoglycemic rats that were fasted showed significantly more Fos+ nuclei in the LHA (96 +/- 10 cells/mm2, P < 0.05, vs. both other groups) and Fos+ orexin neurons (8.4 +/- 3.3 cells/mm2, P < 0.001, vs. both other groups). They also showed two- to threefold more Fos+ nuclei (P < 0.001) in the PVN and ARC than both fed hypoglycemic rats and controls and showed strikingly abundant Fos+ neurons in the NTS and dorsal motor nucleus of the vagus. In parallel studies, whole hypothalamic orexin-A levels were not changed in hypoglycemic rats, whether fasted or freely fed, whereas orexin-B levels were 10-fold higher in hypoglycemic fasted rats than in control and hypoglycemic fed groups. These data support our hypothesis that orexin neurons are stimulated by falling glucose levels but are readily inhibited by signals related to nutrient ingestion and suggest that they may functionally link with neuronal activity in the NTS. Orexin-A and -B may play specific roles in behavioral or neuroendocrine responses to hypoglycemia.
An Agrobacterium tumefaciens-mediated transformation method has been developed for onions (Allium cepa L.) using immature embryos as the explant source. Transgenic plants were recovered from the ...open-pollinated onion cultivar Canterbury Longkeeper at a maximum transformation frequency from immature embryos of 2.7%. The method takes between 3-5 months from explant to primary regenerant entering the glasshouse. Multiple-shoot formation from primary transgenic material made possible the clonal multiplication of transformants. The binary vector used carried the nptII antibiotic resistance gene and the m-gfp5-ER reporter gene. Transgenic cultures were initially screened for their ability to fluoresce and to grow in the presence of geneticin (5-25 mg/l). The transgenic nature of individual plants was confirmed by Southern blot analysis.
The precise mechanism by which PPARγ activation by thiazolidinediones (TZDs) improves insulin sensitivity is still unclear. Recent studies have focused on the role of adipocytokines in metabolic ...control and their regulation by TZDs. In this study, we compared the chronic effects of antihyperglycemic doses of the TZD rosiglitazone, the β3-adrenoceptor agonist BRL-35135, and the PPARα agonist Wy-14,643 on the mRNA expression of adipocytokines in WAT of db/db mice. Rosiglitazone treatment decreased adiponectin and resistin mRNA levels by 57 and 72%, respectively (P < 0.001), with no effect on the level of TNFα or RELMα transcripts. In comparison, Wy-14,643 reduced adiponectin transcript levels by 31% (P = 0.015) while BRL-35135 increased RELMα mRNA expression by 245% (P < 0.001) without effect on the other transcripts. Our results indicate that although a reduction in adiponectin and resistin mRNA levels in WAT by rosiglitazone treatment of diabetic mice may contribute to the antidiabetic effects, an alteration in TNFα, adiponectin, resistin, or RELMα mRNA expression is not absolutely required for the regulation of blood glucose concentration in the db/db mouse.
Cardiac involvement is the most important component of acute rheumatic fever. The role of echocardiography in the evaluation of rheumatic carditis has not been adequately defined. We used ...echocardiography in a large sample of patients with acute rheumatic fever to describe morphological abnormalities associated with rheumatic carditis and to assess its role in the diagnosis of rheumatic carditis.
Cross-sectional and color Doppler echocardiographic examination was performed in 108 consecutive patients with acute rheumatic fever within 24 to 48 hours of diagnosis. Twenty-eight patients had acute rheumatic fever without clinical evidence of carditis (group 1). Thirty-five patients had a presumed first episode of rheumatic carditis (group 2), and 45 patients had a recurrence of carditis (group 3). Patients in group 1 did not demonstrate any evidence of valvular regurgitation. Mitral regurgitation was the most common Doppler echocardiographic feature in groups 2 (94%) and 3 (84%). Valvular thickening with or without restriction of leaflet mobility was frequently seen in rheumatic carditis. One of every 4 patients with rheumatic carditis demonstrated echocardiographic presence of focal valvular nodules. These nodules were found on the body and the tips of the mitral valve leaflets and disappeared on follow-up. Ventricular dilatation (group 2, 54%; group 3, 74%) and restriction of leaflet mobility (group 3, 37%) were common mechanisms of mitral regurgitation in rheumatic carditis; valve prolapse (group 2, 9%; group 3, 16%) and annular dilatation (group 2, 12%; group 3, 21%) were infrequent. The majority of patients with rheumatic carditis had normal left ventricular systolic function. Congestive heart failure (group 2, 17%; group 3, 40%) was invariably associated with the presence of hemodynamically significant valve lesions. On follow-up, no patient in group 1 developed valvular regurgitation. In group 2 patients, a progressive decrease in left ventricular dimensions was observed without any change in ventricular fractional shortening. Valvular regurgitation remained unchanged in 69% of patients, decreased in 22%, and disappeared in 9%.
In patients with rheumatic carditis, the mitral valve is most often involved and mitral regurgitation is the most common finding on color flow imaging. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation and/or restriction of leaflet mobility. Rheumatic carditis does not result in congestive heart failure in the absence of hemodynamically significant valve lesions. In a quarter of patients with rheumatic carditis, we observed valve nodules that may represent echocardiographic equivalents of rheumatic verrucae. Our study failed to reveal any incremental diagnostic utility of echocardiography and Doppler color flow imaging in rheumatic fever without clinical evidence of carditis.
A series of (ureidoethoxy)benzyl-2,4-thiazolidinediones and (heterocyclylamino)alkoxy-benzyl-2,4-thiazolidinediones was synthesized from the corresponding aldehydes. Compounds from the urea series, ...exemplified by 16, showed antihyperglycemic potency comparable with known agents of the type such as pioglitazone and troglitazone (CS-045). The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies. Evaluation of antihyperglycemic activity together with effects on blood hemoglobin content, to determine the therapeutic index, was performed in 8-day repeat administration studies in genetically obese C57 Bl/6 ob/ob mice. From these studies, BRL 49653 (37) has been selected, on the basis of antihyperglycemic potency combined with enhanced selectivity against reductions in blood hemoglobin content, for further evaluation.
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