Three-dimensional simulations of gravitationally confined detonations compared to observations of SN 1991T

The gravitationally confined detonation (GCD) model has been proposed as a possible explosion mechanism for Type Ia supernovae in the single-degenerate evolution channel. Driven by buoyancy, a deflagration flame rises in a narrow cone towards the surface. For the most part, the flow of the expanding ashes remains radial, but upon reaching the outer, low-pressure layers of the white dwarf, an additional lateral component develops. This makes the deflagration ashes converge again at the opposite side, where the compression heats fuel and a detonation may be launched. To test the GCD explosion model, we perform a 3D simulation for a model with an ignition spot offset near the upper limit of what is still justifiable, 200 km. This simulation meets our deliberately optimistic detonation criteria and we initiate a detonation. The detonation burns through the white dwarf and leads to its complete disruption. We determine nucleosynthetic yields by post-processing 10^6 tracer particles with a 384 nuclide reaction network and we present multi-band light curves and time-dependent optical spectra. We find that our synthetic observables show a prominent viewing-angle sensitivity in UV and blue bands, which is in tension with observed SNe Ia. The strong dependence on viewing-angle is caused by the asymmetric distribution of the deflagration ashes in the outer ejecta layers. Finally, we perform a comparison of our model to SN 1991T. The overall flux-level of the model is slightly too low and the model predicts pre-maximum light spectral features due to Ca, S, and Si that are too strong. Furthermore, the model chemical abundance stratification qualitatively disagrees with recent abundance tomography results in two key areas: our model lacks low velocity stable Fe and instead has copious amounts of high-velocity 56Ni and stable Fe. We therefore do not find good agreement of the model with SN 1991T.Comment: 11 pages, accepted for publication in Astronomy & Astrophysic

Associations of Amylin with Inflammatory Markers and Metabolic Syndrome in Apparently Healthy Chinese

BACKGROUND: Cellular and animal studies implicate multiple roles of amylin in regulating insulin action, glucose and lipid metabolisms. However, the role of amylin in obesity related metabolic disorders has not been thoroughly investigated in humans. Therefore, we aimed to evaluate the distribution of circulating amylin and its association with metabolic syndrome (MetS) and explore if this association is influenced by obesity, inflammatory markers or insulin resistance in apparently healthy Chinese. METHODS: A population-based sample of 1,011 Chinese men and women aged 35-54 years was employed to measure plasma amylin, inflammatory markers (C-reactive protein [CRP] and interleukin-6 [IL-6]), insulin, glucose and lipid profiles. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: Plasma amylin concentrations were higher in overweight/obese participants than normal-weight counterparts (P<0.001) without sex difference. Circulating amylin was positively associated with CRP, IL-6, BMI, waist circumference, blood pressure, fasting glucose, insulin, amylin/insulin ratio, HOMA-IR, LDL cholesterol and triglycerides, while negatively associated with HDL cholesterol (all P<0.001). After multiple adjustments, the risk of MetS was significantly higher (odds ratio 3.71; 95% confidence interval: 2.53 to 5.46) comparing the highest with the lowest amylin quartile. The association remained significant even further controlling for BMI, inflammatory markers, insulin or HOMA-IR. CONCLUSIONS: Our study suggests that amylin is strongly associated with inflammatory markers and MetS. The amylin-MetS association is independent of established risk factors of MetS, including obesity, inflammatory markers and insulin resistance. The causal role of hyperamylinemia in the development of MetS needs to be confirmed prospectively

Investigating mechanisms underpinning the detrimental impact of a high-fat diet in the developing and adult hypermuscular myostatin null mouse

Background: Obese adults are prone to develop metabolic and cardiovascular diseases. Furthermore, over-weight expectant mothers give birth to large babies who also have increased likelihood of developing metabolic and cardiovascular diseases. Fundamental advancements to better understand the pathophysiology of obesity are critical in the development of anti-obesity therapies not only for this but also future generations. Skeletal muscle plays a major role in fat metabolism and much work has focused in promoting this activity in order to control the development of obesity. Research has evaluated myostatin inhibition as a strategy to prevent the development of obesity and concluded in some cases that it offers a protective mechanism against a high-fat diet. Results: We hypothesised that myostatin inhibition should protect not only the mother but also its developing foetus from the detrimental effects of a high-fat diet. Unexpectedly, we found muscle development was attenuated in the foetus of myostatin null mice raised on a high-fat diet. We therefore re-examined the effect of the high-fat diet on adults and found myostatin null mice were more susceptible to diet-induced obesity through a mechanism involving impairment of inter-organ fat utilization. Conclusions: Loss of myostatin alters fatty acid uptake and oxidation in skeletal muscle and liver. We show that abnormally high metabolic activity of fat in myostatin null mice is decreased by a high-fat diet resulting in excessive adipose deposition and lipotoxicity. Collectively, our genetic loss-of-function studies offer an explanation of the lean phenotype displayed by a host of animals lacking myostatin signalling. Keywords: Muscle, Obesity, High-fat diet, Metabolism, Myostati

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years

In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation). Whether or not these differences have clinical bearings (and among which patient populations) remains to be determined

Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating the metabolic characteristics and gene expression of in vitro differentiated myotubes established from well characterized PCOS subjects.Using radiotracer techniques, RT-PCR and enzyme kinetic analysis we examined myotubes established from PCOS subjects with or without pioglitazone treatment, versus healthy control subjects who had been extensively metabolically characterized in vivo. Results. Myotubes established from PCOS and matched control subjects comprehensively expressed all insulin-sensitive biomarkers; glucose uptake and oxidation, glycogen synthesis and lipid uptake. There were no significant differences between groups either at baseline or during acute insulin stimulation, although in vivo skeletal muscle was insulin resistant. In particular, we found no evidence for defects in insulin-stimulated glycogen synthase activity between groups. Myotubes established from PCOS patients with or without pioglitazone treatment also showed no significant differences between groups, neither at baseline nor during acute insulin stimulation, although in vivo pioglitazone treatment significantly improved insulin sensitivity. Consistently, the myotube cultures failed to show differences in mRNA levels of genes previously demonstrated to differ in PCOS patients with or without pioglitazone treatment (PLEK, SLC22A16, and TTBK).These results suggest that the mechanisms governing insulin resistance in skeletal muscle of PCOS patients in vivo are not primary, but rather adaptive.ClinicalTrials.gov NCT00145340

Identifying the connection between Roman Conceptions of ‘Pure Air’ and Physical and Mental Health in Pompeian Gardens (c. 150 BC-AD 79): A Multi-Sensory Approach to Ancient Medicine

Different genres of Roman literature commented on the relationship between the condition of the environment and physical and mental health. They often refer to clear, pure, or good air as a beneficial aspect of the environment. Yet, unlike fetid air, they provide few descriptions of what constituted healthy air quality. Moreover, aside from pointing out the association between the environment and bodily condition, the writers also did not explain precisely how the link between the two was made. This paper utilizes a comparative study of ancient literature and the archaeological remains of Roman gardens in Pompeii: archaeobotanical samples, fresco paintings, location, and surviving features. Three questions are addressed in this study: First, how did the Romans identify and define pure? Second, how did air connect to the body? Third, what were the qualities of pure air and how did they benefit the body? Not only was inhalation a means of linking air to the body, but the two were also related through sensory perception. I argue that sight, sound, and olfaction were used to identify the qualities of pure air. Through the sensory process of identification, the beneficial properties of pure air were, in accordance with ancient perceptions of sensory function, taken into the body and affected health. Thus, sensory perception acted as the bridge between the environment and health

Polycystic ovary syndrome

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.Robert J Norman, Ruijin Wu and Marcin T Stankiewic

Models for Type Ia supernovae and related astrophysical transients

We give an overview of recent efforts to model Type Ia supernovae and related astrophysical transients resulting from thermonuclear explosions in white dwarfs. In particular we point out the challenges resulting from the multi-physics multi-scale nature of the problem and discuss possible numerical approaches to meet them in hydrodynamical explosion simulations and radiative transfer modeling. We give examples of how these methods are applied to several explosion scenarios that have been proposed to explain distinct subsets or, in some cases, the majority of the observed events. In case we comment on some of the successes and shortcoming of these scenarios and highlight important outstanding issues.Comment: 20 pages, 2 figures, review published in Space Science Reviews as part of the topical collection on supernovae, replacement corrects typos in the conclusions sectio

Biological maturation and β-adrenergic effectors: development of β-adrenergic receptors in rabbit heart

The β-adrenergic receptor, transduction processes and catalytic activity of the adenylate cyclase enzyme complex have been investigated in rabbit heart at different stages of biological maturation. The binding of [ 3 H]-dihydroalprenolol to a washed membrane preparation isolated from rabbit ventricular muscle was used to characterize β-adrenergic receptors. Significant age-related differences were noted in β-receptor affinity (K d ) and density (RD) of neonatal and adult animals; the adult K d was 3.7-fold greater and the RD 2-fold higher than the neonates. No significant differences in these parameters were detected among the 27-day old fetus and the 1- and 7-day old neonates. Age-dependent differences in agonist isoproterenol affinity for the receptor were not observed in contrast to the significant changes in antagonist (DHA) affinity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45349/1/11010_2004_Article_BF00240617.pd