Fast Traveling-Wave Reactor of the Channel Type

The main aim of this paper is to solve the technological problems of the TWR based on the technical concept described in our priority of invention reference, which makes it impossible, in particular, for the fuel claddings damaging doses of fast neutrons to excess the ~200 dpa limit. Thus the essence of the technical concept is to provide a given neutron flux at the fuel claddings by setting the appropriate speed of the fuel motion relative to the nuclear burning wave. The basic design of the fast uranium-plutonium nuclear traveling-wave reactor with a softened neutron spectrum is developed, which solves the problem of the radiation resistance of the fuel claddings material.Comment: 18 pages, 5 figures, 2 table

[ P³ ] PP, a stable, long‐acting pancreatic polypeptide analogue, evokes weight lowering and pancreatic beta‐cell‐protective effects in obesity‐associated diabetes

Aim: To thoroughly investigate the impact of sustained neuropeptide Y4 receptor (NPY4R) activation in obesity‐associated diabetes. Methods: Initially, the prolonged pharmacodynamic profile of the enzymatically stable pancreatic polypeptide (PP) analogue, [P3]PP, was confirmed in normal mice up to 24 h after injection. Subsequent to this, [P3]PP was administered twice daily (25 nmol/kg) for 28 days to high‐fat‐fed mice with streptozotocin‐induced insulin deficiency, known as HFF/STZ mice. Results: Treatment with [P3]PP for 28 days reduced energy intake and was associated with notable weight loss. In addition, circulating glucose was returned to values of approximately 8 mmol/L in [P3]PP‐treated mice, with significantly increased plasma insulin and decreased glucagon concentrations. Glucose tolerance and glucose‐stimulated insulin secretion were improved in [P3]PP‐treated HFF/STZ mice, with no obvious effect on peripheral insulin sensitivity. Benefits on insulin secretion were associated with elevated pancreatic insulin content as well as islet and beta‐cell areas. Positive effects on islet architecture were linked to increased beta‐cell proliferation and decreased apoptosis. Treatment intervention also decreased islet alpha‐cell area, but pancreatic glucagon content remained unaffected. In addition, [P3]PP‐treated HFF/STZ mice presented with reduced plasma alanine transaminase and aspartate transaminase levels, with no change in circulating amylase concentrations. In terms of plasma lipid profile, triglyceride and cholesterol levels were significantly decreased by [P3]PP treatment, when compared to saline controls. Conclusion: Collectively, these data highlight for the first time the potential of enzymatically stable PP analogues for the treatment of obesity and related diabetes

Geometrical methods in loop calculations and the three-point function

A geometrical way to calculate N-point Feynman diagrams is reviewed. As an example, the dimensionally-regulated three-point function is considered, including all orders of its epsilon-expansion. Analytical continuation to other regions of the kinematical variables is discussed.Comment: 6 pages, LaTeX, 3 eps figures, contribution to proceedings of ACAT2005 (Zeuthen, May 2005

Dopamine signalling in pancreatic islet cells and role in adaptations to metabolic stress

Objectives Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet β-cell stimulus-secretion as well as (patho)physiological role are unclear. Methods The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology. Key findings The dopamine precursor L-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion. The latter effect was echoed by the attenuation of glucose-induced [Ca2+]i dynamics and elevation of ATP levels in individual mouse islet cells. L-DOPA significantly decreased β-cell proliferation rates, acting predominantly via the D2 receptor, which was most abundant at the mRNA level. The administration of streptozotocin (STZ) or high-fat diet (HFD) in mice significantly elevated numbers of dopamine-positive islet cells, with HFD also increasing colocalization of dopamine with insulin. At the same time, colocalization of dopamine with glucagon was increased in STZ-treated and pregnant mice, but unaffected by HFD. Conclusion These findings highlight a role for dopamine receptor signalling in islet cell biology adaptations to various forms of metabolic stress

Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production

© 2018 The Author(s). Published by Elsevier Inc.Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their β cells (Fh1βKO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion. Protein succination, reflecting reduced activity of fumarase, is observed in α cells from hyperglycemic Fh1βKO and β-V59M gain-of-function KATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1βKO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications.Peer reviewe