Glucagon-like peptide 1 improved glycemic control in type 1 diabetes

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. METHODS: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. RESULTS: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 ± 0.9, mean ± se, vs 5.4 ± 0.8 mmol/l, p < .05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 ± 3.1 vs 37 ± 9.6 pmol/l, p < .05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 ± 2.5 vs 3.1 ± 1.9 ng/l, p < .04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 ± 0.33 vs 0.34 ± 0.26 mmol/l, p < .05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. CONCLUSION: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs

Demodulation of Spatial Carrier Images: Performance Analysis of Several Algorithms Using a Single Image

http://link.springer.com/article/10.1007%2Fs11340-013-9741-6#Optical full-field techniques have a great importance in modern experimental mechanics. Even if they are reasonably spread among the university laboratories, their diffusion in industrial companies remains very narrow for several reasons, especially a lack of metrological performance assessment. A full-field measurement can be characterized by its resolution, bias, measuring range, and by a specific quantity, the spatial resolution. The present paper proposes an original procedure to estimate in one single step the resolution, bias and spatial resolution for a given operator (decoding algorithms such as image correlation, low-pass filters, derivation tools ...). This procedure is based on the construction of a particular multi-frequential field, and a Bode diagram representation of the results. This analysis is applied to various phase demodulating algorithms suited to estimate in-plane displacements.GDR CNRS 2519 “Mesures de Champs et Identification en Mécanique des Solide

Répression transcriptionnelle du gène TRH

Les hormones thyroïdiennes (HT : T3, T4) exerçant des effets pléiotropes chez les vertébrés, leur synthèse et leur sécrétion doivent être finement contrôlées. Elles agissent elles-mêmes sur leur production, par un système de rétrocontrôle négatif de l’expression des gènes hypothalamique TRH et hypophysaire TSH. Les fondements moléculaires de cette répression transcriptionnelle des gènes TRH et TSH par l’hormone T3, forme biologiquement la plus active des HT, restent méconnus. Certaines caractéristiques de cette régulation commencent toutefois à être identifiées, notamment le rôle spécifique des isoformes TRβ (versus TRα) des récepteurs des HT. La spécificité fonctionnelle de ces isoformes résiderait principalement dans leur extrémité aminoterminale, qui permettrait une interaction différentielle avec certains comodulateurs. L’objectif, aujourd’hui, est de caractériser ces comodulateurs et d’analyser leur contribution à la régulation transcriptionnelle du gène TRH par l’hormone T3.The synthesis and secretion of thyroid hormones (TH: T3, T4) must be strictly regulated. TH act on their own production via a negative feedback system. The synthesis of thyrotropin-releasing hormone (TRH), produced in the hypothalamus, and thyrotropin (TSH) in the pituitary is inhibited at the transcriptional level by TH. TRH and TSH stimulate production of TH. An outstanding, still open, question is the molecular basis of T3-dependent transcription repression of TRH and TSH genes. However, some regulatory components have been identified, with the β-TH receptor (TRβ) playing a specific regulatory role (versus TRα) in the negative feedback effects of T3 on production of TRH and TSH. Moreover, the N-terminus of TRβ is known to be a key element in this regulation. A hypothesis to explain this isoform specificity could be that TRβ and TRα interact differentially with transcriptional comodulators. Thus, it is critical to characterize these comodulators and to analyse their contribution to the transcription regulation of TRH

Continual State Representation Learning for Reinforcement Learning using Generative Replay

We consider the problem of building a state representation model in a continual fashion. As the environment changes, the aim is to efficiently compress the sensory state's information without losing past knowledge. The learned features are then fed to a Reinforcement Learning algorithm to learn a policy. We propose to use Variational Auto-Encoders for state representation, and Generative Replay, i.e. the use of generated samples, to maintain past knowledge. We also provide a general and statistically sound method for automatic environment change detection. Our method provides efficient state representation as well as forward transfer, and avoids catastrophic forgetting. The resulting model is capable of incrementally learning information without using past data and with a bounded system size