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

Generative Models from the perspective of Continual Learning

Which generative model is the most suitablefor Continual Learning? This paper aims at evaluating andcomparing generative models on disjoint sequential imagegeneration tasks. We investigate how several models learn andforget, considering various strategies: rehearsal, regularization,generative replay and fine-tuning. We used two quantitativemetrics to estimate the generation quality and memory ability.We experiment with sequential tasks on three commonly usedbenchmarks for Continual Learning (MNIST, Fashion MNISTand CIFAR10). We found that among all models, the originalGAN performs best and among Continual Learning strategies,generative replay outperforms all other methods. Even ifwe found satisfactory combinations on MNIST and FashionMNIST, training generative models sequentially on CIFAR10is particularly instable, and remains a challenge. Our code isavailable online

Effects of Relaxation on Conversion Negative Electrode Materials for Li-Ion Batteries: A Study of TiSnSb Using 119Sn Mössbauer and 7Li MAS NMR Spectroscopies

Conversion materials were recently considered as plausible alternatives to conventional insertion negative electrode materials in lithium-ion batteries due to their large gravimetric and volumetric energy densities. The ternary alloy TiSnSb was recently proposed as a suitable negative electrode material due to its large capacity (550 mA h g–1) and rate capability over many cycles. TiSnSb has been investigated at the end of lithiation (discharge) using 119Sn Mössbauer and 7Li magic-angle spinning (MAS) NMR spectroscopies to determine the species formed, their relative stabilities and their behavior during relaxation. During discharge, TiSnSb undergoes a conversion reaction to produce a mixture of phases believed to consist of lithium antimonides, lithium stannides, and titanium metal. In situ 119Sn Mössbauer spectroscopy indicates the presence of Li7Sn2 at the end of discharge, while 7Li NMR experiments suggest the formation of two distinct Sn-containing species (tentatively assigned to Li7Sn2 and Li7Sn3), in addition to two Sb-containing species (tentatively assigned as Li3Sb and a non-stoichiometric phase of Li2Sb, Li2–xSb). To gain insight into the relative stabilities of the species formed, experiments have been completed under open circuit voltage conditions. A new Sn-based species has been identified via 119Sn Mössbauer spectroscopy at the end of relaxation. Similar changes are observed in the 7Li NMR spectra obtained during relaxation. The species created at the end of discharge are extremely unstable and spontaneously evolve towards delithiated phases. Surprisingly, it is possible to resume electrochemical cycling after relaxation. It is likely that this behavior can be extended to this family of electrode materials that undergo the conversion reaction

High Frequency top-down Junction-less Silicon Nanowire Resonators

We report here the first realization of top-down silicon nanowires (SiNW) transduced by both junction-less field effect transistor (FET) and the piezoresistive (PZR) effect. The suspended SiNWs are among the smallest top-down SiNWs reported to date, featuring widths down to ~20nm. This has been achieved thanks to a 200mm-wafer-scale, VLSI process fully amenable to monolithic CMOS co-integration. Thanks to the very small dimensions, the conductance of the silicon nanowire can be controlled by a nearby electrostatic gate. Both the junction-less FET and the previously demonstrated PZR transduction have been performed with the same SiNW. These self-transducing schemes have shown similar signal-to-background ratios, and the PZR transduction has exhibited a relatively higher output signal. Allan deviation AD of the same SiNW has been measured with both schemes, and we obtain AD~20ppm for the FET detection and AD~3ppm for the PZR detection at room temperature and low pressure. Orders of magnitude improvements are expected from tighter electrostatic control via changes in geometry and doping level, as well as from CMOS integration. The compact, simple topology of these elementary SiNW resonators opens up new paths towards ultra-dense arrays for gas and mass sensing, time keeping or logic switching systems in SiNW-CMOS platform

Phase Transition in a Model with Non-Compact Symmetry on Bethe Lattice and the Replica Limit

We solve $O(n,1)$ nonlinear vector model on Bethe lattice and show that it exhibits a transition from ordered to disordered state for $0 \leq n < 1$. If the replica limit $n\to 0$ is taken carefully, the model is shown to reduce to the corresponding supersymmetric model. The latter was introduced by Zirnbauer as a toy model for the Anderson localization transition. We argue thus that the non-compact replica models describe correctly the Anderson transition features. This should be contrasted to their failure in the case of the level correlation problem.Comment: 21 pages, REVTEX, 2 Postscript figures, uses epsf styl

A Pluralistic Theory of Wordhood

What are words and how should we individuate them? There are two main answers on the philosophical market. For some, words are bundles of structural-functional features defining a unique performance profile. For others, words are non-eternal continuants individuated by their causal-historical ancestry. These conceptions offer competing views of the nature of words, and it seems natural to assume that at most one of them can capture the essence of wordhood. This paper makes a case for pluralism about wordhood: the view that there is a plurality of acceptable conceptions of the nature of words, none of which is uniquely entitled to inform us as to what wordhood consists in

General Relativity As an Aether Theory

Most early twentieth century relativists --- Lorentz, Einstein, Eddington, for examples --- claimed that general relativity was merely a theory of the aether. We shall confirm this claim by deriving the Einstein equations using aether theory. We shall use a combination of Lorentz's and Kelvin's conception of the aether. Our derivation of the Einstein equations will not use the vanishing of the covariant divergence of the stress-energy tensor, but instead equate the Ricci tensor to the sum of the usual stress-energy tensor and a stress-energy tensor for the aether, a tensor based on Kelvin's aether theory. A crucial first step is generalizing the Cartan formalism of Newtonian gravity to allow spatial curvature, as conjectured by Gauss and Riemann

Long-duration gamma-ray emissions from 2007 and 2008 winter thunderstorms

The Gamma-Ray Observation of Winter THunderclouds (GROWTH) experiment, consisting of two radiation-detection subsystems, has been operating since 2006 on the premises of Kashiwazaki-Kariwa nuclear power plant located at the coastal area of Japan Sea. By 2010 February, GROWTH detected 7 long-duration $\gamma$-rays emissions associated with winter thunderstorms. Of them, two events, obtained on 2007 December 13 and 2008 December 25, are reported.On both occasions, all inorganic scintillators (NaI, CsI, and BGO) of the two subsystems detected significant gamma-ray signals lasting for >1 minute. Neither of these two events were associated with any lightning. In both cases, the gamma-ray energy spectra extend to 10 MeV, suggesting that the detected gamma-rays are produced by relativistic electrons via bremsstrahlung. Assuming that the initial photon spectrum at the source is expressed by a power-law function,the observed photons can be interpreted as being radiated from a source located at a distance of 290-560 m for the 2007 event and 110-690 m for the 2008 one, both at 90% confidence level.Employing these photon spectra, the number of relativistic electrons is estimated as 10^9 - 10^{11}. The estimation generally agrees with those calculated based on the relativistic runaway electron avalanche model. A GROWTH photon spectrum, summed over 3 individual events including the present two events and another reported previously, has similar features including a cut-off energy, to an averaged spectrum of terrestrial gamma-ray flashes.Comment: 46 pages, 13 figures, accepted for publication in JGR-Atmospher