Spectral approach to linear programming bounds on codes

We give new proofs of asymptotic upper bounds of coding theory obtained within the frame of Delsarte's linear programming method. The proofs rely on the analysis of eigenvectors of some finite-dimensional operators related to orthogonal polynomials. The examples of the method considered in the paper include binary codes, binary constant-weight codes, spherical codes, and codes in the projective spaces.Comment: 11 pages, submitte

Idaho National Engineering and Environmental Laboratory Site Report on the Production and Use of Recycled Uranium

Recent allegations regarding radiation exposure to radionuclides present in recycled uranium sent to the gaseous diffusion plants prompted the Department of Energy to undertake a system-wide study of recycled uranium. Of particular interest, were the flowpaths from site to site operations and facilities in which exposure to plutonium, neptunium and technetium could occur, and to the workers that could receive a significant radiation dose from handling recycled uranium. The Idaho National Engineering and Environmental Laboratory site report is primarily concerned with two locations. Recycled uranium was produced at the Idaho Chemical Processing Plant where highly enriched uranium was recovered from spent fuel. The other facility is the Specific Manufacturing Facility (SMC) where recycled, depleted uranium is manufactured into shapes for use by their customer. The SMC is a manufacturing facility that uses depleted uranium metal as a raw material that is then rolled and cut into shapes. There are no chemical processes that might concentrate any of the radioactive contaminant species. Recyclable depleted uranium from the SMC facility is sent to a private metallurgical facility for recasting. Analyses on the recast billets indicate that there is no change in the concentrations of transuranics as a result of the recasting process. The Idaho Chemical Processing Plant was built to recover high-enriched uranium from spent nuclear fuel from test reactors. The facility processed diverse types of fuel which required uniquely different fuel dissolution processes. The dissolved fuel was passed through three cycles of solvent extraction which resulted in a concentrated uranyl nitrate product. For the first half of the operating period, the uranium was shipped as the concentrated solution. For the second half of the operating period the uranium solution was thermally converted to granular, uranium trioxide solids. The dose reconstruction project has evaluated work exposure and exposure to the public as the result of normal operations and accidents that occurred at the INEEL. As a result of these studies, the maximum effective dose equivalent from site activities did not exceed seventeen percent of the natural background in Eastern Idaho. There was no year in which the radiation dose to the public exceeded the applicable limits for that year. Worker exposure to recycled uranium was minimized by engineering features that reduced the possibility of direct exposure

Progression of Diet-Induced Diabetes in C57BL6J Mice Involves Functional Dissociation of Ca2+ Channels From Secretory Vesicles

OBJECTIVE: The aim of the study was to elucidate the cellular mechanism underlying the suppression of glucose-induced insulin secretion in mice fed a high-fat diet (HFD) for 15 weeks. RESEARCH DESIGN AND METHODS: C57BL6J mice were fed a HFD or a normal diet (ND) for 3 or 15 weeks. Plasma insulin and glucose levels in vivo were assessed by intraperitoneal glucose tolerance test. Insulin secretion in vitro was studied using static incubations and a perfused pancreas preparation. Membrane currents, electrical activity, and exocytosis were examined by patch-clamp technique measurements. Intracellular calcium concentration ([Ca(2+)](i)) was measured by microfluorimetry. Total internal reflection fluorescence microscope (TIRFM) was used for optical imaging of exocytosis and submembrane depolarization-evoked [Ca(2+)](i). The functional data were complemented by analyses of histology and gene transcription. RESULTS: After 15 weeks, but not 3 weeks, mice on HFD exhibited hyperglycemia and hypoinsulinemia. Pancreatic islet content and beta-cell area increased 2- and 1.5-fold, respectively. These changes correlated with a 20-50% reduction of glucose-induced insulin secretion (normalized to insulin content). The latter effect was not associated with impaired electrical activity or [Ca(2+)](i) signaling. Single-cell capacitance and TIRFM measurements of exocytosis revealed a selective suppression (>70%) of exocytosis elicited by short (50 ms) depolarization, whereas the responses to longer depolarizations were (500 ms) less affected. The loss of rapid exocytosis correlated with dispersion of Ca(2+) entry in HFD beta-cells. No changes in gene transcription of key exocytotic protein were observed. CONCLUSIONS: HFD results in reduced insulin secretion by causing the functional dissociation of voltage-gated Ca(2+) entry from exocytosis. These observations suggest a novel explanation to the well-established link between obesity and diabetes

Minimal state models for ionic channels involved in glucagon secretion

Pancreatic alpha cells synthesize and release glucagon. This hormone along with insulin, preserves blood glucose levels within a physiological range. During low glucose levels, alpha cells exhibit electrical activity related to glucagon secretion. In this paper, we introduce minimal state models for those ionic channels involved in this electrical activity in mice alpha cells. For estimation of model parameters, we use Monte Carlo algorithms to fit steadystate channel currents. Then, we simulate dynamic ionic currents following experimental protocols. Our aims are 1) To understand the individual ionic channel functioning and modulation that could affect glucagon secretion, and 2) To simulate ionic currents actually measured in voltage-clamp alpha-cell experiments in mice. Our estimations indicate that alpha cells are highly permeable to sodium and potassium which mainly manage action potentials. We have also found that our estimated N-type calcium channel population and density in alpha cells is in good agreement to those reported for L-type calcium channels in beta cells. This finding is strongly relevant since both, L-type and N-type calcium channels, play a main role in insulin and glucagon secretion, respectively

Evidence That Ca2+ within the Microdomain of the L-Type Voltage Gated Ca2+ Channel Activates ERK in MIN6 Cells in Response to Glucagon-Like Peptide-1

Glucagon like peptide-1 (GLP-1) is released from intestinal L-cells in response to nutrient ingestion and acts upon pancreatic β-cells potentiating glucose-stimulated insulin secretion and stimulating β-cell proliferation, differentiation, survival and gene transcription. These effects are mediated through the activation of multiple signal transduction pathways including the extracellular regulated kinase (ERK) pathway. We have previously reported that GLP-1 activates ERK through a mechanism dependent upon the influx of extracellular Ca2+ through L-type voltage gated Ca2+ channels (VGCC). However, the mechanism by which L-type VGCCs couple to the ERK signalling pathway in pancreatic β-cells is poorly understood. In this report, we characterise the relationship between L-type VGCC mediated changes in intracellular Ca2+ concentration ([Ca2+]i) and the activation of ERK, and demonstrate that the sustained activation of ERK (up to 30 min) in response to GLP-1 requires the continual activation of the L-type VGCC yet does not require a sustained increase in global [Ca2+]i or Ca2+ efflux from the endoplasmic reticulum. Moreover, sustained elevation of [Ca2+]i induced by ionomycin is insufficient to stimulate the prolonged activation of ERK. Using the cell permeant Ca2+ chelators, EGTA-AM and BAPTA-AM, to determine the spatial dynamics of L-type VGCC-dependent Ca2+ signalling to ERK, we provide evidence that a sustained increase in Ca2+ within the microdomain of the L-type VGCC is sufficient for signalling to ERK and that this plays an important role in GLP-1- stimulated ERK activation

Multivesicular exocytosis in rat pancreatic beta cells

AIMS/HYPOTHESIS: To establish the occurrence, modulation and functional significance of compound exocytosis in insulin-secreting beta cells. METHODS: Exocytosis was monitored in rat beta cells by electrophysiological, biochemical and optical methods. The functional assays were complemented by three-dimensional reconstruction of confocal imaging, transmission and block face scanning electron microscopy to obtain ultrastructural evidence of compound exocytosis. RESULTS: Compound exocytosis contributed marginally (<5% of events) to exocytosis elicited by glucose/membrane depolarisation alone. However, in beta cells stimulated by a combination of glucose and the muscarinic agonist carbachol, 15-20% of the release events were due to multivesicular exocytosis, but the frequency of exocytosis was not affected. The optical measurements suggest that carbachol should stimulate insulin secretion by ∼40%, similar to the observed enhancement of glucose-induced insulin secretion. The effects of carbachol were mimicked by elevating [Ca(2+)](i) from 0.2 to 2 μmol/l Ca(2+). Two-photon sulforhodamine imaging revealed exocytotic events about fivefold larger than single vesicles and that these structures, once formed, could persist for tens of seconds. Cells exposed to carbachol for 30 s contained long (1-2 μm) serpentine-like membrane structures adjacent to the plasma membrane. Three-dimensional electron microscopy confirmed the existence of fused multigranular aggregates within the beta cell, the frequency of which increased about fourfold in response to stimulation with carbachol. CONCLUSIONS/INTERPRETATION: Although contributing marginally to glucose-induced insulin secretion, compound exocytosis becomes quantitatively significant under conditions associated with global elevation of cytoplasmic calcium. These findings suggest that compound exocytosis is a major contributor to the augmentation of glucose-induced insulin secretion by muscarinic receptor activation

Older Norwegians' understanding of loneliness

This interpretive study explored older people's understanding of loneliness and what they considered appropriate and effective ways of dealing with it. Thirty elderly people were interviewed in-depth; 12 described themselves as “lonely” and 18 as “not lonely.” We found a striking difference in the way “lonely” and “not lonely” people talked about loneliness. The “not lonely” participants described loneliness as painful, caused by the person's negative way of behaving and a state they should pull themselves out of. The “lonely” participants also described loneliness as painful, and gave more detailed descriptions of loneliness as disconnection from others, from their former home and from today's society. The “lonely” participants were more reserved and subdued in trying to explain loneliness, attributing it partly to themselves, but mostly to the lack of social contact with important others. Some felt able to handle their loneliness, while others felt unable to cope. This study underlines the importance of subjective experiences in trying to understand a phenomenon like loneliness and of developing support for lonely older people unable to cope on their own

Do Zebra Finch Parents Fail to Recognise Their Own Offspring?

Individual recognition systems require the sender to be individually distinctive and the receiver to be able to perceive differences between individuals and react accordingly. Many studies have demonstrated that acoustic signals of almost any species contain individualized information. However, fewer studies have tested experimentally if those signals are used for individual recognition by potential receivers. While laboratory studies using zebra finches have shown that fledglings recognize their parents by their “distance call”, mutual recognition using the same call type has not been demonstrated yet. In a laboratory study with zebra finches, we first quantified between-individual acoustic variation in distance calls of fledglings. In a second step, we tested recognition of fledgling calls by parents using playback experiments. With a discriminant function analysis, we show that individuals are highly distinctive and most measured parameters show very high potential to encode for individuality. The response pattern of zebra finch parents shows that they do react to calls of fledglings, however they do not distinguish between own and unfamiliar offspring, despite individual distinctiveness. This finding is interesting in light of the observation of a high percentage of misdirected feedings in our communal breeding aviaries. Our results demonstrate the importance of adopting a receiver's perspective and suggest that variation in fledgling contact calls might not be used in individual recognition of offspring

Control of the Intracellular Redox State by Glucose Participates in the Insulin Secretion Mechanism

Background: Production of reactive oxygen species (ROS) due to chronic exposure to glucose has been associated with impaired beta cell function and diabetes. However, physiologically, beta cells are well equipped to deal with episodic glucose loads, to which they respond with a fine tuned glucose-stimulated insulin secretion (GSIS). In the present study, a systematic investigation in rat pancreatic islets about the changes in the redox environment induced by acute exposure to glucose was carried out. Methodology/Principal Findings: Short term incubations were performed in isolated rat pancreatic islets. Glucose dose- and time-dependently reduced the intracellular ROS content in pancreatic islets as assayed by fluorescence in a confocal microscope. This decrease was due to activation of pentose-phosphate pathway (PPP). Inhibition of PPP blunted the redox control as well as GSIS in a dose-dependent manner. The addition of low doses of ROS scavengers at high glucose concentration acutely improved beta cell function. The ROS scavenger N-acetyl-L-cysteine increased the intracellular calcium response to glucose that was associated with a small decrease in ROS content. Additionally, the presence of the hydrogen peroxide-specific scavenger catalase, in its membrane-permeable form, nearly doubled glucose metabolism. Interestingly, though an increase in GSIS was also observed, this did not match the effect on glucose metabolism. Conclusions: The control of ROS content via PPP activation by glucose importantly contributes to the mechanisms that couple the glucose stimulus to insulin secretion. Moreover, we identified intracellular hydrogen peroxide as an inhibitor of glucose metabolism intrinsic to rat pancreatic islets. These findings suggest that the intracellular adjustment of the redox environment by glucose plays an important role in the mechanism of GSIS.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)(CAPES) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazi