Ultrafast Graphene Photonics and Optoelectronics

Science.gov (United States)

2017-04-14

AFRL-AFOSR-JP-TR-2017-0032 Ultrafast Graphene Photonics and Optoelectronics Kuang-Hsiung Wu National Chiao Tung University Final Report 04/14/2017...DATES COVERED (From - To) 18 Apr 2013 to 17 Apr 2016 4. TITLE AND SUBTITLE Ultrafast Graphene Photonics and Optoelectronics 5a.  CONTRACT NUMBER 5b...Prescribed by ANSI Std. Z39.18 Final Report for AOARD Grant FA2386-13-1-4022 “Ultrafast Graphene Photonics and Optoelectronics” Date May 23th, 2016

Ultrafast Science Opportunities with Electron Microscopy

Energy Technology Data Exchange (ETDEWEB)

DURR, HERMANN; Wang, X.J., ed.

2016-04-28

X-rays and electrons are two of the most fundamental probes of matter. When the Linac Coherent Light Source (LCLS), the world’s first x-ray free electron laser, began operation in 2009, it transformed ultrafast science with the ability to generate laser-like x-ray pulses from the manipulation of relativistic electron beams. This document describes a similar future transformation. In Transmission Electron Microscopy, ultrafast relativistic (MeV energy) electron pulses can achieve unsurpassed spatial and temporal resolution. Ultrafast temporal resolution will be the next frontier in electron microscopy and can ideally complement ultrafast x-ray science done with free electron lasers. This document describes the Grand Challenge science opportunities in chemistry, material science, physics and biology that arise from an MeV ultrafast electron diffraction & microscopy facility, especially when coupled with linac-based intense THz and X-ray pump capabilities.

A Recirculating Linac-Based Facility for Ultrafast X-Ray Science

International Nuclear Information System (INIS)

Corlett, J. N.; Barletta, W. A.; DeSantis, S.; Doolittle, L.; Fawley, W. M.; Green, M.A.; Heimann, P.; Leone, S.; Lidia, S.; Li, D.; Ratti, A.; Robinson, K.; Schoenlein, R.; Staples, J.; Wan, W.; Wells, R.; Wolski, A.; Zholents, A.; Parmigiani, F.; Placidi, M.; Pirkl, W.; Rimmer, R. A.; Wang, S.

2003-01-01

We present an updated design for a proposed source of ultra-fast synchrotron radiation pulses based on a recirculating superconducting linac [1,2], in particular the incorporation of EUV and soft x-ray production. The project has been named LUX--Linac-based Ultrafast X-ray facility. The source produces intense x-ray pulses with duration of 10-100 fs at a 10 kHz repetition rate, with synchronization of 10's fs, optimized for the study of ultra-fast dynamics. The photon range covers the EUV to hard x-ray spectrum by use of seeded harmonic generation in undulators, and a specialized technique for ultra-short pulse photon production in the 1-10 keV range. High brightness rf photocathodes produce electron bunches which are optimized either for coherent emission in free electron lasers, or to provide a large x/y emittance ration and small vertical emittance which allows for manipulation to produce short-pulse hard x-rays. An injector linac accelerates the beam to 120 MeV, and is followed by f our passes through a 600-720 MeV recirculating linac. We outline the major technical components of the proposed facility

Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size.

Science.gov (United States)

Ahlsson, Fredrik; Diderholm, Barbro; Ewald, Uwe; Jonsson, Björn; Forslund, Anders; Stridsberg, Mats; Gustafsson, Jan

2013-05-01

The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation. Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique. Median (range) rate of glucose production was 805 (653-1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5mg/L and median level of leptin was 47.1 (9.9-58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, pinsulin resistance, r=0.76, pinsulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy. Copyright © 2012 Elsevier Ireland Ltd. All rights

Ultrafast Hierarchical OTDM/WDM Network

Directory of Open Access Journals (Sweden)

Hideyuki Sotobayashi

2003-12-01

Full Text Available Ultrafast hierarchical OTDM/WDM network is proposed for the future core-network. We review its enabling technologies: C- and L-wavelength-band generation, OTDM-WDM mutual multiplexing format conversions, and ultrafast OTDM wavelengthband conversions.

Avant-Garde Ultrafast Laser Writing

Directory of Open Access Journals (Sweden)

Kazansky P. G.

2013-11-01

Full Text Available Ultrafast laser processing of transparent materials reveals new phenomena. Reviewed, are recent demonstrations of 5D optical memory, vortex polarization and Airy beam converters employing self-assembled nanostructuring, ultrafast laser calligraphy and polarization writing control using pulses with tilted front.

Ultrafast nonlinear optics

CERN Document Server

Leburn, Christopher; Reid, Derryck

2013-01-01

The field of ultrafast nonlinear optics is broad and multidisciplinary, and encompasses areas concerned with both the generation and measurement of ultrashort pulses of light, as well as those concerned with the applications of such pulses. Ultrashort pulses are extreme events – both in terms of their durations, and also the high peak powers which their short durations can facilitate. These extreme properties make them powerful experiment tools. On one hand, their ultrashort durations facilitate the probing and manipulation of matter on incredibly short timescales. On the other, their ultrashort durations can facilitate high peak powers which can drive highly nonlinear light-matter interaction processes. Ultrafast Nonlinear Optics covers a complete range of topics, both applied and fundamental in nature, within the area of ultrafast nonlinear optics. Chapters 1 to 4 are concerned with the generation and measurement of ultrashort pulses. Chapters 5 to 7 are concerned with fundamental applications of ultrasho...

Chemical stability of insulin. 2. Formation of higher molecular weight transformation products during storage of pharmaceutical preparations.

Science.gov (United States)

Brange, J; Havelund, S; Hougaard, P

1992-06-01

Formation of covalent, higher molecular weight transformation (HMWT) products during storage of insulin preparations at 4-45 degrees C was studied by size exclusion chromatography. The main products are covalent insulin dimers (CID), but in protamine-containing preparations the concurrent formation of covalent insulin-protamine (CIP) products takes place. At temperatures greater than or equal to 25 degrees C parallel or consecutive formation of covalent oligo- and polymers can also be observed. Rate of HMWT is only slightly influenced by species of insulin but varies with composition and formulation, and for isophane (NPH) preparations, also with the strength of preparation. Temperature has a pronounced effect on CID, CIP, and, especially, covalent oligo- and polymer formation. The CIDs are apparently formed between molecules within the hexameric unit common for all types of preparations and rate of formation is generally faster in glycerol-containing preparations. Compared with insulin hydrolysis reactions (see the preceding paper), HMWT is one order of magnitude slower, except for NPH preparations.

Dairy Product Consumption Interacts with Glucokinase (GCK Gene Polymorphisms Associated with Insulin Resistance

Directory of Open Access Journals (Sweden)

Marine S. Da Silva

2017-08-01

Full Text Available Dairy product intake and a person’s genetic background have been reported to be associated with the risk of type 2 diabetes (T2D. The objective of this study was to examine the interaction between dairy products and genes related to T2D on glucose-insulin homeostasis parameters. A validated food frequency questionnaire, fasting blood samples, and glucokinase (GCK genotypes were analyzed in 210 healthy participants. An interaction between rs1799884 in GCK and dairy intake on the homeostasis model assessment of insulin resistance was identified. Secondly, human hepatocellular carcinoma cells (HepG2 were grown in a high-glucose medium and incubated with either 1-dairy proteins: whey, caseins, and a mixture of whey and casein; and 2-four amino acids (AA or mixtures of AA. The expression of GCK-related genes insulin receptor substrate-1 (IRS-1 and fatty acid synthase (FASN was increased with whey protein isolate or hydrolysate. Individually, leucine increased IRS-1 expression, whereas isoleucine and valine decreased FASN expression. A branched-chain AA mixture decreased IRS-1 and FASN expression. In conclusion, carriers of the A allele for rs1799884 in the GCK gene may benefit from a higher intake of dairy products to maintain optimal insulin sensitivity. Moreover, the results show that whey proteins affect the expression of genes related to glucose metabolism.

Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

International Nuclear Information System (INIS)

Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

2010-01-01

Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

Ultrafast THz saturable absorption in doped semiconductors at room temperature

DEFF Research Database (Denmark)

Turchinovich, Dmitry; Hoffmann, M. V.

2011-01-01

Ultrafast Phenomena XVII presents the latest advances in ultrafast science, including both ultrafast optical technology and the study of ultrafast phenomena. It covers picosecond, femtosecond and attosecond processes relevant to applications in physics, chemistry, biology, and engineering. Ultraf...

Correction of Diabetic Hyperglycemia and Amelioration of Metabolic Anomalies by Minicircle DNA Mediated Glucose-Dependent Hepatic Insulin Production.

Directory of Open Access Journals (Sweden)

Tausif Alam

Full Text Available Type 1 diabetes mellitus (T1DM is caused by immune destruction of insulin-producing pancreatic β-cells. Commonly used insulin injection therapy does not provide a dynamic blood glucose control to prevent long-term systemic T1DM-associated damages. Donor shortage and the limited long-term success of islet transplants have stimulated the development of novel therapies for T1DM. Gene therapy-based glucose-regulated hepatic insulin production is a promising strategy to treat T1DM. We have developed gene constructs which cause glucose-concentration-dependent human insulin production in liver cells. A novel set of human insulin expression constructs containing a combination of elements to improve gene transcription, mRNA processing, and translation efficiency were generated as minicircle DNA preparations that lack bacterial and viral DNA. Hepatocytes transduced with the new constructs, ex vivo, produced large amounts of glucose-inducible human insulin. In vivo, insulin minicircle DNA (TA1m treated streptozotocin (STZ-diabetic rats demonstrated euglycemia when fasted or fed, ad libitum. Weight loss due to uncontrolled hyperglycemia was reversed in insulin gene treated diabetic rats to normal rate of weight gain, lasting ∼1 month. Intraperitoneal glucose tolerance test (IPGT demonstrated in vivo glucose-responsive changes in insulin levels to correct hyperglycemia within 45 minutes. A single TA1m treatment raised serum albumin levels in diabetic rats to normal and significantly reduced hypertriglyceridemia and hypercholesterolemia. Elevated serum levels of aspartate transaminase, alanine aminotransferase, and alkaline phosphatase were restored to normal or greatly reduced in treated rats, indicating normalization of liver function. Non-viral insulin minicircle DNA-based TA1m mediated glucose-dependent insulin production in liver may represent a safe and promising approach to treat T1DM.

NADPH Oxidase-Mediated ROS Production Determines Insulin's Action on the Retinal Microvasculature.

Science.gov (United States)

Kida, Teruyo; Oku, Hidehiro; Horie, Taeko; Matsuo, Junko; Kobayashi, Takatoshi; Fukumoto, Masanori; Ikeda, Tsunehiko

2015-10-01

To determine whether insulin induces nitric oxide (NO) formation in retinal microvessels and to examine the effects of high glucose on the formation of NO. Freshly isolated rat retinal microvessels were incubated in normal (5.5 mM) or high (20 mM) glucose with or without insulin (100 nM). The levels of insulin-induced NO and reactive oxygen species (ROS) in the retinal microvessels were determined semiquantitatively using fluorescent probes, 4,5-diaminofluorescein diacetate, and hydroethidine, respectively, and a laser scanning confocal microscope. The insulin-induced changes of NO in rat retinal endothelial cells and pericytes cultured at different glucose concentrations (5.5 and 25 mM) were determined using flow cytometry. Nitric oxide synthase (NOS) protein levels were determined by Western blot analysis; intracellular levels of ROS were determined using fluorescence-activated cell sorting (FACS) analysis of ethidium fluorescence; and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase RNA expression was quantified using real-time PCR. Exposure of microvessels to insulin under normal glucose conditions led to a significant increase in NO levels; however, this increase was significantly suppressed when the microvessels were incubated under high glucose conditions. Intracellular levels of ROS were significantly increased in both retinal microvessels and cultured microvascular cells under high glucose conditions. The expression of NOS and NADPH oxidase were significantly increased in endothelial cells and pericytes under high glucose conditions. The increased formation of NO by insulin and its suppression by high glucose conditions suggests that ROS production mediated by NADPH oxidase is important by insulin's effect on the retinal microvasculature.

Ultrafast laser spectroscopy in complex solid state materials

Energy Technology Data Exchange (ETDEWEB)

Li, Tianqi [Iowa State Univ., Ames, IA (United States)

2014-12-01

This thesis summarizes my work on applying the ultrafast laser spectroscopy to the complex solid state materials. It shows that the ultrafast laser pulse can coherently control the material properties in the femtosecond time scale. And the ultrafast laser spectroscopy can be employed as a dynamical method for revealing the fundamental physical problems in the complex material systems.

Ultrafast molecular dynamics illuminated with synchrotron radiation

International Nuclear Information System (INIS)

Bozek, John D.; Miron, Catalin

2015-01-01

Highlights: • Ultrafast molecular dynamics probed with synchrotron radiation. • Core-excitation as probe of ultrafast dynamics through core-hole lifetime. • Review of experimental and theoretical methods in ultrafast dynamics using core-level excitation. - Abstract: Synchrotron radiation is a powerful tool for studying molecular dynamics in small molecules in spite of the absence of natural matching between the X-ray pulse duration and the time scale of nuclear motion. Promoting core level electrons to unoccupied molecular orbitals simultaneously initiates two ultrafast processes, nuclear dynamics on the potential energy surfaces of the highly excited neutral intermediate state of the molecule on the one hand and an ultrafast electronic decay of the intermediate excited state to a cationic final state, characterized by a core hole lifetime. The similar time scales of these processes enable core excited pump-probe-type experiments to be performed with long duration X-ray pulses from a synchrotron source. Recent results obtained at the PLIEADES beamline concerning ultrafast dissociation of core excited states and molecular potential energy curve mapping facilitated by changes in the geometry of the short-lived intermediate core excited state are reviewed. High brightness X-ray beams combined with state-of-the art electron and ion-electron coincidence spectrometers and highly sophisticated theoretical methods are required to conduct these experiments and to achieve a full understanding of the experimental results.

Application of simple fed-batch technique to high-level secretory production of insulin precursor using Pichia pastoris with subsequent purification and conversion to human insulin

Directory of Open Access Journals (Sweden)

Chugh Dipti

2010-05-01

Full Text Available Abstract Background The prevalence of diabetes is predicted to rise significantly in the coming decades. A recent analysis projects that by the year 2030 there will be ~366 million diabetics around the world, leading to an increased demand for inexpensive insulin to make this life-saving drug also affordable for resource poor countries. Results A synthetic insulin precursor (IP-encoding gene, codon-optimized for expression in P. pastoris, was cloned in frame with the Saccharomyces cerevisiae α-factor secretory signal and integrated into the genome of P. pastoris strain X-33. The strain was grown to high-cell density in a batch procedure using a defined medium with low salt and high glycerol concentrations. Following batch growth, production of IP was carried out at methanol concentrations of 2 g L-1, which were kept constant throughout the remaining production phase. This robust feeding strategy led to the secretion of ~3 gram IP per liter of culture broth (corresponding to almost 4 gram IP per liter of cell-free culture supernatant. Using immobilized metal ion affinity chromatography (IMAC as a novel approach for IP purification, 95% of the secreted product was recovered with a purity of 96% from the clarified culture supernatant. Finally, the purified IP was trypsin digested, transpeptidated, deprotected and further purified leading to ~1.5 g of 99% pure recombinant human insulin per liter of culture broth. Conclusions A simple two-phase cultivation process composed of a glycerol batch and a constant methanol fed-batch phase recently developed for the intracellular production of the Hepatitis B surface antigen was adapted to secretory IP production. Compared to the highest previously reported value, this approach resulted in an ~2 fold enhancement of IP production using Pichia based expression systems, thus significantly increasing the efficiency of insulin manufacture.

Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

Science.gov (United States)

Heni, Martin; Wagner, Robert; Kullmann, Stephanie; Gancheva, Sofiya; Roden, Michael; Peter, Andreas; Stefan, Norbert; Preissl, Hubert; Häring, Hans-Ulrich; Fritsche, Andreas

2017-07-01

Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6- 2 H 2 ]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis. © 2017 by the American Diabetes Association.

L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2.

Science.gov (United States)

Nakatsu, Daiki; Horiuchi, Yuta; Kano, Fumi; Noguchi, Yoshiyuki; Sugawara, Taichi; Takamoto, Iseki; Kubota, Naoto; Kadowaki, Takashi; Murata, Masayuki

2015-03-10

Increase in the concentration of plasma L-cysteine is closely associated with defective insulin secretion from pancreatic β-cells, which results in type 2 diabetes (T2D). In this study, we investigated the effects of prolonged L-cysteine treatment on glucose-stimulated insulin secretion (GSIS) from mouse insulinoma 6 (MIN6) cells and from mouse pancreatic islets, and found that the treatment reversibly inhibited glucose-induced ATP production and resulting GSIS without affecting proinsulin and insulin synthesis. Comprehensive metabolic analyses using capillary electrophoresis time-of-flight mass spectrometry showed that prolonged L-cysteine treatment decreased the levels of pyruvate and its downstream metabolites. In addition, methyl pyruvate, a membrane-permeable form of pyruvate, rescued L-cysteine-induced inhibition of GSIS. Based on these results, we found that both in vitro and in MIN6 cells, L-cysteine specifically inhibited the activity of pyruvate kinase muscle isoform 2 (PKM2), an isoform of pyruvate kinases that catalyze the conversion of phosphoenolpyruvate to pyruvate. L-cysteine also induced PKM2 subunit dissociation (tetramers to dimers/monomers) in cells, which resulted in impaired glucose-induced ATP production for GSIS. DASA-10 (NCGC00181061, a substituted N,N'-diarylsulfonamide), a specific activator for PKM2, restored the tetramer formation and the activity of PKM2, glucose-induced ATP production, and biphasic insulin secretion in L-cysteine-treated cells. Collectively, our results demonstrate that impaired insulin secretion due to exposure to L-cysteine resulted from its direct binding and inactivation of PKM2 and suggest that PKM2 is a potential therapeutic target for T2D.

Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

NARCIS (Netherlands)

Coomans, Claudia P.; Biermasz, Nienke R.; Geerling, Janine J.; Guigas, Bruno; Rensen, Patrick C. N.; Havekes, Louis M.; Romijn, Johannes A.

2011-01-01

Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

NARCIS (Netherlands)

Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

2011-01-01

OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

Progress in ultrafast laser processing and future prospects

Science.gov (United States)

Sugioka, Koji

2017-03-01

The unique characteristics of ultrafast lasers have rapidly revolutionized materials processing after their first demonstration in 1987. The ultrashort pulse width of the laser suppresses heat diffusion to the surroundings of the processed region, which minimizes the formation of a heat-affected zone and thereby enables ultrahigh precision micro- and nanofabrication of various materials. In addition, the extremely high peak intensity can induce nonlinear multiphoton absorption, which extends the diversity of materials that can be processed to transparent materials such as glass. Nonlinear multiphoton absorption enables three-dimensional (3D) micro- and nanofabrication by irradiation with tightly focused femtosecond laser pulses inside transparent materials. Thus, ultrafast lasers are currently widely used for both fundamental research and practical applications. This review presents progress in ultrafast laser processing, including micromachining, surface micro- and nanostructuring, nanoablation, and 3D and volume processing. Advanced technologies that promise to enhance the performance of ultrafast laser processing, such as hybrid additive and subtractive processing, and shaped beam processing are discussed. Commercial and industrial applications of ultrafast laser processing are also introduced. Finally, future prospects of the technology are given with a summary.

Insulin resistance in dairy cows.

Science.gov (United States)

De Koster, Jenne D; Opsomer, Geert

2013-07-01

Glucose is the molecule that drives milk production, and insulin plays a pivotal role in the glucose metabolism of dairy cows. The effect of insulin on the glucose metabolism is regulated by the secretion of insulin by the pancreas and the insulin sensitivity of the skeletal muscles, the adipose tissue, and the liver. Insulin resistance may develop as part of physiologic (pregnancy and lactation) and pathologic processes, which may manifest as decreased insulin sensitivity or decreased insulin responsiveness. A good knowledge of the normal physiology of insulin is needed to measure the in vivo insulin resistance of dairy cows. Copyright © 2013 Elsevier Inc. All rights reserved.

Perspective: Ultrafast magnetism and THz spintronics

Energy Technology Data Exchange (ETDEWEB)

Walowski, Jakob; Münzenberg, Markus [Institut für Physik, Ernst-Moritz-Arndt-Universität Greifswald, 17489 Greifswald (Germany)

2016-10-14

This year the discovery of femtosecond demagnetization by laser pulses is 20 years old. For the first time, this milestone work by Bigot and coworkers gave insight directly into the time scales of microscopic interactions that connect the spin and electron system. While intense discussions in the field were fueled by the complexity of the processes in the past, it now became evident that it is a puzzle of many different parts. Rather than providing an overview that has been presented in previous reviews on ultrafast processes in ferromagnets, this perspective will show that with our current depth of knowledge the first applications are developed: THz spintronics and all-optical spin manipulation are becoming more and more feasible. The aim of this perspective is to point out where we can connect the different puzzle pieces of understanding gathered over 20 years to develop novel applications. Based on many observations in a large number of experiments. Differences in the theoretical models arise from the localized and delocalized nature of ferromagnetism. Transport effects are intrinsically non-local in spintronic devices and at interfaces. We review the need for multiscale modeling to address the processes starting from electronic excitation of the spin system on the picometer length scale and sub-femtosecond time scale, to spin wave generation, and towards the modeling of ultrafast phase transitions that altogether determine the response time of the ferromagnetic system. Today, our current understanding gives rise to the first usage of ultrafast spin physics for ultrafast magnetism control: THz spintronic devices. This makes the field of ultrafast spin-dynamics an emerging topic open for many researchers right now.

Perspective: Ultrafast magnetism and THz spintronics

International Nuclear Information System (INIS)

Walowski, Jakob; Münzenberg, Markus

2016-01-01

This year the discovery of femtosecond demagnetization by laser pulses is 20 years old. For the first time, this milestone work by Bigot and coworkers gave insight directly into the time scales of microscopic interactions that connect the spin and electron system. While intense discussions in the field were fueled by the complexity of the processes in the past, it now became evident that it is a puzzle of many different parts. Rather than providing an overview that has been presented in previous reviews on ultrafast processes in ferromagnets, this perspective will show that with our current depth of knowledge the first applications are developed: THz spintronics and all-optical spin manipulation are becoming more and more feasible. The aim of this perspective is to point out where we can connect the different puzzle pieces of understanding gathered over 20 years to develop novel applications. Based on many observations in a large number of experiments. Differences in the theoretical models arise from the localized and delocalized nature of ferromagnetism. Transport effects are intrinsically non-local in spintronic devices and at interfaces. We review the need for multiscale modeling to address the processes starting from electronic excitation of the spin system on the picometer length scale and sub-femtosecond time scale, to spin wave generation, and towards the modeling of ultrafast phase transitions that altogether determine the response time of the ferromagnetic system. Today, our current understanding gives rise to the first usage of ultrafast spin physics for ultrafast magnetism control: THz spintronic devices. This makes the field of ultrafast spin-dynamics an emerging topic open for many researchers right now.

American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of Uncoupling Protein-2 in Cultured β Cells

Directory of Open Access Journals (Sweden)

John Zeqi Luo

2006-01-01

Full Text Available American ginseng root displays the ability to achieve glucose homeostasis both experimentally and clinically but the unknown mechanism used by ginseng to achieve its therapeutic effects on diabetes limits its application. Disruption in the insulin secretion of pancreatic β cells is considered the major cause of diabetes. A mitochondrial protein, uncoupling protein-2 (UCP-2 has been found to play a critical role in insulin synthesis and β cell survival. Our preliminary studies found that the extracts of American ginseng inhibit UCP-2 expression which may contribute to the ability of ginseng protecting β cell death and improving insulin synthesis. Therefore, we hypothesized that ginseng extracts suppress UCP-2 in the mitochondria of pancreatic β cells, promoting insulin synthesis and anti-apoptosis (a programmed cell-death mechanism. To test the hypothesis, the serum-deprived quiescent β cells were cultured with or without interleukin-1β (IL-1β, (200 pg ml−1, a cytokine to induce β cell apoptosis and water extracts of American ginseng (25 μg per 5 μl administered to wells of 0.5 ml culture for 24 h. We evaluated effects of ginseng on UCP-2 expression, insulin production, anti-/pro-apoptotic factors Bcl-2/caspase-9 expression and cellular ATP levels. We found that ginseng suppresses UCP-2, down-regulates caspase-9 while increasing ATP and insulin production/secretion and up-regulates Bcl-2, reducing apoptosis. These findings suggest that stimulation of insulin production and prevention of β cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro-apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.

Effect of insulin on albumin production and incorporation of 14C-leucine into proteins in isolated parenchymal liver cells from normal rats

DEFF Research Database (Denmark)

Dich, J; Gluud, C N

1975-01-01

the immunologically determined increment in the incubation medium was 1.7 +/- 0.2 mug albumin/min per g liver wet wt. This is about 30% of the rate of production in the perfused liver. Addition of insulin (10(-6)-10(-10) M) enhanced albumin production (50-17%), and incorporation of 14C-leucine both into albumin (50......Parenchymal rat liver cells were isolated by a modification of the collagenase method of Quistorff, Bondesen and Grunnet. The cells secreted albumin into the medium and incorporated 14C-leucine both into cell proteins and proteins secreted into the medium. Albumin production measured from......-8%), secreted proteins (40-9%) and cell proteins (20-8%). Insulin does not increase the production of albumin by depleting the cells. The effect of insulin on albumin production is compatible with an effect on the rate of synthesis as the specific activity of albumin is unaffected by addition of insulin....

New ways of insulin delivery.

Science.gov (United States)

Heinemann, L

2010-02-01

When Exubera (EXU), the first inhaled insulin formulation to make it through the clinical development process, was introduced to the market some years ago it was hoped that this would be the first in a series of novel insulin formulations applied by this route. In addition, it was hoped that inhaled insulin would pave the way for other alternative routes of insulin administration (ARIA), i.e. oral insulin, nasal insulin or transdermal insulin to mention only some of the different attempts that have been studied in the last 90 years. The failure of EXU, i.e. its withdrawal from the market due to insufficient market success, was followed by the cessation of nearly all other attempts to develop inhaled insulin formulations. Currently there is only one company (MannKind) which moves sturdily ahead with their Technosphere insulin. This company has submitted an NDA for their product recently and hopes to bring it to the market by the end of 2010 or early 2011. Even if the product is able to pass the approval hurdles in the USA and Europe, this does not guarantee that it will become a market success. Many diabetologists were sceptical about the need/advantages of inhaled insulin/EXU from the start and the introduction of this product has raised even more scepticism. Reports about 'side effects' (development of lung cancer in patients treated with EXU) of inhaled insulin are also not helpful, even if the causality of the appearance of cancer with this type of insulin therapy is not proven. One of the very negative consequences of stopping EXU are the huge financial losses to Pfizer. The managers in charge in other pharmaceutical companies and also most venture capitalists are reluctant to invest in ARIA nowadays. This in turn means that many of the small companies that try to develop new forms of insulin administration have issues when they try to find a big brother and/or sufficient financial support. Clearly the economic crisis has further aggravated this issue. One can

Histidine augments the suppression of hepatic glucose production by central insulin action.

Science.gov (United States)

Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-Ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

2013-07-01

Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

Effects of Ursodeoxycholic Acid and Insulin on Palmitate-Induced ROS Production and Down-Regulation of PI3K/Akt Signaling Activity.

Science.gov (United States)

Yokoyama, Kunihiro; Tatsumi, Yasuaki; Hayashi, Kazuhiko; Goto, Hidemi; Ishikawa, Tetsuya; Wakusawa, Shinya

2017-01-01

In obese and diabetic patients, plasma free fatty acid (FFA) levels are often elevated and may play a causal role in insulin resistance and reactive oxygen species (ROS) production. We have previously shown that ursodeoxycholic acid (UDCA) has antioxidative activity through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling-mediated glutathione production. In this study, we investigated the effects of UDCA on insulin response by analyzing intracellular ROS and the activation of the PI3K/Akt signaling pathway in HepG2 cells treated with palmitate. The level of ROS was quantified using 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCFDA), and the activation of the PI3K/Akt signaling pathway was determined by Western blotting assay using appropriate antibodies. The intracellular ROS levels were increased by palmitate but were reduced by treatment with UDCA and insulin. Furthermore, insulin significantly stimulated the phosphorylation of Akt. When the cells were pre-treated with palmitate, insulin-induced Akt-phosphorylation was markedly inhibited. However, when the cells were treated with palmitate and UDCA, the effects of insulin were partially restored. UDCA may have protective effects against palmitate-induced decreases in responsiveness to insulin.

Advanced glycation end products impair glucose-induced insulin secretion from rat pancreatic β-cells.

Science.gov (United States)

Hachiya, Hiroyuki; Miura, Yoshikazu; Inoue, Ken-Ichi; Park, Kyung Hwa; Takeuchi, Masayoshi; Kubota, Keiichi

2014-02-01

Advanced glycation end products (AGEs) are derivative compounds generated from non-enzymatic glycosylation and oxidation. In comparison with glucose-derived AGEs (Glu-AGEs), glyceraldehyde-derived AGEs (Glycer-AGEs) have stronger toxicity to living systems. In this study, we compared the effects of Glu-AGE and Glycer-AGE on insulin secretion. Rat pancreatic islets were isolated by collagenase digestion and primary-cultured in the presence of 0.1 mg/ml bovine serum albumin (BSA) or 0.1 mg/ml Glu-AGE or Glycer-AGE-albumin. After 48 h of culture, we performed an insulin secretion test and identified the defects by a battery of rescue experiments [corrected]. Also, mRNA expression of genes associated with insulin secretion was measured. Insulin secretion induced by a high glucose concentration was 164.1 ± 6.0, 124.4 ± 4.4 (P < 0.05) and 119.8 ± 7.1 (P < 0.05) μU/3 islets/h in the presence of BSA, Glu-AGE, and Glycer-AGE, respectively. Inhibition of insulin secretion by Glu-AGE or Glycer-AGE was rescued by a high extracellular potassium concentration, tolbutamide and α-ketoisocaproic acid, but not by glyceraldehyde, dihydroxacetone, methylpyruvate, glucagon-like peptide-1 and acetylcholine. Glu-AGE or Glycer-AGE reduced the expression of the malate dehydrogenase (Mdh1/2) gene, which plays a critical role in the nicotinamide adenine dinucleotide (NADH) shuttle. Despite its reported cytotoxicity, the effects of Glycer-AGE on insulin secretion are similar to those of Glu-AGE. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Effects of concentrate type and chromium propionate on insulin sensitivity, productive and reproductive parameters of lactating dairy cows consuming excessive energy.

Science.gov (United States)

Leiva, T; Cooke, R F; Brandão, A P; Pardelli, U; Rodrigues, R O; Corrá, F N; Vasconcelos, J L M

2017-03-01

This experiment compared insulin sensitivity parameters, milk production and reproductive outcomes in lactating dairy cows consuming excessive energy, and receiving in a 2×2 factorial arrangement design: (1) concentrate based on ground corn (CRN; n=13) or citrus pulp (PLP; n=13), and (2) supplemented (n=14) or not (n=12) with 2.5 g/day of chromium (Cr)-propionate. During the experiment (day 0 to 182), 26 multiparous, non-pregnant, lactating Gir×Holstein cows (initial days in milk=80±2) were offered corn silage for ad libitum consumption, and individually received concentrate formulated to allow diets to provide 160% of their daily requirements of net energy for lactation. Cow BW and body condition score (BCS) were recorded weekly. Milk production was recorded daily and milk samples collected weekly. Blood samples were collected weekly before the morning concentrate feeding. Glucose tolerance tests (GTT; 0.5 g of glucose/kg of BW) were performed on days -3, 60, 120 and 180. Follicle aspiration for in vitro embryo production was performed via transvaginal ovum pick-up on days -1, 82 and 162. No treatment differences were detected (P⩾0.25) for BW and BCS change during the experiment. Within weekly blood samples, concentrations of serum insulin and glucose, as well as insulin : glucose ratio were similar among treatments (P⩾0.19), whereas CRN had less (Pinsulin : glucose ratio. Serum insulin concentrations were less (P=0.04) in CRN supplemented with Cr-propionate compared with non-supplemented CRN (8.2 v. 13.5 µIU/ml, respectively; SEM=1.7), whereas Cr-propionate supplementation did not impact (P=0.70) serum insulin within PLP cows. Milk production, milk fat and solid concentrations were similar (P⩾0.48) between treatments. However, CRN had greater (Pdairy cows consuming excessive energy did not improve insulin sensitivity, milk production and reproductive outcomes, whereas Cr-propionate supplementation only enhanced insulin sensitivity in cows receiving a

Ultrafast photoinduced structure phase transition in antimony single crystals

NARCIS (Netherlands)

Fausti, Daniele; Misochko, Oleg V.; van Loosdrecht, Paul H. M.

2009-01-01

Picosecond Raman scattering is used to study the photoinduced ultrafast dynamics in Peierls distorted antimony. We find evidence for an ultrafast nonthermal reversible structural phase transition. Most surprisingly, we find evidence that this transition evolves toward a lower symmetry in contrast to

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

Science.gov (United States)

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

Direct Characterization of Ultrafast Energy-Time Entangled Photon Pairs.

Science.gov (United States)

MacLean, Jean-Philippe W; Donohue, John M; Resch, Kevin J

2018-02-02

Energy-time entangled photons are critical in many quantum optical phenomena and have emerged as important elements in quantum information protocols. Entanglement in this degree of freedom often manifests itself on ultrafast time scales, making it very difficult to detect, whether one employs direct or interferometric techniques, as photon-counting detectors have insufficient time resolution. Here, we implement ultrafast photon counters based on nonlinear interactions and strong femtosecond laser pulses to probe energy-time entanglement in this important regime. Using this technique and single-photon spectrometers, we characterize all the spectral and temporal correlations of two entangled photons with femtosecond resolution. This enables the witnessing of energy-time entanglement using uncertainty relations and the direct observation of nonlocal dispersion cancellation on ultrafast time scales. These techniques are essential to understand and control the energy-time degree of freedom of light for ultrafast quantum optics.

Progress in ultrafast intense laser science

CERN Document Server

Yamanouchi, Kaoru; Mathur, Deepak

2014-01-01

The PUILS series delivers up-to-date reviews of progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science, and optical science, which has been stimulated by the recent developments in ultrafast laser technologies. Each volume compiles peer-reviewed articles authored by researchers at the forefront of each their own subfields of UILS. Every chapter opens with an overview of the topics to be discussed, so that researchers unfamiliar to the subfield, as well as graduate students, can grasp the importance

Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR®/ABASAGLAR®) approved in the European Union.

Science.gov (United States)

Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

2017-08-01

Basaglar ® /Abasaglar ® (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus ® (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

DEFF Research Database (Denmark)

Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

2003-01-01

of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

Science.gov (United States)

Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

2011-01-01

In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP. PMID:21865644

Ultrafast THz Saturable Absorption in Doped Semiconductors

DEFF Research Database (Denmark)

Turchinovich, Dmitry; Hoffmann, Matthias C.

2011-01-01

We demonstrate ultrafast THz saturable absorption in n-doped semiconductors by nonlinear THz time-domain spectroscopy. This effect is caused by the semiconductor conductivity modulation due to electron heating and satellite-valley scattering in strong THz fields.......We demonstrate ultrafast THz saturable absorption in n-doped semiconductors by nonlinear THz time-domain spectroscopy. This effect is caused by the semiconductor conductivity modulation due to electron heating and satellite-valley scattering in strong THz fields....

Ultrafast Ultrasound Imaging With Cascaded Dual-Polarity Waves.

Science.gov (United States)

Zhang, Yang; Guo, Yuexin; Lee, Wei-Ning

2018-04-01

Ultrafast ultrasound imaging using plane or diverging waves, instead of focused beams, has advanced greatly the development of novel ultrasound imaging methods for evaluating tissue functions beyond anatomical information. However, the sonographic signal-to-noise ratio (SNR) of ultrafast imaging remains limited due to the lack of transmission focusing, and thus insufficient acoustic energy delivery. We hereby propose a new ultrafast ultrasound imaging methodology with cascaded dual-polarity waves (CDWs), which consists of a pulse train with positive and negative polarities. A new coding scheme and a corresponding linear decoding process were thereby designed to obtain the recovered signals with increased amplitude, thus increasing the SNR without sacrificing the frame rate. The newly designed CDW ultrafast ultrasound imaging technique achieved higher quality B-mode images than coherent plane-wave compounding (CPWC) and multiplane wave (MW) imaging in a calibration phantom, ex vivo pork belly, and in vivo human back muscle. CDW imaging shows a significant improvement in the SNR (10.71 dB versus CPWC and 7.62 dB versus MW), penetration depth (36.94% versus CPWC and 35.14% versus MW), and contrast ratio in deep regions (5.97 dB versus CPWC and 5.05 dB versus MW) without compromising other image quality metrics, such as spatial resolution and frame rate. The enhanced image qualities and ultrafast frame rates offered by CDW imaging beget great potential for various novel imaging applications.

Generation of ultrafast pulse via combined effects of stimulated

Indian Academy of Sciences (India)

A project of ultrafast pulse generation has been presented and demonstrated by utilizing the combined nonlinear effects of stimulated Raman scattering (SRS) and non-degenerate two-photon absorption (TPA) based on silicon nanophotonic chip, in which a continuous wave (CW) and an ultrafast dark pulse are ...

Insulin prevents mitochondrial generation of H₂O₂ in rat brain.

Science.gov (United States)

Muller, Alexandre Pastoris; Haas, Clarissa Branco; Camacho-Pereira, Juliana; Brochier, Andressa Wigner; Gnoatto, Jussânia; Zimmer, Eduardo Rigon; de Souza, Diogo Onofre; Galina, Antonio; Portela, Luis Valmor

2013-09-01

The mitochondrial electron transport system (ETS) is a main source of cellular ROS, including hydrogen peroxide (H₂O₂). The production of H₂O₂ also involves the mitochondrial membrane potential (ΔΨm) and oxygen consumption. Impaired insulin signaling causes oxidative neuronal damage and places the brain at risk of neurodegeneration. We evaluated whether insulin signaling cross-talks with ETS components (complexes I and F₀F₁ATP synthase) and ΔΨm to regulate mitochondrial H₂O₂ production, in tissue preparations from rat brain. Insulin (50 to 100 ng/mL) decreased H₂O₂ production in synaptosomal preparations in high Na(+) buffer (polarized state), stimulated by glucose and pyruvate, without affecting the oxygen consumption. In addition, insulin (10 to 100 ng/mL) decreased H₂O₂ production induced by succinate in synaptosomes in high K(+) (depolarized state), whereas wortmannin and LY290042, inhibitors of the PI3K pathway, reversed this effect; heated insulin had no effect. Insulin decreased H₂O₂ production when complexes I and F₀F₁ATP synthase were inhibited by rotenone and oligomycin respectively suggesting a target effect on complex III. Also, insulin prevented the generation of maximum level of ∆Ψm induced by succinate. The PI3K inhibitors and heated insulin maintained the maximum level of ∆Ψm induced by succinate in synaptosomes in a depolarized state. Similarly, insulin decreased ROS production in neuronal cultures. In mitochondrial preparations, insulin neither modulated H2O2 production or oxygen consumption. In conclusion, the normal downstream insulin receptor signaling is necessary to regulate complex III of ETS avoiding the generation of maximal ∆Ψm and increased mitochondrial H2O2 production. Copyright © 2013 Elsevier Inc. All rights reserved.

Diabetes, insulin and exercise

DEFF Research Database (Denmark)

Richter, Erik; Galbo, H

1986-01-01

The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so......-called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

Non-invasive, in vitro analysis of islet insulin production enabled by an optical porous silicon biosensor.

Science.gov (United States)

Chhasatia, Rinku; Sweetman, Martin J; Harding, Frances J; Waibel, Michaela; Kay, Tom; Thomas, Helen; Loudovaris, Thomas; Voelcker, Nicolas H

2017-05-15

A label-free porous silicon (pSi) based, optical biosensor, using both an antibody and aptamer bioreceptor motif has been developed for the detection of insulin. Two parallel biosensors were designed and optimised independently, based on each bioreceptor. Both bioreceptors were covalently attached to a thermally hydrosilylated pSi surface though amide coupling, with unreacted surface area rendered stable and low fouling by incorporation of PEG moieties. The insulin detection ability of each biosensor was determined using interferometric reflectance spectroscopy, using a range of different media both with and without serum. Sensing performance was compared in terms of response value, response time and limit of detection (LOD) for each platform. In order to demonstrate the capability of the best performing biosensor to detect insulin from real samples, an in vitro investigation with the aptamer-modified surface was performed. This biosensor was exposed to buffer conditioned by glucose-stimulated human islets, with the result showing a positive response and a high degree of selectivity towards insulin capture. The obtained results correlated well with the ELISA used in the clinic for assaying glucose-stimulated insulin release from donor islets. We anticipate that this type of sensor can be applied as a rapid point-of-use biosensor to assess the quality of donor islets in terms of their insulin production efficiency, prior to transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanisms of insulin resistance in obesity

Science.gov (United States)

Ye, Jianping

2014-01-01

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

Update on insulin treatment for dogs and cats: insulin dosing pens and more

Directory of Open Access Journals (Sweden)

Thompson A

2015-04-01

Full Text Available Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses. Keywords: diabetes, mellitus, canine, feline, NPH, glargine, porcine lente

Feed-forward motor control of ultrafast, ballistic movements.

Science.gov (United States)

Kagaya, K; Patek, S N

2016-02-01

To circumvent the limits of muscle, ultrafast movements achieve high power through the use of springs and latches. The time scale of these movements is too short for control through typical neuromuscular mechanisms, thus ultrafast movements are either invariant or controlled prior to movement. We tested whether mantis shrimp (Stomatopoda: Neogonodactylus bredini) vary their ultrafast smashing strikes and, if so, how this control is achieved prior to movement. We collected high-speed images of strike mechanics and electromyograms of the extensor and flexor muscles that control spring compression and latch release. During spring compression, lateral extensor and flexor units were co-activated. The strike initiated several milliseconds after the flexor units ceased, suggesting that flexor activity prevents spring release and determines the timing of strike initiation. We used linear mixed models and Akaike's information criterion to serially evaluate multiple hypotheses for control mechanisms. We found that variation in spring compression and strike angular velocity were statistically explained by spike activity of the extensor muscle. The results show that mantis shrimp can generate kinematically variable strikes and that their kinematics can be changed through adjustments to motor activity prior to the movement, thus supporting an upstream, central-nervous-system-based control of ultrafast movement. Based on these and other findings, we present a shishiodoshi model that illustrates alternative models of control in biological ballistic systems. The discovery of feed-forward control in mantis shrimp sets the stage for the assessment of targets, strategic variation in kinematics and the role of learning in ultrafast animals. © 2016. Published by The Company of Biologists Ltd.

Insulin Resistance and Mitochondrial Dysfunction.

Science.gov (United States)

Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

2017-01-01

Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

Ultrafast Nonlinear Signal Processing in Silicon Waveguides

DEFF Research Database (Denmark)

Oxenløwe, Leif Katsuo; Mulvad, Hans Christian Hansen; Hu, Hao

2012-01-01

We describe recent demonstrations of exploiting highly nonlinear silicon waveguides for ultrafast optical signal processing. We describe wavelength conversion and serial-to-parallel conversion of 640 Gbit/s data signals and 1.28 Tbit/s demultiplexing and all-optical sampling.......We describe recent demonstrations of exploiting highly nonlinear silicon waveguides for ultrafast optical signal processing. We describe wavelength conversion and serial-to-parallel conversion of 640 Gbit/s data signals and 1.28 Tbit/s demultiplexing and all-optical sampling....

Optimization and practical implementation of ultrafast 2D NMR experiments

Energy Technology Data Exchange (ETDEWEB)

Queiroz Junior, Luiz H. K., E-mail: professorkeng@gmail.com [Universidade Federal de Sao Carlos (UFSC), SP (Brazil). Departamento de Quimica; Universidade Federal de Goias (UFGO), Goiania, GO (Brazil). Inst. de Quimica; Ferreira, Antonio G. [Universidade Federal de Sao Carlos (UFSC), SP (Brazil). Departamento de Quimica; Giraudeau, Patrick [Universite de Nantes (France). CNRS, Chimie et Interdisciplinarite: Synthese, Analyse, Modelisation

2013-09-01

Ultrafast 2D NMR is a powerful methodology that allows recording of a 2D NMR spectrum in a fraction of second. However, due to the numerous non-conventional parameters involved in this methodology its implementation is no trivial task. Here, an optimized experimental protocol is carefully described to ensure efficient implementation of ultrafast NMR. The ultrafast spectra resulting from this implementation are presented based on the example of two widely used 2D NMR experiments, COSY and HSQC, obtained in 0.2 s and 41 s, respectively. (author)

Trends in Medicaid Reimbursements for Insulin From 1991 Through 2014.

Science.gov (United States)

Luo, Jing; Avorn, Jerry; Kesselheim, Aaron S

2015-10-01

Insulin is a vital medicine for patients with diabetes mellitus. Newer, more expensive insulin products and the lack of generic insulins in the United States have increased costs for patients and insurers. To examine Medicaid payment trends for insulin products. Cost information is available for all 50 states and has been recorded since the 1990s. A time-series analysis comparing reimbursements and prices. Using state- and national-level Medicaid data from 1991 to 2014, we identified all patients who used 1 or more of the 16 insulin products that were continuously available in the United States between 2006 and 2014. Insulin products were classified into rapid-acting and long-acting analogs, short-acting, intermediate, and premixed insulins based on American Diabetes Association Guidelines. Inflation-adjusted payments made to pharmacies by Medicaid per 1 mL (100 IU) of insulin in 2014 US dollars. Since 1991, Medicaid reimbursement per unit (1 mL) of insulin dispensed has risen steadily. In the 1990s, Medicaid reimbursed pharmacies between $2.36 and $4.43 per unit. By 2014, reimbursement for short-acting insulins increased to $9.64 per unit; intermediate, $9.22; premixed, $14.79; and long-acting, $19.78. Medicaid reimbursement for rapid-acting insulin analogs rose to $19.81 per unit. The rate of increase in reimbursement was higher for insulins with patent protection ($0.20 per quarter) than without ($0.05 per quarter) (Preimbursements peaked at $407.4 million dollars in quarter 2 of 2014. Total volume peaked at 29.9 million units in quarter 4 of 2005 and was 21.2 million units in quarter 2 of 2014. Between 1991 and 2014, there was a near-exponential upward trend in Medicaid payments on a per-unit basis for a wide variety of insulin products regardless of formulation, duration of action, and whether the product was patented. Although reimbursements for newer, patent-protected insulin analogs increased at a faster rate than reimbursements for older insulins, payments

Accelerator-based single-shot ultrafast transmission electron microscope with picosecond temporal resolution and nanometer spatial resolution

Science.gov (United States)

Xiang, D.; Fu, F.; Zhang, J.; Huang, X.; Wang, L.; Wang, X.; Wan, W.

2014-09-01

We present feasibility study of an accelerator-based ultrafast transmission electron microscope (u-TEM) capable of producing a full field image in a single-shot with simultaneous picosecond temporal resolution and nanometer spatial resolution. We study key physics related to performance of u-TEMs and discuss major challenges as well as possible solutions for practical realization of u-TEMs. The feasibility of u-TEMs is confirmed through simulations using realistic electron beam parameters. We anticipate that u-TEMs with a product of temporal and spatial resolution beyond 10-19 ms will open up new opportunities in probing matter at ultrafast temporal and ultrasmall spatial scales.

All-optical temporal integration of ultrafast pulse waveforms.

Science.gov (United States)

Park, Yongwoo; Ahn, Tae-Jung; Dai, Yitang; Yao, Jianping; Azaña, José

2008-10-27

An ultrafast all-optical temporal integrator is experimentally demonstrated. The demonstrated integrator is based on a very simple and practical solution only requiring the use of a widely available all-fiber passive component, namely a reflection uniform fiber Bragg grating (FBG). This design allows overcoming the severe speed (bandwidth) limitations of the previously demonstrated photonic integrator designs. We demonstrate temporal integration of a variety of ultrafast optical waveforms, including Gaussian, odd-symmetry Hermite Gaussian, and (odd-)symmetry double pulses, with temporal features as fast as ~6-ps, which is about one order of magnitude faster than in previous photonic integration demonstrations. The developed device is potentially interesting for a multitude of applications in all-optical computing and information processing, ultrahigh-speed optical communications, ultrafast pulse (de-)coding, shaping and metrology.

Fructose induced neurogenic hypertension mediated by overactivation of p38 MAPK to impair insulin signaling transduction caused central insulin resistance.

Science.gov (United States)

Cheng, Pei-Wen; Lin, Yu-Te; Ho, Wen-Yu; Lu, Pei-Jung; Chen, Hsin-Hung; Lai, Chi-Cheng; Sun, Gwo-Ching; Yeh, Tung-Chen; Hsiao, Michael; Tseng, Ching-Jiunn; Liu, Chun-Peng

2017-11-01

Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group. The Tempol treatment recovered the fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that fructose increased the p38- and fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1 S307 ) and suppressed Akt S473 and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able to impair insulin sensitivity and increase insulin levels in the NTS. Fructose intake also increased the production of superoxide in the NTS. The results of this study suggest that fructose might induce central insulin resistance and elevate BP by enhancing superoxide production and activating p38 phosphorylation in the NTS. Copyright © 2017 Elsevier Inc. All rights reserved.

[An ultrafast liquid chromatography-tandem mass spectrometric method for simultaneous determination of common artificial synthetic pigments in cooked meat products].

Science.gov (United States)

Chen, Xiaohong; Li, Xiaoping; Zhao, Yonggang; Pan, Shengdong; Jin, Micong

2015-07-01

A method based on ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) has been developed for the simultaneous determination of seven synthetic pigments in cooked meat product. After the cooked meat products were extracted by mixed extraction agent, purified by WAX column, the UFLC separation was performed on a Shim-pack XR-ODS II column (75 mm x 2.0 mm, 2.2 µm) with a linear gradient elution program of acetonitrile and ammonium acetate (AmAc, 5 mmol/L) as the mobile phase. Electrospray ionization was applied and operated in the negative ion mode. The limits of quantitation (LOQs) for the seven synthetic pigments were in the range of 0.7-5.0 µg/kg. The calibration curves showed good linearities for the seven analytes in their detection ranges, and the correlative coefficients (r) were more than 0.999. The recoveries were between 88.2%-106.5% with the RSDs in the range of 1.2%-5.0%. The method is sensitive, reproducible, quick and adapts to the simultaneous determination of the seven synthetic pigments in cooked meat product.

On the labelling of insuline and insuline derivatives with tritium and carbon-14

International Nuclear Information System (INIS)

Uschkoreit, J.

1979-01-01

Two different labelling methods were investigated. By means of the Wilzbach labelling with diaminosuberoylinsuline the insuline is irreversibly altered. As a second method the reductive methylation was used, in doing so it was possible to distinguish between mono and dimethylated parts of the reaction product by using C-14 labelled formaldehyde. Furthermore four N,N-dimethylated insuline derivatives were isolated with yields of 25 until 35%. By using C-14 and h-3 labelled reagents insuline can be labelled doubly. Moreover N-terminal amino groups could be protected irreversibly with this method. Furthermore structure-function investigations and investigations concerning the insuline metabolism were done. (SPI) [de

Ultrafast electron diffraction studies of optically excited thin bismuth films

International Nuclear Information System (INIS)

Rajkovic, Ivan

2008-01-01

This thesis contains work on the design and the realization of an experimental setup capable of providing sub-picosecond electron pulses for ultrafast electron diffraction experiments, and performing the study of ultrafast dynamics in bismuth after optical excitation using this setup. (orig.)

Ultrafast electron diffraction studies of optically excited thin bismuth films

Energy Technology Data Exchange (ETDEWEB)

Rajkovic, Ivan

2008-10-21

This thesis contains work on the design and the realization of an experimental setup capable of providing sub-picosecond electron pulses for ultrafast electron diffraction experiments, and performing the study of ultrafast dynamics in bismuth after optical excitation using this setup. (orig.)

UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

Science.gov (United States)

Correia, Manuel; Neves-Petersen, Maria Teresa; Jeppesen, Per Bendix; Gregersen, Søren; Petersen, Steffen B

2012-01-01

In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2)) excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes in protein

UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

Directory of Open Access Journals (Sweden)

Manuel Correia

Full Text Available In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2 excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes

Progress in ultrafast intense laser science XI

CERN Document Server

Yamanouchi, Kaoru; Martin, Philippe

2014-01-01

The PUILS series delivers up-to-date reviews of progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science and optical science, which has been stimulated by the recent developments in ultrafast laser technologies. Each volume compiles peer-reviewed articles authored by researchers at the forefront of each their own subfields of UILS. Every chapter opens with an overview of the topics to be discussed, so that researchers unfamiliar to the subfield, as well as graduate students, can grasp the importance

Progress in Ultrafast Intense Laser Science II

CERN Document Server

Yamanouchi, Kaoru; Agostini, Pierre; Ferrante, Gaetano

2007-01-01

This book series addresses a newly emerging interdisciplinary research field, Ultrafast Intense Laser Science, spanning atomic and molecular physics, molecular science, and optical science. Its progress is being stimulated by the recent development of ultrafast laser technologies. Highlights of this second volume include Coulomb explosion and fragmentation of molecules, control of chemical dynamics, high-order harmonic generation, propagation and filamentation, and laser-plasma interaction. All chapters are authored by foremost experts in their fields and the texts are written at a level accessible to newcomers and graduate students, each chapter beginning with an introductory overview.

Mega-electron-volt ultrafast electron diffraction at SLAC National Accelerator Laboratory

Energy Technology Data Exchange (ETDEWEB)

Weathersby, S. P.; Brown, G.; Chase, T. F.; Coffee, R.; Corbett, J.; Eichner, J. P.; Frisch, J. C.; Fry, A. R.; Gühr, M.; Hartmann, N.; Hast, C.; Hettel, R.; Jobe, R. K.; Jongewaard, E. N.; Lewandowski, J. R.; Li, R. K., E-mail: lrk@slac.stanford.edu; Lindenberg, A. M.; Makasyuk, I.; May, J. E.; McCormick, D. [SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, California 94025 (United States); and others

2015-07-15

Ultrafast electron probes are powerful tools, complementary to x-ray free-electron lasers, used to study structural dynamics in material, chemical, and biological sciences. High brightness, relativistic electron beams with femtosecond pulse duration can resolve details of the dynamic processes on atomic time and length scales. SLAC National Accelerator Laboratory recently launched the Ultrafast Electron Diffraction (UED) and microscopy Initiative aiming at developing the next generation ultrafast electron scattering instruments. As the first stage of the Initiative, a mega-electron-volt (MeV) UED system has been constructed and commissioned to serve ultrafast science experiments and instrumentation development. The system operates at 120-Hz repetition rate with outstanding performance. In this paper, we report on the SLAC MeV UED system and its performance, including the reciprocal space resolution, temporal resolution, and machine stability.

Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

Directory of Open Access Journals (Sweden)

Nicolai J. Wewer Albrechtsen

2017-11-01

Full Text Available Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61 appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in β cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion.

Transfer plate radioassay using adsorbed anti-insulin antibody to detect insulin secreted by islet cell cultures

International Nuclear Information System (INIS)

Scearce, R.M.; Oie, H.K.; Gazdar, A.F.; Chick, W.L.; Eisenbarth, G.S.

1981-01-01

A solid-phase radioimmunoassay for detection of insulin synthesized by islet cell clones is described. This assay employs anti-insulin antibody adsorbed onto fenestrated polyvinyl chloride 96-well plates ('transfer plates'). The calibrated aperture in the bottom of each transfer plate well permits fluid to enter the wells when transfer plates are lowered into microculture wells containing insulin. With this assay it is possible to rapidly screen hundreds of islet cell cultures for insulin production. The authors have used this assay to facilitate cloning of the RIN rat insulinoma cell line. The assay readily detects insulin synthesis by RIN cells and [ 125 I]insulin is not displaced by culture medium from cells which do not produce insulin. The transfer plate format should be applicable to semiautomate other radioimmunoassays. (Auth.)

Effects of chocolate-based products intake on blood glucose, insulin and ghrelin levels and on satiety in young people: a cross-over experimental study.

Science.gov (United States)

Zhang, Cai-Xia; Long, Wei-Qing; Ye, Yan-Bin; Lu, Min-Shan; Zhang, Nai-Qi; Xu, Ming; Huang, Jing; Su, Yi-Xiang

2018-02-19

This cross-over experimental study aimed to examine the effects of filled chocolate consumption on blood glucose, insulin and ghrelin levels in 20 volunteers. After a one-week run-in period, study participants consumed two chocolate-based products, the tested biscuit or water for 21 days as a morning snack. After a two-week wash-out period, participants consumed another tested food for another 21 days. Each participant consumed all four test foods within an 18-week period. The participants' blood insulin increased slowly after two chocolate-based products intakes on the first day and satiety levels after eating chocolate-based products and the tested biscuit were the same. Chocolate consumption for three weeks had no adverse effects on blood glucose, insulin or ghrelin levels. In conclusion, compared to eating the tested biscuit, 21-day consumption of the tested chocolate-based products had no adverse effects on the blood glucose, insulin and ghrelin levels. This trial is registered with chictr.org.cn: ChiCTR-IOR-16009525.

Carrier dynamics in graphene. Ultrafast many-particle phenomena

Energy Technology Data Exchange (ETDEWEB)

Malic, E.; Brem, S.; Jago, R. [Department of Physics, Chalmers University of Technology, Goeteborg (Sweden); Winzer, T.; Wendler, F.; Knorr, A. [Institut fuer Theoretische Physik, Technische Universitaet Berlin (Germany); Mittendorff, M.; Koenig-Otto, J.C.; Schneider, H.; Helm, M.; Winnerl, S. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Ploetzing, T.; Neumaier, D. [Advanced Microelectronic Center Aachen, AMO GmbH, Aachen (Germany)

2017-11-15

Graphene is an ideal material to study fundamental Coulomb- and phonon-induced carrier scattering processes. Its remarkable gapless and linear band structure opens up new carrier relaxation channels. In particular, Auger scattering bridging the valence and the conduction band changes the number of charge carriers and gives rise to a significant carrier multiplication - an ultrafast many-particle phenomenon that is promising for the design of highly efficient photodetectors. Furthermore, the vanishing density of states at the Dirac point combined with ultrafast phonon-induced intraband scattering results in an accumulation of carriers and a population inversion suggesting the design of graphene-based terahertz lasers. Here, we review our work on the ultrafast carrier dynamics in graphene and Landau-quantized graphene is presented providing a microscopic view on the appearance of carrier multiplication and population inversion. (copyright 2017 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Chapter 10: Glucose control: insulin therapy*

African Journals Online (AJOL)

Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits ... control on 2 or 3 oral glucose lowering drugs.

WE-B-210-02: The Advent of Ultrafast Imaging in Biomedical Ultrasound

International Nuclear Information System (INIS)

Tanter, M.

2015-01-01

In the last fifteen years, the introduction of plane or diverging wave transmissions rather than line by line scanning focused beams has broken the conventional barriers of ultrasound imaging. By using such large field of view transmissions, the frame rate reaches the theoretical limit of physics dictated by the ultrasound speed and an ultrasonic map can be provided typically in tens of micro-seconds (several thousands of frames per second). Interestingly, this leap in frame rate is not only a technological breakthrough but it permits the advent of completely new ultrasound imaging modes, including shear wave elastography, electromechanical wave imaging, ultrafast doppler, ultrafast contrast imaging, and even functional ultrasound imaging of brain activity (fUltrasound) introducing Ultrasound as an emerging full-fledged neuroimaging modality. At ultrafast frame rates, it becomes possible to track in real time the transient vibrations – known as shear waves – propagating through organs. Such “human body seismology” provides quantitative maps of local tissue stiffness whose added value for diagnosis has been recently demonstrated in many fields of radiology (breast, prostate and liver cancer, cardiovascular imaging, …). Today, Supersonic Imagine company is commercializing the first clinical ultrafast ultrasound scanner, Aixplorer with real time Shear Wave Elastography. This is the first example of an ultrafast Ultrasound approach surpassing the research phase and now widely spread in the clinical medical ultrasound community with an installed base of more than 1000 Aixplorer systems in 54 countries worldwide. For blood flow imaging, ultrafast Doppler permits high-precision characterization of complex vascular and cardiac flows. It also gives ultrasound the ability to detect very subtle blood flow in very small vessels. In the brain, such ultrasensitive Doppler paves the way for fUltrasound (functional ultrasound imaging) of brain activity with unprecedented

WE-B-210-02: The Advent of Ultrafast Imaging in Biomedical Ultrasound

Energy Technology Data Exchange (ETDEWEB)

Tanter, M. [Laboratoire Ondes et Acoustique (France)

2015-06-15

In the last fifteen years, the introduction of plane or diverging wave transmissions rather than line by line scanning focused beams has broken the conventional barriers of ultrasound imaging. By using such large field of view transmissions, the frame rate reaches the theoretical limit of physics dictated by the ultrasound speed and an ultrasonic map can be provided typically in tens of micro-seconds (several thousands of frames per second). Interestingly, this leap in frame rate is not only a technological breakthrough but it permits the advent of completely new ultrasound imaging modes, including shear wave elastography, electromechanical wave imaging, ultrafast doppler, ultrafast contrast imaging, and even functional ultrasound imaging of brain activity (fUltrasound) introducing Ultrasound as an emerging full-fledged neuroimaging modality. At ultrafast frame rates, it becomes possible to track in real time the transient vibrations – known as shear waves – propagating through organs. Such “human body seismology” provides quantitative maps of local tissue stiffness whose added value for diagnosis has been recently demonstrated in many fields of radiology (breast, prostate and liver cancer, cardiovascular imaging, …). Today, Supersonic Imagine company is commercializing the first clinical ultrafast ultrasound scanner, Aixplorer with real time Shear Wave Elastography. This is the first example of an ultrafast Ultrasound approach surpassing the research phase and now widely spread in the clinical medical ultrasound community with an installed base of more than 1000 Aixplorer systems in 54 countries worldwide. For blood flow imaging, ultrafast Doppler permits high-precision characterization of complex vascular and cardiac flows. It also gives ultrasound the ability to detect very subtle blood flow in very small vessels. In the brain, such ultrasensitive Doppler paves the way for fUltrasound (functional ultrasound imaging) of brain activity with unprecedented

Resistance training enhances insulin suppression of endogenous glucose production in elderly women.

Science.gov (United States)

Honka, Miikka-Juhani; Bucci, Marco; Andersson, Jonathan; Huovinen, Ville; Guzzardi, Maria Angela; Sandboge, Samuel; Savisto, Nina; Salonen, Minna K; Badeau, Robert M; Parkkola, Riitta; Kullberg, Joel; Iozzo, Patricia; Eriksson, Johan G; Nuutila, Pirjo

2016-03-15

An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [(18)F]fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [from 5.4 (interquartile range 3.0, 7.0) to 3.9 (-0.4, 6.1) μmol·kg body wt(-1)·min(-1), P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [-5.6 (7.1) vs. 0.1 (5.4) μmol·kg body wt(-1)·min(-1), P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation (r = -0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training. Copyright © 2016 the American Physiological Society.

Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance.

Science.gov (United States)

Newkirk, Kim M; Ehrensing, Gordon; Odoi, Agricola; Boston, Raymond C; Frank, Nicholas

2018-02-01

OBJECTIVE To assess insulin, glucagon, and somatostatin expression within pancreatic islets of horses with and without insulin resistance. ANIMALS 10 insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each horse, food was withheld for at least 10 hours before a blood sample was collected for determination of serum insulin concentration. Horses with a serum insulin concentration horses with a serum insulin concentration > 20 μU/mL underwent a frequently sampled IV glucose tolerance test to determine sensitivity to insulin by minimal model analysis. Horses with a sensitivity to insulin horses were euthanized with a barbiturate overdose, and pancreatic specimens were harvested and immunohistochemically stained for determination of insulin, glucagon, and somatostatin expression in pancreatic islets. Islet hormone expression was compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%, and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and 64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive horses. Expression of insulin and somatostatin did not differ between insulin-resistant and insulin-sensitive horses, but the median percentage of glucagon-expressing cells in the islets of insulin-resistant horses was significantly less than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in insulin-resistant horses, insulin secretion was not increased but glucagon production might be downregulated as a compensatory response to hyperinsulinemia.

Methylglyoxal Impairs Insulin Secretion of Pancreatic β-Cells through Increased Production of ROS and Mitochondrial Dysfunction Mediated by Upregulation of UCP2 and MAPKs

Directory of Open Access Journals (Sweden)

Jinshuang Bo

2016-01-01

Full Text Available Methylglyoxal (MG is a highly reactive glucose metabolic intermediate and a major precursor of advanced glycation end products. MG level is elevated in hyperglycemic disorders such as diabetes mellitus. Substantial evidence has shown that MG is involved in the pathogenesis of diabetes and diabetic complications. We investigated the impact of MG on insulin secretion by MIN6 and INS-1 cells and the potential mechanisms of this effect. Our study demonstrates that MG impaired insulin secretion by MIN6 or ISN-1 cells in a dose-dependent manner. It increased reactive oxygen species (ROS production and apoptosis rate in MIN6 or ISN-1 cells and inhibited mitochondrial membrane potential (MMP and ATP production. Furthermore, the expression of UCP2, JNK, and P38 as well as the phosphorylation JNK and P38 was increased by MG. These effects of MG were attenuated by MG scavenger N-acetyl cysteine. Collectively, these data indicate that MG impairs insulin secretion of pancreatic β-cells through increasing ROS production. High levels of ROS can damage β-cells directly via JNK/P38 upregulation and through activation of UCP2 resulting in reduced MMP and ATP production, leading to β-cell dysfunction and impairment of insulin production.

Coherent combination of ultrafast fiber amplifiers

International Nuclear Information System (INIS)

Hanna, Marc; Guichard, Florent; Druon, Frédéric; Georges, Patrick; Zaouter, Yoann; Papadopoulos, Dimitris N

2016-01-01

We review recent progress in coherent combining of femtosecond pulses amplified in optical fibers as a way to scale the peak and average power of ultrafast sources. Different methods of achieving coherent pulse addition in space (beam combining) and time (divided pulse amplification) domains are described. These architectures can be widely classified into active methods, where the relative phases between pulses are subject to a servomechanism, and passive methods, where phase matching is inherent to the geometry. Other experiments that combine pulses with different spectral contents, pulses that have been nonlinearly broadened or successive pulses from a mode-locked laser oscillator, are then presented. All these techniques allow access to unprecedented parameter range for fiber ultrafast sources. (topical review)

Insulin biosimilars: the impact on rapid-acting analogue-based therapy.

Science.gov (United States)

Franzè, S; Cilurzo, F; Minghetti, P

2015-04-01

The impending expiration of patent protection for recombinant insulins provides the opportunity to introduce cost-saving copies, named biosimilars, onto the market. Although there is broad experience in the production and characterisation of insulins, the development of copies is still a challenge. In this paper, the main features of insulins and the EU regulatory framework for their biosimilar products are reviewed. The main focus is on rapid-acting insulin analogues (Humalog(®); Novolog(®)/NovoRapid(®); Apidra(®)). Since they differ by one or two amino acids in chain B, production of one biosimilar for all three drug products is not feasible. However, from post-marketing-collected clinical data, rapid-acting insulin analogues seem to have similar therapeutic efficacy. It is reasonable to suppose that, for prescription to treatment-naïve patients, the cheaper biosimilar would be the preferred choice of physicians, either spontaneously or induced by health insurance. Therefore, its introduction will affect the market share of all the other rapid-acting insulin analogues.

Ultrafast optical signal processing using semiconductor quantum dot amplifiers

DEFF Research Database (Denmark)

Berg, Tommy Winther; Mørk, Jesper

2002-01-01

The linear and nonlinear properties of quantum dot amplifiers are discussed on the basis of an extensive theoretical model. These devices show great potential for linear amplification as well as ultrafast signal processing.......The linear and nonlinear properties of quantum dot amplifiers are discussed on the basis of an extensive theoretical model. These devices show great potential for linear amplification as well as ultrafast signal processing....

Ultrafast Thermal Transport at Interfaces

Energy Technology Data Exchange (ETDEWEB)

Cahill, David [Univ. of Illinois, Champaign, IL (United States); Murphy, Catherine [Univ. of Illinois, Champaign, IL (United States); Martin, Lane [Univ. of Illinois, Champaign, IL (United States)

2014-10-21

Our research program on Ultrafast Thermal Transport at Interfaces advanced understanding of the mesoscale science of heat conduction. At the length and time scales of atoms and atomic motions, energy is transported by interactions between single-particle and collective excitations. At macroscopic scales, entropy, temperature, and heat are the governing concepts. Key gaps in fundamental knowledge appear at the transitions between these two regimes. The transport of thermal energy at interfaces plays a pivotal role in these scientific issues. Measurements of heat transport with ultrafast time resolution are needed because picoseconds are the fundamental scales where the lack of equilibrium between various thermal excitations becomes a important factor in the transport physics. A critical aspect of our work has been the development of experimental methods and model systems that enabled more precise and sensitive investigations of nanoscale thermal transport.

Ultrafast vibrations of gold nanorings

DEFF Research Database (Denmark)

Kelf, T; Tanaka, Y; Matsuda, O

2011-01-01

We investigate the vibrational modes of gold nanorings on a silica substrate with an ultrafast optical technique. By comparison with numerical simulations, we identify several resonances in the gigahertz range associated with axially symmetric deformations of the nanoring and substrate. We...

Ultrafast Spectroscopy of Semiconductor Devices

DEFF Research Database (Denmark)

Borri, Paola; Langbein, Wolfgang; Hvam, Jørn Marcher

1999-01-01

In this work we present an experimental technique for investigating ultrafast carrier dynamics in semiconductor optical amplifiers at room temperature. These dynamics, influenced by carrier heating, spectral hole-burning and two-photon absorption, are very important for device applications in inf...

Ultrafast control and monitoring of material properties using terahertz pulses

Energy Technology Data Exchange (ETDEWEB)

Bowlan, Pamela Renee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Lab. for Ultrafast Materials Optical Science (LUMOS)

2016-05-02

These are a set of slides on ultrafast control and monitoring of material properties using terahertz pulses. A few of the topics covered in these slides are: How fast is a femtosecond (fs), Different frequencies probe different properties of molecules or solids, What can a THz pulse do to a material, Ultrafast spectroscopy, Generating and measuring ultrashort THz pulses, Tracking ultrafast spin dynamics in antiferromagnets through spin wave resonances, Coherent two-dimensional THz spectroscopy, and Probing vibrational dynamics at a surface. Conclusions are: Coherent two-dimensional THz spectroscopy: a powerful approach for studying coherence and dynamics of low energy resonances. Applying this to graphene we investigated the very strong THz light mater interaction which dominates over scattering. Useful for studying coupled excitations in multiferroics and monitoring chemical reactions. Also, THz-pump, SHG-probe spectoscopy: an ultrafast, surface sensitive probe of atomic-scale symmetry changes and nonlinear phonon dymanics. We are using this in Bi₂Se₃ to investigate the nonlinear surface phonon dynamics. This is potentially very useful for studying catalysis.

Electrically-driven GHz range ultrafast graphene light emitter (Conference Presentation)

Science.gov (United States)

Kim, Youngduck; Gao, Yuanda; Shiue, Ren-Jye; Wang, Lei; Aslan, Ozgur Burak; Kim, Hyungsik; Nemilentsau, Andrei M.; Low, Tony; Taniguchi, Takashi; Watanabe, Kenji; Bae, Myung-Ho; Heinz, Tony F.; Englund, Dirk R.; Hone, James

2017-02-01

Ultrafast electrically driven light emitter is a critical component in the development of the high bandwidth free-space and on-chip optical communications. Traditional semiconductor based light sources for integration to photonic platform have therefore been heavily studied over the past decades. However, there are still challenges such as absence of monolithic on-chip light sources with high bandwidth density, large-scale integration, low-cost, small foot print, and complementary metal-oxide-semiconductor (CMOS) technology compatibility. Here, we demonstrate the first electrically driven ultrafast graphene light emitter that operate up to 10 GHz bandwidth and broadband range (400 1600 nm), which are possible due to the strong coupling of charge carriers in graphene and surface optical phonons in hBN allow the ultrafast energy and heat transfer. In addition, incorporation of atomically thin hexagonal boron nitride (hBN) encapsulation layers enable the stable and practical high performance even under the ambient condition. Therefore, electrically driven ultrafast graphene light emitters paves the way towards the realization of ultrahigh bandwidth density photonic integrated circuits and efficient optical communications networks.

Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes

Directory of Open Access Journals (Sweden)

Mackenzie RWA

2014-02-01

Full Text Available Richard WA Mackenzie, Bradley T Elliott Department of Human and Health Sciences, Facility of Science and Technology, University of Westminster, London, UK Abstract: Type 2 diabetes is a metabolic disease categorized primarily by reduced insulin sensitivity, β-cell dysfunction, and elevated hepatic glucose production. Treatments reducing hyperglycemia and the secondary complications that result from these dysfunctions are being sought after. Two distinct pathways encourage glucose transport activity in skeletal muscle, ie, the contraction-stimulated pathway reliant on Ca2+/5′-monophosphate-activated protein kinase (AMPK-dependent mechanisms and an insulin-dependent pathway activated via upregulation of serine/threonine protein kinase Akt/PKB. Metformin is an established treatment for type 2 diabetes due to its ability to increase peripheral glucose uptake while reducing hepatic glucose production in an AMPK-dependent manner. Peripheral insulin action is reduced in type 2 diabetics whereas AMPK signaling remains largely intact. This paper firstly reviews AMPK and its role in glucose uptake and then focuses on a novel mechanism known to operate via an insulin-dependent pathway. Inositol hexakisphosphate (IP6 kinase 1 (IP6K1 produces a pyrophosphate group at the position of IP6 to generate a further inositol pyrophosphate, ie, diphosphoinositol pentakisphosphate (IP7. IP7 binds with Akt/PKB at its pleckstrin homology domain, preventing interaction with phosphatidylinositol 3,4,5-trisphosphate, and therefore reducing Akt/PKB membrane translocation and insulin-stimulated glucose uptake. Novel evidence suggesting a reduction in IP7 production via IP6K1 inhibition represents an exciting therapeutic avenue in the treatment of insulin resistance. Metformin-induced activation of AMPK is a key current intervention in the management of type 2 diabetes. However, this treatment does not seem to improve peripheral insulin resistance. In light of this

Ultrafast demagnetisation dependence on film thickness: A TDDFT calculation

Science.gov (United States)

Singh, N.; Sharma, S.

2018-04-01

Ferromagnetic materials when subjected to intense laser pulses leads to reduction of their magnetisation on an ultrafast scale. Here, we perform an ab-initio calculation to study the behavior of ultrafast demagnetisation as a function of film thickness for Nickel as compared to the bulk of the material. In thin films surface formation results in amplification of demagnetisation with the percentage of demagnetisation depending upon the film thickness.

Insulin structure and stability.

Science.gov (United States)

Brange, J; Langkjoer, L

1993-01-01

property of being able to counteract associated insulin from being disassembled. Chemical deterioration of insulin during storage of pharmaceutical preparations is mainly due to two categories of chemical reactions, hydrolysis and intermolecular transformation reactions leading to insulin HMWT products. The predominant hydrolysis reaction is deamidation of Asn residues which in acid solution takes place at residue A21, in neutral medium at residue B3. An amazing hydrolytic cleavage of the backbone A chain, presumably autocatalyzed by an adjacent insulin molecule, has been identified in insulin preparations containing rhombohedral crystals in combination with free zinc ions.(ABSTRACT TRUNCATED AT 400 WORDS)

The interplay between noncoding RNAs and insulin in diabetes.

Science.gov (United States)

Tian, Yan; Xu, Jia; Du, Xiao; Fu, Xianghui

2018-04-10

Noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular RNAs, regulate various biological processes and are involved in the initiation and progression of human diseases. Insulin, a predominant hormone secreted from pancreatic β cells, is an essential factor in regulation of systemic metabolism through multifunctional insulin signaling. Insulin production and action are tightly controlled. Dysregulations of insulin production and action can impair metabolic homeostasis, and eventually lead to the development of multiple metabolic diseases, especially diabetes. Accumulating data indicates that ncRNAs modulate β cell mass, insulin synthesis, secretion and signaling, and their role in diabetes is dramatically emerging. This review summarizes our current knowledge of ncRNAs as regulators of insulin, with particular emphasis on the implications of this interplay in the development of diabetes. We outline the role of ncRNAs in pancreatic β cell mass and function, which is critical for insulin production and secretion. We also highlight the involvement of ncRNAs in insulin signaling in peripheral tissues including liver, muscle and adipose, and discuss ncRNA-mediated inter-organ crosstalk under diabetic conditions. A more in-depth understanding of the interplay between ncRNAs and insulin may afford valuable insights and novel therapeutic strategies for treatment of diabetes, as well as other human diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Ultrafast magnetodynamics with free-electron lasers

Science.gov (United States)

Malvestuto, Marco; Ciprian, Roberta; Caretta, Antonio; Casarin, Barbara; Parmigiani, Fulvio

2018-02-01

The study of ultrafast magnetodynamics has entered a new era thanks to the groundbreaking technological advances in free-electron laser (FEL) light sources. The advent of these light sources has made possible unprecedented experimental schemes for time-resolved x-ray magneto-optic spectroscopies, which are now paving the road for exploring the ultimate limits of out-of-equilibrium magnetic phenomena. In particular, these studies will provide insights into elementary mechanisms governing spin and orbital dynamics, therefore contributing to the development of ultrafast devices for relevant magnetic technologies. This topical review focuses on recent advancement in the study of non-equilibrium magnetic phenomena from the perspective of time-resolved extreme ultra violet (EUV) and soft x-ray spectroscopies at FELs with highlights of some important experimental results.

Femtochemistry and femtobiology ultrafast dynamics in molecular science

CERN Document Server

Douhal, Abderrazzak

2002-01-01

This book contains important contributions from top international scientists on the-state-of-the-art of femtochemistry and femtobiology at the beginning of the new millennium. It consists of reviews and papers on ultrafast dynamics in molecular science.The coverage of topics highlights several important features of molecular science from the viewpoint of structure (space domain) and dynamics (time domain). First of all, the book presents the latest developments, such as experimental techniques for understanding ultrafast processes in gas, condensed and complex systems, including biological mol

Ultrafast spectroscopy of biological photoreceptors

NARCIS (Netherlands)

Kennis, J.T.M.; Groot, M.L.

2007-01-01

We review recent new insights on reaction dynamics of photoreceptors proteins gained from ultrafast spectroscopy. In Blue Light sensing Using FAD (BLUF) domains, a hydrogen-bond rearrangement around the flavin chromophore proceeds through a radical-pair mechanism, by which light-induced electron and

Ultrafast vibrations of gold nanorings

DEFF Research Database (Denmark)

Kelf, T; Tanaka, Y; Matsuda, O

2011-01-01

We investigate the vibrational modes of gold nanorings on a silica substrate with an ultrafast optical technique. By comparison with numerical simulations, we identify several resonances in the gigahertz range associated with axially symmetric deformations of the nanoring and substrate. We elucid...

Ultrafast gas switching experiments

International Nuclear Information System (INIS)

Frost, C.A.; Martin, T.H.; Patterson, P.E.; Rinehart, L.F.; Rohwein, G.J.; Roose, L.D.; Aurand, J.F.; Buttram, M.T.

1993-01-01

We describe recent experiments which studied the physics of ultrafast gas breakdown under the extreme overvoltages which occur when a high pressure gas switch is pulse charged to hundreds of kV in 1 ns or less. The highly overvolted peaking gaps produce powerful electromagnetic pulses with risetimes Khz at > 100 kV/m E field

Ultrafast spin exchange-coupling torque via photo-excited charge-transfer processes

Science.gov (United States)

Ma, X.; Fang, F.; Li, Q.; Zhu, J.; Yang, Y.; Wu, Y. Z.; Zhao, H. B.; Lüpke, G.

2015-10-01

Optical control of spin is of central importance in the research of ultrafast spintronic devices utilizing spin dynamics at short time scales. Recently developed optical approaches such as ultrafast demagnetization, spin-transfer and spin-orbit torques open new pathways to manipulate spin through its interaction with photon, orbit, charge or phonon. However, these processes are limited by either the long thermal recovery time or the low-temperature requirement. Here we experimentally demonstrate ultrafast coherent spin precession via optical charge-transfer processes in the exchange-coupled Fe/CoO system at room temperature. The efficiency of spin precession excitation is significantly higher and the recovery time of the exchange-coupling torque is much shorter than for the demagnetization procedure, which is desirable for fast switching. The exchange coupling is a key issue in spin valves and tunnelling junctions, and hence our findings will help promote the development of exchange-coupled device concepts for ultrafast coherent spin manipulation.

Ultrafast magnetization dynamics

OpenAIRE

Woodford, Simon

2008-01-01

This thesis addresses ultrafast magnetization dynamics from a theoretical perspective. The manipulation of magnetization using the inverse Faraday effect has been studied, as well as magnetic relaxation processes in quantum dots. The inverse Faraday effect – the generation of a magnetic field by nonresonant, circularly polarized light – offers the possibility to control and reverse magnetization on a timescale of a few hundred femtoseconds. This is important both for the technological advant...

Tissue strain rate estimator using ultrafast IQ complex data

OpenAIRE

TERNIFI , Redouane; Elkateb Hachemi , Melouka; Remenieras , Jean-Pierre

2012-01-01

International audience; Pulsatile motion of brain parenchyma results from cardiac and breathing cycles. In this study, transient motion of brain tissue was estimated using an Aixplorer® imaging system allowing an ultrafast 2D acquisition mode. The strain was computed directly from the ultrafast IQ complex data using the extended autocorrelation strain estimator (EASE), which provides great SNRs regardless of depth. The EASE first evaluates the autocorrelation function at each depth over a set...

FTO Inhibits Insulin Secretion and Promotes NF-κB Activation through Positively Regulating ROS Production in Pancreatic β cells.

Directory of Open Access Journals (Sweden)

Hong-Qi Fan

Full Text Available FTO (Fat mass and obesity-associated is associated with increased risk of obesity and type 2 diabetes incurrence. Pancreas islet β cells dysfunction and insulin resistance are major causes of type 2 diabetes. However, whether FTO plays an important functional role in pancreatic β cells as well as the related molecular mechanism is still unclear. In the present study, the tissue expression profile of FTO was firstly determined using quantitative PCR and western blot. FTO is widely expressed in various tissues and presented with relative high expression in pancreas tissue, especially in endocrine pancreas. FTO overexpression in MIN6 cells achieved by lentivirus delivery significantly inhibits insulin secretion in the presence of glucose stimulus as well as KCl. FTO silence has no effect on insulin secretion of MIN6 cells. However, FTO overexpression doesn't affect the transcription of insulin gene. Furthermore, reactive oxygen species (ROS production and NF-κB activation are significantly promoted by FTO overexpression. Inhibition of intracellular ROS production by N-acetyl-L-cysteine (NAC can alleviate NF-κB activation and restore the insulin secretion mediated by FTO overexpression. A whole transcript-microarray is employed to analyze the differential gene expression mediated by FTO overexpression. The genes which are modulated by FTO are involved in many important biological pathways such as G-protein coupled receptor signaling and NF-κB signaling. Therefore, our study indicates that FTO may contribute to pancreas islet β cells dysfunction and the inhibition of FTO activity is a potential target for the treatment of diabetes.

Dual pathways for the intracellular processing of insulin. Relationship between retroendocytosis of intact hormone and the recycling of insulin receptors

International Nuclear Information System (INIS)

Marshall, S.

1985-01-01

Adipocytes process insulin through either of two pathways: a retroendocytotic pathway that culminates in the release of intact insulin, and a degradative pathway that terminates in the intracellular catabolism and release of degraded ligand. Mechanistically, these pathways were found to differ in several ways. First, temporal differences were found in the rate at which intact and degraded products were extruded. After 125 I-insulin was preloaded into the cell interior, intact ligand was completely released during the first 10 min (t 1/2 = 2 min), whereas degraded insulin was released at a much slower rate over 1 h (t 1/2 greater than 8 min). Secondly, it was found that chloroquine profoundly inhibited the insulin degradative pathway, resulting in the intracellular accumulation of intact ligand and a reduction in the release of degraded products. In contrast, however, chloroquine was without effect on the retroendocytotic processing of insulin. Based on the known actions of chloroquine, it appears that retroendocytosis of insulin does not involve vesicular acidification or dissociation of the insulin-receptor complex and that insulin is most likely carried to the cell exterior in the same vesicles (either receptor-bound or free) as those mediating recycling receptors. Interestingly, accumulation of undergraded insulin within chloroquine-treated cells did not result in the release of additional intact ligand, suggesting that once insulin enters the degradative compartment it is committed to catabolism and cannot exit the cell through the retroendocytotic pathway. A third difference was revealed by the finding that extracellular unlabeled insulin (100 ng/ml) markedly accelerated the rate at which preloaded 125 I-insulin was released from adipocytes (t 1/2 of 3 min versus 7 min in controls cells)

The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin

DEFF Research Database (Denmark)

Lobbens, Eva Stephanie; Foderà, Vito; Nyberg, Nils

2016-01-01

, high-performance liquid chromatography and transmission electron microscopy it was found that a degradation product of aloin, formed over weeks of storage, was able to significantly inhibit insulin fibrillation. The activity of the stored aloin was significantly reduced in the presence of small amounts...... of sodium azide or ascorbic acid, suggesting the active compound to be an oxidation product. A high-performance liquid chromatography method and a liquid chromatography-mass spectrometry method were developed to investigate the degradation products in the aged aloin solution. We found that the major...

Induction of insulin secretion in engineered liver cells by nitric oxide

Directory of Open Access Journals (Sweden)

Özcan Sabire

2007-10-01

Full Text Available Abstract Background Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs in a glucose-independent manner. In the present study we engineered liver cells to produce and secrete insulin and insulin secretion can be stimulated via the nitric oxide pathway. Results Expression of either human insulin or the beta cell specific transcription factors PDX-1, NeuroD1 and MafA in the Hepa1-6 cell line or primary liver cells via adenoviral gene transfer, results in production and secretion of insulin. Although, the secretion of insulin is not significantly increased in response to high glucose, treatment of these engineered liver cells with L-arginine stimulates insulin secretion up to three-fold. This L-arginine-mediated insulin release is dependent on the production of nitric oxide. Conclusion Liver cells can be engineered to produce insulin and insulin secretion can be induced by treatment with L-arginine via the production of nitric oxide.

Patellofemoral joint motion: Evaluation by ultrafast computed tomography

International Nuclear Information System (INIS)

Stanford, W.; Phelan, J.; Kathol, M.H.; Rooholamini, S.A.; El-Khoury, G.Y.; Palutsis, G.R.; Albright, J.P.

1988-01-01

Patellofemoral maltracking is a recognized cause of peripatellar pain. Clinicians currently rely on observation, palpation, and static radiographic images to evaluate the symptomatic patient. Ultrafast computed tomography (ultrafast CT) offers objective observations of the dynamic influences of muscle contraction on the patellofemoral joint as the knee is actively moved through a range of motion from 90 0 C flexion of full extension. This study reports our initial observations and establishes a range of normal values so that patients with a clinical suspicion of patellar maltracking may be evaluated. (orig./GDG)

Patellofemoral joint motion: Evaluation by ultrafast computed tomography

Energy Technology Data Exchange (ETDEWEB)

Stanford, W.; Phelan, J.; Kathol, M.H.; Rooholamini, S.A.; El-Khoury, G.Y.; Palutsis, G.R.; Albright, J.P.

1988-10-01

Patellofemoral maltracking is a recognized cause of peripatellar pain. Clinicians currently rely on observation, palpation, and static radiographic images to evaluate the symptomatic patient. Ultrafast computed tomography (ultrafast CT) offers objective observations of the dynamic influences of muscle contraction on the patellofemoral joint as the knee is actively moved through a range of motion from 90/sup 0/C flexion of full extension. This study reports our initial observations and establishes a range of normal values so that patients with a clinical suspicion of patellar maltracking may be evaluated. (orig./GDG).

Mechanisms linking brain insulin resistance to Alzheimer's disease

Science.gov (United States)

Matioli, Maria Niures P.S.; Nitrini, Ricardo

2015-01-01

Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

Mechanisms linking brain insulin resistance to Alzheimer's disease

Directory of Open Access Journals (Sweden)

Maria Niures P.S. Matioli

Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses

Science.gov (United States)

Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

2015-01-01

Abstract Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle

Patient Perspectives on Biosimilar Insulin.

Science.gov (United States)

Wilkins, Alasdair R; Venkat, Manu V; Brown, Adam S; Dong, Jessica P; Ran, Nina A; Hirsch, James S; Close, Kelly L

2014-01-01

Given that a new wave of biosimilar insulins will likely enter the market in coming years, it is important to understand patient perspectives on these biosimilars. A survey (N = 3214) conducted by the market research company dQ&A, which maintains a 10 000-patient panel of people with type 1 or type 2 diabetes in roughly equal measure, investigated these perspectives. The survey asked whether patients would switch to a hypothetical less expensive biosimilar insulin that was approved by their provider. Approximately 66% of respondents reported that they would "definitely" or "likely" use a biosimilar insulin, while 17% reported that they were "unlikely" to use or would "definitely not use" such a product. Type 2 diabetes patients demonstrated slightly more willingness to use biosimilars than type 1 diabetes patients. Common patient concerns included whether biosimilars would be as effective as reference products (~650 respondents), whether side effect profiles would deviate from those of reference products (~220 respondents), and the design of the delivery device (~50 respondents). While cost savings associated with biosimilar insulins could increase patient uptake, especially among patients without health insurance (some recent estimates suggest that biosimilars will come at a substantial discount), patients may still need assurance that a cheaper price tag is not necessarily associated with substandard quality. Overall, the dQ&A survey indicates that the majority of patients are willing to consider biosimilar insulins, but manufacturers will need to work proactively to address and assuage patient concerns regarding efficacy, safety, drug administration, and other factors. © 2014 Diabetes Technology Society.

Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

Energy Technology Data Exchange (ETDEWEB)

Keller, U.; Lustenberger, M.; Mueller-Brand, J.G.; Gerber, P.P.; Stauffacher, W.

1989-05-01

Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and thus releasing free fatty acids, but also by increasing intrahepatic ketogenesis. Thyroid hormone availability was associated with lipolysis and ketogenesis. Ketone body concentrations after an overnight fast were only modestly elevated in hyperthyroidism resulting from increased peripheral ketone body clearance. There was a significant correlation between serum triiodothyronine levels and the ketone body metabolic clearance rate. Thus, ketone body homeostasis in human subjects resulted from the interaction of hormones such as insulin, catecholamines, and thyroid hormones regulating lipolysis, intrahepatic ketogenesis, and peripheral ketone body utilization. 58 references.

Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

International Nuclear Information System (INIS)

Keller, U.; Lustenberger, M.; Mueller-Brand, J.G.; Gerber, P.P.; Stauffacher, W.

1989-01-01

Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and thus releasing free fatty acids, but also by increasing intrahepatic ketogenesis. Thyroid hormone availability was associated with lipolysis and ketogenesis. Ketone body concentrations after an overnight fast were only modestly elevated in hyperthyroidism resulting from increased peripheral ketone body clearance. There was a significant correlation between serum triiodothyronine levels and the ketone body metabolic clearance rate. Thus, ketone body homeostasis in human subjects resulted from the interaction of hormones such as insulin, catecholamines, and thyroid hormones regulating lipolysis, intrahepatic ketogenesis, and peripheral ketone body utilization. 58 references

New ways of insulin delivery.

Science.gov (United States)

Heinemann, L

2011-02-01

The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

Expression of an insulin/interleukin-1 receptor antagonist hybrid gene in insulin-producing cell lines (HIT-T15 and NIT-1) confers resistance against interleukin-1-induced nitric oxide production.

Science.gov (United States)

Welsh, N; Bendtzen, K; Welsh, M

1995-01-01

A hybrid gene consisting of the insulin gene enhancer/promoter region, the signal sequence, the insulin B- and C-chains, and the human interleukin-1 receptor antagonist (IL-1ra) gene was constructed. This hybrid gene was transfected together with the pSV2-neo construct into the insulin-producing cell lines HIT-T15 and NIT-1. One of the geneticin-selected clones, HITra2, expressed a 1.4-kb mRNA, which hybridized both to insulin and IL-1ra-cDNA in Northern blot analysis. Three proteins, with the mol wt 23, 17, and 14 kD, were immunoprecipitated with anti-IL-1ra antibodies from [35S]methionine-labeled HITra2 cells. Both at a low and at a high glucose concentration, 4-5 ng of IL-1ra/10(6) cells (ELISA) was released from these cells. On the other hand, a high glucose concentration evoked a three-fold increase in the release of insulin, suggesting that IL-1ra was released constitutively. Measured by nitrite production, transfected HIT, and NIT-1 cells exhibited a more than 10-fold decrease in IL-1 beta sensitivity. Since the conditioned culture media from the HITra2 cells exhibited an anti-IL-1 beta activity of only 0.5 U/ml, and mixed culture of HITra2 cells and isolated rat islets prevented IL-1 beta induced inhibition of insulin release, it is likely that IL-1ra acts locally at the cell surface. It is concluded that expression of a hybrid insulin/IL-1ra gene confers resistance to IL-1 and that this technique may be used to elucidate the role of IL-1 in autoimmune disorders such as insulin-dependent diabetes mellitus. Images PMID:7706480

Voluntary wheel running selectively augments insulin-stimulated vasodilation in arterioles from white skeletal muscle of insulin-resistant rats.

Science.gov (United States)

Mikus, Catherine R; Roseguini, Bruno T; Uptergrove, Grace M; Morris, E Matthew; Rector, Randy Scott; Libla, Jessica L; Oberlin, Douglas J; Borengasser, Sarah J; Taylor, Angelina M; Ibdah, Jamal A; Laughlin, Maurice Harold; Thyfault, John P

2012-11-01

Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterioles from red and white muscle. Insulin signaling and vasoreactivity to insulin (1-1000 μIU/mL) were assessed in 2A from the Gw and Gr of SED OLETF rats at 12 and 20 weeks of age (SED12, SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12 to 20 weeks. Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (p RUN20 (p RUN selectively improved insulin-mediated vasodilation in Gw 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal. © 2012 John Wiley & Sons Ltd.

Silicon based ultrafast optical waveform sampling

DEFF Research Database (Denmark)

Ji, Hua; Galili, Michael; Pu, Minhao

2010-01-01

A 300 nmx450 nmx5 mm silicon nanowire is designed and fabricated for a four wave mixing based non-linear optical gate. Based on this silicon nanowire, an ultra-fast optical sampling system is successfully demonstrated using a free-running fiber laser with a carbon nanotube-based mode-locker as th......A 300 nmx450 nmx5 mm silicon nanowire is designed and fabricated for a four wave mixing based non-linear optical gate. Based on this silicon nanowire, an ultra-fast optical sampling system is successfully demonstrated using a free-running fiber laser with a carbon nanotube-based mode......-locker as the sampling source. A clear eye-diagram of a 320 Gbit/s data signal is obtained. The temporal resolution of the sampling system is estimated to 360 fs....

Selective Insulin Resistance in the Kidney

Science.gov (United States)

Horita, Shoko; Nakamura, Motonobu; Suzuki, Masashi; Satoh, Nobuhiko; Suzuki, Atsushi; Seki, George

2016-01-01

Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule. PMID:27247938

Ultra-fast framing camera tube

Science.gov (United States)

Kalibjian, Ralph

1981-01-01

An electronic framing camera tube features focal plane image dissection and synchronized restoration of the dissected electron line images to form two-dimensional framed images. Ultra-fast framing is performed by first streaking a two-dimensional electron image across a narrow slit, thereby dissecting the two-dimensional electron image into sequential electron line images. The dissected electron line images are then restored into a framed image by a restorer deflector operated synchronously with the dissector deflector. The number of framed images on the tube's viewing screen is equal to the number of dissecting slits in the tube. The distinguishing features of this ultra-fast framing camera tube are the focal plane dissecting slits, and the synchronously-operated restorer deflector which restores the dissected electron line images into a two-dimensional framed image. The framing camera tube can produce image frames having high spatial resolution of optical events in the sub-100 picosecond range.

Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

Directory of Open Access Journals (Sweden)

Cécile Pierre-Eugene

Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

Six-month exenatide improves HOMA hyperbolic product in type 2 diabetic patients mostly by enhancing beta-cell function rather than insulin sensitivity.

Science.gov (United States)

Preumont, V; Hermans, M-P; Brichard, S; Buysschaert, M

2010-09-01

This study aimed to determine whether or not the improvement of glycaemic control with 6-month exenatide therapy in type 2 diabetic patients with secondary failure to combined oral therapy is related to amelioration of β-cell function and/or insulin sensitivity and their combined product. Thirty-three patients with type 2 diabetes were investigated. Their β-cell function and insulin sensitivity were measured using Homoeostasis Model Assessment [HOMA-B, HOMA-S and HOMA hyperbolic product (BxS)]. Additional endpoints included changes in weight, HbA(1c) and plasma adiponectin, as well as baseline clinical and biological characteristics, as potential predictors of HbA(1c) response. After 6 months, unadjusted HOMA-B increased from 33 ± 24% to 43 ± 23% (P=0.0210), whereas there was no significant change in HOMA-S (from 58 ± 35% to 61 ± 40%). The hyperbolic product increased by a relative 70% (from 15 ± 7% to 22 ± 15%; P=0.0055). Body mass index decreased from 32.2 ± 5.1 kg/m(2) to 31.0 ± 4.8 kg/m(2) (PHOMA-B and hyperbolic product over a 6-month treatment period with no overall change in insulin sensitivity, despite weight loss. Thus, improved β-cell function rather than increased insulin sensitivity accounts for the bulk of HbA(1c) reduction following 6 months of exenatide treatment. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Real-time control of ultrafast laser micromachining by laser-induced breakdown spectroscopy

International Nuclear Information System (INIS)

Tong Tao; Li Jinggao; Longtin, Jon P.

2004-01-01

Ultrafast laser micromachining provides many advantages for precision micromachining. One challenging problem, however, particularly for multilayer and heterogeneous materials, is how to prevent a given material from being ablated, as ultrafast laser micromachining is generally material insensitive. We present a real-time feedback control system for an ultrafast laser micromachining system based on laser-induced breakdown spectroscopy (LIBS). The characteristics of ultrafast LIBS are reviewed and discussed so as to demonstrate the feasibility of the technique. Comparison methods to identify the material emission patterns are developed, and several of the resulting algorithms were implemented into a real-time computer control system. LIBS-controlled micromachining is demonstrated for the fabrication of microheater structures on thermal sprayed materials. Compared with a strictly passive machining process without any such feedback control, the LIBS-based system provides several advantages including less damage to the substrate layer, reduced machining time, and more-uniform machining features

Spin-controlled ultrafast vertical-cavity surface-emitting lasers

Science.gov (United States)

Höpfner, Henning; Lindemann, Markus; Gerhardt, Nils C.; Hofmann, Martin R.

2014-05-01

Spin-controlled semiconductor lasers are highly attractive spintronic devices providing characteristics superior to their conventional purely charge-based counterparts. In particular, spin-controlled vertical-cavity surface emitting lasers (spin-VCSELs) promise to offer lower thresholds, enhanced emission intensity, spin amplification, full polarization control, chirp control and ultrafast dynamics. Most important, the ability to control and modulate the polarization state of the laser emission with extraordinarily high frequencies is very attractive for many applications like broadband optical communication and ultrafast optical switches. We present a novel concept for ultrafast spin-VCSELs which has the potential to overcome the conventional speed limitation for directly modulated lasers by the relaxation oscillation frequency and to reach modulation frequencies significantly above 100 GHz. The concept is based on the coupled spin-photon dynamics in birefringent micro-cavity lasers. By injecting spin-polarized carriers in the VCSEL, oscillations of the coupled spin-photon system can by induced which lead to oscillations of the polarization state of the laser emission. These oscillations are decoupled from conventional relaxation oscillations of the carrier-photon system and can be much faster than these. Utilizing these polarization oscillations is thus a very promising approach to develop ultrafast spin-VCSELs for high speed optical data communication in the near future. Different aspects of the spin and polarization dynamics, its connection to birefringence and bistability in the cavity, controlled switching of the oscillations, and the limitations of this novel approach will be analysed theoretically and experimentally for spin-polarized VCSELs at room temperature.

Ultrafast Terahertz Conductivity of Photoexcited Nanocrystalline Silicon

DEFF Research Database (Denmark)

Cooke, David; MacDonald, A. Nicole; Hryciw, Aaron

2007-01-01

The ultrafast transient ac conductivity of nanocrystalline silicon films is investigated using time-resolved terahertz spectroscopy. While epitaxial silicon on sapphire exhibits a free carrier Drude response, silicon nanocrystals embedded in glass show a response that is best described by a class...... in the silicon nanocrystal films is dominated by trapping at the Si/SiO2 interface states, occurring on a 1–100 ps time scale depending on particle size and hydrogen passivation......The ultrafast transient ac conductivity of nanocrystalline silicon films is investigated using time-resolved terahertz spectroscopy. While epitaxial silicon on sapphire exhibits a free carrier Drude response, silicon nanocrystals embedded in glass show a response that is best described...

Development of Scanning Ultrafast Electron Microscope Capability.

Energy Technology Data Exchange (ETDEWEB)

Collins, Kimberlee Chiyoko [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Talin, Albert Alec [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Chandler, David W. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Michael, Joseph R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2016-11-01

Modern semiconductor devices rely on the transport of minority charge carriers. Direct examination of minority carrier lifetimes in real devices with nanometer-scale features requires a measurement method with simultaneously high spatial and temporal resolutions. Achieving nanometer spatial resolutions at sub-nanosecond temporal resolution is possible with pump-probe methods that utilize electrons as probes. Recently, a stroboscopic scanning electron microscope was developed at Caltech, and used to study carrier transport across a Si p-n junction [ 1 , 2 , 3 ] . In this report, we detail our development of a prototype scanning ultrafast electron microscope system at Sandia National Laboratories based on the original Caltech design. This effort represents Sandia's first exploration into ultrafast electron microscopy.

Quantum modeling of ultrafast photoinduced charge separation

Science.gov (United States)

Rozzi, Carlo Andrea; Troiani, Filippo; Tavernelli, Ivano

2018-01-01

Phenomena involving electron transfer are ubiquitous in nature, photosynthesis and enzymes or protein activity being prominent examples. Their deep understanding thus represents a mandatory scientific goal. Moreover, controlling the separation of photogenerated charges is a crucial prerequisite in many applicative contexts, including quantum electronics, photo-electrochemical water splitting, photocatalytic dye degradation, and energy conversion. In particular, photoinduced charge separation is the pivotal step driving the storage of sun light into electrical or chemical energy. If properly mastered, these processes may also allow us to achieve a better command of information storage at the nanoscale, as required for the development of molecular electronics, optical switching, or quantum technologies, amongst others. In this Topical Review we survey recent progress in the understanding of ultrafast charge separation from photoexcited states. We report the state-of-the-art of the observation and theoretical description of charge separation phenomena in the ultrafast regime mainly focusing on molecular- and nano-sized solar energy conversion systems. In particular, we examine different proposed mechanisms driving ultrafast charge dynamics, with particular regard to the role of quantum coherence and electron-nuclear coupling, and link experimental observations to theoretical approaches based either on model Hamiltonians or on first principles simulations.

Concentrated insulins: the new basal insulins

Directory of Open Access Journals (Sweden)

Lamos EM

2016-03-01

Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

Chirped pulse digital holography for measuring the sequence of ultrafast optical wavefronts

Science.gov (United States)

Karasawa, Naoki

2018-04-01

Optical setups for measuring the sequence of ultrafast optical wavefronts using a chirped pulse as a reference wave in digital holography are proposed and analyzed. In this method, multiple ultrafast object pulses are used to probe the temporal evolution of ultrafast phenomena and they are interfered with a chirped reference wave to record a digital hologram. Wavefronts at different times can be reconstructed separately from the recorded hologram when the reference pulse can be treated as a quasi-monochromatic wave during the pulse width of each object pulse. The feasibility of this method is demonstrated by numerical simulation.

Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

Science.gov (United States)

Ter Horst, K W; van Galen, K A; Gilijamse, P W; Hartstra, A V; de Groot, P F; van der Valk, F M; Ackermans, M T; Nieuwdorp, M; Romijn, J A; Serlie, M J

2017-08-01

Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3- 2 H 5 ]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m -2 ). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, PInsulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, Pinsulin-glycerol product (r=-0.467, PInsulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, PInsulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, Pinsulin resistance (area under the curve ⩾0.801, Pinsulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.

9th International Symposium on Ultrafast Processes in Spectroscopy

CERN Document Server

Silvestri, S; Denardo, G

1996-01-01

This volume is a collection of papers presented at the Ninth International Symposium on "Ultrafast Processes in Spectroscopy" (UPS '95) held at the International Centre for Theo­ retical Physics (ICTP), Trieste (Italy), October 30 -November 3, 1995. These meetings have become recognized as the major forum in Europe for discussion of new work in this rapidly moving field. The UPS'95 Conference in Trieste brought together a multidisciplinary group of researchers sharing common interests in the generation of ultrashort optical pulses and their application to studies of ultrafast phenomena in physics, chemistry, material science, electronics, and biology. It was attended by approximately 250 participants from 20 countries and the five-day program comprises more than 200 papers. The progress of both technology and applications in the field of ultrafast processes during these last years is truly remarkable. The advent of all solid state femtosecond lasers and the extension of laser wavelengths by frequency convers...

Ultrafast Spectroscopic Noninvasive Probe of Vertical Carrier Transport in Heterostructure Devices

Science.gov (United States)

2016-03-01

ARL-TR-7618 ● MAR 2016 US Army Research Laboratory Ultrafast Spectroscopic Noninvasive Probe of Vertical Carrier Transport in...US Army Research Laboratory Ultrafast Spectroscopic Noninvasive Probe of Vertical Carrier Transport in Heterostructure Devices by Blair C...Spectroscopic Noninvasive Probe of Vertical Carrier Transport in Heterostructure Devices 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

Science.gov (United States)

Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

2016-02-01

Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

Science.gov (United States)

Ververis, J; Ku, L; Delafontaine, P

1994-02-01

Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

Progress in Ultrafast Intense Laser Science

CERN Document Server

Yamanouchi, Kaoru; Li, Ruxin; Chin, See Leang

2009-01-01

The PUILS series presents Progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science, and optical science. PUILS has been stimulated by the recent development of ultrafast laser technologies. Each volume contains approximately 15 chapters, authored by researchers at the forefront. Each chapter opens with an overview of the topics to be discussed, so that researchers, who are not experts in the specific topics, as well as graduate students can grasp the importance and attractions of this sub-field of research, and these are followed by reports of cutting-edge discoveries. This fourth volume covers a broad range of topics from this interdisciplinary research field, focusing on strong field ionization of atoms; excitation, ionization and fragmentation of molecules; nonlinear intense optical phenomena and attosecond pulses; and laser - solid interactions and photoemission.

Will the next generation of basal insulins offer clinical advantages?

Science.gov (United States)

Garber, A J

2014-06-01

The 21st century has seen the arrival of several insulin analogue products and the refinement of insulin regimens, with widespread advocacy of continuous titration algorithms and earlier initiation of supplementary insulin therapy (predominantly using basal insulins) in type 2 diabetes. Nevertheless, many insulin-treated diabetes patients remain in poor glycaemic control. This might reflect insufficient titration effort or lax adherence, but these issues could in some cases result from concerns about hypoglycaemia. Certainly there is scope for improving the pharmacokinetic/pharmacodynamic (PK/PD) profile of basal insulin, and three new products offer this prospect. Insulin degludec, now in clinical use, and PEGylated insulin lispro, in development, have greatly extended action profiles that result from two very different, but unique, mechanisms. With once-daily dosing, these insulins produce stable PK/PD profiles at steady state, associated with a low incidence of hypoglycaemia. The feasibility of varied daily dose timing has also been confirmed with insulin degludec. High strength formulations of insulin glargine and insulin degludec offer the prospect of a reduced injection number/volume in high dose users, and in the case of glargine, the PK/PD profile might also be favourably modified. This review considers critically the clinical evidence and expectations we should have for these new basal insulins. © 2013 John Wiley & Sons Ltd.

Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.

Science.gov (United States)

Kuroda, Akio; Yasuda, Tetsuyuki; Takahara, Mitsuyoshi; Sakamoto, Fumie; Kasami, Ryuichi; Miyashita, Kazuyuki; Yoshida, Sumiko; Kondo, Eri; Aihara, Ken-ichi; Endo, Itsuro; Matsuoka, Taka-aki; Kaneto, Hideaki; Matsumoto, Toshio; Shimomura, Iichiro; Matsuhisa, Munehide

2012-11-01

To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; Plunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.

Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle.

Science.gov (United States)

Lefort, Natalie; Glancy, Brian; Bowen, Benjamin; Willis, Wayne T; Bailowitz, Zachary; De Filippis, Elena A; Brophy, Colleen; Meyer, Christian; Højlund, Kurt; Yi, Zhengping; Mandarino, Lawrence J

2010-10-01

The contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle. Mitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-resistant individuals who were otherwise healthy. Respiration and reactive oxygen species (ROS) production rates were measured in vitro. Relative abundances of proteins detected by mass spectrometry were determined using a normalized spectral abundance factor method. NADH- and FADH(2)-linked maximal respiration rates were similar between lean and obese individuals. Rates of pyruvate and palmitoyl-DL-carnitine (both including malate) ROS production were significantly higher in obesity. Mitochondria from obese individuals maintained higher (more negative) extramitochondrial ATP free energy at low metabolic flux, suggesting that stronger mitochondrial thermodynamic driving forces may underlie the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransferase 1B). We provide data suggesting normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in parallel with high rates of ROS production. Furthermore, we show specific abundance differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insulin resistance.

Pump polarization insensitive and efficient laser-diode pumped Yb:KYW ultrafast oscillator.

Science.gov (United States)

Wang, Sha; Wang, Yan-Biao; Feng, Guo-Ying; Zhou, Shou-Huan

2016-02-01

We theoretically and experimentally report and evaluate a novel split laser-diode (LD) double-end pumped Yb:KYW ultrafast oscillator aimed at improving the performance of an ultrafast laser. Compared to a conventional unpolarized single-LD end-pumped ultrafast laser system, we improve the laser performance such as absorption efficiency, slope efficiency, cw mode-locking threshold, and output power by this new structure LD-pumped Yb:KYW ultrafast laser. Experiments were carried out with a 1 W output fiber-coupled LD. Experimental results show that the absorption increases from 38.7% to 48.4%, laser slope efficiency increases from 18.3% to 24.2%, cw mode-locking threshold decreases 12.7% from 630 to 550 mW in cw mode-locking threshold, and maximum output-power increases 28.5% from 158.4 to 221.5 mW when we switch the pump scheme from an unpolarized single-end pumping structure to a split LD double-end pumping structure.

Multiplane wave imaging increases signal-to-noise ratio in ultrafast ultrasound imaging

International Nuclear Information System (INIS)

Tiran, Elodie; Deffieux, Thomas; Correia, Mafalda; Maresca, David; Osmanski, Bruno-Felix; Pernot, Mathieu; Tanter, Mickael; Sieu, Lim-Anna; Bergel, Antoine; Cohen, Ivan

2015-01-01

Ultrafast imaging using plane or diverging waves has recently enabled new ultrasound imaging modes with improved sensitivity and very high frame rates. Some of these new imaging modalities include shear wave elastography, ultrafast Doppler, ultrafast contrast-enhanced imaging and functional ultrasound imaging. Even though ultrafast imaging already encounters clinical success, increasing even more its penetration depth and signal-to-noise ratio for dedicated applications would be valuable.Ultrafast imaging relies on the coherent compounding of backscattered echoes resulting from successive tilted plane waves emissions; this produces high-resolution ultrasound images with a trade-off between final frame rate, contrast and resolution. In this work, we introduce multiplane wave imaging, a new method that strongly improves ultrafast images signal-to-noise ratio by virtually increasing the emission signal amplitude without compromising the frame rate. This method relies on the successive transmissions of multiple plane waves with differently coded amplitudes and emission angles in a single transmit event. Data from each single plane wave of increased amplitude can then be obtained, by recombining the received data of successive events with the proper coefficients.The benefits of multiplane wave for B-mode, shear wave elastography and ultrafast Doppler imaging are experimentally demonstrated. Multiplane wave with 4 plane waves emissions yields a 5.8  ±  0.5 dB increase in signal-to-noise ratio and approximately 10 mm in penetration in a calibrated ultrasound phantom (0.7 d MHz −1 cm −1 ). In shear wave elastography, the same multiplane wave configuration yields a 2.07  ±  0.05 fold reduction of the particle velocity standard deviation and a two-fold reduction of the shear wave velocity maps standard deviation. In functional ultrasound imaging, the mapping of cerebral blood volume results in a 3 to 6 dB increase of the contrast-to-noise ratio in

Tracking ultrafast relaxation dynamics of furan by femtosecond photoelectron imaging

International Nuclear Information System (INIS)

Liu, Yuzhu; Knopp, Gregor; Qin, Chaochao; Gerber, Thomas

2015-01-01

Graphical abstract: - Highlights: • Relaxation dynamics of furan are tracked by femtosecond photoelectron imaging. • The mechanism for ultrafast formation of α-carbene and β-carbene is proposed. • Ultrafast internal conversion from S 2 to S 1 is observed. • The transient characteristics of the fragment ions are obtained. • Single-color multi-photon ionization dynamics at 800 nm are also studied. - Abstract: Ultrafast internal conversion dynamics of furan has been studied by femtosecond photoelectron imaging (PEI) coupled with photofragmentation (PF) spectroscopy. Photoelectron imaging of single-color multi-photon ionization and two-color pump–probe ionization are obtained and analyzed. Photoelectron bands are assigned to the related states. The time evolution of the photoelectron signal by pump–probe ionization can be well described by a biexponential decay: two rapid relaxation pathways with time constants of ∼15 fs and 85 (±11) fs. The rapid relaxation is ascribed to the ultrafast internal conversion (IC) from the S 2 state to the vibrationally hot S 1 state. The second relaxation process is attributed to the redistributions and depopulation of secondarily populated high vibronic S 1 state and the formation of α-carbene and β-carbene by H immigration. Additionally, the transient characteristics of the fragment ions are also measured and discussed as a complementary understanding

Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

International Nuclear Information System (INIS)

Dorn, A.; Bernstein, H.G.; Rinne, A.; Hahn, H.J.; Ziegler, M.

1983-01-01

The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

Fast MR imaging and ultrafast MR imaging of fetal central nervous system abnormalities

Energy Technology Data Exchange (ETDEWEB)

Shakudo, Miyuki; Manabe, Takao; Murata, Katsuko; Matsuo, Ryoichi; Oda, Junro [Osaka City General Hospital (Japan); Inoue, Yuichi; Mochizuki, Kunizo; Yamada, Ryusaku

2001-12-01

The aims of this study were two: to compare the efficacy of fast MRI (breath-hold fast spin-echo T2-weighted and fast gradient-echo T1-weighted sequence) and ultrafast MRI (half-Fourier acquisition single-shot turbo spin-echo sequence) in evaluation of fetal central nervous system (CNS) abnormalities at late gestational age, and to compare the capability of fast MRI and ultrafast MRI to assess fetal CNS abnormalities with that of prenatal ultrasonography (US). Forty-nine women with fetuses at gestational ages of 26-39 weeks underwent fast MRI (29 patients) or ultrafast MRI (20 patients). In detection of motion artifact, visualization of the lateral and 4th ventricles, and differentiation between gray and white matter in cerebral hemispheres, ultrafast MRI was significantly superior to fast MRI (p<0.0001, Mann-Whitney U test). In 25 of 43 cases, US and MR diagnoses were the same and consistent with postnatal diagnosis. In 10 of 43 cases, MRI demonstrated findings additional to or different from those of US, and MR findings were confirmed postnatally. MRI, particularly ultrafast MRI, is useful for demonstrating CNS abnormalities in situations in which US is suggestive but not definitive. (author)

Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice.

Science.gov (United States)

Coomans, Claudia P; Biermasz, Nienke R; Geerling, Janine J; Guigas, Bruno; Rensen, Patrick C N; Havekes, Louis M; Romijn, Johannes A

2011-12-01

Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated tissue-specific glucose uptake. Tolbutamide, an inhibitor of ATP-sensitive K(+) channels (K(ATP) channels), or vehicle was infused into the lateral ventricle in the basal state and during hyperinsulinemic-euglycemic conditions in postabsorptive, chow-fed C57Bl/6J mice and in postabsorptive C57Bl/6J mice with diet-induced obesity. Whole-body glucose uptake was measured by d-[(14)C]glucose kinetics and tissue-specific glucose uptake by 2-deoxy-d-[(3)H]glucose uptake. During clamp conditions, intracerebroventricular administration of tolbutamide impaired the ability of insulin to inhibit EGP by ∼20%. In addition, intracerebroventricular tolbutamide diminished insulin-stimulated glucose uptake in muscle (by ∼59%) but not in heart or adipose tissue. In contrast, in insulin-resistant mice with diet-induced obesity, intracerebroventricular tolbutamide did not alter the effects of insulin during clamp conditions on EGP or glucose uptake by muscle. Insulin stimulates glucose uptake in muscle in part through effects via K(ATP) channels in the central nervous system, in analogy with the inhibitory effects of insulin on EGP. High-fat diet-induced obesity abolished the central effects of insulin on liver and muscle. These observations stress the role of central insulin resistance in the pathophysiology of diet-induced insulin resistance.

Ultrafast biophotonics

CERN Document Server

Vasa, P

2016-01-01

This book presents emerging contemporary optical techniques of ultrafast science which have opened entirely new vistas for probing biological entities and processes. The spectrum reaches from time-resolved imaging and multiphoton microscopy to cancer therapy and studies of DNA damage. The book displays interdisciplinary research at the interface of physics and biology. Emerging topics on the horizon are also discussed, like the use of squeezed light, frequency combs and terahertz imaging as the possibility of mimicking biological systems. The book is written in a manner to make it readily accessible to researchers, postgraduate biologists, chemists, engineers, and physicists and students of optics, biomedical optics, photonics and biotechnology.

Ultrafast photoelectron spectroscopy of small molecule organic films

Science.gov (United States)

Read, Kendall Laine

As research in the field of ultrafast optics has produced shorter and shorter pulses, at an ever-widening range of frequencies, ultrafast spectroscopy has grown correspondingly. In particular, ultrafast photoelectron spectroscopy allows direct observation of electrons in transient or excited states, regardless of the eventual relaxation mechanisms. High-harmonic conversion of 800nm, femtosecond, Ti:sapphire laser pulses allows excite/probe spectroscopy down into atomic core level states. To this end, an ultrafast, X-UV photoelectron spectroscopic system is described, including design considerations for the high-harmonic generation line, the time of flight detector, and the subsequent data collection electronics. Using a similar experimental setup, I have performed several ultrafast, photoelectron excited state decay studies at the IBM, T. J. Watson Research Center. All of the observed materials were electroluminescent thin film organics, which have applications as the emitter layer in organic light emitting devices. The specific materials discussed are: Alq, BAlq, DPVBi, and Alq doped with DCM or DMQA. Alq:DCM is also known to lase at low photoexcitation thresholds. A detailed understanding of the involved relaxation mechanisms is beneficial to both applications. Using 3.14 eV excite, and 26.7 eV probe, 90 fs laser pulses, we have observed the lowest unoccupied molecular orbital (LUMO) decay rate over the first 200 picoseconds. During this time, diffusion is insignificant, and all dynamics occur in the absence of electron transport. With excitation intensities in the range of 100μJ/cm2, we have modeled the Alq, BAlq, and DPVBi decays via bimolecular singlet-singlet annihilation. At similar excitations, we have modeled the Alq:DCM decay via Förster transfer, stimulated emission, and excimeric formation. Furthermore, the Alq:DCM occupied to unoccupied molecular orbital energy gap was seen to shrink as a function of excite-to-probe delay, in accordance with the

Ultrafast Holographic Image Recording by Single Shot Femtosecond Spectral Hole Burning

National Research Council Canada - National Science Library

Rebane, Aleksander

2001-01-01

.... This allowed us to record image holograms with 150-fs duration pulses without need to accumulate the SHB effect from many exposures. Results of this research show that it is possible to perform optical recording of data in frequency-domain on ultrafast time scale. These results can be used also as a new diagnostic tool for femtosecond dynamics in various ultrafast optical interactions.

Ultra-fast ipsilateral DPOAE adaptation not modulated by attention?

Science.gov (United States)

Dalhoff, Ernst; Zelle, Dennis; Gummer, Anthony W.

2018-05-01

Efferent stimulation of outer hair cells is supposed to attenuate cochlear amplification of sound waves and is accompanied by reduced DPOAE amplitudes. Recently, a method using two subsequent f2 pulses during presentation of a longer f1 pulse was introduced to measure fast ipsilateral adaptation effects on separated DPOAE components. Compensating primary-tone onsets for their latencies at the f2-tonotopic place, the average adaptation measured in four normal-hearing subjects was 5.0 dB with a time constant below 5 ms. In the present study, two experiments were performed to determine the origin of this ultra-fast ipsilateral adaptation effect. The first experiment measured ultra-fast ipsilateral adaptation using a two-pulse paradigm at three frequencies in the four subjects, while controlling for visual attention of the subjects. The other experiment also controlled for visual attention, but utilized a sequence of f2 short pulses in the presence of a continuous f1 tone to sample ipsilateral adaptation effects with longer time constants in eight subjects. In the first experiment, no significant change in the ultra-fast adaptation between non-directed attention and visual attention could be detected. In contrast, the second experiment revealed significant changes in the magnitude of the slower ipsilateral adaptation in the visual-attention condition. In conclusion, the lack of an attentional influence indicates that the ultra-fast ipsilateral DPOAE adaptation is not solely mediated by the medial olivocochlear reflex.

Enzymatic radioiodination of insulin for radioimmunoassay use

Energy Technology Data Exchange (ETDEWEB)

Awh, O D; Kim, J R [Korea Atomic Energy Research Inst., Seoul (Republic of Korea)

1980-06-01

Insulin was labelled with /sup 125/I using lactoperoxidase as an oxidizing agent. The reaction product was purified via two stages; a starch gel electrophoresis(SGE) and a Sephadex gel filtration(SF). Upon comparison of the labelling yields and the bindabilities of the labelled insulin to its antibody, it has been found that the enzyme method shows higher yields (50%) and the better bindability to its antibody than the conventional chloramine-T method (35%). By checking the insulin blank labelling mixture with a SGE, a paper chromatography, and a radioautography technique, a by-product in the lactoperoxidase method has been identified. The separated fractions in SGE and SF were also analyzed and discussed.

Inverse association between soya food consumption and insulin resistance in Japanese adults.

Science.gov (United States)

Nakamoto, Mariko; Uemura, Hirokazu; Sakai, Tohru; Katsuura-Kamano, Sakurako; Yamaguchi, Miwa; Hiyoshi, Mineyoshi; Arisawa, Kokichi

2015-08-01

The purpose of the present study was to examine the association between soya food consumption and insulin resistance using baseline data of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan. This cross-sectional study included 1274 subjects, aged 34-70 years at baseline, living in Tokushima Prefecture between 2008 and 2013. Fasting blood samples were collected and information on lifestyle characteristics including soya food intake and medical history were obtained using a structured self-administered questionnaire. The homeostasis model assessment of insulin resistance (HOMA-IR) was measured and those with HOMA-IR ≥ 2.5 were defined as having insulin resistance. Multiple logistic regression models were used to analyse the association between soya product intake and the prevalence of insulin resistance. Rural communities located in Tokushima Prefecture, Japan, between 2008 and 2013. A total of 1148 adults (565 men and 583 women), aged 34-70 years. The frequency of intake of miso soup, total non-fried soya products and total soya products showed significant inverse dose-response relationships with insulin resistance, after adjustments for potential confounders. When soya product intake was calculated as soya protein and isoflavone, the odds ratios of insulin resistance decreased significantly as the estimated intake of soya protein increased. Furthermore, significant inverse dose-response relationships were observed for total non-fried soya products and total soya products, after adjustment for total vegetable or total fibre consumption. The present results indicate that the intake of soya products and non-fried soya products is associated with reduced insulin resistance in the Japanese population.

Peripheral insulin resistance and impaired insulin signaling contribute to abnormal glucose metabolism in preterm baboons.

Science.gov (United States)

Blanco, Cynthia L; McGill-Vargas, Lisa L; Gastaldelli, Amalia; Seidner, Steven R; McCurnin, Donald C; Leland, Michelle M; Anzueto, Diana G; Johnson, Marney C; Liang, Hanyu; DeFronzo, Ralph A; Musi, Nicolas

2015-03-01

Premature infants develop hyperglycemia shortly after birth, increasing their morbidity and death. Surviving infants have increased incidence of diabetes as young adults. Our understanding of the biological basis for the insulin resistance of prematurity and developmental regulation of glucose production remains fragmentary. The objective of this study was to examine maturational differences in insulin sensitivity and the insulin-signaling pathway in skeletal muscle and adipose tissue of 30 neonatal baboons using the euglycemic hyperinsulinemic clamp. Preterm baboons (67% gestation) had reduced peripheral insulin sensitivity shortly after birth (M value 12.5 ± 1.5 vs 21.8 ± 4.4 mg/kg · min in term baboons) and at 2 weeks of age (M value 12.8 ± 2.6 vs 16.3 ± 4.2, respectively). Insulin increased Akt phosphorylation, but these responses were significantly lower in preterm baboons during the first week of life (3.2-fold vs 9.8-fold). Preterm baboons had lower glucose transporter-1 protein content throughout the first 2 weeks of life (8%-12% of term). In preterm baboons, serum free fatty acids (FFAs) did not decrease in response to insulin, whereas FFAs decreased by greater than 80% in term baboons; the impaired suppression of FFAs in the preterm animals was paired with a decreased glucose transporter-4 protein content in adipose tissue. In conclusion, peripheral insulin resistance and impaired non-insulin-dependent glucose uptake play an important role in hyperglycemia of prematurity. Impaired insulin signaling (reduced Akt) contributes to the defect in insulin-stimulated glucose disposal. Counterregulatory hormones are not major contributors.

Advanced ultrafast fiber laser sources enabled by fiber nonlinearities

International Nuclear Information System (INIS)

Liu, Wei

2017-05-01

Development of high power/energy ultrafast fiber lasers for scientific research and industrial applications is one of the most exciting fields in ultrafast optics. This thesis demonstrated new means to improve two essential properties - which are indispensable for novel applications such as high-harmonic generation (HHG) and multiphoton microscopy (MPM) - of an ultrafast fiber laser system: energy scaling capability and wavelength tunability. High photon-flux extreme ultraviolet sources enabled by HHG desire high power (>100 W), high repetition-rate (>1 MHz) ultrafast driving laser sources. We have constructed from scratch a high-power Yb-fiber laser system using the well-known chirped-pulse amplification (CPA) technique. Such a CPA system capable of producing ∝200-W average power consists of a monolithic Yb-fiber oscillator, an all-fiber stretcher, a pre-amplifier chain, a main amplifier constructed from rode-type large pitch fiber, and a diffraction-grating based compressor. To increase the HHG efficiency, ultrafast pulses with duration 130-W average power. The amplified pulses are compressed to 60-fs pulses with 100-W average power, constituting a suitable HHG driving source. MPM is a powerful biomedical imaging tool, featuring larger penetration depth while providing the capability of optical sectioning. Although femtosecond solid-state lasers have been widely accepted as the standard option as MPM driving sources, fiber-based sources have received growing research efforts due to their superior performance. In the second part of this thesis, we both theoretically and experimentally demonstrated a new method of producing wavelength widely tunable femtosecond pulses for driving MPM. We employed self-phase modulation to broaden a narrowband spectrum followed by bandpass filters to select the rightmost/leftmost spectral lobes. Widely tunable in 820-1225 nm, the resulting sources generated nearly transform-limited, ∝100 fs pulses. Using short fibers with large

Octave-Spanning Mid-IR Supercontinuum Generation with Ultrafast Cascaded Nonlinearities

DEFF Research Database (Denmark)

Zhou, Binbin; Guo, Hairun; Liu, Xing

2014-01-01

An octave-spanning mid-IR supercontinuum is observed experimentally using ultrafast cascaded nonlinearities in an LiInS2 quadratic nonlinear crystal pumped with 70 fs energetic mid-IR pulses and cut for strongly phase-mismatched second-harmonic generation.......An octave-spanning mid-IR supercontinuum is observed experimentally using ultrafast cascaded nonlinearities in an LiInS2 quadratic nonlinear crystal pumped with 70 fs energetic mid-IR pulses and cut for strongly phase-mismatched second-harmonic generation....

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Directory of Open Access Journals (Sweden)

Tsuyoshi Okura

2017-01-01

Full Text Available Objective. Advanced glycation end products (AGEs are important in the pathophysiology of type 2 diabetes mellitus (T2DM. They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL, carboxymethyllysine (CML, and methyl-glyoxal-hydro-imidazolone (MG-H1. Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes.

Photonic-assisted ultrafast THz wireless access

DEFF Research Database (Denmark)

Yu, Xianbin; Chen, Ying; Galili, Michael

THz technology has been considered feasible for ultrafast wireless data communi- cation, to meet the increasing demand on next-generation fast wireless access, e.g., huge data file transferring and fast mobile data stream access. This talk reviews recent progress in high-speed THz wireless...

[The effect of mineral water on serotonin and insulin production (an experimental study)].

Science.gov (United States)

Polushina, N D

1998-01-01

Radioimmunoassay (DRG kits) and orthotoluidine test were conducted to measure blood serotonin, insulin and glucose in 70 intact Wistar rat males before and after a course of drinking mineral water Essentuki 17 (MW). After the MW drinking course, a single dose of mineral water increases basal levels of serotonin and insulin, sensitivity of endocrine cells to MW. Serotonin and insulin rose maximally on minute 5 after the drink while in contrast to minute 15 and 30 before initiation of the MW drinking course. A direct correlation was found between blood concentrations of serotonin and insulin.

Discrete decoding based ultrafast multidimensional nuclear magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Wei, Zhiliang; Lin, Liangjie; Ye, Qimiao; Li, Jing; Cai, Shuhui; Chen, Zhong

2015-01-01

The three-dimensional (3D) nuclear magnetic resonance (NMR) spectroscopy constitutes an important and powerful tool in analyzing chemical and biological systems. However, the abundant 3D information arrives at the expense of long acquisition times lasting hours or even days. Therefore, there has been a continuous interest in developing techniques to accelerate recordings of 3D NMR spectra, among which the ultrafast spatiotemporal encoding technique supplies impressive acquisition speed by compressing a multidimensional spectrum in a single scan. However, it tends to suffer from tradeoffs among spectral widths in different dimensions, which deteriorates in cases of NMR spectroscopy with more dimensions. In this study, the discrete decoding is proposed to liberate the ultrafast technique from tradeoffs among spectral widths in different dimensions by focusing decoding on signal-bearing sites. For verifying its feasibility and effectiveness, we utilized the method to generate two different types of 3D spectra. The proposed method is also applicable to cases with more than three dimensions, which, based on the experimental results, may widen applications of the ultrafast technique

Discrete decoding based ultrafast multidimensional nuclear magnetic resonance spectroscopy

Science.gov (United States)

Wei, Zhiliang; Lin, Liangjie; Ye, Qimiao; Li, Jing; Cai, Shuhui; Chen, Zhong

2015-07-01

The three-dimensional (3D) nuclear magnetic resonance (NMR) spectroscopy constitutes an important and powerful tool in analyzing chemical and biological systems. However, the abundant 3D information arrives at the expense of long acquisition times lasting hours or even days. Therefore, there has been a continuous interest in developing techniques to accelerate recordings of 3D NMR spectra, among which the ultrafast spatiotemporal encoding technique supplies impressive acquisition speed by compressing a multidimensional spectrum in a single scan. However, it tends to suffer from tradeoffs among spectral widths in different dimensions, which deteriorates in cases of NMR spectroscopy with more dimensions. In this study, the discrete decoding is proposed to liberate the ultrafast technique from tradeoffs among spectral widths in different dimensions by focusing decoding on signal-bearing sites. For verifying its feasibility and effectiveness, we utilized the method to generate two different types of 3D spectra. The proposed method is also applicable to cases with more than three dimensions, which, based on the experimental results, may widen applications of the ultrafast technique.

Tracking ultrafast relaxation dynamics of furan by femtosecond photoelectron imaging

Energy Technology Data Exchange (ETDEWEB)

Liu, Yuzhu, E-mail: yuzhu.liu@gmail.com [School of Physics and Optoelectronic Engineering, Nanjing University of Information Science and Technology, Nanjing 210044 (China); Knopp, Gregor [Paul Scherrer Institute, Villigen 5232 (Switzerland); Qin, Chaochao [Department of Physics, Henan Normal University, Xinxiang 453007 (China); Gerber, Thomas [Paul Scherrer Institute, Villigen 5232 (Switzerland)

2015-01-13

Graphical abstract: - Highlights: • Relaxation dynamics of furan are tracked by femtosecond photoelectron imaging. • The mechanism for ultrafast formation of α-carbene and β-carbene is proposed. • Ultrafast internal conversion from S{sub 2} to S{sub 1} is observed. • The transient characteristics of the fragment ions are obtained. • Single-color multi-photon ionization dynamics at 800 nm are also studied. - Abstract: Ultrafast internal conversion dynamics of furan has been studied by femtosecond photoelectron imaging (PEI) coupled with photofragmentation (PF) spectroscopy. Photoelectron imaging of single-color multi-photon ionization and two-color pump–probe ionization are obtained and analyzed. Photoelectron bands are assigned to the related states. The time evolution of the photoelectron signal by pump–probe ionization can be well described by a biexponential decay: two rapid relaxation pathways with time constants of ∼15 fs and 85 (±11) fs. The rapid relaxation is ascribed to the ultrafast internal conversion (IC) from the S{sub 2} state to the vibrationally hot S{sub 1} state. The second relaxation process is attributed to the redistributions and depopulation of secondarily populated high vibronic S{sub 1} state and the formation of α-carbene and β-carbene by H immigration. Additionally, the transient characteristics of the fragment ions are also measured and discussed as a complementary understanding.

Ultrafast pulse lasers jump to macro applications

Science.gov (United States)

Griebel, Martin; Lutze, Walter; Scheller, Torsten

2016-03-01

Ultrafast Lasers have been proven for several micro applications, e.g. stent cutting, for many years. Within its development of applications Jenoptik has started to use ultrafast lasers in macro applications in the automotive industry. The JenLas D2.fs-lasers with power output control via AOM is an ideal tool for closed loop controlled material processing. Jenoptik enhanced his well established sensor controlled laser weakening process for airbag covers to a new level. The patented process enables new materials using this kind of technology. One of the most sensitive cover materials is genuine leather. As a natural product it is extremely inhomogeneous and sensitive for any type of thermal load. The combination of femtosecond pulse ablation and closed loop control by multiple sensor array opens the door to a new quality level of defined weakening. Due to the fact, that the beam is directed by scanning equipment the process can be split in multiple cycles additionally reducing the local energy input. The development used the 5W model as well as the latest 10W release of JenLas D2.fs and achieved amazing processing speeds which directly fulfilled the requirements of the automotive industry. Having in mind that the average cycle time of automotive processes is about 60s, trials had been done of processing weakening lines in genuine leather of 1.2mm thickness. Parameters had been about 15 cycles with 300mm/s respectively resulting in an average speed of 20mm/s and a cycle time even below 60s. First samples had already given into functional and aging tests and passed successfully.

Ultrafast photocurrents in monolayer MoS2

Science.gov (United States)

Parzinger, Eric; Wurstbauer, Ursula; Holleitner, Alexander W.

Two-dimensional transition metal dichalcogenides such as MoS2 have emerged as interesting materials for optoelectronic devices. In particular, the ultrafast dynamics and lifetimes of photoexcited charge carriers have attracted great interest during the last years. We investigate the photocurrent response of monolayer MoS2 on a picosecond time scale utilizing a recently developed pump-probe spectroscopy technique based on coplanar striplines. We discuss the ultrafast dynamics within MoS2 including photo-thermoelectric currents and the impact of built-in fields due to Schottky barriers as well as the Fermi level pinning at the contact region. We acknowledge support by the ERC via Project 'NanoREAL', the DFG via excellence cluster 'Nanosystems Initiative Munich' (NIM), and through the TUM International Graduate School of Science and Engineering (IGSSE) and BaCaTeC.

Improvement of glycaemic control and elevation of C-peptide following a diet free of dairy products in an insulin-treated, patient with type 2 diabetes with ulcerative colitis.

Science.gov (United States)

Tandeter, Howard

2009-01-01

An insulin-treated patient with type 2 diabetes mellitus started a diet free of dairy products. Unexpectedly, she developed episodes of hypoglycaemia, without any change in her usual medication (insulin NPH at bedtime and Metformin). Laboratory tests showed an improvement of endogenous insulin secretion as demonstrated by the induction of hypoglycaemia and the elevation to normalisation of C-peptide levels. The patient was rechallenged with dairy products, leading to the lowering of the C-peptide levels back to abnormal levels, and an increase in HBA1C levels. The findings in our patient contrast with the insulinotropic effect of milk in healthy subjects described in the literature. The two main "milk debates" on the relation between milk (or its components) and diabetes are presented. Further observations will be needed to clarify the question of whether a diet free of dairy products can improve glycaemic control in other insulin-treated patients with type 2 diabetes.

Ultrafast spectroscopy of model biological membranes

NARCIS (Netherlands)

Ghosh, Avishek

2009-01-01

In this PhD thesis, I have described the novel time-resolved sum-frequency generation (TR-SFG) spectroscopic technique that I developed during the course of my PhD research and used it study the ultrafast vibrational, structural and orientational dynamics of water molecules at model biological

Effect of ballistic electrons on ultrafast thermomechanical responses of a thin metal film

International Nuclear Information System (INIS)

Xiong Qi-lin; Tian Xin

2017-01-01

The ultrafast thermomechanical coupling problem in a thin gold film irradiated by ultrashort laser pulses with different electron ballistic depths is investigated via the ultrafast thermoelasticity model. The solution of the problem is obtained by solving finite element governing equations. The comparison between the results of ultrafast thermomechanical coupling responses with different electron ballistic depths is made to show the ballistic electron effect. It is found that the ballistic electrons have a significant influence on the ultrafast thermomechanical coupling behaviors of the gold thin film and the best laser micromachining results can be achieved by choosing the specific laser technology (large or small ballistic range). In addition, the influence of simplification of the ultrashort laser pulse source on the results is studied, and it is found that the simplification has a great influence on the thermomechanical responses, which implies that care should be taken when the simplified form of the laser source term is applied as the Gaussian heat source. (paper)

Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-α both in vitro and in vivo systems

Science.gov (United States)

Vassiliou, Evros K; Gonzalez, Andres; Garcia, Carlos; Tadros, James H; Chakraborty, Goutam; Toney, Jeffrey H

2009-01-01

Background Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-α in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy. Methods The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-α and oleic acid treated cells was evaluated using flow cytometry. PPAR-γ translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer. Results Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-α inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-α and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid. Conclusion

Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems.

Science.gov (United States)

Vassiliou, Evros K; Gonzalez, Andres; Garcia, Carlos; Tadros, James H; Chakraborty, Goutam; Toney, Jeffrey H

2009-06-26

Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-alpha in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy. The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-alpha and oleic acid treated cells was evaluated using flow cytometry. PPAR-gamma translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer. Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-alpha inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-alpha and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid. Oleic acid was found to

Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

DEFF Research Database (Denmark)

Jing, Enxuan; Emanuelli, Brice; Hirschey, Matthew D

2011-01-01

Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout...... mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species......, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle....

Cutting-Edge High-Power Ultrafast Thin Disk Oscillators

Directory of Open Access Journals (Sweden)

Thomas Südmeyer

2013-04-01

Full Text Available A growing number of applications in science and industry are currently pushing the development of ultrafast laser technologies that enable high average powers. SESAM modelocked thin disk lasers (TDLs currently achieve higher pulse energies and average powers than any other ultrafast oscillator technology, making them excellent candidates in this goal. Recently, 275 W of average power with a pulse duration of 583 fs were demonstrated, which represents the highest average power so far demonstrated from an ultrafast oscillator. In terms of pulse energy, TDLs reach more than 40 μJ pulses directly from the oscillator. In addition, another major milestone was recently achieved, with the demonstration of a TDL with nearly bandwidth-limited 96-fs long pulses. The progress achieved in terms of pulse duration of such sources enabled the first measurement of the carrier-envelope offset frequency of a modelocked TDL, which is the first key step towards full stabilization of such a source. We will present the key elements that enabled these latest results, as well as an outlook towards the next scaling steps in average power, pulse energy and pulse duration of such sources. These cutting-edge sources will enable exciting new applications, and open the door to further extending the current performance milestones.

Ultrafast photoinduced charge separation in metal-semiconductor nanohybrids.

Science.gov (United States)

Mongin, Denis; Shaviv, Ehud; Maioli, Paolo; Crut, Aurélien; Banin, Uri; Del Fatti, Natalia; Vallée, Fabrice

2012-08-28

Hybrid nano-objects formed by two or more disparate materials are among the most promising and versatile nanosystems. A key parameter in their properties is interaction between their components. In this context we have investigated ultrafast charge separation in semiconductor-metal nanohybrids using a model system of gold-tipped CdS nanorods in a matchstick architecture. Experiments are performed using an optical time-resolved pump-probe technique, exciting either the semiconductor or the metal component of the particles, and probing the light-induced change of their optical response. Electron-hole pairs photoexcited in the semiconductor part of the nanohybrids are shown to undergo rapid charge separation with the electron transferred to the metal part on a sub-20 fs time scale. This ultrafast gold charging leads to a transient red-shift and broadening of the metal surface plasmon resonance, in agreement with results for free clusters but in contrast to observation for static charging of gold nanoparticles in liquid environments. Quantitative comparison with a theoretical model is in excellent agreement with the experimental results, confirming photoexcitation of one electron-hole pair per nanohybrid followed by ultrafast charge separation. The results also point to the utilization of such metal-semiconductor nanohybrids in light-harvesting applications and in photocatalysis.

Advanced Instrumentation for Ultrafast Science at the LCLS

Energy Technology Data Exchange (ETDEWEB)

Berrah, Nora [Univ. of Connecticut, Storrs, CT (United States)

2015-10-13

This grant supported a Single Investigator and Small Group Research (SISGR) application to enable multi-user research in Ultrafast Science using the Linac Coherent Light Source (LCLS), the world’s first hard x-ray free electron laser (FEL) which lased for the first time at 1.5 Å on April 20, 2009. The goal of our proposal was to enable a New Era of Science by requesting funds to purchase and build Advanced Instrumentation for Ultrafast Science (AIUS), to utilize the intense, short x-ray pulses produced by the LCLS. The proposed instrumentation will allow peer review selected users to probe the ultrasmall and capture the ultrafast. These tools will expand on the investment already made in the construction of the light source and its instrumentation in both the LCLS and LUSI projects. The AIUS will provide researchers in the AMO, Chemical, Biological and Condensed Matter communities with greater flexibility in defining their scientific agenda at the LCLS. The proposed instrumentation will complement and significantly augment the present AMO instrument (funded through the LCLS project) through detectors and capabilities not included in the initial suite of instrumentation at the facility. We have built all of the instrumentations and they have been utilized by scientists. Please see report attached.

Feasibility of UltraFast Doppler in Post-operative Evaluation of Hepatic Artery in Recipients following Liver Transplantation.

Science.gov (United States)

Kim, Se-Young; Kim, Kyoung Won; Choi, Sang Hyun; Kwon, Jae Hyun; Song, Gi-Won; Kwon, Heon-Ju; Yun, Young Ju; Lee, Jeongjin; Lee, Sung-Gyu

2017-11-01

To determine the feasibility of using UltraFast Doppler in post-operative evaluation of the hepatic artery (HA) after liver transplantation (LT), we evaluated 283 simultaneous conventional and UltraFast Doppler sessions in 126 recipients over a 2-mo period after LT, using an Aixplorer scanner The Doppler indexes of the HA (peak systolic velocity [PSV], end-diastolic velocity [EDV], resistive index [RI] and systolic acceleration time [SAT]) by retrospective analysis of retrieved waves from UltraFast Doppler clips were compared with those obtained by conventional spectral Doppler. Correlation, performance in diagnosing the pathologic wave, examination time and reproducibility were evaluated. The PSV, EDV, RI and SAT of spectral and UltraFast Doppler measurements exhibited excellent correlation with favorable diagnostic performance. During the bedside examination, the mean time spent for UltraFast clip storing was significantly shorter than that for conventional Doppler US measurements. Both conventional and UltraFast Doppler exhibited good to excellent inter-analysis consistency. In conclusion, compared with conventional spectral Doppler, UltraFast Doppler values correlated excellently and yielded acceptable pathologic wave diagnostic performance with reduced examination time at the bedside and excellent reproducibility. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

High-speed ultrafast laser machining with tertiary beam positioning (Conference Presentation)

Science.gov (United States)

Yang, Chuan; Zhang, Haibin

2017-03-01

For an industrial laser application, high process throughput and low average cost of ownership are critical to commercial success. Benefiting from high peak power, nonlinear absorption and small-achievable spot size, ultrafast lasers offer advantages of minimal heat affected zone, great taper and sidewall quality, and small via capability that exceeds the limits of their predecessors in via drilling for electronic packaging. In the past decade, ultrafast lasers have both grown in power and reduced in cost. For example, recently, disk and fiber technology have both shown stable operation in the 50W to 200W range, mostly at high repetition rate (beyond 500 kHz) that helps avoid detrimental nonlinear effects. However, to effectively and efficiently scale the throughput with the fast-growing power capability of the ultrafast lasers while keeping the beneficial laser-material interactions is very challenging, mainly because of the bottleneck imposed by the inertia-related acceleration limit and servo gain bandwidth when only stages and galvanometers are being used. On the other side, inertia-free scanning solutions like acoustic optics and electronic optical deflectors have small scan field, and therefore not suitable for large-panel processing. Our recent system developments combine stages, galvanometers, and AODs into a coordinated tertiary architecture for high bandwidth and meanwhile large field beam positioning. Synchronized three-level movements allow extremely fast local speed and continuous motion over the whole stage travel range. We present the via drilling results from such ultrafast system with up to 3MHz pulse to pulse random access, enabling high quality low cost ultrafast machining with emerging high average power laser sources.

Ultrafast Photoinduced Electron Transfer in a π-Conjugated Oligomer/Porphyrin Complex

KAUST Repository

Aly, Shawkat Mohammede

2014-10-02

Controlling charge transfer (CT), charge separation (CS), and charge recombination (CR) at the donor-acceptor interface is extremely important to optimize the conversion efficiency in solar cell devices. In general, ultrafast CT and slow CR are desirable for optimal device performance. In this Letter, the ultrafast excited-state CT between platinum oligomer (DPP-Pt(acac)) as a new electron donor and porphyrin as an electron acceptor is monitored for the first time using femtosecond (fs) transient absorption (TA) spectroscopy with broad-band capability and 120 fs temporal resolution. Turning the CT on/off has been shown to be possible either by switching from an organometallic oligomer to a metal-free oligomer or by controlling the charge density on the nitrogen atom of the porphyrin meso unit. Our time-resolved data show that the CT and CS between DPP-Pt(acac) and cationic porphyrin are ultrafast (approximately 1.5 ps), and the CR is slow (ns time scale), as inferred from the formation and the decay of the cationic and anionic species. We also found that the metallic center in the DPP-Pt(acac) oligomer and the positive charge on the porphyrin are the keys to switching on/off the ultrafast CT process.

Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

Science.gov (United States)

Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

2011-01-01

The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

International Nuclear Information System (INIS)

Naidoo, C.

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

Energy Technology Data Exchange (ETDEWEB)

Naidoo, C

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, /sup 125/I-insulin binding to the solubilized erythrocyte membrane receptor and /sup 125/I-insulin binding to fibroblasts in culture.

Progress in ultrafast intense laser science XIII

CERN Document Server

III, Wendell; Paulus, Gerhard

2017-01-01

This thirteenth volume covers a broad range of topics from this interdisciplinary research field, focusing on atoms, molecules, and clusters interacting in intense laser field and high-order harmonics generation and their applications. The PUILS series delivers up-to-date reviews of progress in Ultrafast Intense Laser Science, the interdisciplinary research field spanning atomic and molecular physics, molecular science, and optical science, which has been stimulated by the recent developments in ultrafast laser technologies. Each volume compiles peer-reviewed articles authored by researchers at the forefront of each their own subfields of UILS. Every chapter opens with an overview of the topics to be discussed, so that researchers unfamiliar to the subfield, as well as graduate students, can grasp the importance and attractions of the research topic at hand; these are followed by reports of cutting-edge discoveries.   .

Progress in ultrafast intense laser science XII

CERN Document Server

Roso, Luis; Li, Ruxin; Mathur, Deepak; Normand, Didier

2015-01-01

This  volume covers a broad range of topics focusing on atoms, molecules, and clusters interacting in intense laser field, laser induced filamentation, and laser plasma interaction and application. The PUILS series delivers up-to-date reviews of progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science, and optical science, which has been stimulated by the recent developments in ultrafast laser technologies. Each volume compiles peer-reviewed articles authored by researchers at the forefront of each their own subfields of UILS. Every chapter opens with an overview of the topics to be discussed, so that researchers unfamiliar to the subfield, as well as graduate students, can grasp the importance and attractions of the research topic at hand; these are followed by reports of cutting-edge discoveries. .

Ultrafast electron diffraction with megahertz MeV electron pulses from a superconducting radio-frequency photoinjector

Energy Technology Data Exchange (ETDEWEB)

Feng, L. W.; Lin, L.; Huang, S. L.; Quan, S. W.; Hao, J. K.; Zhu, F.; Wang, F.; Liu, K. X., E-mail: kxliu@pku.edu.cn [Institute of Heavy Ion Physics and State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Jiang, T.; Zhu, P. F.; Fu, F.; Wang, R.; Zhao, L.; Xiang, D., E-mail: dxiang@sjtu.edu.cn [Key Laboratory for Laser Plasmas (Ministry of Education), Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240 (China); IFSA Collaborative Innovation Center, Shanghai Jiao Tong University, Shanghai 200240 (China)

2015-11-30

We report ultrafast relativistic electron diffraction operating at the megahertz repetition rate where the electron beam is produced in a superconducting radio-frequency (rf) photoinjector. We show that the beam quality is sufficiently high to provide clear diffraction patterns from gold and aluminium samples. With the number of electrons, several orders of magnitude higher than that from a normal conducting photocathode rf gun, such high repetition rate ultrafast MeV electron diffraction may open up many new opportunities in ultrafast science.

Advanced ultrafast fiber laser sources enabled by fiber nonlinearities

Energy Technology Data Exchange (ETDEWEB)

Liu, Wei

2017-05-15

Development of high power/energy ultrafast fiber lasers for scientific research and industrial applications is one of the most exciting fields in ultrafast optics. This thesis demonstrated new means to improve two essential properties - which are indispensable for novel applications such as high-harmonic generation (HHG) and multiphoton microscopy (MPM) - of an ultrafast fiber laser system: energy scaling capability and wavelength tunability. High photon-flux extreme ultraviolet sources enabled by HHG desire high power (>100 W), high repetition-rate (>1 MHz) ultrafast driving laser sources. We have constructed from scratch a high-power Yb-fiber laser system using the well-known chirped-pulse amplification (CPA) technique. Such a CPA system capable of producing ∝200-W average power consists of a monolithic Yb-fiber oscillator, an all-fiber stretcher, a pre-amplifier chain, a main amplifier constructed from rode-type large pitch fiber, and a diffraction-grating based compressor. To increase the HHG efficiency, ultrafast pulses with duration <60 fs are highly desired. We proposed and demonstrated a novel amplification technique, named as pre-chirp managed amplification (PCMA). We successfully constructed an Yb-fiber based PCMA system that outputs 75-MHz spectrally broadened pulses with >130-W average power. The amplified pulses are compressed to 60-fs pulses with 100-W average power, constituting a suitable HHG driving source. MPM is a powerful biomedical imaging tool, featuring larger penetration depth while providing the capability of optical sectioning. Although femtosecond solid-state lasers have been widely accepted as the standard option as MPM driving sources, fiber-based sources have received growing research efforts due to their superior performance. In the second part of this thesis, we both theoretically and experimentally demonstrated a new method of producing wavelength widely tunable femtosecond pulses for driving MPM. We employed self-phase modulation

Environmental arsenic as a disruptor of insulin signaling

OpenAIRE

Paul, David S.; Devesa, Vicenta; Hernandez-Zavala, Araceli; Adair, Blakely M.; Walton, Felecia S.; Drobnâ, Zuzana; Thomas, David J.; Styblo, Miroslav

2008-01-01

Previous laboratory studies have shown that exposures to inorganic As (iAs) disrupt insulin production or glucose metabolism in cellular and animal models. Epidemiological evidence has also linked chronic human exposures to iAs to an increased risk of diabetes mellitus, a metabolic disease characterized by impaired glucose tolerance and insulin resistance. We have recently shown that arsenite and its methylated metabolites inhibit insulin-stimulated glucose uptake in cultured adipocytes by di...

Degludec insulin: A novel basal insulin

OpenAIRE

Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

2011-01-01

This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

Fast and ultrafast MR-imaging of the heart

International Nuclear Information System (INIS)

Schulthess, G.K. von; Davis, C.P.; Debatin, J.F.; McKinnon, G.C.

1995-01-01

MRI has been hampered by long image acquisition times. This combined with its non-realtime nature and the limited spatial resolution has made it difficult to extend MRT to the study of small cardiac structures. Recent technical improvements have made breath-held or realtime MRI feasible and thus laid the foundations for further applications in the field of cardiovascular imaging, notably MR coronary angiography, imaging of cardiac valve leaflets, as well as firstpass perfusion studies. Moreover ultrafast MR techniques may eventually replace conventional data acquisition strategies and thus drastically increase patient throughput by shortening acquisition time. This article provides an overview of the technical advances in MRI and their application to the cardiovascular system and discusses possibilities of combined ultrafast and interventional strategies. (orig.) [de

Production of functional human insulin-like growth factor binding proteins (IGFBPs) using recombinant expression in HEK293 cells

DEFF Research Database (Denmark)

Wanscher, Anne Sofie Molsted; Williamson, Michael; Ebersole, Tasja Wainani

2015-01-01

on human proteins with therapeutic relevance is needed to design and process the next generation of protein therapeutics. In order to conduct structural and functional investigations large quantities of recombinant proteins are needed. However, finding a suitable recombinant production system for proteins...... and the final protein yields were between 1 and 12mg protein per liter culture media. The recombinant IGFBPs contained PTMs and exhibited high-affinity interactions with their natural ligands IGF-1 and IGF-2.......Insulin-like growth factor binding proteins (IGFBPs) display many functions in humans including regulation of the insulin-like growth factor (IGF) signaling pathway. The various roles of human IGFBPs make them attractive protein candidates in drug discovery. Structural and functional knowledge...

Quantum Computation with Ultrafast Laser Pulse Shaping

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 6. Quantum Computation with Ultrafast Laser Pulse Shaping. Debabrata Goswami. General Article Volume 10 Issue 6 June 2005 pp 8-14. Fulltext. Click here to view fulltext PDF. Permanent link:

Multiple growth hormone-binding proteins are expressed on insulin-producing cells

DEFF Research Database (Denmark)

Møldrup, A; Billestrup, N; Thorn, N A

1989-01-01

The insulin-producing rat islet tumor cell line, RIN-5AH, expresses somatogen binding sites and responds to GH by increased proliferation and insulin production. Affinity cross-linking shows that RIN-5AH cells contain two major GH-binding subunits of Mr 100-130K (110K), which appear to exist as d....... It is concluded that the RIN-5AH cells have multiple GH-binding proteins which may mediate signals for either proliferation and/or insulin production....

Palmitate and insulin synergistically induce IL-6 expression in human monocytes

Directory of Open Access Journals (Sweden)

Lumpkin Charles K

2010-11-01

Full Text Available Abstract Background Insulin resistance is associated with a proinflammatory state that promotes the development of complications such as type 2 diabetes mellitus (T2DM and atherosclerosis. The metabolic stimuli that initiate and propagate proinflammatory cytokine production and the cellular origin of proinflammatory cytokines in insulin resistance have not been fully elucidated. Circulating proinflammatory monocytes show signs of enhanced inflammation in obese, insulin resistant subjects and are thus a potential source of proinflammatory cytokine production. The specific, circulating metabolic factors that might stimulate monocyte inflammation in insulin resistant subjects are poorly characterized. We have examined whether saturated nonesterified fatty acids (NEFA and insulin, which increase in concentration with developing insulin resistance, can trigger the production of interleukin (IL-6 and tumor necrosis factor (TNF-α in human monocytes. Methods Messenger RNA and protein levels of the proinflammatory cytokines IL-6 and TNF-α were measured by quantitative real-time PCR (qRT-PCR and Luminex bioassays. Student's t-test was used with a significance level of p Results Esterification of palmitate with coenzyme A (CoA was necessary, while β-oxidation and ceramide biosynthesis were not required, for the induction of IL-6 and TNF-α in THP-1 monocytes. Monocytes incubated with insulin and palmitate together produced more IL-6 mRNA and protein, and more TNF-α protein, compared to monocytes incubated with palmitate alone. Incubation of monocytes with insulin alone did not affect the production of IL-6 or TNF-α. Both PI3K-Akt and MEK/ERK signalling pathways are important for cytokine induction by palmitate. MEK/ERK signalling is necessary for synergistic induction of IL-6 by palmitate and insulin. Conclusions High levels of saturated NEFA, such as palmitate, when combined with hyperinsulinemia, may activate human monocytes to produce

Design of ultra-stable insulin analogues for the developing world

Directory of Open Access Journals (Sweden)

Michael A Weiss

2013-01-01

Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

Detection of coronary calcification in ultrafast CT compared to coronary angiography

International Nuclear Information System (INIS)

Koesling, S.; Hoffmann, U.; Rother, T.; Lieberenz, S.; Heywang-Koebrunner, S.H.; Schulz, H.G.

1994-01-01

The angiographical findings of 24 patients with coronary artery disease were compared with qualitative and quantitative detection of coronary calcification by ultrafast CT. Doubts concerning the capabilities of the ultrafast CT for a screening of coronary artery disease arise when the results of one third false positive and fase negative findings are considered. Variations in the quantification of coronary calcification were too great to allow a realistic assessment of the degree of stenosis of the coronary arteries. (orig.) [de

Propagation of complex shaped ultrafast pulses in highly optically dense samples

International Nuclear Information System (INIS)

Davis, J. C.; Fetterman, M. R.; Warren, W. S.; Goswami, D.

2008-01-01

We examine the propagation of shaped (amplitude- and frequency-modulated) ultrafast laser pulses through optically dense rubidium vapor. Pulse reshaping, stimulated emission dynamics, and residual electronic excitation all strongly depend on the laser pulse shape. For example, frequency swept pulses, which produce adiabatic passage in the optically thin limit (independent of the sign of the frequency sweep), behave unexpectedly in optically dense samples. Paraxial Maxwell optical Bloch equations can model our ultrafast pulse propagation results well and provide insight

BSSF: a fingerprint based ultrafast binding site similarity search and function analysis server

Directory of Open Access Journals (Sweden)

Jiang Hualiang

2010-01-01

Full Text Available Abstract Background Genome sequencing and post-genomics projects such as structural genomics are extending the frontier of the study of sequence-structure-function relationship of genes and their products. Although many sequence/structure-based methods have been devised with the aim of deciphering this delicate relationship, there still remain large gaps in this fundamental problem, which continuously drives researchers to develop novel methods to extract relevant information from sequences and structures and to infer the functions of newly identified genes by genomics technology. Results Here we present an ultrafast method, named BSSF(Binding Site Similarity & Function, which enables researchers to conduct similarity searches in a comprehensive three-dimensional binding site database extracted from PDB structures. This method utilizes a fingerprint representation of the binding site and a validated statistical Z-score function scheme to judge the similarity between the query and database items, even if their similarities are only constrained in a sub-pocket. This fingerprint based similarity measurement was also validated on a known binding site dataset by comparing with geometric hashing, which is a standard 3D similarity method. The comparison clearly demonstrated the utility of this ultrafast method. After conducting the database searching, the hit list is further analyzed to provide basic statistical information about the occurrences of Gene Ontology terms and Enzyme Commission numbers, which may benefit researchers by helping them to design further experiments to study the query proteins. Conclusions This ultrafast web-based system will not only help researchers interested in drug design and structural genomics to identify similar binding sites, but also assist them by providing further analysis of hit list from database searching.

Complete elimination of nonlinear light-matter interactions with broadband ultrafast laser pulses

DEFF Research Database (Denmark)

Shu, Chuan-Cun; Dong, Daoyi; Petersen, Ian R.

2017-01-01

optical effects, however, the probability of pure single-photon absorption is usually very low, which is particularly pertinent in the case of strong ultrafast laser pulses with broad bandwidth. Here we demonstrate theoretically a counterintuitive coherent single-photon absorption scheme by eliminating...... nonlinear interactions of ultrafast laser pulses with quantum systems. That is, a completely linear response of the system with respect to the spectral energy density of the incident light at the transition frequency can be obtained for all transition probabilities between 0 and 100% in multilevel quantum...... systems. To that end, a multiobjective optimization algorithm is developed to find an optimal spectral phase of an ultrafast laser pulse, which is capable of eliminating all possible nonlinear optical responses while maximizing the probability of single-photon absorption between quantum states. This work...

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

Science.gov (United States)

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production

DEFF Research Database (Denmark)

Lee, Ying Shiuan; De Vadder, Filipe; Tremaroli, Valentina

2016-01-01

expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5......-/- and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5-/- mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5-/- mice. CONCLUSIONS: We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy...... availability. We propose that INSL5 is a hormone that could play a role in promoting hepatic glucose production during periods of energy deprivation....

OSA Trends in Optics and Photonics Series. Volume 13: Ultrafast Electronics and Optoelectronics

Science.gov (United States)

1997-01-01

tomography. Many materials such as plastics, cardboard, wood and rubber have good transparency in the terahertz frequency range. Hence, this new...Ultrafast processes in semiconductors. Introduction Nonlinear Bragg reflector ( NBR ) consists of periodically distributed optical nonlinearity coexisting...with multiple reflection and group-delay dispersion. Recent theoretical analyses showed the potential of NBR in ultrafast optoelectronics such as all

Ultrafast secondary emission x-ray imaging detectors

International Nuclear Information System (INIS)

Akkerman, A.; Gibrekhterman, A.; Majewski, S.

1991-07-01

Fast high accuracy, x-ray imaging at high photon flux can be achieved when coupling thin solid convertors to gaseous electron multipliers, operating at low gas pressures. Secondary electron emitted from the convertor foil are multiplied in several successive amplification elements. The obvious advantage of solid x-ray detectors, as compared to gaseous conversion, are the production of parallax-free images and the fast (subnanoseconds) response. These x-ray detectors have many potential applications in basic and applied research. Of particular interest is the possibility of an efficient and ultrafast high resolution imaging of transition radiation,with a reduced dE/dx background. We present experimental results on the operation of the secondary emission x-ray (SEX) detectors, their detection efficiency, localization and time resolution. The experimental work is accompanied by mathematical modelling and computer simulation of transition radiation detectors based on CsI transition radiation convertors. (author)

Progress in Ultrafast Intense Laser Science III

CERN Document Server

Yamanouchi, Kaoru; Agostini, Pierre; Ferrante, Gaetano

2008-01-01

The PUILS series presents Progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science, and optical science. PUILS has been stimulated by the recent development of ultrafast laser technologies. Each volume contains approximately 15 chapters, authored by researchers at the forefront. Each chapter opens with an overview of the topics to be discussed, so that researchers, who are not experts in the specific topics, as well as graduate students can grasp the importance and attractions of this sub-field of research, and these are followed by reports of cutting-edge discoveries. This third volume covers a diverse range of disciplines, focusing on such topics as strong field ionization of atoms, ionization and fragmentation of molecules and clusters, generation of high-order harmonics and attosecond pulses, filamentation and laser plasma interaction, and the development of ultrashort and ultrahigh-intensity light sources.

Progress in Ultrafast Intense Laser Science VIII

CERN Document Server

Nisoli, Mauro; Hill, Wendell; III, III

2012-01-01

The PUILS series delivers up-to-date reviews of progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science and optical science which has been stimulated by the recent developments in ultrafast laser technologies. Each volume compiles peer-reviewed articles authored by researchers at the forefront of each their own subfields of UILS. Every chapter opens with an overview of the topics to be discussed, so that researchers unfamiliar to the subfield as well as graduate students can grasp the importance and attractions of the research topic at hand. These are followed by reports of cutting-edge discoveries. This eighth volume covers a broad range of topics from this interdisciplinary research field, focusing on molecules interacting with ultrashort and intense laser fields, advanced technologies for the characterization of ultrashort laser pulses and their applications, laser plasma formation and laser acceleration.

Progress in Ultrafast Intense Laser Science VI

CERN Document Server

Yamanouchi, Kaoru; Bandrauk, André D

2010-01-01

The PUILS series delivers up-to-date reviews of progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science, and optical science, which has been stimulated by the recent developments in ultrafast laser technologies. Each volume compiles peer-reviewed articles authored by researchers at the forefront of each their own subfields of UILS. Every chapter opens with an overview of the topics to be discussed, so that researchers unfamiliar to the subfield, as well as graduate students, can grasp the importance and attractions of the research topic at hand; these are followed by reports of cutting-edge discoveries. This sixth volume covers a broad range of topics from this interdisciplinary research field, focusing on responses of molecules to ultrashort intense laser pulses, generation and characterization of attosecond pulses and high-order harmonics, and filamentation and laser-plasma interaction.

Insulin resistance in obesity as the underlying cause for the metabolic syndrome.

Science.gov (United States)

Gallagher, Emily J; Leroith, Derek; Karnieli, Eddy

2010-01-01

The metabolic syndrome affects more than a third of the US population, predisposing to the development of type 2 diabetes and cardiovascular disease. The 2009 consensus statement from the International Diabetes Federation, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, and the National Heart, Lung, and Blood Institute defines the metabolic syndrome as 3 of the following elements: abdominal obesity, elevated blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia. Many factors contribute to this syndrome, including decreased physical activity, genetic predisposition, chronic inflammation, free fatty acids, and mitochondrial dysfunction. Insulin resistance appears to be the common link between these elements, obesity and the metabolic syndrome. In normal circumstances, insulin stimulates glucose uptake into skeletal muscle, inhibits hepatic gluconeogenesis, and decreases adipose-tissue lipolysis and hepatic production of very-low-density lipoproteins. Insulin signaling in the brain decreases appetite and prevents glucose production by the liver through neuronal signals from the hypothalamus. Insulin resistance, in contrast, leads to the release of free fatty acids from adipose tissue, increased hepatic production of very-low-density lipoproteins and decreased high-density lipoproteins. Increased production of free fatty acids, inflammatory cytokines, and adipokines and mitochondrial dysfunction contribute to impaired insulin signaling, decreased skeletal muscle glucose uptake, increased hepatic gluconeogenesis, and β cell dysfunction, leading to hyperglycemia. In addition, insulin resistance leads to the development of hypertension by impairing vasodilation induced by nitric oxide. In this review, we discuss normal insulin signaling and the mechanisms by which insulin resistance contributes to the development of the metabolic

Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome ...

African Journals Online (AJOL)

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. Insulin can stimulate ovarian androgen production in normal women and in women with PCOS. Leptin levels were reduced among women with PCOS treated with insulin sensitizers. Aim: This study aims to ...

Simple and robust generation of ultrafast laser pulse trains using polarization-independent parallel-aligned thin films

Science.gov (United States)

Wang, Andong; Jiang, Lan; Li, Xiaowei; Wang, Zhi; Du, Kun; Lu, Yongfeng

2018-05-01

Ultrafast laser pulse temporal shaping has been widely applied in various important applications such as laser materials processing, coherent control of chemical reactions, and ultrafast imaging. However, temporal pulse shaping has been limited to only-in-lab technique due to the high cost, low damage threshold, and polarization dependence. Herein we propose a novel design of ultrafast laser pulse train generation device, which consists of multiple polarization-independent parallel-aligned thin films. Various pulse trains with controllable temporal profile can be generated flexibly by multi-reflections within the splitting films. Compared with other pulse train generation techniques, this method has advantages of compact structure, low cost, high damage threshold and polarization independence. These advantages endow it with high potential for broad utilization in ultrafast applications.

Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

DEFF Research Database (Denmark)

Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand

2012-01-01

To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves

International Nuclear Information System (INIS)

Kamal, M.M.; Van Eetvelde, M.; Bogaert, H.; Hostens, M.; Vandaele, L.; Shamsuddin, M.; Opsomer, G.

2016-01-01

Full text: The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves. Birth weight and gestational age of the calves at delivery were determined. On the next day, heart girth, wither height and diagonal length of both the calves and their dams were measured. Parity, body condition score and age at calving were recorded for all dams. For the cows, days open before last gestation, lactation length (LL), lenght of dry period (DP) and calving interval were also calculated. The magnitude and shape of the lactation curve both quantified using the MilkBot model based on monthly milk weights, were used to calculate the amount of milk produced during gestation. Using the same procedure, cumulative milk production from conception to drying off (MGEST) was calculated. A blood sample was collected from all calves (n=481; 169 born to heifers and 312 born to cows) at least 5 h after a milk meal on day 3 of life to measure basal glucose and insulin levels. In addition, an intravenous glucose-stimulated insulin secretion test was performed in a subset of the calves (n=316). After descriptive analysis, generalized linear mixed models were used to identify factors that were significantly associated with the major insulin traits (Insb, basal insulin level; QUICKI, quantitative insulin sensitivity check index; AIR, acute insulin response; DI, disposition index) of the newborn calves. The overall average birth weight of the calves was 42.7 ± 5.92 kg. The insulin traits were significantly associated with MGEST (P=0.076) and longer DP (P=0.034). The QUICKI was estimated to be lower in calves born to the cows having passed a higher MGEST (P=0.030) and longer DP (P=0.058). Moreover, the AIR (P=0.009) and DI (P=0.049) were estimated to be lower in male compared with female calves. Furthermore, the AIR

Ultrafast comparison of personal genomes

OpenAIRE

Mauldin, Denise; Hood, Leroy; Robinson, Max; Glusman, Gustavo

2017-01-01

We present an ultra-fast method for comparing personal genomes. We transform the standard genome representation (lists of variants relative to a reference) into 'genome fingerprints' that can be readily compared across sequencing technologies and reference versions. Because of their reduced size, computation on the genome fingerprints is fast and requires little memory. This enables scaling up a variety of important genome analyses, including quantifying relatedness, recognizing duplicative s...

Parametric spectro-temporal analyzer (PASTA) for ultrafast optical performance monitoring

Science.gov (United States)

Zhang, Chi; Wong, Kenneth K. Y.

2013-12-01

Ultrafast optical spectrum monitoring is one of the most challenging tasks in observing ultrafast phenomena, such as the spectroscopy, dynamic observation of the laser cavity, and spectral encoded imaging systems. However, conventional method such as optical spectrum analyzer (OSA) spatially disperses the spectrum, but the space-to-time mapping is realized by mechanical rotation of a grating, so are incapable of operating at high speed. Besides the spatial dispersion, temporal dispersion provided by dispersive fiber can also stretches the spectrum in time domain in an ultrafast manner, but is primarily confined in measuring short pulses. In view of these constraints, here we present a real-time spectrum analyzer called parametric spectro-temporal analyzer (PASTA), which is based on the time-lens focusing mechanism. It achieves a 100-MHz frame rate and can measure arbitrary waveforms. For the first time, we observe the dynamic spectrum of an ultrafast swept-source: Fourier domain mode-locked (FDML) laser, and the spectrum evolution of a laser cavity during its stabilizing process. In addition to the basic single-lens structure, the multi-lens configurations (e.g. telescope or wide-angle scope) will provide a versatile operating condition, which can zoom in to achieve 0.05-nm resolution and zoom out to achieve 10-nm observation range, namely 17 times zoom in/out ratio. In view of the goal of achieving spectrum analysis with fine accuracy, PASTA provides a promising path to study the real-time spectrum of some dynamic phenomena and non-repetitive events, with orders of magnitude enhancement in the frame rate over conventional OSAs.

All-optical devices for ultrafast packet switching

DEFF Research Database (Denmark)

Dorren, H.J.S.; HerreraDorren, J.; Raz, O.

2007-01-01

We discuss integrated devices for all-optical packet switching. We focus on monolithically integrated all-optical flip-flops, ultra-fast semiconductor based wavelength converters and explain the operation principles. Finally, a 160 Gb/s all-optical packet switching experiment over 110 km of field...

rf streak camera based ultrafast relativistic electron diffraction.

Science.gov (United States)

Musumeci, P; Moody, J T; Scoby, C M; Gutierrez, M S; Tran, T

2009-01-01

We theoretically and experimentally investigate the possibility of using a rf streak camera to time resolve in a single shot structural changes at the sub-100 fs time scale via relativistic electron diffraction. We experimentally tested this novel concept at the UCLA Pegasus rf photoinjector. Time-resolved diffraction patterns from thin Al foil are recorded. Averaging over 50 shots is required in order to get statistics sufficient to uncover a variation in time of the diffraction patterns. In the absence of an external pump laser, this is explained as due to the energy chirp on the beam out of the electron gun. With further improvements to the electron source, rf streak camera based ultrafast electron diffraction has the potential to yield truly single shot measurements of ultrafast processes.

Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

Science.gov (United States)

Çakir, Evrim; Topaloğlu, Oya; Çolak Bozkurt, Nujen; Karbek Bayraktar, Başak; Güngüneş, Aşkın; Sayki Arslan, Müyesser; Öztürk Ünsal, İlknur; Tutal, Esra; Uçan, Bekir; Delıbaşi, Tuncay

2014-01-01

Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.

The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

OpenAIRE

Messier, Claude; Teutenberg, Kevin

2005-01-01

Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

Real-time visualization of soliton molecules with evolving behavior in an ultrafast fiber laser

Science.gov (United States)

Liu, Meng; Li, Heng; Luo, Ai-Ping; Cui, Hu; Xu, Wen-Cheng; Luo, Zhi-Chao

2018-03-01

Ultrafast fiber lasers have been demonstrated to be great platforms for the investigation of soliton dynamics. The soliton molecules, as one of the most fascinating nonlinear phenomena, have been a hot topic in the field of nonlinear optics in recent years. Herein, we experimentally observed the real-time evolving behavior of soliton molecule in an ultrafast fiber laser by using the dispersive Fourier transformation technology. Several types of evolving soliton molecules were obtained in our experiments, such as soliton molecules with monotonically or chaotically evolving phase, flipping and hopping phase. These results would be helpful to the communities interested in soliton nonlinear dynamics as well as ultrafast laser technologies.

Ultrafast quenching of tryptophan fluorescence in proteins: Interresidue and intrahelical electron transfer

Energy Technology Data Exchange (ETDEWEB)

Qiu Weihong; Li Tanping; Zhang Luyuan; Yang Yi; Kao Yating; Wang Lijuan [Department of Physics, Chemistry, and Biochemistry, Program of Biophysics, Chemical Physics, and Biochemistry, Ohio State University, Columbus, OH 43210 (United States); Zhong Dongping [Department of Physics, Chemistry, and Biochemistry, Program of Biophysics, Chemical Physics, and Biochemistry, Ohio State University, Columbus, OH 43210 (United States)], E-mail: dongping@mps.ohio-state.edu

2008-06-23

Quenching of tryptophan fluorescence in proteins has been critical to the understanding of protein dynamics and enzyme reactions using tryptophan as a molecular optical probe. We report here our systematic examinations of potential quenching residues with more than 40 proteins. With site-directed mutation, we placed tryptophan to desired positions or altered its neighboring residues to screen quenching groups among 20 amino acid residues and of peptide backbones. With femtosecond resolution, we observed the ultrafast quenching dynamics within 100 ps and identified two ultrafast quenching groups, the carbonyl- and sulfur-containing residues. The former is glutamine and glutamate residues and the later is disulfide bond and cysteine residue. The quenching by the peptide-bond carbonyl group as well as other potential residues mostly occurs in longer than 100 ps. These ultrafast quenching dynamics occur at van der Waals distances through intraprotein electron transfer with high directionality. Following optimal molecular orbital overlap, electron jumps from the benzene ring of the indole moiety in a vertical orientation to the LUMO of acceptor quenching residues. Molecular dynamics simulations were invoked to elucidate various correlations of quenching dynamics with separation distances, relative orientations, local fluctuations and reaction heterogeneity. These unique ultrafast quenching pairs, as recently found to extensively occur in high-resolution protein structures, may have significant biological implications.

Insulin and the early bovine embryo

OpenAIRE

Laskowski, Denise

2017-01-01

Metabolic imbalance is a problem in the dairy industry because the metabolic demands of increased milk production can lead to decreased fertility, and more knowledge about improving the management and physical conditions of the cow (the links between fertility, nutrition, milking, and dry period) is needed. Insulin is an important hormone regulating the energy balance in the body, and insulin concentrations change in situations of energy deficiency or excess, both of which a...

High Harmonic Generation XUV Spectroscopy for Studying Ultrafast Photophysics of Coordination Complexes

Science.gov (United States)

Ryland, Elizabeth S.; Lin, Ming-Fu; Benke, Kristin; Verkamp, Max A.; Zhang, Kaili; Vura-Weis, Josh

2017-06-01

Extreme ultraviolet (XUV) spectroscopy is an inner shell technique that probes the M_{2,3}-edge excitation of atoms. Absorption of the XUV photon causes a 3p→3d transition, the energy and shape of which is directly related to the element and ligand environment. This technique is thus element-, oxidation state-, spin state-, and ligand field specific. A process called high-harmonic generation (HHG) enables the production of ultrashort (˜20fs) pulses of collimated XUV photons in a tabletop instrument. This allows transient XUV spectroscopy to be conducted as an in-lab experiment, where it was previously only possible at accelerator-based light sources. Additionally, ultrashort pulses provide the capability for unprecedented time resolution (˜50fs IRF). This technique has the capacity to serve a pivotal role in the study of electron and energy transfer processes in materials and chemical biology. I will present the XUV transient absorption instrument we have built, along with ultrafast transient M_{2,3}-edge absorption data of a series of small inorganic molecules in order to demonstrate the high specificity and time resolution of this tabletop technique as well as how our group is applying it to the study of ultrafast electronic dynamics of coordination complexes.

The role of exogenous insulin in the complex of hepatic lipidosis and ketosis associated with insulin resistance phenomenon in postpartum dairy cattle.

Science.gov (United States)

Hayirli, A

2006-10-01

As a result of a marked decline in dry matter intake (DMI) prior to parturition and a slow rate of increase in DMI relative to milk production after parturition, dairy cattle experience a negative energy balance. Changes in nutritional and metabolic status during the periparturient period predispose dairy cattle to develop hepatic lipidosis and ketosis. The metabolic profile during early lactation includes low concentrations of serum insulin, plasma glucose, and liver glycogen and high concentrations of serum glucagon, adrenaline, growth hormone, plasma beta-hydroxybutyrate and non-esterified fatty acids, and liver triglyceride. Moreover, during late gestation and early lactation, flow of nutrients to fetus and mammary tissues are accorded a high degree of metabolic priority. This priority coincides with lowered responsiveness and sensitivity of extrahepatic tissues to insulin, which presumably plays a key role in development of hepatic lipidosis and ketosis. Hepatic lipidosis and ketosis compromise production, immune function, and fertility. Cows with hepatic lipidosis and ketosis have low tissue responsiveness to insulin owing to ketoacidosis. Insulin has numerous roles in metabolism of carbohydrates, lipids and proteins. Insulin is an anabolic hormone and acts to preserve nutrients as well as being a potent feed intake regulator. In addition to the major replacement therapy to alleviate severity of negative energy balance, administration of insulin with concomitant delivery of dextrose increases efficiency of treatment for hepatic lipidosis and ketosis. However, data on use of insulin to prevent these lipid-related metabolic disorders are limited and it should be investigated.

Tracking Ultrafast Carrier Dynamics in Single Semiconductor Nanowire Heterostructures

Directory of Open Access Journals (Sweden)

Taylor A.J.

2013-03-01

Full Text Available An understanding of non-equilibrium carrier dynamics in silicon (Si nanowires (NWs and NW heterostructures is very important due to their many nanophotonic and nanoelectronics applications. Here, we describe the first measurements of ultrafast carrier dynamics and diffusion in single heterostructured Si nanowires, obtained using ultrafast optical microscopy. By isolating individual nanowires, we avoid complications resulting from the broad size and alignment distribution in nanowire ensembles, allowing us to directly probe ultrafast carrier dynamics in these quasi-one-dimensional systems. Spatially-resolved pump-probe spectroscopy demonstrates the influence of surface-mediated mechanisms on carrier dynamics in a single NW, while polarization-resolved femtosecond pump-probe spectroscopy reveals a clear anisotropy in carrier lifetimes measured parallel and perpendicular to the NW axis, due to density-dependent Auger recombination. Furthermore, separating the pump and probe spots along the NW axis enabled us to track space and time dependent carrier diffusion in radial and axial NW heterostructures. These results enable us to reveal the influence of radial and axial interfaces on carrier dynamics and charge transport in these quasi-one-dimensional nanosystems, which can then be used to tailor carrier relaxation in a single nanowire heterostructure for a given application.

The Ultrafast Wolff Rearrangement in the Gas Phase

Science.gov (United States)

Steinbacher, Andreas; Roeding, Sebastian; Brixner, Tobias; Nuernberger, Patrick

The Wolff rearrangement of gas-phase 5-diazo Meldrum's acid is disclosed with femtosecond ion spectroscopy. Distinct differences are found for 267 nm and 200 nm excitation, the latter leading to even two ultrafast rearrangement reactions.

Proposal to DOE Basic Energy Sciences Ultrafast X-ray science facility at the Advanced Light Source

CERN Document Server

Schönlein, R W; Alivisatos, A P; Belkacem, A; Berrah, N; Bozek, J; Bressler, C; Cavalleri, A; Chang, Z; Chergui, M; Falcone, R W; Glover, T E; Heimann, P A; Hepburn, J; Larsson, J; Lee, R W; McCusker, J; Padmore, H A; Pattison, P; Pratt, S T; Robin, D W; Schlüter, Ross D; Shank, C V; Wark, J; Zholents, A A; Zolotorev, M S

2001-01-01

We propose to develop a true user facility for ultrafast x-ray science at the Advanced Light Source. This facility will be unique in the world, and will fill a critical need for the growing ultrafast x-ray research community. The development of this facility builds upon the expertise from long-standing research efforts in ultrafast x-ray spectroscopy and the development of femtosecond x-ray sources and techniques at both the Lawrence Berkeley National Laboratory and at U.C. Berkeley. In particular, the technical feasibility of a femtosecond x-ray beamline at the ALS has already been demonstrated, and existing ultrafast laser technology will enable such a beamline to operate near the practical limit for femtosecond x-ray flux and brightness from a 3rd generation synchrotron.

Proposal to DOE Basic Energy Sciences: Ultrafast X-ray science facility at the Advanced Light Source

Energy Technology Data Exchange (ETDEWEB)

Schoenlein, Robert W.; Falcone, Roger W.; Abela, R.; Alivisatos, A.P.; Belkacem, A.; Berrah, N.; Bozek, J.; Bressler, C.; Cavalleri, A.; Chergui, M.; Glover, T.E.; Heimann, P.A.; Hepburn, J.; Larsson, J.; Lee, R.W.; McCusker, J.; Padmore, H.A.; Pattison, P.; Pratt, S.T.; Shank, C.V.; Wark, J.; Chang, Z.; Robin, D.W.; Schlueter, R.D.; Zholents, A.A.; Zolotorev, M.S.

2001-12-12

We propose to develop a true user facility for ultrafast x-ray science at the Advanced Light Source. This facility will be unique in the world, and will fill a critical need for the growing ultrafast x-ray research community. The development of this facility builds upon the expertise from long-standing research efforts in ultrafast x-ray spectroscopy and the development of femtosecond x-ray sources and techniques at both the Lawrence Berkeley National Laboratory and at U.C. Berkeley. In particular, the technical feasibility of a femtosecond x-ray beamline at the ALS has already been demonstrated, and existing ultrafast laser technology will enable such a beamline to operate near the practical limit for femtosecond x-ray flux and brightness from a 3rd generation synchrotron.

Proposal to DOE Basic Energy Sciences: Ultrafast X-ray science facility at the Advanced Light Source

International Nuclear Information System (INIS)

Schoenlein, Robert W.; Falcone, Roger W.; Abela, R.; Alivisatos, A.P.; Belkacem, A.; Berrah, N.; Bozek, J.; Bressler, C.; Cavalleri, A.; Chergui, M.; Glover, T.E.; Heimann, P.A.; Hepburn, J.; Larsson, J.; Lee, R.W.; McCusker, J.; Padmore, H.A.; Pattison, P.; Pratt, S.T.; Shank, C.V.; Wark, J.; Chang, Z.; Robin, D.W.; Schlueter, R.D.; Zholents, A.A.; Zolotorev, M.S.

2001-01-01

We propose to develop a true user facility for ultrafast x-ray science at the Advanced Light Source. This facility will be unique in the world, and will fill a critical need for the growing ultrafast x-ray research community. The development of this facility builds upon the expertise from long-standing research efforts in ultrafast x-ray spectroscopy and the development of femtosecond x-ray sources and techniques at both the Lawrence Berkeley National Laboratory and at U.C. Berkeley. In particular, the technical feasibility of a femtosecond x-ray beamline at the ALS has already been demonstrated, and existing ultrafast laser technology will enable such a beamline to operate near the practical limit for femtosecond x-ray flux and brightness from a 3rd generation synchrotron

Ultrafast X-Ray Spectroscopy of Conical Intersections

Science.gov (United States)

Neville, Simon P.; Chergui, Majed; Stolow, Albert; Schuurman, Michael S.

2018-06-01

Ongoing developments in ultrafast x-ray sources offer powerful new means of probing the complex nonadiabatically coupled structural and electronic dynamics of photoexcited molecules. These non-Born-Oppenheimer effects are governed by general electronic degeneracies termed conical intersections, which play a key role, analogous to that of a transition state, in the electronic-nuclear dynamics of excited molecules. Using high-level ab initio quantum dynamics simulations, we studied time-resolved x-ray absorption (TRXAS) and photoelectron spectroscopy (TRXPS) of the prototypical unsaturated organic chromophore, ethylene, following excitation to its S2(π π*) state. The TRXAS, in particular, is highly sensitive to all aspects of the ensuing dynamics. These x-ray spectroscopies provide a clear signature of the wave packet dynamics near conical intersections, related to charge localization effects driven by the nuclear dynamics. Given the ubiquity of charge localization in excited state dynamics, we believe that ultrafast x-ray spectroscopies offer a unique and powerful route to the direct observation of dynamics around conical intersections.

A PSF-shape-based beamforming strategy for robust 2D motion estimation in ultrafast data

NARCIS (Netherlands)

Saris, Anne E.C.M.; Fekkes, Stein; Nillesen, Maartje; Hansen, Hendrik H.G.; de Korte, Chris L.

2018-01-01

This paper presents a framework for motion estimation in ultrafast ultrasound data. It describes a novel approach for determining the sampling grid for ultrafast data based on the system's point-spread-function (PSF). As a consequence, the cross-correlation functions (CCF) used in the speckle

Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

DEFF Research Database (Denmark)

Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry

2011-01-01

Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells.......Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells....

Fusion of Ultraviolet-Visible and Infrared Transient Absorption Spectroscopy Data to Model Ultrafast Photoisomerization.

Science.gov (United States)

Debus, Bruno; Orio, Maylis; Rehault, Julien; Burdzinski, Gotard; Ruckebusch, Cyril; Sliwa, Michel

2017-08-03

Ultrafast photoisomerization reactions generally start at a higher excited state with excess of internal vibrational energy and occur via conical intersections. This leads to ultrafast dynamics which are difficult to investigate with a single transient absorption spectroscopy technique, be it in the ultraviolet-visible (UV-vis) or infrared (IR) domain. On one hand, the information available in the UV-vis domain is limited as only slight spectral changes are observed for different isomers. On the other hand, the interpretation of vibrational spectra is strongly hindered by intramolecular relaxation and vibrational cooling. These limitations can be circumvented by fusing UV-vis and IR transient absorption spectroscopy data in a multiset multivariate curve resolution analysis. We apply this approach to describe the spectrodynamics of the ultrafast cis-trans photoisomerization around the C-N double bond observed for aromatic Schiff bases. Twisted intermediate states could be elucidated, and isomerization was shown to occur through a continuous complete rotation. More broadly, data fusion can be used to rationalize a vast range of ultrafast photoisomerization processes of interest in photochemistry.

High speed fluorescence imaging with compressed ultrafast photography

Science.gov (United States)

Thompson, J. V.; Mason, J. D.; Beier, H. T.; Bixler, J. N.

2017-02-01

Fluorescent lifetime imaging is an optical technique that facilitates imaging molecular interactions and cellular functions. Because the excited lifetime of a fluorophore is sensitive to its local microenvironment,1, 2 measurement of fluorescent lifetimes can be used to accurately detect regional changes in temperature, pH, and ion concentration. However, typical state of the art fluorescent lifetime methods are severely limited when it comes to acquisition time (on the order of seconds to minutes) and video rate imaging. Here we show that compressed ultrafast photography (CUP) can be used in conjunction with fluorescent lifetime imaging to overcome these acquisition rate limitations. Frame rates up to one hundred billion frames per second have been demonstrated with compressed ultrafast photography using a streak camera.3 These rates are achieved by encoding time in the spatial direction with a pseudo-random binary pattern. The time domain information is then reconstructed using a compressed sensing algorithm, resulting in a cube of data (x,y,t) for each readout image. Thus, application of compressed ultrafast photography will allow us to acquire an entire fluorescent lifetime image with a single laser pulse. Using a streak camera with a high-speed CMOS camera, acquisition rates of 100 frames per second can be achieved, which will significantly enhance our ability to quantitatively measure complex biological events with high spatial and temporal resolution. In particular, we will demonstrate the ability of this technique to do single-shot fluorescent lifetime imaging of cells and microspheres.

Ultrafast terahertz electrodynamics of photonic and electronic nanostructures

Energy Technology Data Exchange (ETDEWEB)

Luo, Liang [Iowa State Univ., Ames, IA (United States)

2015-01-01

This thesis summarizes my work on using ultrafast laser pulses to study Terahertz (THz) electrodynamics of photonic and electronic nanostructures and microstructures. Ultrafast timeresolved (optical, NIR, MIR, THz) pump-probe spectroscopy setup has been successfully built, which enables me to perform a series of relevant experiments. Firstly, a novel high e ciency and compact THz wave emitter based on split-ring-resonators has been developed and characterized. The emitter can be pumped at any wavelength by tailoring the magnetic resonance and could generate gapless THz waves covering the entire THz band. Secondly, two kinds of new photonic structures for THz wave manipulation have been successfully designed and characterized. One is based on the 1D and 2D photo-imprinted di ractive elements. The other is based on the photoexcited double-split-ring-resonator metamaterials. Both structures are exible and can modulate THz waves with large tunability. Thirdly, the dark excitons in semiconducting singlewalled carbon nanotubes are studied by optical pump and THz probe spectroscopy, which provides the rst insights into the THz responses of nonequilibrium excitonic correlations and dynamics from the dark ground states in carbon nanotubes. Next, several on-going projects are brie y presented such as the study of ultrafast THz dynamics of Dirac fermions in topological insulator Bi₂Se₃ with Mid-infrared excitation. Finally, the thesis ends with a summary of the completed experiments and an outlook of the future plan.

Mechanisms of action of brain insulin against neurodegenerative diseases.

Science.gov (United States)

Ramalingam, Mahesh; Kim, Sung-Jin

2014-06-01

Insulin, a pancreatic hormone, is best known for its peripheral effects on the metabolism of glucose, fats and proteins. There is a growing body of evidence linking insulin action in the brain to neurodegenerative diseases. Insulin present in central nervous system is a regulator of central glucose metabolism nevertheless this glucoregulation is not the main function of insulin in the brain. Brain is known to be specifically vulnerable to oxidative products relative to other organs and altered brain insulin signaling may cause or promote neurodegenerative diseases which invalidates and reduces the quality of life. Insulin located within the brain is mostly of pancreatic origin or is produced in the brain itself crosses the blood-brain barrier and enters the brain via a receptor-mediated active transport system. Brain Insulin, insulin receptor and insulin receptor substrate-mediated signaling pathways play important roles in the regulation of peripheral metabolism, feeding behavior, memory and maintenance of neural functions such as neuronal growth and differentiation, neuromodulation and neuroprotection. In the present review, we would like to summarize the novel biological and pathophysiological roles of neuronal insulin in neurodegenerative diseases and describe the main signaling pathways in use for therapeutic strategies in the use of insulin to the cerebral tissues and their biological applications to neurodegenerative diseases.

Demonstration of Ultra-Fast Switching in Nano metallic Resistive Switching Memory Devices

International Nuclear Information System (INIS)

Yang, Y.

2016-01-01

Interdependency of switching voltage and time creates a dilemma/obstacle for most resistive switching memories, which indicates low switching voltage and ultra-fast switching time cannot be simultaneously achieved. In this paper, an ultra-fast (sub-100 ns) yet low switching voltage resistive switching memory device (“nano metallic ReRAM”) was demonstrated. Experimental switching voltage is found independent of pulse width (intrinsic device property) when the pulse is long but shows abrupt time dependence (“cliff”) as pulse width approaches characteristic RC time of memory device (extrinsic device property). Both experiment and simulation show that the onset of cliff behavior is dependent on physical device size and parasitic resistance, which is expected to diminish as technology nodes shrink down. We believe this study provides solid evidence that nano metallic resistive switching memory can be reliably operated at low voltage and ultra-fast regime, thus beneficial to future memory technology.

Real-time observation of ultrafast electron injection at graphene–Zn porphyrin interfaces

KAUST Repository

Masih, Dilshad

2015-02-25

We report on the ultrafast interfacial electron transfer ( ET) between zinc( II) porphyrin ( ZnTMPyP) and negatively charged graphene carboxylate ( GC) using state- of- the- art femtosecond laser spectroscopy with broadband capabilities. The steady- state interaction between GC and ZnTMPyP results in a red- shifted absorption spectrum, providing a clear indication for the binding affinity between ZnTMPyP and GC via electrostatic and p- p stacking interactions. Ultrafast transient absorption ( TA) spectra in the absence and presence of three different GC concentrations reveal ( i) the ultrafast formation of singlet excited ZnTMPyP*, which partially relaxes into a long- lived triplet state, and ( ii) ET from the singlet excited ZnTMPyP* to GC, forming ZnTMPyP + and GC , as indicated by a spectral feature at 650- 750 nm, which is attributed to a ZnTMPyP radical cation resulting from the ET process.

Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster

Science.gov (United States)

Yu, Yue; Sun, Ying; He, Shengqi; Yan, Cheng; Rui, Liangyou; Li, Wenjun

2012-01-01

The Cbl family proteins function as both E3 ubiquitin ligases and adaptor proteins to regulate various cellular signaling events, including the insulin/insulin-like growth factor 1 (IGF1) and epidermal growth factor (EGF) pathways. These pathways play essential roles in growth, development, metabolism, and survival. Here we show that in Drosophila melanogaster, Drosophila Cbl (dCbl) regulates longevity and carbohydrate metabolism through downregulating the production of Drosophila insulin-like peptides (dILPs) in the brain. We found that dCbl was highly expressed in the brain and knockdown of the expression of dCbl specifically in neurons by RNA interference increased sensitivity to oxidative stress or starvation, decreased carbohydrate levels, and shortened life span. Insulin-producing neuron-specific knockdown of dCbl resulted in similar phenotypes. dCbl deficiency in either the brain or insulin-producing cells upregulated the expression of dilp genes, resulting in elevated activation of the dILP pathway, including phosphorylation of Drosophila Akt and Drosophila extracellular signal-regulated kinase (dERK). Genetic interaction analyses revealed that blocking Drosophila epidermal growth factor receptor (dEGFR)-dERK signaling in pan-neurons or insulin-producing cells by overexpressing a dominant-negative form of dEGFR abolished the effect of dCbl deficiency on the upregulation of dilp genes. Furthermore, knockdown of c-Cbl in INS-1 cells, a rat β-cell line, also increased insulin biosynthesis and glucose-stimulated secretion in an ERK-dependent manner. Collectively, these results suggest that neuronal dCbl regulates life span, stress responses, and metabolism by suppressing dILP production and the EGFR-ERK pathway mediates the dCbl action. Cbl suppression of insulin biosynthesis is evolutionarily conserved, raising the possibility that Cbl may similarly exert its physiological actions through regulating insulin production in β cells. PMID:22778134

Four-Dimensional Ultrafast Electron Microscopy: Insights into an Emerging Technique

KAUST Repository

Adhikari, Aniruddha

2016-12-15

Four-dimensional ultrafast electron microscopy (4D-UEM) is a novel analytical technique that aims to fulfill the long-held dream of researchers to investigate materials at extremely short spatial and temporal resolutions by integrating the excellent spatial resolution of electron microscopes with the temporal resolution of ultrafast femtosecond laser-based spectroscopy. The ingenious use of pulsed photoelectrons to probe surfaces and volumes of materials enables time-resolved snapshots of the dynamics to be captured in a way hitherto impossible by other conventional techniques. The flexibility of 4D-UEM lies in the fact that it can be used in both the scanning (S-UEM) and transmission (UEM) modes depending upon the type of electron microscope involved. While UEM can be employed to monitor elementary structural changes and phase transitions in samples using real-space mapping, diffraction, electron energy-loss spectroscopy, and tomography, S-UEM is well suited to map ultrafast dynamical events on materials surfaces in space and time. This review provides an overview of the unique features that distinguish these techniques and also illustrates the applications of both S-UEM and UEM to a multitude of problems relevant to materials science and chemistry.

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Microwave-controlled ultrafast synthesis of uniform silver nanocubes and nanowires

Science.gov (United States)

Zhao, Tian; Fan, Jun-Bing; Cui, Jing; Liu, Jin-Hua; Xu, Xiao-Bo; Zhu, Ming-Qiang

2011-01-01

Synthesis of well-defined silver nanostructure in terms of size and shape has been strongly motivated by the requirements to their size- and shape-dependent optical properties which achieve their practical applications ranging from biosensing to catalysis and optics. In this Letter, an ultrafast synthetic process for the well-defined Ag nanocubes and nanowires have been developed, which simply involve the microwave-mediated polyol reduction of silver nitrate in ethylene glycol by adding different amount sodium sulfide (Na2S) into the solution. The possible growth and evolution process of the Ag nanocubes and nanowires involves the microwave ultrafast nucleation and growth followed by oxidative etching of Ag nanocrystals.

An ultrafast study of Zinc Phthalocyanine in DMSO

CSIR Research Space (South Africa)

Ombinda-Lemboumba, Saturnin

2010-10-01

Full Text Available The ultrafast dynamics of Zinc Phthalocyanine was studied using trasient absorption pump probe spectroscopy. Zinc Phthalocyanine was excited (pumped) at 672nm and probed by a white light continuum. The pump-probe technique used in this study...

PREFACE: Ultrafast and nonlinear optics in carbon nanomaterials

Science.gov (United States)

Kono, Junichiro

2013-02-01

Carbon-based nanomaterials—single-wall carbon nanotubes (SWCNTs) and graphene, in particular—have emerged in the last decade as novel low-dimensional systems with extraordinary properties. Because they are direct-bandgap systems, SWCNTs are one of the leading candidates to unify electronic and optical functions in nanoscale circuitry; their diameter-dependent bandgaps can be utilized for multi-wavelength devices. Graphene's ultrahigh carrier mobilities are promising for high-frequency electronic devices, while, at the same time, it is predicted to have ideal properties for terahertz generation and detection due to its unique zero-gap, zero-mass band structure. There have been a large number of basic optical studies on these materials, but most of them were performed in the weak-excitation, quasi-equilibrium regime. In order to probe and assess their performance characteristics as optoelectronic materials under device-operating conditions, it is crucial to strongly drive them and examine their optical properties in highly non-equilibrium situations and with ultrashot time resolution. In this section, the reader will find the latest results in this rapidly growing field of research. We have assembled contributions from some of the leading experts in ultrafast and nonlinear optical spectroscopy of carbon-based nanomaterials. Specific topics featured include: thermalization, cooling, and recombination dynamics of photo-generated carriers; stimulated emission, gain, and amplification; ultrafast photoluminescence; coherent phonon dynamics; exciton-phonon and exciton-plasmon interactions; exciton-exciton annihilation and Auger processes; spontaneous and stimulated emission of terahertz radiation; four-wave mixing and harmonic generation; ultrafast photocurrents; the AC Stark and Franz-Keldysh effects; and non-perturbative light-mater coupling. We would like to express our sincere thanks to those who contributed their latest results to this special section, and the

Improved insulin sensitivity after exercise: focus on insulin signaling

DEFF Research Database (Denmark)

Frøsig, Christian; Richter, Erik

2009-01-01

After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

Ultrafast Structural Dynamics in InSb Probed by Time-Resolved X-Ray Diffraction

International Nuclear Information System (INIS)

Chin, A.H.; Shank, C.V.; Chin, A.H.; Schoenlein, R.W.; Shank, C.V.; Glover, T.E.; Leemans, W.P.; Balling, P.

1999-01-01

Ultrafast structural dynamics in laser-perturbed InSb are studied using time-resolved x-ray diffraction with a novel femtosecond x-ray source. We report the first observation of a delay in the onset of lattice expansion, which we attribute to energy relaxation processes and lattice strain propagation. In addition, we observe direct indications of ultrafast disordering on a subpicosecond time scale. copyright 1999 The American Physical Society

Differential regulation of insulin-like growth factor binding protein-1 and -2 by insulin in the baboon (Papio anubis endometrium

Directory of Open Access Journals (Sweden)

Fazleabas Asgerally T

2008-01-01

Full Text Available Abstract Background The purpose of this study was to examine the effect of insulin on expression and synthesis of IGFBP-1 and IGFBP-2 in the baboon endometrium in vitro. Methods Baboon endometrial explants collected from cycling, ovariectomized, steroid-treated, simulated-pregnant and pregnant animals were cultured for 48 h in the presence or absence of insulin, with or without estradiol, progesterone and hCG. Results Insulin clearly inhibited IGFBP-1 production and mRNA expression in a time- and dose-dependent manner, whereas IGFBP-2 synthesis was not significantly affected. The inhibitory effects of insulin on IGFBP-1 were more evident in explants of non-pregnant tissue or tissue away from the implantation site. In the absence of insulin, synthesis of IGFBP-1 was induced in explants with low levels of de novo synthesis whereas IGFBP-2 synthesis was inhibited. This effect was potentiated by steroids and hCG in the explant cultures. Conclusion Insulin differentially regulates endometrial IGFBP-1 and IGFBP-2 secretion in the baboon.

Ultrafast gain recovery and modulation limitations in self-assembled quantum-dot devices

DEFF Research Database (Denmark)

Berg, Tommy Winther; Bischoff, Svend; Magnúsdóttir, Ingibjörg

2001-01-01

Measurements of ultrafast gain recovery in self-assembled InAs quantum-dot (QD) amplifiers are explained by a comprehensive numerical model. The on excited state carriers are found to act as a reservoir for the optically active ground state carriers resulting in an ultrafast gain recovery as long...... as the excited state is well populated. However, when pulses are injected into the device at high-repetition frequencies, the response of a on amplifier is found to be limited by the wetting-layer dynamics....

Ultrafast, 2 min synthesis of monolayer-protected gold nanoclusters (d < 2 nm)

Science.gov (United States)

Martin, Matthew N.; Li, Dawei; Dass, Amala; Eah, Sang-Kee

2012-06-01

An ultrafast synthesis method is presented for hexanethiolate-coated gold nanoclusters (d gold nanoclusters are separated from the reaction byproducts fast and easily without any need for post-synthesis cleaning.An ultrafast synthesis method is presented for hexanethiolate-coated gold nanoclusters (d gold nanoclusters are separated from the reaction byproducts fast and easily without any need for post-synthesis cleaning. Electronic supplementary information (ESI) available: Experimental details of gold nanocluster synthesis and mass-spectrometry. See DOI: 10.1039/c2nr30890h

Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

DEFF Research Database (Denmark)

Jensen, Christine B; Storgaard, Heidi; Holst, Jens J

2003-01-01

We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...... Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux......, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but...

Retroendocytosis of insulin in rat adipocytes

International Nuclear Information System (INIS)

Levy, J.R.; Olefsky, J.M.

1986-01-01

A variety of ligands internalized by receptor-mediated endocytosis follow a short circuit pathway that does not lead to degradation but results in rapid exocytosis of intact ligand, a process termed retroendocytosis. We studied the time course of [ 125 I]iodoinsulin processing and retroendocytosis after internalization in isolated rat adipocytes. After steady state binding and internalization, surface receptor-bound insulin was removed by exposing cells to a low pH at low temperatures. The cells containing internalized [ 125 I]iodoinsulin were reincubated in fresh medium; subsequently, the radioactivity remaining within the cells and released into the medium were analyzed at various times by trichloroacetic acid (TCA) precipitation, Sephadex G-50 gel filtration, and reverse phase HPLC. Cell-associated radioactivity progressively decreased after reincubation in 37 C buffer, with 50% released in 9 min and 85% by 45 min. In the media, TCA-precipitable material appeared quickly, with a t1/2 of 2 min, and plateaued by 10 min. TCA-soluble material was released continually throughout the 45-min period. The release of both TCA-precipitable and TCA-soluble material was temperature and energy dependent. Sephadex G-50 chromatography demonstrated the loss of insulin from the intracellular pool and its appearance in the medium with a time course similar to that of TCA-precipitable material. Reverse phase HPLC demonstrated that the intracellular and medium radioactivity eluting in peak II (insulin peak) on Sephadex G-50 was composed of both intact insulin and intermediates. After the internalization of insulin, rat adipocytes release not only small mol wt degradation products of insulin, but also insulin intermediates and intact insulin. The rate of retroendocytosis reported here is almost identical to the rate of insulin receptor recycling in rat adipocytes

Ultrafast scanning tunneling microscopy

Energy Technology Data Exchange (ETDEWEB)

Botkin, D.A. [California Univ., Berkeley, CA (United States). Dept. of Physics]|[Lawrence Berkeley Lab., CA (United States)

1995-09-01

I have developed an ultrafast scanning tunneling microscope (USTM) based on uniting stroboscopic methods of ultrafast optics and scanned probe microscopy to obtain nanometer spatial resolution and sub-picosecond temporal resolution. USTM increases the achievable time resolution of a STM by more than 6 orders of magnitude; this should enable exploration of mesoscopic and nanometer size systems on time scales corresponding to the period or decay of fundamental excitations. USTM consists of a photoconductive switch with subpicosecond response time in series with the tip of a STM. An optical pulse from a modelocked laser activates the switch to create a gate for the tunneling current, while a second laser pulse on the sample initiates a dynamic process which affects the tunneling current. By sending a large sequence of identical pulse pairs and measuring the average tunnel current as a function of the relative time delay between the pulses in each pair, one can map the time evolution of the surface process. USTM was used to measure the broadband response of the STM`s atomic size tunnel barrier in frequencies from tens to hundreds of GHz. The USTM signal amplitude decays linearly with the tunnel junction conductance, so the spatial resolution of the time-resolved signal is comparable to that of a conventional STM. Geometrical capacitance of the junction does not appear to play an important role in the measurement, but a capacitive effect intimately related to tunneling contributes to the measured signals and may limit the ultimate resolution of the USTM.

Experiments with trapped ions and ultrafast laser pulses

Science.gov (United States)

Johnson, Kale Gifford

Since the dawn of quantum information science, laser-cooled trapped atomic ions have been one of the most compelling systems for the physical realization of a quantum computer. By applying qubit state dependent forces to the ions, their collective motional modes can be used as a bus to realize entangling quantum gates. Ultrafast state-dependent kicks [1] can provide a universal set of quantum logic operations, in conjunction with ultrafast single qubit rotations [2], which uses only ultrafast laser pulses. This may present a clearer route to scaling a trapped ion processor [3]. In addition to the role that spin-dependent kicks (SDKs) play in quantum computation, their utility in fundamental quantum mechanics research is also apparent. In this thesis, we present a set of experiments which demonstrate some of the principle properties of SDKs including ion motion independence (we demonstrate single ion thermometry from the ground state to near room temperature and the largest Schrodinger cat state ever created in an oscillator), high speed operations (compared with conventional atom-laser interactions), and multi-qubit entanglement operations with speed that is not fundamentally limited by the trap oscillation frequency. We also present a method to provide higher stability in the radial mode ion oscillation frequencies of a linear radiofrequency (rf) Paul trap-a crucial factor when performing operations on the rf-sensitive modes. Finally, we present the highest atomic position sensitivity measurement of an isolated atom to date of 0.5 nm Hz. (-1/2) with a minimum uncertaintyof 1.7 nm using a 0.6 numerical aperature (NA) lens system, along with a method to correct aberrations and a direct position measurement of ion micromotion (the inherent oscillations of an ion trapped in an oscillating rf field). This development could be used to directly image atom motion in the quantum regime, along with sensing forces at the yoctonewton [10. (-24) N)] scale forgravity sensing

Ultrafast transmission electron microscopy using a laser-driven field emitter: Femtosecond resolution with a high coherence electron beam

Energy Technology Data Exchange (ETDEWEB)

Feist, Armin; Bach, Nora; Rubiano da Silva, Nara; Danz, Thomas; Möller, Marcel; Priebe, Katharina E.; Domröse, Till; Gatzmann, J. Gregor; Rost, Stefan; Schauss, Jakob; Strauch, Stefanie; Bormann, Reiner; Sivis, Murat; Schäfer, Sascha, E-mail: sascha.schaefer@phys.uni-goettingen.de; Ropers, Claus, E-mail: claus.ropers@uni-goettingen.de

2017-05-15

We present the development of the first ultrafast transmission electron microscope (UTEM) driven by localized photoemission from a field emitter cathode. We describe the implementation of the instrument, the photoemitter concept and the quantitative electron beam parameters achieved. Establishing a new source for ultrafast TEM, the Göttingen UTEM employs nano-localized linear photoemission from a Schottky emitter, which enables operation with freely tunable temporal structure, from continuous wave to femtosecond pulsed mode. Using this emission mechanism, we achieve record pulse properties in ultrafast electron microscopy of 9 Å focused beam diameter, 200 fs pulse duration and 0.6 eV energy width. We illustrate the possibility to conduct ultrafast imaging, diffraction, holography and spectroscopy with this instrument and also discuss opportunities to harness quantum coherent interactions between intense laser fields and free-electron beams. - Highlights: • First implementation of an ultrafast TEM employing a nanoscale photocathode. • Localized single photon-photoemission from nanoscopic field emitter yields low emittance ultrashort electron pulses. • Electron pulses focused down to ~9 Å, with a duration of 200 fs and an energy width of 0.6 eV are demonstrated. • Quantitative characterization of ultrafast electron gun emittance and brightness. • A range of applications of high coherence ultrashort electron pulses is shown.

Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves

International Nuclear Information System (INIS)

Kamal, M.M.; Van Eetvelde, M.; Bogaert, H.; Hostens, M.; Vandaele, L.; Shamsuddin, M.; Opsomer, G.

2015-01-01

The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves

Ultrafast terahertz scanning tunneling microscopy with atomic resolution

DEFF Research Database (Denmark)

Jelic, Vedran; Iwaszczuk, Krzysztof; Nguyen, Peter H.

2016-01-01

We demonstrate that ultrafast terahertz scanning tunneling microscopy (THz-STM) can probe single atoms on a silicon surface with simultaneous sub-nanometer and sub-picosecond spatio-temporal resolution. THz-STM is established as a new technique for exploring high-field non-equilibrium tunneling...

Ultrafast Laser-Based Spectroscopy and Sensing: Applications in LIBS, CARS, and THz Spectroscopy

Science.gov (United States)

Leahy-Hoppa, Megan R.; Miragliotta, Joseph; Osiander, Robert; Burnett, Jennifer; Dikmelik, Yamac; McEnnis, Caroline; Spicer, James B.

2010-01-01

Ultrafast pulsed lasers find application in a range of spectroscopy and sensing techniques including laser induced breakdown spectroscopy (LIBS), coherent Raman spectroscopy, and terahertz (THz) spectroscopy. Whether based on absorption or emission processes, the characteristics of these techniques are heavily influenced by the use of ultrafast pulses in the signal generation process. Depending on the energy of the pulses used, the essential laser interaction process can primarily involve lattice vibrations, molecular rotations, or a combination of excited states produced by laser heating. While some of these techniques are currently confined to sensing at close ranges, others can be implemented for remote spectroscopic sensing owing principally to the laser pulse duration. We present a review of ultrafast laser-based spectroscopy techniques and discuss the use of these techniques to current and potential chemical and environmental sensing applications. PMID:22399883

Ultrafast Laser-Based Spectroscopy and Sensing: Applications in LIBS, CARS, and THz Spectroscopy

Directory of Open Access Journals (Sweden)

Megan R. Leahy-Hoppa

2010-04-01

Full Text Available Ultrafast pulsed lasers find application in a range of spectroscopy and sensing techniques including laser induced breakdown spectroscopy (LIBS, coherent Raman spectroscopy, and terahertz (THz spectroscopy. Whether based on absorption or emission processes, the characteristics of these techniques are heavily influenced by the use of ultrafast pulses in the signal generation process. Depending on the energy of the pulses used, the essential laser interaction process can primarily involve lattice vibrations, molecular rotations, or a combination of excited states produced by laser heating. While some of these techniques are currently confined to sensing at close ranges, others can be implemented for remote spectroscopic sensing owing principally to the laser pulse duration. We present a review of ultrafast laser-based spectroscopy techniques and discuss the use of these techniques to current and potential chemical and environmental sensing applications.

Action of insulin on the surface morphology of hepatocytes: role of phosphatidylinositol 3-kinase in insulin-induced shape change of microvilli.

Science.gov (United States)

Lange, K; Brandt, U; Gartzke, J; Bergmann, J

1998-02-25

In previous studies we have shown that the insulin-responding glucose transporter isoform of 3T3-L1 adipocytes, GluT4, is almost completely located on microvilli. Furthermore, insulin caused the integration of these microvilli into the plasma membrane, suggesting that insulin-induced stimulation of glucose uptake may be due to the destruction of the cytoskeletal diffusion barrier formed by the actin filament bundle of the microvillar shaft regions [Lange et al. (1990) FEBS Lett. 261, 459-463; Lange et al. (1990) FEBS Lett. 276, 39-41]. Similar shape changes in microvilli were observed when the transport rates of adipocytes were modulated by glucose feeding or starvation. Here we demonstrate that the action of insulin on the surface morphology of hepatocytes is identical to that on 3T3L1 adipocytes; small and narrow microvilli on the surface of unstimulated hepatocytes were rapidly shortened and dilated on top of large domed surface areas. The aspect and mechanism of this effect are closely related to "membrane ruffling" induced by insulin and other growth factors. Pretreatment of hepatocytes with the PI 3-kinase inhibitor wortmannin (100 nM), which completely prevents transport stimulation by insulin in adipocytes and other cell types, also inhibited insulin-induced shape changes in microvilli on the hepatocyte surface. In contrast, vasopressin-induced microvillar shape changes in hepatocytes [Lange et al. (1997) Exp. Cell Res. 234, 486-497] were insensitive to wortmannin pretreatment. These findings indicate that PI 3-kinase products are necessary for stimulation of submembrane microfilament dynamics and that cytoskeletal reorganization is critically involved in insulin stimulation of transport processes. The mechanism of the insulin-induced cytoskeletal reorganization can be explained on the basis of the recent finding of Lu et al. [Biochemistry 35(1996) 14027-14034] that PI 3-kinase products exhibit much higher affinity for the profilin-actin complex than the

Progress in Ultrafast Intense Laser Science Volume V

CERN Document Server

Yamanouchi, Kaoru; Ledingham, Kenneth

2010-01-01

The PUILS series delivers up-to-date reviews of progress in Ultrafast Intense Laser Science, a newly emerging interdisciplinary research field spanning atomic and molecular physics, molecular science, and optical science, which has been stimulated by the recent developments in ultrafast laser technologies. Each volume compiles peer-reviewed articles authored by researchers at the forefront of each their own subfields of UILS. Every chapter opens with an overview of the topics to be discussed, so that researchers unfamiliar to the subfield, as well as graduate students, can grasp the importance and attractions of the research topic at hand; these are followed by reports of cutting-edge discoveries. This fifth volume covers a broad range of topics from this interdisciplinary research field, focusing on coherent responses of gaseous and condensed matter to ultrashort intense laser pulses, propagation of intense laser pulses, and laser-plasma interaction and its applications.

Ultrafast collinear scattering and carrier multiplication in graphene.

Science.gov (United States)

Brida, D; Tomadin, A; Manzoni, C; Kim, Y J; Lombardo, A; Milana, S; Nair, R R; Novoselov, K S; Ferrari, A C; Cerullo, G; Polini, M

2013-01-01

Graphene is emerging as a viable alternative to conventional optoelectronic, plasmonic and nanophotonic materials. The interaction of light with charge carriers creates an out-of-equilibrium distribution, which relaxes on an ultrafast timescale to a hot Fermi-Dirac distribution, that subsequently cools emitting phonons. Although the slower relaxation mechanisms have been extensively investigated, the initial stages still pose a challenge. Experimentally, they defy the resolution of most pump-probe setups, due to the extremely fast sub-100 fs carrier dynamics. Theoretically, massless Dirac fermions represent a novel many-body problem, fundamentally different from Schrödinger fermions. Here we combine pump-probe spectroscopy with a microscopic theory to investigate electron-electron interactions during the early stages of relaxation. We identify the mechanisms controlling the ultrafast dynamics, in particular the role of collinear scattering. This gives rise to Auger processes, including charge multiplication, which is key in photovoltage generation and photodetectors.

Ultrafast dynamics and laser action of organic semiconductors

CERN Document Server

Vardeny, Zeev Valy

2009-01-01

Spurred on by extensive research in recent years, organic semiconductors are now used in an array of areas, such as organic light emitting diodes (OLEDs), photovoltaics, and other optoelectronics. In all of these novel applications, the photoexcitations in organic semiconductors play a vital role. Exploring the early stages of photoexcitations that follow photon absorption, Ultrafast Dynamics and Laser Action of Organic Semiconductors presents the latest research investigations on photoexcitation ultrafast dynamics and laser action in pi-conjugated polymer films, solutions, and microcavities.In the first few chapters, the book examines the interplay of charge (polarons) and neutral (excitons) photoexcitations in pi-conjugated polymers, oligomers, and molecular crystals in the time domain of 100 fs-2 ns. Summarizing the state of the art in lasing, the final chapters introduce the phenomenon of laser action in organics and cover the latest optoelectronic applications that use lasing based on a variety of caviti...

Ultrafast optical ranging using microresonator soliton frequency combs

Science.gov (United States)

Trocha, P.; Karpov, M.; Ganin, D.; Pfeiffer, M. H. P.; Kordts, A.; Wolf, S.; Krockenberger, J.; Marin-Palomo, P.; Weimann, C.; Randel, S.; Freude, W.; Kippenberg, T. J.; Koos, C.

2018-02-01

Light detection and ranging is widely used in science and industry. Over the past decade, optical frequency combs were shown to offer advantages in optical ranging, enabling fast distance acquisition with high accuracy. Driven by emerging high-volume applications such as industrial sensing, drone navigation, or autonomous driving, there is now a growing demand for compact ranging systems. Here, we show that soliton Kerr comb generation in integrated silicon nitride microresonators provides a route to high-performance chip-scale ranging systems. We demonstrate dual-comb distance measurements with Allan deviations down to 12 nanometers at averaging times of 13 microseconds along with ultrafast ranging at acquisition rates of 100 megahertz, allowing for in-flight sampling of gun projectiles moving at 150 meters per second. Combining integrated soliton-comb ranging systems with chip-scale nanophotonic phased arrays could enable compact ultrafast ranging systems for emerging mass applications.

Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

DEFF Research Database (Denmark)

Gustavsson, Natalia; Lao, Ye; Maximov, Anton

2008-01-01

and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium...... secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance...... responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor...

Ultrafast dynamic ellipsometry and spectroscopies of laser shocked materials

Energy Technology Data Exchange (ETDEWEB)

Mcgrane, Shawn David [Los Alamos National Laboratory; Bolme, Cindy B [Los Alamos National Laboratory; Whitley, Von H [Los Alamos National Laboratory; Moore, David S [Los Alamos National Laboratory

2010-01-01

Ultrafast ellipsometry and transient absorption spectroscopies are used to measure material dynamics under extreme conditions of temperature, pressure, and volumetric compression induced by shock wave loading with a chirped, spectrally clipped shock drive pulse.

Compression of Ultrafast Laser Beams

Science.gov (United States)

2016-03-01

Copyright 2003, AIP Publishing LLC. DOI: http://dx.doi.org/10.1063/1.1611998.) When designing the pulse shaper, the laser beam must completely fill the...for the design of future versions of this device. The easiest way to align the pulse shaper is to use the laser beam that will be shaped, without...Afterward, an ultrafast thin beam splitter is placed into the system after the diameter of the laser beam is reduced; this is done to monitor the beam

Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice

NARCIS (Netherlands)

Heijboer, A. C.; van den Hoek, A. M.; Parlevliet, E. T.; Havekes, L. M.; Romijn, J. A.; Pijl, H.; Corssmit, E. P. M.

2006-01-01

This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the action of insulin,

Ultrafast Dynamics of Quantum-Dot Semiconductor Optical Amplifiers

DEFF Research Database (Denmark)

Poel, Mike van der; Hvam, Jørn Märcher

2007-01-01

We report on a series of experiments on the dynamical properties of quantum-dot semiconductor optical amplifiers. We show how the amplifier responds to one or several ultrafast (170 fs) pulses in rapid succession and our results demonstrate applicability and ultimate limitations to application...

Functional MRI of the patellofemoral joint: comparison of ultrafast MRI, motion-triggered cine MRI and static MRI

Energy Technology Data Exchange (ETDEWEB)

Muhle, C. [Klinik fuer Radiologische Diagnostik, Univ. Kiel (Germany); Brossmann, J. [Klinik fuer Radiologische Diagnostik, Univ. Kiel (Germany); Melchert, U.H. [Klinik fuer Radiologische Diagnostik, Univ. Kiel (Germany); Schroeder, C. [Radiologische Abt., Universitaets-Kinderklinik, Christian-Albrechts-Universitaet, Kiel (Germany); Boer, R. de [Philips Medical Systems, Best (Netherlands); Spielmann, R.P. [Klinik fuer Radiologische Diagnostik, Univ. Kiel (Germany); Heller, M. [Klinik fuer Radiologische Diagnostik, Univ. Kiel (Germany)

1995-12-31

To evaluate the feasibility and usefulness of ultrafast MRI (u), patellar tracking from 30 of flexion to knee extension (0 ) was analysed and compared with motion-triggered cine MRI (m) and a static MRI technique (s). The different imaging methods were compared in respect of the patellofemoral relationship, the examination time and image quality. Eight healthy subjects and four patients (in total 18 joints) with patellar subluxation or luxation were examined. Significant differences between the static MRI series without quadriceps contraction and the functional MRI studies (motion-triggered cine MRI and ultrafast MRI) were found for the patellar tilt angle. In the dynamic joint studies there was no statistical difference of the regression coefficients between the motion-triggered cine MRI studies and the ultrafast MRI studies. The findings of the functional MRI studies compared with the static MRI images were significantly different for the lateralisation of the patella, expressed by the lateral patellar displacement and bisect offset. No significant differences in patellar lateralisation were found between motion-triggered cine MRI and ultrafast MRI. Ultrafast MRI was superior to motion-triggered cine MRI in terms of the reduction in imaging time and improvement of the image quality. (orig.)

Functional MRI of the patellofemoral joint: comparison of ultrafast MRI, motion-triggered cine MRI and static MRI

International Nuclear Information System (INIS)

Muhle, C.; Brossmann, J.; Melchert, U.H.; Schroeder, C.; Boer, R. de; Spielmann, R.P.; Heller, M.

1995-01-01

To evaluate the feasibility and usefulness of ultrafast MRI (u), patellar tracking from 30 of flexion to knee extension (0 ) was analysed and compared with motion-triggered cine MRI (m) and a static MRI technique (s). The different imaging methods were compared in respect of the patellofemoral relationship, the examination time and image quality. Eight healthy subjects and four patients (in total 18 joints) with patellar subluxation or luxation were examined. Significant differences between the static MRI series without quadriceps contraction and the functional MRI studies (motion-triggered cine MRI and ultrafast MRI) were found for the patellar tilt angle. In the dynamic joint studies there was no statistical difference of the regression coefficients between the motion-triggered cine MRI studies and the ultrafast MRI studies. The findings of the functional MRI studies compared with the static MRI images were significantly different for the lateralisation of the patella, expressed by the lateral patellar displacement and bisect offset. No significant differences in patellar lateralisation were found between motion-triggered cine MRI and ultrafast MRI. Ultrafast MRI was superior to motion-triggered cine MRI in terms of the reduction in imaging time and improvement of the image quality. (orig.)

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

Science.gov (United States)

Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Time-resolved single-shot terahertz time-domain spectroscopy for ultrafast irreversible processes

Science.gov (United States)

Zhai, Zhao-Hui; Zhong, Sen-Cheng; Li, Jun; Zhu, Li-Guo; Meng, Kun; Li, Jiang; Liu, Qiao; Peng, Qi-Xian; Li, Ze-Ren; Zhao, Jian-Heng

2016-09-01

Pulsed terahertz spectroscopy is suitable for spectroscopic diagnostics of ultrafast events. However, the study of irreversible or single shot ultrafast events requires ability to record transient properties at multiple time delays, i.e., time resolved at single shot level, which is not available currently. Here by angular multiplexing use of femtosecond laser pulses, we developed and demonstrated a time resolved, transient terahertz time domain spectroscopy technique, where burst mode THz pulses were generated and then detected in a single shot measurement manner. The burst mode THz pulses contain 2 sub-THz pulses, and the time gap between them is adjustable up to 1 ns with picosecond accuracy, thus it can be used to probe the single shot event at two different time delays. The system can detect the sub-THz pulses at 0.1 THz-2.5 THz range with signal to noise ratio (SNR) of ˜400 and spectrum resolution of 0.05 THz. System design was described here, and optimizations of single shot measurement of THz pulses were discussed in detail. Methods to improve SNR were also discussed in detail. A system application was demonstrated where pulsed THz signals at different time delays of the ultrafast process were successfully acquired within single shot measurement. This time resolved transient terahertz time domain spectroscopy technique provides a new diagnostic tool for irreversible or single shot ultrafast events where dynamic information can be extracted at terahertz range within one-shot experiment.

High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo.

Directory of Open Access Journals (Sweden)

Li Zhi

Full Text Available Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS production. Western blot analysis was used to examine the levels of insulin receptor (IR, phosphorylated insulin receptor substrate 1 (IRS1, Ser307 and phospho-Akt (Ser473. We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307 and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC, a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307 response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307 and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease.

Impact of local order and stoichiometry on the ultrafast magnetization dynamics of Heusler compounds

International Nuclear Information System (INIS)

Steil, Daniel; Schmitt, Oliver; Fetzer, Roman; Aeschlimann, Martin; Cinchetti, Mirko; Kubota, Takahide; Naganuma, Hiroshi; Oogane, Mikihiko; Ando, Yasuo; Rodan, Steven; Blum, Christian G F; Wurmehl, Sabine; Balke, Benjamin

2015-01-01

Nowadays, a wealth of information on ultrafast magnetization dynamics of thin ferromagnetic films exists in the literature. Information is, however, scarce on bulk single crystals, which may be especially important for the case of multi-sublattice systems. In Heusler compounds, representing prominent examples for such multi-sublattice systems, off-stoichiometry and degree of order can significantly change the magnetic properties of thin films, while bulk single crystals may be generally produced with a much more well-defined stoichiometry and a higher degree of ordering. A careful characterization of the local structure of thin films versus bulk single crystals combined with ultrafast demagnetization studies can, thus, help to understand the impact of stoichiometry and order on ultrafast spin dynamics.Here, we present a comparative study of the structural ordering and magnetization dynamics for thin films and bulk single crystals of the family of Heusler alloys with composition Co 2 Fe 1 − x Mn x Si. The local ordering is studied by 59 Co nuclear magnetic resonance (NMR) spectroscopy, while the time-resolved magneto-optical Kerr effect gives access to the ultrafast magnetization dynamics. In the NMR studies we find significant differences between bulk single crystals and thin films, both regarding local ordering and stoichiometry. The ultrafast magnetization dynamics, on the other hand, turns out to be mostly unaffected by the observed structural differences, especially on the time scale of some hundreds of femtoseconds. These results confirm hole-mediated spin-flip processes as the main mechanism for ultrafast demagnetization and the robustness of this demagnetization channel against defect states in the minority band gap as well as against the energetic position of the band gap with respect to the Fermi energy. The very small differences observed in the magnetization dynamics on the picosecond time-scale, on the other hand, can be explained by considering the

Ultrafast, laser-based, x-ray science: the dawn of atomic-scale cinematography

International Nuclear Information System (INIS)

Barty, C.P.J.

2000-01-01

The characteristics of ultrafast chirped pulse amplification systems are reviewed. Application of ultrafast chirped pulse amplification to the generation of femtosecond, incoherent, 8-keV line radiation is outlined and the use of femtosecond laser-based, x-rays for novel time-resolved diffraction studies of crystalline dynamics with sub-picosecond temporal resolution and sub-picometer spatial resolution is reviewed in detail. Possible extensions of laser-based, x-ray technology and evaluation of alternative x-ray approaches for time-resolved studies of the atomic scale dynamics are given. (author)

Ultrafast, laser-based, x-ray science: the dawn of atomic-scale cinematography

Energy Technology Data Exchange (ETDEWEB)

Barty, C.P.J. [University of California, Department of Applied Mechanics and Engineering Science, Urey Hall, Mali Code 0339, San Diego, La Jolla, CA (United States)

2000-03-01

The characteristics of ultrafast chirped pulse amplification systems are reviewed. Application of ultrafast chirped pulse amplification to the generation of femtosecond, incoherent, 8-keV line radiation is outlined and the use of femtosecond laser-based, x-rays for novel time-resolved diffraction studies of crystalline dynamics with sub-picosecond temporal resolution and sub-picometer spatial resolution is reviewed in detail. Possible extensions of laser-based, x-ray technology and evaluation of alternative x-ray approaches for time-resolved studies of the atomic scale dynamics are given. (author)

Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

Science.gov (United States)

Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

2015-01-01

A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

Science.gov (United States)

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and

Dietary Anthocyanins and Insulin Resistance: When Food Becomes a Medicine.

Science.gov (United States)

Belwal, Tarun; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Habtemariam, Solomon

2017-10-12

Insulin resistance is an abnormal physiological state that occurs when insulin from pancreatic β-cells is unable to trigger a signal transduction pathway in target organs such as the liver, muscles and adipose tissues. The loss of insulin sensitivity is generally associated with persistent hyperglycemia (diabetes), hyperinsulinemia, fatty acids and/or lipid dysregulation which are often prevalent under obesity conditions. Hence, insulin sensitizers are one class of drugs currently employed to treat diabetes and associated metabolic disorders. A number of natural products that act through multiple mechanisms have also been identified to enhance insulin sensitivity in target organs. One group of such compounds that gained interest in recent years are the dietary anthocyanins. Data from their in vitro, in vivo and clinical studies are scrutinized in this communication to show their potential health benefit through ameliorating insulin resistance. Specific mechanism of action ranging from targeting specific signal transduction receptors/enzymes to the general antioxidant and anti-inflammatory mechanisms of insulin resistance are presented.

Studies of insulin resistance in congenital generalized lipodystrophy

DEFF Research Database (Denmark)

Søvik, O; Vestergaard, H; Trygstad, O

1996-01-01

suppressed lipid oxidation in the controls. It is concluded that patients with congenital generalized lipodystrophy may present severe insulin resistance with regard to hepatic glucose production as well as muscle glycogen synthesis and lipid oxidation. The results suggest a postreceptor defect in the action......, immunoreactive protein and mRNA levels. The patients had fasting hyperinsulinaemia, and the rate of total glucose disposal was severely impaired, primarily due to a decreased non-oxidative glucose metabolism. In the patient studied with muscle biopsy, the expected activation of glycogen synthase by insulin did...... not occur. In both patients there was severely increased hepatic glucose output in the basal state, suggesting a failure of insulin to suppress hepatic gluconeogenesis. During insulin infusion a substantially elevated rate of lipid oxidation remained in the patients, in contrast to the almost completely...

Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

Science.gov (United States)

Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

2017-09-01

Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

International Nuclear Information System (INIS)

Androlewicz, M.J.; Straus, D.S.; Brandenburg, D.F.

1989-01-01

Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125 I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degree C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation

Ultrafast quantum control of ionization dynamics in krypton.

Science.gov (United States)

Hütten, Konrad; Mittermair, Michael; Stock, Sebastian O; Beerwerth, Randolf; Shirvanyan, Vahe; Riemensberger, Johann; Duensing, Andreas; Heider, Rupert; Wagner, Martin S; Guggenmos, Alexander; Fritzsche, Stephan; Kabachnik, Nikolay M; Kienberger, Reinhard; Bernhardt, Birgitta

2018-02-19

Ultrafast spectroscopy with attosecond resolution has enabled the real time observation of ultrafast electron dynamics in atoms, molecules and solids. These experiments employ attosecond pulses or pulse trains and explore dynamical processes in a pump-probe scheme that is selectively sensitive to electronic state of matter via photoelectron or XUV absorption spectroscopy or that includes changes of the ionic state detected via photo-ion mass spectrometry. Here, we demonstrate how the implementation of combined photo-ion and absorption spectroscopy with attosecond resolution enables tracking the complex multidimensional excitation and decay cascade of an Auger auto-ionization process of a few femtoseconds in highly excited krypton. In tandem with theory, our study reveals the role of intermediate electronic states in the formation of multiply charged ions. Amplitude tuning of a dressing laser field addresses different groups of decay channels and allows exerting temporal and quantitative control over the ionization dynamics in rare gas atoms.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

Directory of Open Access Journals (Sweden)

Nicole M. Templeman

2017-07-01

Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

Science.gov (United States)

Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

2017-07-11

The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Estimation of Insulin Resistance in Mexican Adults by the [13C]Glucose Breath Test Corrected for Endogenous Total CO2 Production

Directory of Open Access Journals (Sweden)

Erika Ibarra-Pastrana

2012-01-01

Full Text Available Objective. To evaluate the efficacy of the [13C]glucose breath test for measuring insulin resistance in Mexican adults with different glycemic states. Research Design and Methods. Fifty-eight adults underwent a [13C]glucose breath test with simultaneous measurement of total CO2 production by indirect calorimetry, at baseline and 90 minutes after the ingestion of 15 g of dextrose and 25 mg of [13C]glucose. HOMA was used as a marker of insulin resistance. Results. We found an inverse correlation between HOMA and the breath test δ13CO2 (‰, r=-0.41 (P=0.001. After adjusting for total CO2 production, correlations between HOMA and fasting glucose were less strong but remained significant. An ROC curve was constructed using δ13CO2 (‰ and HOMA values; the cut-off point was 9.99‰ δ13CO2, corresponding to a sensitivity of 80.0 (95% CI: 51.9, 95.7 and a specificity of 67.4 (95% CI: 51.5, 80.9. Conclusions. The [13C]glucose breath test is a simple noninvasive procedure but was not sufficiently robust for an accurate diagnosis of insulin resistance. Our findings suggest that the test might be helpful in identifying individuals who are not IR, which in turn may contribute to improved diabetes prevention.

Ultrafast dynamics of Coulomb correlated excitons in GaAs quantum wells

Energy Technology Data Exchange (ETDEWEB)

Mycek, M.A. [Univ. of California, Berkeley, CA (United States). Dept. of Physics]|[Lawrence Berkeley National Lab., CA (United States). Materials Sciences Div.

1995-12-01

The author measures the transient nonlinear optical response of room temperature excitons in gallium arsenide quantum wells via multi-wave mixing experiments. The dynamics of the resonantly excited excitons is directly reflected by the ultrafast decay of the induced nonlinear polarization, which radiates the detected multi-wave mixing signal. She characterizes this ultrafast coherent emission in both amplitude and phase, using time- and frequency-domain measurement techniques, to better understand the role of Coulomb correlation in these systems. To interpret the experimental results, the nonlinear optical response of a dense medium is calculated using a model including Coulomb interaction. She contributes three new elements to previous theoretical and experimental studies of these systems. First, surpassing traditional time-integrated measurements, she temporally resolves the amplitude of the ultrafast coherent emission. Second, in addition to measuring the third-order four-wave mixing signal, she also investigates the fifth-order six-wave mixing response. Third, she characterizes the ultrafast phase dynamics of the nonlinear emission using interferometric techniques with an unprecedented resolution of approximately 140 attoseconds. The author finds that effects arising from Coulomb correlation dominate the nonlinear optical response when the density of excitons falls below 3 {times} 10{sup 11} cm{sup {minus}2}, the saturation density. These signatures of Coulomb correlation are investigated for increasing excitation density to gradually screen the interactions and test the validity of the model for dense media. The results are found to be qualitatively consistent with both the predictions of the model and with numerical solutions to the semiconductor Bloch equations. Importantly, the results also indicate current experimental and theoretical limitations, which should be addressed in future research.

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

Directory of Open Access Journals (Sweden)

Chih-Ting Su

2016-11-01

Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

Intracellular and extracellular adenosine triphosphate in regulation of insulin secretion from pancreatic β cells (β).

Science.gov (United States)

Wang, Chunjiong; Geng, Bin; Cui, Qinghua; Guan, Youfei; Yang, Jichun

2014-03-01

Adenosine triphosphate (ATP) synthesis and release in mitochondria play critical roles in regulating insulin secretion in pancreatic β cells. Mitochondrial dysfunction is mainly characterized by a decrease in ATP production, which is a central event in the progression of pancreatic β cell dysfunction and diabetes. ATP has been demonstrated to regulate insulin secretion via several pathways: (i) Intracellular ATP directly closes ATP-sensitive potassium channel to open L-type calcium channel, leading to an increase in free cytosolic calcium levels and exocytosis of insulin granules; (ii) A decrease in ATP production is always associated with an increase in production of reactive oxygen species, which exerts deleterious effects on pancreatic β cell survival and insulin secretion; and (iii) ATP can be co-secreted with insulin from pancreatic β cells, and the released ATP functions as an autocrine signal to modulate insulin secretory process via P2 receptors on the cell membrane. In this review, the recent findings regarding the role and mechanism of ATP synthesis and release in regulation of insulin secretion from pancreatic β cells will be summarized and discussed. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Postprandial Glucose and Insulin Responses to Grain Products in ...

African Journals Online (AJOL)

Prof. Ogunji

diabetes was low in women who consumed more cereal and vegetable fiber. Under normal ... Body Mass Index (BMI) was calculated, and obesity was defined as a ... much they could eat and be satisfied. There was no .... advantageous with respect to the insulin resistance syndrome since from this study the low glycaemic.

Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

Directory of Open Access Journals (Sweden)

Pešić Milica

2007-01-01

Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Robust Stacking-Independent Ultrafast Charge Transfer in MoS2/WS2 Bilayers.

Science.gov (United States)

Ji, Ziheng; Hong, Hao; Zhang, Jin; Zhang, Qi; Huang, Wei; Cao, Ting; Qiao, Ruixi; Liu, Can; Liang, Jing; Jin, Chuanhong; Jiao, Liying; Shi, Kebin; Meng, Sheng; Liu, Kaihui

2017-12-26

Van der Waals-coupled two-dimensional (2D) heterostructures have attracted great attention recently due to their high potential in the next-generation photodetectors and solar cells. The understanding of charge-transfer process between adjacent atomic layers is the key to design optimal devices as it directly determines the fundamental response speed and photon-electron conversion efficiency. However, general belief and theoretical studies have shown that the charge transfer behavior depends sensitively on interlayer configurations, which is difficult to control accurately, bringing great uncertainties in device designing. Here we investigate the ultrafast dynamics of interlayer charge transfer in a prototype heterostructure, the MoS 2 /WS 2 bilayer with various stacking configurations, by optical two-color ultrafast pump-probe spectroscopy. Surprisingly, we found that the charge transfer is robust against varying interlayer twist angles and interlayer coupling strength, in time scale of ∼90 fs. Our observation, together with atomic-resolved transmission electron characterization and time-dependent density functional theory simulations, reveals that the robust ultrafast charge transfer is attributed to the heterogeneous interlayer stretching/sliding, which provides additional channels for efficient charge transfer previously unknown. Our results elucidate the origin of transfer rate robustness against interlayer stacking configurations in optical devices based on 2D heterostructures, facilitating their applications in ultrafast and high-efficient optoelectronic and photovoltaic devices in the near future.

Extrinsic factors promoting insulin producing cell-differentiation and insulin expression enhancement-hope for diabetics.

Science.gov (United States)

Dave, Shruti

2013-11-01

Diabetes mellitus (DM) is considered to be an autoimmune disorder leading to destruction of beta-cells resulting in to a loss of blood sugar control. Attempts using many pharmacological compositions including exogenous insulin have failed to show tight control of glycemia and associated manifestations. Stem cells are considered a potential tool for the supply of insulin-producing cells (IPC) generation in vitro. Stem cell differentiation in to pancreatic lineages requires influence of both intrinsic and extrinsic factors. Application of islet growth factors is considered to be potential for enhancement of beta-cell replication, function and survival. Use of certain extrinsic factors is known to facilitate expression of transcription factors known to be important for beta-cell differentiation and production of insulin enabling IPC generation. Hierarchies of secreted signals and transcription factors have been identified by studies from several laboratories that guide cell differentiation in to IPC. This knowledge provides insights for in vitro IPC differentiation from stem cells. Current advancement in medical knowledge promises an insulin independency for DM patients. The review sheds light on few specific extrinsic factors which facilitate differentiation of stem cells in to IPC in vitro have been discussed; which can be proven as a potential therapeutic option for treatment of DM and associated diseases.

Ultra-Fast Low Energy Switching Using an InP Photonic Crystal H0 Nanocavity

DEFF Research Database (Denmark)

Yu, Yi; Palushani, Evarist; Heuck, Mikkel

2013-01-01

Pump-probe measurements on InP photonic crystal H0 nanocavities show large-contrast ultrafast switching at low pulse energy. For large pulse energies, high-frequency carrier density oscillations are induced, leading to pulsesplitting.......Pump-probe measurements on InP photonic crystal H0 nanocavities show large-contrast ultrafast switching at low pulse energy. For large pulse energies, high-frequency carrier density oscillations are induced, leading to pulsesplitting....

A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin).

Science.gov (United States)

Brange, J; Dodson, G G; Edwards, D J; Holden, P H; Whittingham, J L

1997-04-01

The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.

A one-step strategy for ultra-fast and low-cost mass production of plastic membrane microfluidic chips.

Science.gov (United States)

Hu, Chong; Lin, Sheng; Li, Wanbo; Sun, Han; Chen, Yangfan; Chan, Chiu-Wing; Leung, Chung-Hang; Ma, Dik-Lung; Wu, Hongkai; Ren, Kangning

2016-10-05

An ultra-fast, extremely cost-effective, and environmentally friendly method was developed for fabricating flexible microfluidic chips with plastic membranes. With this method, we could fabricate plastic microfluidic chips rapidly (within 12 seconds per piece) at an extremely low cost (less than $0.02 per piece). We used a heated perfluoropolymer perfluoroalkoxy (often called Teflon PFA) solid stamp to press a pile of two pieces of plastic membranes, low density polyethylene (LDPE) and polyethylene terephthalate (PET) coated with an ethylene-vinyl acetate copolymer (EVA). During the short period of contact with the heated PFA stamp, the pressed area of the membranes permanently bonded, while the LDPE membrane spontaneously rose up at the area not pressed, forming microchannels automatically. These two regions were clearly distinguishable even at the micrometer scale so we were able to fabricate microchannels with widths down to 50 microns. This method combines the two steps in the conventional strategy for microchannel fabrication, generating microchannels and sealing channels, into a single step. The production is a green process without using any solvent or generating any waste. Also, the chips showed good resistance against the absorption of Rhodamine 6G, oligonucleotides, and green fluorescent protein (GFP). We demonstrated some typical microfluidic manipulations with the flexible plastic membrane chips, including droplet formation, on-chip capillary electrophoresis, and peristaltic pumping for quantitative injection of samples and reagents. In addition, we demonstrated convenient on-chip detection of lead ions in water samples by a peristaltic-pumping design, as an example of the application of the plastic membrane chips in a resource-limited environment. Due to the high speed and low cost of the fabrication process, this single-step method will facilitate the mass production of microfluidic chips and commercialization of microfluidic technologies.

Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

Science.gov (United States)

Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

2017-12-01

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lasing cavities and ultra-fast switch based on self-collimation of photonic crystal

International Nuclear Information System (INIS)

Zhao Deyin; Zhou Chuanhong; Gong Qian; Jiang Xunya

2008-01-01

The lasing cavities and ultra-fast switch based on the self-collimation (SC) of photonic crystal have been studied in this work. Some special properties of these devices are demonstrated, such as the higher quality factors and concise integration of the lasing cavities, the tolerance of the non-parallel reflectors in Fabry-Perot cavities. With nonlinearity, the ultra-fast switch can also be realized around the SC frequency. All these functional devices are designed based on the strong beam confinement of SC

Lasing cavities and ultra-fast switch based on self-collimation of photonic crystal

Energy Technology Data Exchange (ETDEWEB)

Zhao Deyin; Zhou Chuanhong; Gong Qian; Jiang Xunya [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China)], E-mail: xyjiang@mit.edu

2008-06-07

The lasing cavities and ultra-fast switch based on the self-collimation (SC) of photonic crystal have been studied in this work. Some special properties of these devices are demonstrated, such as the higher quality factors and concise integration of the lasing cavities, the tolerance of the non-parallel reflectors in Fabry-Perot cavities. With nonlinearity, the ultra-fast switch can also be realized around the SC frequency. All these functional devices are designed based on the strong beam confinement of SC.

Measuring and understanding ultrafast phenomena using X-rays

DEFF Research Database (Denmark)

Haldrup, Kristoffer; Nielsen, Martin Meedom

2014-01-01

Within the last decade, significant advances in X-ray sources and instrumentation as well as simultaneous developments in analysis methodology has allowed the field of fast- and ultrafast time-resolved X-ray studies of solution-state systems to truly come of age. We here describe some aspects of ...

Sulfation of insulin and electrophoresis of the products obtained

NARCIS (Netherlands)

Sluyterman, L.A.A.E.; Kwestroo - van de Bosch, J.M.

1960-01-01

The SO3 complexes of a few tertiary amines were tested for their ability to introduce SO3 groups into insulin. Pyridinium sulphonic acid was found to be the most suitable one. This reagent is not hydrolyzed immediately and therefore is able to exert a sulphating action for some time after being

Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster

OpenAIRE

Yu, Yue; Sun, Ying; He, Shengqi; Yan, Cheng; Rui, Liangyou; Li, Wenjun; Liu, Yong

2012-01-01

The Cbl family proteins function as both E3 ubiquitin ligases and adaptor proteins to regulate various cellular signaling events, including the insulin/insulin-like growth factor 1 (IGF1) and epidermal growth factor (EGF) pathways. These pathways play essential roles in growth, development, metabolism, and survival. Here we show that in Drosophila melanogaster, Drosophila Cbl (dCbl) regulates longevity and carbohydrate metabolism through downregulating the production of Drosophila insulin-lik...

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

Science.gov (United States)

Yamazaki, Ricardo K; Brito, Gleisson A P; Coelho, Isabela; Pequitto, Danielle C T; Yamaguchi, Adriana A; Borghetti, Gina; Schiessel, Dalton Luiz; Kryczyk, Marcelo; Machado, Juliano; Rocha, Ricelli E R; Aikawa, Julia; Iagher, Fabiola; Naliwaiko, Katya; Tanhoffer, Ricardo A; Nunes, Everson A; Fernandes, Luiz Claudio

2011-04-28

Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Ultrafast Non-Thermal Electron Dynamics in Single Layer Graphene

Directory of Open Access Journals (Sweden)

Novoselov K.S.

2013-03-01

Full Text Available We study the ultrafast dynamics of non-thermal electron relaxation in graphene upon impulsive excitation. The 10-fs resolution two color pump-probe allows us to unveil the non-equilibrium electron gas decay at early times.

Ultrafast Photovoltaic Response in Ferroelectric Nanolayers

Science.gov (United States)

2016-04-19

the free energy of the system [3,4,8]. Intensive research has been aimed at bypassing the intrinsic size limits imposed by the depolarization field...Page 1 of 21   Ultrafast photovoltaic response in ferroelectric nanolayers Dan Daranciang1,2, Matthew J. Highland3, Haidan Wen4, Steve M. Young5...ferroelectric PbTiO3 via direct coupling to its intrinsic photovoltaic response. Using time-resolved x-ray scattering to visualize atomic displacements on

Influence of Flavonoids on Mechanism of Modulation of Insulin Secretion.

Science.gov (United States)

Soares, Juliana Mikaelly Dias; Pereira Leal, Ana Ediléia Barbosa; Silva, Juliane Cabral; Almeida, Jackson R G S; de Oliveira, Helinando Pequeno

2017-01-01

The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells. Twelve articles were included and represent the basis of discussion on mechanisms of insulin secretion of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44, PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases. According to the literature, the majority of flavonoid subclasses can modulate insulin secretion through several pathways, in an indication that corresponding molecule is a potential candidate for active materials to be applied in the treatment of diabetes. The action of natural products on insulin secretion represents an important investigation topic due to their importance in the diabetes controlIn addition to their typical antioxidant properties, flavonoids contribute to the insulin secretionThe modulation of insulin secretion is induced by flavonoids according to different mechanisms. Abbreviations used: K ATP channels: ATP-sensitive K + channels, GLUT4: Glucose transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L-VDCCs: L-type voltage-dependent Ca +2 channels, GLUT1: Glucose transporter 1, AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II: Ca 2+ /calmodulin

Anti-insulin antibody test

Science.gov (United States)

Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

Science.gov (United States)

Zeng, Yi; Zhang, Le; Hu, Zhiping

2016-01-01

Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

Attosecond electron pulse trains and quantum state reconstruction in ultrafast transmission electron microscopy

Science.gov (United States)

Priebe, Katharina E.; Rathje, Christopher; Yalunin, Sergey V.; Hohage, Thorsten; Feist, Armin; Schäfer, Sascha; Ropers, Claus

2017-12-01

Ultrafast electron and X-ray imaging and spectroscopy are the basis for an ongoing revolution in the understanding of dynamical atomic-scale processes in matter. The underlying technology relies heavily on laser science for the generation and characterization of ever shorter pulses. Recent findings suggest that ultrafast electron microscopy with attosecond-structured wavefunctions may be feasible. However, such future technologies call for means to both prepare and fully analyse the corresponding free-electron quantum states. Here, we introduce a framework for the preparation, coherent manipulation and characterization of free-electron quantum states, experimentally demonstrating attosecond electron pulse trains. Phase-locked optical fields coherently control the electron wavefunction along the beam direction. We establish a new variant of quantum state tomography—`SQUIRRELS'—for free-electron ensembles. The ability to tailor and quantitatively map electron quantum states will promote the nanoscale study of electron-matter entanglement and new forms of ultrafast electron microscopy down to the attosecond regime.

Large lateral photovoltaic effect with ultrafast relaxation time in SnSe/Si junction

Energy Technology Data Exchange (ETDEWEB)

Wang, Xianjie; Zhao, Xiaofeng; Hu, Chang; Zhang, Yang; Song, Bingqian; Zhang, Lingli; Liu, Weilong; Lv, Zhe; Zhang, Yu; Sui, Yu, E-mail: suiyu@hit.edu.cn [Department of Physics, Harbin Institute of Technology, Harbin 150001 (China); Tang, Jinke [Department of Physics and Astronomy, University of Wyoming, Laramie, Wyoming 82071 (United States); Song, Bo, E-mail: songbo@hit.edu.cn [Department of Physics, Harbin Institute of Technology, Harbin 150001 (China); Academy of Fundamental and Interdisciplinary Sciences, Harbin Institute of Technology, Harbin 150001 (China)

2016-07-11

In this paper, we report a large lateral photovoltaic effect (LPE) with ultrafast relaxation time in SnSe/p-Si junctions. The LPE shows a linear dependence on the position of the laser spot, and the position sensitivity is as high as 250 mV mm{sup −1}. The optical response time and the relaxation time of the LPE are about 100 ns and 2 μs, respectively. The current-voltage curve on the surface of the SnSe film indicates the formation of an inversion layer at the SnSe/p-Si interface. Our results clearly suggest that most of the excited-electrons diffuse laterally in the inversion layer at the SnSe/p-Si interface, which results in a large LPE with ultrafast relaxation time. The high positional sensitivity and ultrafast relaxation time of the LPE make the SnSe/p-Si junction a promising candidate for a wide range of optoelectronic applications.

Role of increased insulin demand in the adaptation of the endocrine pancreas to pregnancy

NARCIS (Netherlands)

Nieuwenhuizen, AG; Schuiling, GA; Moes, H; Koiter, TR

During gestation the demand for insulin increases due to a decrease in insulin sensitivity of the maternal tissues. Simultaneously, pancreatic islet-cell proliferation, as well as insulin production and secretion increase. Both phenomena appear to be caused by the actions of pregnancy hormones. We

Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat.

OpenAIRE

Walker, A P; Flint, D J

1983-01-01

Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to ...

Ultrafast Charge Photogeneration in MEH-PPV Charge-Transfer Complexes

NARCIS (Netherlands)

Bakulin, Artem A.; Paraschuk, Dmitry Yu; Pshenichnikov, Maxim S.; van Loosdrecht, Paul H. M.; Corkum, P; DeSilvestri, S; Nelson, KA; Riedle, E; Schoenlein, RW

2009-01-01

Visible-pump - IR-probe spectroscopy is used to study the ultrafast charge dynamics in MEH-PPV based charge-transfer complexes and donor-acceptor blends. Transient anisotropy of the polymer polaron band provides invaluable insights into excitation localisation and charge-transfer pathways.

Clinical use of the co-formulation of insulin degludec and insulin aspart

DEFF Research Database (Denmark)

Kumar, A; Awata, T; Bain, S C

2016-01-01

(HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...... a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins....

Intensified CCD for ultrafast diagnostics

International Nuclear Information System (INIS)

Cheng, J.; Tripp, G.; Coleman, L.

1978-01-01

Many of the present laser fusion diagnostics are recorded on either ultrafast streak cameras or on oscilloscopes. For those experiments in which a large volume of data is accumulated, direct computer processing of the information becomes important. We describe an approach which uses a RCA 52501 back-thinned CCD sensor to obtain direct electron readouts for both the streak camera and the CRT. Performance of the 100 GHz streak camera and the 4 GHz CRT are presented. Design parameters and computer interfacing for both systems are described in detail

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.

Science.gov (United States)

Shi, Xuemei; Chacko, Shaji; Li, Feng; Li, Depei; Burrin, Douglas; Chan, Lawrence; Guan, Xinfu

2017-11-01

Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS. We characterized the metabolic impact of PPG neuron activation on glucose homeostasis and insulin sensitivity using stable isotopic tracers coupled with hyperinsulinemic euglycemic clamp. We showed that after ip injection of clozapine N-oxide, Gcg-Cre lean mice transduced with hM3Dq in the brainstem NTS downregulated basal endogenous glucose production and enhanced glucose tolerance following ip glucose tolerance test. Moreover, acute activation of PPG neurons NTS enhanced whole-body insulin sensitivity as indicated by increased glucose infusion rate as well as augmented insulin-suppression of endogenous glucose production and gluconeogenesis. In contrast, insulin-stimulation of glucose disposal was not altered significantly. We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Aneurysmatic dissection of an aberrant right subclavian artery; Disseziierendes Aneurysma einer aberranten Arteria subclavia dextra: Diagnose mittels Ultrafast-CT

Energy Technology Data Exchange (ETDEWEB)

Reittner, P. [Universitaetsklinik fuer Radiologie, Graz (Austria). Abt. fuer Allgemeine Radiologie; Stacher, R. [Universitaetsklinik fuer Radiologie, Graz (Austria). Abt. fuer Allgemeine Radiologie

1996-01-01

Diagnosis with Ultrafast-CT: An aneurysm of an aberrant right subclavian artery is a very rare cause for dysphagia. We describe such a case in a 67-year-old patient, diagnosed with Ultrafast-CT and discuss it together in concert with the embryology and the radiological findings. (orig.) [Deutsch] Eine aberrierende Arteria subclavia dextra ist eine seltene Ursache fuer Dysphagie. Anhand eines 67jaehrigen Patienten werden Embryologie und radiologische Charakteristika, diagnostiziert mittels Ultrafast-CT, diskutiert. (orig.)

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

DEFF Research Database (Denmark)

Højlund, Kurt

2014-01-01

. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

21 CFR 522.1160 - Insulin.

Science.gov (United States)

2010-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a... IU per kilogram of body weight by subcutaneous injection concurrently with or right after a meal...

The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.

Science.gov (United States)

Guerrero-Romero, Fernando; Simental-Mendía, Luis E; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Ramos-Zavala, María G; Hernández-González, Sandra O; Jacques-Camarena, Omar; Rodríguez-Morán, Martha

2010-07-01

To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. We performed a euglycemic-hyperinsulinemic clamp test. Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney

DEFF Research Database (Denmark)

Laustsen, Christoffer; Lipsø, Hans Kasper Wigh; Østergaard, Jakob Appel

2014-01-01

with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which...... administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization...... and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates...

Multilayer-WS2:ferroelectric composite for ultrafast tunable metamaterial-induced transparency applications

Science.gov (United States)

Yang, Xiaoyu; Yang, Jinghuan; Hu, Xiaoyong; Zhu, Yu; Yang, Hong; Gong, Qihuang

2015-08-01

An ultrafast and low-power all-optical tunable metamaterial-induced transparency is realized, using polycrystalline barium titanate doped gold nanoparticles and multilayer tungsten disulfide microsheets as nonlinear optical materials. Large nonlinearity enhancement is obtained associated with quantum confinement effect, local-field effect, and reinforced interaction between light and multilayer tungsten disulfide. Low threshold pump intensity of 20 MW/cm2 is achieved. An ultrafast response time of 85 ps is maintained because of fast carrier relaxation dynamics in nanoscale crystal grains of polycrystalline barium titanate. This may be useful for the study of integrated photonic devices based on two-dimensional materials.

Multilayer-WS2:ferroelectric composite for ultrafast tunable metamaterial-induced transparency applications

International Nuclear Information System (INIS)

Yang, Xiaoyu; Yang, Jinghuan; Zhu, Yu; Yang, Hong; Hu, Xiaoyong; Gong, Qihuang

2015-01-01

An ultrafast and low-power all-optical tunable metamaterial-induced transparency is realized, using polycrystalline barium titanate doped gold nanoparticles and multilayer tungsten disulfide microsheets as nonlinear optical materials. Large nonlinearity enhancement is obtained associated with quantum confinement effect, local-field effect, and reinforced interaction between light and multilayer tungsten disulfide. Low threshold pump intensity of 20 MW/cm 2 is achieved. An ultrafast response time of 85 ps is maintained because of fast carrier relaxation dynamics in nanoscale crystal grains of polycrystalline barium titanate. This may be useful for the study of integrated photonic devices based on two-dimensional materials

Modern basal insulins: an ongoing story or the start of a new era?

Directory of Open Access Journals (Sweden)

Ivan Ivanovich Dedov

2015-11-01

Full Text Available Basal insulin represents an essential tool in the treatment of both type 1 and type 2 diabetes mellitus. The development of insulin analogues has improved the possibilities of diabetes treatment. Despite significant progress in understanding the physiology, chemistry, kinetics and action of insulin, currently available basal insulin products do not optimally mimic the endogenous profile of insulin. Although basal insulin analogues have some advantages over neutral protamine Hagedorn insulin in diabetes treatment, hypoglycaemia remains the main problem in the achievement of optimal glycaemic control in most patients with diabetes. These unmet clinical needs have stimulated the development of new basal insulin analogues with improved pharmacological profiles. This article reviews the specific characteristics of new long-acting insulin analogues to try and understand their benefits and limitations in the improvement of diabetes management and their possibilities in physiologic and safe insulin replacement.

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

Science.gov (United States)

Petrak, Frank; Herpertz, Stephan; Stridde, Elmar; Pfützner, Andreas

2013-08-01

"Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but

Theory of pump–probe ultrafast photoemission and X-ray absorption spectra

Energy Technology Data Exchange (ETDEWEB)

Fujikawa, Takashi, E-mail: tfujikawa@faculty.chiba-u.jp; Niki, Kaori

2016-01-15

Highlights: • Pump–probe ultrafast XAFS and XPS spectra are theoretically studied. • Keldysh Green's function theory is applied. • Important many-body effects are explicitly included. - Abstract: Keldysh Green's function approach is extensively used in order to derive practical formulas to analyze pump–probe ultrafast photoemission and X-ray absorption spectra. Here the pump pulse is strong enough whereas the probe X-ray pulse can be treated by use of a perturbation theory. We expand full Green's function in terms of renormalized Green's function without the interaction between electrons and probe pulse. The present theoretical formulas allow us to handle the intrinsic and extrinsic losses, and furthermore resonant effects in X-ray Absorption Fine Structures (XAFS). To understand the radiation field screening in XPS spectra, we have to use more sophisticated theoretical approach. In the ultrafast XPS and XAFS analyses the intrinsic and extrinsic loss effects can interfere as well. In the XAFS studies careful analyses are necessary to handle extrinsic losses in terms of damped photoelectron propagation. The nonequilibrium dynamics after the pump pulse irradiation is well described by use of the time-dependent Dyson orbitals. Well above the edge threshold, ultrafast photoelectron diffraction and extended X-ray absorption fine structure (EXAFS) provide us with transient structural change after the laser pump excitations. In addition to these slow processes, the rapid oscillation in time plays an important role related to pump electronic excitations. Near threshold detailed information could be obtained for the combined electronic and structural dynamics. In particular high-energy photoemission and EXAFS are not so influenced by the details of excited states by pump pulse. Random-Phase Approximation (RPA)-boson approach is introduced to derive some practical formulas for time-dependent intrinsic amplitudes.

Enhanced cortisol production rates, free cortisol, and 11beta-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss.

Science.gov (United States)

Purnell, Jonathan Q; Kahn, Steven E; Samuels, Mary H; Brandon, David; Loriaux, D Lynn; Brunzell, John D

2009-02-01

Controversy exists as to whether endogenous cortisol production is associated with visceral obesity and insulin resistance in humans. We therefore quantified cortisol production and clearance rates, abdominal fat depots, insulin sensitivity, and adipocyte gene expression in a cohort of 24 men. To test whether the relationships found are a consequence rather than a cause of obesity, eight men from this larger group were studied before and after weight loss. Daily cortisol production rates (CPR), free cortisol levels (FC), and metabolic clearance rates (MCR) were measured by stable isotope methodology and 24-h sampling; intra-abdominal fat (IAF) and subcutaneous fat (SQF) by computed tomography; insulin sensitivity (S(I)) by frequently sampled intravenous glucose tolerance test; and adipocyte 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1) gene expression by quantitative RT-PCR from subcutaneous biopsies. Increased CPR and FC correlated with increased IAF, but not SQF, and with decreased S(I). Increased 11beta-HSD-1 gene expression correlated with both IAF and SQF and with decreased S(I). With weight loss, CPR, FC, and MCR did not change compared with baseline; however, with greater loss in body fat than lean mass during weight loss, both CPR and FC increased proportionally to final fat mass and IAF and 11beta-HSD-1 decreased compared with baseline. These data support a model in which increased hypothalamic-pituitary-adrenal activity in men promotes selective visceral fat accumulation and insulin resistance and may promote weight regain after diet-induced weight loss, whereas 11beta-HSD-1 gene expression in SQF is a consequence rather than cause of adiposity.

sup 123 I-tyrosine-(A14)-insulin: preparation and preliminary clinical studies. sup 123 I-tyrosin-(A14)-Insulin: Entwicklung und erste klinische Anwendung

Energy Technology Data Exchange (ETDEWEB)

Pantev, T; Virgolini, I; Sinzinger, H; Prager, R; Neuhold, N; Angelberger, P; Banyai, M; Knoebl, P [Oesterreichisches Forschungszentrum Seibersdorf GmbH (Austria). Inst. fuer Chemie Vienna Univ. (Austria). Abt. fuer Nuklearmedizin

1991-01-01

Insulin was radioiodinated with {sup 123}I ({sup 123}I-tyrosine-(A14)-insulin) to a specific activity of 1 {mu}g/mCi, corresponding to 0.025 I.U. of insulin/mCi. This preparation was used for in vitro binding experiments with adipose tissue, showing active binding to the two subunits of the known insulin receptor. In a preliminary clinical investigation, 5 adipose patients with (n = 2) and without (n = 3) diabetes mellitus Type II, were subject to in vivo injection of the same radiolabeled product using 3 mCi/patient. During the first minutes of dynamic imaging, the liver was the major organ of tracer uptake in all patients. Furthermore, the pancreas, and in one patient the kidneys, were visualised. Further studies on insulin in vivo kinetics and quantification are under way. (authors).

Hot-electrons-induced ultrafast demagnitization in Co/Pt multilayers

NARCIS (Netherlands)

Bergeard, N.; Hehn, M.; Mangin, S.; Lengaigne, G.; Montaigne, F.; Lalieu, M. L. M.; Koopmans, B.; Malinowski, G.

2016-01-01

Using specially engineered structures to tailor the optical absorption in a metallic multilayer, we analyze the magnetization dynamics of a Co/Pt multilayer buried below a thick Cu layer. We demonstrate that hot electrons alone can very efficiently induce ultrafast demagnetization. Simulations based

Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging

Science.gov (United States)

Errico, Claudia; Pierre, Juliette; Pezet, Sophie; Desailly, Yann; Lenkei, Zsolt; Couture, Olivier; Tanter, Mickael

2015-11-01

Non-invasive imaging deep into organs at microscopic scales remains an open quest in biomedical imaging. Although optical microscopy is still limited to surface imaging owing to optical wave diffusion and fast decorrelation in tissue, revolutionary approaches such as fluorescence photo-activated localization microscopy led to a striking increase in resolution by more than an order of magnitude in the last decade. In contrast with optics, ultrasonic waves propagate deep into organs without losing their coherence and are much less affected by in vivo decorrelation processes. However, their resolution is impeded by the fundamental limits of diffraction, which impose a long-standing trade-off between resolution and penetration. This limits clinical and preclinical ultrasound imaging to a sub-millimetre scale. Here we demonstrate in vivo that ultrasound imaging at ultrafast frame rates (more than 500 frames per second) provides an analogue to optical localization microscopy by capturing the transient signal decorrelation of contrast agents—inert gas microbubbles. Ultrafast ultrasound localization microscopy allowed both non-invasive sub-wavelength structural imaging and haemodynamic quantification of rodent cerebral microvessels (less than ten micrometres in diameter) more than ten millimetres below the tissue surface, leading to transcranial whole-brain imaging within short acquisition times (tens of seconds). After intravenous injection, single echoes from individual microbubbles were detected through ultrafast imaging. Their localization, not limited by diffraction, was accumulated over 75,000 images, yielding 1,000,000 events per coronal plane and statistically independent pixels of ten micrometres in size. Precise temporal tracking of microbubble positions allowed us to extract accurately in-plane velocities of the blood flow with a large dynamic range (from one millimetre per second to several centimetres per second). These results pave the way for deep non

Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus

International Nuclear Information System (INIS)

Bolinder, J.; Ostman, J.; Arner, P.

1982-01-01

The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono- 125 I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis

Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

Science.gov (United States)

Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

2017-10-01

Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

A spectroelectrochemical cell for ultrafast two-dimensional infrared spectroscopy

Energy Technology Data Exchange (ETDEWEB)

El Khoury, Youssef; Van Wilderen, Luuk J. G. W.; Vogt, Tim; Winter, Ernst; Bredenbeck, Jens, E-mail: bredenbeck@biophysik.uni-frankfurt.org, E-mail: bredenbeck@biophysik.uni-frankfurt.de [Institut für Biophysik, Johann Wolfgang Goethe-Universität, Max-von-Laue-Strasse 1, 60438 Frankfurt (Germany)

2015-08-15

A spectroelectrochemical cell has been designed to combine electrochemistry and ultrafast two-dimensional infrared (2D-IR) spectroscopy, which is a powerful tool to extract structure and dynamics information on the femtosecond to picosecond time scale. Our design is based on a gold mirror with the dual role of performing electrochemistry and reflecting IR light. To provide the high optical surface quality required for laser spectroscopy, the gold surface is made by electron beam evaporation on a glass substrate. Electrochemical cycling facilitates in situ collection of ultrafast dynamics of redox-active molecules by means of 2D-IR. The IR beams are operated in reflection mode so that they travel twice through the sample, i.e., the signal size is doubled. This methodology is optimal for small sample volumes and successfully tested with the ferricyanide/ferrocyanide redox system of which the corresponding electrochemically induced 2D-IR difference spectrum is reported.

Various manifestations of hypertrophic cardiomyopathy on ultrafast computed tomography

International Nuclear Information System (INIS)

Sekiya, Tohru; Karikomi, Masahito; Ohshiro, Masaya; Iwakami, Masayoshi; Takamoto, Toshihiko; Sakamoto, Tsuguya

1992-01-01

Ultrafast computed tomography was performed in 30 patients with hypertrophic cardiomyopathy and images were assessed on variability of left ventricular hypertrophy, the pattern of left ventricular contraction, right ventricular hypertrophy, dilatation of the left atrium, and thickening of the mitral valve. Fifteen (50.0%) of 30 patients had asymmetric septal hypertrophy, six (20.0%) had diffuse hypertrophy, and nine (30.0%) had apical hypertrophy. In eleven patients with asymmetric septal hypertrophy and two with apical hypertrophy, non-hypertrophied segments in end-diastole showed vigorous contraction. Sixteen patients showed homogeneous left ventricular contraction and one showed partial apical contraction. Right ventricular hypertrophy was noted in 12 patients (40.0%), dilatation of the left atrium in 13 patients (43.3%), and mitral valve thickening in three (10.0%). Ultrafast computed tomography was useful in the evaluation of apical hypertrophy and right ventricular hypertrophy, which could be difficult to obtain by echocardiography. (author)

A spectroelectrochemical cell for ultrafast two-dimensional infrared spectroscopy

International Nuclear Information System (INIS)

El Khoury, Youssef; Van Wilderen, Luuk J. G. W.; Vogt, Tim; Winter, Ernst; Bredenbeck, Jens

2015-01-01

A spectroelectrochemical cell has been designed to combine electrochemistry and ultrafast two-dimensional infrared (2D-IR) spectroscopy, which is a powerful tool to extract structure and dynamics information on the femtosecond to picosecond time scale. Our design is based on a gold mirror with the dual role of performing electrochemistry and reflecting IR light. To provide the high optical surface quality required for laser spectroscopy, the gold surface is made by electron beam evaporation on a glass substrate. Electrochemical cycling facilitates in situ collection of ultrafast dynamics of redox-active molecules by means of 2D-IR. The IR beams are operated in reflection mode so that they travel twice through the sample, i.e., the signal size is doubled. This methodology is optimal for small sample volumes and successfully tested with the ferricyanide/ferrocyanide redox system of which the corresponding electrochemically induced 2D-IR difference spectrum is reported

Bunch evolution study in optimization of MeV ultrafast electron diffraction

International Nuclear Information System (INIS)

Lu Xianhai; Du Yingchao; Huang Wenhui; Tang Chuanxiang

2014-01-01

transverse ultrafast electron diffraction (UED) is a promising detection tool for ultrafast processes. The quality of diffraction image is determined by the transverse evolution of the probe bunch. In this paper, we study the contributing terms of the emittance and space charge effects to the bunch evolution in the MeV UED scheme, employing a mean-field model with an ellipsoidal distribution as well as particle tracking simulation. The small transverse dimension of the drive laser is found to be critical to improve the reciprocal resolution, exploiting both smaller emittance and larger transverse bunch size before the solenoid. The degradation of the reciprocal spatial resolution caused by the space charge effects should be carefully controlled. (authors)

Bunch evolution study in optimization of MeV ultrafast electron diffraction

Science.gov (United States)

Lu, Xian-Hai; Du, Ying-Chao; Huang, Wen-Hui; Tang, Chuan-Xiang

2014-12-01

Megaelectronvolt ultrafast electron diffraction (UED) is a promising detection tool for ultrafast processes. The quality of diffraction image is determined by the transverse evolution of the probe bunch. In this paper, we study the contributing terms of the emittance and space charge effects to the bunch evolution in the MeV UED scheme, employing a mean-field model with an ellipsoidal distribution as well as particle tracking simulation. The small transverse dimension of the drive laser is found to be critical to improve the reciprocal resolution, exploiting both smaller emittance and larger transverse bunch size before the solenoid. The degradation of the reciprocal spatial resolution caused by the space charge effects should be carefully controlled.

Differential effects of insulin injections and insulin infusions on levels ...

African Journals Online (AJOL)

Studies have shown that while injections of insulin cause an increase in fat mass, infusions of insulin increase fat mass. The aim of this paper was to test the hypothesis that if an increase in glycogen is an indicator of an impending increase in adipose mass, then insulin infusions should not increase glycogen, while insulin ...

Development of Ultra-Fast Silicon Detectors for 4D tracking

Science.gov (United States)

Staiano, A.; Arcidiacono, R.; Boscardin, M.; Dalla Betta, G. F.; Cartiglia, N.; Cenna, F.; Ferrero, M.; Ficorella, F.; Mandurrino, M.; Obertino, M.; Pancheri, L.; Paternoster, G.; Sola, V.

2017-12-01

In this contribution we review the progress towards the development of a novel type of silicon detectors suited for tracking with a picosecond timing resolution, the so called Ultra-Fast Silicon Detectors. The goal is to create a new family of particle detectors merging excellent position and timing resolution with GHz counting capabilities, very low material budget, radiation resistance, fine granularity, low power, insensitivity to magnetic field, and affordability. We aim to achieve concurrent precisions of ~ 10 ps and ~ 10 μm with a 50 μm thick sensor. Ultra-Fast Silicon Detectors are based on the concept of Low-Gain Avalanche Detectors, which are silicon detectors with an internal multiplication mechanism so that they generate a signal which is factor ~10 larger than standard silicon detectors. The basic design of UFSD consists of a thin silicon sensor with moderate internal gain and pixelated electrodes coupled to full custom VLSI chip. An overview of test beam data on time resolution and the impact on this measurement of radiation doses at the level of those expected at HL-LHC is presented. First I-V and C-V measurements on a new FBK sensor production of UFSD, 50 μm thick, with B and Ga, activated at two diffusion temperatures, with and without C co-implantation (in Low and High concentrations), and with different effective doping concentrations in the Gain layer, are shown. Perspectives on current use of UFSD in HEP experiments (UFSD detectors have been installed in the CMS-TOTEM Precision Protons Spectrometer for the forward physics tracking, and are currently taking data) and proposed applications for a MIP timing layer in the HL-LHC upgrade are briefly discussed.

Case study on the dynamics of ultrafast laser heating and ablation of gold thin films by ultrafast pump-probe reflectometry and ellipsometry

Science.gov (United States)

Pflug, T.; Wang, J.; Olbrich, M.; Frank, M.; Horn, A.

2018-02-01

To increase the comprehension of ultrafast laser ablation, the ablation process has to be portrayed with sufficient temporal resolution. For example, the temporal modification of the complex refractive index {\\tilde{n}} and the relative reflectance of a sample material after irradiation with ultrafast single-pulsed laser radiation can be measured with a pump-probe setup. This work describes the construction and validation of a pump-probe setup enabling spatially, temporally, and spectroscopically resolved Brewster angle microscopy, reflectometry, ellipsometry, and shadow photography. First pump-probe reflectometry and ellipsometry measurements are performed on gold at λ _{probe}= 440 nm and three fluences of the single-pulsed pump radiation at λ _{pump}= 800 nm generating no, gentle, and strong ablation. The relative reflectance overall increases at no and gentle ablation. At strong ablation, the relative reflectance locally decreases, presumable caused by emitted thermal electrons, ballistic electrons, and ablating material. The refractive index n is slightly decreasing after excitation, while the extinction coefficient k is increasing.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

Directory of Open Access Journals (Sweden)

Iagher Fabiola

2011-04-01

Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Economic benefits of improved insulin stability in insulin pumps.

Science.gov (United States)

Weiss, Richard C; van Amerongen, Derek; Bazalo, Gary; Aagren, Mark; Bouchard, Jonathan R

2011-05-01

Insulin pump users discard unused medication and infusion sets according to labeling and manufacturer's instructions. The stability labeling for insulin aspart (rDNA origin] (Novolog) was increased from two days to six. The associated savings was modeled from the perspective of a hypothetical one-million member health plan and the total United States population. The discarded insulin volume and the number of infusion sets used under a two-day stability scenario versus six were modeled. A mix of insulin pumps of various reservoir capacities with a range of daily insulin dosages was used. Average daily insulin dose was 65 units ranging from 10 to 150 units. Costs of discarded insulin aspart [rDNA origin] were calculated using WAC (Average Wholesale Price minus 16.67%). The cost of pump supplies was computed for the two-day scenario assuming a complete infusion set change, including reservoirs, every two days. Under the six-day scenario complete infusion sets were discarded every six days while cannulas at the insertion site were changed midway between complete changes. AWP of least expensive supplies was used to compute their costs. For the hypothetical health plan (1,182 pump users) the annual reduction in discarded insulin volume between scenarios was 19.8 million units. The corresponding cost reduction for the plan due to drug and supply savings was $3.4 million. From the U.S. population perspective, savings of over $1 billion were estimated. Using insulin that is stable for six days in pump reservoirs can yield substantial savings to health plans and other payers, including patients.

Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance

Directory of Open Access Journals (Sweden)

Bruno Melo Carvalho

2013-01-01

Full Text Available Obesity is the main condition that is correlated with the appearance of insulin resistance, which is the major link among its comorbidities, such as type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. Obesity affects a large number of individuals worldwide; it degrades human health and quality of life. Here, we review the role of the gut microbiota in the pathophysiology of obesity and type 2 diabetes, which is promoted by a bacterial diversity shift mediated by overnutrition. Whole bacteria, their products, and metabolites undergo increased translocation through the gut epithelium to the circulation due to degraded tight junctions and the consequent increase in intestinal permeability that culminates in inflammation and insulin resistance. Several strategies focusing on modulation of the gut microbiota (antibiotics, probiotics, and prebiotics are being experimentally employed in metabolic derangement in order to reduce intestinal permeability, increase the production of short chain fatty acids and anorectic gut hormones, and promote insulin sensitivity to counteract the inflammatory status and insulin resistance found in obese individuals.

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.

Science.gov (United States)

Højlund, Kurt

2014-07-01

Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

Theory and Modelling of Ultrafast X-ray Imaging of Dynamical Non-equilibrium Systems

DEFF Research Database (Denmark)

Lorenz, Ulf

Over the next few years, a new generation of x-ray sources is going online. These freeelectron lasers will provide extremely bright subpicosecond x-ray pulses. Traditionally, x-ray diraction has the advantage of directly determining the atomic positions within a sample. With these new machines......, it becomes feasible to exploit this concept for ultrafast processes; in eect, we can study chemical reactions as they occur. This thesis deals with theoretical aspect of ultrafast time-resolved x-ray diraction (TRXD).We derive general formulas for calculating the diraction signal that are closely related...

Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy.

Science.gov (United States)

Zuckerwise, Lisa C; Werner, Erika F; Pettker, Christian M; McMahon-Brown, Erin K; Thung, Stephen F; Han, Christina S

2012-08-01

Increased insulin requirements in pregnancy can hinder attainment of glycemic control in diabetic patients. U-500 insulin is a concentrated form of regular insulin that can be a valuable tool in the treatment of patients with severe insulin resistance. A 24-year-old woman with pregestational diabetes mellitus experienced increasing insulin requirements during pregnancy, peaking at 650 units daily. The frequent, large-volume injections of standard-concentration insulin were poorly tolerated by the patient and resulted in nonadherence. She subsequently achieved glycemic control on thrice-daily U-500 insulin. Pregnancy exacerbates insulin resistance in diabetic patients, and these patients may require high doses of insulin. U-500 insulin is an effective alternative for patients with severe insulin resistance and should be considered for pregnant women with difficulty achieving glycemic control.

Development and Optimization of Insulin-Chitosan Nanoparticles

African Journals Online (AJOL)

Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. ... positive zeta potential and longer drug delivery. ... a thorough research on physico-chemical ... Biological Product Co., Ltd, China, while insulin.

Effects of supplemental calcium salts of palm oil and chromium-propionate on insulin sensitivity and productive and reproductive traits of mid- to late-lactating Holstein × Gir dairy cows consuming excessive energy.

Science.gov (United States)

Leiva, T; Cooke, R F; Brandão, A P; Bertin, R D; Colombo, E A; Miranda, V F B; Lourenço, L A C; Rodrigues, S M B; Vasconcelos, J L M

2018-01-01

This experiment compared insulin sensitivity, milk production, and reproductive outcomes in dairy cows consuming excessive energy during mid to late lactation and receiving in a 2 × 2 factorial design (1) concentrate based on ground corn (CRN; n = 20) or including 8% (DM basis) of Ca salts of palm oil (CSPO; n = 20), and (2) supplemented (n = 20) or not (n = 20) with 2.5 g/d of Cr-propionate. During the experiment (d 0-203), 40 multiparous, nonpregnant, lactating 3/4 Holstein × 1/4 Gir cows (initial days in milk = 81 ± 2; mean ± SE) were offered corn silage for ad libitum consumption, and individually received concentrate formulated to allow diets to provide 160% of their daily net energy for lactation requirements. From d -15 to 203, milk production was recorded daily, blood samples collected weekly, and cow body weight (BW) and body condition score (BCS) recorded on d 0 and 203. For dry matter intake evaluation, cows from both treatments were randomly divided in 5 groups of 8 cows each, and allocated to 8 individual feeding stations for 3 d. Intake was evaluated 6 times/group. Glucose tolerance tests (GTT; 0.5 g of glucose/kg of BW) were performed on d -3, 100, and 200. Follicle aspiration for in vitro embryo production was performed via transvaginal ovum pick-up on d -1, 98, and 198. Mean DMI, net energy for lactation intake, as well as BW and BCS change were similar across treatments. On average, cows gained 40 kg of BW and 0.49 BCS during the experiment. Within weekly blood samples, CRN cows had lower serum concentrations of glucose, insulin, fatty acids, and insulin-to-glucose ratio compared with CSPO cows, suggesting increased insulin sensitivity in CRN cows. During the GTT, insulin-sensitivity traits were also greater in CRN versus CSPO cows. Supplemental Cr-propionate resulted in lower serum insulin concentrations and insulin-to-glucose ratio within CRN cows only, indicating that Cr-propionate improved basal insulin sensitivity in CRN but not in CSPO

Ultrafast Plasmonic Electron Emission from Ag Nanolayers with Different Roughness

Czech Academy of Sciences Publication Activity Database

Márton, I.; Ayadi, V.; Rácz, P.; Stefaniuk, T.; Wróbel, Piotr; Földi, P.; Dombi, P.

2016-01-01

Roč. 11, č. 3 (2016), s. 811-816 ISSN 1557-1955 Institutional support: RVO:67985882 Keywords : Nanoparticles * Ultrafast phenomena * Electron emission Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 2.139, year: 2016

Development of Ultrafast Indirect Flash Heating Methods for RDX

Science.gov (United States)

2014-02-01

8 1 1. Introduction The mission of the Multiscale Response of Energetic Materials program is to establish...vinyl nitrate ) Films. J. Phys. Chem. A 2004, 108 (43), 9342–9347. 11 12. Gottfried, J. L.; de Lucia, F. C., Jr.; Piraino, S. M. Ultrafast Laser

FoxO6 Integrates Insulin Signaling With Gluconeogenesis in the Liver

Science.gov (United States)

Kim, Dae Hyun; Perdomo, German; Zhang, Ting; Slusher, Sandra; Lee, Sojin; Phillips, Brett E.; Fan, Yong; Giannoukakis, Nick; Gramignoli, Roberto; Strom, Stephen; Ringquist, Steven; Dong, H. Henry

2011-01-01

OBJECTIVE Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied the ability of forkhead box O6 (FoxO6) to mediate insulin action on hepatic gluconeogenesis and its contribution to glucose metabolism. RESEARCH DESIGN AND METHODS We characterized FoxO6 in glucose metabolism in cultured hepatocytes and in rodent models of dietary obesity, insulin resistance, or insulin-deficient diabetes. We determined the effect of FoxO6 on hepatic gluconeogenesis in genetically modified mice with FoxO6 gain- versus loss-of-function and in diabetic db/db mice with selective FoxO6 ablation in the liver. RESULTS FoxO6 integrates insulin signaling to hepatic gluconeogenesis. In mice, elevated FoxO6 activity in the liver augments gluconeogenesis, raising fasting blood glucose levels, and hepatic FoxO6 depletion suppresses gluconeogenesis, resulting in fasting hypoglycemia. FoxO6 stimulates gluconeogenesis, which is counteracted by insulin. Insulin inhibits FoxO6 activity via a distinct mechanism by inducing its phosphorylation and disabling its transcriptional activity, without altering its subcellular distribution in hepatocytes. FoxO6 becomes deregulated in the insulin-resistant liver, accounting for its unbridled activity in promoting gluconeogenesis and correlating with the pathogenesis of fasting hyperglycemia in diabetes. These metabolic abnormalities, along with fasting hyperglycemia, are reversible by selective inhibition of hepatic FoxO6 activity in diabetic mice. CONCLUSIONS Our data uncover a FoxO6-dependent pathway by which the liver orchestrates insulin regulation of gluconeogenesis, providing the proof-of-concept that selective FoxO6 inhibition is beneficial for curbing excessive hepatic glucose production and improving glycemic control in diabetes. PMID:21940782

Microchip capillary gel electrophoresis using programmed field strength gradients for the ultra-fast analysis of genetically modified organisms in soybeans.

Science.gov (United States)

Kim, Yun-Jeong; Chae, Joon-Seok; Chang, Jun Keun; Kang, Seong Ho

2005-08-12

We have developed a novel method for the ultra-fast analysis of genetically modified organisms (GMOs) in soybeans by microchip capillary gel electrophoresis (MCGE) using programmed field strength gradients (PFSG) in a conventional glass double-T microchip. Under the programmed electric field strength and 0.3% poly(ethylene oxide) sieving matrix, the GMO in soybeans was analyzed within only 11 s of the microchip. The MCGE-PFSG method was a program that changes the electric field strength during GMO analysis, and was also applied to the ultra-fast analysis of PCR products. Compared to MCGE using a conventional and constantly applied electric field, the MCGE-PFSG analysis generated faster results without the loss of resolving power and reproducibility for specific DNA fragments (100- and 250-bp DNA) of GM-soybeans. The MCGE-PFSG technique may prove to be a new tool in the GMO analysis due to its speed, simplicity, and high efficiency.

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

Science.gov (United States)

Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

2015-01-01

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

Generation of insulin-producing human mesenchymal stem cells using recombinant adeno-associated virus.

Science.gov (United States)

Kim, Jeong Hwan; Park, Si-Nae; Suh, Hwal

2007-02-28

The purpose of current experiment is the generation of insulin-producing human mesenchymal stem cells as therapeutic source for the cure of type 1 diabetes. Type 1 diabetes is generally caused by insulin deficiency accompanied by the destruction of islet beta-cells. In various trials for the treatment of type 1 diabetes, cell-based gene therapy using stem cells is considered as one of the most useful candidate for the treatment. In this experiment, human mesenchymal stem cells were transduced with AAV which is containing furin-cleavable human preproinsulin gene to generate insulin-producing cells as surrogate beta-cells for the type 1 diabetes therapy. In the rAAV production procedure, rAAV was generated by transfection of AD293 cells. Human mesenchymal stems cells were transduced using rAAV with a various multiplicity of infection. Transduction of recombinant AAV was also tested using beta-galactosidse expression. Cell viability was determined by using MTT assay to evaluate the toxicity of the transduction procedure. Expression and production of Insulin were tested using reverse transcriptase-polymerase chain reaction and immunocytochemistry. Secretion of human insulin and C-peptide from the cells was assayed using enzyme-linked immunosorbent assay. Production of insulin and C-peptide from the test group represented a higher increase compared to the control group. In this study, we examined generation of insulin-producing cells from mesenchymal stem cells by genetic engineering for diabetes therapy. This work might be valuable to the field of tissue engineering for diabetes treatment.

Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin resistance.

Science.gov (United States)

Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae

2018-06-01

Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.

Conversion from insulin glargine U-100 to insulin glargine U-300 or insulin degludec and the impact on dosage requirements.

Science.gov (United States)

Pearson, Scott M; Trujillo, Jennifer M

2018-04-01

We wanted to determine whether basal insulin requirements change when patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or insulin degludec. This study involved subjects seen in the University of Colorado Health Endocrine Clinic who were transitioned from Gla-100 to either Gla-300 ( n = 95) or insulin degludec ( n = 39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-300 or insulin degludec prescribed after first follow-up visit within 1-12 months. Secondary outcomes included changes in glycemic control and empiric dose conversion from Gla-100 to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated changes in insulin doses, and paired t tests assessed changes in glycemic control using GraphPad statistical software. Median daily basal insulin dose increased for individuals transitioned from Gla-100 to Gla-300 from 30 [19-60 interquartile range (IQR)] units at baseline to 34.5 (19-70 IQR) units after follow up ( p = 0.01). For patients transitioned to insulin degludec, dose changes from baseline to follow up were not significantly different ( p = 0.56). At the time of transition, the prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous dose of Gla-100 ( p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments were not routinely prescribed. Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin requirements between visits, while basal insulin requirements for those transitioned from Gla-100 to insulin degludec were not significantly different.

The effect of an insulin releasing agent, BTS 67582, on advanced glycation end product formation in vitro.

Science.gov (United States)

Simpson, A E; Jones, R B

1999-01-01

BTS 67582 (1,1-dimethyl-2-(2-morpholinophenyl) guanidine fumarate) is an insulin-releasing agent currently in phase II clinical trials. Its effect on advanced glycation end product (AGE) formation was measured in the BSA/D-glucose and L-lysine/glucose-6-phosphate assay systems and Amadori product formation was measured in the BSA/D-glucose assay system, following a 3 week incubation period. In the BSA/D-glucose assay system, 200 mM BTS 67582 caused an approximate 70% inhibition in AGE formation (pBTS 67582 and 200 mM aminoguanidine-HCl retarded Amadori product formation by 88% (pBTS 67582 at 20 mM and 2 mM was shown to inhibit Amadori product formation by 67% and 57%, respectively, (pBTS 67582 and 200 mM aminoguanidine-HCl were shown to inhibit AGE formation by about 70% and 96% (p<0.001), respectively. Tolbutamide (200 microM) and glibenclamide (100 microM) had no significant effect on AGE formation.

Pregnancy-induced insulin resistance in liver and skeletal muscles of the conscious rabbit

International Nuclear Information System (INIS)

Hauguel, S.; Gilbert, M.; Girard, J.

1987-01-01

Insulin sensitivity of maternal nonuterine tissues (liver and skeletal muscles) has been investigated in the conscious rabbit during late gestation (24 and 30 days). The specific effect of insulin on glucose production and utilization was evaluated with the hyperinsulinemic euglycemic clamp technique using two types of labelled microspheres ( 57 Co and 113 Sn). The net balance of glucose across the hindlimb muscles was studied by means of the Fick principle in basal and insulin stimulated conditions (clamp study). The results show that an insulin-resistant state developed between days 24 and 30 of gestation in the rabbit and involves both glucose producing (liver) and utilizing (muscles) tissues. On day 30 of gestation, muscle glucose uptake was not significantly stimulated at a plasma insulin concentration of 700 μU/ml determined by radioimmunoassay, whereas it was stimulated by 30-40% in nonpregnant and 24 day pregnant rabbits. At similar plasma insulin concentration, endogenous glucose production was suppressed by 85% in both nonpregnant and 24 day pregnant rabbits, whereas it was decreased by only 30% in 30 day pregnant rabbits. The present data suggest that hindlimb muscles of late pregnant rabbits are able to reduce their insulin-induced glucose utilization. This could contribute to meet the glucose requirements of pregnant uterus in late gestation

An ultrafast electron microscope gun driven by two-photon photoemission from a nanotip cathode

International Nuclear Information System (INIS)

Bormann, Reiner; Strauch, Stefanie; Schäfer, Sascha; Ropers, Claus

2015-01-01

We experimentally and numerically investigate the performance of an advanced ultrafast electron source, based on two-photon photoemission from a tungsten needle cathode incorporated in an electron microscope gun geometry. Emission properties are characterized as a function of the electrostatic gun settings, and operating conditions leading to laser-triggered electron beams of very low emittance (below 20 nm mrad) are identified. The results highlight the excellent suitability of optically driven nano-cathodes for the further development of ultrafast transmission electron microscopy

Four-Dimensional Ultrafast Electron Microscopy: Insights into an Emerging Technique

KAUST Repository

Adhikari, Aniruddha; Eliason, Jeffrey K.; Sun, Jingya; Bose, Riya; Flannigan, David J.; Mohammed, Omar F.

2016-01-01

Four-dimensional ultrafast electron microscopy (4D-UEM) is a novel analytical technique that aims to fulfill the long-held dream of researchers to investigate materials at extremely short spatial and temporal resolutions by integrating the excellent

Ultrafast Non-thermal Response of Plasmonic Resonance in Gold Nanoantennas

Science.gov (United States)

Soavi, Giancarlo; Valle, Giuseppe Della; Biagioni, Paolo; Cattoni, Andrea; Longhi, Stefano; Cerullo, Giulio; Brida, Daniele

Ultrafast thermalization of electrons in metal nanostructures is studied by means of pump-probe spectroscopy. We track in real-time the plasmon resonance evolution, providing a tool for understanding and controlling gold nanoantennas non-linear optical response.

Measurements of ultrafast spin-profiles and spin-diffusion properties in the domain wall area at a metal/ferromagnetic film interface.

Science.gov (United States)

Sant, T; Ksenzov, D; Capotondi, F; Pedersoli, E; Manfredda, M; Kiskinova, M; Zabel, H; Kläui, M; Lüning, J; Pietsch, U; Gutt, C

2017-11-08

Exciting a ferromagnetic material with an ultrashort IR laser pulse is known to induce spin dynamics by heating the spin system and by ultrafast spin diffusion processes. Here, we report on measurements of spin-profiles and spin diffusion properties in the vicinity of domain walls in the interface region between a metallic Al layer and a ferromagnetic Co/Pd thin film upon IR excitation. We followed the ultrafast temporal evolution by means of an ultrafast resonant magnetic scattering experiment in surface scattering geometry, which enables us to exploit the evolution of the domain network within a 1/e distance of 3 nm to 5 nm from the Al/FM film interface. We observe a magnetization-reversal close to the domain wall boundaries that becomes more pronounced closer to the Al/FM film interface. This magnetization-reversal is driven by the different transport properties of majority and minority carriers through a magnetically disordered domain network. Its finite lateral extension has allowed us to measure the ultrafast spin-diffusion coefficients and ultrafast spin velocities for majority and minority carriers upon IR excitation.

Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

Science.gov (United States)

Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

2016-04-01

In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Ultrafast Digital Printing toward 4D Shape Changing Materials.

Science.gov (United States)

Huang, Limei; Jiang, Ruiqi; Wu, Jingjun; Song, Jizhou; Bai, Hao; Li, Bogeng; Zhao, Qian; Xie, Tao

2017-02-01

Ultrafast 4D printing (printing converts the structure into 3D. An additional dimension can be incorporated by choosing the printing precursors. The process overcomes the speed limiting steps of typical 3D (4D) printing. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tunable third-harmonic probe for non-degenerate ultrafast pump ...

Indian Academy of Sciences (India)

2014-02-12

Feb 12, 2014 ... 413–417. Tunable third-harmonic probe for non-degenerate ultrafast ... A beam splitter was used to split the beam into two with the power ratio of ... Now polarization of the 800-nm beam is made to be parallel with the 400-nm.

Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

International Nuclear Information System (INIS)

Shankar, T.P.; Drake, S.; Solomon, S.S.

1987-01-01

Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125 I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers. Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance

Rat liver responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia

Directory of Open Access Journals (Sweden)

H.M. de Souza

2001-06-01

Full Text Available Hepatic responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia was investigated. For this purpose, livers were perfused with a saturating concentration of 2 mM glycerol, 5 mM L-alanine or 5 mM L-glutamine as gluconeogenic substrates. All experiments were performed 1 h after an ip injection of saline (CN group or 1 IU/kg of insulin (IN group. The IN group showed higher (P<0.05 hepatic glucose production from glycerol, L-alanine and L-glutamine and higher (P<0.05 production of L-lactate, pyruvate and urea from L-alanine and L-glutamine. In addition, ip injection of 100 mg/kg glycerol, L-alanine and L-glutamine promoted glucose recovery. The results indicate that the hepatic capacity to produce glucose from gluconeogenic precursors was increased during insulin-induced hypoglycemia.

Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance.

Science.gov (United States)

Potenza, Maria A; Marasciulo, Flora L; Tarquinio, Mariela; Quon, Michael J; Montagnani, Monica

2006-12-01

Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome.

Ultrafast phenomena in molecular sciences femtosecond physics and chemistry

CERN Document Server

Bañares, Luis

2014-01-01

This book presents the latest developments in Femtosecond Chemistry and Physics for the study of ultrafast photo-induced molecular processes. Molecular systems, from the simplest H2 molecule to polymers or biological macromolecules, constitute central objects of interest for Physics, Chemistry and Biology, and despite the broad range of phenomena that they exhibit, they share some common behaviors. One of the most significant of those is that many of the processes involving chemical transformation (nuclear reorganization, bond breaking, bond making) take place in an extraordinarily short time, in or around the femtosecond temporal scale (1 fs = 10-15 s). A number of experimental approaches - very particularly the developments in the generation and manipulation of ultrashort laser pulses - coupled with theoretical progress, provide the ultrafast scientist with powerful tools to understand matter and its interaction with light, at this spatial and temporal scale. This book is an attempt to reunite some of the ...

Phosphorene quantum dot saturable absorbers for ultrafast fiber lasers

Science.gov (United States)

Du, J.; Zhang, M.; Guo, Z.; Chen, J.; Zhu, X.; Hu, G.; Peng, P.; Zheng, Z.; Zhang, H.

2017-01-01

We fabricate ultrasmall phosphorene quantum dots (PQDs) with an average size of 2.6 ± 0.9 nm using a liquid exfoliation method involving ultrasound probe sonication followed by bath sonication. By coupling the as-prepared PQDs with microfiber evanescent light field, the PQD-based saturable absorber (SA) device exhibits ultrafast nonlinear saturable absorption property, with an optical modulation depth of 8.1% at the telecommunication band. With the integration of the all-fiber PQD-based SA, a continuous-wave passively mode-locked erbium-doped (Er-doped) laser cavity delivers stable, self-starting pulses with a pulse duration of 0.88 ps and at the cavity repetition rate of 5.47 MHz. Our results contribute to the growing body of work studying the nonlinear optical properties of ultrasmall PQDs that present new opportunities of this two-dimensional (2D) nanomaterial for future ultrafast photonic technologies. PMID:28211471

Precision machining of pig intestine using ultrafast laser pulses

Science.gov (United States)

Beck, Rainer J.; Góra, Wojciech S.; Carter, Richard M.; Gunadi, Sonny; Jayne, David; Hand, Duncan P.; Shephard, Jonathan D.

2015-07-01

Endoluminal surgery for the treatment of early stage colorectal cancer is typically based on electrocautery tools which imply restrictions on precision and the risk of harm through collateral thermal damage to the healthy tissue. As a potential alternative to mitigate these drawbacks we present laser machining of pig intestine by means of picosecond laser pulses. The high intensities of an ultrafast laser enable nonlinear absorption processes and a predominantly nonthermal ablation regime. Laser ablation results of square cavities with comparable thickness to early stage colorectal cancers are presented for a wavelength of 1030 nm using an industrial picosecond laser. The corresponding histology sections exhibit only minimal collateral damage to the surrounding tissue. The depth of the ablation can be controlled precisely by means of the pulse energy. Overall, the application of ultrafast lasers to ablate pig intestine enables significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional techniques.

Ultrafast dissociation: An unexpected tool for probing molecular dynamics

International Nuclear Information System (INIS)

Morin, Paul; Miron, Catalin

2012-01-01

Highlights: ► Ultrafast dissociation has been investigated by means of XPS and mass spectrometry. ► The interplay between electron relaxation and molecular dynamics is evidenced. ► Extension toward polyatomics, clusters, adsorbed molecules is considered. ► Quantum effects (spectral hole, angular effects) evidence the molecular field anisotropy. -- Abstract: Ultrafast dissociation following core–shell excitation into an antibonding orbital led to the early observation in HBr of atomic Auger lines associated to the decay of dissociated excited atoms. The purpose of this article is to review the very large variety of systems where such a situation has been encountered, extending from simple diatomic molecules toward more complex systems like polyatomics, clusters, or adsorbed molecules. Interestingly, this phenomenon has revealed an extremely rich and powerful tool for probing nuclear dynamics and its subtle interplay with electron relaxation occurring on a comparable time scale. Consequently this review covers a surprisingly large period, starting in 1986 and still ongoing.

Optical Detection in Ultrafast Short Wavelength Science

International Nuclear Information System (INIS)

Fullagar, Wilfred K.; Hall, Chris J.

2010-01-01

A new approach to coherent detection of ionising radiation is briefly motivated and recounted. The approach involves optical scattering of coherent light fields by colour centres in transparent solids. It has significant potential for diffractive imaging applications that require high detection dynamic range from pulsed high brilliance short wavelength sources. It also motivates new incarnations of Bragg's X-ray microscope for pump-probe studies of ultrafast molecular structure-dynamics.

Effects of a fibre-enriched milk drink on insulin and glucose levels in healthy subjects

Directory of Open Access Journals (Sweden)

Pilvi Taru K

2009-10-01

Full Text Available Abstract Background The glycaemic response to foods is dependent on the quality and content of carbohydrates. Carbohydrates in the form of dietary fibre have favourable effects on insulin and glucose metabolism and may help to control energy intake. Dairy products have a relatively low carbohydrate content, and most of the carbohydrate is in the form of lactose which causes gastrointestinal symptoms in part of the population. In order to avoid these symptoms, dairy products can be replaced with lactose-free dairy products which are on the market in many parts of the world. However, the effects of lactose-free products on insulin and glucose metabolism have not been studied. Methods In the present study, we investigated the effects of 1 a lactose-free milk drink, 2 a novel fibre-enriched, fat- and lactose-free milk drink and 3 normal fat-free milk on serum glucose and insulin levels and satiety using a randomized block design. Following an overnight fast, 26 healthy volunteers ingested 200 ml of one of these drinks on three non-consecutive days. Insulin and glucose levels and subjective satiety ratings were measured before the ingestion of the milk product and 20, 40, 60, 120 and 180 minutes after ingestion. The responses were calculated as the area under the curve subtracted by the baseline value (AUC minus baseline. Results The insulin response was significantly lower for the fibre-enriched milk drink than it was for the other milk products (AUC, P = 0.007. There were no differences in the response for glucose or in the AUC for the subjective satiety ratings between the studied milk products. Conclusion The present results suggest that this novel milk drink could have positive effects on insulin response.

Morphological changes in ultrafast laser ablation plumes with varying spot size.

Science.gov (United States)

Harilal, S S; Diwakar, P K; Polek, M P; Phillips, M C

2015-06-15

We investigated the role of spot size on plume morphology during ultrafast laser ablation of metal targets. Our results show that the spatial features of fs LA plumes are strongly dependent on the focal spot size. Two-dimensional self-emission images showed that the shape of the ultrafast laser ablation plumes changes from spherical to cylindrical with an increasing spot size from 100 to 600 μm. The changes in plume morphology and internal structures are related to ion emission dynamics from the plasma, where broader angular ion distribution and faster ions are noticed for the smallest spot size used. The present results clearly show that the morphological changes in the plume with spot size are independent of laser pulse width.

Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

DEFF Research Database (Denmark)

Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

2012-01-01

An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

DEFF Research Database (Denmark)

Madsbad, Sten

2002-01-01

To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

Alteration in insulin action

DEFF Research Database (Denmark)

Tanti, J F; Gual, P; Grémeaux, T

2004-01-01

Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

Midkine, a potential link between obesity and insulin resistance.

Directory of Open Access Journals (Sweden)

Nengguang Fan

Full Text Available Obesity is associated with increased production of inflammatory mediators in adipose tissue, which contributes to chronic inflammation and insulin resistance. Midkine (MK is a heparin-binding growth factor with potent proinflammatory activities. We aimed to test whether MK is associated with obesity and has a role in insulin resistance. It was found that MK was expressed in adipocytes and regulated by inflammatory modulators (TNF-α and rosiglitazone. In addition, a significant increase in MK levels was observed in adipose tissue of obese ob/ob mice as well as in serum of overweight/obese subjects when compared with their respective controls. In vitro studies further revealed that MK impaired insulin signaling in 3T3-L1 adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 and decreased translocation of glucose transporter 4 (GLUT4 to the plasma membrane in response to insulin stimulation. Moreover, MK activated the STAT3-suppressor of cytokine signaling 3 (SOCS3 pathway in adipocytes. Thus, MK is a novel adipocyte-secreted factor associated with obesity and inhibition of insulin signaling in adipocytes. It may provide a potential link between obesity and insulin resistance.

Development of an Ultrafast Scanning Tunneling Microscope for Dynamic Surface Studies

National Research Council Canada - National Science Library

Nunes

1999-01-01

.... The microscope has demonstrated atomic resolution. We have a femtosecond laser system, optics for delivering ultrafast laser pulses to the STM, and a computer controlled delay line for time-resolved measurements...

Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

Science.gov (United States)

Hinton, Pamela S

2016-08-01

Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

123I-tyrosine-(A14)-insulin: preparation and preliminary clinical studies

International Nuclear Information System (INIS)

Pantev, T.; Virgolini, I.; Sinzinger, H.; Prager, R.; Neuhold, N.; Angelberger, P.; Banyai, M.; Knoebl, P.; Vienna Univ.

1991-01-01

Insulin was radioiodinated with 123 I ( 123 I-tyrosine-(A14)-insulin) to a specific activity of 1 μg/mCi, corresponding to 0.025 I.U. of insulin/mCi. This preparation was used for in vitro binding experiments with adipose tissue, showing active binding to the two subunits of the known insulin receptor. In a preliminary clinical investigation, 5 adipose patients with (n = 2) and without (n = 3) diabetes mellitus Type II, were subject to in vivo injection of the same radiolabeled product using 3 mCi/patient. During the first minutes of dynamic imaging, the liver was the major organ of tracer uptake in all patients. Furthermore, the pancreas, and in one patient the kidneys, were visualised. Further studies on insulin in vivo kinetics and quantification are under way. (authors)

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P

Observation of an octave-spanning supercontinuum in the mid-infrared using ultrafast cascaded nonlinearities

DEFF Research Database (Denmark)

Bache, Morten; Liu, Xing; Zhou, Binbin

2014-01-01

An octave-spanning mid-IR supercontinuum is observed experimentally using ultrafast cascaded nonlinearities in an LiInS2 quadratic nonlinear crystal pumped with 70 fs energetic mid-IR pulses and cut for strongly phase-mismatched second-harmonic generation. ©OSA 2014.......An octave-spanning mid-IR supercontinuum is observed experimentally using ultrafast cascaded nonlinearities in an LiInS2 quadratic nonlinear crystal pumped with 70 fs energetic mid-IR pulses and cut for strongly phase-mismatched second-harmonic generation. ©OSA 2014....

[Insulin resistance in the pathogenesis of polycystic ovarian disease (PCOD)].

Science.gov (United States)

Jakowicki, J

1994-10-01

In polycystic ovarian disease there is a strong association between hyperinsulinemia and hyperandrogenism but not with obesity alone. The magnitude of peripheral insulin resistance is similar to that seen in non-insulin-dependent diabetes mellitus. Mild hyperinsulinemia in PCOD patients is not impair the carbohydrate metabolism. The elimination of the cause of hyperandrogenism by bilateral oophorectomy, long-acting Gn-RH agonist or antiandrogen cyproterone acetate did not improve the associated insulin resistance. In opposition to insulin resistance in the tissues responsible for metabolism of carbohydrate, the ovary remains sensitive to the effects of pancreatic hormone. Presumably this mechanism involved the interaction with IGF-I receptors to stimulate thecal and stromal androgen production. Insulin may sensitize the stroma to the stimulatory effect of LH. In the mechanism of follicular arrest take part increased level of binding proteins for IGF-I, mainly IGFBP 2, -4 and 5 inhibit FSH and IGF-I action.

Ultrafast demagnetization enhancement in CoFeB/MgO/CoFeB magnetic tunneling junction driven by spin tunneling current.

Science.gov (United States)

He, Wei; Zhu, Tao; Zhang, Xiang-Qun; Yang, Hai-Tao; Cheng, Zhao-Hua

2013-10-07

The laser-induced ultrafast demagnetization of CoFeB/MgO/CoFeB magnetic tunneling junction is exploited by time-resolved magneto-optical Kerr effect (TRMOKE) for both the parallel state (P state) and the antiparallel state (AP state) of the magnetizations between two magnetic layers. It was observed that the demagnetization time is shorter and the magnitude of demagnetization is larger in the AP state than those in the P state. These behaviors are attributed to the ultrafast spin transfer between two CoFeB layers via the tunneling of hot electrons through the MgO barrier. Our observation indicates that ultrafast demagnetization can be engineered by the hot electrons tunneling current. It opens the door to manipulate the ultrafast spin current in magnetic tunneling junctions.

Update on The Ultra-Fast Flash Observatory (UFFO) Pathfinder

DEFF Research Database (Denmark)

Grossan, B.; Brandt, Søren; Budtz-Jørgensen, Carl

2011-01-01

The Ultra-Fast Flash Observatory (UFFO) uses an X/gamma and an optical/UV instrument to observe gamma-ray bursts (GRB) starting milliseconds after burst trigger and location. The X/gamma instrument, a standard coded-mask camera, locates the GRB and triggers the system. The optical/UV instrument, ...

Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

Directory of Open Access Journals (Sweden)

Tine N Vinther

Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

Insulin resistance in obesity can be reliably identified from fasting plasma insulin

NARCIS (Netherlands)

ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

2015-01-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

Science.gov (United States)

Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

2014-08-01

Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

A US Based Ultrafast Interdisciplinary Research Facility

Science.gov (United States)

Gueye, Paul; Hill, Wendell; Johnson, Anthony

2006-10-01

The US scientific competitiveness on the world arena has substantially decreased due to the lack of funding and training of qualified personnel. Most of the potential workforce found in higher education is composed of foreign students and post-docs. In the specific field of low- and high-field science, the European and Asian communities are rapidly catching-up with the US, even leading in some areas. To remain the leader in ultrafast science and technology, new visions and commitment must be embraced. For that reason, an international effort of more than 70 countries for a US-based interdisciplinary research facility using ultrafast laser technology is under development. It will provide research and educational training, as well as new venues for a strong collaboration between the fields of astrophysics, nuclear/high energy physics, plasma physics, optical sciences, biological and medical physics. This facility will consist of a uniquely designed high contrast multi-lines concept housing twenty experimental rooms shared between four beams:[0.1 TW, 1 kHz], [10 TW, 9 kHz], [100-200 TW, 10 Hz] and [500 TW, 10 Hz]. The detail schematic of this multi-laser system, foreseen research and educational programs, and organizational structure of this facility will be presented.

Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway.

Science.gov (United States)

Huetson, Pernilla; Palmer, James L; Levorsen, Andrée; Fournier, Marie; Germe, Maeva; McLeod, Euan

2015-01-01

Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia. To assess the cost-effectiveness of lixisenatide versus bolus insulin, both in combination with basal insulin, in patients with type 2 diabetes in Norway. The IMS CORE Diabetes Model, a non-product-specific and validated simulation model, was used to make clinical and cost projections. Transition probabilities, risk adjustments and the progression of complication risk factors were derived from the UK Prospective Diabetes Study, supplemented with Norwegian data. Patients were assumed to receive combination treatment with basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by intensification of a basal-bolus insulin regimen for their remaining lifetime. Simulated healthcare costs, taken from the public payer perspective, were derived from microcosting and diagnosis related groups, discounted at 4% per annum and reported in Norwegian krone (NOK). Productivity costs were also captured based on extractions from the Norwegian Labor and Welfare Administration. Health state utilities were derived from a systematic literature review. Sensitivity and scenario analyses were performed. Lixisenatide in combination with basal insulin was associated with increased quality-adjusted life years (QALYs) and reduced lifetime healthcare costs compared to bolus insulin in combination with basal insulin in patients with Type 2 diabetes, and can be considered dominant. The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per patient. Results were sensitive to discounting, the application of excess body weight associated disutility and uncertainty surrounding the changes in HbA1c. Lixisenatide may be considered an economically efficient therapy in combination

Ultra-fast relaxation kinetics in semiconductors

International Nuclear Information System (INIS)

Luzzi, R.

1983-01-01

It is presented a brief description of relaxation processes in highly excited semiconductor plasmas (HESP). Comparison with experimental data obtained by means of ultra-fast laser light spectroscopy (UFLS) is made. Some aspects of response funtion theory in systems far-from-equilibrium are reviewed in Section II. In Section III we present some comments on the question of nonequilibrium thermodynamics relevant to the problem to be considered. In last section we present a brief summary of the different aspects of the subject. (author) [pt

Ultra-fast relaxation kinetics in semiconductors

International Nuclear Information System (INIS)

Luzzi, R.

1983-01-01

It is presented a brief description of relaxation processes in highly excited semiconductor plasmas (HESP). Comparison with experimental data obtained by means of ultra-fast laser light spectroscopy (UFLS) is made. Some aspects of response function theory in systems far-from-equilibrium are reviewed in Section II. In Section III some comments on the question of nonequilibrium thermodynamics relevant to the problem to be considered are presented. In last Section a brief summary of the different aspects of the subject is also presented. (Author) [pt

Ultrafast Ge-Te bond dynamics in a phase-change superlattice

NARCIS (Netherlands)

Malvestuto, Marco; Caretta, Antonio; Casarin, Barbara; Cilento, Federico; Dell'Angela, Martina; Fausti, Daniele; Calarco, Raffaella; Kooi, Bart J.; Varesi, Enrico; Robertson, John; Parmigiani, Fulvio

2016-01-01

A long-standing question for avant-garde data storage technology concerns the nature of the ultrafast photoinduced phase transformations in the wide class of chalcogenide phase-change materials (PCMs). Overall, a comprehensive understanding of the microstructural evolution and the relevant kinetics

Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes

DEFF Research Database (Denmark)

Niskanen, Leo; Leiter, Lawrence A; Franek, Edward

2012-01-01

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30)....

Is Insulin Action in the Brain Relevant in Regulating Blood Glucose in Humans?

Science.gov (United States)

Dash, Satya; Xiao, Changting; Morgantini, Cecilia; Koulajian, Khajag; Lewis, Gary F

2015-07-01

In addition to its direct action on the liver to lower hepatic glucose production, insulin action in the central nervous system (CNS) also lowers hepatic glucose production in rodents after 4 hours. Although CNS insulin action (CNSIA) modulates hepatic glycogen synthesis in dogs, it has no net effect on hepatic glucose output over a 4-hour period. The role of CNSIA in regulating plasma glucose has recently been examined in humans and is the focus of this review. Intransal insulin (INI) administration increases CNS insulin concentration. Hence, INI can address whether CNSIA regulates plasma glucose concentration in humans. We and three other groups have sought to answer this question, with differing conclusions. Here we will review the critical aspects of each study, including its design, which may explain these discordant conclusions. The early glucose-lowering effect of INI is likely due to spillover of insulin into the systemic circulation. In the presence of simultaneous portal and CNS hyperinsulinemia, portal insulin action is dominant. INI administration does lower plasma glucose independent of peripheral insulin concentration (between ∼3 and 6 h after administration), suggesting that CNSIA may play a role in glucose homeostasis in the late postprandial period when its action is likely greatest and portal insulin concentration is at baseline. The potential physiological role and purpose of this pathway are discussed in this review. Because the effects of INI are attenuated in patients with type 2 diabetes and obesity, this is unlikely to be of therapeutic utility.

Molecular Mechanisms of Insulin Secretion and Insulin Action.

Science.gov (United States)

Flatt, Peter R.; Bailey, Clifford J.

1991-01-01

Information and current ideas on the factors regulating insulin secretion, the mechanisms underlying the secretion and biological actions of insulin, and the main characteristics of diabetes mellitus are presented. (Author)

Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction.

Science.gov (United States)

Kirk, Erik; Reeds, Dominic N; Finck, Brian N; Mayurranjan, S Mitra; Mayurranjan, Mitra S; Patterson, Bruce W; Klein, Samuel

2009-05-01

We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate (HC) diet or a low-carbohydrate (LC) diet on hepatic and skeletal muscle insulin sensitivity. Twenty-two obese subjects (body mass index, 36.5 +/- 0.8 kg/m2) were randomized to an HC (>180 g/day) or LC (vs 8.9% +/- 1.4%; P vs 7.2% +/- 1.4%; P vs 7.9% +/- 1.2%; P < .05). Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7% weight loss (48.4% +/- 14.3%; P < .05). In both groups, insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29% +/- 13% and phosphorylation of Akt and insulin receptor substrate 1 increased by 35% +/- 9% and 36% +/- 9%, respectively, after 7% weight loss (all P < .05). Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 hours of calorie restriction affects the liver (IHTG content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

A PSF-Shape-Based Beamforming Strategy for Robust 2D Motion Estimation in Ultrafast Data

OpenAIRE

Anne E. C. M. Saris; Stein Fekkes; Maartje M. Nillesen; Hendrik H. G. Hansen; Chris L. de Korte

2018-01-01

This paper presents a framework for motion estimation in ultrafast ultrasound data. It describes a novel approach for determining the sampling grid for ultrafast data based on the system’s point-spread-function (PSF). As a consequence, the cross-correlation functions (CCF) used in the speckle tracking (ST) algorithm will have circular-shaped peaks, which can be interpolated using a 2D interpolation method to estimate subsample displacements. Carotid artery wall motion and parabolic blood flow...

Tracking the ultrafast motion of a single molecule by femtosecond orbital imaging

Science.gov (United States)

Cocker, Tyler L.; Peller, Dominik; Yu, Ping; Repp, Jascha; Huber, Rupert

2016-11-01

Watching a single molecule move on its intrinsic timescale has been one of the central goals of modern nanoscience, and calls for measurements that combine ultrafast temporal resolution with atomic spatial resolution. Steady-state experiments access the requisite spatial scales, as illustrated by direct imaging of individual molecular orbitals using scanning tunnelling microscopy or the acquisition of tip-enhanced Raman and luminescence spectra with sub-molecular resolution. But tracking the intrinsic dynamics of a single molecule directly in the time domain faces the challenge that interactions with the molecule must be confined to a femtosecond time window. For individual nanoparticles, such ultrafast temporal confinement has been demonstrated by combining scanning tunnelling microscopy with so-called lightwave electronics, which uses the oscillating carrier wave of tailored light pulses to directly manipulate electronic motion on timescales faster even than a single cycle of light. Here we build on ultrafast terahertz scanning tunnelling microscopy to access a state-selective tunnelling regime, where the peak of a terahertz electric-field waveform transiently opens an otherwise forbidden tunnelling channel through a single molecular state. It thereby removes a single electron from an individual pentacene molecule’s highest occupied molecular orbital within a time window shorter than one oscillation cycle of the terahertz wave. We exploit this effect to record approximately 100-femtosecond snapshot images of the orbital structure with sub-ångström spatial resolution, and to reveal, through pump/probe measurements, coherent molecular vibrations at terahertz frequencies directly in the time domain. We anticipate that the combination of lightwave electronics and the atomic resolution of our approach will open the door to visualizing ultrafast photochemistry and the operation of molecular electronics on the single-orbital scale.

Insulin Biosynthetic Interaction Network Component, TMEM24, Facilitates Insulin Reserve Pool Release

Directory of Open Access Journals (Sweden)

Anita Pottekat

2013-09-01

Full Text Available Insulin homeostasis in pancreatic β cells is now recognized as a critical element in the progression of obesity and type II diabetes (T2D. Proteins that interact with insulin to direct its sequential synthesis, folding, trafficking, and packaging into reserve granules in order to manage release in response to elevated glucose remain largely unknown. Using a conformation-based approach combined with mass spectrometry, we have generated the insulin biosynthetic interaction network (insulin BIN, a proteomic roadmap in the β cell that describes the sequential interacting partners of insulin along the secretory axis. The insulin BIN revealed an abundant C2 domain-containing transmembrane protein 24 (TMEM24 that manages glucose-stimulated insulin secretion from a reserve pool of granules, a critical event impaired in patients with T2D. The identification of TMEM24 in the context of a comprehensive set of sequential insulin-binding partners provides a molecular description of the insulin secretory pathway in β cells.

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

Science.gov (United States)

Ilag, L L; Deeg, M A; Costigan, T; Hollander, P; Blevins, T C; Edelman, S V; Konrad, R J; Ortmann, R A; Pollom, R K; Huster, W J; Zielonka, J S; Prince, M J

2016-02-01

To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (Insulin antibody levels or developing TEAR was not associated with clinical outcomes. LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Pancreatic Transdifferentiation and Glucose-Regulated Production of Human Insulin in the H4IIE Rat Liver Cell Line

Directory of Open Access Journals (Sweden)

Binhai Ren

2016-04-01

Full Text Available Due to the limitations of current treatment regimes, gene therapy is a promising strategy being explored to correct blood glucose concentrations in diabetic patients. In the current study, we used a retroviral vector to deliver either the human insulin gene alone, the rat NeuroD1 gene alone, or the human insulin gene and rat NeuroD1 genes together, to the rat liver cell line, H4IIE, to determine if storage of insulin and pancreatic transdifferentiation occurred. Stable clones were selected and expanded into cell lines: H4IIEins (insulin gene alone, H4IIE/ND (NeuroD1 gene alone, and H4IIEins/ND (insulin and NeuroD1 genes. The H4IIEins cells did not store insulin; however, H4IIE/ND and H4IIEins/ND cells stored 65.5 ± 5.6 and 1475.4 ± 171.8 pmol/insulin/5 × 106 cells, respectively. Additionally, several β cell transcription factors and pancreatic hormones were expressed in both H4IIE/ND and H4IIEins/ND cells. Electron microscopy revealed insulin storage vesicles in the H4IIE/ND and H4IIEins/ND cell lines. Regulated secretion of insulin to glucose (0–20 mmol/L was seen in the H4IIEins/ND cell line. The H4IIEins/ND cells were transplanted into diabetic immunoincompetent mice, resulting in normalization of blood glucose. This data shows that the expression of NeuroD1 and insulin in liver cells may be a useful strategy for inducing islet neogenesis and reversing diabetes.

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme

Energy Technology Data Exchange (ETDEWEB)

Affholter, J.A.; Roth, R.A. (Stanford Univ. School of Medicine, CA (USA)); Cascieri, M.A.; Bayne, M.L. (Merck Sharp and Dohme Research Labs., Rahway, NJ (USA)); Brange, J. (Novo Research Institute, Bagsvaerd (Denmark)); Casaretto, M. (Deutsches Wollforschungsinstitut an der Technischen, Aachen (West Germany))

1990-08-21

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, the authors have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor, the first set of analogues studied were hybrid molecules of insulin and IGF I. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants (B25-Asp)insulin and (B25-His)insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin. Similar decreases in affinity are observed with the C-terminal truncation mutants (B1-24-His{sup 25}-NH{sub 2})insulin and (B1-24-Leu{sup 25}-NH{sub 2})insulin, but not (B1-24-Trp{sup 25}-NH{sub 2})insulin and (B1-24-Tyr{sup 25}-NH{sub 2})insulin. The truncated analogue with the lowest affinity for IDE ((B1-24-His{sup 25}-NH{sub 2})insulin) has one of the highest affinities for the insulin receptor. Therefore, they have identified a region of the insulin molecule responsible for its high-affinity interaction with IDE. Although the same region has been implicated in the binding of insulin to its receptor, the data suggest that the structural determinants required for binding to receptor and IDE differ.

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme

International Nuclear Information System (INIS)

Affholter, J.A.; Roth, R.A.; Cascieri, M.A.; Bayne, M.L.; Brange, J.; Casaretto, M.

1990-01-01

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, the authors have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor, the first set of analogues studied were hybrid molecules of insulin and IGF I. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25-Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin. Similar decreases in affinity are observed with the C-terminal truncation mutants [B1-24-His 25 -NH 2 ]insulin and [B1-24-Leu 25 -NH 2 ]insulin, but not [B1-24-Trp 25 -NH 2 ]insulin and [B1-24-Tyr 25 -NH 2 ]insulin. The truncated analogue with the lowest affinity for IDE ([B1-24-His 25 -NH 2 ]insulin) has one of the highest affinities for the insulin receptor. Therefore, they have identified a region of the insulin molecule responsible for its high-affinity interaction with IDE. Although the same region has been implicated in the binding of insulin to its receptor, the data suggest that the structural determinants required for binding to receptor and IDE differ

Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

NARCIS (Netherlands)

Swinnen, S. G.; Dain, M.-P.; Mauricio, D.; DeVries, J. H.; Hoekstra, J. B.; Holleman, F.

2010-01-01

We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2

Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients.

Science.gov (United States)

Hu, Xiaolei; Chen, Fengling

2018-01-01

Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. © 2018 The authors.

The effect of tubing dwell time on insulin adsorption during intravenous insulin infusions.

Science.gov (United States)

Thompson, Cecilia D; Vital-Carona, Jessica; Faustino, E Vincent S

2012-10-01

Insulin adsorbs to plastic tubing, which decreases the concentration of an insulin solution delivered from an intravenous infusion set. Dwelling insulin within tubing before starting the infusion decreases adsorption but delays treatment initiation and wastes time in infusion preparation. The lack of data on dwell time effects results in wide variability in practice. We aim to determine the effect of dwell time on insulin concentration from intravenous infusion tubing. In this in vitro study, we used insulin solutions with concentrations of 0.1 unit/mL, 1 unit/mL, and 10 units/mL. Each solution dwelled in intravenous infusion sets for 0, 15, 30, or 60 min. After the dwell, we measured insulin concentrations from the solution bags and tubing. We repeated each insulin concentration-dwell time combination five times. Comparisons were performed using analyses of variance. For each of the three insulin concentrations, the mean insulin concentrations from the tubing were not significantly different between dwell times. Duration of dwell time did not affect insulin adsorption in polypropylene intravenous infusion sets. We recommend that following a 20-mL flush, insulin infusions can be started without any dwell time. Removal of dwell times may improve clinical practice by minimizing preparation time and will allow faster initiation of insulin infusion therapy.

Ultrafast Electron Dynamics in Solar Energy Conversion.

Science.gov (United States)

Ponseca, Carlito S; Chábera, Pavel; Uhlig, Jens; Persson, Petter; Sundström, Villy

2017-08-23

Electrons are the workhorses of solar energy conversion. Conversion of the energy of light to electricity in photovoltaics, or to energy-rich molecules (solar fuel) through photocatalytic processes, invariably starts with photoinduced generation of energy-rich electrons. The harvesting of these electrons in practical devices rests on a series of electron transfer processes whose dynamics and efficiencies determine the function of materials and devices. To capture the energy of a photogenerated electron-hole pair in a solar cell material, charges of opposite sign have to be separated against electrostatic attractions, prevented from recombining and being transported through the active material to electrodes where they can be extracted. In photocatalytic solar fuel production, these electron processes are coupled to chemical reactions leading to storage of the energy of light in chemical bonds. With the focus on the ultrafast time scale, we here discuss the light-induced electron processes underlying the function of several molecular and hybrid materials currently under development for solar energy applications in dye or quantum dot-sensitized solar cells, polymer-fullerene polymer solar cells, organometal halide perovskite solar cells, and finally some photocatalytic systems.

Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

Science.gov (United States)

Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Mlcak, Ronald P; Qian, Ting; Chinkes, David L; Herndon, David N

2010-06-01

To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Prospective, randomized study. An acute pediatric burn unit in a tertiary teaching hospital. Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p protocol improves insulin sensitivity and mitochondrial

Ultrafast spontaneous emission modulation of graphene quantum dots interacting with Ag nanoparticles in solution

Energy Technology Data Exchange (ETDEWEB)

Zhao, Jianwei [Department of Physics, Shanghai University, Shanghai 200444 (China); Research Center of Quantum Macro-Phenomenon and Application, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210 (China); Lu, Jian, E-mail: luj@sari.ac.cn; Wang, Zhongyang, E-mail: wangzy@sari.ac.cn [Research Center of Quantum Macro-Phenomenon and Application, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210 (China); Wang, Liang [School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444 (China); Tian, Linfan [Research Center of Quantum Macro-Phenomenon and Application, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210 (China); School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210 (China); Deng, Xingxia [Research Center of Quantum Macro-Phenomenon and Application, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210 (China); School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Tian, Lijun [Department of Physics, Shanghai University, Shanghai 200444 (China); Pan, Dengyu [School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China)

2016-07-11

We investigated the strong interaction between graphene quantum dots and silver nanoparticles in solution using time-resolved photoluminescence techniques. In solution, the silver nanoparticles are surrounded by graphene quantum dots and interacted with graphene quantum dots through exciton-plasmon coupling. An ultrafast spontaneous emission process (lifetime 27 ps) was observed in such a mixed solution. This ultrafast lifetime corresponds to the emission rate exceeding 35 GHz, with the purcell enhancement by a factor of ∼12. These experiment results pave the way for the realization of future high speed light sources applications.

Adiponectin inhibits insulin function in primary trophoblasts by PPARα-mediated ceramide synthesis.

Science.gov (United States)

Aye, Irving L M H; Gao, Xiaoli; Weintraub, Susan T; Jansson, Thomas; Powell, Theresa L

2014-04-01

Maternal adiponectin (ADN) levels are inversely correlated with birth weight, and ADN infusion in pregnant mice down-regulates placental nutrient transporters and decreases fetal growth. In contrast to the insulin-sensitizing effects in adipose tissue and muscle, ADN inhibits insulin signaling in the placenta. However, the molecular mechanisms involved are unknown. We hypothesized that ADN inhibits insulin signaling and insulin-stimulated amino acid transport in primary human trophoblasts by peroxisome proliferator-activated receptor-α (PPARα)-mediated ceramide synthesis. Primary human term trophoblast cells were treated with ADN and/or insulin. ADN increased the phosphorylation of p38 MAPK and PPARα. ADN inhibited insulin signaling and insulin-stimulated amino acid transport. This effect was dependent on PPARα, because activation of PPARα with an agonist (GW7647) inhibited insulin signaling and function, whereas PPARα-small interfering RNA reversed the effects of ADN on the insulin response. ADN increased ceramide synthase expression and stimulated ceramide production. C2-ceramide inhibited insulin signaling and function, whereas inhibition of ceramide synthase (with Fumonisin B1) reversed the effects of ADN on insulin signaling and amino acid transport. These findings are consistent with the model that maternal ADN limits fetal growth mediated by activation of placental PPARα and ceramide synthesis, which inhibits placental insulin signaling and amino acid transport, resulting in reduced fetal nutrient availability.

Trimethylamine N-oxide (TMAO) as a New Potential Therapeutic Target for Insulin Resistance and Cancer

DEFF Research Database (Denmark)

Oellgaard, Jens; Winther, Signe Abitz; Hansen, Tobias Schmidt

2017-01-01

BACKGROUND: The intake of animal products in food has been associated with both the development of insulin resistance and gastrointestinal cancers (GIC). Through the digestion of animal protein and other constituents of animal products, the commensal bacteria in the gut (the gut microbiota) forms....... METHODS: We review the literature on TMAO as a shared risk factor and/or pathway between insulin resistance and GIC risk and take the reader through the literature of interventions that could reduce formation of TMAO and thereby the risk of insulin resistance and GIC. The purpose of the work...

Ultrafast dynamic computed tomography myelography for the precise identification of high-flow cerebrospinal fluid leaks caused by spiculated spinal osteophytes.

Science.gov (United States)

Thielen, Kent R; Sillery, John C; Morris, Jonathan M; Hoxworth, Joseph M; Diehn, Felix E; Wald, John T; Rosebrock, Richard E; Yu, Lifeng; Luetmer, Patrick H

2015-03-01

Precise localization and understanding of the origin of spontaneous high-flow spinal CSF leaks is required prior to targeted treatment. This study demonstrates the utility of ultrafast dynamic CT myelography for the precise localization of high-flow CSF leaks caused by spiculated spinal osteophytes. This study reports a series of 14 patients with high-flow CSF leaks caused by spiculated spinal osteophytes who underwent ultrafast dynamic CT myelography between March 2009 and December 2010. There were 10 male and 4 female patients, with an average age of 49 years (range 37-74 years). The value of ultrafast dynamic CT myelography in depicting the CSF leak site was qualitatively assessed. In all 14 patients, ultrafast dynamic CT myelography was technically successful at precisely demonstrating the site of the CSF leak, the causative spiculated osteophyte piercing the dura, and the relationship of the implicated osteophyte to adjacent structures. Leak sites included 3 cervical, 11 thoracic, and 0 lumbar levels, with 86% of the leaks occurring from C-5 to T-7. Information obtained from the ultrafast dynamic CT myelogram was considered useful in all treated CSF leaks. Spinal osteophytes piercing the dura are a more frequent cause of high-flow CSF leaks than previously recognized. Ultrafast dynamic CT myelography adds value beyond standard dynamic myelography or digital subtraction myelography in the diagnosis and anatomical characterization of high-flow spinal CSF leaks caused by these osteophytes. This information allows for appropriate planning for percutaneous or surgical treatment.

Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system.

Science.gov (United States)

de Araújo, Thiago M; Teixeira, Zaine; Barbosa-Sampaio, Helena C; Rezende, Luiz F; Boschero, Antonio C; Durán, Nelson; Höehr, Nelci F

2013-06-01

The aim of this work was to develop an efficient, biodegradable, biocompatible and safe controlled release system using insulin-loaded poly(epsilon-caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as emulsifier. Using the double emulsion method a high insulin encapsulation efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles showed no toxicity to MIN6 cells. Insulin nanoparticles administered subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels after 15 minutes, and presented a sustainable hypoglycemic effect on insulin-dependent type 1 diabetic rats, showing to be more efficient than unencapsulated insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by the effect over liver cell-death and oxidative stress scavenger system in rats. These results suggest that insulin-loaded PCL nanoparticles prepared by water-in-oil-in-water emulsion method are biocompatible, efficient and safe insulin-delivering system with controlled insulin release, which indicates that it may be a powerful tool for insulin-dependent patients care.

Sexual dimorphism in hepatic, adipose tissue and peripheral tissue insulin sensitivity in obese humans

Directory of Open Access Journals (Sweden)

Kasper W. ter Horst

2015-11-01

Full Text Available Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue and whole-body insulin sensitivity between severely obese men and women. In this study, we aimed to determine the differences in glucose metabolism between severely obese men and women using tissue-specific measurements of insulin sensitivity. Insulin sensitivity was compared between age and body mass index (BMI-matched obese men and women by a two-step euglycemic hyperinsulinemic clamp with infusion of [6,6-2H2]glucose. Basal endogenous glucose production and insulin sensitivity of the liver, adipose tissue and peripheral tissues were assessed. Liver fat content was assessed by proton magnetic resonance spectroscopy in a subset of included subjects. We included 46 obese men and women (age, 48±2 vs 46±2 years, p=0.591; BMI, 41±1 vs 41±1 kg/m2, p=0.832. There was no difference in basal endogenous glucose production (14.4±1.0 vs 15.3±0.5 µmol•kg fat-free mass-1•min-1, p=0.410, adipose tissue insulin sensitivity (insulin-mediated suppression of free fatty acids, 71.6±3.6 vs 76.1±2.6%, p=0.314 or peripheral insulin sensitivity (insulin-stimulated rate of disappearance of glucose, 26.2±2.1 vs 22.7±1.7 µmol•kg-1•min-1, p=0.211. Obese men were characterized by lower hepatic insulin sensitivity (insulin-mediated suppression of endogenous glucose production, 61.7±4.1 vs 72.8±2.5% in men vs women, resp., p=0.028. Finally, these observations could not be explained by differences in liver fat content (men vs women, 16.5±3.1 vs 16.0±2.5%, p=0.913, n=27.We conclude that obese men have lower hepatic, but comparable adipose tissue and peripheral tissue, insulin sensitivity compared to similarly obese women. Hepatic insulin resistance may

Silicon nanowires for ultra-fast and ultrabroadband optical signal processing

DEFF Research Database (Denmark)

Ji, Hua; Hu, Hao; Pu, Minhao

2015-01-01

In this paper, we present recent research on silicon nanowires for ultra-fast and ultra-broadband optical signal processing at DTU Fotonik. The advantages and limitations of using silicon nanowires for optical signal processing are revealed through experimental demonstrations of various optical...

Insulin pumps and insulin quality--requirements and problems.

Science.gov (United States)

Brange, J; Havelund, S

1983-01-01

In developing insulin solution suitable for delivery devices the chemical and biological stability, as well as the physical stability, must be taken into consideration. Addition of certain mono- and disaccharides increases the physical stability of neutral insulin solutions, but concurrently the chemical and biological stability decrease to an unacceptable degree. Addition of Ca-ions in low concentrations offers a physiologically acceptable method for stabilizing neutral insulin solutions against heat precipitation without affecting the quality, including the chemical and biological stability.

Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle

DEFF Research Database (Denmark)

Deshmukh, Atul S

2016-01-01

transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle....

Multiphoton microscopy in every lab: the promise of ultrafast semiconductor disk lasers

Science.gov (United States)

Emaury, Florian; Voigt, Fabian F.; Bethge, Philipp; Waldburger, Dominik; Link, Sandro M.; Carta, Stefano; van der Bourg, Alexander; Helmchen, Fritjof; Keller, Ursula

2017-07-01

We use an ultrafast diode-pumped semiconductor disk laser (SDL) to demonstrate several applications in multiphoton microscopy. The ultrafast SDL is based on an optically pumped Vertical External Cavity Surface Emitting Laser (VECSEL) passively mode-locked with a semiconductor saturable absorber mirror (SESAM) and generates 170-fs pulses at a center wavelength of 1027 nm with a repetition rate of 1.63 GHz. We demonstrate the suitability of this laser for structural and functional multiphoton in vivo imaging in both Drosophila larvae and mice for a variety of fluorophores (including mKate2, tdTomato, Texas Red, OGB-1, and R-CaMP1.07) and for endogenous second-harmonic generation in muscle cell sarcomeres. We can demonstrate equivalent signal levels compared to a standard 80-MHz Ti:Sapphire laser when we increase the average power by a factor of 4.5 as predicted by theory. In addition, we compare the bleaching properties of both laser systems in fixed Drosophila larvae and find similar bleaching kinetics despite the large difference in pulse repetition rates. Our results highlight the great potential of ultrafast diode-pumped SDLs for creating a cost-efficient and compact alternative light source compared to standard Ti:Sapphire lasers for multiphoton imaging.

A two-week reduction of ambulatory activity attenuates peripheral insulin sensitivity

DEFF Research Database (Denmark)

Krogh-Madsen, Rikke; Thyfault, John P; Broholm, Christa

2009-01-01

after step reduction, with a post hoc analysis revealing the most pronounced effect after 4 h of insulin infusion. In addition, the two-week period induced a 7% decline in VO2max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and truck, decreased concurrently. Taken together, one...... possible biological cause for the public health problem of type 2 diabetes has been identified. Reduced ambulatory activity for two weeks in healthy, non-exercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass. Key words: Inactivity, Insulin...... number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAkt(thr308)/total Akt decreased...

Ultrafast-laser-inscribed 3D integrated photonics: challenges and emerging applications

Directory of Open Access Journals (Sweden)

Gross S.

2015-11-01

Full Text Available Since the discovery that tightly focused femtosecond laser pulses can induce a highly localised and permanent refractive index modification in a large number of transparent dielectrics, the technique of ultrafast laser inscription has received great attention from a wide range of applications. In particular, the capability to create three-dimensional optical waveguide circuits has opened up new opportunities for integrated photonics that would not have been possible with traditional planar fabrication techniques because it enables full access to the many degrees of freedom in a photon. This paper reviews the basic techniques and technological challenges of 3D integrated photonics fabricated using ultrafast laser inscription as well as reviews the most recent progress in the fields of astrophotonics, optical communication, quantum photonics, emulation of quantum systems, optofluidics and sensing.

Ultrafast Ge-Te bond dynamics in a phase-change superlattice

Science.gov (United States)

Malvestuto, Marco; Caretta, Antonio; Casarin, Barbara; Cilento, Federico; Dell'Angela, Martina; Fausti, Daniele; Calarco, Raffaella; Kooi, Bart J.; Varesi, Enrico; Robertson, John; Parmigiani, Fulvio

2016-09-01

A long-standing question for avant-garde data storage technology concerns the nature of the ultrafast photoinduced phase transformations in the wide class of chalcogenide phase-change materials (PCMs). Overall, a comprehensive understanding of the microstructural evolution and the relevant kinetics mechanisms accompanying the out-of-equilibrium phases is still missing. Here, after overheating a phase-change chalcogenide superlattice by an ultrafast laser pulse, we indirectly track the lattice relaxation by time resolved x-ray absorption spectroscopy (tr-XAS) with a sub-ns time resolution. The approach to the tr-XAS experimental results reported in this work provides an atomistic insight of the mechanism that takes place during the cooling process; meanwhile a first-principles model mimicking the microscopic distortions accounts for a straightforward representation of the observed dynamics. Finally, we envisage that our approach can be applied in future studies addressing the role of dynamical structural strain in PCMs.

Structural Transformation of LiFePO4 during Ultrafast Delithiation.

Science.gov (United States)

Kuss, Christian; Trinh, Ngoc Duc; Andjelic, Stefan; Saulnier, Mathieu; Dufresne, Eric M; Liang, Guoxian; Schougaard, Steen B

2017-12-21

The prolific lithium battery electrode material lithium iron phosphate (LiFePO 4 ) stores and releases lithium ions by undergoing a crystallographic phase change. Nevertheless, it performs unexpectedly well at high rate and exhibits good cycling stability. We investigate here the ultrafast charging reaction to resolve the underlying mechanism while avoiding the limitations of prevailing electrochemical methods by using a gaseous oxidant to deintercalate lithium from the LiFePO 4 structure. Oxidizing LiFePO 4 with nitrogen dioxide gas reveals structural changes through in situ synchrotron X-ray diffraction and electronic changes through in situ UV/vis reflectance spectroscopy. This study clearly shows that ultrahigh rates reaching 100% state of charge in 10 s does not lead to a particle-wide union of the olivine and heterosite structures. An extensive solid solution phase is therefore not a prerequisite for ultrafast charge/discharge.

Toward understanding insulin fibrillation.

Science.gov (United States)

Brange, J; Andersen, L; Laursen, E D; Meyn, G; Rasmussen, E

1997-05-01

Formation of insulin fibrils is a physical process by which partially unfolded insulin molecules interact with each other to form linear aggregates. Shielding of hydrophobic domains is the main driving force for this process, but formation of intermolecular beta-sheet may further stabilize the fibrillar structure. Conformational displacement of the B-chain C-terminal with exposure of nonpolar, aliphatic core residues, including A2, A3, B11, and B15, plays a crucial role in the fibrillation process. Recent crystal analyses and molecular modeling studies have suggested that when insulin fibrillates this exposed domain interacts with a hydrophobic surface domain formed by the aliphatic residues A13, B6, B14, B17, and B18, normally buried when three insulin dimers form a hexamer. In rabbit immunization experiments, insulin fibrils did not elicit an increased immune response with respect to formation of IgG insulin antibodies when compared with native insulin. In contrast, the IgE response increased with increasing content of insulin in fibrillar form. Strategies and practical approaches to prevent insulin from forming fibrils are reviewed. Stabilization of the insulin hexameric structure and blockage of hydrophobic interfaces by addition of surfactants are the most effective means of counteracting insulin fibrillation.