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Sample records for non-metabolizable glucose analogue

  1. Glucose as substrate and signal in priming: Results from experiments with non-metabolizable glucose analogues

    Science.gov (United States)

    Mason-Jones, Kyle; Kuzyakov, Yakov

    2016-04-01

    Priming of soil organic matter remains the subject of intense research, but a mechanistic explanation of the phenomenon remains to be demonstrated. This is largely due to the multiple effects of easily available carbon on the soil microbial community, and the challenge of separating these influences from one another. Several glucose analogues can be taken up by microbial glucose transporters and have similar regulatory effects on metabolism. These substances are, however, not easily catabolized by the common glycolytic pathway, limiting their energy value. Therefore, they can be used to distinguish between the action of glucose as a metabolic signal, and its influence as an energy source. We incubated an agricultural Haplic Luvisol under controlled conditions for 24 days after addition of: 1) glucose, 2) 3-O-methyl-glucose, 3) α-methylglucoside or 4) 2-deoxyglucose, at three concentration levels, along with a control treatment of water addition. CO2 efflux from soil was monitored by trapping evolved CO2 in NaOH and back-titration with HCl. On the first day after amendment, CO2 efflux from soil increased strongly for glucose and much less for the analogues, relative to the control. Only glucose caused a peak in efflux within the first two days. Peak mineralization of 2-deoxyglucose and α-methylglucoside was delayed until the third day, while CO2 from 3-O-methyl-glucose increased gradually, with a peak delayed by approximately a week. For glucose, the immediate increase in respiration was strongly dependent on the amount of glucose added, but this was not the case for the analogues, indicating that the catabolic potential for these substances was saturated. This is consistent with only a small part of the microbial community being capable of utilizing these carbon sources. In a subsequent experiment, 14C-labelled glucose or 14C-labelled 3-O-methyl-glucose were added to the same soil, enabling quantification of the priming effect. For 3-O-methyl-glucose, priming was

  2. Cysteine analogues potentiate glucose-induced insulin release in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ammon, H.P.; Hehl, K.H.; Enz, G.; Setiadi-Ranti, A.; Verspohl, E.J.

    1986-12-01

    In rat pancreatic islets, cysteine analogues, including glutathione, acetylcysteine, cysteamine, D-penicillamine, L-cysteine ethyl ester, and cysteine-potentiated glucose (11.1 mM) induced insulin secretion in a concentration-dependent manner. Their maximal effects were similar and occurred at approximately 0.05, 0.05, 0.1, 0.5, 1.0, 1.0 mM, respectively. At substimulatory glucose levels (2.8 mM), insulin release was not affected by these compounds. In contrast, thiol compounds, structurally different from cysteine and its analogues, such as mesna, tiopronin, meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), beta-thio-D-glucose, as well as those cysteine analogues that lack a free-thiol group, including L-cystine, cystamine, D-penicillamine disulfide, S-carbocysteine, and S-carbamoyl-L-cysteine, did not enhance insulin release at stimulatory glucose levels (11.1 mM); cystine (5 mM) was inhibitory. These in vitro data indicate that among the thiols tested here, only cysteine and its analogues potentiate glucose-induced insulin secretion, whereas thiols that are structurally not related to cysteine do not. This suggests that a cysteine moiety in the molecule is necessary for the insulinotropic effect. For their synergistic action to glucose, the availability of a sulfhydryl group is also a prerequisite. The maximal synergistic action is similar for all cysteine analogues tested, whereas the potency of action is different, suggesting similarity in the mechanism of action but differences in the affinity to the secretory system.

  3. Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell line by TCDD.

    OpenAIRE

    1994-01-01

    This study examined the changes in cellular glucose uptake induced by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) as measured by quantification of intracellular radioactivity in the NIH 3T3 L1 preadipocyte cell line after a 30-minute incubation with the non-metabolizable radioactive analogue of glucose, 3-O-methyl-D-[1-3H] glucose. Treatment of differentiated NIH 3T3 L1 cells with TCDD produced a time- and dose-dependent decrease in the cellular uptake of glucose. Treatment of cells for 3 hr w...

  4. The non-metabolizable sucrose analog sucralose is a potent inhibitor of hormogonium differentiation in the filamentous cyanobacterium Nostoc punctiforme.

    Science.gov (United States)

    Splitt, Samantha D; Risser, Douglas D

    2016-03-01

    Nostoc punctiforme is a filamentous cyanobacterium which forms nitrogen-fixing symbioses with several different plants and fungi. Establishment of these symbioses requires the formation of motile hormogonium filaments. Once infected, the plant partner is thought to supply a hormogonium-repressing factor (HRF) to maintain the cyanobacteria in a vegetative, nitrogen-fixing state. Evidence implies that sucrose may serve as a HRF. Here, we tested the effects of sucralose, a non-metabolizable sucrose analog, on hormogonium differentiation. Sucralose inhibited hormogonium differentiation at a concentration approximately one-tenth that of sucrose. This result implies that: (1) sucrose, not a sucrose catabolite, is perceived by the cell and (2) inhibition is not due to a more general osmolarity-dependent effect. Additionally, both sucrose and sucralose induced the accrual of a polysaccharide sheath which bound specifically to the lectin ConA, indicating the presence of α-D-mannose and/or α-D-glucose. A ConA-specific polysaccharide was also found to be expressed in N. punctiforme colonies from tissue sections of the symbiotically grown hornwort Anthoceros punctatus. These findings imply that plant-derived sucrose or sucrose analogs may have multiple effects on N. punctiforme, including both repression of hormogonia and the induction of a polysaccharide sheath that may be essential to establish and maintain the symbiotic state.

  5. Design and synthesis of lupeol analogues and their glucose uptake stimulatory effect in L6 skeletal muscle cells.

    Science.gov (United States)

    Khan, Mohammad Faheem; Maurya, Chandan Kumar; Dev, Kapil; Arha, Deepti; Rai, Amit Kumar; Tamrakar, Akhilesh Kumar; Maurya, Rakesh

    2014-06-15

    Structure modifications of lupeol at the isopropylene moiety have been described via allylic oxidation using selenium dioxide. The antidiabetic efficacy of lupeol analogues were evaluated in vitro as glucose uptake stimulatory effect in L6 skeletal muscle cells. From all tested compounds, 2, 3, 4b and 6b showed significant stimulation of glucose uptake with respective percent stimulation of 173.1 (p <0.001), 114.1 (p <0.001), 98.3 (p <0.001) and 107.3 (p <0.001) at 10μM concentration. Stimulation of glucose uptake by these compounds is associated with enhanced translocation of glucose transporter 4 (GLUT4) and activation of IRS-1/PI3-K/AKT-dependent signaling pathway in L6 cells. Structure-activity relationship analysis of these analogues demonstrated that the integrity of α,β-unsaturated carbonyl and acetyl moieties were important in the retention of glucose uptake stimulatory effect. It is therefore proposed that naturally occurring lupeol and their analogues might reduce blood glucose, at least in part, through stimulating glucose utilization by skeletal muscles.

  6. Modelling the glucose-insulin-glucagon dynamics after subcutaneous administration of native glucagon and a novel glucagon analogue in dogs

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Boye Knudsen, Carsten; Jørgensen, John Bagterp;

    Zealand Pharma has invented a glucagon analogue, ZP-GA-1, with increased stability in liquid formulation for treatment of hypoglycemia. A pharmacodynamic (PD) model is needed to compare ZP-GA-1 with marketed glucagon. We aim to develop a model of the complex glucose-insulin-glucagon dynamics based...

  7. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    Science.gov (United States)

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (PPiracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

  8. PK/PD modelling of glucose-insulin-glucagon dynamics in healthy dogs after a subcutaneous bolus administration of native glucagon or a novel glucagon analogue

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Boye Knudsen, Carsten;

    Objective We aim to develop a simulation model of the complex glucose-insulin-glucagon dynamics based on physiology and data. Furthermore, we compare pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of marketed reconstituted glucagon with a stable liquid glucagon analogue invented...... satisfactorily for both glucagon and the analogue. Parameter estimates of the PD model were not significantly different between the two compounds. Conclusions The new PK/PD model enables simulations of the glucose-insulin-glucagon dynamics after a SC bolus of glucagon or glucagon analogue. The novel glucagon...... by Zealand Pharma A/S. Research Design and Methods We expanded a physiological model of endogenous glucose production with multiplicative effects of insulin and glucagon and combined it with the Hovorka glucoregulatory model. We used a Bayesian framework to perform multidimensional MAP estimation of model...

  9. 2-NBDG, a fluorescent analogue of glucose, as a marker for detecting cell electropermeabilization in vitro.

    Science.gov (United States)

    Raeisi, Elham; Mir, Lluis M

    2012-10-01

    This study investigated whether molecules spontaneously transported inside cells, like glucose derivatives, can also be used as electropermeabilization markers. Uptake of a fluorescent deoxyglucose derivative (2-NBDG) by normal and electropermeabilized cells in culture was analyzed. 2-NBDG was added to DC-3F cell suspensions and cells, exposed or not to eight square-wave electric pulses of 100-μs duration and of appropriate field amplitude at a repetition frequency of 1 Hz or 5 kHz, were incubated at 37 °C. 2-NBDG uptake was temperature-, concentration- and time-dependent in cells submitted or not to the electric pulses. In spite of significant uptake of 2-NBDG mediated by GLUT transporters into nonpermeabilized cells, the electric pulses significantly increased about ten to hundred times the 2-NBDG uptake into the cells. The increase in the field amplitude from 900 to 1,500 V/cm resulted in a progressive increase of 2-NDBG. Our results show that under the conditions of in vivo exposure duration to FDG and the physiological concentration of D-glucose, electric pulses increased 2-NBDG uptake into electropermeabilized cells. Under our experimental conditions, the percentage of permeabilized cells within the population of cells exposed to electric pulses remained at the same level regardless of the pulse frequency used, 1 Hz or 5 kHz. The findings showed that glucose derivatives can also be used to detect electropermeabilized cells exposed to electric pulses.

  10. Rheology and density of glucose syrup and honey: Determining their suitability for usage in analogue and fluid dynamic models of geological processes

    Science.gov (United States)

    Schellart, W. P.

    2011-06-01

    Analogue models of lithospheric deformation and fluid dynamic models of mantle flow mostly use some kind of syrup such as honey or glucose syrup to simulate the low-viscosity sub-lithospheric mantle. This paper describes detailed rheological tests and density measurements of three brands of glucose syrup and three brands of honey. Additional tests have been done for one brand of glucose syrup that was diluted with water to various degrees (2%, 5% and 10% by weight). The rheological tests have been done to test the effect of shear strain, shear rate and temperature on the dynamic viscosity of the syrup. The results show that the viscosity of all glucose syrups and honeys is independent of shear strain (i.e. no strain hardening or softening). The viscosity of the glucose syrups is independent of shear rate (γ˙), i.e. linear-viscous or Newtonian, in the range γ˙=10-4-10 s with stress exponents that are almost identical to one ( n = 0.995-1.004). All the honeys show a very weak, but consistent, decrease in viscosity with increasing shear rate of 7-14% from 10 -3 to 10 0 s -1 and have stress exponents more distinct from one ( n = 1.007-1.026). All syrups have a viscosity that is strongly dependent on temperature in the range 0-50 °C, where viscosity decreases with increasing temperature. Such decrease can be fitted with exponential and Arrhenius functions, with the latter giving the best results. Furthermore, the viscosity of glucose syrup decreases approximately exponentially with increasing water content. Oscillation tests indicate that the rheology of all the syrups is entirely dominated by viscous behaviour and not by elastic behaviour at frequencies of 10 -3-10 2 Hz. Finally, the density investigations show that the density of glucose syrup and honey decreases approximately linearly with increasing temperature in the range 10-70 °C, with coefficients of thermal volumetric expansion at 20 °C of 3.89-3.95 × 10 -4 °C -1 and 4.57-4.81 × 10 -4 °C -1 for

  11. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    OpenAIRE

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide...

  12. Increased insulin sensitivity and reduced micro and macro vascular disease induced by 2-deoxy-D-glucose during metabolic syndrome in obese JCR: LA-cp rats.

    Science.gov (United States)

    Russell, J C; Proctor, S D

    2007-05-01

    The metabolic syndrome, characterized by obesity, insulin resistance and dyslipidemia, is a major cause of cardiovascular disease. The origins of the syndrome have been hypothesized to lie in continuous availability of energy dense foods in modern societies. In contrast, human physiology has evolved in an environment of sporadic food supply and frequent food deprivation. Intermittent food restriction in rats has previously been shown to lead to reduction of cardiovascular risk and a greater life span. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) is taken up by cells and induces pharmacological inhibition of metabolism of glucose. We hypothesized that intermittent inhibition of glucose metabolism, a metabolic deprivation, may mimic intermittent food deprivation and ameliorate metabolic and pathophysiological aspects of the metabolic syndrome. Insulin resistant, atherosclerosis-prone JCR:LA-cp rats were treated with 2-DG (0.3% w/w in chow) on an intermittent schedule (2 days treated, one day non-treated, two days treated and two days non-treated) or continuously at a dose to give an equivalent averaged intake. Intermittent 2-DG-treatment improved insulin sensitivity, which correlated with increased adiponectin concentrations. Further, intermittent treatment (but not continuous treatment) reduced plasma levels of leptin and the inflammatory cytokine IL-1 beta. Both 2-DG treatments reduced micro-vascular glomerular sclerosis, but only the intermittent schedule improved macro-vascular dysfunction. Our findings are consistent with reduction in severity of the metabolic syndrome and protection against end stage micro- and macro-vascular disease through intermittent metabolic deprivation at a cellular level by inhibition of glucose oxidation with 2-DG.

  13. Assessment of biochemical control of acromegaly during treatment with somatostatin analogues by oral glucose load and insulin-like growth factor I.

    Science.gov (United States)

    Scacchi, M; Carzaniga, C; Vitale, G; Fatti, L M; Pecori Giraldi, F; Andrioli, M; Cattaneo, A; Cavagnini, F

    2011-10-01

    The use of oral glucose tolerance test (OGTT) in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) has recently been questioned. To gain further insights into this topic, we analyzed basal and nadir GH levels during OGTT in acromegalic patients on SSA. Basal IGF-I and GH values, as well as GH levels along the test, were analyzed in 115 standard OGTT performed in 33 acromegalic patients followed up between 1993 and 2009. All patients were on SSA at the time of the study; 22 of them had previously undergone unsuccessful surgery. No patient had undergone radiotherapy. GH suppression was considered normal when the hormonal value fell to 3.9 μg/l displayed lack of GH suppression after OGTT and 80% also displayed high IGF-I. Conversely, patients with basal GH3.9 μg/l are predictive of absent OGTT-dependent GH suppression; however, 20% of these patients display partial biochemical control (normal IGF-I levels). On the other hand, basal GH values <3.9 μg/l are not predictive of GH suppressibility by glucose and are often discordant with IGF-I levels.

  14. Mathematical model of metabolism and electrophysiology of amino acid and glucose stimulated insulin secretion: in vitro validation using a β-cell line.

    Directory of Open Access Journals (Sweden)

    Manuela Salvucci

    Full Text Available We integrated biological experimental data with mathematical modelling to gain insights into the role played by L-alanine in amino acid-stimulated insulin secretion (AASIS and in D-glucose-stimulated insulin secretion (GSIS, details important to the understanding of complex β-cell metabolic coupling relationships. We present an ordinary differential equations (ODEs based simplified kinetic model of core metabolic processes leading to ATP production (glycolysis, TCA cycle, L-alanine-specific reactions, respiratory chain, ATPase and proton leak and Ca(2+ handling (essential channels and pumps in the plasma membrane in pancreatic β-cells and relate these to insulin secretion. Experimental work was performed using a clonal rat insulin-secreting cell line (BRIN-BD11 to measure the consumption or production of a range of important biochemical parameters (D-glucose, L-alanine, ATP, insulin secretion and Ca(2+ levels. These measurements were then used to validate the theoretical model and fine-tune the parameters. Mathematical modelling was used to predict L-lactate and L-glutamate concentrations following D-glucose and/or L-alanine challenge and Ca(2+ levels upon stimulation with a non metabolizable L-alanine analogue. Experimental data and mathematical model simulations combined suggest that L-alanine produces a potent insulinotropic effect via both a stimulatory impact on β-cell metabolism and as a direct result of the membrane depolarization due to Ca(2+ influx triggered by L-alanine/Na(+ co-transport. Our simulations indicate that both high intracellular ATP and Ca(2+ concentrations are required in order to develop full insulin secretory responses. The model confirmed that K(+ ATP channel independent mechanisms of stimulation of intracellular Ca(2+ levels, via generation of mitochondrial coupling messengers, are essential for promotion of the full and sustained insulin secretion response in β-cells.

  15. 2-Deoxy-D-Glucose Modified Magnetic Nanoparticles with Dual Functional Properties: Nanothermotherapy and Magnetic Resonance Imaging.

    Science.gov (United States)

    Zhao, Lingyun; Zheng, Yajing; Yan, Hao; Xie, WenSheng; Sun, Xiaodan; Li, Ning; Tang, Jintian

    2016-03-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) with appropriate surface chemistry have attracted wild attention in medical and biological application because of their current and potential usefulness such as magnetic resonance imaging (MRI) contrast enhancement, magnetic mediated hyperthermia (MMH), immunoassay, and in drug delivery, etc. In this study, we investigated the MRI contrast agents and MMH mediators properties of the novel 2-deoxy-D-glucose (2-DG) modified SPIONs. As a non-metabolizable glucose analogue, 2-DG can block glycolysis and inhibits protein glycosylation. Moreover, SPIONs coated with 2-DG molecules can be particularly attractive to resource-hungry cancer cells, therefore to realize the targeting strategy for the SPIONs. SPIONs with amino silane as the capping agent for amino-group surface modification were synthesized by the chemical co-precipitation method with modification. Glutaraldehyde was further applied as an activation agent through which 2-DG was conjugated to the amino-coated SPIONs. Physicochemical characterizations of the 2-DG-SPIONs, such as surface morphology, surface charge and magnetic properties were investigated by Transmission Electron Microscopy (TEM), ζ-Potential and Vibrating Sample Magnetometer (VSM), etc. Magnetic inductive heating characteristics of the 2-DG-SPIONs were analyzed by exposing the SPIONs suspension (magnetic fluid) under alternative magnetic field (AMF). U-251 human glioma cells with expression of glucose transport proteins type 1 and 3 (GLUT1 and GLUT 3), and L929 murine fibroblast cell as negative control, were employed to study the effect of 2-DG modification on the cell uptake for SPIONs. TEM images for ultra-thin sections as well as ICP-MS were applied to evaluate the SPIONs internalization within the cells. In vitro MRI was performed after cells were co-incubated with SPIONs and the T2 relaxation time was measured and compared. The results demonstrate that 2-DG-SPIONs were supermagnetic and in

  16. 2-Deoxy-D-glucose treatment changes the Golgi apparatus architecture without blocking synthesis of complex lipids.

    Science.gov (United States)

    Ranftler, Carmen; Meisslitzer-Ruppitsch, Claudia; Stangl, Herbert; Röhrl, Clemens; Fruhwürth, Stefanie; Neumüller, Josef; Pavelka, Margit; Ellinger, Adolf

    2015-04-01

    The classic Golgi apparatus organization, an arrangement of highly ordered cisternal stacks with tubular-vesicular membrane specializations on both sides, is the functional image of a continuous flow of contents and membranes with input, metabolization, and output in a dynamic steady state. In response to treatment with 2-deoxy-D-glucose (2-DG), which lowers the cellular ATP level by about 70% within minutes, this organization is rapidly replaced by tubular-glomerular membrane convolutes described as Golgi networks and bodies. 2-DG is a non-metabolizable glucose analogue and competitive inhibitor of glycolysis, which has become attractive in the context of therapeutic approaches for several kinds of tumors specifically targeting glycolysis in cancer. With the question of whether the functions of the Golgi apparatus in lipid synthesis would be influenced by the 2-DG-induced Golgi apparatus reorganization, we focused on lipid metabolism within the Golgi bodies. For this, we applied a fluorophore-labeled short-chain ceramide (BODIPY-Cer) in various combinations with 2-DG treatment to HepG2 cell cultures and followed uptake, enrichment and metabolization to higher ordered lipids. The cellular ATP status in each experiment was controlled with a bioluminescence assay, and the response of the Golgi apparatus was tracked by immunostaining of the trans-Golgi network protein TGN46. For electron microscopy, the fluorescent BODIPY-Cer signals were converted into electron-dense precipitates by photooxidation of diaminobenzidine (DAB); DAB precipitates labeled trans-Golgi areas in control cultures but also compartments at the periphery of the Golgi bodies formed in response to 2-DG treatment, thus indicating that concentration of ceramide takes place in spite of the Golgi apparatus reorganization. Lipid analyses by thin-layer chromatography (TLC) performed in parallel showed that BODIPY-Cer is not only concentrated in compartments of the 2-DG-induced Golgi bodies but is partly

  17. Changes in 2-fluoro-2-deoxy-D-glucose incorporation, hexokinase activity and lactate production by breast cancer cells responding to treatment with the anti-HER-2 antibody trastuzumab

    Energy Technology Data Exchange (ETDEWEB)

    Cheyne, Richard W. [School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Trembleau, Laurent; McLaughlin, Abbie [School of Natural and Computing Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Smith, Tim A.D., E-mail: t.smith@abdn.ac.u [School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom)

    2011-04-15

    Introduction: Changes in 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) incorporation by tumors, detected using positron emission tomography, during response to chemotherapy are utilized clinically in patient management. Here, the effect of treatment with growth-inhibitory doses of the anti-human epidermal growth factor receptor-2 antibody trastuzumab (Herceptin) on the incorporation of FDG by breast tumor cells was measured along with hexokinase (HK) and glucose transport to determine the potential of FDG-positron emission tomography in predicting response to these biological anti-cancer therapies and their modulatory effects on the steps involved in FDG incorporation. Methods: The sensitivity to trastuzumab of three breast tumor cell lines, SKBr3, MDA-MB-453 and MDA-MB-468, expressing human epidermal growth factor receptor-2 at high, medium and low levels, respectively, was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay over a 6-day period, and a clonogenic assay was carried out after 7- and 10-day exposures. FDG incorporation by cells treated with growth-inhibitory doses of trastuzumab was carried out after 4 h and 2, 4 and 6 days of treatment. Glucose transport (rate of uptake of the non-metabolizable analogue [{sup 3}H]O-methyl-D-glucose), HK activity and lactate production were measured on cells treated with inhibitory doses of trastuzumab for 6 days. Results: The IC{sub 50} doses for SKBr3 and MDA-MB-453 and the IC{sub 20} dose for MDA-MB-468 after 6 days of treatment with trastuzumab were 0.25, 1 and 170 {mu}g/ml, respectively. FDG incorporation by SKBr3 and MDA-MB-453 cells was found to be decreased using IC{sub 50} doses of trastuzumab for 6 days. At the IC{sub 50} doses, FDG incorporation was also decreased at 4 days and, in the case of MDA-MB-453, even after 4 h of treatment. Decreased FDG incorporation corresponded with decreased HK activity in these cells. Lactate production, previously suggested to be a

  18. Gastric inhibitory polypeptide analogues

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2002-01-01

    of GIP and GLP-1 receptors, the incretin effect is essential for normal glucose tolerance. In patients with type 2 diabetes mellitus it turns out that the incretin effect is severely impaired or abolished. The explanation seems to be that both the secretion of GLP-1 and the effect of GIP are impaired...... (whereas both the secretion of GIP and the effect of GLP-1 are near normal). The impaired GLP-1 secretion is probably a consequence of diabetic metabolic disturbances. The known genetic variations in the GIP receptor sequence are not associated with type 2 diabetes mellitus, but a defective insulinotropic...... and its analogues are attractive as therapeutic agents for type 2 diabetes mellitus, analogues of GIP are unlikely to be effective. On the other hand, GIP seems to play an important role in lipid metabolism, promoting the disposal of ingested lipids, and mice with a targeted deletion of the GIP receptor...

  19. BALANOL ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid-phase s...... be immobilised to the polymer support either as the monoallyl ester or as the internal anhydride. The libraries produced by the method are especially suited for high throughput screening of potential drug candidates for the treatment of mammals, especially humans....

  20. Comparisons between glucose analogue 2-deoxy-2-(18F)fluoro-D-glucose and 18F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

    Institute of Scientific and Technical Information of China (English)

    Selene Capitanio; Francesca Bongioanni; Arnoldo Piccardo; Claudio Campus; Roberta Gonella; Lucia Tixi; Mehrdad Naseri; Michele Pennone; Vania Altrinetti; Ambra Buschiazzo; Irene Bossert; Francesco Fiz; Andrea Bruno; Andrea DeCensi; Gianmario Sambuceti; Silvia Morbelli

    2016-01-01

    AIM: To compare 2-deoxy-2-(18F)fluoro-D-glucose(18FFDG) and 18F-sodium(18F-NaF) positron emission tomography/computed tomography(PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent 18F-FDG and 18F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity(Se), specificity(Sp), overall accuracy, positive and negative predictive values, error rate, and Youden’s index. Mc Nemar’s χ2 test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the coregistered CT(sclerotic, lytic, mixed, no-lesions) and the divergent site of disease(skull, spine, ribs, extremities, pelvis). The impact of adding 18F-Na F PET/CT to the work-up of patients was also measured in terms of change in their management due to 18F-Na F PET/CT findings. RESULTS: The two imaging methods of 18F-FDG and 18F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively(Mc Nemar’s χ2 = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis(Mc Nemar’s χ2 = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, 18F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis(P < 0.002) and vertebral localizations(P < 0.002); 18F-Na F PET/CT was more accurate in detecting sclerotic(P < 0.005) and rib lesions

  1. Analogue computing methods

    CERN Document Server

    Welbourne, D

    1965-01-01

    Analogue Computing Methods presents the field of analogue computation and simulation in a compact and convenient form, providing an outline of models and analogues that have been produced to solve physical problems for the engineer and how to use and program the electronic analogue computer. This book consists of six chapters. The first chapter provides an introduction to analogue computation and discusses certain mathematical techniques. The electronic equipment of an analogue computer is covered in Chapter 2, while its use to solve simple problems, including the method of scaling is elaborat

  2. Dietary glucose regulates yeast consumption in adult Drosophila males

    Directory of Open Access Journals (Sweden)

    Sebastien eLebreton

    2014-12-01

    Full Text Available The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males.

  3. Analogue MIMO Detection

    Directory of Open Access Journals (Sweden)

    McNamara Darren

    2006-01-01

    Full Text Available In this contribution we propose an analogue receiver that can perform turbo detection in MIMO systems. We present the case for a receiver that is built from nonlinear analogue devices, which perform detection in a "free-flow" network (no notion of iterations. This contribution can be viewed as an extension of analogue turbo decoder concepts to include MIMO detection. These first analogue implementations report reductions of few orders of magnitude in the number of required transistors and in consumed energy, and the same order of improvement in processing speed. It is anticipated that such analogue MIMO decoder could bring about the same advantages, when compared to traditional digital implementations.

  4. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the huma

  5. Survey of analogue spacetimes

    CERN Document Server

    Visser, Matt

    2013-01-01

    Analogue spacetimes, (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole, (mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid --- and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: Analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this introductory chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  6. Primary metabolism and medium-chain fatty acid alterations precede long-chain fatty acid changes impacting neutral lipid metabolism in response to an anti-cancer lysophosphatidylcholine analogue in yeast.

    Science.gov (United States)

    Tambellini, Nicolas P; Zaremberg, Vanina; Krishnaiah, Saikumari; Turner, Raymond Joseph; Weljie, Aalim M

    2017-08-29

    The non-metabolizable lysophosphatidylcholine (LysoPC) analogue edelfosine is the prototype of a class of compounds being investigated for their potential as selective chemotherapeutic agents. Edelfosine targets membranes, disturbing cellular homeostasis. Is not clear at this point how membrane alterations are communicated between intracellular compartments leading to growth inhibition and eventual cell death. In the present study, a combined metabolomics/lipidomics approach for the unbiased identification of metabolic pathways altered in yeast treated with sub-lethal concentrations of the LysoPC analogue was employed. Mass spectrometry of polar metabolites, fatty acids and lipidomic profiling was used to study the effects of edelfosine on yeast metabolism. Amino acid and sugar metabolism, the Krebs cycle, and fatty acid profiles were most disrupted, with polar metabolites and short-medium chain fatty acid changes preceding long and very long-chain fatty acid variations. Initial increase in metabolites like trehalose, proline and gamma-amino butyric acid with a concomitant decrease in metabolites of the Krebs cycle, citrate and fumarate, are interpreted as a cellular attempt to offset oxidative stress in response to mitochondrial dysfunction induced by the treatment. Notably, alanine, inositol and myristoleic acid showed a steady increase during the period analyzed (2,4 and 6 hours after treatment). Of importance was the finding that edelfosine induced significant alterations in neutral glycerolipid metabolism resulting in a significant increase in the signalling lipid diacylglycerol.

  7. Synthesis of Tonghaosu Analogues

    Institute of Scientific and Technical Information of China (English)

    SUN Hai; LIN Yingjie; WU Yulin; WU Yikang

    2009-01-01

    Several new analogues of natural antifeedant tonghaosu were synthesized via m-CPBA (m-chloroperoxybenzoic acid) oxidation of corresponding 3-(a-furyl)propanols, Luche reduction of the resulting enone, epoxidation, acid-mediated spiroketalization, and radical mediated dehydration.

  8. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  9. 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 studi......, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring....

  10. Specific analogues uncouple transport, signalling, oligo-ubiquitination and endocytosis in the yeast Gap1 amino acid transceptor.

    Science.gov (United States)

    Van Zeebroeck, Griet; Rubio-Texeira, Marta; Schothorst, Joep; Thevelein, Johan M

    2014-07-01

    The Saccharomyces cerevisiae amino acid transceptor Gap1 functions as receptor for signalling to the PKA pathway and concomitantly undergoes substrate-induced oligo-ubiquitination and endocytosis. We have identified specific amino acids and analogues that uncouple to certain extent signalling, transport, oligo-ubiquitination and endocytosis. L-lysine, L-histidine and L-tryptophan are transported by Gap1 but do not trigger signalling. Unlike L-histidine, L-lysine triggers Gap1 oligo-ubiquitination without substantial induction of endocytosis. Two transported, non-metabolizable signalling agonists, β-alanine and D-histidine, are strong and weak inducers of Gap1 endocytosis, respectively, but both causing Gap1 oligo-ubiquitination. The non-signalling agonist, non-transported competitive inhibitor of Gap1 transport, L-Asp-γ-L-Phe, induces oligo-ubiquitination but no discernible endocytosis. The Km of L-citrulline transport is much lower than the threshold concentration for signalling and endocytosis. These results show that molecules can be transported without triggering signalling or substantial endocytosis, and that oligo-ubiquitination and endocytosis do not require signalling nor metabolism. Oligo-ubiquitination is required, but apparently not sufficient to trigger endocytosis. In addition, we demonstrate intracellular cross-induction of endocytosis of transport-defective Gap1(Y395C) by ubiquitination- and endocytosis-deficient Gap1(K9R,K16R). Our results support the concept that different substrates bind to partially overlapping binding sites in the same general substrate-binding pocket of Gap1, triggering divergent conformations, resulting in different conformation-induced downstream processes.

  11. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g...

  12. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g...

  13. Simultaneous utilization of glucose, xylose and arabinose in the presence of acetate by a consortium of Escherichia coli strains

    Directory of Open Access Journals (Sweden)

    Xia Tian

    2012-06-01

    Full Text Available Abstract Background The efficient microbial utilization of lignocellulosic hydrolysates has remained challenging because this material is composed of multiple sugars and also contains growth inhibitors such as acetic acid (acetate. Using an engineered consortium of strains derived from Escherichia coli C and a synthetic medium containing acetate, glucose, xylose and arabinose, we report on both the microbial removal of acetate and the subsequent simultaneous utilization of the sugars. Results In a first stage, a strain unable to utilize glucose, xylose and arabinose (ALS1392, strain E. coli C ptsG manZ glk crr xylA araA removed 3 g/L acetate within 30 hours. In a subsequent second stage, three E. coli strains (ALS1370, ALS1371, ALS1391, which are each engineered to utilize only one sugar, together simultaneously utilized glucose, xylose and arabinose. The effect of non-metabolizable sugars on the metabolism of the target sugar was minimal. Additionally the deletions necessary to prevent the consumption of one sugar only minimally affected the consumption of a desired sugar. For example, the crr deletion necessary to prevent glucose consumption reduced xylose and arabinose utilization by less than 15% compared to the wild-type. Similarly, the araA deletion used to exclude arabinose consumption did not affect xylose- and glucose-consumption. Conclusions Despite the modest reduction in the overall rate of sugar consumption due to the various deletions that were required to generate the consortium of strains, the approach constitutes a significant improvement in any single-organism approach to utilize sugars found in lignocellulosic hydrolysate in the presence of acetate.

  14. Aspartame and Its Analogues

    Science.gov (United States)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  15. Quantum analogue computing.

    Science.gov (United States)

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  16. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  17. Analogue Methods in Palaeoecology: Using the analogue Package

    OpenAIRE

    Simpson, Gavin L.

    2007-01-01

    Palaeoecology is an important branch of ecology that uses the subfossil remains of organisms preserved in lake, ocean and bog sediments to inform on changes in ecosystems and the environment through time. The analogue package contains functions to perform modern analogue technique (MAT) transfer functions, which can be used to predict past changes in the environment, such as climate or lake-water pH from species data. A related technique is that of analogue matching, which is concerned with i...

  18. Synthesis of a novel uridine analogue and its use in attempts to form new cyclonucleosides using ring-closing metathesis

    Institute of Scientific and Technical Information of China (English)

    MONDON; Martine; LEN; Christophe

    2010-01-01

    One novel nucleoside analogue having a hex-5-enyl group and an allyl group in the 5’-C and 3-N position was synthesized regioand diastereoselectively from D-glucose in twelve steps.In order to reach a particular conformation of nucleosides the nucleoside formation of restricted cyclonucleoside analogues was studied via Ring-Closing Metathesis.

  19. Radioiodinated glucose analogues for use as imaging agents

    Science.gov (United States)

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1988-01-01

    A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

  20. Vorticity in analogue gravity

    CERN Document Server

    Cropp, Bethan; Turcati, Rodrigo

    2015-01-01

    In the analogue gravity framework, the acoustic disturbances in a moving fluid can be described by an equation of motion identical to a relativistic scalar massless field propagating in a curved spacetime. This description is possible only when the fluid under consideration is barotropic, inviscid and irrotational. In this case, the propagation of the perturbations is governed by an acoustic metric which depends algebrically on the local speed of sound, density and the background flow velocity, the latter assumed to be vorticity free. In this work we provide an straightforward extension in order to go beyond the irrotational constraint. Using a charged --- relativistic and non-relativistic --- Bose--Einstein condensate as a physical system, we show that in the low momentum limit and performing the eikonal approximation we can derive a d'Alembertian equation of motion for the charged phonons where the emergent acoustic metric depends on a flow velocity in the presence of vorticity.

  1. Mechanical stress and glucose concentration modulate glucose transport in cultured rat podocytes.

    Science.gov (United States)

    Lewko, Barbara; Bryl, Ewa; Witkowski, Jacek M; Latawiec, Elzbieta; Angielski, Stefan; Stepinski, Jan

    2005-02-01

    Recent studies show that mechanical stress modifies both morphology and protein expression in podocytes. Ambient glucose is another factor modulating protein synthesis in these cells. In diabetes, podocytes experience elevated glucose concentrations as well as mechanical strain generated by high intracapillary pressures. Both these factors are responsible for podocyte injury, leading to impairment of kidney glomerular function. In the present study, we examined the effects of glucose concentration and mechanical stress on glucose uptake in podocytes. Following a 24 h pre-incubation in low (2.5 mM, LG), normal (5.6 mM, NG) or high (30 mM, HG) glucose media, cultured rat podocytes were exposed to 4 h mechanical stress. We used the labelled glucose analogue, [3H]2-deoxy-D-glucose, to measure glucose uptake. The distribution of facilitative glucose transporters GLUT2 and GLUT4 was assessed by flow cytometry. In the control (static) cells, glucose uptake was similar in the three glucose groups. In mechanically stressed podocytes, glucose uptake increased 2-fold in the LG and NG groups but increased 3-fold in the HG group. In the NG cells, mechanical load increased the membrane expression of GLUT2 and reduced the membrane-bound GLUT4. In stretched HG cells, the membrane expression of both GLUT2 and GLUT4 was decreased. High glucose decreased the plasma membrane GLUT2 content in the stretched cells, whereas both static and stretched podocytes showed an elevation in GLUT4. Mechanical stress potentiated glucose uptake in podocytes and this effect was enhanced by high ambient glucose. The decreased expression of GLUT2 and GLUT4 on the surface of stretched cells suggests that the activity of other glucose transporters may be regulated by mechanical stress in podocytes.

  2. [Cloning, expressing of exendin-4 analogue and bioactivity analysis in vivo].

    Science.gov (United States)

    Li, Taiming; Gu, Chunjiao; Ge, Xiaoyu; Li, Zhezhe; Wang, Dan; Ma, Yanhong; Liu, Tao; Zhang, Meiyou; Li, Li; Liu, Jingjing

    2012-07-01

    To construct, express and purify Exendin-4 analogue and detect its biological activity in vivo. Insert gene sequence into fusion partner ofpED plasmid which is helped to purification, entitled the new recombinant plasmid 5 Exendin-4 analogue polypeptide gene and fusion partner gene was linked by acid hydrolysisgene, transformed to E. coli BL21 and the fusion protein was induced by lactose. After acid hydrolysis, the Exendin-4 analogue polypeptide separated from fusion chaperon. Anion charge chromatography were used to further purification. 6 to 8 week-old ICR mice were injected (s.c) with Exendin-4 analogue, blood glucose and plasma insulin level was detected in different period after oral glucose tolerance test. The results show that high expression of inclusion body was induced by lactose, which accounted for 40% of germ proteins, the Exendin-4 analogue was obtained with the purity of 91.8% after being purified by anion charge chromatography. Bioactivity assay showed that the level of blood glucose of mouse which treated with exendin-4 analogue was obviously decreased to normal (P < 0.01), and the level of plasma insulin was increased obviously (P < 0.01).

  3. NASA/ESMD Analogue Mission Plans

    Science.gov (United States)

    Hoffman, Stephen J.

    2007-01-01

    A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

  4. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...... of CorA. METHODS: HC-CorA were quantified in paired samples of cord serum from newborns and serum from mothers (n = 69). RESULTS: The CorA-concentration was higher in cord serum (median = 380, range: 41-780 pmol/L) than in serum from the mothers (median = 160, range: 64-330 pmol/L), (p...-analysis showed CorA-peaks with retention times of 13.5, 14,5 and 16.5 min in samples from both the mother and cord serum. The peak with retention time 16.5 min constituted 24% (mother) and 45% (cord serum) of the total amount CorA, and eluted as does dicyanocobinamide. CONCLUSION: Our results support that CorA...

  5. Glucosamine and glucosamine-6-phosphate derivatives: catalytic cofactor analogues for the glmS ribozyme.

    Science.gov (United States)

    Posakony, Jeffrey J; Ferré-D'Amaré, Adrian R

    2013-05-17

    Two analogues of glucosamine-6-phosphate (GlcN6P, 1) and five of glucosamine (GlcN, 2) were prepared for evaluation as catalytic cofactors of the glmS ribozyme, a bacterial gene-regulatory RNA that controls cell wall biosynthesis. Glucosamine and allosamine with 3-azido substitutions were prepared by SN2 reactions of the respective 1,2,4,6-protected sugars; final acidic hydrolysis afforded the fully deprotected compounds as their TFA salts. A 6-phospho-2-aminoglucolactam (31) was prepared from glucosamine in a 13-step synthesis, which included a late-stage POCl3-phosphorylation. A simple and widely applicable 2-step procedure with the triethylsilyl (TES) protecting group was developed to selectively expose the 6-OH group in N-protected glucosamine analogues, which provided another route to chemical phosphorylation. Mitsunobu chemistry afforded 6-cyano (35) and 6-azido (36) analogues of GlcN-(Cbz), and the selectivity for the 6-position was confirmed by NMR (COSY, HMBC, HMQC) experiments. Compound 36 was converted to the fully deprotected 6-azido-GlcN (37) and 2,6-diaminoglucose (38) analogues. A 2-hydroxylamino glucose (42) analogue was prepared via an oxaziridine (41). Enzymatic phosphorylation of 42 and chemical phosphorylation of its 6-OH precursor (43) were possible, but 42 and the 6-phospho product (44) were unstable under neutral or basic conditions. Chemical phosphorylation of the previously described 2-guanidinyl-glucose (46) afforded its 6-phospho analogue (49) after final deprotection.

  6. Introduction to electronic analogue computers

    CERN Document Server

    Wass, C A A

    1965-01-01

    Introduction to Electronic Analogue Computers, Second Revised Edition is based on the ideas and experience of a group of workers at the Royal Aircraft Establishment, Farnborough, Hants. This edition is almost entirely the work of Mr. K. C. Garner, of the College of Aeronautics, Cranfield. As various advances have been made in the technology involving electronic analogue computers, this book presents discussions on the said progress, including some acquaintance with the capabilities of electronic circuits and equipment. This text also provides a mathematical background including simple differen

  7. Menstrual regulation with prostaglandin analogues.

    Science.gov (United States)

    Hagenfeldt, K; Bygdeman, M

    1981-01-01

    The development of generally applicable, simple non-surgical methods for menstrual regulation has been desired for a long time. Such an approach to fertility control depends on the availability of a suitable therapeutic agent that should be effective, reliable, simple to administer and free from disturbing side effects. The classical prostaglandins have shown the capability but are unsuitable mainly due to high incidence of side effects. Most of these drawbacks seem to be overcome when prostaglandin analogues are used; however, vaginal administration caused appreciable pain in 10-30% of women, and so severely limits self-administration of these analogues.

  8. Analogue Methods in Palaeoecology: Using the analogue Package

    Directory of Open Access Journals (Sweden)

    Gavin L. Simpson

    2007-08-01

    Full Text Available Palaeoecology is an important branch of ecology that uses the subfossil remains of organisms preserved in lake, ocean and bog sediments to inform on changes in ecosystems and the environment through time. The analogue package contains functions to perform modern analogue technique (MAT transfer functions, which can be used to predict past changes in the environment, such as climate or lake-water pH from species data. A related technique is that of analogue matching, which is concerned with identifying modern sites that are floristically and faunistically similar to fossil samples. These techniques, and others, are increasingly being used to inform public policy on environmental pollution and conservation practices. These methods and other functionality in analogue are illustrated using the Surface Waters Acidification Project diatom:pH training set and diatom counts on samples of a sediment core from the Round Loch of Glenhead, Galloway, Scotland. The paper is aimed at palaeoecologists who are familiar with the techniques described but not with R.

  9. Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

    DEFF Research Database (Denmark)

    Hovind, Peter; Simonsen, Lene; Bülow, Jens

    2010-01-01

    During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before...... and during leg exercise....

  10. Novel acetylcholine and carbamoylcholine analogues

    DEFF Research Database (Denmark)

    Hansen, Camilla Petrycer; Jensen, Anders Asbjørn; Christensen, Jeppe K.

    2008-01-01

    A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity for this ...

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

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    in a long half-life with a residual activity of about 50% 24 h after injection. Insulin glargine is a peakless insulin and studies in both type 1 and type 2 diabetic patients indicate that glargine improves fasting blood glucose control and reduces the incidence of nocturnal hypoglycaemia. Surprisingly...... have not been able to show any improvement in overall glycaemic control with the fast-acting analogues. A reduced post-prandial increase in blood glucose has been found in all studies, whereas between 3 and 5 h after the meal and during the night an increased blood glucose level is the normal course....... 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...

  12. Measuring Mental Imagery with Visual Analogue Scales.

    Science.gov (United States)

    Quilter, Shawn M.; Band, Jennie P.; Miller, Gary M.

    1999-01-01

    Investigates some of the psychometric characteristics of the results from visual-analogue scales used to measure mental imagery. Reports that the scores from visual-analogue scales are positively related to scores from longer pencil-and-paper measures of mental imagery. Implications and limitations for the use of visual-analogue scales to measure…

  13. Low Blood Glucose (Hypoglycemia)

    Science.gov (United States)

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low blood glucose or low blood sugar, occurs when ...

  14. Pharmacological evaluation of a β-hydroxyphosphonate analogue of l-carnitine in obese Zucker fa/fa rats.

    Science.gov (United States)

    Reyes-Esparza, Jorge; Mendoza-Rivera, Brissa; De la Cruz-Cordero, Ricardo; Rosado, Jorge L; Duarte-Vázquez, Miguel Á; Solis, Mario G; Vite-Vallejo, Odón; Rodríguez-Fragoso, Lourdes

    2013-04-01

    In this study, we evaluated the effect of an analogue of l-carnitine on parameters involved with Metabolic Syndrome in obese Zucker rats. Twenty-four rats were treated for 5 weeks with l-carnitine (300 mg/kg) and its analogue at two concentrations (100 and 250 mg/kg) to assess their impact on glucose, triglycerides and cholesterol in liver and blood samples, as well as the amount of liver glycogen. Liver slices were also analysed. The analogue reduced the levels of glucose, triglycerides and cholesterol in liver and the level of triglycerides in serum. At 100 mg/kg, the analogue proved more effective than l-carnitine in improving the biochemical alterations present in liver. The amount of liver glycogen content was higher in obese animals treated with both l-carnitine and the analogue. No changes on insulin and leptin were observed in animals treated. l-carnitine and its analogue reduced the microvesicular fatty infiltration in liver. This study demonstrated that the analogue tested is more potent and efficient than l-carnitine and improves the pharmacological profile of l-carnitine.

  15. Insulin analogues may accelerate progression of diabetic retinopathy after impairment of inner blood-retinal barrier.

    Science.gov (United States)

    Kaya, Abdullah; Kar, Taner; Aksoy, Yakup; Özalper, Veysel; Başbuğ, Barbaros

    2013-12-01

    Diabetic retinopathy regresses after spontaneous infarction or surgical ablation of pituitary gland. Growth hormone deficiency seems to be a protective factor for development of diabetic retinopathy in dwarfs. Despite the same glycemic control, development of diabetic retinopathy is significantly higher in pubertal subjects than pre-pubertal subjects. These evidences indicate a strong relationship between growth hormone and progression of diabetic retinopathy. Insulin like growth factor-1 (IGF-1) is the most important mediator of effects of growth hormone (GH). It stimulates IGF-1 receptor. Insulin analogues also stimulate IGF-1 receptor. Therefore insulin analogues may show similar effects like growth hormone and deteriorate diabetic retinopathy. However we suggest that impairment degree of inner blood-retinal barrier should be considered for this claim. We hypothesize that insulin analogues have dual effects (beneficial and worsening) depending on stage of impairment of inner blood-retinal barrier. Insulin analogues protect pericytes and blood-retinal barrier by decreasing blood glucose level. Analogues may pass into the retinal tissue in very low amounts when inner blood-retinal barrier is intact. Therefore, insulin analogues may not deteriorate diabetic retinopathy but also have beneficial effect by protecting blood-retinal barrier at this stage. However, they may pass into the retinal tissue in much more amounts when inner blood-retinal barrier impairs. Analogues may deteriorate cellular composition of retina through stimulation of IGF-1 receptors. A number of different cell types, including glia, retinal pigment epithelial cells and fibroblast-like cells have been identified in diabetic epiretinal tissues. Insulin analogues may cause proliferation in these cells. A type of glial cell named Non-astrocytic Inner Retinal Glia-like (NIRG) cell was identified to be stimulated and proliferate by IGF-1. IGF has been reported to generate traction force in retinal

  16. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  17. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis.

    Science.gov (United States)

    Branis, Natalia M; Wittlin, Steven D

    2015-01-01

    Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA) after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35-7.45), bicarbonate 16 mmol/L (22-29 mmol/L), and anion gap 19 mmol/L (8-16 mmol/L). Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA) availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  18. A Short Term Analogue Memory

    DEFF Research Database (Denmark)

    Shah, Peter Jivan

    1992-01-01

    A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...... rate of 0.075mV per second with a 1pF hold capacitor. This is equivalent to a retention time of approximately 1½ minute with 10 bits accuracy, assuming a full scale of +/-3.5V. It is expected that this can be improved by more than an order of magnitude by improving the layout of the hold capacitor...

  19. Neuronal Analogues of Conditioning Paradigms

    Science.gov (United States)

    1984-04-24

    Although the mechanisms of interneuronal communication have been well established, the changes underlying most forms of learning have thus far eluded...stimulating electrodes on one of the connectives was adjusted so as to produce a small excitatory postsynaptic potential ( EPSP ) in the impaled cell...two stimuli would constitute a neuronal analogue of conditioning by producing an increased EPSP in response to the test stimulus alone. If so, then

  20. Substrate analogues for isoprenoid enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  1. GnRH analogue attenuated apoptosis of rat hippocampal neuron after ischemia-reperfusion injury.

    Science.gov (United States)

    Chu, Chenyu; Xu, Bainan; Huang, Weiquan

    2010-12-01

    The expression and new functions of reproductive hormones in organs beyond hypothalamus-pituitary-gonad axis have been reported. So far, there is no report about the protective effects of GnRH analogue to hippocampal neurons suffering from ischemia-reperfusion injury. Middle cerebral artery occlusion model together with TUNEL staining were made in vivo and oxygen-glucose deprivation model together with double staining of Annexin V/PI with flow cytometer were made in vitro to observe the anti-apoptotic effects of GnRH analogue to hippocampal neurons after ischemia-reperfusion injury. The results found that the number of TUNEL positive pyramidal neurons in CA1 region in GnRH analogue experiment group was less than that in control group in vivo; the percentage of apoptotic neurons in GnRH analogue experiment group was less than that in control group in vitro. These findings suggested that pretreatment with certain concentration of GnRH analogue could attenuate apoptosis of hippocampal neurons. GnRH analogue has the protective effects to neurons.

  2. Antimicrobial evaluation of mangiferin analogues

    Directory of Open Access Journals (Sweden)

    Singh S

    2009-01-01

    Full Text Available The naturally occurring xanthone glycoside mangiferin has been isolated by column chromatography from the ethanol extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N-phenylaminomethylenomangiferin, 5-(N-p-chlorophenylaminomethyleno mangiferin, 5-(N-2-methylphenylaminomethyleno mangiferin, 5-(N-p-methoxyphenylaminomethyleno mangiferin, 5-(N,N-diphenylaminomethyleno mangiferin, 5-(N--napthylaminomethyleno mangiferin and 5-(N-4-methylphenylaminomethyleno mangiferin. Mangiferin and its analogues were characterized by melting point and R f value determination and through spectral technique like UV, IR, and NMR spectral analysis. The synthesized compounds were screened for antimicrobial activity.

  3. Antimicrobial Evaluation of Mangiferin Analogues

    Science.gov (United States)

    Singh, S. K.; Kumar, Y.; Kumar, S. Sadish; Sharma, V. K.; Dua, K.; Samad, A.

    2009-01-01

    The naturally occurring xanthone glycoside mangiferin has been isolated by column chromatography from the ethanol extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N-phenylaminomethyleno)mangiferin, 5-(N-p-chlorophenylaminomethyleno) mangiferin, 5-(N-2-methylphenylaminomethyleno) mangiferin, 5-(N-p-methoxyphenylaminomethyleno) mangiferin, 5-(N, N-diphenylaminomethyleno) mangiferin, 5-(N--napthylaminomethyleno) mangiferin and 5-(N-4-methylphenylaminomethyleno) mangiferin. Mangiferin and its analogues were characterized by melting point and Rf value determination and through spectral technique like UV, IR, and NMR spectral analysis. The synthesized compounds were screened for antimicrobial activity. PMID:20490307

  4. Ecstasy analogues found in cacti.

    Science.gov (United States)

    Bruhn, Jan G; El-Seedi, Hesham R; Stephanson, Nikolai; Beck, Olof; Shulgin, Alexander T

    2008-06-01

    Human interest in psychoactive phenethylamines is known from the use of mescaline-containing cacti and designer drugs such as Ecstasy. From the alkaloid composition of cacti we hypothesized that substances resembling Ecstasy might occur naturally. In this article we show that lophophine, homopiperonylamine and lobivine are new minor constituents of two cactus species, Lophophora williamsii (peyote) and Trichocereus pachanoi (San Pedro). This is the first report of putatively psychoactive phenethylamines besides mescaline in these cacti. A search for further biosynthetic analogues may provide new insights into the structure-activity relationships of mescaline. An intriguing question is whether the new natural compounds can be called "designer drugs."

  5. A graphical approach to analogue behavioural modelling

    OpenAIRE

    Moser, Vincent; Nussbaum, Pascal; Amann, Hans-Peter; Astier, Luc; Pellandini, Fausto

    2007-01-01

    In order to master the growing complexity of analogue electronic systems, modelling and simulation of analogue hardware at various levels is absolutely necessary. This paper presents an original modelling method based on the graphical description of analogue electronic functional blocks. This method is intended to be automated and integrated into a design framework: specialists create behavioural models of existing functional blocks, that can then be used through high-level selection and spec...

  6. What Can We Learn From Analogue Experiments?

    CERN Document Server

    Thebault, Karim P Y

    2016-01-01

    In 1981 Unruh proposed that fluid mechanical experiments could be used to probe key aspects of the quantum phenomenology of black holes. In particular, he claimed that an analogue to Hawking radiation could be created within a fluid mechanical `dumb hole', with the event horizon replaced by a sonic horizon. Since then an entire sub-field of `analogue gravity' has been created. In 2016 Steinhauer reported the experimental observation of quantum Hawking radiation and its entanglement in a Bose-Einstein condensate analogue black hole. What can we learn from such analogue experiments? In particular, in what sense can they provide evidence of novel phenomena such as black hole Hawking radiation?

  7. The Valles natural analogue project

    Energy Technology Data Exchange (ETDEWEB)

    Stockman, H.; Krumhansl, J.; Ho, C. [Sandia National Labs., Albuquerque, NM (United States); McConnell, V. [Alaska Univ., Fairbanks, AK (United States). Geophysical Inst.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and {sup 39}Ar/{sup 4O} isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

  8. Coupling between mantle and surface processes: Insights from analogue modelling

    Science.gov (United States)

    Király, Ágnes; Sembroni, Andrea; Faccenna, Claudio; Funiciello, Francesca

    2014-05-01

    Thermal or density anomalies located beneath the lithosphere are thought to generate dynamic topography. Such a topographic signal compensates the viscous stresses originating from the anomaly driven mantle flow. It has been demonstrated that the erosion modulates the dynamic signal of topography changing the uplift rate by unload. The characteristic time for adjustments of dynamic topography due to surface erosion is likely similar to post-glacial rebound time (10000 - 50000 years). Here we present preliminary results of a new set of analogue models realized to study and quantify the contribution given by erosion to dynamic topography, during a process specifically driven by a positively buoyant deep anomaly. The adopted set up consists of a Plexiglas box (40x40x50 cm3) filled with glucose syrup as analogue upper mantle. A silicon plate positioned on the top of the syrup simulates the lithosphere. On the silicone plate is placed a thin layer of a high viscous glucose syrup which reproduces the upper, erodible layer of the crust. To simulate the positively buoyant anomaly we used an elastic, undeformable silicon ball free to rise by buoyancy in the syrup until the floating silicone plate is hit. The changes in topography have been monitored by using a 3D laser scan, while a side-view camera recorded the position of the rising ball in time. Data have been post-processed with image analysis techniques (e.g., Particle Image Velocimetry) in order to obtain the evolution of topography, uplift rate, erosion patterns of the top layer, bulge width and mantle circulation during the experiment. We ran experiments with and without the shallow, erodible crustal layer in order to quantify the effect of erosion on dynamic topography. Preliminary results showed that both the maximum topography and uplift rate are inversely proportional to the lithospheric thickness. The maximum uplift rate and the deformation of the lithospheric plate occurred just before the arrival of the

  9. The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

    Directory of Open Access Journals (Sweden)

    Hui Wu

    2014-01-01

    Full Text Available Objective. Glucagon-like peptide-1 (GLP-1 analogues (e.g., exenatide increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C; nondiabetic + exenatide (C + E; diabetic (D; diabetic + exenatide (D + E with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra of glucose and glycerol and gluconeogenesis from glycerol (GNG. During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose. Results. In the diabetic rats, exenatide reduced the basal Ra of glucose (P<0.01 and glycerol (P<0.01 and GNG (P<0.001. During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P<0.01 during the clamp. In the nondiabetic rats, exenatide had no effect. Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  12. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that helps red ...

  13. Your Glucose Meter

    Science.gov (United States)

    ... Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco ... Tips for Testing Your Blood Sugar and Caring for Your Meter Glucose meters test and record how much sugar (called glucose) is in your ...

  14. Two Series of Synthetic Territrem B Analogues and their Biological Activities

    Institute of Scientific and Technical Information of China (English)

    Feng ZHAO; Jin Hao ZHAO; Hai Bo LI; Lei Xiang YANG; Hua BAI; Yan Guang WANG; Shoei Sheng LEE; Yu ZHAO

    2005-01-01

    Two series of territrem B analogues (6, 11) were designed and synthesized from jujubogenin 2. Compound 11c inhibited AChE with the ratio of 70% at 10-4 mol/L. Compounds5a, 5b, 6a and 11b showed moderate cytotoxicity on cultured KB cells at 10-6 mol/L.Compounds 5c and 6b alleviated injury arising from oxygen-glucose deprivation (OGD).

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High blood glucose happens when the body has too little insulin or when the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: ...

  16. CO2 Capture with Enzyme Synthetic Analogue

    Energy Technology Data Exchange (ETDEWEB)

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  17. The future of somatostatin analogue therapy.

    Science.gov (United States)

    Stewart, P M; James, R A

    1999-10-01

    Since its discovery almost 30 years ago, the mode of action and therapeutic applications of somatostatin have been defined. In particular the cloning and characterization of somatostatin receptor subtypes has facilitated the development of high affinity analogues. In the context of pituitary disease, long-acting somatostatin analogues (octreotide, lanreotide) have been used to treat a variety of pituitary tumours but are most efficacious for the treatment of GH and TSH-secreting adenomas. In patients with acromegaly, depot preparations of these analogues are administered intramuscularly every 10-28 days and provide consistent suppression of GH levels to < 5 mU/l in approximately 50-65% of all cases. Even more specific somatostatin receptor analogues are under development. Finally, radiolabelled somatostatin analogue scintigraphy and, in larger doses, therapy, are now established tools in the evaluation and treatment of neuroendocrine tumours.

  18. Strategy and methodology of dynamical analogue prediction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In order to effectively improve numerical prediction level by using current models and data, the strategy and methodology of dynamical analogue prediction (DAP) is deeply studied in the present paper. A new idea to predict the prediction errors of dynamical model on the basis of historical analogue information is put forward so as to transform the dynamical prediction problem into the estimation problem of prediction errors. In terms of such an idea, a new prediction method of final analogue correction of errors (FACE) is developed. Furthermore, the FACE is applied to extra-seasonal prediction experiments on an operational atmosphere-ocean coupled general circulation model. Prediction results of summer mean circulation and total precipitation show that the FACE can to some extent reduce prediction errors, recover prediction variances, and improve prediction skills. Besides, sensitive experiments also show that predictions based on the FACE are evidently influenced by the number of analogues, analogue-selected variables and analogy metric.

  19. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    Science.gov (United States)

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

  20. Flavonoids have differential effects on glucose absorption in rats (Rattus norvegicus) and American robins (Turdis migratorius).

    Science.gov (United States)

    Skopec, Michele M; Green, Adam K; Karasov, William H

    2010-02-01

    Mounting evidence suggests that small birds rely largely on non-mediated intestinal absorption of glucose through the paracellular pathway, while non-flying mammals rely on mediated absorption across the enterocyte membranes by using glucose transporters SGLT-1 and GLUT-2. Relying on non-mediated transport of glucose may decrease its absorption rate at low glucose concentrations but may release small birds from the effects of glucose transport inhibitors. We evaluated transport by using flavonoids known to inhibit glucose transport in vitro. Quercetin, isoquercetrin, and phloridzin were tested in rats (Rattus norvegicus) and robins (Turdis migratirius), and naringenin, naringenin-7-glucoside, genistein, epigallocatechin gallate (EGCG), and phloretin were used only in rats. By using a pharmacokinetic approach that involves serial blood collection and area under the curve calculations, we determined the bioavailability of 3-0-methyl D-glucose, the non-metabolized analogue of D-glucose. Six of the eight flavonoids tested in rats significantly decreased the absorption of 3-0-methyl D-glucose, while none of the flavonoids tested in robins significantly decreased the bioavailability of 3-0-methyl D-glucose. We conclude that flavonoids effectively decrease glucose absorption in rats, which rely on mediated absorption of glucose, but that flavonoids do not have an effect in robins, which rely on non-mediated absorption of glucose.

  1. Polymorphisms of GLP-1 Receptor Gene and Response to GLP-1 Analogue in Patients with Poorly Controlled Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Chia-Hung Lin

    2015-01-01

    Full Text Available Aim. The relationship between genetic polymorphisms of the glucagon-like peptide-1 (GLP-1 receptor (GLP1R gene and unresponsiveness to GLP-1 analogue treatment in patients with poorly controlled type 2 diabetes mellitus (DM is unclear. Methods. Thirty-six patients with poorly controlled type 2 DM were enrolled and they received six days of continuous subcutaneous insulin infusion for this study. After the normalization of blood glucose in the first 3 days, the patients then received a combination therapy with injections of the GLP-1 analogue, exenatide, for another 3 days. All 13 exons and intron-exon boundaries of the GLP1R gene were amplified to investigate the association. Results. The short tandem repeat at 8GA/7GA (rs5875654 had complete linkage disequilibrium (LD, with r2=1 with single nucleotide polymorphism (SNP rs761386. Quantitative trait loci analysis of GLP1R gene variation with clinical response of GLP1 analogue showed the missense rs3765467 and rs761386 significantly associated with changes in the standard deviation of plasma glucose (SDPGbaseline-SDPGtreatment with GLP-1 analogue (P=0.041 and 0.019, resp.. The reported P values became insignificant after multiple testing adjustments. Conclusion. The variable response to the GLP-1 analogue was not statistically correlated with polymorphisms of the GLP1R gene in patients with poorly controlled type 2 DM.

  2. Space analogue studies in Antarctica

    Science.gov (United States)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  3. Space analogue studies in Antarctica

    Science.gov (United States)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  4. Condensed matter analogues of cosmology

    Science.gov (United States)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the

  5. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    Malik Chalal

    2014-06-01

    Full Text Available Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew. Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold. The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups and antimicrobial activity.

  6. Characterization of glucose uptake by cultured rat podocytes.

    Science.gov (United States)

    Lewko, Barbara; Bryl, Ewa; Witkowski, Jacek M; Latawiec, Elzbieta; Gołos, Magdalena; Endlich, Nicole; Hähnel, Brunhilde; Koksch, Claudia; Angielski, Stefan; Kriz, Wilhelm; Stepinski, Jan

    2005-01-01

    The nonmetabolizable glucose analogue [(3)H]-2-deoxy-D-glucose ((3)H-2DG) was used to study glucose transport in cultured rat podocytes. Intracellular accumulation of (3)H-2DG was linear up to 20 min and was inhibited by cytochalasin B (80% inhibition) and by phlorizin (20% inhibition). Pretreatment with insulin stimulated the (3)H-2DG uptake 1.5-fold. A Hill analysis of the rate of glucose transport yielded a V(max) value of approximately 10 mM and S(0.5)of 7.8 mM. The value h = 1.0 for a Hill coefficient confirmed that glucose uptake exhibited a Michaelis-Menten kinetics. Transporters GLUT2 and GLUT4 were expressed in over 90% podocytes. Of the GLUT2- and GLUT4-expressing cells, approximately one-fourth expressed the membrane-bound fraction. We conclude that cultured rat podocytes possess a differentiated glucose transport system consisting chiefly of facilitative GLUT2 and GLUT4 transporters. It seems likely that a sodium-dependent glucose cotransporter may also be present in these cells.

  7. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  8. Blood Glucose Levels

    Directory of Open Access Journals (Sweden)

    Carlos Estela

    2011-01-01

    Full Text Available The purpose of this study was to establish a mathematical model which can be used to estimate glucose levels in the blood over time. The equations governing this process were manipulated with the use of techniques such as separation of variables and integration of first order differential equations, which resulted in a function that described the glucose concentration in terms of time. This function was then plotted, which allowed us to find when glucose concentration was at its highest. The model was then used to analyze two cases where the maximum glucose level could not exceed a certain level while the amount of carbohydrates and glycemic index were varied, independently.

  9. Adaptive evolution for fast growth on glucose and the effects on the regulation of glucose transport system in Clostridium tyrobutyricum.

    Science.gov (United States)

    Jiang, Ling; Li, Shuang; Hu, Yi; Xu, Qing; Huang, He

    2012-03-01

    Laboratory adaptive evolution of microorganisms offers the possibility of relating acquired mutations to increased fitness of the organism under the conditions used. By combining a fibrous-bed bioreactor, we successfully developed a simple and valuable adaptive evolution strategy in repeated-batch fermentation mode with high initial substrate concentration and evolved Clostridium tyrobutyricum mutant with significantly improved butyric acid volumetric productivity up to 2.25 g/(L h), which is the highest value in batch fermentation reported so far. Further experiments were conducted to pay attention to glucose transport system in consideration of the high glucose consumption rate resulted from evolution. Complete characterization and comparison of the glucose phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS) were carried out in the form of toluene-treated cells and cell-free extracts derived from both C. tyrobutyricum wide-type and mutant, while an alternative glucose transport route that requires glucokinase was confirmed by the phenomena of resistance to the glucose analogue 2-deoxyglucose and ATP-dependent glucose phosphorylation. Our results suggest that C. tyrobutyricum mutant is defective in PTS activity and compensates for this defect with enhanced glucokinase activity, resulting in the efficient uptake and consumption of glucose during the whole metabolism.

  10. Total Synthesis of the Analogue of Icogenin

    Institute of Scientific and Technical Information of China (English)

    Shu Jie HOU; Peng XU; Liang ZHOU; De Quan YU; Ping Sheng LEI; Chuan Chun ZOU

    2006-01-01

    One of the analogues of icogenin, a natural furostanol saponin showing strong cytotoxic effect on cancer cell, was first synthesized via convergent strategy by using diosgenin and available monosaccharides as starting materials,

  11. Heterocyclic chalcone analogues as potential anticancer agents.

    Science.gov (United States)

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties.

  12. Second-Generation Fluorescent Quadracyclic Adenine Analogues

    DEFF Research Database (Denmark)

    Dumat, Blaise; Bood, Mattias; Wranne, Moa S.;

    2015-01-01

    Fluorescent base analogues comprise a group of increasingly important molecules for the investigation of nucleic acid structure, dynamics, and interactions with other molecules. Herein, we report on the quantum chemical calculation aided design, synthesis, and characterization of four new putativ...

  13. The glucose oxidase-peroxidase assay for glucose

    Science.gov (United States)

    The glucose oxidase-peroxidase assay for glucose has served as a very specific, sensitive, and repeatable assay for detection of glucose in biological samples. It has been used successfully for analysis of glucose in samples from blood and urine, to analysis of glucose released from starch or glycog...

  14. Sulfur analogues of psychotomimetic agents. Monothio analogues of mescaline and isomescaline.

    Science.gov (United States)

    Jacob, P; Shulgin, A T

    1981-11-01

    Two monothio analogues of mescaline and three monothio analogues of 2,3,4-trimethoxyphenethylamine (isomescaline) have been synthesized and characterized. Only the two mescaline analogues (3-and 4-thiomescaline) were found to be psychotomimetics in man, being 6 and 12 times more potent than mescaline, respectively. All five compounds can serve as substrates for bovine plasma monoamine oxidase in vitro, but no positive correlation is apparent between the extent of enzymatic degradation and human psychotomimetic potency.

  15. The structure activity relationship of discodermolide analogues.

    Science.gov (United States)

    Shaw, Simon J

    2008-03-01

    The marine polyketide discodermolide is a member of a class of natural products that stabilize microtubules. Many analogues have been synthesized suggesting that few changes can be made to the internal carbon backbone. Both ends of the molecule, however, can be modified. The majority of analogues have been generated via modification of the lactone region. This suggests that significant simplifications can be made in this region provided that the lactone moiety is maintained.

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... events, such as eating breakfast, take on exaggerated importance. It's a world where a person needs a ... Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood Glucose A1C and eAG Hypoglycemia ( ...

  17. Regression Methods for Ophthalmic Glucose Sensing Using Metamaterials

    Directory of Open Access Journals (Sweden)

    Philipp Rapp

    2011-01-01

    Full Text Available We present a novel concept for in vivo sensing of glucose using metamaterials in combination with automatic learning systems. In detail, we use the plasmonic analogue of electromagnetically induced transparency (EIT as sensor and evaluate the acquired data with support vector machines. The metamaterial can be integrated into a contact lens. This sensor changes its optical properties such as reflectivity upon the ambient glucose concentration, which allows for in situ measurements in the eye. We demonstrate that estimation errors below 2% at physiological concentrations are possible using simulations of the optical properties of the metamaterial in combination with an appropriate electrical circuitry and signal processing scheme. In the future, functionalization of our sensor with hydrogel will allow for a glucose-specific detection which is insensitive to other tear liquid substances providing both excellent selectivity and sensitivity.

  18. Resolving futile glucose cycling and glycogenolytic contributions to plasma glucose levels following a glucose load

    NARCIS (Netherlands)

    Nunes, P.M.; Jarak, I.; Heerschap, A.; Jones, J.G.

    2014-01-01

    PURPOSE: After a glucose load, futile glucose/glucose-6-phosphate (G6P) cycling (FGC) generates [2-(2) H]glucose from (2) H2 O thereby mimicking a paradoxical glycogenolytic contribution to plasma glucose levels. Contributions of load and G6P derived from gluconeogenesis, FGC, and glycogenolysis to

  19. Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ming V. [Program of Cardiovascular Sciences, Houston, TX 77030 (United States); Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Chen, Weiqin [Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Harmancey, Romain N. [Division of Cardiology, The University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Nuotio-Antar, Alli M.; Imamura, Minako; Saha, Pradip [Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Taegtmeyer, Heinrich [Division of Cardiology, The University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Chan, Lawrence, E-mail: lchan@bcm.tmc.edu [Program of Cardiovascular Sciences, Houston, TX 77030 (United States); Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); St. Luke' s Episcopal Hospital, Houston, TX 77030 (United States)

    2010-05-07

    Carbohydrate response element binding protein (ChREBP) is a Mondo family transcription factor that activates a number of glycolytic and lipogenic genes in response to glucose stimulation. We have previously reported that high glucose can activate the transcriptional activity of ChREBP independent of the protein phosphatase 2A (PP2A)-mediated increase in nuclear entry and DNA binding. Here, we found that formation of glucose-6-phosphate (G-6-P) is essential for glucose activation of ChREBP. The glucose response of GAL4-ChREBP is attenuated by D-mannoheptulose, a potent hexokinase inhibitor, as well as over-expression of glucose-6-phosphatase (G6Pase); kinetics of activation of GAL4-ChREBP can be modified by exogenously expressed GCK. Further metabolism of G-6-P through the two major glucose metabolic pathways, glycolysis and pentose-phosphate pathway, is not required for activation of ChREBP; over-expression of glucose-6-phosphate dehydrogenase (G6PD) diminishes, whereas RNAi knockdown of the enzyme enhances, the glucose response of GAL4-ChREBP, respectively. Moreover, the glucose analogue 2-deoxyglucose (2-DG), which is phosphorylated by hexokinase, but not further metabolized, effectively upregulates the transcription activity of ChREBP. In addition, over-expression of phosphofructokinase (PFK) 1 and 2, synergistically diminishes the glucose response of GAL4-ChREBP. These multiple lines of evidence support the conclusion that G-6-P mediates the activation of ChREBP.

  20. Between Analogue and Digital Diagrams

    Directory of Open Access Journals (Sweden)

    Zoltan Bun

    2012-10-01

    Full Text Available This essay is about the interstitial. About how the diagram, as a method of design, has lead fromthe analogue deconstruction of the eighties to the digital processes of the turn of the millennium.Specifically, the main topic of the text is the interpretation and the critique of folding (as a diagramin the beginning of the nineties. It is necessary then to unfold its relationship with immediatelypreceding and following architectural trends, that is to say we have to look both backwards andforwards by about a decade. The question is the context of folding, the exchange of the analogueworld for the digital. To understand the process it is easier to investigate from the fields of artand culture, rather than from the intentionally perplicated1 thoughts of Gilles Deleuze. Both fieldsare relevant here because they can similarly be used as the yardstick against which the era itselfit measured. The cultural scene of the eighties and nineties, including performing arts, movies,literature and philosophy, is a wide milieu of architecture. Architecture responds parallel to itsera; it reacts to it, and changes with it and within it. Architecture is a medium, it has always beena medium, yet the relations are transformed. That’s not to say that technical progress, for exampleusing CAD-software and CNC-s, has led to the digital thinking of certain movements ofarchitecture, (it is at most an indirect tool. But the ‘up-to-dateness’ of the discipline, however,a kind of non-servile reading of an ‘applied culture’ or ‘used philosophy’2 could be the key.(We might recall here, parenthetically, the fortunes of the artistic in contemporary mass society.The proliferation of museums, the magnification of the figure of the artist, the existence of amassive consumption of printed and televised artistic images, the widespread appetite for informationabout the arts, all reflect, of course, an increasingly leisured society, but also relateprecisely to the fact

  1. Glucose screening tests during pregnancy

    Science.gov (United States)

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... screening test between 24 and 28 weeks of pregnancy. The test may be done earlier if you ...

  2. Reduced peptide bond pseudopeptide analogues of neurotensin.

    Science.gov (United States)

    Doulut, S; Rodriguez, M; Lugrin, D; Vecchini, F; Kitabgi, P; Aumelas, A; Martinez, J

    1992-01-01

    Pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (H-Arg-Arg-Pro-Tyr-Ile-Leu-OH) were obtained by replacing each peptide bond by the reduced peptide bond CH2NH. The resulting analogues were then examined for their ability to inhibit binding of labeled neurotensin to new-born mouse brain membranes and for stimulation of guinea pig ileum contraction. Replacement of the Ile12-Leu13, Tyr11-Ile12, Pro10-Tyr11 and Lys9-Pro10 peptide bonds resulted in about 2000-, 3400-, 200- and 3400-fold losses, respectively, in binding affinity and 400-, 750-, 250- and 300-fold losses, respectively, in biological activity. Replacement of both Arg8 and Arg9 by lysine led to an analogue exhibiting the same pharmacological profile as the C-terminal hexapeptide of neurotensin. Interestingly, replacement of the Lys8-Lys9 peptide bond by the CH2NH bond produced an analogue exhibiting the same affinity for neurotensin receptors, but 10 times more potent in stimulating guinea pig ileum contraction. N-terminal protected analogues (by the Boc group) showed decreased potency as compared with their amino-free corresponding compounds.

  3. Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.

    Science.gov (United States)

    Duan, Shudong; Huang, Suling; Gong, Jian; Shen, Yu; Zeng, Limin; Feng, Ying; Ren, Wenming; Leng, Ying; Hu, Youhong

    2015-04-09

    Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.

  4. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    Science.gov (United States)

    Valla, Vasiliki

    2010-01-01

    Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients. PMID:20589066

  5. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    Directory of Open Access Journals (Sweden)

    Vasiliki Valla

    2010-01-01

    Full Text Available Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.

  6. Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Damm, Peter; Jovanovic, Lois

    2011-01-01

    As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ... Islanders American Indian/Alaska Native Programs Older Adults Family Link Diabetes EXPO Upcoming Diabetes EXPOs EXPO Volunteer ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... how to handle this condition. Medical IDs Many people with diabetes, particularly those who use insulin, should ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... Type 2 Diabetes Program Food & Fitness Food Recipes Planning Meals What Can I Eat Weight Loss Fitness ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's Diabetes Challenge Type ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Us in the Fight for a Cure Your tax-deductible gift today can fund critical diabetes research ... glucose for fuel, so your body breaks down fats to use for energy. When your body breaks ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ... Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get Started Safely Get And ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers ... updated, this is the "take-you-by-the-hand" guide that will become a trusted friend and ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... an Employer Options for the Uninsured Medicare Medicaid & CHIP For Parents & Kids Safe at School Everyday Life ... blood sugar). High blood glucose happens when the body has too little insulin or when the body ...

  15. Nocturnal continuous glucose monitoring

    DEFF Research Database (Denmark)

    Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik;

    2013-01-01

    Abstract Background: A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... also help. Work with your dietitian to make changes in your meal plan. If exercise and changes ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... Sleeve Custom jerseys for your Tour de Cure team benefits the cause. Ask the Experts: Learn to ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin ... Diabetes Pro: Professional Resources Online We Support Your Doctor Clinical Practice Guidelines Patient Education Materials Scientific Sessions ...

  20. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy ...

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ... Options for the Uninsured Medicare Medicaid & CHIP For Parents & Kids Safe at School Everyday Life Children and ...

  2. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Clinical Practice Guidelines Patient Education Materials Scientific Sessions Journals for Professionals Professional Books Patient Access to Research ...

  4. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To ... Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get Started Safely Get And ...

  5. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health Insurance Health ... glucose happens when the body has too little insulin or when the body can't use insulin ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C ... your doctor may change the amount of your medication or insulin or possibly the timing of when ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... blood glucose early will help you avoid problems associated with hyperglycemia. How Do I Treat Hyperglycemia? You ... Advocacy Take Action Advocacy Priorities News & Events The Cost of Diabetes Advocate Toolkit Call to Congress Research & ...

  9. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  10. Synthesis and anticancer evaluation of spermatinamine analogues.

    Science.gov (United States)

    Moosa, Basem A; Sagar, Sunil; Li, Song; Esau, Luke; Kaur, Mandeep; Khashab, Niveen M

    2016-03-15

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcysteine carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines, that is, cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5-10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Geomagnetic properties of Proxima Centauri b analogues

    CERN Document Server

    Zuluaga, Jorge I

    2016-01-01

    The recent discovery of a planet around the closest star, Proxima Centauri, could represent a quantum leap on the testability of models in exoplanet sciences. Unlike any other discovered exoplanet, models of planetary processes in Proxima b could be contrasted against near future telescopic observations and far future in-situ measurements. In this paper we study the geomagnetic properties of Proxima b analogues, namely, solid planets with masses close but larger than Earth's mass, periods of rotation of several days and habitable surface conditions. Assuming different planetary masses, bulk compositions and periods of rotations, we calculate for each planetary analogue its radius, heat flux, time of inner core formation, dynamo lifetime and minimum dipole magnetic moment. We find that most ($\\gtrsim$70\\%) Proxima b analogues develop intrinsic dynamos that last at least 3 Gyr, although only half of them are older than the present age of the host star ($4-6$ Gyr). Relying in our planetary evolution models, we p...

  12. Benzoylphenylurea sulfur analogues with potent antitumor activity.

    Science.gov (United States)

    Hallur, Gurulingappa; Jimeno, Antonio; Dalrymple, Susan; Zhu, Tao; Jung, M Katherine; Hidalgo, Manuel; Isaacs, John T; Sukumar, Saraswati; Hamel, Ernest; Khan, Saeed R

    2006-04-06

    A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to 1 (NSC-639829), against cancer cell lines. 6n was more effective than 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM.

  13. Analogue alternative the electronic analogue computer in Britain and the USA, 1930-1975

    CERN Document Server

    Small, James S

    2013-01-01

    We are in the midst of a digital revolution - until recently, the majority of appliances used in everyday life have been developed with analogue technology. Now, either at home or out and about, we are surrounded by digital technology such as digital 'film', audio systems, computers and telephones. From the late 1940s until the 1970s, analogue technology was a genuine alternative to digital, and the two competing technologies ran parallel with each other. During this period, a community of engineers, scientists, academics and businessmen continued to develop and promote the analogue computer.

  14. Solanapyrone analogues from a Hawaiian fungicolous fungus

    Science.gov (United States)

    Four new solanayrone analogues (solanapyrones J-M; 1-4) have been isolated from an unidentified fungicolous fungus collected in Hawaii. The structures and relative configurations of these compounds were determined by analysis of ID NMR, 2D NMR, and MS data. Solanapyrone J(1) showed antifungal acti...

  15. Dumb holes: analogues for black holes.

    Science.gov (United States)

    Unruh, W G

    2008-08-28

    The use of sonic analogues to black and white holes, called dumb or deaf holes, to understand the particle production by black holes is reviewed. The results suggest that the black hole particle production is a low-frequency and low-wavenumber process.

  16. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While mol

  17. Synthesis and antimicrobial activity of squalamine analogue.

    Science.gov (United States)

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine.

  18. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While

  19. A great disappearing act: the electronic analogue computer

    OpenAIRE

    Bissell, C.C.

    2004-01-01

    One historian of technology has called the analogue computer 'one of the great disappearing acts of the Twentieth Century'. This paper will look briefly at the origins, development and decline of the electronic analogue computer ..

  20. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    Science.gov (United States)

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment.

  1. Sodium-glucose cotransport

    Science.gov (United States)

    Poulsen, Søren Brandt; Fenton, Robert A.; Rieg, Timo

    2017-01-01

    Purpose of review Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs. Recent findings Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways. Summary SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2. PMID:26125647

  2. Analogue VLSI for probabilistic networks and spike-time computation.

    Science.gov (United States)

    Murray, A

    2001-02-01

    The history and some of the methods of analogue neural VLSI are described. The strengths of analogue techniques are described, along with residual problems to be solved. The nature of hardware-friendly and hardware-appropriate algorithms is reviewed and suggestions are offered as to where analogue neural VLSI's future lies.

  3. A q-analogue of the four functions theorem

    OpenAIRE

    Christofides, Demetres

    2009-01-01

    In this article we give a proof of a q-analogue of the celebrated four functions theorem. This analogue was conjectured by Bjorner and includes as special cases both the four functions theorem and also Bjorner's q-analogue of the FKG inequality.

  4. Tryptophan analogues. 1. Synthesis and antihypertensive activity of positional isomers.

    Science.gov (United States)

    Safdy, M E; Kurchacova, E; Schut, R N; Vidrio, H; Hong, E

    1982-06-01

    A series of tryptophan analogues having the carboxyl function at the beta-position was synthesized and tested for antihypertensive activity. The 5-methoxy analogue 46 exhibited antihypertensive activity in the rat via the oral route and was much more potent than the normal tryptophan analogue. The methyl ester was found to be a critical structural feature for activity.

  5. Glucose effectiveness in nondiabetic relatives

    DEFF Research Database (Denmark)

    Egede, M B; Henriksen, J-E; Durck, T T;

    2014-01-01

    AIMS: Reduced glucose effectiveness is a predictor of future glucose tolerance in individuals with a family history of type 2 diabetes. We examined retrospectively at 10 years in normoglycemic relatives of diabetic subjects (RELs) the pathophysiological role of glucose effectiveness...... in the development of isolated impaired fasting glucose, glucose intolerance, and acute insulin release. METHODS: At 0 years, 19 RELs and 18 matched control subjects had glucose effectiveness (GE), insulin sensitivity, acute insulin release (AIR)IVGTT, and disposition index measured during an iv glucose tolerance...... test (IVGTT), using the minimal model analysis. At 0 and 10 years, oral glucose tolerance (OGTT) and AIROGTT were determined. RESULTS: At 0 years, fasting glucose (FG) and GE were raised in RELs, but insulin sensitivity and AIROGTT were reduced (P ≤ .05) compared with controls. At 10 years, RELs...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... work with your doctor to find the safest way for you to lower your blood glucose level. Cutting down on the amount of food you eat might also help. Work with your dietitian to make changes in your meal plan. If exercise and changes ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online Community ... Page Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- Support a Cure - 2017-05-donation- ... well with diabetes. Shopdiabetes.org: Your Stress-Free System for Family Dinners! - 2017-03-book-oclock-scramble. ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's Diabetes Challenge Type 1 Type 2 Facts About Type 2 Enroll in ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health Insurance Health Insurance ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Care > Blood Glucose Testing Share: Print Page Text Size: A A A Listen En Español Hyperglycemia ( ... Advocacy Take Action Advocacy Priorities News & Events The Cost of Diabetes Advocate ... Resources Shop Diabetes » Close nonprofit software

  12. Effects of GLP-1 and 2,5-Anhydro-D-Mannitol on Insulin Secretion and Plasma Glucose in Mice

    NARCIS (Netherlands)

    Ahrén, B.; Lindskog, S.; Dijk, G. van; Scheurink, A.J.W.; Steffens, A.B.

    1995-01-01

    The truncated glucagon-like peptide-1 (GLP-1((7.36))amide or GLP-1) stimulates insulin secretion, enhances glucose elimination and is of potential interest in diabetes treatment. We studied the hypoglycemic action of GLP-1 in normal mice when given alone or together with the fructose analogue, 2,5-a

  13. Confirmation via Analogue Simulation: A Bayesian Analysis

    CERN Document Server

    Dardashti, Radin; Thebault, Karim P Y; Winsberg, Eric

    2016-01-01

    Analogue simulation is a novel mode of scientific inference found increasingly within modern physics, and yet all but neglected in the philosophical literature. Experiments conducted upon a table-top 'source system' are taken to provide insight into features of an inaccessible 'target system', based upon a syntactic isomorphism between the relevant modelling frameworks. An important example is the use of acoustic 'dumb hole' systems to simulate gravitational black holes. In a recent paper it was argued that there exists circumstances in which confirmation via analogue simulation can obtain; in particular when the robustness of the isomorphism is established via universality arguments. The current paper supports these claims via an analysis in terms of Bayesian confirmation theory.

  14. Spectroscopic study of solar twins and analogues

    CERN Document Server

    Datson, Juliet; Portinari, Laura

    2014-01-01

    Context. Many large stellar surveys have been and are still being carried out, providing huge amounts of data, for which stellar physical parameters will be derived. Solar twins and analogues provide a means to test the calibration of these stellar catalogues because the Sun is the best-studied star and provides precise fundamental parameters. Solar twins should be centred on the solar values. Aims. This spectroscopic study of solar analogues selected from the Geneva-Copenhagen Survey (GCS) at a resolution of 48,000 provides effective temperatures and metallicities for these stars. We test whether our spectroscopic parameters, as well as the previous photometric calibrations, are properly centred on the Sun. In addition, we search for more solar twins in our sample. Methods. The methods used in this work are based on literature methods for solar twin searches and on methods we developed in previous work to distinguish the metallicity-temperature degeneracies in the differential comparison of spectra of solar ...

  15. Optimization of propafenone analogues as antimalarial leads.

    Science.gov (United States)

    Lowes, David J; Guiguemde, W Armand; Connelly, Michele C; Zhu, Fangyi; Sigal, Martina S; Clark, Julie A; Lemoff, Andrew S; Derisi, Joseph L; Wilson, Emily B; Guy, R Kiplin

    2011-11-10

    Propafenone, a class Ic antiarrythmic drug, inhibits growth of cultured Plasmodium falciparum. While the drug's potency is significant, further development of propafenone as an antimalarial would require divorcing the antimalarial and cardiac activities as well as improving the pharmacokinetic profile of the drug. A small array of propafenone analogues was designed and synthesized to address the cardiac ion channel and PK liabilities. Testing of this array revealed potent inhibitors of the 3D7 (drug sensitive) and K1 (drug resistant) strains of P. falciparum that possessed significantly reduced ion channel effects and improved metabolic stability. Propafenone analogues are unusual among antimalarial leads in that they are more potent against the multidrug resistant K1 strain of P. falciparum compared to the 3D7 strain.

  16. Holographic Fluids with Vorticity and Analogue Gravity

    CERN Document Server

    Leigh, Robert G; Petropoulos, P Marios

    2012-01-01

    We study holographic three-dimensional fluids with vorticity in local equilibrium and discuss their relevance to analogue gravity systems. The Fefferman-Graham expansion leads to the fluid's description in terms of a comoving and rotating Papapetrou-Randers frame. A suitable Lorentz transformation brings the fluid to the non-inertial Zermelo frame, which clarifies its interpretation as moving media for light/sound propagation. We apply our general results to the Lorentzian Kerr-AdS_4 and Taub-NUT-AdS_4 geometries that describe fluids in cyclonic and vortex flows respectively. In the latter case we associate the appearance of closed timelike curves to analogue optical horizons. In addition, we derive the classical rotational Hall viscosity of three-dimensional fluids with vorticity. Our formula remarkably resembles the corresponding result in magnetized plasmas.

  17. Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

    Directory of Open Access Journals (Sweden)

    Yogendra Nayak

    2014-01-01

    Full Text Available Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D was induced in Wistar rats by streptozotocin (60 mg/kg, i.p. followed by nicotinamide (120 mg/kg i.p.. Rats having fasting blood glucose (FBG >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT, and insulin tolerance test (ITT were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

  18. Polyamine analogues targeting epigenetic gene regulation.

    Science.gov (United States)

    Huang, Yi; Marton, Laurence J; Woster, Patrick M; Casero, Robert A

    2009-11-04

    Over the past three decades the metabolism and functions of the polyamines have been actively pursued as targets for antineoplastic therapy. Interactions between cationic polyamines and negatively charged nucleic acids play a pivotal role in DNA stabilization and RNA processing that may affect gene expression, translation and protein activity. Our growing understanding of the unique roles that the polyamines play in chromatin regulation, and the discovery of novel proteins homologous with specific regulatory enzymes in polyamine metabolism, have led to our interest in exploring chromatin remodelling enzymes as potential therapeutic targets for specific polyamine analogues. One of our initial efforts focused on utilizing the strong affinity that the polyamines have for chromatin to create a backbone structure, which could be combined with active-site-directed inhibitor moieties of HDACs (histone deacetylases). Specific PAHAs (polyaminohydroxamic acids) and PABAs (polyaminobenzamides) polyamine analogues have demonstrated potent inhibition of the HDACs, re-expression of p21 and significant inhibition of tumour growth. A second means of targeting the chromatin-remodelling enzymes with polyamine analogues was facilitated by the recent identification of flavin-dependent LSD1 (lysine-specific demethylase 1). The existence of this enzyme demonstrated that histone lysine methylation is a dynamic process similar to other histone post-translational modifications. LSD1 specifically catalyses demethylation of mono- and di-methyl Lys4 of histone 3, key positive chromatin marks associated with transcriptional activation. Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1. Cellular inhibition of LSD1 by these unique compounds led to the re-activation of multiple epigenetically silenced genes important in tumorigenesis. The use of

  19. The Brookhaven electron analogue, 1953--1957

    Energy Technology Data Exchange (ETDEWEB)

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  20. Synthesis of constrained analogues of tryptophan

    Directory of Open Access Journals (Sweden)

    Elisabetta Rossi

    2015-10-01

    Full Text Available A Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues.

  1. Electromagnetic wave analogue of electronic diode

    OpenAIRE

    Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.; Fedotov, Vassili A.; Zheludev, Nikolay I.

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by ...

  2. Synthesis of a Cyclic Analogue of Galardin

    Institute of Scientific and Technical Information of China (English)

    马大为; 吴问根; 钱静; 郎深慧; 叶其壮

    2001-01-01

    A cyclic analogue 4 of galardin,a known MMP inhibitor,is designed to improve its selectivity.The synthesis of 4starts from dimethyl(S)-malate using diaselective alkylation and subsequent cyclization and amide formation as key steps.The compound 4 showed MMP inhibitory activity on all MMPs tested with IC50 ranging from 20.1 μM to 104 μM.

  3. Benchmarking analogue models of brittle thrust wedges

    Science.gov (United States)

    Schreurs, Guido; Buiter, Susanne J. H.; Boutelier, Jennifer; Burberry, Caroline; Callot, Jean-Paul; Cavozzi, Cristian; Cerca, Mariano; Chen, Jian-Hong; Cristallini, Ernesto; Cruden, Alexander R.; Cruz, Leonardo; Daniel, Jean-Marc; Da Poian, Gabriela; Garcia, Victor H.; Gomes, Caroline J. S.; Grall, Céline; Guillot, Yannick; Guzmán, Cecilia; Hidayah, Triyani Nur; Hilley, George; Klinkmüller, Matthias; Koyi, Hemin A.; Lu, Chia-Yu; Maillot, Bertrand; Meriaux, Catherine; Nilfouroushan, Faramarz; Pan, Chang-Chih; Pillot, Daniel; Portillo, Rodrigo; Rosenau, Matthias; Schellart, Wouter P.; Schlische, Roy W.; Take, Andy; Vendeville, Bruno; Vergnaud, Marine; Vettori, Matteo; Wang, Shih-Hsien; Withjack, Martha O.; Yagupsky, Daniel; Yamada, Yasuhiro

    2016-11-01

    We performed a quantitative comparison of brittle thrust wedge experiments to evaluate the variability among analogue models and to appraise the reproducibility and limits of model interpretation. Fifteen analogue modeling laboratories participated in this benchmark initiative. Each laboratory received a shipment of the same type of quartz and corundum sand and all laboratories adhered to a stringent model building protocol and used the same type of foil to cover base and sidewalls of the sandbox. Sieve structure, sifting height, filling rate, and details on off-scraping of excess sand followed prescribed procedures. Our analogue benchmark shows that even for simple plane-strain experiments with prescribed stringent model construction techniques, quantitative model results show variability, most notably for surface slope, thrust spacing and number of forward and backthrusts. One of the sources of the variability in model results is related to slight variations in how sand is deposited in the sandbox. Small changes in sifting height, sifting rate, and scraping will result in slightly heterogeneous material bulk densities, which will affect the mechanical properties of the sand, and will result in lateral and vertical differences in peak and boundary friction angles, as well as cohesion values once the model is constructed. Initial variations in basal friction are inferred to play the most important role in causing model variability. Our comparison shows that the human factor plays a decisive role, and even when one modeler repeats the same experiment, quantitative model results still show variability. Our observations highlight the limits of up-scaling quantitative analogue model results to nature or for making comparisons with numerical models. The frictional behavior of sand is highly sensitive to small variations in material state or experimental set-up, and hence, it will remain difficult to scale quantitative results such as number of thrusts, thrust spacing

  4. Electromagnetic wave analogue of electronic diode

    OpenAIRE

    Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.; Fedotov, Vassili A.; Zheludev, Nikolay I.

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by ...

  5. Thymidine analogues for tracking DNA synthesis.

    Science.gov (United States)

    Cavanagh, Brenton L; Walker, Tom; Norazit, Anwar; Meedeniya, Adrian C B

    2011-09-15

    Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU) and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in "tagging DNA synthesis" is the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU). The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using 'Huisgen's reaction' (1,3-dipolar cycloaddition or 'click chemistry'). This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other "unnatural bases". These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.

  6. Thymidine Analogues for Tracking DNA Synthesis

    Directory of Open Access Journals (Sweden)

    Brenton L. Cavanagh

    2011-09-01

    Full Text Available Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in “tagging DNA synthesis” is the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU. The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using ‘Huisgen’s reaction’ (1,3-dipolar cycloaddition or ‘click chemistry’. This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other “unnatural bases”. These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.

  7. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000528.htm Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition in which ...

  8. ORAL GLUCOSE TOLERANCE TEST REVISITED

    African Journals Online (AJOL)

    Determinant for the usefulness or otherwise of oral glucose tolerance test for the diagnosis ... personnel, poverty and poor economic management, 8'9 that are known to .... Symptoms of diabetes plus casual plasma glucose ... WHO 2-hr plasma glucose criteria of 1l.1mmol/L .... Diagnostic criteria and performance revisited.

  9. Glucose metabolism and hyperglycemia.

    Science.gov (United States)

    Giugliano, Dario; Ceriello, Antonio; Esposito, Katherine

    2008-01-01

    Islet dysfunction and peripheral insulin resistance are both present in type 2 diabetes and are both necessary for the development of hyperglycemia. In both type 1 and type 2 diabetes, large, prospective clinical studies have shown a strong relation between time-averaged mean values of glycemia, measured as glycated hemoglobin (HbA1c), and vascular diabetic complications. These studies are the basis for the American Diabetes Association's current recommended treatment goal that HbA1c should be regulation is accompanied by a significant improvement of many pathways supposed to be involved in diabetic complications, including oxidative stress, endothelial dysfunction, inflammation, and nuclear factor-kappaB activation. The goal of therapy should be to achieve glycemic status as near to normal as safely possible in all 3 components of glycemic control: HbA1c, fasting glucose, and postmeal glucose peak.

  10. Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Sharma Pawana

    2010-12-01

    Full Text Available Abstract Background Glucagon-like peptide (GLP-1 analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs. Methods MEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events. Results Studies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 μg twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily. Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists

  11. Glucose-6-phosphatase deficiency.

    OpenAIRE

    Labrune Philippe; Gajdos Vincent; Eberschweiler Pascale; Hubert-Buron Aurélie; Petit François; Vianey-Saban Christine; Boudjemline Alix; Piraud Monique; Froissart Roseline

    2011-01-01

    Abstract Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, betw...

  12. Analogue to Digital and Digital to Analogue Converters (ADCs and DACs): A Review Update

    CERN Document Server

    Pickering, J

    2015-01-01

    This is a review paper updated from that presented for CAS 2004. Essentially, since then, commercial components have continued to extend their performance boundaries but the basic building blocks and the techniques for choosing the best device and implementing it in a design have not changed. Analogue to digital and digital to analogue converters are crucial components in the continued drive to replace analogue circuitry with more controllable and less costly digital processing. This paper discusses the technologies available to perform in the likely measurement and control applications that arise within accelerators. It covers much of the terminology and 'specmanship' together with an application-oriented analysis of the realisable performance of the various types. Finally, some hints and warnings on system integration problems are given.

  13. [Glucose-lowering therapy in patients with cardiac comorbidities].

    Science.gov (United States)

    Meier, Juris J

    2015-04-01

    The risk for cardiovascular events, congestive heart failure and cardiac arrhythmia is significantly increased in patients with diabetes. Although poor glycaemic control has been associated with an increased cardiovascular event rate, aggressive glucose-lowering strategies have failed to improve cardiovascular endpoints or mortality. Therefore, treatment-associated adverse effects, especially hypoglycaemia and weight gain, must be carefully outbalanced against the potential benefits of better glycaemic control. Furthermore, certain drug-specific aspects must be considered: Pioglitazone is contraindicated in patients with heart failure, and DPP-4 inhibitors have recently been associated with an increased heart failure rate. Heart rate may increase during treatment with GLP-1 analogues. Only with metformin a reduction in cardiovascular endpoint has been demonstrated in patients with diabetes. Insulin and sulphonylureas have yielded neutral results in the available endpoint trials. Endpoint studies with GLP-1 analogues or SGLT-2 inhibitors have not yet been completed. These various drug-specific actions in the cardiovascular system need to be born in mind for the choice of the optimal glucose-lowering strategy in patients with cardiac comorbidities.

  14. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel Bring

    2016-01-01

    The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted by enteroendocrine cells in the intestinal mucosa in response to nutrient ingestion. They are called incretin hormones because of their ability to enhance insulin secretion. However...... the blood glucose levels. In Study 3, we also used stable glucose isotopes to estimate the endogenous glucose production and assessed symptoms and cognitive function during hypoglycaemia. The results from the three studies indicate that GIP has effects on insulin and glucagon responses highly dependent upon...... glucose to prevent hypoglycaemia. In conclusion, the studies position GIP as a bifunctional blood glucose stabilising hormone that glucose-dependently regulates insulin and glucagon responses in humans....

  15. The Greenland analogue project. Yearly report 2010

    Energy Technology Data Exchange (ETDEWEB)

    Harper, J.; Brinkerhoff, D.; Johnson, J. [University of Montana, Missoula (United States); Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I. [Geological Survey of Finland (Finland)] [and others

    2012-04-15

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  16. Synthesis and study of ceramide analogues

    OpenAIRE

    Školová, Barbora

    2015-01-01

    Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of inorganic and organic chemistry Candidate: Mgr. Barbora Školová Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of doctoral thesis: Synthesis and study of ceramide analogues Ceramides (Cer) together with free fatty acids and cholesterol form intercellular lamellar space of the uppermost skin layer (stratum corneum, SC). This lipid matrix presents the proper skin barrier - it protects organism against out...

  17. Analogues of Euler and Poisson Summation Formulae

    Indian Academy of Sciences (India)

    Vivek V Rane

    2003-08-01

    Euler–Maclaurin and Poisson analogues of the summations $\\sum_{a < n ≤ b}(n)f(n), \\sum_{a < n ≤ b}d(n) f(n), \\sum_{a < n ≤ b}d(n)(n) f(n)$ have been obtained in a unified manner, where (()) is a periodic complex sequence; () is the divisor function and () is a sufficiently smooth function on [, ]. We also state a generalised Abel's summation formula, generalised Euler's summation formula and Euler's summation formula in several variables.

  18. Analogue cosmology in a hadronic fluid

    Directory of Open Access Journals (Sweden)

    Bilić Neven

    2014-01-01

    Full Text Available Analog gravity models of general relativity seem promising routes to providing laboratory tests of the foundation of quantum field theory in curved space-time. In contrast to general relativity, where geometry of a spacetime is determined by the Einstein equations, in analog models geometry and evolution of analog spacetime are determined by the equations of fluid mechanics. In this paper we study the analogue gravity model based on massless pions propagating in a expanding hadronic fluid. The analog expanding spacetime takes the form of an FRW universe, with the apparent and trapping horizons defined in the standard way.

  19. Technical Considerations in Magnetic Analogue Models

    CERN Document Server

    Adams, Patrick W M

    2016-01-01

    The analogy between vorticity and magnetic fields has been a subject of interest to researchers for a considerable period of time, mainly because of the structural similarities between the systems of equations that govern the evolution of the two fields. We recently presented the analysis of magnetic fields and hydrodynamics vorticity fields and argued for a formal theory of analogue magnetism. This article provides in depth technical details of the relevant considerations for the simulation procedures and extends the analyses to a range of fluids.

  20. Satellite television analogue and digital reception techniques

    CERN Document Server

    Benoit, Herve

    1999-01-01

    Satellite television is part of the lives of millions of television viewers worldwide and its influence is set to increase significantly with the launch of digital satellite television services.This comprehensive reference book, written by the author of the highly successful 'Digital Television', provides a technical overview of both analogue and digital satellite TV. Written concisely and thoroughly, it covers all aspects of satellite TV necessary to understand its operation and installation. It also covers the evolution of satellite television, and contains a detailed glossary of tec

  1. U.S. Nuclear Regulatory Commission natural analogue research program

    Energy Technology Data Exchange (ETDEWEB)

    Kovach, L.A.; Ott, W.R. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process.

  2. Self-Powered Analogue Smart Skin.

    Science.gov (United States)

    Shi, Mayue; Zhang, Jinxin; Chen, Haotian; Han, Mengdi; Shankaregowda, Smitha A; Su, Zongming; Meng, Bo; Cheng, Xiaoliang; Zhang, Haixia

    2016-04-26

    The progress of smart skin technology presents unprecedented opportunities for artificial intelligence. Resolution enhancement and energy conservation are critical to improve the perception and standby time of robots. Here, we present a self-powered analogue smart skin for detecting contact location and velocity of the object, based on a single-electrode contact electrification effect and planar electrostatic induction. Using an analogue localizing method, the resolution of this two-dimensional smart skin can be achieved at 1.9 mm with only four terminals, which notably decreases the terminal number of smart skins. The sensitivity of this smart skin is remarkable, which can even perceive the perturbation of a honey bee. Meanwhile, benefiting from the triboelectric mechanism, extra power supply is unnecessary for this smart skin. Therefore, it solves the problems of batteries and connecting wires for smart skins. With microstructured poly(dimethylsiloxane) films and silver nanowire electrodes, it can be covered on the skin with transparency, flexibility, and high sensitivity.

  3. Long-term predictions using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, R.C. [Univ. of New Mexico, Albuquerque, NM (United States)

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  4. Dynamic Analogue Initialization for Ensemble Forecasting

    Institute of Scientific and Technical Information of China (English)

    LI Shan; RONG Xingyao; LIU Yun; LIU Zhengyu; Klaus FRAEDRICH

    2013-01-01

    This paper introduces a new approach for the initialization of ensemble numerical forecasting:Dynamic Analogue Initialization (DAI).DAI assumes that the best model state trajectories for the past provide the initial conditions for the best forecasts in the future.As such,DAI performs the ensemble forecast using the best analogues from a full size ensemble.As a pilot study,the Lorenz63 and Lorenz96 models were used to test DAI's effectiveness independently.Results showed that DAI can improve the forecast significantly.Especially in lower-dimensional systems,DAI can reduce the forecast RMSE by ~50% compared to the Monte Carlo forecast (MC).This improvement is because DAI is able to recognize the direction of the analysis error through the embedding process and therefore selects those good trajectories with reduced initial error.Meanwhile,a potential improvement of DAI is also proposed,and that is to find the optimal range of embedding time based on the error's growing speed.

  5. Glucose repression in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Kayikci, Omur; Nielsen, Jens

    2015-01-01

    Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluc......Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration...... and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression...

  6. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel; Vedtofte, Louise; Holst, Jens Juul

    2011-01-01

    OBJECTIVE To evaluate the glucose dependency of glucose-dependent insulinotropic polypeptide (GIP) effects on insulin and glucagon release in 10 healthy male subjects ([means ± SEM] aged 23 ± 1 years, BMI 23 ± 1 kg/m2, and HbA1c 5.5 ± 0.1%). RESEARCH DESIGN AND METHODS Saline or physiological doses....... In contrast, GIP increases glucagon levels during fasting and hypoglycemic conditions, where it has little or no effect on insulin secretion. Thus, GIP seems to be a physiological bifunctional blood glucose stabilizer with diverging glucose-dependent effects on the two main pancreatic glucoregulatory hormones....

  7. Glucose Regulation of Load‐Induced mTOR Signaling and ER Stress in Mammalian Heart

    Science.gov (United States)

    Sen, Shiraj; Kundu, Bijoy K.; Wu, Henry Cheng‐Ju; Hashmi, S. Shahrukh; Guthrie, Patrick; Locke, Landon W.; Roy, R. Jack; Matherne, G. Paul; Berr, Stuart S.; Terwelp, Matthew; Scott, Brian; Carranza, Sylvia; Frazier, O. Howard; Glover, David K.; Dillmann, Wolfgang H.; Gambello, Michael J.; Entman, Mark L.; Taegtmeyer, Heinrich

    2013-01-01

    Background Changes in energy substrate metabolism are first responders to hemodynamic stress in the heart. We have previously shown that hexose‐6‐phosphate levels regulate mammalian target of rapamycin (mTOR) activation in response to insulin. We now tested the hypothesis that inotropic stimulation and increased afterload also regulate mTOR activation via glucose 6‐phosphate (G6P) accumulation. Methods and Results We subjected the working rat heart ex vivo to a high workload in the presence of different energy‐providing substrates including glucose, glucose analogues, and noncarbohydrate substrates. We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation). The histone deacetylase inhibitor 4‐phenylbutyrate, which relieves ER stress, also improved contractile function. In contrast, adding the glucose analogue 2‐deoxy‐d‐glucose, which is phosphorylated but not further metabolized, to the perfusate resulted in mTOR activation and contractile dysfunction. Next we tested our hypothesis in vivo by transverse aortic constriction in mice. Using a micro‐PET system, we observed enhanced glucose tracer analog uptake and contractile dysfunction preceding dilatation of the left ventricle. In contrast, in hearts overexpressing SERCA2a, ER stress was reduced and contractile function was preserved with hypertrophy. Finally, we examined failing human hearts and found that mechanical unloading decreased G6P levels and ER stress markers. Conclusions We propose that glucose metabolic changes precede and regulate functional (and possibly also structural) remodeling of the heart. We implicate a critical role for G6P in load‐induced mTOR activation and ER stress. PMID:23686371

  8. Dopamine and glucose, obesity and Reward Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Kenneth eBlum

    2014-09-01

    Full Text Available Obesity and many well described eating disorders are accurately considered a global epidemic. The consequences of Reward Deficiency Syndrome, a genetic and epigenetic phenomena that involves the interactions of powerful neurotransmitters, are impairments of brain reward circuitry, hypodopaminergic function and abnormal craving behavior. Numerous sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Important facts which could translate to potential therapeutic targets espoused in this review include: 1 brain dopamine (DA production and use is stimulated by consumption of alcohol in large quantities or carbohydrates bingeing; 2 in the mesolimbic system the enkephalinergic neurons are in close proximity, to glucose receptors; 3 highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; 4 blood glucose and cerebrospinal fluid concentrations of homovanillic acid, the dopamine metabolite, are significantly correlated and 5 2-deoxyglucose the glucose analogue, in pharmacological doses associates with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and human fMRI support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and DA-modulated reward circuits are involved in pathologic eating behaviors. Treatment for addiction to glucose and drugs alike, based on a consensus of neuroscience research, should incorporate dopamine agonist therapy, in contrast to current theories and practices that use dopamine antagonists. Until now, powerful dopamine-D2 agonists have failed clinically, due to chronic down regulation of D2 receptors instead, consideration of novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of

  9. Space Analogue Environments: Are the Populations Comparable?

    Science.gov (United States)

    Sandal, G. M.

    Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that

  10. Fatty acyl-CoA esters inhibit glucose-6-phosphatase in rat liver microsomes.

    Science.gov (United States)

    Fulceri, R; Gamberucci, A; Scott, H M; Giunti, R; Burchell, A; Benedetti, A

    1995-01-01

    In native rat liver microsomes glucose 6-phosphatase activity is dependent not only on the activity of the glucose-6-phosphatase enzyme (which is lumenal) but also on the transport of glucose-6-phosphate, phosphate and glucose through the respective translocases T1, T2 and T3. By using enzymic assay techniques, palmitoyl-CoA or CoA was found to inhibit glucose-6-phosphatase activity in intact microsomes. The effect of CoA required ATP and fatty acids to form fatty acyl esters. Increasing concentrations (2-50 microM) of CoA (plus ATP and 20 microM added palmitic acid) or of palmitoyl-CoA progressively decreased glucose-6-phosphatase activity to 50% of the control value. The inhibition lowered the Vmax without significantly changing the Km. A non-hydrolysable analogue of palmitoyl-CoA also inhibited, demonstrating that binding of palmitoyl-CoA rather than hydrolysis produces the inhibition. Light-scattering measurements of osmotically induced changes in the size of rat liver microsomal vesicles pre-equilibrated in a low-osmolality buffer demonstrated that palmitoyl-CoA alone or CoA plus ATP and palmitic acid altered the microsomal permeability to glucose 6-phosphate, but not to glucose or phosphate, indicating that T1 is the site of palmitoyl-CoA binding and inhibition of glucose-6-phosphatase activity in native microsomes. The type of inhibition found suggests that liver microsomes may comprise vesicles heterogeneous with respect to glucose-6-phosphate translocase(s), i.e. sensitive or insensitive to fatty acid ester inhibition. PMID:7733874

  11. Dipeptide analogues containing 4-ethoxy-3-pyrrolin-2-ones

    DEFF Research Database (Denmark)

    Hosseini, Masood; Kringelum, Henriette; Murray, A.;

    2006-01-01

    Pyrrolidine-2,4-diones (1) are naturally occurring analogues of amino acids. We herein present a facile synthesis of N-acylated, O-alkylated pyrrolin-2-ones (2) in high yield and excellent enantiopurity. Molecular mechanics calculations suggest that the resulting dipeptide analogues adopt a linea...

  12. Black Hole Analogue in Bose–Einstein Condensation

    Indian Academy of Sciences (India)

    Tangmei He

    2014-09-01

    We have proposed a black hole analogue in a Bose–Einstein condensation. By introducing the Painlevé co-ordinates and using K–G equations, we have obtained the critical temperature of the black hole analogue in a Bose–Einstein condensation.

  13. A Comparison of Two Types of Counseling Analogues

    Science.gov (United States)

    Helms, Janet E.

    1976-01-01

    Subjects' attraction to the counselor, self-reported and physiological anxiety, and susceptibility to persuasion were compared using two types of counseling analogues, quasi-counseling and vicarious-participation. Participants in the quasi-counseling analogue were significantly more attracted to the counselor than were vicarious-participation…

  14. Functional Analysis: The Use of Analogues in Applied Settings.

    Science.gov (United States)

    Stichter, Janine Peck

    2001-01-01

    This article suggests possible applications of experimental analyses using analogues to empirically verify results of functional assessments in classrooms for students with autism and related disabilities. Analogue assessments involve creating conditions in which antecedents and consequences are held constant and specific variables suspected to…

  15. Synthesis of an Orthogonal Topological Analogue of Helicene

    DEFF Research Database (Denmark)

    Wixe, Torbjörn; Wallentin, Carl‐Johan; Johnson, Magnus T.

    2013-01-01

    The synthesis of an orthogonal topological pentamer analogue of helicene is presented. This analogue forms a tubular structure with its aromatic systems directed parallel to the axis of propagation, which creates a cavity with the potential to function as a host molecule. The synthetic strategy r...

  16. Insulin analogues and severe hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Kristensen, P L; Hansen, L S; Jespersen, M J

    2012-01-01

    The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed...

  17. [Glucose homeostasis in children. I. Regulation of blood glucose].

    Science.gov (United States)

    Otto Buczkowska, E; Szirer, G; Jarosz-Chobot, P

    2001-01-01

    The amount of glucose in the circulation depends on its absorption from the intestine, uptake by and release from the liver and uptake by peripheral tissues. Insulin and glucagon together control the metabolities required by peripheral tissues and both are involved in maintaining glucose homeostasis. Insulin is considered to be an anabolic hormone in that it promotes the synthesis of protein, lipid and glycogen. The key target tissues for insulin are liver, muscles and adipose tissue. Glucagon acts largely to increase catabolic processes. Between meals or during fast, the most tightly regulated process is the release of glucose from the liver. During fasting glucose is produced from glycogen and is formed by enzymes on the gluconeogenic pathway. Fetal metabolism is directed to ensure anabolism with formation of glycogen, fat and protein. Glucogen is stored in the liver and serves as the immediate source of new glucose during first few hours after birth. Glucose is the most important substrate for brain metabolism. Due to the large size of neonatal brain in relation to body weight cerebral glucose consumption is particularly high. Postnatal hormonal changes have a central role in regulating glucose mobilization through glycogenolysis and gluconeogenesis. The initial glucagon surge is the key adaptive change which triggers the switch to glucose production. The control of insulin and glucagon secretion is of fundamental importance during first hours after birth. Children have a decreased tolerance to starvation when compared with adults, they are more prone to develop hypoglycaemia after short fasting. The faster rate in the fall of blood glucose and gluconeogenic substrates and rapid rate of ketogenesis are characteristic features of fasting adaptation in children.

  18. Derivatisable Cyanobactin Analogues: A Semisynthetic Approach.

    Science.gov (United States)

    Oueis, Emilia; Adamson, Catherine; Mann, Greg; Ludewig, Hannes; Redpath, Philip; Migaud, Marie; Westwood, Nicholas J; Naismith, James H

    2015-12-01

    Many natural cyclic peptides have potent and potentially useful biological activities. Their use as therapeutic starting points is often limited by the quantities available, the lack of known biological targets and the practical limits on diversification to fine-tune their properties. We report the use of enzymes from the cyanobactin family to heterocyclise and macrocyclise chemically synthesised substrates so as to allow larger-scale syntheses and better control over derivatisation. We have made cyclic peptides containing orthogonal reactive groups, azide or dehydroalanine, that allow chemical diversification, including the use of fluorescent labels that can help in target identification. We show that the enzymes are compatible and efficient with such unnatural substrates. The combination of chemical synthesis and enzymatic transformation could help renew interest in investigating natural cyclic peptides with biological activity, as well as their unnatural analogues, as therapeutics.

  19. Electromagnetic wave analogue of electronic diode

    CERN Document Server

    Shadrivov, Ilya V; Kivshar, Yuri S; Fedotov, Vassili A; Zheludev, Nikolay I

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by an extraordinary strong nonlinear wave propagation effect in the same way as electronic diode function is provided by a nonlinear current characteristic of a semiconductor junction. The effect exploited in this new electromagnetic diode is an intensity-dependent polarization change in an artificial chiral metamolecule. This microwave effect exceeds a similar optical effect previously observed in natural crystals by more than 12 orders of magnitude and a direction-dependent transmission that differing by a factor of 65.

  20. Helical chirality induction of expanded porphyrin analogues

    Indian Academy of Sciences (India)

    Jun-Ichiro Setsune

    2012-11-01

    Expanded porphyrin analogues with unique figure-eight conformation were prepared by way of useful pyrrole intermediates such as bis(azafulvene)s and 2-borylpyrrole. Supramolecular chirogenesis of cyclooctapyrrole O1 with 32-cycloconjugation was successfully applied to determine absolute configuration of chiral carboxylic acids. Dinuclear CuII complex of cyclooctapyrrole O2 with interrupted -conjugation was resolved by HPLC into enantiomers and their helical handedness was determined by theoretical simulation of their CD spectral pattern. Enantioselective induction of helicity in the metal helicate formation in the presence of a chiral promoter was demonstrated by using ()-(+)-1-(1-phenyl)ethylamine that favoured , helicity. Dinuclear CoII complexes of cyclotetrapyrroletetrapyridine O3 were found to be substitution labile and pick up amino acid anions in water. Those amino acid complexes of O3Co2 were rendered to adopt a particular unidirectional helical conformation preferentially depending on the ligated amino acid anion.

  1. New pentamidine analogues in medicinal chemistry.

    Science.gov (United States)

    Porcheddu, A; Giacomelli, G; De Luca, L

    2012-01-01

    Sixty years after its introduction, 1,5-bis(4-amidinophenoxy)pentane (Pentamidine) is still one of the most used drugs for the treatment of the first stage of Human African trypanosomiasis and other neglected diseases such as malaria and leishmaniasis. These protozoan infections are prevalent in the poorest world areas such as sub-saharian and developing countries, however the increasing immigration from these countries to the richest part of the world and the overlap of HIV with parasitic infections result in a growing number of cases in developed nations. A great effort has been made to develop new generations of diamidines for the treatment of these infections transmitted by insects. This review summarises the synthesis and evaluation of pentamidine analogues reported in the last years in the effort to find new drugs with better pharmaceutical activity, higher lipophilicity and lower citotoxycicty.

  2. Gravitational analogue of the Witten effect

    Energy Technology Data Exchange (ETDEWEB)

    Foda, O. (International Centre for Theoretical Physics, Trieste (Italy))

    1985-07-22

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP violation, the Witten effect (a shift in the electric charge of a magnetic monopole due to CP non-conservation) is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a thetaR tildeR term in the lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed.

  3. Analogue Divider by Averaging a Triangular Wave

    Science.gov (United States)

    Selvam, Krishnagiri Chinnathambi

    2017-08-01

    A new analogue divider circuit by averaging a triangular wave using operational amplifiers is explained in this paper. The triangle wave averaging analog divider using operational amplifiers is explained here. The reference triangular waveform is shifted from zero voltage level up towards positive power supply voltage level. Its positive portion is obtained by a positive rectifier and its average value is obtained by a low pass filter. The same triangular waveform is shifted from zero voltage level to down towards negative power supply voltage level. Its negative portion is obtained by a negative rectifier and its average value is obtained by another low pass filter. Both the averaged voltages are combined in a summing amplifier and the summed voltage is given to an op-amp as negative input. This op-amp is configured to work in a negative closed environment. The op-amp output is the divider output.

  4. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg University (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Institute, Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  5. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg Univ. (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Inst., Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  6. Current european regulatory perspectives on insulin analogues

    Directory of Open Access Journals (Sweden)

    Enzmann Harald G

    2011-07-01

    Full Text Available Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions.

  7. Terrestrial analogues for lunar impact melt flows

    Science.gov (United States)

    Neish, C. D.; Hamilton, C. W.; Hughes, S. S.; Nawotniak, S. Kobs; Garry, W. B.; Skok, J. R.; Elphic, R. C.; Schaefer, E.; Carter, L. M.; Bandfield, J. L.; Osinski, G. R.; Lim, D.; Heldmann, J. L.

    2017-01-01

    Lunar impact melt deposits have unique physical properties. They have among the highest observed radar returns at S-Band (12.6 cm wavelength), implying that they are rough at the decimeter scale. However, they are also observed in high-resolution optical imagery to be quite smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pāhoehoe and ´a´ā lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will help to inform us as to the circumstances under which they were formed. In this work, we seek to find a terrestrial analogue for well-preserved lunar impact melt flows by examining fresh lava flows on Earth. We compare the radar return and high-resolution topographic variations of impact melt flows to terrestrial lava flows with a range of surface textures. The lava flows examined in this work range from smooth Hawaiian pāhoehoe to transitional basaltic flows at Craters of the Moon (COTM) National Monument and Preserve in Idaho to rubbly and spiny pāhoehoe-like flows at the recent eruption at Holuhraun in Iceland. The physical properties of lunar impact melt flows appear to differ from those of all the terrestrial lava flows studied in this work. This may be due to (a) differences in post-emplacement modification processes or (b) fundamental differences in the surface texture of the melt flows due to the melts' unique emplacement and/or cooling environment. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  8. Natural analogues of nuclear waste glass corrosion.

    Energy Technology Data Exchange (ETDEWEB)

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-06

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

  9. Tren-based analogues of bacillibactin: structure and stability.

    Science.gov (United States)

    Dertz, Emily A; Xu, Jide; Raymond, Kenneth N

    2006-07-10

    Synthetic analogues were designed to highlight the effect of the glycine moiety of bacillibactin on the overall stability of the ferric complex as compared to synthetic analogues of enterobactin. Insertion of a variety of amino acids to catecholamide analogues based on a Tren (tris(2-aminoethyl)amine) backbone increased the overall acidity of the ligands, causing an enhancement of the stability of the resulting ferric complex as compared to TRENCAM. Solution thermodynamic behavior of these siderophores and their synthetic analogues was investigated through potentiometric and spectrophotometric titrations. X-ray crystallography, circular dichroism, and molecular modeling were used to determine the chirality and geometry of the ferric complexes of bacillibactin and its analogues. In contrast to the Tren scaffold, addition of a glycine to the catechol chelating arms causes an inversion of the trilactone backbone, resulting in opposite chiralities of the two siderophores and a destabilization of the ferric complex of bacillibactin compared to ferric enterobactin.

  10. Sex differences in glucose levels

    DEFF Research Database (Denmark)

    Faerch, K; Borch-Johnsen, Knut; Vaag, A

    2010-01-01

    We aimed to examine whether sex differences in fasting plasma glucose (FPG), 2 h post-OGTT plasma glucose (2hPG) and HbA(1c) could be explained by differences in body size and/or body composition between men and women in a general non-diabetic Danish population. Moreover, we aimed to study to what...

  11. Glucose-dependent Insulinotropic Polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul

    2014-01-01

    CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). OBJECTIVE: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses...

  12. Alginate cryogel based glucose biosensor

    Science.gov (United States)

    Fatoni, Amin; Windy Dwiasi, Dian; Hermawan, Dadan

    2016-02-01

    Cryogel is macroporous structure provides a large surface area for biomolecule immobilization. In this work, an alginate cryogel based biosensor was developed to detect glucose. The cryogel was prepared using alginate cross-linked by calcium chloride under sub-zero temperature. This porous structure was growth in a 100 μL micropipette tip with a glucose oxidase enzyme entrapped inside the cryogel. The glucose detection was based on the colour change of redox indicator, potassium permanganate, by the hydrogen peroxide resulted from the conversion of glucose. The result showed a porous structure of alginate cryogel with pores diameter of 20-50 μm. The developed glucose biosensor was showed a linear response in the glucose detection from 1.0 to 5.0 mM with a regression of y = 0.01x+0.02 and R2 of 0.994. Furthermore, the glucose biosensor was showed a high operational stability up to 10 times of uninterrupted glucose detections.

  13. Antihypertensive drugs and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Christos; V; Rizos; Moses; S; Elisaf

    2014-01-01

    Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

  14. Analogue to Digital and Digital to Analogue (AD/DA) Conversion Techniques: An Overview

    CERN Document Server

    CERN. Geneva

    2002-01-01

    The basic ideas behind modern Analogue to Digital and Digital to Analogue (AD/DA) conversion methods will be introduced: a general view of the importance of these devices will be given, along with the digital representation of time-varying, real-world analogue signals. Some CERN applications will be outlined. The variety of conversion methods, their limitations, error sources and measurement methods will form the major part of this presentation. A review of the technological progress in this field over the last 30 years will be presented, concluding with the present 'state of the art' and a quick look at what is just around the corner. This Technical Training Seminar is in the framework of the FEED-2002 Lecture Series, and it is a prerequisite to attending to any of the FEED-2002 Terms. FEED-2002 is a two-term course that will review the techniques dealing with closed loop systems, focussing on time-invariant linear systems. (free attendance, no registration required) More information on the FEED-2002 ...

  15. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    Science.gov (United States)

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  16. Blood glucose in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj

    2009-01-01

    Blood glucose is often elevated in acute stroke, and higher admission glucose levels are associated with larger lesions, greater mortality and poorer functional outcome. In patients treated with thrombolysis, hyperglycemia is associated with an increased risk of hemorrhagic transformation...... of infarcts. For a number of years, tight glycemic control has been regarded as beneficial in critically illness, but recent research has been unable to support this notion. The only completed randomized study on glucose-lowering therapy in stroke has failed to demonstrate effect, and concerns relating...... to the risk of inducing potentially harmful hypoglycemia has been raised. Still, basic and observational research is overwhelmingly in support of a causal relationship between blood glucose and stroke outcome and further research on glucose-lowering therapy in acute stroke is highly warranted....

  17. Predicting Plasma Glucose From Interstitial Glucose Observations Using Bayesian Methods

    DEFF Research Database (Denmark)

    Hansen, Alexander Hildenbrand; Duun-Henriksen, Anne Katrine; Juhl, Rune

    2014-01-01

    One way of constructing a control algorithm for an artificial pancreas is to identify a model capable of predicting plasma glucose (PG) from interstitial glucose (IG) observations. Stochastic differential equations (SDEs) make it possible to account both for the unknown influence of the continuous...... glucose monitor (CGM) and for unknown physiological influences. Combined with prior knowledge about the measurement devices, this approach can be used to obtain a robust predictive model. A stochastic-differential-equation-based gray box (SDE-GB) model is formulated on the basis of an identifiable...

  18. The Greenland Analogue Project. Yearly Report 2009

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

  19. ALENCE OF DIABETES LITUS AND IMPAIRED GLUCOSE ...

    African Journals Online (AJOL)

    majority of the adult male population(> 20 years of age) work in the mines .... Age and sex distribution of subjects with diabetes and impaired glucose tolerance .... glucose tolerance and plasma glucose levels in US population aged 20- 74 yr.

  20. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik A.

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  1. Functionalized Congener Approach to Muscarinic Antagonists: Analogues of Pirenzepine

    Science.gov (United States)

    Karton, Yishai; Bradbury, Barton J.; Baumgold, Jesse; Paek, Robert; Jacobson, Kenneth A.

    2012-01-01

    The M1-selective muscarinic receptor antagonist pirenzepine (5,11-dihydro-11-[(4-methyl-1-piperazinyl)acetyl]-6H-pyrido[2,3-b] [1,4]benzodiazepin-6-one) was derivatized to explore points of attachment of functionalized side chains for the synthesis of receptor probes and ligands for affinity chromatography. The analogues prepared were evaluated in competitive binding assays versus [3H]-N-methylscopolamine at four muscarinic receptor subtypes (m1AChR-m4AChR) in membranes from rat heart tissue and transfected A9L cells. 9-(Hydroxymethyl)pirenzepine, 8-(methylthio)pirenzepine, and a series of 8-aminosulfonyl derivatives were synthesized. Several 5-substituted analogues of pirenzepine also were prepared. An alternate series of analogues substituted on the 4-position of the piperazine ring was prepared by reaction of 4-desmethylpirenzepine with various electrophiles. An N-chloroethyl analogue of pirenzepine was shown to form a reactive aziridine species in aqueous buffer yet failed to affinity label muscarinic receptors. Within a series of aminoalkyl analogues, the affinity increased as the length of the alkyl chain increased. Shorter chain analogues were generally much less potent than pirenzepine, and longer analogues (7–10 carbons) were roughly as potent as pirenzepine at m1 receptors, but were nonselective. Depending on the methylene chain length, acylation or alkyl substitution of the terminal amine also influenced the affinity at muscarinic receptors. PMID:2066986

  2. Glucose Binding Protein as a Novel Optical Glucose Nanobiosensor

    Directory of Open Access Journals (Sweden)

    Majed DWEIK

    2009-11-01

    Full Text Available Development of an in vivo optical sensor requires the utilization of Near Infra Red (NIR fluorophores due to their ability to operate within the biological tissue window. Alexa Fluor 750 (AF750 and Alexa Fluor 680 (AF680 were examined as potential NIR fluorophores for an in vivo fluorescence resonance energy transfer (FRET glucose biosensor. AF680 and AF750 found to be a FRET pair and percent energy transfer was calculated. Next, the tested dye pair was utilized in a competitive binding assay in order to detect glucose. Concanavalin A (Con A and dextran have binding affinity, but in the presence of glucose, glucose displaces dextran due to its higher affinity to Con A than dextran. Finally, the percent signal transfer through porcine skin was examined. The results showed with approximately 4.0 mm porcine skin thickness, 1.98 % of the fluorescence was transmitted and captured by the detector.

  3. How to measure blood glucose

    Directory of Open Access Journals (Sweden)

    Dianne Pickering

    2014-12-01

    Full Text Available The level of glucose in the blood can be measured by applying a drop of blood to a chemically treated, disposable ‘test-strip’, which is then inserted into an electronic blood glucose meter. The reaction between the test strip and the blood is detected by the meter and displayed in units of mg/dL or mmol/L. There are a number of different types of meters available, and all are slightly different. Take care when applying the general principles described in this article to the specific glucose meter you are using.

  4. Conversion of glucose to sorbose

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Mark E.; Gounder, Rajamani

    2016-02-09

    The present invention is directed to methods for preparing sorbose from glucose, said method comprising: (a) contacting the glucose with a silica-containing structure comprising a zeolite having a topology of a 12 membered-ring or larger, an ordered mesoporous silica material, or an amorphous silica, said structure containing Lewis acidic Ti.sup.4+ or Zr.sup.4+ or both Ti.sup.4+ and Zr.sup.4+ framework centers, said contacting conducted under reaction conditions sufficient to isomerize the glucose to sorbose. The sorbose may be (b) separated or isolated; or (c) converted to ascorbic acid.

  5. Glucose biosensor enhanced by nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Glucose biosensors have been formed with glucose oxidase (GOD) immobilized in composite immobilization membrane matrix, which is composed of hydrophobic gold, or hydrophilic gold, or hydrophobic silica nanoparticles, or the combination of gold and silica nanoparticles, and polyvinyl butyral (PVB) by a sol-gel method. The experiments show that nanoparticles can significantly enhance the catalytic activity of the immobilization enzyme. The current response can be increased from tens of nanoamperometer (nA) to thousands of nanoamperometer to the same glucose concentration, and the electrodes respond very quickly, to about 1 min. The function of nanoparticles effect on immobilization enzyme has been discussed.

  6. Glucose biosensor enhanced by nanoparticles

    Institute of Scientific and Technical Information of China (English)

    唐芳琼; 孟宪伟; 陈东; 冉均国; 郑昌琼

    2000-01-01

    Glucose biosensors have been formed with glucose oxidase (GOD) immobilized in composite immobilization membrane matrix, which is composed of hydrophobic gold, or hydro-philic gold, or hydrophobic silica nanoparticles, or the combination of gold and silica nanoparticles, and polyvinyl butyral (PVB) by a sol-gel method. The experiments show that nanoparticles can significantly enhance the catalytic activity of the immobilization enzyme. The current response can be increased from tens of nanoamperometer (nA) to thousands of nanoamperometer to the same glucose concentration, and the electrodes respond very quickly, to about 1 min. The function of nanoparticles effect on immobilization enzyme has been discussed.

  7. A Low-cost Multi-channel Analogue Signal Generator

    CERN Document Server

    Müller, F; The ATLAS collaboration; Shen, W; Stamen, R

    2009-01-01

    A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The signal generator was successfully used as independent test bed for the ATLAS Level-1 Trigger Pre-Processor, providing up to 16 analogue signals.

  8. Epoxyeicosatrienoic acids and glucose homeostasis in mice and men.

    Science.gov (United States)

    Luther, James M; Brown, Nancy J

    2016-09-01

    Epoxyeicosatrienoic acids (EETs) are formed from arachidonic acid by the action of P450 epoxygenases (CYP2C and CYP2J). Effects of EETs are limited by hydrolysis by soluble epoxide hydrolase to less active dihydroxyeicosatrienoic acids. Studies in rodent models provide compelling evidence that epoxyeicosatrienoic acids exert favorable effects on glucose homeostasis, either by enhancing pancreatic islet cell function or by increasing insulin sensitivity in peripheral tissues. Specifically, the tissue expression of soluble epoxide hydrolase appears to be increased in rodent models of obesity and diabetes. Pharmacological inhibition of epoxide hydrolase or deletion of the gene encoding soluble epoxide hydrolase (Ephx2) preserves islet cells in rodent models of type 1 diabetes and enhances insulin sensitivity in models of type 2 diabetes, as does administration of epoxyeicosatrienoic acids or their stable analogues. In humans, circulating concentrations of epoxyeicosatrienoic acids correlate with insulin sensitivity, and a loss-of-function genetic polymorphism in EPHX2 is associated with insulin sensitivity.

  9. Bedside Blood Glucose Monitoring in Hospitals

    National Research Council Canada - National Science Library

    American Diabetes Association

    2004-01-01

    Bedside Blood Glucose Monitoring in Hospitals American Diabetes Association The modern management of hospitalized patients with diabetes includes capillary blood glucose determinations at the bedside...

  10. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  11. Glucose-6-phosphatase deficiency.

    Science.gov (United States)

    Froissart, Roseline; Piraud, Monique; Boudjemline, Alix Mollet; Vianey-Saban, Christine; Petit, François; Hubert-Buron, Aurélie; Eberschweiler, Pascale Trioche; Gajdos, Vincent; Labrune, Philippe

    2011-05-20

    Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed

  12. Toward a Molecular Lego Approach for the Diversity-Oriented Synthesis of Cyclodextrin Analogues Designed as Scaffolds for Multivalent Systems.

    Science.gov (United States)

    Lepage, Mathieu L; Schneider, Jérémy P; Bodlenner, Anne; Compain, Philippe

    2015-11-06

    A modular strategy has been developed to access a diversity of cyclic and acyclic oligosaccharide analogues designed as prefunctionalized scaffolds for the synthesis of multivalent ligands. This convergent approach is based on bifunctional sugar building blocks with two temporarily masked functionalities that can be orthogonally activated to perform Cu(I)-catalyzed azide-alkyne cycloaddition reactions (CuAAC). The reducing end is activated as a glycosyl azide and masked as a 1,6-anhydro sugar, while the nonreducing end is activated as a free alkyne and masked as a triethylsilyl-alkyne. Following a cyclooligomerization approach, the first examples of close analogues of cyclodextrins composed of d-glucose residues and triazole units bound together through α-(1,4) linkages were obtained. The cycloglucopyranoside analogue containing four sugar units was used as a template to prepare multivalent systems displaying a protected d-mannose derivative or an iminosugar by way of CuAAC. On the other hand, the modular approach led to acyclic alkyne-functionalized scaffolds of a controlled size that were used to synthesize multivalent iminosugars.

  13. Developing Skin Analogues for a Robotic Octopus

    Institute of Scientific and Technical Information of China (English)

    Jinping Hou; Richard H.C.Bonser; George Jeronimidis

    2012-01-01

    In order to fabricate a biomimetic skin for an octopus inspired robot,a new process was developed based on mechanical properties measured from real octopus skin.Various knitted nylon textiles were tested and the one of 10-denier nylon was chosen as reinforcement.A combination of Ecoflex 0030 and 0010 silicone rubbers was used as matrix of the composite to obtain the right stiffness for the skin-analogue system.The open mould fabrication process developed allows air bubble to escape easily and the artificial skin produced was thin and waterproof.Material properties of the biomimetic skin were characterised using static tensile and instrumented scissors cutting tests.The Young's moduli of the artificial skin are 0.08 MPa and 0.13 MPa in the longitudinal and transverse directions,which are much lower than those of the octopus skin.The strength and fracture toughness of the artificial skin,on the other hand are higher than those of real octopus skins.Conically-shaped skin prototypes to be used to cover the robotic arm unit were manufactured and tested.The biomimetic skin prototype was stiff enough to maintain it conical shape when filled with water.The driving force for elongation was reduced significantly compared with previous prototypes.

  14. A positive Grassmannian analogue of the permutohedron

    CERN Document Server

    Williams, Lauren K

    2015-01-01

    The classical permutohedron Perm is the convex hull of the points (w(1),...,w(n)) in R^n where w ranges over all permutations in the symmetric group. This polytope has many beautiful properties -- for example it provides a way to visualize the weak Bruhat order: if we orient the permutohedron so that the longest permutation w_0 is at the "top" and the identity e is at the "bottom," then the one-skeleton of Perm is the Hasse diagram of the weak Bruhat order. Equivalently, the paths from e to w_0 along the edges of Perm are in bijection with the reduced decompositions of w_0. Moreover, the two-dimensional faces of the permutohedron correspond to braid and commuting moves, which by the Tits Lemma, connect any two reduced expressions of w_0. In this note we introduce some polytopes Br(k,n) (which we call bridge polytopes) which provide a positive Grassmannian analogue of the permutohedron. In this setting, BCFW bridge decompositions of reduced plabic graphs play the role of reduced decompositions. We define Br(k,...

  15. Insulin, insulin analogues and diabetic retinopathy.

    Science.gov (United States)

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  16. Automated Layout Generation of Analogue and Mixed-Signal ASIC's

    DEFF Research Database (Denmark)

    Bloch, Rene

    The research and development carried out in this Ph.D. study focusses on two key areas of the design flow for analogue and mixed-signal integrated circuit design, the mixed-signal floorplanning and the analogue layout generation.A novel approach to floorplanning is presented which provides true...... flow.A new design flow for automated layout generation of general analogue integrated circuits is presented. The design flow provides an automated design path from a sized circuit schematic to the final layout containing the placed, but unrouted, devices of the circuit. The analogue circuit layout...... interactive floorplanning capabilities due to a new implementation variant of a Genetic Algorithm. True interactive floorplanning allows the designer to communicate with existing floorplans during optimization. By entering the "ideas" and expertise of the designer into the optimization algorithm the automated...

  17. From BPA to its analogues: Is it a safe journey?

    Science.gov (United States)

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful?

  18. Doing it with Mirrors Classical analogues for Black Hole radiation

    CERN Document Server

    Srinivasan, K

    1998-01-01

    We construct analogues for the quantum phenomena of black hole radiation in the context of {\\it classical field theory}. Hawking radiation from a (radially) collapsing star is mathematically equivalent to radiation from a mirror moving along a specific trajectory in Minkowski spacetime. We construct a classical analogue for this quantum phenomenon and use it to construct a classical analogue for black hole radiation. The radiation spectrum in quantum field theory has the power spectrum as its classical analogue. Monochromatic light is continually reflected off a moving mirror or the silvered surface of a collapsing star.The reflected light is fourier analysed by the observer and the power spectrum is constructed. For a mirror moving along the standard black hole trajectory,it is seen that the power spectrum has a ``thermal'' nature. Mirror-observer configurations like an inertial mirror observed in an accelerated observer's frame and an accelerated mirror observed in a Rindler frame are investigated and condi...

  19. Analogue gravitational phenomena in Bose-Einstein condensates

    CERN Document Server

    Finazzi, Stefano

    2012-01-01

    Analogue gravity is based on the simple observation that perturbations propagating in several physical systems can be described by a quantum field theory in a curved spacetime. While phenomena like Hawking radiation are hardly detectable in astrophysical black holes, these effects may be experimentally tested in analogue systems. In this Thesis, focusing on Bose-Einstein condensates, we present our recent results about analogue models of gravity from three main perspectives: as laboratory tests of quantum field theory in curved spacetime, for the techniques that they provide to address various issues in general relativity, and as toy models of quantum gravity. The robustness of Hawking-like particle creation is investigated in flows with a single black hole horizon. Furthermore, we find that condensates with two (white and black) horizons develop a dynamical instability known in general relativity as black hole laser effect. Using techniques borrowed from analogue gravity, we also show that warp drives, which...

  20. Solistatinol, a novel phenolic compactin analogue from Penicillium solitum

    DEFF Research Database (Denmark)

    Larsen, Thomas Ostenfeld; Lange, Lene; Schnorr, Kirk

    2007-01-01

    Solistatinol, a novel phenolic compactin analogue, has been isolated from Penicillium solitum using a UV-guided strategy. The structure and relative stereochemistry were determined by NMR spectroscopy and mass spectrometry. The absolute stereochemistry was determined by chemical degradation...

  1. Sulphur Spring: Busy Intersection and Possible Martian Analogue

    Science.gov (United States)

    Nankivell, A.; Andre, N.; Thomas-Keprta, K.; Allen, C.; McKay, D.

    2000-01-01

    Life in extreme environments exhibiting conditions similar to early Earth and Mars, such as Sulphur Spring, may harbor microbiota serving as both relics from the past as well as present day Martian analogues.

  2. Analogue and Mixed-Signal Integrated Circuits for Space Applications

    CERN Document Server

    2014-01-01

    The purpose of AMICSA 2014 (organised in collaboration of ESA and CERN) is to provide an international forum for the presentation and discussion of recent advances in analogue and mixed-signal VLSI design techniques and technologies for space applications.

  3. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa

    2016-01-01

    in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small...... included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate...... samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. Copyright © 2015 John Wiley & Sons, Ltd....

  4. Synthesis of Novel Isoxazole-contained Analogues of Losartan

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of novel isoxazole-contained analogues of Losartan were designed and synthesized with 1,3-DC reaction. The regioselectivity of the reaction was discussed and the compounds are potential antihypertensive.

  5. A q-Analogue of the Dirichlet L-Function

    Institute of Scientific and Technical Information of China (English)

    Min-Soo Kim; Jin-Woo Son

    2002-01-01

    In this paper, we will treat some interesting formulae which are slightly different from Kim's results by more or less the same method in [4-9]. At first, we consider a new definition of a q-analogue of Bernoulli numbers and polynomials.We construct a q-analogue of the Riemann ζ-function, Hurwitz ζ-function, and Dirichlet L-series. Also, we investigate the relation between the q-analogue of generalized Bernoulli numbers and the generalized Euler numbers. As an application, we prove that the q-analogue of Bernoulli numbers occurs in the coefficients of some Stirling type series for the p-adic analytic q-log-gamma function.

  6. Current prodrug strategies for improving oral absorption of nucleoside analogues

    Directory of Open Access Journals (Sweden)

    Youxi Zhang

    2014-04-01

    Full Text Available Nucleoside analogues are first line chemotherapy in various severe diseases: AIDS (acquired immunodeficiency disease syndrome, cytomegalovirus infections, cancer, etc. However, many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability. In order to get around this drawback, prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug. Alternatively, prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues. Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1. The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport, but is readily degraded to the parent drug once at the target. This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.

  7. Trustworthiness and Influence: A Reexamination in an Extended Counseling Analogue.

    Science.gov (United States)

    Rothmeier, Rosemarie C.; Dixon, David N.

    1980-01-01

    The study demonstrated that: (1) interviewer trustworthiness can be manipulated in an analogue interview setting; and (2) interviewer trustworthiness is related to interpersonal influence in the interview setting. Findings follow a pattern of outcomes predicted by cognitive dissonance theory. (Author)

  8. Cell-cycle analyses using thymidine analogues in fission yeast.

    Directory of Open Access Journals (Sweden)

    Silje Anda

    Full Text Available Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2'-deoxyuridine (EdU and 5-Chloro-2'-deoxyuridine (CldU using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2'-deoxyuridine (BrdU. Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry.

  9. Cell-cycle analyses using thymidine analogues in fission yeast.

    Science.gov (United States)

    Anda, Silje; Boye, Erik; Grallert, Beata

    2014-01-01

    Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2'-deoxyuridine (EdU) and 5-Chloro-2'-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2'-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry.

  10. Glucose sensing and signalling; regulation of intestinal glucose transport.

    Science.gov (United States)

    Shirazi-Beechey, S P; Moran, A W; Batchelor, D J; Daly, K; Al-Rammahi, M

    2011-05-01

    Epithelial cells lining the inner surface of the intestinal epithelium are in direct contact with a lumenal environment that varies dramatically with diet. It has long been suggested that the intestinal epithelium can sense the nutrient composition of lumenal contents. It is only recently that the nature of intestinal nutrient-sensing molecules and underlying mechanisms have been elucidated. There are a number of nutrient sensors expressed on the luminal membrane of endocrine cells that are activated by various dietary nutrients. We showed that the intestinal glucose sensor, T1R2+T1R3 and the G-protein, gustducin are expressed in endocrine cells. Eliminating sweet transduction in mice in vivo by deletion of either gustducin or T1R3 prevented dietary monosaccharide- and artificial sweetener-induced up-regulation of the Na+/glucose cotransporter, SGLT1 observed in wild-type mice. Transgenic mice, lacking gustducin or T1R3 had deficiencies in secretion of glucagon-like peptide 1 (GLP-1) and, glucose-dependent insulinotrophic peptide (GIP). Furthermore, they had an abnormal insulin profile and prolonged elevation of postprandial blood glucose in response to orally ingested carbohydrates. GIP and GLP-1 increase insulin secretion, while glucagon-like peptide 2 (GLP-2) modulates intestinal growth, blood flow and expression of SGLT1. The receptor for GLP-2 resides in enteric neurons and not in any surface epithelial cells, suggesting the involvement of the enteric nervous system in SGLT1 up-regulation. The accessibility of the glucose sensor and the important role that it plays in regulation of intestinal glucose absorption and glucose homeostasis makes it an attractive nutritional and therapeutic target for manipulation.

  11. Orienteering performance and ingestion of glucose and glucose polymers.

    Science.gov (United States)

    Kujala, U M; Heinonen, O J; Kvist, M; Kärkkäinen, O P; Marniemi, J; Niittymäki, K; Havas, E

    1989-06-01

    The benefit of glucose polymer ingestion in addition to 2.5 per cent glucose before and during a prolonged orienteering competition was studied. The final time in the competition in the group ingesting 2.5 per cent glucose (group G, n = 10) was 113 min 37 s +/- 8 min 11 s, and in the group which had additionally ingested glucose polymer (group G + GP, n = 8) 107 min 18s +/- 4 min 41 s (NS). One fifth (21 per cent) of the time difference between the two groups was due to difference in orienteering errors. Group G + GP orienteered the last third of the competition faster than group G (p less than 0.05). The time ratio between the last third of the competition and the first third of the competition was lower in group G + GP than in group G (p less than 0.05). After the competition, there was statistically insignificant tendency to higher serum glucose and lower serum free fatty acid concentrations in group G + GP, and serum insulin concentration was higher in group G + GP than in group G (p less than 0.05). Three subjects reported that they exhausted during the competition. These same three subjects had the lowest serum glucose concentrations after the competition (2.9 mmol.1(-1), 2.9 mmol.1(-1), 3.5 mmol.1(-1] and all of them were from group G. It is concluded that glucose polymer syrup ingestion is beneficial for prolonged psychophysical performance.

  12. Adjuvant properties of a simplified C32 monomycolyl glycerol analogue.

    Science.gov (United States)

    Bhowruth, Veemal; Minnikin, David E; Agger, Else Marie; Andersen, Peter; Bramwell, Vincent W; Perrie, Yvonne; Besra, Gurdyal S

    2009-04-01

    A simplified C(32) monomycolyl glycerol (MMG) analogue demonstrated enhanced immunostimulatory activity in a dioctadecyl ammonium bromide (DDA)/Ag85B-ESAT-6 formulation. Elevated levels of IFN-gamma and IL-6 were produced in spleen cells from mice immunised with a C(32) MMG analogue comparable activity to the potent Th1 adjuvant, trehalose 6,6'-di-behenate (TDB).

  13. Semisynthesis of salviandulin E analogues and their antitrypanosomal activity.

    Science.gov (United States)

    Aoyagi, Yutaka; Fujiwara, Koji; Yamazaki, Akira; Sugawara, Naoko; Yano, Reiko; Fukaya, Haruhiko; Hitotsuyanagi, Yukio; Takeya, Koichi; Ishiyama, Aki; Iwatsuki, Masato; Otoguro, Kazuhiko; Yamada, Haruki; Ōmura, Satoshi

    2014-01-15

    A series of analogues of salviandulin E, a rearranged neoclerodane diterpene originally isolated from Salvia leucantha (Lamiaceae), were prepared and their in vitro activity against Trypanosoma brucei brucei was evaluated with currently used therapeutic drugs as positive controls. One of the 19 compounds prepared and assayed in the present study, butanoyl 3,4-dihydrosalviandulin E analogue was found to be a possible candidate for an antitrypanosomal drug with fairly strong antitrypanosomal activity and lower cytotoxicity.

  14. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

  15. Analogue Signal Processing: Collected Papers 1996-97

    DEFF Research Database (Denmark)

    1997-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997....

  16. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

  17. Analogue and digital linear modulation techniques for mobile satellite

    Science.gov (United States)

    Whitmarsh, W. J.; Bateman, A.; Mcgeehan, J. P.

    1990-01-01

    The choice of modulation format for a mobile satellite service is complex. The subjective performance is summarized of candidate schemes and voice coder technologies. It is shown that good performance can be achieved with both analogue and digital voice systems, although the analogue system gives superior performance in fading. The results highlight the need for flexibility in the choice of signaling format. Linear transceiver technology capable of using many forms of narrowband modulation is described.

  18. An azumamide C analogue without the zinc-binding functionality

    DEFF Research Database (Denmark)

    Villadsen, Jesper; Kitir, Betül; Wich, Kathrine;

    2014-01-01

    + - coordinating moiety. Herein, we describe the synthesis of an azumamide analogue lacking its native Zn 2+ -binding group and evaluation of its inhibitory activity against recombinant human HDAC1 – 11. Furthermore, kinetic investigation of the inhibitory mechanism of both parent natural product and synthetic...... analogue against HDAC3-NCoR2 is reported as well as their activity against Burkitt's lymphoma cell proliferation....

  19. A new antiproliferative noscapine analogue: chemical synthesis and biological evaluation

    OpenAIRE

    Ghaly, Peter E.; Abou El-Magd, Rabab M.; Churchill, Cassandra D. M.; Tuszynski, Jack A.; West, F. G.

    2016-01-01

    Noscapine, a naturally occurring opium alkaloid, is a widely used antitussive medication. Noscapine has low toxicity and recently it was also found to possess cytotoxic activity which led to the development of many noscapine analogues. In this paper we report on the synthesis and testing of a novel noscapine analogue. Cytotoxicity was assessed by MTT colorimetric assay using SKBR-3 and paclitaxel-resistant SKBR-3 breast cancer cell lines using different concentrations for both noscapine and t...

  20. Safety and Efficacy of Modern Insulin Analogues

    Directory of Open Access Journals (Sweden)

    Hye Jin Yoo

    2013-06-01

    Full Text Available BackgroundA1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart.MethodsKorean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints.ResultsOut of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%. No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year. The overall quality of life score improved (from 66.7±15.9 to 72.5±13.5 while the mean body weight was slightly increased (0.6±3.0 kg. The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%±2.2%, 2.5±4.7 mmol/L, and 4.0±6.4 mmol/L, respectively.ConclusionThe studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

  1. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

    Science.gov (United States)

    2017-01-01

    Conspectus Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition

  2. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers.

    Science.gov (United States)

    Liu, Yun; Lehn, Jean-Marie; Hirsch, Anna K H

    2017-02-21

    Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular

  3. The relevance of analogue studies for understanding obsessions and compulsions.

    Science.gov (United States)

    Abramowitz, Jonathan S; Fabricant, Laura E; Taylor, Steven; Deacon, Brett J; McKay, Dean; Storch, Eric A

    2014-04-01

    Analogue samples are often used to study obsessive-compulsive (OC) symptoms and related phenomena. This approach is based on the hypothesis that results derived from such samples are relevant to understanding OC symptoms in individuals with a diagnosis of obsessive-compulsive disorder (OCD). Two decades ago, Gibbs (1996) reviewed the available literature and found initial support for this hypothesis. Since then there have been many important advances addressing this issue. The purpose of the present review was to synthesize various lines of research examining the assumptions of using analogue samples to draw inferences about people with OCD. We reviewed research on the prevalence of OC symptoms in non-clinical populations, the dimensional (vs. categorical) nature of these symptoms, phenomenology, etiology, and studies on developmental and maintenance factors in clinical and analogue samples. We also considered the relevance of analogue samples in OCD treatment research. The available evidence suggests research with analogue samples is highly relevant for understanding OC symptoms. Guidelines for the appropriate use of analogue designs and samples are suggested.

  4. Cladribine Analogues via O6-(Benzotriazolyl Derivatives of Guanine Nucleosides

    Directory of Open Access Journals (Sweden)

    Sakilam Satishkumar

    2015-10-01

    Full Text Available Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxytris(dimethylaminophosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL, T-cell lymphoma (TCL and chronic lymphocytic leukemia (CLL, cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active.

  5. Novel purine nucleoside analogues for hematological malignancies.

    Science.gov (United States)

    Korycka, Anna; Lech-Marańda, Ewa; Robak, Tadeusz

    2008-06-01

    Recently, the search for more effective and safer antineoplastic agents has led to synthesis and introduction into preclinical and clinical studies of a few new purine nucleoside analogues (PNA). Three of them: clofarabine (CAFdA), nelarabine, and forodesine (immucillin H, BCX-1777), despite belonging to the same group of drugs such as PNA, have shown some differences concerning their active forms, metabolic properties and mechanism of action. However, all these drugs have demonstrated promising activity in patients with relapsed and refractory acute lymphoblastic leukemia (ALL). CAFdA was approved for the therapy of relapsed or refractory ALL in the third line of treatment. It has proved promising in pediatric patients as well as in some patients who are able to proceed to allogenic hematopietic stem cell transplantation (HSCT). Moreover, the drug exhibits an efficacy in acute myeloid leukemia (AML), blast crisis of chronic myelogenous leukemia (CML-BP) and myelodysplastic syndrome (MDS). Nelarabine is recommended for T-ALL and T-cell lymphoblastic lymphoma (T-LBL) with the overall response rates ranging from 11 to 60%. However, the use of the drug is limited by potentially severe neurotoxicity. Forodesine is a purine nucleoside phosphorylase (PNP) inhibitor and it has shown activity in relapsed and refractory T- and B-cells leukemias as well as in cutaneous T-cell lymphoma (CTCL). Recently patented, a few of inventions in the field of pharmaceutical preparation of new PNA have also been published. Great hopes are currently set on the use of these drugs in the treatment of lymphoid and myeloid malignancies in adult and in pediatric patients, however ongoing studies will help to define their role in the standard therapy.

  6. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    Science.gov (United States)

    Foing, Bernard

    2014-05-01

    We performed a series of field research campaigns (ILEWG EuroMoonMars) in the extreme Utah desert relevant to Mars environments, and in order to help in the interpretation of Mars missions measurements from orbit (MEX, MRO) or from the surface (MER, MSL), or Moon geochemistry (SMART-1, LRO). We shall give an update on the sample analysis in the context of habitability and astrobiology. Methods & Results: In the frame of ILEWG EuroMoonMars campaigns (2009 to 2013) we deployed at Mars Desert Research station, near Hanksville Utah, a suite of instruments and techniques [A, 1, 2, 9-11] including sample collection, context imaging from remote to local and microscale, drilling, spectrometers and life sensors. We analyzed how geological and geochemical evolution affected local parameters (mineralogy, organics content, environment variations) and the habitability and signature of organics and biota. Among the important findings are the diversity in the composition of soil samples even when collected in close proximity, the low abundances of detectable PAHs and amino acids and the presence of biota of all three domains of life with significant heterogeneity. An extraordinary variety of putative extremophiles was observed [3,4,9]. A dominant factor seems to be soil porosity and lower clay-sized particle content [6-8]. A protocol was developed for sterile sampling, contamination issues, and the diagnostics of biodiversity via PCR and DGGE analysis in soils and rocks samples [10, 11]. We compare the 2009 campaign results [1-9] to new measurements from 2010-2013 campaigns [10-12] relevant to: comparison between remote sensing and in-situ measurements; the study of minerals; the detection of organics and signs of life. Keywords: field analogue research, astrobiology, habitability, life detection, Earth-Moon-Mars, organics References [A] Foing, Stoker & Ehrenfreund (Editors, 2011) "Astrobiology field Research in Moon/Mars Analogue Environments", Special Issue of International

  7. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    Science.gov (United States)

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 7.8 and 11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of 2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  8. The Glucose-Insulin Control System

    DEFF Research Database (Denmark)

    Hallgreen, Christine Erikstrup; Korsgaard, Thomas Vagn; Hansen, RenéNormann N.

    2008-01-01

    experimental scenarios like the fasting state, the fed state, glucose tolerance tests, and glucose clamps. The main finding is that the glucose-insulin control system does not work as an isolated control of the plasma glucose concentration. The system seems more designed to control the different nutrient...

  9. Identification and preliminary SAR studies of (+)-Geodin as a glucose uptake stimulator for rat adipocytes.

    Science.gov (United States)

    Sato, Seiichi; Okusa, Noriyuki; Ogawa, Akiyo; Ikenoue, Takao; Seki, Tetsuya; Tsuji, Takashi

    2005-09-01

    (+)-Geodin (1) was isolated from Penicillium glabrum AJ117540 with activity that stimulates glucose uptake by rat adipocytes. Unlike insulin it is active in the presence of wortmannin. Dihydrogeodin (2) and sulochrin (3) which are the precursors of (+)-geodin biosynthesis were also isolated from the same fungus. Preliminary SAR studies of 1 showed some analogues had enhanced activity. Especially, the activities of racemic geodin and dibromo analogue (7a) were comparable to that of the natural product. Geodin (1), a known fungal metabolite, was isolated from Penicillium glabrum AJ117540 as an active substance (Fig. 1). Dihydrogeodin (2) and sulochrin (3), the precursors of 1, were also isolated from the same fungal extract. In this study, preliminary mechanistic insight and SAR are reported.

  10. Zinc Oxide Nanostructured Biosensor for Glucose Detection

    Institute of Scientific and Technical Information of China (English)

    X. W.Sun; J.X. Wang; A. Wei

    2008-01-01

    Zinc oxide (ZnO) nanocombs were fabricated by vapor phase transport, and nanorods and hierarchical nanodisk structures by aqueous thermal decomposition. Glucose biosensors were constructed using these ZnO nanostructures as supporting materials for glucose oxidase (GOx) loading. These ZnO glucose biosensors showed a high sensitivity for glucose detection and high affinity of GOx to glucose as well as the low detection limit. The results demonstrate that ZnO nanostructures have potential applications in biosensors.

  11. Terrestrial research in Mars analogue environments

    Science.gov (United States)

    Osipov, G.

    Fatty acids (FA) content was measured by GC-MS SIM technique in Sulfide ores of present day (Mid-Atlantic Ridge and others) and ancient (Ural Paleocene, Russia) black smokers; Early Proterozoic kerites of Volyn; Siberian, Canadian and Antarctic permafrosts and also in rocks of East-European platform Achaean crystalline basement. Analysis was shown presence those and only those fatty acids which are specific to microorganisms. FA with 12 up 19 of carbon atoms are thought to be a bacterial biomass sign. 3-Hydroxy fatty acids also found in samples and are strong specific markers of gram-negative bacteria. Cultivation yield living bacteria in some cases. The East-European platform Achaean crystalline basement rocks opened by Vorotilov Deep Well (VDW) drilled through Puchezh-Katunski impact structure were studied within depths 2575 - 2805 m. 34 microbial lipid markers were detected by GC-MS and 22 species were identified. Bacteria of g. Bacillus reached 6,8 % in subsurface communities. However, members of gg. Clostridium (37,1 - 33,2 %) and Rhodococcus (27,6 - 33,7 %) were absolute dominants within studied depth interval. Some lipid patterns of kerite samples could be assessed to definite genera or, in special cases, to species of contemporary microorganisms. For instance, 2-hydroxylauric acid is specific to Pseudomonas putida group or Acinetobacter spp., and hydroxymyristic together with hydroxypalmitic are specific to P.cepacea and cyanobacteria. 3-hydroxystearic acid was known as component of Acetobacter diazothrophycus and Gloebacter violaceous cyanobacterium. 10-hydroxystearic acid associated with Nocardia spp., which oxidizes oleic acid in organic substrates. 10-methylhexadecanoic (10Me16) acid together with 10Me14, 10Me15 and 10Me17 analogues are markers of actinomycetes. Significant part of Black Smokers organic matter is probably biogenic. Fatty acid features strongly assigns it to bacterial, microeucariotic and planta cells. Par example 3-hydroxy acids are

  12. Iron isotopes in an Archean ocean analogue

    Science.gov (United States)

    Busigny, Vincent; Planavsky, Noah J.; Jézéquel, Didier; Crowe, Sean; Louvat, Pascale; Moureau, Julien; Viollier, Eric; Lyons, Timothy W.

    2014-05-01

    Iron isotopes have been extensively used to trace the history of microbial metabolisms and the redox evolution of the oceans. Archean sedimentary rocks display greater variability in iron isotope ratios and more markedly negative values than those deposited in the Proterozoic and Phanerozoic. This increased variability has been linked to changes in either water column iron cycling or the extent of benthic microbial iron reduction through time. We tested these contrasting scenarios through a detailed study of anoxic and ferruginous Lac Pavin (France), which can serve as a modern analogue of the Archean ocean. A depth-profile in the water column of Lac Pavin shows a remarkable increase in dissolved Fe concentration (0.1-1200 μM) and δ56Fe values (-2.14‰ to +0.31‰) across the oxic-anoxic boundary to the lake bottom. The largest Fe isotope variability is found at the redox boundary and is related to partial oxidation of dissolved ferrous iron, leaving the residual Fe enriched in light isotopes. The analysis of four sediment cores collected along a lateral profile (one in the oxic layer, one at the redox boundary, one in the anoxic zone, and one at the bottom of the lake) indicates that bulk sediments, porewaters, and reactive Fe mostly have δ56Fe values near 0.0 ± 0.2‰, similar to detrital iron. In contrast, pyrite δ56Fe values in sub-chemocline cores (60, 65, and 92 m) are highly variable and show significant deviations from the detrital iron isotope composition (δ56Fepyrite between -1.51‰ and +0.09‰; average -0.93‰). Importantly, the pyrite δ56Fe values mirror the δ56Fe of dissolved iron at the redox boundary—where near quantitative sulfate and sulfide drawdown occurs—suggesting limited iron isotope fractionation during iron sulfide formation. This finding has important implications for the Archean environment. Specifically, this work suggests that in a ferruginous system, most of the Fe isotope variability observed in sedimentary pyrites can

  13. Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives.

    Science.gov (United States)

    Monte, A P; Waldman, S R; Marona-Lewicka, D; Wainscott, D B; Nelson, D L; Sanders-Bush, E; Nichols, D E

    1997-09-12

    hallucinogens, that such compounds must be full agonists at the 5-HT2A receptor subtype. In contrast to the 2,5-dimethoxy-substituted phenethylamines, where rigidification of the methoxy groups had no deleterious effect on activity, the loss of activity in the 3,4,5-trioxygenated mescaline analogues may suggest that the 3 and 5 methoxy groups must remain conformationally mobile to enable receptor activation.

  14. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Science.gov (United States)

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin.

  15. Insulin analogues and cancer: a note of caution

    Directory of Open Access Journals (Sweden)

    Joseph A.M.J.L. eJanssen

    2014-05-01

    Full Text Available Abstract In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogues are safe. In line with these findings, we observed that serum of diabetic patients treated with insulin analogues, compared to that of diabetic patients treated with human insulin, did not induce an increased phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor (IGF-IR. However, the classical model of the IGF-IR signaling may be insufficient to explain (all mitogenic effects of insulin analogues since also non-canonical signaling pathways of the IGF-IR may play a major role in this respect. Although phosphorylation of tyrosine residues of the IGF-IR is generally considered to be the initial activation step within the intracellular IGF-IR signaling pathway, it has been found that cells undergo a signaling switch under hyperglycemic conditions. After this switch, a completely different mechanism is utilized to activate the mitogenic (mitogen-activated protein kinase (MAPK pathways of the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At present it is unknown whether activation of this alternative intracellular pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is stronger in patients treated with (some insulin analogues than in patients treated with human insulin. In addition, it is unknown whether the insulin receptors (IRs also undergo a signaling switch during hyperglycemia. This should be investigated in future studies. Finally, relative overexpression of IR isoform A (IR-A in (pre cancer tissues may play a key role in the development and progression of human cancers during treatment with insulin (analogues. Further

  16. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel Bring

    2016-01-01

    glucagon secretion are essential contributors to the hyperglycaemia that characterise patients with type 2 diabetes. Moreover, the near absence of a well-timed glucagon response contributes to an increased risk of hypoglycaemia in patients with type 1 diabetes. The overall aim of this PhD thesis...... insulin secretion (Study 3). The investigations in the three mentioned study populations have been described in three original articles. The employed study designs were in randomised, placebo-controlled, crossover set-up, in which the same research subject is subjected to several study days thereby acting...... the blood glucose levels. In Study 3, we also used stable glucose isotopes to estimate the endogenous glucose production and assessed symptoms and cognitive function during hypoglycaemia. The results from the three studies indicate that GIP has effects on insulin and glucagon responses highly dependent upon...

  17. MARKOV GRAPHS OF ONE–DIMENSIONAL DYNAMICAL SYSTEMS AND THEIR DISCRETE ANALOGUES AND THEIR DISCRETE ANALOGUES

    Directory of Open Access Journals (Sweden)

    SERGIY KOZERENKO

    2016-04-01

    Full Text Available One feature of the famous Sharkovsky’s theorem is that it can be proved using digraphs of a special type (the so–called Markov graphs. The most general definition assigns a Markov graph to every continuous map from the topological graph to itself. We show that this definition is too broad, i.e. every finite digraph can be viewed as a Markov graph of some one–dimensional dynamical system on a tree. We therefore consider discrete analogues of Markov graphs for vertex maps on combinatorial trees and characterize all maps on trees whose discrete Markov graphs are of the following types: complete, complete bipartite, the disjoint union of cycles, with every arc being a loop.

  18. Reusable glucose fiber sensor for measuring glucose concentration in serum

    Institute of Scientific and Technical Information of China (English)

    Cheng-Chih Hsu; Yi-Cheng Chen; Ju-Yi Lee; Chyan-Chyi Wu

    2011-01-01

    We demonstrate a glucose fiber sensor for measuring glucose concentration in serum. High resolution and rapid measurement are achieved through the integration of highly selective enzymes and heterodyne interferometry. The best resolution and response time obtained are 0.14mg/dL and 1.3 s, respectively. The stability of the sensor is also verified by investigating the initial phase variation. Experimental results show that the fiber sensor can be reused more than 10 times.%We demonstrate a glucose fiber sensor for measuring glucose concentration in serum.High resolution and rapid measurement are achieved through the integration of highly selective enzymes and heterodyne interferometry.The best resolution and response time obtained are 0.14 mg/dL and 1.3 s,respectively.The stability of the sensor is also verified by investigating the initial phase variation.Experimental results show that the fiber sensor can be reused more than 10 times.Fiber sensors have attracted considerable attention over the past two decades.Various kinds of fiber sensors have been proposed for measnring specific chemical concentrations[1-8].Most previously reported methods[1-5] involved measuring the variations in fluorescence intensity[2-4] or transmitted light[3,4].Hence,avoiding the inflnence of snrrounding light and the use of expensive photon detection equipment are important requirements.Furthermore,procedures for manufacturing optical biosensors are complicated[3] and qualitv is difficult to control[4]..

  19. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    Science.gov (United States)

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury. Copyright © 2017, American Journal of Physiology-Endocrinology and Metabolism.

  20. Engineering of insulin receptor isoform-selective insulin analogues.

    Directory of Open Access Journals (Sweden)

    Tine Glendorf

    Full Text Available BACKGROUND: The insulin receptor (IR exists in two isoforms, A and B, and the isoform expression pattern is tissue-specific. The C-terminus of the insulin B chain is important for receptor binding and has been shown to contact the IR just adjacent to the region where the A and B isoforms differ. The aim of this study was to investigate the importance of the C-terminus of the B chain in IR isoform binding in order to explore the possibility of engineering tissue-specific/liver-specific insulin analogues. METHODOLOGY/PRINCIPAL FINDINGS: Insulin analogue libraries were constructed by total amino acid scanning mutagenesis. The relative binding affinities for the A and B isoform of the IR were determined by competition assays using scintillation proximity assay technology. Structural information was obtained by X-ray crystallography. Introduction of B25A or B25N mutations resulted in analogues with a 2-fold preference for the B compared to the A isoform, whereas the opposite was observed with a B25Y substitution. An acidic amino acid residue at position B27 caused an additional 2-fold selective increase in affinity for the receptor B isoform for analogues bearing a B25N mutation. Furthermore, the combination of B25H with either B27D or B27E also resulted in B isoform-preferential analogues (2-fold preference even though the corresponding single mutation analogues displayed no differences in relative isoform binding affinity. CONCLUSIONS/SIGNIFICANCE: We have discovered a new class of IR isoform-selective insulin analogues with 2-4-fold differences in relative binding affinities for either the A or the B isoform of the IR compared to human insulin. Our results demonstrate that a mutation at position B25 alone or in combination with a mutation at position B27 in the insulin molecule confers IR isoform selectivity. Isoform-preferential analogues may provide new opportunities for developing insulin analogues with improved clinical benefits.

  1. Central effects of angiotensin II, its fragment and analogues.

    Science.gov (United States)

    Georgiev, V P; Klousha, V E; Petkov, V D; Markovska, V L; Svirskis, S V; Mountsinietse, R K; Anouans, Z E

    1984-01-01

    The effects of the octapeptide angiotensin II (AT II), its fragment Ile8 AT3-8 and the analogues Sar1 Ala8 AT II, Ala8 AT II and Ile8 AT II were studied with respect to: the level of biogenic amines (DA, 5-HT and their metabolites HVA and 5-HIAA) in the forebrain; the behaviour of the animals--haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction (UJR), convulsive threshold. Good correlation was found between the biochemical and behavioural effects. The fragment of AT II where phenylalanine is substituted at the C-terminal by Ile reduces the haloperidol-increased content of HVA, potentiates apomorphine stereotypy and reduces catalepsy, whereas the AT II analogues (where the C-terminal phenylalanine is substituted by Ala, and the N-terminal--by Sar) potentiate the effect of haloperidol increasing the HVA content, reduce apomorphine stereotypy and potentiate catalepsy; saralasine independently applied induces brief catalepsy; AT II, its fragment and analogues inhibit UJR, in combination with amphetamine and PTZ this effect becomes deeper; the duration of hexobarbital sleep is increased. The peptides investigated increase the convulsive threshold. The results show that the hexapeptide fragment has preserved the effects of AT II, whereas in the analogues (with changed C- and N-terminals) they are changed. The results obtained may be explained with the modulating influence of AT II-receptors on the DA-ergic receptors in the brain structures with which AT II and its fragment and analogues enter in contact.

  2. Analogue earthquakes and seismic cycles: experimental modelling across timescales

    Science.gov (United States)

    Rosenau, Matthias; Corbi, Fabio; Dominguez, Stephane

    2017-05-01

    Earth deformation is a multi-scale process ranging from seconds (seismic deformation) to millions of years (tectonic deformation). Bridging short- and long-term deformation and developing seismotectonic models has been a challenge in experimental tectonics for more than a century. Since the formulation of Reid's elastic rebound theory 100 years ago, laboratory mechanical models combining frictional and elastic elements have been used to study the dynamics of earthquakes. In the last decade, with the advent of high-resolution monitoring techniques and new rock analogue materials, laboratory earthquake experiments have evolved from simple spring-slider models to scaled analogue models. This evolution was accomplished by advances in seismology and geodesy along with relatively frequent occurrences of large earthquakes in the past decade. This coincidence has significantly increased the quality and quantity of relevant observations in nature and triggered a new understanding of earthquake dynamics. We review here the developments in analogue earthquake modelling with a focus on those seismotectonic scale models that are directly comparable to observational data on short to long timescales. We lay out the basics of analogue modelling, namely scaling, materials and monitoring, as applied in seismotectonic modelling. An overview of applications highlights the contributions of analogue earthquake models in bridging timescales of observations including earthquake statistics, rupture dynamics, ground motion, and seismic-cycle deformation up to seismotectonic evolution.

  3. Glucose Sensing Neurons in the Ventromedial Hypothalamus

    Directory of Open Access Journals (Sweden)

    Vanessa H. Routh

    2010-10-01

    Full Text Available Neurons whose activity is regulated by glucose are found in a number of brain regions. Glucose-excited (GE neurons increase while glucose-inhibited (GI neurons decrease their action potential frequency as interstitial brain glucose levels increase. We hypothesize that these neurons evolved to sense and respond to severe energy deficit (e.g., fasting that threatens the brains glucose supply. During modern times, they are also important for the restoration of blood glucose levels following insulin-induced hypoglycemia. Our data suggest that impaired glucose sensing by hypothalamic glucose sensing neurons may contribute to the syndrome known as hypoglycemia-associated autonomic failure in which the mechanisms which restore euglycemia following hypoglycemia become impaired. On the other hand, increased responses of glucose sensing neurons to glucose deficit may play a role in the development of Type 2 Diabetes Mellitus and obesity. This review will discuss the mechanisms by which glucose sensing neurons sense changes in interstitial glucose and explore the roles of these specialized glucose sensors in glucose and energy homeostasis.

  4. Effects of rapid-acting insulin analogues insulin glulisine and insulin aspart on postprandial glycemic excursion with single bout of exercise in patients with type 2 diabetes.

    Science.gov (United States)

    Tanaka, Nagaaki; Hiura, Yoshikazu

    2015-01-01

    The analogue insulin glulisine (Glu) shows both more rapid onset and shorter duration of action compared with the other rapid-acting insulin analogues. The current study investigates these properties in regard to the occurrence of hypoglycemia related to exercise. A randomized, single-center, open-label, crossover study was conducted in 12 hospitalized type 2 diabetes patients (all male, mean ± SD age of 51.9 ± 11.3 years; BMI: 25.5 ± 3.9 kg/m2; HbA1c: 11.2 ± 2.4 %). Glu or insulin aspart (Asp) was subcutaneously administered just before breakfast. Insulin dosage was determined as the usual dose of pre-prandial rapid-acting insulin for patients treated with insulin therapy or as 0.1 unit/kg for patients treated with oral anti-hyperglycemic agents. Sixty min after the start of eating, the patients began aerobic exercise on a bicycle ergometer for 30 min at 50% of maximum heart rate. Hypoglycemic episodes (plasma glucose level exercise plasma glucose levels at 90, 120, and 150 min were significantly lower in Asp group (p exercise blood glucose levels were significantly lower in Asp group (p type 2 diabetes who are at high risk of post-exercise hypoglycemia.

  5. Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

    Science.gov (United States)

    Van Der Gugten, J Grace; Wong, Sophia; Holmes, Daniel T

    2016-01-01

    Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 μU/mL in patient serum samples.

  6. Glucose transport in adipose tissue

    NARCIS (Netherlands)

    Schoonen, AJM; Wientjes, KJC

    2005-01-01

    Based on the well-known extraction equation and the histology of subcutaneous adipose tissue, transport of glucose from capillary to microdialysis probe is described. Results are evaluated of previous studies by our group and others. Arguments are presented for a simple scheme in which the mean

  7. Hepatocytes: critical for glucose homeostasis.

    Science.gov (United States)

    Klover, Peter J; Mooney, Robert A

    2004-05-01

    Maintaining blood glucose levels within a narrow range is a critical physiological function requiring multiple metabolic pathways and involving several cell types, including a prominent role for hepatocytes. Under hormonal control, hepatocytes can respond to either feeding or fasting conditions by storing or producing glucose as necessary. In the fasting state, the effects of glucagon avoid hypoglycemia by stimulating glucogenesis and glycogenolysis and initiating hepatic glucose release. Postprandially, insulin prevents hyperglycemia, in part, by suppressing hepatic gluconeogenesis and glycogenolysis and facilitating hepatic glycogen synthesis. Both transcriptional regulation of rate limiting enzymes and modulation of enzyme activity through phosphorylation and allosteric regulation are involved. Type 2 diabetes mellitus is the most common serious metabolic condition in the world, and results from a subnormal response of tissues to insulin (insulin resistance) and a failure of the insulin-secreting beta cells to compensate. In type 2 diabetes, glucose is overproduced by the hepatocyte and is ineffectively metabolized by other organs. Impairments in the insulin signal transduction pathway appear to be critical lesions contributing to insulin resistance and type 2 diabetes.

  8. Controlled analogue experiments on propagation of seismic electromagnetic signals

    Institute of Scientific and Technical Information of China (English)

    HUANG Qinghua

    2005-01-01

    This study presented a method of laboratory analogue experiments based on a geographical scaling model and a waveguide model to investigate the characteristics of the propagation of seismic electromagnetic signals in the crust and the atmosphere. Some controlled experiments were done to evaluate the possible influence on the experimental results from the background electromagnetic field, geographical conditions, boundary effects, the source of electromagnetic signals (position, magnitude, and frequency), and media conductivity. The reliability and the extensibility of the above analogue experimental method were also investigated. This study indicated that such kind of analogue experimental method provided an intuitionistic way of studying the propagation of seismic electromagnetic signals, which is one of the most difficult research topics in seismo-electro- magnetism.

  9. Conception, synthesis, and biological evaluation of original discodermolide analogues.

    Science.gov (United States)

    de Lemos, Elsa; Agouridas, Evangelos; Sorin, Geoffroy; Guerreiro, Antonio; Commerçon, Alain; Pancrazi, Ange; Betzer, Jean-François; Lannou, Marie-Isabelle; Ardisson, Janick

    2011-08-29

    Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive "U" shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)-diene moiety, of the methyl group at the C14-position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.

  10. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    Science.gov (United States)

    Tadpetch, Kwanruthai; Kaewmee, Benyapa; Chantakaew, Kittisak; Kantee, Kawalee; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

    Science.gov (United States)

    López-Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T; Beutler, John A; Echavarren, Antonio M

    2016-05-01

    We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).

  12. Analogue peptides for the immunotherapy of human acute myeloid leukemia.

    Science.gov (United States)

    Hofmann, Susanne; Mead, Andrew; Malinovskis, Aleksandrs; Hardwick, Nicola R; Guinn, Barbara-Ann

    2015-11-01

    The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies.

  13. New rubrolide analogues as inhibitors of photosynthesis light reactions.

    Science.gov (United States)

    Varejão, Jodieh O S; Barbosa, Luiz C A; Ramos, Gabriela Álvarez; Varejão, Eduardo V V; King-Díaz, Beatriz; Lotina-Hennsen, Blas

    2015-04-01

    Natural products called rubrolides have been investigated as a model for the development of new herbicides that act on the photosynthesis apparatus. This study comprises a comprehensive analysis of the photosynthesis inhibitory ability of 27 new structurally diverse rubrolide analogues. In general, the results revealed that the compounds exhibited efficient inhibition of the photosynthetic process, but in some cases low water solubility may be a limiting factor. To elucidate their mode of action, the effects of the compounds on PSII and PSI, as well as their partial reaction on chloroplasts and the chlorophyll a fluorescence transients were measured. Our results showed that some of the most active rubrolide analogues act as a Hill reaction inhibitors at the QB level by interacting with the D1 protein at the reducing side of PSII. All of the active analogues follow Tice's rule of 5, which indicates that these compounds present physicochemical properties suitable for herbicides. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Synthesis and cytotoxic activity of novel curcumin analogues

    Institute of Scientific and Technical Information of China (English)

    Qin Zhang; Yao Fu; Hao Wei Wang; Tao Gong; Yong Qin; Zhi Rong Zhang

    2008-01-01

    Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues (1A-1C, 1E) with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.

  15. The Immucillins: Design, Synthesis and Application of Transition- State Analogues.

    Science.gov (United States)

    Evans, Gary B; Schramm, Vern L; Tyler, Peter C

    2015-01-01

    Transition-state analysis based on kinetic isotope effects and computational chemistry provides electrostatic potential maps to serve as blueprints for the design and chemical synthesis of transition-state analogues. The utility of these molecules is exemplified by potential clinical applications toward leukemia, autoimmune disorders, gout, solid tumors, bacterial quorum sensing and bacterial antibiotics. In some cases, transition-state analogues have chemical features that have allowed them to be repurposed for new indications, including potential antiviral use. Three compounds from this family have entered clinical trials. The transition-state analogues bind to their target proteins with high affinity and specificity. The physical and structural properties of binding teach valuable and often surprising lessons about the nature of tight-binding inhibitors.

  16. Ensemble meteorological reconstruction using circulation analogues of 1781–1785

    Directory of Open Access Journals (Sweden)

    P. Yiou

    2013-09-01

    Full Text Available This paper uses a method of atmospheric flow analogues to reconstruct an ensemble of atmospheric variables (namely sea-level pressure, surface temperature and wind speed between 1781 and 1785. The properties of this ensemble are investigated and tested against observations of temperature. The goal of the paper is to assess whether the atmospheric circulation during the Laki volcanic eruption (in 1783 and the subsequent winter were similar to the conditions that prevailed in the winter 2009/2010 and during spring 2010. We find that the three months following the Laki eruption in June 1783 barely have analogues in 2010. The cold winter of 1783/1784 yields circulation analogues in 2009/2010. Our analysis suggests that it is unlikely that the Laki eruption was responsible for the cold winter of 1783/1784, of the relatively short memory of the atmospheric circulation.

  17. Gold Nanoparticles Decorated with Mannose-6-phosphate Analogues

    Directory of Open Access Journals (Sweden)

    Stéphanie Combemale

    2014-01-01

    Full Text Available Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b introduction of spacers on the mannose-6-phosphate analogues via Huisgen’s cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound activation. With the resulting compounds in hand, gold nanoparticles could be functionalized with various carbohydrate derivatives (glycoconjugates and then tested for angiogenic activity. It was observed that the length and flexibility of the spacer separating the sugar analogue from the nanoparticle have little influence on the biological response. One particular nanoparticle system substantially inhibits blood vessel growth in contrast to activation by the corresponding monomeric glycoconjugate, thereby demonstrating the importance of multivalency in angiogenic activity.

  18. Largazole Analogues Embodying Radical Changes in the Depsipeptide Ring: Development of a More Selective and Highly Potent Analogue.

    Science.gov (United States)

    Almaliti, Jehad; Al-Hamashi, Ayad A; Negmeldin, Ahmed T; Hanigan, Christin L; Perera, Lalith; Pflum, Mary Kay H; Casero, Robert A; Tillekeratne, L M Viranga

    2016-12-08

    A number of analogues of the marine-derived histone deacetylase inhibitor largazole incorporating major structural changes in the depsipeptide ring were synthesized. Replacing the thiazole-thiazoline fragment of largazole with a bipyridine group gave analogue 7 with potent cell growth inhibitory activity and an activity profile similar to that of largazole, suggesting that conformational change accompanying switching hybridization from sp(3) to sp(2) at C-7 is well tolerated. Analogue 7 was more class I selective compared to largazole, with at least 464-fold selectivity for class I HDAC proteins over class II HDAC6 compared to a 22-fold selectivity observed with largazole. To our knowledge 7 represents the first example of a potent and highly cytotoxic largazole analogue not containing a thiazoline ring. The elimination of a chiral center derived from the unnatural amino acid R-α-methylcysteine makes the molecule more amenable to chemical synthesis, and coupled with its increased class I selectivity, 7 could serve as a new lead compound for developing selective largazole analogues.

  19. Synthesis of daidzin analogues as potential agents for alcohol abuse.

    Science.gov (United States)

    Gao, Guang-Yao; Li, Dian-Jun; Keung, Wing Ming

    2003-09-01

    Daidzin, the active principle of an herbal remedy for 'alcohol addiction', has been shown to reduce alcohol consumption in all laboratory animals tested to date. Correlation studies using structural analogues of daidzin suggests that it acts by raising the monoamine oxidase (MAO)/mitochondrial aldehyde dehydrogenase (ALDH-2) activity ratio (J. Med. Chem. 2000, 43, 4169). Structure-activity relationship (SAR) studies on the 7-O-substituted analogues of daidzin have revealed structural features important for ALDH-2 and MAO inhibition (J. Med. Chem. 2001, 44, 3320). We here evaluated effects of substitutions at 2, 5, 6, 8, 3' and 4' positions of daidzin on its potencies for ALDH-2 and MAO inhibition. Results show that analogues with 4'-substituents that are small, polar and with hydrogen bonding capacities are most potent ALDH-2 inhibitors, whereas those that are non-polar and with electron withdrawing capacities are potent MAO inhibitors. Analogues with a 5-OH group are less potent ALDH-2 inhibitors but are more potent MAO inhibitors. All the 2-, 6-, 8- and 3'-substituted analogues tested so far do not inhibit ALDH-2 and/or have decreased potencies for MAO inhibition. This, together with the results obtained from previous studies, suggests that a potent antidipsotropic analogue would be a 4',7-disubstituted isoflavone. The 4'-substituent should be small, polar, and with hydrogen bonding capacities such as, -OH and -NH(2); whereas the 7-substituent should be a straight-chain alkyl with a terminal polar function such as -(CH(2))(n)-OH with 2 or =4.

  20. Anti-diabetic actions of esculentin-2CHa(1-30) and its stable analogues in a diet-induced model of obesity-diabetes.

    Science.gov (United States)

    Vasu, Srividya; Ojo, Opeolu O; Moffett, R Charlotte; Conlon, J Michael; Flatt, Peter R; Abdel-Wahab, Yasser H A

    2017-08-23

    Actions of esculentin-2CHa(1-30) (GFSSIFRGVAKFASKGLGKDLAKLGVDLVA) and its analogues, ([D-Arg(7), D-Lys(15), D-Lys(23)]-esculentin-2CHa(1-30) and [Lys(15)-octanoate]-esculentin-2CHa(1-30), were evaluated in high-fat fed NIH Swiss mice with impaired glucose tolerance and insulin resistance. Twice-daily i.p. administration of the esculentin-2CHa(1-30) peptides (75 nmol/kg body weight) or exendin-4 (25 nmol/kg) for 28 days reduced body weight, without altering cumulative energy intake. All peptides reduced blood glucose levels by 6-12 mmol/l concomitant with lower plasma insulin levels, with significance evident from day 6. All peptides improved glucose tolerance, insulin sensitivity, blood glucose profile over 24 h and decreased HbA1c to a similar extent as exendin-4. The peptides also reduced high fat diet-induced increases in plasma GLP-1 and glucagon. None of the peptides altered bone mineral density/content or lean mass but decreased fat mass. Islets isolated from peptide-treated mice exhibited improved glucose-, alanine- and GLP-1-stimulated insulin secretion. Islet morphometric analyses revealed that exendin-4 and the esculentin-2CHa(1-30) peptides significantly reduced islet, beta and alpha cell areas compared to high-fat controls. Esculentin-2CHa(1-30) peptides markedly reduced high fat diet-induced increase in beta cell proliferation and apoptosis. Peptide treatments had beneficial effects on expression of islet genes (Ins1, Slc2a2, Pdx1) and skeletal muscle genes involved in insulin action (Slc2a4, Pdk1, Irs1, Akt1). High-fat diet significantly increased LDL cholesterol which was reduced by the acylated esculentin-2CHa(1-30) analogue. Peptide treatments did not alter circulating concentrations of amylase and marker enzymes of liver function, indicating a lack of toxicity. These data indicate that esculentin-2CHa(1-30) and its analogues may be useful for improvement of blood glucose control and weight loss in type 2 diabetes.

  1. Letter to the Editor - responses to Weisntein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and antiactivity in cultured cancer cells.

    Science.gov (United States)

    Weinstein, Doron; Simon, Meital; Yehezkel, Einat; Laron, Zvi; Werner, Haim

    2013-08-20

    We thank the team of Eli Lilly and Company for their critical appraisal of our study and for giving us the opportunity to clarify a number of points [1]. We agree with Kazda et al. that randomized clinical trials will best address any direct relationship between insulin analogues and cancer in man. We do not question the fact that tight control of blood glucose has dramatically advanced the lives of patients with diabetes. This article is protected by copyright. All rights reserved.

  2. Effect of lupine as cheese base substitution on technological and nutritional properties of processed cheese analogue.

    Science.gov (United States)

    Awad, Rezik Azab; Salama, Wafaa Mohammed; Farahat, Azza Mahmoud

    2014-01-01

    Healthy foods have been met with marked success in the last two decades. Lupine flours, protein concentrates, and isolates can be applied as a substance for enriching different kinds of food systems such as bakery products, lupine pasta, ice cream, milk substitutes. Imitation processed cheese is made from mixtures of dairy and/or non dairy proteins and fat/oils and is variously labeled analogue, artificial, extruded, synthetic and/or filled. Processed cheese can be formulated using different types of cheese with different degree of maturation, flavorings, emulsifying, salts, and/or several ingredients of non-dairy components. Non-dairy ingredients have been used in processed cheese for many dietary and economic reasons. In this study, lupine paste was used to substitute 25, 50, 75 and 100% of cheese in base formula of processed cheese analogue (PCA). Matured Ras cheese (3 months old) was manufactured using fresh cow milk. Soft cheese curd was manufactured using fresh buffalo skim milk. Emulsifying salts S9s and Unsalted butter were used. Lupine termis paste was prepared by soaking the seeds in tap water for week with changing the water daily, and then boiled in water for 2 hrs, cooled and peeled. The peeled seeds were minced, blended to get very fine paste and kept frozen until used. Lupine paste was used to substitute 25, 50, 75 and 100% of cheese in base formula of processed cheese analogue (PCA). The obtained PCA were analysed when fresh and during storage up to 3 months at 5±2°C for chemical composition, physical and sensory properties. The histopathological effect of lupines on alloxan diabetic albino rats and nutritional parameters were also investigated. Incorporation of lupine paste in PCA increased the ash and protein contents while meltability and penetration values of resultant products were decreased. Adding lupine in PSA formula had relatively increased the oil index and firmness of products. Feeding rats a balanced diet containing processed cheese

  3. Effect of lupine as cheese base substitution on technological and nutritional properties of processed cheese analogue

    Directory of Open Access Journals (Sweden)

    Rezik Azab Awad

    2014-03-01

    Full Text Available Background. Healthy foods have been met with marked success in the last two decades. Lupine flours, protein concentrates, and isolates can be applied as a substance for enriching different kinds of food systems such as bakery products, lupine pasta, ice cream, milk substitutes. Imitation processed cheese is made from mixtures of dairy and/or non dairy proteins and fat/oils and is variously labeled analogue, artifi cial, extruded, synthetic and/or fi lled. Processed cheese can be formulated using different types of cheese with different degree of maturation, fl avorings, emulsifying, salts, and/or several ingredients of non-dairy components. Non-dairy ingredients have been used in processed cheese for many dietary and economic reasons. In this study, lupine paste was used to substitute 25, 50, 75 and 100% of cheese in base formula of processed cheese analogue (PCA. Material and methods. Matured Ras cheese (3 months old was manufactured using fresh cow milk. Soft cheese curd was manufactured using fresh buffalo skim milk. Emulsifying salts S9s and Unsalted butter were used. Lupine termis paste was prepared by soaking the seeds in tap water for week with changing the water daily, and then boiled in water for 2 hrs, cooled and peeled. The peeled seeds were minced, blended to get very fi ne paste and kept frozen until used. Results. Lupine paste was used to substitute 25, 50, 75 and 100% of cheese in base formula of processed cheese analogue (PCA. The obtained PCA were analysed when fresh and during storage up to 3 months at 5±2°C for chemical composition, physical and sensory properties. The histopathological effect of lupines on alloxan diabetic albino rats and nutritional parameters were also investigated. Incorporation of lupine paste in PCA increased the ash and protein contents while meltability and penetration values of resultant products were decreased. Adding lupine in PSA formula had relatively increased the oil index and fi rmness of

  4. Analogue Kerr-like geometries in a MHD inflow

    CERN Document Server

    Noda, Sousuke; Takahashi, Masaaki

    2016-01-01

    We present a model of the analogue black hole in magnetohydrodynamic (MHD) flow. For a two dimensional axisymmetric stationary trans-magnetosonic inflow with a sink, using the dispersion relation of the MHD waves, we introduce the effective geometries for magnetoacoustic waves propagating in the MHD flow. Investigating the properties of the effective potentials for magnetoacoustic rays, we find that the effective geometries can be classified into five types which include analogue spacetimes of the Kerr black hole, ultra spinning stars with ergoregions and spinning stars without ergoregions. We address the effects of the magnetic pressure and the magnetic tension on each magnetoacoustic geometries.

  5. Naturally occurring crystalline phases: analogues for radioactive waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  6. Synthesis and evaluation of heterocyclic analogues of bromoxynil.

    Science.gov (United States)

    Cutulle, Matthew A; Armel, Gregory R; Brosnan, James T; Best, Michael D; Kopsell, Dean A; Bruce, Barry D; Bostic, Heidi E; Layton, Donovan S

    2014-01-15

    One attractive strategy to discover more active and/or crop-selective herbicides is to make structural changes to currently registered compounds. This strategy is especially appealing for those compounds with limited herbicide resistance and whose chemistry is accompanied with transgenic tools to enable herbicide tolerance in crop plants. Bromoxynil is a photosystem II (PSII) inhibitor registered for control of broadleaf weeds in several agronomic and specialty crops. Recently at the University of Tennessee-Knoxville several analogues of bromoxynil were synthesized including a previously synthesized pyridine (2,6-dibromo-5-hydroxypyridine-2-carbonitrile sodium salt), a novel pyrimidine (4,6-dibromo-5-hydroxypyrimidine-2-carbonitrile sodium salt), and a novel pyridine N-oxide (2,6-dibromo-1-oxidopyridin-1-ium-4-carbonitrile). These new analogues of bromoxynil were also evaluated for their herbicidal activity on soybean (Glycine max), cotton (Gossypium hirsutum), redroot pigweed (Amaranthus retroflexus), velvetleaf (Abutilon theophrasti), large crabgrass (Digitaria sanguinalis), and pitted morningglory ( Ipomoea lacunose ) when applied at 0.28 kg ha(-1). A second study was conducted on a glyphosate-resistant weed (Amaranthus palmeri) with the compounds being applied at 0.56 kg ha(-1). Although all compounds were believed to inhibit PSII by binding in the quinone binding pocket of D1, the pyridine and pyridine-N-oxide analogues were clearly more potent than bromoxynil on Amaranthus retroflexus. However, application of the pyrimidine herbicide resulted in the least injury to all species tested. These variations in efficacy were investigated using molecular docking simulations, which indicate that the pyridine analogue may form a stronger hydrogen bond in the pocket of the D1 protein than the original bromoxynil. A pyridine analogue was able to control the glyphosate-resistant Amaranthus palmeri with >80% efficacy. The pyridine analogues of bromoxynil showed potential

  7. Five new discodermolide analogues from the marine sponge Discodermia species.

    Science.gov (United States)

    Gunasekera, Sarath P; Paul, Gopal K; Longley, Ross E; Isbrucker, Richard A; Pomponi, Shirley A

    2002-11-01

    Discodermolide (1) and five new discodermolide analogues trivially named 2-epi-discodermolide (2), 2-des-methyldiscodermolide (3), 5-hydroxymethyldiscodermolate (4), 19-des-aminocarbonyldiscodermolide (5), and 9(13)-cyclodiscodermolide (6) have been isolated from marine sponges belonging to the genus Discodermia collected from the Caribbean Sea. The isolation, structure elucidation, and biological activities of 2-6 are described. The natural analogues, which were isolated in trace amounts, exhibited significant variation of cytotoxicity against the cultured murine P-388 leukemia and A-549 human adenocarcinoma cells and suggested the importance of the C(7) through C(17) moiety for potency against cultured tumor cell lines.

  8. Synthesis of Novel 1,3-Dioxolane Nucleoside Analogues

    Institute of Scientific and Technical Information of China (English)

    蔡冬梅; 林昆华; 李明宗; 温集武; 李鸿艳; 尤田耙

    2004-01-01

    Novel 1,3-dioxolane C-nucleoside analogues of tiazofurin 2-(2-hydroxymethyl-1,3-dioxolan-4-yl)-1,3-thiazole-4-carboxamide as well as N-nucleoside analogues of substituted imidazoles 1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-4-nitroimidazole and 1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-4,5-dicyanoimidazole were synthesized frommethyl acrylate through a multistep procedure. Their structures were confirmed by IR, 1H NMR, 13C NMR spectra and elemental analysis.

  9. Analogue Building Blocks Based on Digital CMOS Gates

    DEFF Research Database (Denmark)

    Mucha, Igor

    1996-01-01

    Low-performance analogue circuits built of digital MOS gates are presented. Depending on the threshold voltages of the technology used the final circuits can be operated using low supply voltages. The main advantage using the proposed circuits is the simplicity and ultimate compatibility with the......Low-performance analogue circuits built of digital MOS gates are presented. Depending on the threshold voltages of the technology used the final circuits can be operated using low supply voltages. The main advantage using the proposed circuits is the simplicity and ultimate compatibility...

  10. Meglitinide analogues in adolescent patients with HNF1A-MODY (MODY 3).

    Science.gov (United States)

    Becker, Marianne; Galler, Angela; Raile, Klemens

    2014-03-01

    For pediatric patients with hepatocyte nuclear factor-1A (HNF1A)-maturity-onset diabetes of the young (MODY 3), treatment with sulfonylureas is recommended. In adults with HNF1A-MODY, meglitinide analogues achieve lower postprandial glucose levels and pose a lower risk of delayed hypoglycemia compared with sulfonylureas. This therapy has not yet been reviewed in pediatric patients. We report on meglitinide analogue treatment in 3 adolescents with HNF1A-MODY. Case 1 (14-year-old girl) was diagnosed asymptomatically but had an hemoglobin A1c (HbA1c) level of 7.4%; her father had been recently diagnosed with HNF1A-MODY. With repaglinide, her HbA1c level decreased to 5.5%, with no hypoglycemic episodes. Case 2 (14-year-old boy) was diagnosed incidentally with glucosuria (HbA1c level: 7.0%) and was treated with insulin. After the HNF1A-MODY diagnosis, he was switched to glibenclamide. Due to several hypoglycemic episodes, treatment was changed to nateglinide and his HbA1c level decreased to 6.2% with no further hypoglycemic episodes. Case 3 (11-year-old girl) presented with polyuria and polydipsia (HbA1c level: 10.1%) and was initially treated with insulin. After the HNF1A-MODY diagnosis, treatment was changed to repaglinide. She was obese (BMI: 28.8 kg/m(2); z-score: +2.2), and glucose control with repaglinide alone was insufficient. Therefore, neutral protamine Hagedorn insulin (0.27 U/kg per day) was added. With this combination therapy, her HbA1c level decreased to 8.2%. The use of meglitinides in these 3 adolescent patients was well tolerated and effective. Furthermore, hypoglycemic episodes were rare compared with treatment with insulin or sulfonylureas. We therefore suggest considering meglitinides as the primary oral treatment option for adolescents suffering from HNF1A-MODY.

  11. Glucose sensing by means of silicon photonics

    Science.gov (United States)

    Bockstaele, Ronny; Ryckeboer, Eva; Hattasan, Nannicha; De Koninck, Yannick; Muneeb, Muhammad; Verstuyft, Steven; Delbeke, Danaë; Bogaerts, Wim; Roelkens, Gunther; Baets, Roel

    2014-03-01

    Diabetes is a fast growing metabolic disease, where the patients suffer from disordered glucose blood levels. Monitoring the blood glucose values in combination with extra insulin injection is currently the only therapy to keep the glucose concentration in diabetic patients under control, minimizing the long-term effects of elevated glucose concentrations and improving quality of life of the diabetic patients. Implantable sensors allow continuous glucose monitoring, offering the most reliable data to control the glucose levels. Infrared absorption spectrometers offer a non-chemical measurement method to determine the small glucose concentrations in blood serum. In this work, a spectrometer platform based on silicon photonics is presented, allowing the realization of very small glucose sensors suitable for building implantable sensors. A proof-of-concept of a spectrometer with integrated evanescent sample interface is presented, and the route towards a fully implantable spectrometer is discussed.

  12. CALIBRATION OF A WEARABLE GLUCOSE SENSOR

    NARCIS (Netherlands)

    SCHMIDT, FJ; AALDERS, AL; SCHOONEN, AJM; DOORENBOS, H

    1992-01-01

    Calibration of glucose sensors proved difficult for electrodes with immobilized glucose-oxidase. The correlation between the sensitivity of the electrodes in vitro and in vivo appeared to be poor. We developed a new type of glucose sensor, based on a microdialysis system, in which an oxygen electrod

  13. Autonomic regulation of hepatic glucose production

    NARCIS (Netherlands)

    Bisschop, Peter H; Fliers, Eric; Kalsbeek, A.

    2015-01-01

    Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system

  14. Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy (Conference Presentation)

    Science.gov (United States)

    Hu, Fanghao; Chen, Zhixing; Zhang, Luyuan; Shen, Yihui; Wei, Lu; Min, Wei

    2016-03-01

    Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.

  15. Extraction of Silver by Glucose.

    Science.gov (United States)

    Baksi, Ananya; Gandi, Mounika; Chaudhari, Swathi; Bag, Soumabha; Gupta, Soujit Sen; Pradeep, Thalappil

    2016-06-27

    Unprecedented silver ion leaching, in the range of 0.7 ppm was seen when metallic silver was heated in water at 70 °C in presence of simple carbohydrates, such as glucose, making it a green method of silver extraction. Extraction was facilitated by the presence of anions, such as carbonate and phosphate. Studies confirm a two-step mechanism of silver release, first forming silver ions at the metal surface and later complexation of ionic silver with glucose; such complexes have been detected by mass spectrometry. Extraction leads to microscopic roughening of the surface making it Raman active with an enhancement factor of 5×10(8) .

  16. Analogues of estradiol as potential breast tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, R.E.; Rzeszotarski, W.J.; Ferriera, N.L.; Jagoda, E.M.; Reba, R.C.; Eckelman, W.C.

    1984-01-01

    The radioiodinated analogue of estradiol, 11..beta..-methoxy-17..cap alpha..-(/sup 125/I)iodovinylestradiol (MIVE/sub 2/), has been shown to be a good candidate for the imaging of estrogen dependent breast tumors. Although there has been no extensive study on the sensitivity of radiotracers of this type, the authors have not observed localization of the radiotracer in metastatic lesions containing less than 20 fmole estrogen receptor/mg protein or in bone metasteses. In order to improve the sensitivity, they have examined several structural analogues of moxestrol (the parent structure for MIVE/sub 2/) for affinity to the ER isolated from immature rat uterus. The 11..beta..-ethyl analogue (EEE/sub 2/) of ethynyl estradiol (EE/sub 2/) exhibits the highest affinity with the 11..beta..-methyl analogue second best. Although the lipophilicity is also very high this compound should not be much more lipophilic than 16-iodoestradiol or MIVE/sub 2/ since the introduction of iodine increases the log P by greater than 1. The distribution of the tritiated derivative of EEE/sub 2/ is under study.

  17. Synthesis of pyrophosphonic acid analogues of farnesyl pyrophosphate

    NARCIS (Netherlands)

    Valentijn, A.R.P.M.; Berg, O. van den; Marel, G.A. van der; Cohen, L.H.; Boom, J.H. van

    1995-01-01

    The synthesis of four new analogues (i.e. 3-6) of farnesyl pyrophosphate (FPP), which may function as inhibitor of squalene synthase, is described. Compounds 3 and 4 were readily accessible by reaction of farnesal with diethyl phosphite or dimethyl lithiomethylphosphonate, respectively, followed by

  18. Simulated Milky Way analogues: implications for dark matter direct searches

    NARCIS (Netherlands)

    Bozorgnia, N.; Calore, F.; Schaller, M.; Lovell, M.; Bertone, G.; Frenk, C.S.; Crain, R.A.; Navarro, J.F.; Schaye, J.; Theuns, T.

    2016-01-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation

  19. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    1999-01-01

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were ac

  20. Aromaticity in Polyacene Analogues of Inorganic Ring Compounds

    CERN Document Server

    Chattaraj, P K; Chattaraj, Pratim Kumar; Roy, Debesh Ranjan

    2006-01-01

    The aromaticity in the polyacene analogues of several inorganic ring compounds (BN-acenes, CN-acenes, BO-acenes and Na6-acenes) is reported here for the first time. Conceptual density functional theory based reactivity descriptors and the nucleus independent chemical shift (NICS) values are used in this analysis.

  1. Synthesis of 4” manipulated Lewis X trisaccharide analogues

    Directory of Open Access Journals (Sweden)

    Christopher J. Moore

    2012-07-01

    Full Text Available Three analogues of the Lex trisaccharide antigen (β-D-Galp(1→4[α-L-Fucp(1→3]-D-GlcNAcp in which the galactosyl residue is modified at O-4 as a methyloxy, deoxychloro or deoxyfluoro, were synthesized. We first report the preparation of the modified 4-OMe, 4-Cl and 4-F trichloroacetimidate galactosyl donors and then report their use in the glycosylation of an N-acetylglucosamine glycosyl acceptor. Thus, we observed that the reactivity of these donors towards the BF3·OEt2-promoted glycosylation at O-4 of the N-acetylglucosamine glycosyl acceptors followed the ranking 4-F > 4-OAc ≈ 4-OMe > 4-Cl. The resulting disaccharides were deprotected at O-3 of the glucosamine residue and fucosylated, giving access to the desired protected Lex analogues. One-step global deprotection (Na/NH3 of the protected 4”-methoxy analogue, and two-step deprotections (removal of a p-methoxybenzyl with DDQ, then Zemplén deacylation of the 4”-deoxychloro and 4”-deoxyfluoro protected Lex analogues gave the desired compounds in good yields.

  2. BlockLevel Bayesian Diagnosis of Analogue Electronic Circuits

    NARCIS (Netherlands)

    Krishnan, Shaji; Krishnan, Shaji; Kerkhoff, Hans G.; Doornbosch, Klaas D.; Brand, Rudi

    2010-01-01

    Daily experience with product designers, test and diagnosis engineers it is realized that the depth of interaction among them, ought to be high for successful diagnosis of analogue circuits. With this knowledge in mind, a responsibility was undertaken to choose a popular diagnostic method and define

  3. Design and Synthesis of Muramyl Dipeptide Cyclic Analogue

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our "Meshed-Bag Gathered-Bunch" method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl-2,6-dioxocyclo-hexylidene)ethyl chemical protection strategy.

  4. Reproducibility along a 10 cm vertical visual analogue scale.

    OpenAIRE

    Dixon, J. S.; Bird, H A

    1981-01-01

    Reproducibility along a vertical 10 cm visual analogue scale (VAS) was investigated. Eight normal volunteers attempted to duplicate a set of marked VAS. There was a tendency to estimate too high on the scale, and reproducibility was found to be variable along its length. This indicates that the error involved in the use of VASs is even more complex than previously thought.

  5. Direct neutron decay of analogue resonances in 105Rh

    Institute of Scientific and Technical Information of China (English)

    Hu Bi-Tao; P.P.Zarubin; U.U.Juravlev

    2006-01-01

    A new method, while takes into account the contribution of direct neutron decay of analogue resonances to the isomeric ratio resulting from (p,n) reaction, is used to analyse the published experimental data for the reaction 104Ru(p,n)104Rh and also estimate a minimum probability of direct decay.

  6. A Macroscopic Analogue of the Nuclear Pairing Potential

    Science.gov (United States)

    Dunlap, Richard A.

    2013-01-01

    A macroscopic system involving permanent magnets is used as an analogue to nucleons in a nucleus to illustrate the significance of the pairing interaction. This illustrates that the view of the total nuclear energy based only on the nucleon occupancy of the energy levels can yield erroneous results and it is only when the pairing interaction is…

  7. Nucleic Acid Analogue Induced Transcription of Double Stranded DNA

    DEFF Research Database (Denmark)

    1998-01-01

    RNA is transcribed from a double stranded DNA template by forming a complex by hybridizing to the template at a desired transcription initiation site one or more oligonucleic acid analogues of the PNA type capable of forming a transcription initiation site with the DNA and exposing the complex...

  8. An Analysis of an Autoclitic Analogue in Pigeons

    Science.gov (United States)

    Kuroda, Toshikazu; Lattal, Kennon A.; García-Penagos, Andrés

    2014-01-01

    Using a conditional discrimination procedure, pigeons were exposed to a nonverbal analogue of qualifying autoclitics such as "definitely" and "maybe." It has been suggested that these autoclitics are similar to tacts except that they are under the control of private discriminative stimuli. Instead of the conventional assumption…

  9. Combined treatment of somatostatin analogues with pegvisomant in acromegaly

    NARCIS (Netherlands)

    S.E. Franck (Sanne); A. Muhammad (Ammar); A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)

    2016-01-01

    textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups

  10. Combined treatment of somatostatin analogues with pegvisomant in acromegaly

    NARCIS (Netherlands)

    S.E. Franck; A. Muhammad; A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)

    2016-01-01

    textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups ha

  11. Are Structural Analogues to Bisphenol A Safe Alternatives?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Mikael

    2014-01-01

    Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives, ...

  12. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were

  13. A highly efficient synthesis of itraconazole intermediates and their analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Chong Il; Myoung, Young Chan; Choi, Ha Young; Kim, Seung Jin [Agency for Technology and Standards, Gwacheon (Korea, Republic of)

    1999-12-01

    Itraconazole is an important drug for oral treatment of histoplasmosis and blastomycosis. Itraconazole has been the targets of many synthetic efforts due to their diverse antifungal activities. In this study, an efficient synthetic route for Itraconazole intermediates has been developed using new procedures. Also, Itraconazole analogues introducing 2- and 3-methoxy group instead of Itraconazole intermediates with 4-methoxy group were synthesized.

  14. Vitamin D analogues: Potential use in cancer treatment.

    Science.gov (United States)

    Duffy, Michael J; Murray, Alyson; Synnott, Naoise C; O'Donovan, Norma; Crown, John

    2017-04-01

    The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)2D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers. These associations apply especially in colorectal and breast cancer. Consistent with these findings, calcitriol as well as several of its synthetic analogues have been shown to inhibit tumor cell growth in vitro and in diverse animal model systems. Indeed, some of these vitamin D analogues with low calcemic inducing activity (e.g., EB1089, inecalcitol, paricalcitol) have progressed to clinical trials in patients with cancer. Preliminary results from these trials suggest that these vitamin D analogues have minimal toxicity, but clear evidence of efficacy remains to be shown. Although evidence of efficacy for mono-treatment with vitamin D analogues is currently lacking, several studies have reported that supplementation with calcitriol or the presence of high endogenous circulating levels of vitamin D enhances response to standard therapies.

  15. Synthesis, DNA interaction and antimicrobial activities of three rimantadine analogues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bing-Mi; Zhang, Jun [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Wang, Xin, E-mail: wangxinlnu@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Zhang, Li-Ping; Liu, Yang [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Niu, Hua-Ying [Jinan Dachpharm Development Co., Ltd., Jinan 250100 (China); Liu, Bin, E-mail: liubinzehao@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China)

    2015-03-15

    The interactions of three rimantadine analogues (RAs) with calf thymus deoxyribonucleic acid (ct-DNA) in buffer solution (pH 7.4) were investigated using berberine (BR) as a probe by various methods. Fluorescence studies revealed that the RAs interacted with DNA in vitro and the quenchings were all static. Furthermore, the binding modes of these compounds to DNA were disclosed as groove binding supported by absorption spectroscopy, viscosity measurement and denatured DNA experiment. The antimicrobial activities of the RAs were also evaluated in Staphylococcus aureus and Escherichia coli, and they all exhibited good bacteriostasic effects. The results might provide an important reference for investigation of the molecular mechanism associated with the DNA binding of the RAs. - Highlights: • Three rimantadine analogues were synthesized. • The RAs effectively quenched the intrinsic fluorescence of DNA via a static combination. • These analogues can bind to DNA via groove binding mode. • The antimicrobial activities of three analogues were also evaluated by the disk diffusion method.

  16. Click-based synthesis and proteomic profiling of lipstatin analogues

    OpenAIRE

    Ngai, Mun H.; Yang, Peng-Yu; Liu, Kai; Shen, Yuan; Wenk, Markus R; Yao, Shao Q.; Lear, Martin J.

    2010-01-01

    Using click chemistry to enable both structural diversity and proteome profiling within a natural product derived library, two out of nineteen lipstatin analogues showed similar activity to Orlistat against fatty acid synthase (FAS), but with an improved ability to induce tumour cell death.

  17. Solution-phase synthesis of a muramyl dipeptide analogue MDA

    Institute of Scientific and Technical Information of China (English)

    Nan Zhao; Yao Ma; Gang Liu

    2011-01-01

    The solution-phase synthesis of a muramyl dipeptide (MDP) analogue of Nα- [4-chlorocinnamoyl-L-alanyl-D-isoglutaminyl]-L-lysine (MDA, 2) is reported that possesses the features of easy feasibility, safety and low cost in large scale of synthesis.

  18. Design and Synthesis of Muramyl Dipeptide Cyclic Analogue

    Institute of Scientific and Technical Information of China (English)

    SuoDeZHANG; GangLIU; 等

    2002-01-01

    A new conformationalloy restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our “Meshed-Bag Gathered-Bunch” method with a combination of Fmoc,ally and N-1-(4,4-dimethyl-2,6-dioxocyclo-hexylidene) ethyl chemical protection strategy.

  19. Charged Analogues of Henning Knutsen Type Solutions in General Relativity

    Science.gov (United States)

    Gupta, Y. K.; Kumar, Sachin; Pratibha

    2011-11-01

    In the present article, we have found charged analogues of Henning Knutsen's interior solutions which join smoothly to the Reissner-Nordstrom metric at the pressure free interface. The solutions are singularity free and analyzed numerically with respect to pressure, energy-density and charge-density in details. The solutions so obtained also present the generalization of A.L. Mehra's solutions.

  20. Synthesis of pyrophosphonic acid analogues of farnesyl pyrophosphate

    NARCIS (Netherlands)

    Valentijn, A.R.P.M.; Berg, O. van den; Marel, G.A. van der; Cohen, L.H.; Boom, J.H. van

    1995-01-01

    The synthesis of four new analogues (i.e. 3-6) of farnesyl pyrophosphate (FPP), which may function as inhibitor of squalene synthase, is described. Compounds 3 and 4 were readily accessible by reaction of farnesal with diethyl phosphite or dimethyl lithiomethylphosphonate, respectively, followed by

  1. The influence of no fault found in analogue CMOS circuits

    NARCIS (Netherlands)

    Wan, Jinbo; Kerkhoff, Hans G.

    2014-01-01

    The most difficult fault category in electronic systems is the “No Fault Found” (NFF). It is considered to be the most costly fault category in, for instance, avionics. The relatively few papers in this area rarely deal with analogue integrated systems. In this paper a simple simulation model has be

  2. Synthesis and Antioxidant Properties of Novel Silybin Analogues

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Eight novel silybin analogues (7a-h) were synthesized and their antioxidant properties including the capability of scavenging superoxide anion free radicals and the inhibitory effect on DPPH free radicals were determined. Several synthetic compounds showed comparable antioxidative effect to that of quercetin.

  3. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    1999-01-01

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were ac

  4. Concise synthesis of new bridged-nicotine analogues

    DEFF Research Database (Denmark)

    Crestey, François; Hooyberghs, Geert; Kristensen, Jesper Langgaard

    2012-01-01

    This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively....

  5. Rubrene analogues with the aggregation-induced emission enhancement behaviour

    DEFF Research Database (Denmark)

    Zhang, Xiaoxu; Sørensen, Jakob Kryger; Fu, Xiaowei;

    2014-01-01

    In the light of the principle of aggregation-induced emission enhancement (AIEE), the rubrene analogue with orange light-emitting properties is designed and synthesized by substituting the phenyl side groups of rubrene with thienyl groups. To the best of our knowledge, this is the first report...

  6. Glucose isotope, carbon recycling, and gluconeogenesis using [U-13C]glucose and mass isotopomer analysis.

    Science.gov (United States)

    Lee, W N; Sorou, S; Bergner, E A

    1991-06-01

    Experimental determinations of glucose carbon recycling using 14C or 13C glucose tracer often underestimate true Cori cycle activity because of dilution and exchange of isotope tracer through the tricarboxylic acid (TCA) cycle. The term glucose isotope recycling therefore is used to distinguish recycling of isotope from recycling of glucose carbon, the actual quantity of circulating glucose recycled. Recently, per-labeled glucose ([U-13C6]glucose) has been used to estimate glucose appearance rate and glucose isotope recycling. Chemical structural information determined by mass isotopomer analysis has been used to correct for dilution of isotope through the TCA cycle. In this report, we present experiments in the study of glucose turnover and recycling using [U-13C6]glucose. Methods of single injection and continuous infusion of [U-13C6]glucose are compared. A formula for the calculation of a dilution factor using TCA cycle parameters is derived. In this study of six rabbits, glucose turnover rate ranged from 3.4 to 8.8 mg/kg/min, and glucose m + 3 mass isotopomer recycling from 7 to 12%. The rate of pyruvate carboxylation (Y) was comparable to that of citrate synthetase, having an average relative flux of 0.89. Applying the correction factor for tracer dilution to the observed mass isotopomer recycling, we determined glucose carbon recycling (or Cori cycle activity) to be 22-35% of hepatic glucose output.

  7. Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S. (Karolinska Hospital, Stockholm (Sweden))

    1990-11-01

    We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with (2-3H)glucose and HGP with (6-3H)glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). (2-3H)- minus (6-3H)glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

  8. Fursemida Influence on glucose tolerance

    OpenAIRE

    Valdivia, Héctor; Departamento de Medicina, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Garmendia, Fausto; Departamento de Medicina, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Dávila, Enrique; Departamento de Medicina, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    We have investigated the effect of Fursemida on glucose tolerance in 82 patients : 14 mormales , 15 cirrhotic , 15 diabetics, 7 patients with cardioesclerosis , 8 with hypertension , 8 nephropathy without failure and 15 with failure, for which administered daily 80 me . diuretic for one week. In 8 patients (4 diabetic , cirrhotic March 1 with hypertension ) occurred a pathological increase in basal glycemia. Except with nephropathy , elevated in all groups glycemia curves was observed , which...

  9. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    Science.gov (United States)

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

  10. Non-robust numerical simulations of analogue extension experiments

    Science.gov (United States)

    Naliboff, John; Buiter, Susanne

    2016-04-01

    Numerical and analogue models of lithospheric deformation provide significant insight into the tectonic processes that lead to specific structural and geophysical observations. As these two types of models contain distinct assumptions and tradeoffs, investigations drawing conclusions from both can reveal robust links between first-order processes and observations. Recent studies have focused on detailed comparisons between numerical and analogue experiments in both compressional and extensional tectonics, sometimes involving multiple lithospheric deformation codes and analogue setups. While such comparisons often show good agreement on first-order deformation styles, results frequently diverge on second-order structures, such as shear zone dip angles or spacing, and in certain cases even on first-order structures. Here, we present finite-element experiments that are designed to directly reproduce analogue "sandbox" extension experiments at the cm-scale. We use material properties and boundary conditions that are directly taken from analogue experiments and use a Drucker-Prager failure model to simulate shear zone formation in sand. We find that our numerical experiments are highly sensitive to numerous numerical parameters. For example, changes to the numerical resolution, velocity convergence parameters and elemental viscosity averaging commonly produce significant changes in first- and second-order structures accommodating deformation. The sensitivity of the numerical simulations to small parameter changes likely reflects a number of factors, including, but not limited to, high angles of internal friction assigned to sand, complex, unknown interactions between the brittle sand (used as an upper crust equivalent) and viscous silicone (lower crust), highly non-linear strain weakening processes and poor constraints on the cohesion of sand. Our numerical-analogue comparison is hampered by (a) an incomplete knowledge of the fine details of sand failure and sand

  11. Combining insulins for optimal blood glucose control in type 1 and 2 diabetes: focus on insulin glulisine

    Directory of Open Access Journals (Sweden)

    Heather Ulrich

    2007-07-01

    Full Text Available Heather Ulrich1,4, Benjamin Snyder1,Satish K Garg1,2,31Barbara Davis Center for Childhood Diabetes; 2Department of Medicine; 3Pediatrics; 4Department of Clinical Pharmacy, School of Pharmacy, University of Colorado at Denver and Health Sciences Center, Denver, CO, USAAbstract: Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI. Insulin glulisine (Apidra® is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs. The safety and tolerability profile of insulin glulisine is also comparable to that of insulin

  12. Analogue Electrical Circuit for Simulation of the Duffing-Holmes Equation

    DEFF Research Database (Denmark)

    Tamaseviciute, E.; Tamasevicius, A.; Mykolaitis, G.

    2008-01-01

    An extremely simple second order analogue electrical circuit for simulating the two-well Duffing-Holmes mathematical oscillator is described. Numerical results and analogue electrical simulations are illustrated with the snapshots of chaotic waveforms, phase portraits (Lissajous figures...

  13. Synthesis and Characterization of the Tetrazole Analogues of α-Amino Acids

    Institute of Scientific and Technical Information of China (English)

    Yan Min HUO; Gen Hu LEI; Yin Mao WEI; Xiao Hui ZHENG

    2006-01-01

    The tetrazole analogues have been synthesized from fluorenylmethoxycarbonyl (Fmoc)protected amino acids by three steps. The structures of the analogues were characterized by HPLC-MS, 1H NMR and 13C NMR.

  14. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

    Science.gov (United States)

    Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

    2012-08-15

    Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity.

  15. Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults

    OpenAIRE

    Riby, Leigh; McLaughlin, Jennifer; Riby , Deborah, M.

    2008-01-01

    Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addit...

  16. Synthesis of anti-tumour phosphatidylinositol analogues from glucose by the use of ring-closing olefin metathesis

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Skytte, Dorthe M.; Madsen, Robert

    2004-01-01

    -closing metathesis to afford the key conduritol B intermediate 7. This can trifurcate to form three different benzyl-protected myo-inositol headgroups 4-6, which after phosphorylation and attachment of the glycerolipid part give phosphatidylinositols 1-3. Preliminary biological testing against human colon...

  17. THE EFFECT OF THE SOMATOSTATIN ANALOGUE OCTREOTIDE ON EXPERIMENTAL INTESTINAL OBSTRUCTION IN RATS

    Directory of Open Access Journals (Sweden)

    Paran Haim

    1998-01-01

    Full Text Available Background: Somatostatin has an inhibitory effect on the endocrine and exocrine secretions of the gut. It may have a beneficial effect in the conservative treatment of intestinal obstruction. The aim of the present study is to investigate the effect of octreotide in mechanical intestinal obstruction in rats. Method: Intestinal obstruction was induced in rats by ligation of a segment of the distal ileum. Animals were treated with the somatostatin analogue octreotide (n=16, or saline (n=16. Eight rats were operated but their intestine was not ligated (n=8 serving as sham controls. Forty eight hours after the operation, the animals were operated upon again and blood samples from the femoral vein were tested for electrolytes, urea, glucose, lactic acid, amylase, ph and bicarbonate. Portal vein blood samples were also obtained and tested for lactic acid and amylase. Results: Intestinal obstruction resulted, after 48 hours, in severe dilatation of bowel loops. A significant increase in plasma levels of urea, amylase and lactic acid was observed. Plasma pH decreased. In blood samples from the portal vein, a significant increase in lactic acid was observed, indicating metabolic acidosis, probably secondary to bowel ischemia. Octreotide treatment, resulted in less acidosis, with concomitant lower urea and lactic acid levels in the plasma and especially in the portal vein. Conclusion: Octreotide treatment may have a beneficial effect in the conservative treatment of selected cases of intestinal obstruction.

  18. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    Energy Technology Data Exchange (ETDEWEB)

    Skagius, K. [Kemakta Consultants co., Stockholm (Sweden); Wingefors, S. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    1992-12-31

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  19. Hepatic glucose sensing is impaired, but can be normalized, in people with impaired fasting glucose.

    Science.gov (United States)

    Perreault, Leigh; Færch, Kristine; Kerege, Anna A; Bacon, Samantha D; Bergman, Bryan C

    2014-07-01

    Abnormal endogenous glucose production (EGP) is a characteristic feature in people with impaired fasting glucose (IFG). We sought to determine whether impaired hepatic glucose sensing contributes to abnormal EGP in IFG and whether it could be experimentally restored. Glucose production (rate of appearance; Ra) and flux (glucose cycling) were assessed during a hyperglycemic-euinsulinemic somatostatin clamp with an infusion of [6,6-(2)H2-]glucose and [2-(2)H]glucose before and after enhanced hepatic glucokinase activity via an infusion of low-dose fructose in people with IFG and normal glucose tolerance (NGT). During euglycemia, neither endogenous glucose production [(6,6-(2)H2)-glucose Ra; P = 0.53] or total glucose output (TGO; [2-(2)H]-glucose Ra; P = .12) was different between groups, but glucose cycling ([2-(2)H]glucose Ra to [6,6-(2)H2-]glucose Ra; a surrogate measure of hepatic glucokinase activity in the postabsorptive state) was lower in IFG than NGT (P = .04). Hyperglycemia suppressed EGP more in NGT than IFG (P vs IFG), whereas TGO decreased similarly in both groups (P = .77). The addition of fructose completely suppressed EGP in IFG (P Glucose cycling (which reflects glucose-6-phosphatase activity during glucose infusion) was similar in IFG and NGT (P = .51) during hyperglycemia and was unchanged and comparable between groups with the addition of fructose (P = .24). In summary, glucose sensing is impaired in IFG but can be experimentally restored with low-dose fructose. Glucokinase activation may prove to be a novel strategy for the prevention of diabetes in this high-risk group.

  20. Phosphorylation of inositol 1,4,5-trisphosphate analogues by 3-kinase and dephosphorylation of inositol 1,3,4,5-tetrakisphosphate analogues by 5-phosphatase

    NARCIS (Netherlands)

    Dijken, Peter van; Lammers, Aleida A.; Ozaki, Shoichiro; Potter, Barry V.L.; Erneux, Christophe; Haastert, Peter J.M. van

    1994-01-01

    A series of P-32-labeled D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P-4] analogues was enzymically prepared from the corresponding D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] analogues using recombinant rat brain Ins(1,4,5)P-3 3-kinase and [gamma-P-32]ATP. Ins(1,4,5)P-3 analogues

  1. An analogue conceptual rainfall-runoff model for educational purposes

    Science.gov (United States)

    Herrnegger, Mathew; Riedl, Michael; Schulz, Karsten

    2016-04-01

    Conceptual rainfall-runoff models, in which runoff processes are modelled with a series of connected linear and non-linear reservoirs, remain widely applied tools in science and practice. Additionally, the concept is appreciated in teaching due to its somewhat simplicity in explaining and exploring hydrological processes of catchments. However, when a series of reservoirs are used, the model system becomes highly parametrized and complex and the traceability of the model results becomes more difficult to explain to an audience not accustomed to numerical modelling. Since normally the simulations are performed with a not visible digital code, the results are also not easily comprehensible. This contribution therefore presents a liquid analogue model, in which a conceptual rainfall-runoff model is reproduced by a physical model. This consists of different acrylic glass containers representing different storage components within a catchment, e.g. soil water or groundwater storage. The containers are equipped and connected with pipes, in which water movement represents different flow processes, e.g. surface runoff, percolation or base flow. Water from a storage container is pumped to the upper part of the model and represents effective rainfall input. The water then flows by gravity through the different pipes and storages. Valves are used for controlling the flows within the analogue model, comparable to the parameterization procedure in numerical models. Additionally, an inexpensive microcontroller-based board and sensors are used to measure storage water levels, with online visualization of the states as time series data, building a bridge between the analogue and digital world. The ability to physically witness the different flows and water levels in the storages makes the analogue model attractive to the audience. Hands-on experiments can be performed with students, in which different scenarios or catchment types can be simulated, not only with the analogue but

  2. Synthesis and antioxidant activity of peptide-based ebselen analogues.

    Science.gov (United States)

    Satheeshkumar, Kandhan; Mugesh, Govindasamy

    2011-04-18

    A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration.

  3. Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

    DEFF Research Database (Denmark)

    Hulman, Adam; Simmons, Rebecca Kate; Vistisen, Dorte

    2017-01-01

    We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies...... in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different...... patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak...

  4. Postprandial glucose response to selected tropical fruits in normal glucose-tolerant Nigerians.

    Science.gov (United States)

    Edo, A; Eregie, A; Adediran, O; Ohwovoriole, A; Ebengho, S

    2011-01-01

    The glycemic response to commonly eaten fruits in Nigeria has not been reported. Therefore, this study assessed the plasma glucose response to selected fruits in Nigeria. Ten normal glucose-tolerant subjects randomly consumed 50 g carbohydrate portions of three fruits: banana (Musa paradisiaca), pineapple (Ananus comosus), and pawpaw (Carica papaya), and a 50-g glucose load at 1-week intervals. Blood samples were collected in the fasting state and half-hourly over a 2-h period post-ingestion of the fruits or glucose. The samples were analyzed for plasma glucose concentrations. Plasma glucose responses were assessed by the peak plasma glucose concentration, maximum increase in plasma glucose, 2-h postprandial plasma glucose level, and incremental area under the glucose curve and glycemic index (GI). The results showed that the blood glucose response to these three fruits was similar in terms of their incremental areas under the glucose curve, maximum increase in plasma glucose, and glycemic indices (GIs). The 2-h postprandial plasma glucose level of banana was significantly higher than that of pineapple, P fruits may be used as fruit exchanges with pineapple having the most favorable glycemic response.

  5. Spectrophotometric Assay of Immobilized Glucose Oxidase

    Directory of Open Access Journals (Sweden)

    Nojan Noorbehesht

    2016-06-01

    Full Text Available Enzyme results in change the substrate of product. Each enzyme may act on specific substrates, resulting in product or different products. The enzyme glucose oxidase (GOX is a bio catalyst. It accelerates the process of transforming glucose into hydrogen peroxide (H2O2 . These enzymes are used in the chemical industry, food industry, cosmetics and kits for diagnosis of glucose. There are many researches about immobilizations of Glucose Oxide to increase specifications such as repeated use, recovery, stability, shelf life and other features In this work, glucose oxidase enzyme using covalent bonding is placed on the carrier of carbon nanotubes. In this study, multi-walled carbon nanotubes have been used as adsorbents. Also, carbon nanotubes have been functionalized by sulfuric acid and nitric acid with a high concentration. Glucose oxidase is a biological biocatalyst enzyme. It accelerates changing glucose to H2O2. This enzyme is used in the chemical industry, food industry, cosmetics and glucose diagnostic kits. For example, as a result of ongoing research working focuses on the development of glucose biosensors, GOX in practice as standard enzyme has been revealed for immobilization of oxidative enzyme.GOX correct fixation on the MWNTs carrier is a way to reuse enzyme and miniature of biosensor devices and structures. In this study, a spectrophotometer was used to determine the absorbance of the enzyme glucose oxidase (GOX to review its activities after stabilizing the carbon nanotubes.

  6. Uptake and metabolism of D-glucose in isolated acinar and ductal cells from rat submandibular glands.

    Science.gov (United States)

    Cetik, Sibel; Rzajeva, Aigun; Hupkens, Emeline; Malaisse, Willy J; Sener, Abdullah

    2014-07-01

    The present study deals with the possible effects of selected environmental agents upon the uptake and metabolism of d-glucose in isolated acinar and ductal cells from the rat submandibular salivary gland. In acinar cells, the uptake of d-[U-(14) C]glucose and its non-metabolised analogue 3-O-[(14) C-methyl]-d-glucose was not affected significantly by phloridzin (0.1 mM) or substitution of extracellular NaCl (115 mM) by an equimolar amount of CsCl, whilst cytochalasin B (20 μM) decreased significantly such an uptake. In ductal cells, both phloridzin and cytochalasin B decreased the uptake of d-glucose and 3-O-methyl-d-glucose. Although the intracellular space was comparable in acinar and ductal cells, the catabolism of d-glucose (2.8 or 8.3 mM) was two to four times higher in ductal cells than in acinar cells. Phloridzin (0.1 mM), ouabain (1.0 mM) and cytochalasin B (20 μM) all impaired d-glucose catabolism in ductal cells. Such was also the case in ductal cells incubated in the absence of extracellular Ca(2+) or in media in which NaCl was substituted by CsCl. It is proposed that the ductal cells in the rat submandibular gland are equipped with several systems mediating the insulin-sensitive, cytochalasin B-sensitive and phloridzin-sensitive transport of d-glucose across the plasma membrane.

  7. The analogue method for precipitation prediction: finding better analogue situations at a sub-daily time step

    Science.gov (United States)

    Horton, Pascal; Obled, Charles; Jaboyedoff, Michel

    2017-07-01

    Analogue methods (AMs) predict local weather variables (predictands) such as precipitation by means of a statistical relationship with predictors at a synoptic scale. The analogy is generally assessed on gradients of geopotential heights first to sample days with a similar atmospheric circulation. Other predictors such as moisture variables can also be added in a successive level of analogy. The search for candidate situations similar to a given target day is usually undertaken by comparing the state of the atmosphere at fixed hours of the day for both the target day and the candidate analogues. This is a consequence of using standard daily precipitation time series, which are available over longer periods than sub-daily data. However, it is unlikely for the best analogy to occur at the exact same hour for the target and candidate situations. A better analogue situation may be found with a time shift of several hours since a better fit can occur at different times of the day. In order to assess the potential for finding better analogues at a different hour, a moving time window (MTW) has been introduced. The MTW resulted in a better analogy in terms of the atmospheric circulation and showed improved values of the analogy criterion on the entire distribution of the extracted analogue dates. The improvement was found to increase with the analogue rank due to an accumulation of better analogues in the selection. A seasonal effect has also been identified, with larger improvements shown in winter than in summer. This may be attributed to stronger diurnal cycles in summer that favour predictors taken at the same hour for the target and analogue days. The impact of the MTW on the precipitation prediction skill has been assessed by means of a sub-daily precipitation series transformed into moving 24 h totals at 12, 6, and 3 h time steps. The prediction skill was improved by the MTW, as was the reliability of the prediction. Moreover, the improvements were greater for days

  8. Thyroid hormone excess and glucose intolerance.

    Science.gov (United States)

    Dimitriadis, G D; Raptis, S A

    2001-01-01

    The elevated plasma glucose levels in hyperthyroidism may be explained by increased rates of endogenous glucose production, due mainly to increased gluconeogenesis. The rates of insulin-stimulated glucose disposal in peripheral tissues in hyperthyroidism have been found, in general, either normal or increased. Skeletal muscle is the most important tissue for the disposal of glucose in response to insulin. In this tissue, insulin increases glucose disposal by stimulating glucose transport, glucose phosphorylation/glycolysis, glycogen synthesis and glucose oxidation. Studies examining insulin-stimulated glucose metabolism in skeletal muscle have suggested that, in the hyperthyroid state, it may be of primary importance to increase the rates of glycolysis and lactate formation relative to glucose oxidation in this tissue in order to provide substrate for gluconeogenesis (increase Cori cycle activity). This effect will be achieved primarily by a decrease in glycogen synthesis and an increase in glycogenolysis. When hyperthyroidism becomes more severe, an increased rate of glucose uptake into muscle may then be necessary since the increased conversion of glycogen to lactate could not be sustained for prolonged periods and might lead to a depletion in glycogen stores. This mechanism would ensure that the level of glucose in plasma is kept normal or slightly increased. Thus, an increased Cori cycle activity may be a necessary mechanism to provide optimal conditions in hyperthyroidism for the control of glucose utilization without increasing the risk of hypoglycemia. In addition to lactate, increased rates of gluconeogenesis in hyperthyroidism can also be sustained by increased plasma concentrations of amino acids (mostly glutamine and alanine) and glycerol, as well as by increased plasma concentrations of free fatty acids.

  9. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    OpenAIRE

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or c...

  10. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    OpenAIRE

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or c...

  11. New selenium-75 labeled radiopharmaceuticals: selenonium analogues of dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Sadek, S.A.; Basmadjian, G.P.; Hsu, P.M.; Rieger, J.A.

    1983-07-01

    Selenium-75 labeled selenonium analogues of dopamine, (2-(3,4-dimethoxyphenyl)ethyl)dimethylselenonium iodide and its dihydroxy analogue, were prepared by reducing (/sup 75/Se)selenious acid with sodium borohydride at pH 6.0 and reacting the NaSeH produced with 1-(3,4-dimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethane. Tissue distribution studies in rats given the /sup 75/Se-labeled selenonium agents intravenously demonstrated high initial heart uptake. Prolonged adrenal retention and high adrenal to blood ratio of compound 4 were observed. The high uptake and adrenal to blood ratio suggest the potential use of compound 4 as a radiopharmaceutical for the adrenal gland.

  12. The theory of Hawking radiation in laboratory analogues

    CERN Document Server

    Robertson, Scott

    2015-01-01

    Hawking radiation, despite being known to theoretical physics for nearly forty years, remains elusive and undetected. It also suffers, in its original context of gravitational black holes, from practical and conceptual difficulties. Of particular note is the trans-Planckian problem, which is concerned with the apparent origin of the radiation in absurdly high frequencies. In order to gain better theoretical understanding and, it is hoped, experimental verification of Hawking radiation, much study is being devoted to laboratory systems which use moving media to model the spacetime geometry of black holes, and which, by analogy, are also thought to emit Hawking radiation. These analogue systems typically exhibit dispersion, which regularizes the wave behaviour at the horizon at the cost of a more complicated theoretical framework. This tutorial serves as an introduction to Hawking radiation and its analogues, developing the moving medium analogy for black holes and demonstrating how dispersion can be incorporat...

  13. Basic entwinements: unassuming analogue inserts in basic digital modeling (courses)

    DEFF Research Database (Denmark)

    Wiesner, Thomas

    2012-01-01

    to diverse inter-active discussions and a more conscious re-plays of material transcending the dichotomies of digital/analogue. Keywords Simple didactics, analogue sketching, cognitive space awareness, digital modelling, bachelor first year, morphology of body and space, pataphysics...... of options for speedily produced material for various attuned and conscious, supplementary oblique architectural assessments. The simple procedure(s) advance a certain amount of beneficial cognitive complementarities: Beneficial interplay-changes between right and left brain concentrations; Change...... of tactility (whole hand gestures v/s mouse directed fixed “digits”); Fast production of simple material to re-assess various architectural spatial conditions; Fast toggling between scale/scaleless, conceptual-abstract/ and figurative/concrete; The fast exercises permit various interactive dealings, opening up...

  14. Noncommutative analogue Aharonov-Bohm effect and superresonance

    CERN Document Server

    Anacleto, M A; Passos, E

    2012-01-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in this background. We mainly show that the scattering of planar waves by a draining bathtub vortex leads to a modified AB effect and due to spacetime noncommutativity, the phase shift persists even in the limit where the parameters associated with the circulation and draining vanish. Finally, we also find that the analogue AB effect and superresonance are competing phenomena at a noncommutative spacetime.

  15. Noncommutative analogue Aharonov-Bohm effect and superresonance

    Science.gov (United States)

    Anacleto, M. A.; Brito, F. A.; Passos, E.

    2013-06-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in this background. We mainly show that the scattering of planar waves by a draining bathtub vortex leads to a modified AB effect and due to spacetime noncommutativity, the phase shift persists even in the limit where the parameters associated with the circulation and draining vanish. Finally, we also find that the analogue AB effect and superresonance are competing phenomena at a noncommutative spacetime.

  16. Alligator rivers analogue project an OECD/NEA international project

    Energy Technology Data Exchange (ETDEWEB)

    Duerden, P.; Airey, P. [ANSTO, Menai (Australia); Pescatore, C. [OECD/NEA Issy-les-Moulineaux (France)

    1994-12-31

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as a natural analogue of the far field behaviour of high level waste repositories following groundwater ingress. A number of mathematical modelling approaches were developed for processes as diverse as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained.

  17. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V. (Tulane Univ. School of Medicine, New Orleans, LA (USA))

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin (cis-diamminedichloroplatinum(II)) and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  18. Acoustic clouds: standing sound waves around a black hole analogue

    CERN Document Server

    Benone, Carolina L; Herdeiro, Carlos; Radu, Eugen

    2014-01-01

    Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic black holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

  19. Optical analogue of relativistic Dirac solitons in binary waveguide arrays

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Truong X., E-mail: truong.tran@mpl.mpg.de [Department of Physics, Le Quy Don University, 236 Hoang Quoc Viet str., 10000 Hanoi (Viet Nam); Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); Longhi, Stefano [Department of Physics, Politecnico di Milano and Istituto di Fotonica e Nanotecnologie del Consiglio Nazionale delle Ricerche, Piazza L. da Vinci 32, I-20133 Milano (Italy); Biancalana, Fabio [Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); School of Engineering and Physical Sciences, Heriot-Watt University, EH14 4AS Edinburgh (United Kingdom)

    2014-01-15

    We study analytically and numerically an optical analogue of Dirac solitons in binary waveguide arrays in the presence of Kerr nonlinearity. Pseudo-relativistic soliton solutions of the coupled-mode equations describing dynamics in the array are analytically derived. We demonstrate that with the found soliton solutions, the coupled mode equations can be converted into the nonlinear relativistic 1D Dirac equation. This paves the way for using binary waveguide arrays as a classical simulator of quantum nonlinear effects arising from the Dirac equation, something that is thought to be impossible to achieve in conventional (i.e. linear) quantum field theory. -- Highlights: •An optical analogue of Dirac solitons in nonlinear binary waveguide arrays is suggested. •Analytical solutions to pseudo-relativistic solitons are presented. •A correspondence of optical coupled-mode equations with the nonlinear relativistic Dirac equation is established.

  20. Analogue transformations in physics and their application to acoustics.

    Science.gov (United States)

    García-Meca, C; Carloni, S; Barceló, C; Jannes, G; Sánchez-Dehesa, J; Martínez, A

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft.

  1. New Immunosuppressive Sphingoid Base and Ceramide Analogues in Wild Cordyceps.

    Science.gov (United States)

    Mi, Jia-Ning; Han, Yuwei; Xu, Yingqiong; Kou, Junping; Wang, Jing-Rong; Jiang, Zhi-Hong

    2016-12-14

    A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps.

  2. Anisotropic metamaterial as an analogue of a black hole

    Energy Technology Data Exchange (ETDEWEB)

    Fernández-Núñez, Isabel; Bulashenko, Oleg, E-mail: oleg.bulashenko@ub.edu

    2016-01-08

    Propagation of light in a metamaterial medium which mimics curved spacetime and acts like a black hole is studied. We show that for a particular type of spacetimes and wave polarization, the time dilation appears as dielectric permittivity, while the spatial curvature manifests as magnetic permeability. The optical analogue to the relativistic Hamiltonian which determines the ray paths (null geodesics) in the anisotropic metamaterial is obtained. By applying the formalism to the Schwarzschild metric, we compare the ray paths with full-wave simulations in the equivalent optical medium. - Highlights: • Optical analogue to the static anisotropic spacetime metric obeying rotational symmetries is studied. • Explicit expressions for the permittivity and permeability tensors are obtained. • Explicit expression for the optical Hamiltonian is found. • Ray paths are compared with full-wave simulations for the Schwarzschild metric in anisotropic and isotropic cases.

  3. Insulin analogues display atypical differentiative activities in skin keratinocytes.

    Science.gov (United States)

    Solomon Zemler, Ravid; Weingarten, Galina; Sarfstein, Rive; Laron, Zvi; Werner, Haim; Wertheimer, Efrat

    2015-02-01

    We have previously shown that both insulin and IGF1 lead to increased proliferation of keratinocytes. However, whereas insulin supports keratinocytes differentiation, IGF1 inhibits this process. The aim of the present study was to examine the proliferative and differentiative effects of insulin analogues (glargine, detemir, lispro and aspart) in primary keratinocytes in comparison with insulin and IGF1. Primary keratinocytes cultures were produced from newborn BALB/c mice skin. Proliferation rates were assessed by [(3)H]-thymidine incorporation and XTT assays and differentiation was evaluated by Western blots analysis. Insulin receptor and IGF1 receptor phosphorylation was assessed by immunoprecipitation assays. Treatment with glargine or detemir resulted in an insulin-like effect on the differentiation process whereas lispro and aspart treatment led to an IGF1-like effect. In addition, treatment of keratinocytes with aspart led to a rapid phosphorylation of the IGF1 receptor. Our study provides evidence that insulin analogues elicit atypical actions in the skin.

  4. Liquid Crystal Analogue of Abrikosov Vortex Flow in Superconductors

    CERN Document Server

    Tanaka, A; Hayakawa, R

    1996-01-01

    We extend the correspondence between the Renn-Lubensky Twist-Grain-Boundary-A phase in chiral liquid crystals and the Abrikosov mixed state in superconductors to dynamical aspects. We find that for a TGB sample with free boundaries, an external electric field applied along the helical axis induces a uniform translational motion of the grain boundary system - an analogue of the well-known mixed state flux flow. Likewise, an analogue of the mixed state Nernst effect is found. In much the same way in which the flux flow carries intercore electric fields generating Joule heat in an otherwise dissipation-free system, the grain boundary flow carries along polarized charges, resulting in a finite electric conductivity in a ferroelectric.

  5. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  6. Tunneling approach and thermality in dispersive models of analogue gravity

    CERN Document Server

    Belgiorno, F; Piazza, F Dalla

    2014-01-01

    We set up a tunneling approach to the analogue Hawking effect in the case of models of analogue gravity which are affected by dispersive effects. An effective Schroedinger-like equation for the basic scattering phenomenon IN->P+N*, where IN is the incident mode, P is the positive norm reflected mode, and N* is the negative norm one, signalling particle creation, is derived, aimed to an approximate description of the phenomenon. Horizons and barrier penetration play manifestly a key-role in giving rise to pair-creation. The non-dispersive limit is also correctly recovered. Drawbacks of the model are also pointed out and a possible solution ad hoc is suggested.

  7. Modelling a river catchment using an electrical circuit analogue

    Directory of Open Access Journals (Sweden)

    C. G. Collier

    1998-01-01

    Full Text Available An electrical circuit analogue of a river catchment is described from which is derived an hydrological model of river flow called the River Electrical Water Analogue Research and Development (REWARD model. The model is based upon an analytic solution to the equation governing the flow of electricity in an inductance-capacitance-resistance (LCR circuit. An interpretation of L, C and R in terms of catchment parameters and physical processes is proposed, and tested for the River Irwell catchment in northwest England. Hydrograph characteristics evaluated using the model are compared with observed hydrographs, confirming that the modelling approach does provide a reliable framework within which to investigate the impact of variations in model input data.

  8. Analogue Wormholes and Black Hole LASER Effect in Hydrodynamics

    CERN Document Server

    Peloquin, Cédric; Philbin, Thomas; Rousseaux, Germain

    2015-01-01

    We numerically study water wave packets on a spatially varying counter-current in the presence of surface tension. Depending on the details of the velocity profile, we show that traversable and bi-directional analogue wormholes exist in fluid mechanics. The limitations on traversability of wormholes in general relativity are absent here because of the dispersion of water waves and the ability to form flow profiles that are not solutions of Einstein's equations. We observe that negative energy can be trapped between analogue horizons forming a LASER-like cavity. Six horizons are involved in the trapping cavity because of the existence of two dispersive scales, in contrast to previous treatments which considered two horizons and one dispersive scale.

  9. Retro-1 Analogues Differentially Affect Oligonucleotide Delivery and Toxin Trafficking.

    Science.gov (United States)

    Yang, Bing; Ming, Xin; Abdelkafi, Hajer; Pons, Valerie; Michau, Aurelien; Gillet, Daniel; Cintrat, Jean-Christophe; Barbier, Julien; Juliano, Rudy

    2016-11-21

    Retro-1 is a small molecule that displays two important biological activities: First, it blocks the actions of certain toxins by altering their intracellular trafficking. Second, it enhances the activity of oligonucleotides by releasing them from entrapment in endosomes. This raises the question of whether the two actions involve the same cellular target. Herein we report the effects of several Retro-1 analogues on both toxins and oligonucleotides. We found analogues that affect toxins but not oligonucleotides and vice-versa, while Retro-1 is the only compound that affects both. This indicates that the molecular target(s) involved in the two processes are distinct. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Neutral Diboron Analogues of Archetypal Aromatic Species by Spontaneous Cycloaddition.

    Science.gov (United States)

    Arrowsmith, Merle; Böhnke, Julian; Braunschweig, Holger; Celik, Mehmet Ali; Claes, Christina; Ewing, William C; Krummenacher, Ivo; Lubitz, Katharina; Schneider, Christoph

    2016-09-05

    Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaromatic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron-boron multiple bonds under ambient conditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6 π-aromatic diborabenzene compound, a 2 π-aromatic triplet biradical 1,3-diborete, and a phosphine-stabilized 2 π-homoaromatic 1,3-dihydro-1,3-diborete. DFT calculations suggest that all three compounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C6 H6 and C4 H4 (2+) , and homoaromatic C4 H5 (+) .

  11. Basic entwinements: unassuming analogue inserts in basic digital modeling (courses)

    DEFF Research Database (Denmark)

    Wiesner, Thomas

    2012-01-01

    to diverse inter-active discussions and a more conscious re-plays of material transcending the dichotomies of digital/analogue. Keywords Simple didactics, analogue sketching, cognitive space awareness, digital modelling, bachelor first year, morphology of body and space, pataphysics...... between the various intentions and the student’s actual grasp of the many basic architectural element’s interplays of form and space can become apparent. To alleviate, calibrate and cognitively fine-tune the potential for more acute and lasting cognitive understandings of (scaled) body and space...... of options for speedily produced material for various attuned and conscious, supplementary oblique architectural assessments. The simple procedure(s) advance a certain amount of beneficial cognitive complementarities: Beneficial interplay-changes between right and left brain concentrations; Change...

  12. Matrices with restricted entries and q-analogues of permutations

    CERN Document Server

    Lewis, Joel Brewster; Morales, Alejandro H; Panova, Greta; Sam, Steven V; Zhang, Yan

    2010-01-01

    We study the functions that count matrices of given rank over a finite field with specified positions equal to zero. We show that these matrices are $q$-analogues of permutations with certain restricted values. We obtain a simple closed formula for the number of invertible matrices with zero diagonal, a $q$-analogue of derangements, and a curious relationship between invertible skew-symmetric matrices and invertible symmetric matrices with zero diagonal. In addition, we provide recursions to enumerate matrices and symmetric matrices with zero diagonal by rank, and we frame some of our results in the context of Lie theory. Finally, we provide a brief exposition of polynomiality results for enumeration questions related to those mentioned, and give several open questions.

  13. Stark absorption spectroscopy of peridinin and allene-modified analogues

    Energy Technology Data Exchange (ETDEWEB)

    Kusumoto, Toshiyuki; Horibe, Tomoko [Department of Physics and CREST-JST, Graduated School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kajikawa, Takayuki; Hasegawa, Shinji [Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Gakuen 2-1, Sanda, Hyogo 669-1337 (Japan); Iwashita, Takashi [Suntory Institute for Bioorganic Research, Wakayamadai 1-1-1, Shimamoto, Mishimagunn, Osaka 618-8503 (Japan); Cogdell, Richard J. [Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8QQ, Scotland (United Kingdom); Birge, Robert R.; Frank, Harry A. [Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060 (United States); Katsumura, Shigeo [Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Gakuen 2-1, Sanda, Hyogo 669-1337 (Japan); Hashimoto, Hideki, E-mail: hassy@sci.osaka-cu.ac.jp [Department of Physics and CREST-JST, Graduated School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan)

    2010-07-19

    Stark absorption spectra of peridinin (Per) and five allene-modified analogues and their angular dependence as a function of an externally applied electric field were measured in methyl methacrylate polymer at 77 K. In all cases, the energetically lowest absorption band has a significant change of static dipole-moment upon photoexcitation ({Delta}{mu}). In particular, Per has the largest value of |{Delta}{mu}|. The angles between {Delta}{mu} and the transition dipole-moment of all the analogues were determined. It is suggested that the allene group in Per plays a key role as the electron donor in the charge transfer process following photoexcitation. The results of MNDO-PSDCI calculations support this idea.

  14. Establishment of antenna membrane states FEM on analogue method

    Institute of Scientific and Technical Information of China (English)

    JIANG Wen-hui; CAO Xi-bin; ZHAO Yang

    2008-01-01

    On the basis of choosing the basic element as the bar and choosing the basic mesh as the triangle as well as supposing the conditions of the element,the membrane states of an antenna reflector were researched by the analogue method,because the membrane effect Was not omitted during the ending deployment process of the radial rib antenna.The expressions of the bar element's section area and density were obtained.while the expression of the stress state during the ending deployment process of antenna was attained.During the establishment process of the analogue method,the analysis method of the net shell structure was employed.Moreover,during the backward deduction of membrane stress,the continuation method Was adopted.Because the expression of the membrane stress state can realize the analysis on the antenna membrane state.this research has great significance of theoretical direction to the normal operation of the space deployable antenna.

  15. Geoscience in Support of a Mars Methane Analogue Mission

    Science.gov (United States)

    Boivin, Alexandre

    The Mars Methane Analogue Mission, funded by the Canadian Space Agency through its Analogue Missions program, simulates a Mars rover mission whose purpose is to detect, analyse, and determine the source of methane emissions on the planet's surface. As part of this project, both an electromagnetic induction sounder (EMIS) and a high-resolution triangulation-based 3D laser scanner were tested in the field to demonstrate the benefit of including these instruments on future rover missions. EMIS data was inverted in order to derive information on the conductivity and magnetic susceptibility of the near subsurface. 3D laser scanner data was processed with fracture detection as a goal in order to simplify the search for areas of potential methane seepage. Both instruments were found to be very valuable for future rover missions of this type.

  16. Some fluorescence properties of dimethylaminochalcone and its novel cyclic analogues

    Science.gov (United States)

    Tomečková, Vladimíra; Poškrobová, Martina; Štefanišinová, Miroslava; Perjési, Pál

    2009-12-01

    This paper demonstrates the basic character (polarity, solubility, colour, absorption and fluorescence quantum yield) of synthetic dimethylaminochalcone ( 1) and its cyclic analogues measured in toluene, chloroform, dimethylsulfoxide and ethanol, which have been studied by absorption and fluorescence spectroscopy. The biologically active dye 4'-dimethylaminochalcone ( 1b) and its less flexible analogues 4-dimethylaminoindanone ( 2b), -tetralone ( 3b), and -benzosuberone ( 4b) are lipophilic molecules that displayed the best solubility in toluene and chloroform. The highest fluorescence and quantum yields of compounds 1 and 2 have been obtained in DMSO and chloroform. Quenching effect of fluorescence compounds ( 1- 4) has been studied in the mixture of the most polar organic solvents DMSO and water. In the presence of water, fluorescence of compound 1 has been quenched the best from all studied chalcones and emission maxima of molecules 1- 4 have been shifted to the longer wavelengths. Quenching effect of fluorescence by water was in order 1 > 2 > 3 > 4.

  17. (18)F-labelled metomidate analogues as adrenocortical imaging agents.

    Science.gov (United States)

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Långström, Bengt

    2009-05-01

    Two- and one-step syntheses of (18)F-labelled analogues of metomidate, such as 2-[(18)F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[(18)F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[(18)F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[(18)F]fluoroethyl 4-methylbenzenesulfonate or 3-[(18)F]fluoropropyl 4-methylbenzenesulfonate. These were used as (18)F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46+/-3% and 79+/-30%, respectively. Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  18. Analogue Square Root Calculator Circuit Designed With Logarithmic Amplifiers

    OpenAIRE

    2016-01-01

    In many applications, it has been necessary to calculate square roots of some numbers which are correspond to some voltages values. In this study such an analogue calculator has been designed and simulated in computer medium. Circuit consist of one logarithmic and one antilogarithmic amplifier connected in cascade. The component values of circuit chosen so that the output voltage of circuit is equal to square root of input voltage. The performance of designed circuit is investigated by applyi...

  19. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues

    OpenAIRE

    Monika Stompor; Barbara Żarowska

    2016-01-01

    The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group—...

  20. Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

    Directory of Open Access Journals (Sweden)

    Pitak Nasomjai

    2009-07-01

    Full Text Available The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the α- and β-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each α-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya.

  1. Synthesis of phosphonate and phostone analogues of ribose-1-phosphates.

    Science.gov (United States)

    Nasomjai, Pitak; O'Hagan, David; Slawin, Alexandra M Z

    2009-07-27

    The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the alpha- and beta-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each alpha-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya.

  2. Projected Future Climate Analogues and Climate "Velocities" in North America

    Science.gov (United States)

    Shafer, S. L.; Bartlein, P. J.

    2014-12-01

    Future climate changes may have significant effects on many North American ecosystems. One way of assessing the potential impacts of future climate change is to use future climate analogues of present climate to evaluate the spatial extent and rates of future climate change. We used a set of Coupled Model Intercomparison Project phase 5 (CMIP5) coupled atmosphere-ocean general circulation model (AOGCM) future climate simulations (2006-2100) produced under representative concentration pathway scenario RCP8.5. We regridded these data to a 10-km equal-area grid of North America. Modern climate data (1961-1990 30-year mean) were interpolated to the same 10-km grid. The projected future climate data were analyzed using 10-year mean values of monthly and seasonal temperature and precipitation and a set of derived annual bioclimatic variables (e.g., growing degree days) considered to be ecologically significant. Potential future climate analogues were calculated for each grid cell using Euclidean distances to identify similar climates occurring elsewhere in North America. We identify regions that are projected to retain climates similar to present in the future (e.g., parts of the southeastern United States) and regions where present climates are projected to become less common or to disappear in the future (e.g., high elevation sites in western North America). We also calculate the rates of change in locations of similar climates (i.e., climate analogue velocities) and compare our results with simulated paleoclimate velocities over the past 22 kyr (from TraCE-21ka transient climate simulations for 22 ka-present). We discuss the implications of these results for conservation and natural resource management in North America. We also describe a web application being developed to allow researchers, decision makers, and members of the public, to visualize, explore, and use the climate analogue data.

  3. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...... including MSNT-mediated esterification of both support-bound alcohols and carboxylic acids has been implemented successfully. Copyright (C) 1996 Elsevier Science Ltd....

  4. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...... including MSNT-mediated esterification of both support-bound alcohols and carboxylic acids has been implemented successfully. Copyright (C) 1996 Elsevier Science Ltd....

  5. Differential membrane fluidization by active and inactive cannabinoid analogues.

    Science.gov (United States)

    Mavromoustakos, T; Papahatjis, D; Laggner, P

    2001-06-06

    The effects of the two cannabinomimetic drugs (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl-2-(hexyl)-1,3-dithiolane (AMG-3) and its pharmacologically less active 1-methoxy analogue (AMG-18) on the thermotropic and structural properties of dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) liposomes have been studied by X-ray diffraction and differential scanning calorimetry (DSC). DSC data revealed that the incorporation of the drugs affect differently the thermotropic properties of DPPC. The presence of the more active drug distinctly broadened and attenuated both the pretransition and main phase transition of DPPC bilayers, while the inactive analogue had only minor effects. Small and wide angle X-ray diffraction data showed that the two cannabinoids have different effects on the lipid phase structures and on the hydrocarbon chain packing. The pharmacologically active analogue, AMG-3, was found to efficiently fluidize domains of the lipids in the L(beta)' gel phase, and to perturb the regular multibilayer lattice. In the liquid crystalline L(alpha) phase, AMG-3 was also found to cause irregularities in packing, suggesting that the drug induces local curvature. At the same concentration, the inactive AMG-18 had only minor structural effects on the lipids. At about 10-fold or higher concentrations, AMG-18 was found to produce similar but still less pronounced effects in comparison to those observed by AMG-3. The dose-dependent, different thermotropic and structural effects by the two cannabinoid analogues suggest that these may be related to their biological activity.

  6. Ungeremine and Its hemisynthesized analogues as bactericides against Flavobacterium columnare.

    Science.gov (United States)

    Schrader, Kevin K; Avolio, Fabiana; Andolfi, Anna; Cimmino, Alessio; Evidente, Antonio

    2013-02-13

    The Gram-negative bacterium Flavobacterium columnare is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine.

  7. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  8. Sums of multiplicative characters analogue of Kloosterman sums

    CERN Document Server

    Xi, Ping

    2010-01-01

    Let $q$ be a positive integer, $\\chi$ a nontrivial character mod $q$. In this paper the authors prove some estimates for the character sum which is analogue of incomplete Kloostermann sums\\[\\sum_{\\substack{a\\in\\mathcal{I}\\\\ \\gcd(a,q)=1}}\\chi(ma+n\\overline{a}),\\] where $\\overline{a}$ is the multiplicative inverse of $a\\bmod q$, and $\\mathcal{I}$ is a subinterval of $[x+1,x+q]$ for certain integer $x.$

  9. Active postoperative acromegaly: sustained remission after discontinuation of somatostatin analogues

    Science.gov (United States)

    Cardenas-Salas, Jersy

    2016-01-01

    Summary In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH) and insulin-like growth factor (IGF1) levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status). The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission. Learning points: The probability of disease recurrence is high after discontinuation of treatment with somatostatin analogues. Current data indicate that remission after treatment discontinuation may be more likely in patients with low GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on MRI, and/or in patients receiving prolonged treatment. This case report suggests that prolonged treatment with somatostatin analogues can be curative in carefully selected patients. PMID:27933171

  10. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  11. Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-02

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively.

  12. 3D-QSAR Studies of Dimethoxyphenoxyphenoxy pyrimidines and Analogues

    Institute of Scientific and Technical Information of China (English)

    李爱秀; 王瑾玲; 苏华庆; 缪方明

    2000-01-01

    Three-dimensional quantitative structure-activity relationships (3DQSAR) of a series of dimethoxyphenoxyphenoxypyrimidines and analogues which are known to be photosystem Ⅱ (PS Ⅱ )inhibitors have been studied using comparative molecular field analysis (CoMFA) method. The results suggest that the steric and electronic properties of substitutes at m-position on the end phenyl ring have important influence on the Hill reaction inhibition.

  13. Do film soundtracks contain nonlinear analogues to influence emotion?

    OpenAIRE

    Daniel T. Blumstein; Davitian, Richard; Kaye, Peter D.

    2010-01-01

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly rega...

  14. Dimerization and DNA recognition rules of mithramycin and its analogues.

    Science.gov (United States)

    Weidenbach, Stevi; Hou, Caixia; Chen, Jhong-Min; Tsodikov, Oleg V; Rohr, Jürgen

    2016-03-01

    The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me(2+))-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incompletely understood. Towards this goal, we quantitatively investigated dimerization of MTM and several of its analogues, MTM SDK (for Short side chain, DiKeto), MTM SA-Trp (for Short side chain and Acid), MTM SA-Ala, and a biosynthetic precursor premithramycin B (PreMTM B), and measured the binding affinities of these molecules to DNA oligomers of different sequences and structural forms at physiological salt concentrations. We show that MTM and its analogues form stable dimers even in the absence of DNA. All molecules, except for PreMTM B, can bind DNA with the following rank order of affinities (strong to weak): MTM=MTM SDK>MTM SA-Trp>MTM SA-Ala. An X(G/C)(G/C)X motif, where X is any base, is necessary and sufficient for MTM binding to DNA, without a strong dependence on DNA conformation. These recognition rules will aid in mapping MTM sites across different promoters towards development of MTM analogues as useful anticancer agents.

  15. Matrix diffusion model. In situ tests using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rasilainen, K. [VTT Energy, Espoo (Finland)

    1997-11-01

    Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories. 98 refs. The thesis includes also eight previous publications by author.

  16. Sex steroids and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Carolyn A Allan

    2014-04-01

    Full Text Available Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

  17. Why control blood glucose levels?

    Science.gov (United States)

    Rossini, A A

    1976-03-01

    The controversy as to the relationship between the degree of control of diabetes and the progression of the complications of the disease has not been solved. However, in this review, various studies suggesting a relationship between the metabolic abnormality and the diabetic complications are examined. The disadvantages of the uncontrolled diabetes mellitus can be divided into two major categories-short-term and long-term. The short-term disadvantages of controlled diabetes mellitus include the following: (1) ketoacidosis and hyperosmolar coma; (2) intracellular dehydration; (3) electrolyte imbalance; (4) decreased phagocytosis; (5) immunologic and lymphocyte activity; (6) impairment of wound healing; and (7) abnormality of lipids. The long-term disadvantages of uncontrolled diabetes melitus include the following: (1) nephropathy; (2) neuropathy; (3) retinopathy; (4) cataract formation; (5) effect on perinatal mortality; (6) complications of vascular disease; and (7) the evaluation of various clinical studies suggesting the relationship of elevated blood glucose levels and complications of diabetes mellitus. It is suggested that until the question of control can absolutely be resolved, the recommendation is that the blood glucose levels should be controlled as close to the normal as possible.

  18. Spin Alignment in Analogues of The Local Sheet

    Science.gov (United States)

    Conidis, George J.

    2016-10-01

    Tidal torque theory and simulations of large scale structure predict spin vectors of massive galaxies should be coplanar with sheets in the cosmic web. Recently demonstrated, the giants (K s Torque Theory. However, the giants in the Local Sheet encircling the Local Group display a distinctly different arrangement, suggesting that the mass asymmetry of the Local Group or its progenitor torqued them from their primordial spin directions. To investigate the origin of the spin alignment of giants locally, analogues of the Local Sheet were identified in the SDSS DR9. Similar to the Local Sheet, analogues have an interacting pair of disk galaxies isolated from the remaining sheet members. Modified sheets in which there is no interacting pair of disk galaxies were identified as a control sample. Galaxies in face-on control sheets do not display axis ratios predominantly weighted toward low values, contrary to the expectation of tidal torque theory. For face-on and edge-on sheets, the distribution of axis ratios for galaxies in analogues is distinct from that in controls with a confidence of 97.6% & 96.9%, respectively. This corroborates the hypothesis that an interacting pair can affect spin directions of neighbouring galaxies.

  19. Natural analogue studies as supplements to biomineralization research

    Energy Technology Data Exchange (ETDEWEB)

    McNeil, M.B. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu{sub 4}SO{sub 4}(OH){sub 6{center_dot}}H{sub 2}O] and mineral morphologies unusual in corrosion [malachite, Cu{sub 2}CO{sub 3}(OH){sub 2}, rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena].

  20. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G. Saulnier and W. Statham

    2006-04-16

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

  1. Simulated Milky Way analogues: implications for dark matter direct searches

    CERN Document Server

    Bozorgnia, Nassim; Schaller, Matthieu; Lovell, Mark; Bertone, Gianfranco; Frenk, Carlos S; Crain, Robert A; Navarro, Julio F; Schaye, Joop; Theuns, Tom

    2016-01-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation curve and total stellar mass. We then extract the dark matter density and velocity distribution in the Solar neighbourhood for this set of Milky Way analogues, and use them to analyse the results of current direct detection experiments. For most Milky Way analogues, the event rates in direct detection experiments obtained from the best fit Maxwellian distribution (with peak speed of 223 - 289 km/s) are similar to those obtained directly from the simulations. As a consequence, the allowed regions and exclusion limits set by direct detection experiments in the dark matter mass and spin-independent cross section plane shift by a few GeV compared to the Standard Halo Model, at low dark matter masses. For each dark matter...

  2. Four-quadrant analogue multiplier using operational amplifier

    Science.gov (United States)

    Riewruja, Vanchai; Rerkratn, Apinai

    2011-04-01

    A method to realise a four-quadrant analogue multiplier using general-purpose operational amplifiers (opamps) as only the active elements is described in this article. The realisation method is based on the quarter-square technique, which utilises the inherent square-law characteristic of class AB output stage of the opamp. The multiplier can be achieved from the proposed structure with using either bipolar or complementary metal-oxide-semiconductor (CMOS) opamps. The operation principle of the proposed multiplier has been confirmed by PSPICE analogue simulation program. Simulation results reveal that the principle of proposed scheme provides an adequate performance for a four-quadrant analogue multiplier. Experimental implementations of the proposed multiplier using bipolar and CMOS opamps are performed to verify the circuit performances. Measured results of the experimental proposed schemes based on the use of bipolar and CMOS opamps with supply voltage ±2.4 V show the worst-case relative errors of 0.32% and 0.47%, and the total harmonic distortions of 0.47% and 0.98%, respectively.

  3. Design and synthesis of biotin analogues reversibly binding with streptavidin.

    Science.gov (United States)

    Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

    2015-04-01

    Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin.

  4. The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression.

    Science.gov (United States)

    Ferronato, María Julia; Alonso, Eliana Noelia; Gandini, Norberto Ariel; Fermento, María Eugenia; Villegas, María Emilia; Quevedo, Mario Alfredo; Arévalo, Julián; López Romero, Alejandro; Rivadulla, Marcos Lois; Gómez, Generosa; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2016-10-01

    Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease.

  5. Antimicrobial evaluation of mangiferin and its synthesized analogues

    Institute of Scientific and Technical Information of China (English)

    Shashi Kant Singh; Rupali M Tiwari; Saurabh K Sinha; Chhanda C Danta; Satyendra K Prasad

    2012-01-01

    Objective: To isolate the mangiferin from Mangifera indica (M. indica) and assess the antimicrobial activity of different analogues synthesized from mangiferin. Methods: Mangiferin was isolated by column chromatography from the ethanolic extract of stem bark of M. indica. Mangiferin was further converted to 5-(N-phenylamino methyleno) mangiferin, 5-(N-p-chlorophenylamino methyleno) mangiferin, 5-(N-2-methyl phenylamino methyleno) mangiferin, 5-(N-p-methoxy phenylamino methyleno) mangiferin, 5-(N, N-diphenylamino methyleno) mangiferin, 5-(N-α-napthylamino methyleno) mangiferin and 5-(N-4-methyl phenylamino methyleno) mangiferin. Mangiferin and its analogues were characterized by melting point and Rf value determination and through spectral technique like UV, IR, and NMR spectral analysis. The antimicrobial effect of mangiferin and its derivatives was studied according to the disc diffusion method. Results: The solutions of mangiferin and its derivatives in polyethylene glycol-400 showed an activity with regard to four bacterial species-Bacillus pumilus (B. pumilus), Bacillus cereus (B. cereus) and Salmonella virchow (S. virchow) and two fungal species-Thermoascus (T. aurantiacus) and Aspergillus flavus (A. flavus). Conclusion: The present study aurantiacus confirms the antimicrobial activity of different analogues of mangiferin which could be further processed for the development of a potential antimicrobial agent.

  6. Do film soundtracks contain nonlinear analogues to influence emotion?

    Science.gov (United States)

    Blumstein, Daniel T; Davitian, Richard; Kaye, Peter D

    2010-12-23

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly regarded films to generate a set of highly ranked action/adventure, dramatic, horror and war films. We then scored the presence of a variety of nonlinear analogues in these film soundtracks. Dramatic films suppressed noise of all types, contained more abrupt frequency transitions and musical sidebands, and fewer noisy screams than expected. Horror films suppressed abrupt frequency transitions and musical sidebands, but had more non-musical sidebands, and noisy screams than expected. Adventure films had more male screams than expected. Together, our results suggest that film-makers manipulate sounds to create nonlinear analogues in order to manipulate our emotional responses.

  7. Continuous Glucose Monitoring Systems: A Review

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar Vashist

    2013-10-01

    Full Text Available There have been continuous advances in the field of glucose monitoring during the last four decades, which have led to the development of highly evolved blood glucose meters, non-invasive glucose monitoring (NGM devices and continuous glucose monitoring systems (CGMS. Glucose monitoring is an integral part of diabetes management, and the maintenance of physiological blood glucose concentration is the only way for a diabetic to avoid life-threatening diabetic complications. CGMS have led to tremendous improvements in diabetic management, as shown by the significant lowering of glycated hemoglobin (HbA1c in adults with type I diabetes. Most of the CGMS have been minimally-invasive, although the more recent ones are based on NGM techniques. This manuscript reviews the advances in CGMS for diabetes management along with the future prospects and the challenges involved.

  8. Application of Semipermeable Membranes in Glucose Biosensing

    Directory of Open Access Journals (Sweden)

    Tanmay Kulkarni

    2016-12-01

    Full Text Available Glucose biosensors have received significant attention in recent years due to the escalating mortality rate of diabetes mellitus. Although there is currently no cure for diabetes mellitus, individuals living with diabetes can lead a normal life by maintaining tight control of their blood glucose levels using glucose biosensors (e.g., glucometers. Current research in the field is focused on the optimization and improvement in the performance of glucose biosensors by employing a variety of glucose selective enzymes, mediators and semipermeable membranes to improve the electron transfer between the active center of the enzyme and the electrode substrate. Herein, we summarize the different semipermeable membranes used in the fabrication of the glucose biosensor, that result in improved biosensor sensitivity, selectivity, dynamic range, response time and stability.

  9. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue

    Science.gov (United States)

    Lee, Hyun Chul; Kim, Su-Jin; Kim, Kyung-Sup; Shin, Hang-Cheol; Yoon, Ji-Won

    2000-11-01

    A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

  10. Lactate-glucose interrelations, glucose recycling and the Cori cycle in normal fed rats.

    Science.gov (United States)

    Freminet, A; Poyart, C

    1975-12-19

    1. Turnover and oxidation rates of glucose and lactate were determined using a priming dose-continuous infusion of 14C-(u)-glucose and 14C-(U)-lactate in anesthetized and mechanically ventilated non-fasted rats. The rates of glucose-lactate interconversions were computed from the two-compartment model of Depocas and De Freitas (1970). The rate of total glucose recycling is known as the difference between the rate of true glucose turnover measured with 3H-(2)-glucose (RGT) and the rate of apparent glucose turnover measured with 14C-glucose (RG). This value was compared with the Cori cycle. 2. In normal conditions 17% of RG come from lactate, 43% are directed to lactate and 49% are oxidized. 3. 71% of the rate of lactate turnover come from glucose, 28% are directed to glucose and 51% are oxidized. 4. The rate of total glucose recycling (RGT-RG) is 3.7 mg - mn(-1) per kg0.75 and represents 60% of RG or 38% of RGT. 5. The Cori cycle is 0.8 - 1.2 mg - mn(-1) per kg0.75 and represents 8 - 20% of the rate of glucose turnover and 20 - 32% of total glucose recycling.

  11. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, H; Richter, E A

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  12. Glucose metabolism in rat retinal pigment epithelium.

    Science.gov (United States)

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress.

  13. Glucose Transporters in Cardiac Metabolism and Hypertrophy

    Science.gov (United States)

    Shao, Dan; Tian, Rong

    2016-01-01

    The heart is adapted to utilize all classes of substrates to meet the high-energy demand, and it tightly regulates its substrate utilization in response to environmental changes. Although fatty acids are known as the predominant fuel for the adult heart at resting stage, the heart switches its substrate preference toward glucose during stress conditions such as ischemia and pathological hypertrophy. Notably, increasing evidence suggests that the loss of metabolic flexibility associated with increased reliance on glucose utilization contribute to the development of cardiac dysfunction. The changes in glucose metabolism in hypertrophied hearts include altered glucose transport and increased glycolysis. Despite the role of glucose as an energy source, changes in other nonenergy producing pathways related to glucose metabolism, such as hexosamine biosynthetic pathway and pentose phosphate pathway, are also observed in the diseased hearts. This article summarizes the current knowledge regarding the regulation of glucose transporter expression and translocation in the heart during physiological and pathological conditions. It also discusses the signaling mechanisms governing glucose uptake in cardiomyocytes, as well as the changes of cardiac glucose metabolism under disease conditions. PMID:26756635

  14. Enzyme Analysis to Determine Glucose Content

    Science.gov (United States)

    Carpenter, Charles; Ward, Robert E.

    Enzyme analysis is used for many purposes in food science and technology. Enzyme activity is used to indicate adequate processing, to assess enzyme preparations, and to measure constituents of foods that are enzyme substrates. In this experiment, the glucose content of corn syrup solids is determined using the enzymes, glucose oxidase and peroxidase. Glucose oxidase catalyzes the oxidation of glucose to form hydrogen peroxide (H2O2), which then reacts with a dye in the presence of peroxidase to give a stable colored product.

  15. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

  16. Past and present of analogue modelling, and its future trend

    Science.gov (United States)

    Koyi, Hemin

    2015-04-01

    Since Hull (1815) published his article on modelling, analogue modelling has expanded to simulate both a wider range of tectonic regimes and target more challenging set-ups, and has become an integrated part of the fields of tectonics and structural geology. Establishment of new laboratories testifies for the increased attention the technique receives. The ties between modellers and field geoscientists have become stronger with the focus being on understanding the parameters that govern the evolution of a tectonic regime and the processes that dominate it. Since the first sand castle was built with damp sand on a beach, sand has proven to be an appropriate material analogue. Even though granular materials is the most widely used analogue material, new materials are also (re)introduced as rock analogues. Emphasis has been on more precise measurements of the mechanical properties of the materials and on minimizing the preparation effects, which have a great impact on scaling, interpretations and benchmarking. The analytical technique used to quantify model results has also seen a great deal of improvement. In addition to X-ray tomography used to visualise internal structures of models, new techniques (e.g. PIV, high-resolution laser scanning, and interferometry) have enabled monitoring kinematics with a higher precision. Benchmarking exercises have given modelling an additional checking tool by outlining, in addition to the rheology of the modelling materials, the impact of different preparation approaches, the effect of boundary conditions, and the human factor on model results. However, despite the different approaches and deformation rigs, results of models of different tectonic laboratories have shown a great deal of similarities. Even with the introduction of more sophisticated numerical codes and usage of more powerful computers which enable the simulation of more challenging material properties and combinations of those, and 3D model set-up, analogue modelling

  17. Mechanical behaviour of granular materials used in analogue modelling: insights from grain characterisation, ring-shear tests and analogue experiments

    Science.gov (United States)

    Panien, Marion; Schreurs, Guido; Pfiffner, Adrian

    2006-09-01

    The mechanical behaviour of several dry granular materials is investigated through ring-shear tests, grain characterisation, and simple analogue experiments analysed by X-ray computed tomography. An improved knowledge of granular materials is essential to determine their suitability as analogues for upper crustal rocks in experimental models and to compare analogue and numerical experiments. The ring-shear tests show that the granular materials have an elastic/frictional plastic behaviour with strain-hardening preceding failure at peak strength, followed by strain softening until a dynamic-stable value is reached. This is similar to the behaviour exhibited by experimentally deformed rocks. The physical characteristics of the grains determine the amount of diffuse deformation before failure, the percentage of strain softening and act on the thickness of the shear zones before broadening. Initial shear zone width in extensional and contractional experiments is between 11 and 16 times the mean grain size. The angle of internal friction defining one of the mechanical properties of granular materials and thus fault dip is not only related to physical characteristics of the grains and to the handling technique used (e.g. sieving or pouring), but also to the overburden and to the experimental setup used.

  18. Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor

    DEFF Research Database (Denmark)

    Murphy, R; Tura, A; Clark, P M

    2008-01-01

    AIMS/HYPOTHESIS: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP) are released from intestinal endocrine cells in response to luminal glucose. Glucokinase is present in these cells and has been proposed as a glucose sensor. The physiological...... role of glucokinase can be tested using individuals with heterozygous glucokinase gene (GCK) mutations. If glucokinase is the gut glucose sensor, GLP-1 and GIP secretion during a 75 g OGTT would be lower in GCK mutation carriers compared with controls. METHODS: We compared GLP-1 and GIP concentrations....../INTERPRETATION: Glucokinase, the major pancreatic glucose sensor, is not the main gut glucose sensor. By modelling OGTT data in GCK mutation carriers we were able to distinguish a specific beta cell glucose-sensing defect. Our data suggest a reduction in potentiation of insulin secretion by glucose that is independent...

  19. Impact of Glucose Tolerance Status, Sex, and Body Size on Glucose Absorption Patterns During OGTTs

    DEFF Research Database (Denmark)

    Faerch, K.; Pacini, G.; Nolan, J. J.;

    2013-01-01

    OBJECTIVEWe studied whether patterns of glucose absorption during oral glucose tolerance tests (OGTTs) were abnormal in individuals with impaired glucose regulation and whether they were related to sex and body size (height and fat-free mass). We also examined how well differences in insulin......), isolated impaired fasting glucose (i-IFG), or isolated impaired glucose tolerance (i-IGT). Insulin sensitivity and -cell function were measured with the euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance tests, respectively. Surrogate markers of both conditions were calculated from OGTTs...... size were taken into account (P > 0.28). Faster glucose absorption was related to higher fasting (P = 0.001) and lower 2-h (P = 0.001) glucose levels and to greater height and fat-free mass (P

  20. A tale of two compartments: interstitial versus blood glucose monitoring.

    Science.gov (United States)

    Cengiz, Eda; Tamborlane, William V

    2009-06-01

    Self-monitoring of blood glucose was described as one of the most important advancements in diabetes management since the invention of insulin in 1920. Recent advances in glucose sensor technology for measuring interstitial glucose concentrations have challenged the dominance of glucose meters in diabetes management, while raising questions about the relationships between interstitial and blood glucose levels. This article will review the differences between interstitial and blood glucose and some of the challenges in measuring interstitial glucose levels accurately.

  1. Glucose control in critical care

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Glycemic control among critically-ill patients has beena topic of considerable attention for the past 15 years.An initial focus on the potentially deleterious effects ofhyperglycemia led to a series of investigations regardingintensive insulin therapy strategies that targeted tightglycemic control. As knowledge accumulated, the pursuitof tight glycemic control among critically-ill patients cameto be seen as counterproductive, and moderate glycemiccontrol came to dominate as the standard practice inintensive care units. In recent years, there has beenincreased focus on the importance of hypoglycemicepisodes, glycemic variability, and premorbid diabeticstatus as factors that contribute to outcomes amongcritically-ill patients. This review provides a survey ofkey studies on glucose control in critical care, and aimsto deliver perspective regarding glycemic managementamong critically-ill patients.

  2. Thermoinactivation Mechanism of Glucose Isomerase

    Science.gov (United States)

    Lim, Leng Hong; Saville, Bradley A.

    In this article, the mechanisms of thermoinactivation of glucose isomerase (GI) from Streptomyces rubiginosus (in soluble and immobilized forms) were investigated, particularly the contributions of thiol oxidation of the enzyme's cysteine residue and a "Maillard-like" reaction between the enzyme and sugars in high fructose corn syrup (HFCS). Soluble GI (SGI) was successfully immobilized on silica gel (13.5 μm particle size), with an activity yield between 20 and 40%. The immobilized GI (IGI) has high enzyme retention on the support during the glucose isomerization process. In batch reactors, SGI (half-life =145 h) was more stable than IGI (half-life=27 h) at 60°C in HFCS, whereas at 80°C, IGI (half-life=12 h) was more stable than SGI (half-life=5.2 h). IGI was subject to thiol oxidation at 60°C, which contributed to the enzyme's deactivation. IGI was subject to thiol oxidation at 80°C, but this did not contribute to the deactivation of the enzyme. SGI did not undergo thiol oxidation at 60°C, but at 80°C SGI underwent severe precipitation and thiol oxidation, which caused the enzyme to deactivate. Experimental results show that immobilization suppresses the destablizing effect of thiol oxidation on GI. A "Maillard-like" reaction between SGI and the sugars also caused SGI thermoinactivation at 60, 70, and 80°C, but had minimal effect on IGI. At 60 and 80°C, IGI had higher thermostability in continuous reactors than in batch reactors, possibily because of reduced contact with deleterious compounds in HFCS.

  3. Structure-based approach to the identification of a novel group of selective glucosamine analogue inhibitors of Trypanosoma cruzi glucokinase.

    Science.gov (United States)

    D'Antonio, Edward L; Deinema, Mason S; Kearns, Sean P; Frey, Tyler A; Tanghe, Scott; Perry, Kay; Roy, Timothy A; Gracz, Hanna S; Rodriguez, Ana; D'Antonio, Jennifer

    2015-12-01

    Glucokinase and hexokinase from pathogenic protozoa Trypanosoma cruzi are potential drug targets for antiparasitic chemotherapy of Chagas' disease. These glucose kinases phosphorylate d-glucose with co-substrate ATP and yield glucose 6-phosphate and are involved in essential metabolic pathways, such as glycolysis and the pentose phosphate pathway. An inhibitor class was conceived that is selective for T. cruzi glucokinase (TcGlcK) using structure-based drug design involving glucosamine having a linker from the C2 amino that terminates with a hydrophobic group either being phenyl, p-hydroxyphenyl, or dioxobenzo[b]thiophenyl groups. The synthesis and characterization for two of the four compounds are presented while the other two compounds were commercially available. Four high-resolution X-ray crystal structures of TcGlcK inhibitor complexes are reported along with enzyme inhibition constants (Ki) for TcGlcK and Homo sapiens hexokinase IV (HsHxKIV). These glucosamine analogue inhibitors include three strongly selective TcGlcK inhibitors and a fourth inhibitor, benzoyl glucosamine (BENZ-GlcN), which is a similar variant exhibiting a shorter linker. Carboxybenzyl glucosamine (CBZ-GlcN) was found to be the strongest glucokinase inhibitor known to date, having a Ki of 0.71±0.05μM. Also reported are two biologically active inhibitors against in vitro T. cruzi culture that were BENZ-GlcN and CBZ-GlcN, with intracellular amastigote growth inhibition IC50 values of 16.08±0.16μM and 48.73±0.69μM, respectively. These compounds revealed little to no toxicity against mammalian NIH-3T3 fibroblasts and provide a key starting point for further drug development with this class of compound.

  4. Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

    Directory of Open Access Journals (Sweden)

    Anders Lyngvi Fougner

    2016-04-01

    Full Text Available Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP sensor sites, as an alternative to the SC location. Intraarterial (IA and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70--360 mg/dL (approximately 3.8--20 mmol/L. Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing. The time delay in glucose excursions from central circulation (IA to IP sensor location was found to be in the range 0--26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s, and the time constant was found to be 0.5--10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min. IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies. This study may provide a benchmark for future, rapid IP glucose sensors.

  5. Development of a Robust Optical Glucose Sensor

    Science.gov (United States)

    Cote, Gerard Laurence

    1990-01-01

    The long term objective of this research was the development of a noninvasive, optically-based, polarimetric sensor to monitor in vivo glucose concentrations. The goal of diabetes therapy is to approximate the 24-hour blood glucose profile of a normal individual. There have been major advances in the development of reliable, versatile, and accurate pumps for the delivery of insulin to diabetic patients and in the development of control algorithms for closed-loop insulin delivery, however, there remain major obstacles to the development of clinically useful, continuous glucose sensors. The development of an accurate noninvasive glucose sensor would have significant application in the diagnosis and management of diabetes mellitis both in conjunction with, and independent of, the glucose pump controller applications. The linear polarization vector of light routes when it interacts with an optically active material such as glucose. The amount of rotation of polarization is directly proportional to the glucose concentration and to the path length. The ability to quantitate blood glucose levels for the limited available path length in our primary sensing site, namely, the anterior chamber of the eye, therefore depends on the signal-to-noise ratio of the polarization detector. Our primary research focused on the development and testing of a prototype optical polarimetry system using D + glucose solution in a test cell, as well as using an enucleated human eye to assess the sensitivity of the system to measure physiologic glucose levels for the approximate one centimeter path length present in the anterior chamber of the eye. Our research has led to the development of a true phase technique in which helium neon laser light was coupled through a rotating linear polarizer along with two stationary linear polarizers and two detectors to produce reference and signal outputs whose amplitudes varied sinusoidally and whose phase was proportional to the rotation of light caused by

  6. Correlation between blood glucose levels and salivary glucose levels with oral ulcer in diabetic patients

    Directory of Open Access Journals (Sweden)

    Fildzah Rahman

    2016-06-01

    Full Text Available Diabetes Mellitus (DM is a syndrome in metabolism of carbohydrates which indicated by the increased level of blood glucose and also may increase salivary glucose levels. Oral ulcer has been frequently recognized in diabetic patients, which can be due to increased glucose in oral fluids and immune dysfunction. This study aimed to determine the correlation of blood glucose levels and salivary glucose levels with oral ulcer in diabetic patients. Analytic observational study was carried out through the determination of blood glucose levels just by way of strip using a glucometer and salivary glucose levels with the method "GOD-PAP test enzymatic colorimetric". Oral ulcer was determined in presenting ulcer on 30 patients with DM. The results showed r = 0.228, which is higher salivary glucose levels followed by high levels of blood glucose, and intraoral examination of oral ulcer found in the whole sample and the most location commonly found in buccal mucosa and lingual. It was concluded that there is a correlation between blood glucose levels and salivary glucose levels, and glucose levels affect the occurrence of oral ulcer in patients with DM

  7. Nonfermentable, glucose-containing products formed from glucose under cellulose acid hydrolysis conditions

    Science.gov (United States)

    J. L. Minor

    1983-01-01

    Solutions of D-glucose in dilute sulfuric acid were allowed to react under time and temperature conditions which simulated the production of glucose from cellulose. Under these conditions, glucose undergoes a number of reactions including isomerization, dehydration, transglycosidation, polymerization, and anhydride formation. The specific interest in this report was to...

  8. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

    NARCIS (Netherlands)

    R. Saxena (Richa); M.-F. Hivert (Marie-France); C. Langenberg (Claudia); T. Tanaka (Toshiko); J.S. Pankow (James); P. Vollenweider (Peter); V. Lyssenko (Valeriya); N. Bouatia-Naji (Nabila); J. Dupuis (Josée); A.U. Jackson (Anne); W.H.L. Kao (Wen); M. Li (Man); N.L. Glazer (Nicole); A.K. Manning (Alisa); J. Anluan (Jian); H.M. Stringham (Heather); I. Prokopenko (Inga); T. Johnson (Toby); N. Grarup (Niels); T.W. Boesgaard (Trine); C. Lecoeur (Cécile); P. Shrader (Peter); J.R. O´Connell; E. Ingelsson (Erik); D.J. Couper (David); K. Rice (Kenneth); K. Song (Kijoung); C.H. Andreasen (Camilla); C. Dina (Christian); A. Köttgen (Anna); O.L. Bacquer (Olivier); F. Pattou (François); J. Taneera (Jalal); V. Steinthorsdottir (Valgerdur); D. Rybin (Denis); K.G. Ardlie (Kristin); M.J. Sampson (Michael); L. Qi (Lu); M.V. Hoek; M.N. Weedon (Michael); Y.S. Aulchenko (Yurii); B.F. Voight (Benjamin); H. Grallert (Harald); B. Balkau (Beverley); R.N. Bergman (Richard); S.J. Bielinski (Suzette); A. Bonnefond (Amélie); L.L. Bonnycastle (Lori); K. Borch-Johnsen; Y. Böttcher (Yvonne); E. Brunner (Eric); T.A. Buchanan (Thomas); S. Bumpstead (Suzannah); C. Cavalcanti-Proença (Christine); G. Charpentier (Guillaume); C. Chen (Chao); P.S. Chines (Peter); F.S. Collins (Francis); M. Cornelis (Marilyn); G. Crawford (Gabe); J. Delplanque (Jerome); A.S.F. Doney (Alex); J.M. Egan (Josephine); M.R. Erdos (Michael); M. Firmann (Mathieu); N.G. Forouhi (Nita); C.S. Fox (Caroline); M. Goodarzi (Mark); J. Graessler (Jürgen); A. Hingorani (Aroon); B. Isomaa (Bo); T. Jørgensen (Torben); M. Kivimaki (Mika); P. Kovacs (Peter); K. Krohn (Knut); M. Kumari (Meena); T. Lauritzen (Torsten); C. Lévy-Marchal (Claire); V. Mayor (Vladimir); J.B. McAteer (Jarred); D. Meyre (David); B.D. Mitchell (Braxton); K.L. Mohlke (Karen); M.A. Morken (Mario); N. Narisu (Narisu); C.N.A. Palmer (Colin); R. Pakyz (Ruth); L. Pascoe (Laura); F. Payne (Felicity); D. Pearson (Daniel); W. Rathmann (Wolfgang); A. Sandbaek (Annelli); A.A. Sayer; L.J. Scott (Laura); S.J. Sharp (Stephen); E.J.G. Sijbrands (Eric); A. Singleton (Andrew); D.S. Siscovick (David); N.L. Smith (Nicholas); T. Sparsø (Thomas); A.J. Swift (Amy); H. Syddall (Holly); G. Thorleifsson (Gudmar); A. Tönjes (Anke); T. Tuomi (Tiinamaija); J. Tuomilehto (Jaakko); T.T. Valle (Timo); G. Waeber (Gérard); A. Walley (Andrew); D. Waterworth (Dawn); E. Zeggini (Eleftheria); J.H. Zhao; G. Consortium (Giant); T. Illig (Thomas); H.E. Wichmann (Erich); J.F. Wilson (James); C.M. van Duijn (Cock); F.B. Hu (Frank); A.D. Morris (Andrew); T.M. Frayling (Timothy); A.T. Hattersley (Andrew); U. Thorsteinsdottir (Unnur); J-A. Zwart (John-Anker); P. Nilsson (Peter); A.C. Syvänen; A.R. Shuldiner (Alan); M. Walker (Mark); S.R. Bornstein (Stefan); P. Schwarz (Peter); G.H. Williams (Gordon); D.M. Nathan (David); J. Kuusisto (Johanna); M. Laakso (Markku); C. Cooper (Charles); M. Marmot (Michael); L. Ferrucci (Luigi); V. Mooser (Vincent); M. Stumvoll (Michael); R.J.F. Loos (Ruth); D. Altshuler (David); B.M. Psaty (Bruce); J.I. Rotter (Jerome); E.A. Boerwinkle (Eric); T. Hansen (Torben); O. Pedersen (Oluf); J.C. Florez (Jose); M.I. McCarthy (Mark); M. Boehnke (Michael); I. Barroso (Inês); R. Sladek (Rob); P. Froguel (Philippe); J.B. Meigs (James); L. Groop (Leif); N.J. Wareham (Nick); R.M. Watanabe (Richard)

    2010-01-01

    textabstractGlucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n =

  9. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

    NARCIS (Netherlands)

    R. Saxena (Richa); M.-F. Hivert (Marie-France); C. Langenberg (Claudia); T. Tanaka (Toshiko); J.S. Pankow (James); P. Vollenweider (Peter); V. Lyssenko (Valeriya); N. Bouatia-Naji (Nabila); J. Dupuis (Josée); A.U. Jackson (Anne); W.H.L. Kao (Wen); M. Li (Man); N.L. Glazer (Nicole); A.K. Manning (Alisa); J. Anluan (Jian); H.M. Stringham (Heather); I. Prokopenko (Inga); T. Johnson (Toby); N. Grarup (Niels); T.W. Boesgaard (Trine); C. Lecoeur (Cécile); P. Shrader (Peter); J.R. O´Connell; E. Ingelsson (Erik); D.J. Couper (David); K. Rice (Kenneth); K. Song (Kijoung); C.H. Andreasen (Camilla); C. Dina (Christian); A. Köttgen (Anna); O.L. Bacquer (Olivier); F. Pattou (François); J. Taneera (Jalal); V. Steinthorsdottir (Valgerdur); D. Rybin (Denis); K.G. Ardlie (Kristin); M.J. Sampson (Michael); L. Qi (Lu); M.V. Hoek; M.N. Weedon (Michael); Y.S. Aulchenko (Yurii); B.F. Voight (Benjamin); H. Grallert (Harald); B. Balkau (Beverley); R.N. Bergman (Richard); S.J. Bielinski (Suzette); A. Bonnefond (Amélie); L.L. Bonnycastle (Lori); K. Borch-Johnsen; Y. Böttcher (Yvonne); E. Brunner (Eric); T.A. Buchanan (Thomas); S. Bumpstead (Suzannah); C. Cavalcanti-Proença (Christine); G. Charpentier (Guillaume); C. Chen (Chao); P.S. Chines (Peter); F.S. Collins (Francis); M. Cornelis (Marilyn); G. Crawford (Gabe); J. Delplanque (Jerome); A.S.F. Doney (Alex); J.M. Egan (Josephine); M.R. Erdos (Michael); M. Firmann (Mathieu); N.G. Forouhi (Nita); C.S. Fox (Caroline); M. Goodarzi (Mark); J. Graessler (Jürgen); A. Hingorani (Aroon); B. Isomaa (Bo); T. Jørgensen (Torben); M. Kivimaki (Mika); P. Kovacs (Peter); K. Krohn (Knut); M. Kumari (Meena); T. Lauritzen (Torsten); C. Lévy-Marchal (Claire); V. Mayor (Vladimir); J.B. McAteer (Jarred); D. Meyre (David); B.D. Mitchell (Braxton); K.L. Mohlke (Karen); M.A. Morken (Mario); N. Narisu (Narisu); C.N.A. Palmer (Colin); R. Pakyz (Ruth); L. Pascoe (Laura); F. Payne (Felicity); D. Pearson (Daniel); W. Rathmann (Wolfgang); A. Sandbaek (Annelli); A.A. Sayer; L.J. Scott (Laura); S.J. Sharp (Stephen); E.J.G. Sijbrands (Eric); A. Singleton (Andrew); D.S. Siscovick (David); N.L. Smith (Nicholas); T. Sparsø (Thomas); A.J. Swift (Amy); H. Syddall (Holly); G. Thorleifsson (Gudmar); A. Tönjes (Anke); T. Tuomi (Tiinamaija); J. Tuomilehto (Jaakko); T.T. Valle (Timo); G. Waeber (Gérard); A. Walley (Andrew); D. Waterworth (Dawn); E. Zeggini (Eleftheria); J.H. Zhao; G. Consortium (Giant); T. Illig (Thomas); H.E. Wichmann (Erich); J.F. Wilson (James); C.M. van Duijn (Cock); F.B. Hu (Frank); A.D. Morris (Andrew); T.M. Frayling (Timothy); A.T. Hattersley (Andrew); U. Thorsteinsdottir (Unnur); J-A. Zwart (John-Anker); P. Nilsson (Peter); A.C. Syvänen; A.R. Shuldiner (Alan); M. Walker (Mark); S.R. Bornstein (Stefan); P. Schwarz (Peter); G.H. Williams (Gordon); D.M. Nathan (David); J. Kuusisto (Johanna); M. Laakso (Markku); C. Cooper (Charles); M. Marmot (Michael); L. Ferrucci (Luigi); V. Mooser (Vincent); M. Stumvoll (Michael); R.J.F. Loos (Ruth); D. Altshuler (David); B.M. Psaty (Bruce); J.I. Rotter (Jerome); E.A. Boerwinkle (Eric); T. Hansen (Torben); O. Pedersen (Oluf); J.C. Florez (Jose); M.I. McCarthy (Mark); M. Boehnke (Michael); I. Barroso (Inês); R. Sladek (Rob); P. Froguel (Philippe); J.B. Meigs (James); L. Groop (Leif); N.J. Wareham (Nick); R.M. Watanabe (Richard)

    2010-01-01

    textabstractGlucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,95

  10. Allosteric competitive inhibitors of the glucose-1-phosphate thymidylyltransferase (RmlA) from Pseudomonas aeruginosa.

    Science.gov (United States)

    Alphey, Magnus S; Pirrie, Lisa; Torrie, Leah S; Boulkeroua, Wassila Abdelli; Gardiner, Mary; Sarkar, Aurijit; Maringer, Marko; Oehlmann, Wulf; Brenk, Ruth; Scherman, Michael S; McNeil, Michael; Rejzek, Martin; Field, Robert A; Singh, Mahavir; Gray, David; Westwood, Nicholas J; Naismith, James H

    2013-02-15

    Glucose-1-phosphate thymidylyltransferase (RmlA) catalyzes the condensation of glucose-1-phosphate (G1P) with deoxy-thymidine triphosphate (dTTP) to yield dTDP-d-glucose and pyrophosphate. This is the first step in the l-rhamnose biosynthetic pathway. l-Rhamnose is an important component of the cell wall of many microorganisms, including Mycobacterium tuberculosis and Pseudomonas aeruginosa. Here we describe the first nanomolar inhibitors of P. aeruginosa RmlA. These thymine analogues were identified by high-throughput screening and subsequently optimized by a combination of protein crystallography, in silico screening, and synthetic chemistry. Some of the inhibitors show inhibitory activity against M. tuberculosis. The inhibitors do not bind at the active site of RmlA but bind at a second site remote from the active site. Despite this, the compounds act as competitive inhibitors of G1P but with high cooperativity. This novel behavior was probed by structural analysis, which suggests that the inhibitors work by preventing RmlA from undergoing the conformational change key to its ordered bi-bi mechanism.

  11. PPARgamma agonist induced cardiac enlargement is associated with reduced fatty acid and increased glucose utilization in myocardium of Wistar rats.

    Science.gov (United States)

    Edgley, Amanda J; Thalén, Pia G; Dahllöf, Björn; Lanne, Boel; Ljung, Bengt; Oakes, Nicholas D

    2006-05-24

    In toxicological studies, high doses of peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists cause cardiac enlargement. To investigate whether this could be explained by a large shift from free fatty acid to glucose utilization by the heart, Wistar rats were treated for 2-3 weeks with a potent, selective PPARgamma agonist (X334, 3 micromol/kg/d), or vehicle. X334 treatment increased body-weight gain and ventricular mass. Treatment lowered plasma triglycerides by 61%, free fatty acid levels by 72%, insulin levels by 45%, and reduced total plasma protein concentration by 7% (indicating plasma volume expansion) compared to vehicle animals. Fasting plasma glucose levels were unaltered. To assess cardiac free fatty acid and glucose utilization in vivo we used simultaneous infusions of non-beta-oxidizable free fatty acid analogue, [9,10-(3)H](R)-2-bromopalmitate and [U-(14)C]2-deoxy-d-glucose tracers, which yield indices of local free fatty acid and glucose utilization. In anesthetized, 7 h fasted animals, left ventricular glucose utilization was increased to 182% while free fatty acid utilization was reduced by 28% (P<0.05) compared to vehicle. In separate studies we attempted to prevent the X334-induced hypolipidemia. Various dietary fat supplements were unsuccessful. By contrast, restricting the time during which the treated animals had access to food (promoting endogenous lipolysis), restored plasma free fatty acid from 27% to 72% of vehicle control levels and prevented the cardiac enlargement. Body-weight gain in these treated-food restricted rats was not different from vehicle controls. In conclusion, the cardiac enlargement caused by intense PPARgamma activation in normal animals is associated with marked changes in free fatty acid/glucose utilization and the enlargement can be prevented by restoring free fatty acid availability.

  12. Glucose and galactose metabolism in Gluconabacter liquefaciens

    NARCIS (Netherlands)

    Stouthamer, A.H.

    1961-01-01

    Glucose-grown cells of Gluconobacter liquefaciens oxidize glucose, gluconate and 2-ketogluconate practically completely to 2,5-diketogluconate by particulate enzymes, localized in the protoplasmic membrane. The bulk of the 2,5-diketgluconate (and 5-ketogluconate) enters the cytoplasm and is metaboli

  13. Roles of the Gut in Glucose Homeostasis

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Gribble, Fiona; Horowitz, Michael

    2016-01-01

    The gastrointestinal tract plays a major role in the regulation of postprandial glucose profiles. Gastric emptying is a highly regulated process, which normally ensures a limited and fairly constant delivery of nutrients and glucose to the proximal gut. The subsequent digestion and absorption of ...

  14. Blood glucose response to pea fiber

    DEFF Research Database (Denmark)

    Hamberg, O; Rumessen, J J; Gudmand-Høyer, E

    1989-01-01

    Two new fiber types, pea fiber (PF) and sugar beet fiber (BF), were compared with wheat bran (WB) to investigate the effect on postprandial blood glucose and serum insulin responses in normal subjects. The control meal consisted of 150 g ground beef mixed with 50 g glucose and 20 g lactulose. Only...

  15. Toward a Continuous Intravascular Glucose Monitoring System

    Directory of Open Access Journals (Sweden)

    Pedro Irazoqui

    2010-12-01

    Full Text Available Proof-of-concept studies that display the potential of using a glucose-sensitive hydrogel as a continuous glucose sensor are presented. The swelling ratio, porosity, and diffusivity of the hydrogel increased with glucose concentration. In glucose solutions of 50, 100, 200, and 300 mg/dL, the hydrogel swelling ratios were 4.9, 12.3, 15.9, and 21.7, respectively, and the swelling was reversible. The impedance across the hydrogel depended solely on the thickness and had an average increase of 47 W/mm. The hydrogels exposed to a hyperglycemic solution were more porous than the hydrogels exposed to a normal glycemic solution. The diffusivity of 390 Da MW fluorescein isothiocyanate in hydrogels exposed to normal and hyperglycemic solutions was examined using fluorescence recovery after photobleaching and was found to be 9.3 × 10−14 and 41.4 × 10−14 m2/s, respectively, compared to 6.2 × 10−10 m2/s in glucose solution. There was no significant difference between the permeability of hydrogels in normal and hyperglycemic glucose solutions with averages being 5.26 × 10−17 m2 and 5.80 × 10−17 m2, respectively, which resembles 2–4% agarose gels. A prototype design is presented for continuous intravascular glucose monitoring by attaching a glucose sensor to an FDA-approved stent.

  16. [Intracellular signals involved in glucose control].

    Science.gov (United States)

    Cruz, M; Velasco, E; Kumate, J

    2001-01-01

    Many proteins are involved in glucose control. The first step for glucose uptake is insulin receptor-binding. Stimulation of the insulin receptor results in rapid autophosphorylation and conformational changes in the beta chain and the subsequent phosphorylation of the insulin receptor substrate. This results in the docking of several SH2 domain proteins, including PI 3-kinase and other adapters. The final event is glucose transporter (GLUT) translocation to the cell surface. GLUT is in the cytosol but after insulin stimulation, several proteins are activated either in the GLUT vesicles or in the inner membrane. The role of the cytoskeleton is not well known, but it apparently participates in membrane fusion and vesicle mobilization. After glucose uptake, several hexokines metabolize the glucose to generate energy, convert the glucose in glycogen and store it. Type 2 diabetes is characterized by high glucose levels and insulin resistance. The insulin receptor is diminished on the cell surface membrane, tyrosine phosphorylation is decreased, serine and threonine phosphorylation is augmented. Apparently, the main problem with GLUT protein is in its translocation to the cell surface. At present, we know the role of many proteins involved in glucose control. However, we do not understand the significance of insulin resistance at the molecular level with type 2 diabetes.

  17. Molecular pathophysiology of hepatic glucose production.

    Science.gov (United States)

    Sharabi, Kfir; Tavares, Clint D J; Rines, Amy K; Puigserver, Pere

    2015-12-01

    Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays a major role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM.

  18. Effects on plasma glucose and lactate.

    Science.gov (United States)

    Young, Andrew

    2005-01-01

    Injection of amylin or amylin agonists, including human and rat amylin, pramlintide, salmon calcitonin, and calcitonin gene-related peptide (CGRP), increases the plasma levels of lactate and glucose in non-diabetic fasting rats and mice. This response can be useful in identifying and defining amylin agonists (amylinomimetic agents) (Cooper et al.) and has been investigated in several studies. Increases in plasma glucose and lactate are not present in all species. In humans, for example, increases in lactate are observed at high pramlintide doses but not at doses that would be used to therapeutically regulate plasma glucose. In species where it occurs, the increase in plasma lactate with amylin is comparable to that observed with exercise or adrenergic agents, and it is distinguishable from the very high levels observed during lactic acidosis (as may occur with biguanides). In contrast to lactic acidosis, the plasma lactate with amylin is derived from skeletal muscle rather than liver. Increases in plasma lactate and glucose in some species may initially appear inconsistent with a glucose-lowering effect of amylin agonists. But glycemic effects are due to actions in skeletal muscle and are present only in some species, whereas glucose-lowering actions are attributable to effects in gastrointestinal systems and are present in all species studied to date. And while glycemic effects are most pronounced in the fasted state, glucose-lowering effects are most pronounced in the postprandial state. Since they were discovered first, effects of higher doses of amylin on plasma glucose, especially in the fasted state, are described first and are related to concomitant changes in plasma lactate. These effects are prominent in rodents but are barely discernible in humans. Effects of lower doses of pramlintide to suppress plasma glucose profiles in the postprandial period are also observable in normal and diabetic rats, however, and are covered here as well. The relationship

  19. Quantitative comparisons of analogue models of brittle wedge dynamics

    Science.gov (United States)

    Schreurs, Guido

    2010-05-01

    Analogue model experiments are widely used to gain insights into the evolution of geological structures. In this study, we present a direct comparison of experimental results of 14 analogue modelling laboratories using prescribed set-ups. A quantitative analysis of the results will document the variability among models and will allow an appraisal of reproducibility and limits of interpretation. This has direct implications for comparisons between structures in analogue models and natural field examples. All laboratories used the same frictional analogue materials (quartz and corundum sand) and prescribed model-building techniques (sieving and levelling). Although each laboratory used its own experimental apparatus, the same type of self-adhesive foil was used to cover the base and all the walls of the experimental apparatus in order to guarantee identical boundary conditions (i.e. identical shear stresses at the base and walls). Three experimental set-ups using only brittle frictional materials were examined. In each of the three set-ups the model was shortened by a vertical wall, which moved with respect to the fixed base and the three remaining sidewalls. The minimum width of the model (dimension parallel to mobile wall) was also prescribed. In the first experimental set-up, a quartz sand wedge with a surface slope of ˜20° was pushed by a mobile wall. All models conformed to the critical taper theory, maintained a stable surface slope and did not show internal deformation. In the next two experimental set-ups, a horizontal sand pack consisting of alternating quartz sand and corundum sand layers was shortened from one side by the mobile wall. In one of the set-ups a thin rigid sheet covered part of the model base and was attached to the mobile wall (i.e. a basal velocity discontinuity distant from the mobile wall). In the other set-up a basal rigid sheet was absent and the basal velocity discontinuity was located at the mobile wall. In both types of experiments

  20. Glucose Recognition in Vitro Using Fluorescent Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Noronha, G; Heiss, A M; Reilly, J R; Vachon, Jr, D J; Cary, D R; Zaitseva, N P; Reibold, R A; Lane, S M; Peyser, T A; Satcher, J H

    2001-04-25

    Diabetes is a disease that affects over 16 million people in the USA at a cost of 100 billion dollars annually. The ability to regulate insulin delivery in people with Type 1 diabetes is imperative as is the need to manage glucose levels in all people with this disease. Our current method for monitoring glucose is a (FDA approved) minimally invasive enzymatic sensor that can measure glucose levels in vivo for three days. We are focused on developing a noninvasive implantable glucose sensor that will be interrogated by an external device. The material must be robust, easy to process, biocompatible and resistant to biofouling. In this Presentation we will discuss the development of a new polymeric matrix that can recognize physiological levels of glucose in vitro using fluorescent spectroscopy.

  1. Hydrogen production from glucose by anaerobes.

    Science.gov (United States)

    Ogino, Hiroyasu; Miura, Takashi; Ishimi, Kosaku; Seki, Minoru; Yoshida, Hiroyuki

    2005-01-01

    Various anaerobes were cultivated in media containing glucose. When 100 mL of thioglycollate medium containing 2.0% (w/v) glucose was used, Clostridium butyricum ATCC 859, NBRC 3315, and NBRC 13949 evolved 227-243 mL of biogas containing about 180 mL of hydrogen in 1 day. Although some strains had some resistance against oxygen, C. butyricum ATCC 859 and 860 did not have it. C. butyricum NBRC 3315 and Enterobacter aerogenes NBRC 13534 produced hydrogen in the presence of glucose or pyruvic acid, and E. aerogenes NBRC 13534 produced hydrogen by not only glucose and pyruvic acid but also dextrin, sucrose, maltose, galactose, fructose, mannose, and mannitol. When a medium containing 0.5% (w/v) yeast extract and 2.0% (w/v) glucose was used, E. aerogenes NBRC 13534 evolved more biogas and hydrogen than C. butyricum NBRC 3315 in the absence of reducing agent.

  2. Glucose Biosensor Based on Immobilization of Glucose Oxidase in Platinum Nanoparticles/Graphene/Chitosan Nanocomposite Film

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Wang, Jun; Kang, Xinhuang; Wang, Chong M.; Wang, Donghai; Liu, Jun; Aksay, Ilhan A.; Lin, Yuehe

    2009-09-01

    The bionanocomposite film consisting of glucose oxidase/Pt/functional graphene sheets/chitosan (GOD/Pt/FGS/chitosan) for glucose sensing was described. With the electrocatalytic synergy of FGS and Pt nanoparticles to hydrogen peroxide, a sensitive biosensor with detection limit of 0.6 µM glucose was achieved. The biosensor also had good reproducibility, long term stability and negligible interfering signals from ascorbic acid and uric acid comparing to the response to glucose. The large surface area and good conductivity of graphene suggests that graphene is a potential candidate for sensor material. The hybrid nanocomposite glucose sensor provides new opportunity for clinical diagnosis and point-of-care applications.

  3. Properties of granular analogue model materials: A community wide survey

    Science.gov (United States)

    Klinkmüller, M.; Schreurs, G.; Rosenau, M.; Kemnitz, H.

    2016-08-01

    We report the material properties of 26 granular analogue materials used in 14 analogue modelling laboratories. We determined physical characteristics such as bulk density, grain size distribution, and grain shape, and performed ring shear tests to determine friction angles and cohesion, and uniaxial compression tests to evaluate the compaction behaviour. Mean grain size of the materials varied between c. 100 and 400 μm. Analysis of grain shape factors shows that the four different classes of granular materials (14 quartz sands, 5 dyed quartz sands, 4 heavy mineral sands and 3 size fractions of glass beads) can be broadly divided into two groups consisting of 12 angular and 14 rounded materials. Grain shape has an influence on friction angles, with most angular materials having higher internal friction angles (between c. 35° and 40°) than rounded materials, whereas well-rounded glass beads have the lowest internal friction angles (between c. 25° and 30°). We interpret this as an effect of intergranular sliding versus rolling. Most angular materials have also higher basal friction angles (tested for a specific foil) than more rounded materials, suggesting that angular grains scratch and wear the foil. Most materials have an internal cohesion in the order of 20-100 Pa except for well-rounded glass beads, which show a trend towards a quasi-cohesionless (C < 20 Pa) Coulomb-type material. The uniaxial confined compression tests reveal that rounded grains generally show less compaction than angular grains. We interpret this to be related to the initial packing density after sifting, which is higher for rounded grains than for angular grains. Ring-shear test data show that angular grains undergo a longer strain-hardening phase than more rounded materials. This might explain why analogue models consisting of angular grains accommodate deformation in a more distributed manner prior to strain localisation than models consisting of rounded grains.

  4. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  5. Radio-protective effect of some new curcumin analogues.

    Science.gov (United States)

    El-Gazzar, Marwa G; Zaher, Nashwa H; El-Hossary, Ebaa M; Ismail, Amel F M

    2016-09-01

    In the present study, novel symmetrical curcumin analogues (2-7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2-7) were elucidated by elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2-7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2-7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition.

  6. Quinazoline antifolates inhibiting thymidylate synthase: 4-thio-substituted analogues.

    Science.gov (United States)

    Thornton, T J; Jones, T R; Jackman, A L; Flinn, A; O'Connor, B M; Warner, P; Calvert, A H

    1991-03-01

    We report the synthesis of four new 4-thio-5,8-dideazafolic acid analogues and a 4-(methylthio) analogue structurally related to the thymidylate synthase (TS) inhibitor N10-propargyl-5,8-dideazafolic acid. Three N10-propargyl-4-thio-5,8-dideazafolic acid analogues had C2 amino, hydrogen, and methyl substituents. A 4-thio and a 4-(methylthio) compound each with hydrogen at C2 and ethyl at N10 were also synthesized. In general, the synthetic route involved thionation of the appropriate 4-oxoquinazoline; the sulfur thus introduced was then protected by methylation. Further protection with a pivaloyl group was required for the quinazoline bearing a 2-amino substituent. The protected quinazolines were treated with N-bromosuccinimide and the resulting 6-(bromomethyl) compounds were then coupled to the appropriate N-monoalkylated diethyl N-(4-aminobenzoyl)-L-glutamate in N,N-dimethylacetamide with calcium carbonate as base. The 4-thio-5,8-dideazafolic acids were obtained by removal of the methylthio group with sodium hydrosulfide, followed by deprotection of the carboxyl groups with cold dilute alkali. For the compound containing a pivaloyl protecting group, hot dilute alkali was used. To obtain the 5,8-dideazafolic acid containing a 4-(methylthio) substituent, the corresponding diester was treated with lithium hydroxide which selectively deprotected the carboxyl groups. The five compounds were tested as inhibitors of L1210 TS. It was found that replacement of the 4-oxygen of the quinazoline moiety by sulfur did not alter the TS inhibition. However, the introduction of a methylthio substituent at position 4 severely impaired TS inhibition. All 4-thio compounds were less cytotoxic to L1210 cells in culture than their 4-oxo counterparts.

  7. A novel noninvasive blood glucose monitor.

    Science.gov (United States)

    Malchoff, Carl D; Shoukri, Kamal; Landau, Julian I; Buchert, Janusz M

    2002-12-01

    To evaluate the precision and accuracy of a new advanced prototype of a noninvasive blood glucose monitor across a wide range of serum glucose concentrations. An advanced handheld noninvasive glucose monitor prototype was calibrated and tested using patients recruited by the General Research Center of the University of Connecticut Health Center. The monitor, developed by Infratec, uses principles of thermal emission spectroscopy. The noninvasive measurement of tympanic membrane glucose concentration was calibrated to the serum glucose concentration using 432 paired measurements from 20 subjects with insulin-requiring diabetes. This calibration was subsequently tested (results of power analyses) in a blind fashion with 126 paired measurements from six diabetic subjects who require insulin. In vivo measurements demonstrated the reproducibility of the methodology of the noninvasive glucose monitor. Based on the calibration model, predicted glucose concentrations for six subjects were as follows (for 126 data points): SD = 32 mg/dl, mean absolute relative error (%MARE) = 11.6, with a correlation coefficient of r = 0.87. Noninvasive glucose results were also compared with laboratory reference measurements using an error-in-variables method. Clark error grid analysis showed that 100% of the measurements fell within zones A and B (90% in zone A and 10% in zone B). The SD for all noninvasive measured concentrations was 27 mg/dl, %MARE was 8.6, and the correlation coefficient was r = 0.94. This first independent clinical study of an advanced noninvasive blood glucose prototype based on thermal emission in the mid-infrared spectral region has demonstrated glucose measurements with clinically acceptable accuracy but without the necessity of individual daily calibration.

  8. Identification of Glucose Transporters in Aspergillus nidulans

    Science.gov (United States)

    dos Reis, Thaila Fernanda; Menino, João Filipe; Bom, Vinícius Leite Pedro; Brown, Neil Andrew; Colabardini, Ana Cristina; Savoldi, Marcela; Goldman, Maria Helena S.; Rodrigues, Fernando; Goldman, Gustavo Henrique

    2013-01-01

    To characterize the mechanisms involved in glucose transport, in the filamentous fungus Aspergillus nidulans, we have identified four glucose transporter encoding genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was able to restore growth on glucose, fructose, mannose or galactose, indicating that these transporters accept multiple sugars as a substrate through an energy dependent process. A tenfold excess of unlabeled maltose, galactose, fructose, and mannose were able to inhibit glucose uptake to different levels (50 to 80 %) in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m-chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and –E mediate glucose transport via active proton symport. The A. nidulans ΔhxtB, ΔhxtC or ΔhxtE null mutants showed ~2.5-fold reduction in the affinity for glucose, while ΔhxtB and -C also showed a 2-fold reduction in the capacity for glucose uptake. The ΔhxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold increase in the capacity for glucose uptake. However, only the ΔhxtB mutant strain showed a detectable decreased rate of glucose consumption at low concentrations and an increased resistance to 2-deoxyglucose. PMID:24282591

  9. Stimulated Raman adiabatic passage analogues in classical physics

    Energy Technology Data Exchange (ETDEWEB)

    Rangelov, A A [University of Kassel, Heinrich-Plett-Str. 40, D-34132 Kassel (Germany); Vitanov, N V [Department of Physics, Sofia University, James Bourchier 5 blvd., 1164 Sofia (Bulgaria); Shore, B W [618 Escondido Cir., Livermore, CA (United States)

    2009-03-14

    Stimulated Raman adiabatic passage (STIRAP) is a well-established technique for producing coherent population transfer in a three-state quantum system. We here exploit the resemblance between the Schroedinger equation for such a quantum system and the Newton equation of motion for a classical system undergoing torque to discuss several classical analogues of STIRAP, notably the motion of a moving charged particle subject to the Lorentz force of a quasistatic magnetic field, the orientation of a magnetic moment in a slowly varying magnetic field and the Coriolis effect. Like STIRAP, these phenomena occur for counterintuitive motion of the torque and are robustly insensitive to small changes in the interaction properties.

  10. Towards bottom-up nanopatterning of Prussian blue analogues

    Directory of Open Access Journals (Sweden)

    Virgile Trannoy

    2014-10-01

    Full Text Available Ordered nanoperforated TiO2 monolayers fabricated through sol–gel chemistry were used to grow isolated particles of Prussian blue analogues (PBA. The elaboration of the TiO2/CoFe PBA nanocomposites involves five steps. The samples were characterized by scanning electron microscopy (SEM, atomic force microscopy (AFM, infrared spectroscopy and X-ray photoelectron spectroscopy (XPS all along the synthesis process. Selected physico-chemical parameters have been varied in order to determine the key steps of the synthesis process and to optimize it. This study is an important step towards the full control of the fabrication process.

  11. Pena Blanca Natural Analogue Project: Summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-02-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  12. Application of FPGA's in Flexible Analogue Electronic Image Generator Design

    Directory of Open Access Journals (Sweden)

    Peter Kulla

    2006-01-01

    Full Text Available This paper focuses on usage of the FPGAs (Field Programmable Gate Arrays Xilinx as a part of our more complex workdedicated to design of flexible analogue electronic images generator for application in TV measurement technique or/and TV servicetechnique or/and education process. The FPGAs performs here the role of component colour R, G, B, synchronization and blanking signals source. These signals are next processed and amplified in other parts of the generator as NTSC/PAL source encoder and RF modulator. The main aim of this paper is to show the possibilities how with suitable development software use a FPGAs in analog TV technology.

  13. Are structural analogues to bisphenol A a safe alternative?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Gitte Alsing

    2013-01-01

    Bisphenol A (BPA) is often used in polycarbonate plastics, coatings of food and drink cans, and in thermal papers. Foods are thought to be a major human exposure route and human biomonitoring data suggest widespread exposure. BPA is suspected of contributing to effects such as increased birth...... weight, behavioral changes in children, cardiovascular disease, and diabetes. Regulatory initiatives and increased public awareness, related to the potential adverse effects of BPA, has led to an incitement to find alternative compounds. Structural analogues of BPA are available on the market, some...

  14. Synthesis, preliminary bioevaluation and computational analysis of caffeic acid analogues.

    Science.gov (United States)

    Liu, Zhiqian; Fu, Jianjun; Shan, Lei; Sun, Qingyan; Zhang, Weidong

    2014-05-16

    A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO) generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.

  15. Pena blanca natural analogue project: summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

    2010-12-08

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  16. [Visual analogue scale for measuring post-operative pain].

    Science.gov (United States)

    Rauh, Katja Halladin; Andersen, Rikke Søby; Rosenberg, Jacob

    2013-06-10

    All patients with pain who are admitted to hospitals in Denmark must be assessed for levels of pain. However, it is not certain how pain should be measured. One way to measure pain is to use a visual analogue scale (VAS). This article focuses on how the VAS should be used in clinical practice in the assessment of post-operative pain. Furthermore, other suitable methods are compared with VAS. VAS is particularly useful for clinical research, but for daily clinical practice it may be easier to use a numeric rating scale.

  17. Captopril analogues as metallo-β-lactamase inhibitors.

    Science.gov (United States)

    Yusof, Yusralina; Tan, Daniel T C; Arjomandi, Omid Khalili; Schenk, Gerhard; McGeary, Ross P

    2016-03-15

    A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure-activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Stimulated emission in black holes and in analogue gravity

    Science.gov (United States)

    Belgiorno, F.; Cacciatori, S. L.

    2016-11-01

    Stimulated emission by black holes is discussed in light of the analogue gravity program. We first consider initial quantum states containing a definite number of particles, and then we take into account the case where the initial state is a coherent state. The latter case is particularly significant in the case where Hawking radiation is studied in dielectric black holes, and the emission is stimulated by a laser probe. We are particularly interested in the case of the electromagnetic field, for which examples of stimulated radiation are considered.

  19. The Canadian space agency planetary analogue materials suite

    Science.gov (United States)

    Cloutis, Edward A.; Mann, Paul; Izawa, Matthew R. M.; Applin, Daniel M.; Samson, Claire; Kruzelecky, Roman; Glotch, Timothy D.; Mertzman, Stanley A.; Mertzman, Karen R.; Haltigin, Timothy W.; Fry, Christopher

    2015-12-01

    The Canadian Space Agency (CSA) recently commissioned the development of a suite of over fifty well-characterized planetary analogue materials. These materials are terrestrial rocks and minerals that are similar to those known or suspected to occur on the lunar or martian surfaces. These include: Mars analogue sedimentary, hydrothermal, igneous and low-temperature alteration rock suites; lunar analogue basaltic and anorthositic rock suites; and a generic impactite rock suite from a variety of terrestrial impact structures. Representative thin sections of the materials have been characterized by optical microscopy and electron probe microanalysis (EPMA). Reflectance spectra have been collected in the ultraviolet, visible, near-infrared and mid-infrared, covering 0.2-25 μm. Thermal infrared emission spectra were collected from 5 to 50 μm. Raman spectra with 532 nm excitation, and laser-induced fluorescence spectra with 405 nm excitation were also measured. Bulk chemical analysis was carried out using X-ray fluorescence, with Fe valence determined by wet chemistry. Chemical and mineralogical data were collected using a field-portable Terra XRD-XRF instrument similar to CheMin on the MSL Curiosity rover. Laser-induced breakdown spectroscopy (LIBS) data similar to those measured by ChemCam on MSL were collected for powdered samples, cut slab surfaces, and as depth profiles into weathered surfaces where present. Three-dimensional laser camera images of rock textures were collected for selected samples. The CSA intends to make available sample powders (science community. Aiming to complement existing planetary analogue rock and mineral libraries, the CSA suite represents a new resource for planetary scientists and engineers. We envision many potential applications for these materials in the definition, development and testing of new analytical instruments for use in planetary missions, as well as possible calibration and ground-truthing of remote sensing data sets

  20. Histone Deacetylase Inhibitors: Synthesis of Tetrapeptide Analogue SAHA/TPX

    Directory of Open Access Journals (Sweden)

    Lynda Ekou

    2011-01-01

    Full Text Available The inhibition of HDAC (histone deacetylase activity by specific inhibitors induces growth arrest, differentiation and apoptosis of transformed or several cancer cells. Some of these inhibitors are in clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy. In this paper we describe the synthesis of simple inhibitor B hybrid analogue suberoylanilide hydroxamic acid (SAHA, trapoxin B (TPX B in as little as five steps. This compound is interesting lead for the design of potent inhibitors of histone deacetylase.

  1. Discodermolide analogues as the chemical component of combination bacteriolytic therapy.

    Science.gov (United States)

    Smith, Amos B; Freeze, B Scott; LaMarche, Matthew J; Sager, Jason; Kinzler, Kenneth W; Vogelstein, Bert

    2005-08-01

    The marine natural product (+)-discodermolide (1) and several simplified analogues of this microtubule-stabilizing agent have proven to be potent in vitro cell growth inhibitory agents in several human cancer cell lines. Here, we demonstrate the in vivo efficacy of discodermolide and several simplified congeners, both as stand-alone anti-tumor agents and, in the case of (+)-2,3-anhydrodiscodermolide (3), as a chemical component of the combination bacteriolytic therapy. A single intravenous injection of (+)-3 plus genetically modified Clostridium novyi-NT spores caused rapid and complete regressions of tumors in mice bearing HCT116 colorectal cancer xenografts.

  2. Synthesis of a Nitro Analogue of Plakoric Acid

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Qi; JIN,Hong-Xia; LIU,He-Hua; WU,Yi-Kang

    2006-01-01

    Synthesis of a nitro analogue of plakoric acid is presented. The peroxy bond was incorporated into the substrate structure through a boron trifluoride etherate catalyzed methoxy-hydroperoxy group partial exchange reaction in djethyl ether with urea-hydrogen peroxide complex (UHP, a commercially available solid reagent) as the source of the hydrogen peroxide. Under the given conditions, only one of the two methoxyl groups underwent the MeO-OOH exchange and the resulting hydroperoxy hemiketal proceeded directly to the end product through an intramolecular Michael addition of the hydroperoxyl group to the nitro group activated carbon-carbon double bond.

  3. Enantioselctive Syntheses of Sulfur Analogues of Flavan-3-Ols

    Directory of Open Access Journals (Sweden)

    Richard Lombardy

    2010-08-01

    Full Text Available The first enantioselective syntheses of sulfur flavan-3-ol analogues 1–8 have been accomplished, whereby the oxygen atom of the pyran ring has been replaced by a sulfur atom. The key steps were: (a Pd(0 catalyzed introduction of –S t-butyl group, (b Sharpless enantioselective dihydroxylation of the alkene, (c acid catalyzed ring closure to produce the thiopyran ring, and (d removal of benzyl groups using N,N-dimethylaniline and AlCl3. The compounds were isolated in high chemical and optical purity.

  4. Nonclassical mechanical states in an optomechanical micromaser analogue

    OpenAIRE

    Nation, P. D.

    2013-01-01

    Here we show that quantum states of a mechanical oscillator can be generated in an optomechanical analogue of the micromaser, in absence of any atom-like subsystem, thus exhibiting single-atom masing effects in a system composed solely of oscillator components. In the regime where the single-photon coupling strength is on the order of the cavity decay rate, a cavity mode with at most a single-excitation present gives rise to sub-Poissonian oscillator limit-cycles that generate quantum feature...

  5. Synthesis and Characterization of New Diketone Analogues of Podophyllotoxin

    Directory of Open Access Journals (Sweden)

    K. H. Hemakumar

    2008-01-01

    Full Text Available The new compounds 6,6a-dihydro-2,3-dimethoxy-9-nitro–11bH benzo [C]-fluoren 5,7-dione, 6,6a-dihydro-2,3-dimethoxy-9-chloro–11bH benzo[C]-fluoren-5,7-dione and 6,6a-dihydro-2,3-dimethoxy-9-fluoro–11bH benzo[C]-fluoren-5,7- dione were synthesized in high yields. They are analogues of naturally occurring lignan podophyllotoxin which exhibits anticancer activity. They are very essential to study anticancer activity.

  6. Astrobiology Field Research in Moon/Mars Analogue Environments: Preface

    Science.gov (United States)

    Foing, B. H.; Stoker, C.; Ehrenfreund, P.

    2011-01-01

    Extreme environments on Earth often provide similar terrain conditions to landing/operation sites on Moon and Mars. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) were conducted at the Mars Desert Research Station (MDRS) in Utah. Some of the key astrobiology results are presented in this special issue on Astrobiology field research in Moon/Mars analogue environments relevant to investigate the link between geology, minerals, organics and biota. Preliminary results from a multidisciplinary field campaign at Rio Tinto in Spain are presented.

  7. Association of VO2 and VCO2 rate variability with serum glucose, insulin, and glucose intolerance.

    Science.gov (United States)

    Satué-Rodríguez, Julián; Méndez, José D

    2012-08-01

    Changes in the cellular metabolism assessed by the variability of oxygen consumption (VO(2) ) and carbon dioxide production (VCO(2) ) as well as the association of serum glucose and insulin to energy spectral density (ESD) of VO(2) and VCO(2) were evaluated. Ten nonglucose intolerant and 10 glucose intolerant subjects, aged 21-70 years, were included. Glucose and insulin concentrations and VO(2) and VCO(2) records were collected every 10 min during 3 h. ESD of VO(2) and VCO(2) was estimated and associated with glucose and insulin concentrations. Statistical significance in glucose levels, insulin, and ESD of VO(2) and VCO(2) among nonglucose intolerant subjects and glucose and insulin among glucose intolerance subjects at postload glucose (PLG) state compared with basal state was found. Moreover, glucose was significantly higher in glucose intolerance subjects than nonglucose intolerant subjects for basal and PLG states. These results show an increment in ESD of VO(2) and VCO(2) at PLG state among nonglucose intolerant subjects and suggest that their measurement may be a key indicator of the variability of cellular metabolic activity and contribute to confirm disturbances in glucose metabolism.

  8. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

  9. Enantioselective reduction of acetophenone analogues using carrot and celeriac enzymes system

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The enantioselective reduction of acetophenone analogues catalyzed by carrot and celeriac was performed in moderate conversions and excellent enantiomeric excesses.The steric factors and electronic effects of the substituents at the aromatic ring were found to significantly affect the efficiency of the enantioselective reduction of acetophenone analogues,while they had a little effect on the enantioselectivity of acetophenone analogues reduction.It was also found that the conversions of acetophenone anal...

  10. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Qin; Sha, Sha; Sun, Lei; Zhang, Jing; Dong, Ming, E-mail: dr_dongming@126.com

    2016-08-05

    The incidence of nonalcoholic fatty liver disease (NAFLD) keeps rising year by year, and NAFLD is rapidly becoming the most common liver disease worldwide. Clinical studies have found that glucagon-like peptide-1 (GLP-1) analogue, liraglutide (LRG), cannot only reduce glucose levels, but also improve hepatic lipase, especially in patients also with type 2 diabetes mellitus (T2DM). In addition, enhancing autophagy decreases lipid accumulation in hepatocytes. The aim of the present study is to explore the effect of LRG on hepatocyte steatosis and the possible role of autophagy. We set up an obesity mouse model with a high-fat diet (HFD) and induced hepatocyte steatosis with free fatty acids (FFA) in human L-O2 cells. LRG and two inhibitors of autophagy, Chloroquine (CQ) and bafilomycin A1 (Baf), were added into each group, respectively. The lipid profiles and morphological modifications of each group were tested. Immunohistochemistry, immunofluorescence staining and transmission electron microscopy (TEM) were used to measure autophagy in this study. The autophagy protein expression of SQSTM1 (P62), and LC3B, along with the signaling pathway proteins of mTOR, phosphorylated mTOR (p-mTOR), AMPK, phosphorylated AMPK (p-AMPK) and Beclin1, were evaluated by western blot. Our results showed that LRG improved hepatocyte steatosis by inducing autophagy, and the AMPK/mTOR pathway is involved. These findings suggest an important mechanism for the positive effects of LRG on hepatic steatosis, and provide new evidence for clinical use of LRG in NAFLD. -- Highlights: •Liraglutide reduces lipid accumulation in hepatic steatosis both in vivo and in vitro. •Autophagy was involved in relieving effects of liraglutide on hepatic steatosis. •AMPK/mTOR pathway was involved in liraglutide-induced autophagy.

  11. Semisynthetic analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.

    Science.gov (United States)

    Gunasekera, Sarath P; Longley, Ross E; Isbrucker, Richard A

    2002-12-01

    A series of 12 semisynthetic discodermolide analogues, 2-13, have been prepared using natural (+)-discodermolide (1) and evaluated for in vitro cytotoxicity against cultured murine P-388 leukemia and A-549 human adenocarcinoma cells. These semisynthetic analogues showed a significant variation of cytotoxicity and confirmed the importance of the C-7 through C-19 molecular fragment for potency. Specifically, these analogues suggested the importance of the C-11 and C-17 hydroxyl groups and the C-13 double bond for the potency of discodermolide. The preparation, structure elucidation, and biological activity of these new analogues are described.

  12. THE OBJECTIVE ANALOGUE PREDICTION MODEL FOR TROPICAL CYCLONE TRACK WITH COMPREHENSIVE ASSESSMENT OF THE ENVIRONMENT

    Institute of Scientific and Technical Information of China (English)

    钟元

    2002-01-01

    An objective analogue prediction model for tropical cyclone (TC) track is put forward that comprehensively assesses the environmental field. With the parameters of the tropical cyclone and environmental field at initial and future time, objective analogue criteria are set up in the model. Analogous samples are recognized by comprehensive assessment of historical TC cases for similarity with multivariate criteria, using non-linear analogue indexes especially defined for the purpose. When the historical tracks are coordinateconverted and weighted with reference to analogue indexes, forecast tracks are determined. As shown in model verification and forecast experiments, the model has forecasting skill.

  13. Large scale biosynthesis of ganglioside analogues by RERF-LC-AI cells cultured in HYPERFlask.

    Science.gov (United States)

    Shimura, Yumiko; Suzuki, Junya; Muraoka, Miho; Kasuya, Maria Carmelita Zulueta; Matsuoka, Koji; Hatanaka, Kenichi

    2012-01-01

    The efficient production of ganglioside analogues was accomplished using RERF-LC-AI cells cultured in HYPERFlask (High Yield PERformance Flask). Eight kinds of ganglioside analogues (GM3, GM2, sialylparagloboside, GD3, di-sialylated lacto-N-tetraose, and another three kinds of analogues with intricate structures) were synthesized by the saccharide primer method using lung squamous-cell carcinoma line RERF-LC-AI and 12-azidododecyl β-lactoside primer. The yield for each analogue obtained using HYPERFlask was higher than yields obtained from 100-mm dishes.

  14. Synthesis, Physiochemical Properties, Photochemical Probe, and Antimicrobial Effects of Novel Norfloxacin Analogues

    National Research Council Canada - National Science Library

    Bakhotmah, Dina A; Abdul-Rahman, Reda M; Makki, Mohammad S; El-Zahabi, Mohamed A; Suliman, Mansor

    2011-01-01

    .... The present work aimed to synthesize novel norfloxacin analogues using modified Vilsmeier approach and conduct preliminary investigations for the evaluation of their physicochemical properties...

  15. Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes

    DEFF Research Database (Denmark)

    Frølund, Sidsel; Bella, Angelo; Kristensen, Anders Skov;

    2010-01-01

    -electrode voltage-clamp electrophysiology employing Xenopus laevis oocytes expressing GluA1(i) AMPA or GluN1/2A NMDA receptors. Several of the analogues showed significantly increased inhibition of the GluN1/2A NMDA receptor. Thus, an analogue containing N-(1-naphtyl)acetyl group showed an IC(50) value of 47 n......M. For the diamino acid-based analogues, the optimal spacer length between two N-acyl groups was determined, resulting in an analogue with an IC(50) value of 106 nM....

  16. Synthesis of cyclic analogues of cholecystokinin highly selective for central receptors.

    Science.gov (United States)

    Rodriguez, M; Amblard, M; Galas, M C; Lignon, M F; Aumelas, A; Martinez, J

    1990-05-01

    Cyclic CCK analogues in which positions 28 and 31 have been replaced by lysine residues and whose side chains are bridged by a succinic moiety, were synthesized. They were tested for their ability to inhibit the binding of 125I-BH-CCK-8 to isolated rat pancreatic acini and to guinea pig brain membranes. These cyclic CCK-analogues were compared to the potent CCK analogue Boc-[Nle28,31]-CCK-7 and to Boc-Trp-Leu-Asp-Phe-NH2, analogue of CCK-4. These cyclic compounds appeared to be highly selective for central CCK receptors.

  17. Salivary Glucose Concentration and Excretion in Normal and Diabetic Subjects

    Directory of Open Access Journals (Sweden)

    Cedric Jurysta

    2009-01-01

    saliva glucose concentration was comparable, however, to that of blood glucose concentration. The relationship between these two variables was also documented in normal subjects and diabetic patients undergoing an oral glucose tolerance test.

  18. Characterizing Accuracy and Precision of Glucose Sensors and Meters

    National Research Council Canada - National Science Library

    Rodbard, David

    2014-01-01

    Background: There is need for a method to describe precision and accuracy of glucose measurement as a smooth continuous function of glucose level rather than as a step function for a few discrete ranges of glucose...

  19. Taeniid tapeworm responses to in vitro glucose.

    Science.gov (United States)

    Willms, Kaethe; Presas, Ana María Fernández; Jiménez, José Agustín; Landa, Abraham; Zurabián, Rimma; Ugarte, María Eugenia Juárez; Robert, Lilia

    2005-07-01

    Experimental taeniid strobilae from Taenia solium and T. crassiceps (WFU strain) were incubated for 0-72 h in 0, 5 or 20 mM glucose solutions and further exposed for 15 min to the gap junction fluorochrome Lucifer Yellow. Frozen sections were obtained from each worm and observed under an epifluorescent microscope. Worm sections from strobilae incubated with glucose, revealed intense fluorescence in the base of the tegumentary surface, suggesting that this tissue behaves as a gap junction complex. Fluorescence intensity differences between control worms not exposed to glucose and worms incubated with glucose, were highly significant. The results demonstrate that under in vitro conditions, glucose is taken up along the whole strobilar tegument in both taeniid species, suggesting, that although taeniids attached to the duodenum probably take up most of their nutrients directly from the mucosal wall, the capacity for absorbing glucose along the tegumentary surface is always active and may increase the survival capacity of these intestinal worms by promoting glucose absorption at other points in the intestinal lumen.

  20. Altered glucose metabolism in metastatic carcinoma.

    Science.gov (United States)

    Holroyde, C P; Gabuzda, T G; Putnam, R C; Paul, P; Reichard, G A

    1975-12-01

    To evaluate the possible role of altered glucose metabolism in malignant cachexia, metabolic parameters including total glucose turnover, glucose oxidation, and Cori cycle activity were measured in fourteen patients with metastatic carcinoma. Eight patients with progressive weight loss (PWL) were compared to 6 without (controls). Cori cycle activity was significantly increased (p less than 0.02) in PWL patients, 90 mg/kg/hr (range, 22 to 193) compared to 18 mg/kg/hr (range, 13 to 24) in controls. Total glucose turnover was moderately increased in PWL patients, 196 mg/kg/hr compared to 110 mg/kg/hr in controls. Glucose oxidation was 62 mg/kg/hr versus 48 mg/kg/hr, and total caloric expenditure was 36 kcal/sq m/hr compared to 33 Kcal/sq m/hr. PWL patients were metabolically heterogenous and mean values are skewed by four patients with increased glucose turnover, oxidation, and markedly high recycling rates that were equivalent to total endogenous glucose turnover of a normal subject. Total caloric expenditure was greatest in three of the four patients with a marked increase in Cori cycle activity. Energy loss associated with a high rate of gluconeogenesis from lactate has been suggested as an explanation for increased energy expenditure in some cancer patients, thus contributing to mechanisms that promote weight loss.