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Sample records for analog benfotiamine prevents

  1. Vitamin B1 Analog Benfotiamine Prevents Diabetes-Induced Diastolic Dysfunction and Heart Failure Through Akt/Pim-1–Mediated Survival Pathway

    Science.gov (United States)

    Katare, Rajesh G.; Caporali, Andrea; Oikawa, Atsuhiko; Meloni, Marco; Emanueli, Costanza; Madeddu, Paolo

    2010-01-01

    Background The increasing incidence of diabetes mellitus will result in a new epidemic of heart failure unless novel treatments able to halt diabetic cardiomyopathy early in its course are introduced. This study aimed to determine whether the activity of the Akt/Pim-1 signaling pathway is altered at critical stages of diabetic cardiomyopathy and whether supplementation with vitamin B1 analog benfotiamine (BFT) helps to sustain the above prosurvival mechanism, thereby preserving cardiomyocyte viability and function. Methods and Results Untreated streptozotocin-induced type 1 or leptin-receptor mutant type 2 diabetic mice showed diastolic dysfunction evolving to contractile impairment and cardiac dilatation and failure. BFT (70 mg/kg−1/d−1) improved diastolic and systolic function and prevented left ventricular end-diastolic pressure increase and chamber dilatation in both diabetic models. Moreover, BFT improved cardiac perfusion and reduced cardiomyocyte apoptosis and interstitial fibrosis. In hearts of untreated diabetic mice, the expression and activity of Akt/Pim-1 signaling declined along with O-N-acetylglucosamine modification of Akt, inhibition of pentose phosphate pathway, activation of oxidative stress, and accumulation of glycation end products. Furthermore, diabetes reduced signal transducer and activator of transcription 3 phosphorylation independently of Akt. BFT inhibited these effects of diabetes mellitus, thereby conferring cardiomyocytes with improved resistance to high glucose-induced damage. The phosphoinositide-3-kinase inhibitor LY294002 and dominant-negative Akt inhibited antiapoptotic action of BFT and Pim-1 upregulation in high glucose-challenged cardiomyocytes. Conclusions These results show that BFT protects from diabetes mellitus-induced cardiac dysfunction through pleiotropic mechanisms, culminating in the activation of prosurvival signaling pathway. Thus, BFT merits attention for application in clinical practice. PMID:20107192

  2. Vitamin B1 analog benfotiamine prevents diabetes-induced diastolic dysfunction and heart failure through Akt/Pim-1-mediated survival pathway.

    Science.gov (United States)

    Katare, Rajesh G; Caporali, Andrea; Oikawa, Atsuhiko; Meloni, Marco; Emanueli, Costanza; Madeddu, Paolo

    2010-03-01

    The increasing incidence of diabetes mellitus will result in a new epidemic of heart failure unless novel treatments able to halt diabetic cardiomyopathy early in its course are introduced. This study aimed to determine whether the activity of the Akt/Pim-1 signaling pathway is altered at critical stages of diabetic cardiomyopathy and whether supplementation with vitamin B1 analog benfotiamine (BFT) helps to sustain the above prosurvival mechanism, thereby preserving cardiomyocyte viability and function. Untreated streptozotocin-induced type 1 or leptin-receptor mutant type 2 diabetic mice showed diastolic dysfunction evolving to contractile impairment and cardiac dilatation and failure. BFT (70 mg/kg(-1)/d(-1)) improved diastolic and systolic function and prevented left ventricular end-diastolic pressure increase and chamber dilatation in both diabetic models. Moreover, BFT improved cardiac perfusion and reduced cardiomyocyte apoptosis and interstitial fibrosis. In hearts of untreated diabetic mice, the expression and activity of Akt/Pim-1 signaling declined along with O-N-acetylglucosamine modification of Akt, inhibition of pentose phosphate pathway, activation of oxidative stress, and accumulation of glycation end products. Furthermore, diabetes reduced pSTAT3 independently of Akt. BFT inhibited these effects of diabetes mellitus, thereby conferring cardiomyocytes with improved resistance to high glucose-induced damage. The phosphoinositide-3-kinase inhibitor LY294002 and dominant-negative Akt inhibited antiapoptotic action of BFT-induced and Pim-1 upregulation in high glucose-challenged cardiomyocytes. These results show that BFT protects from diabetes mellitus-induced cardiac dysfunction through pleiotropic mechanisms, culminating in the activation of prosurvival signaling pathway. Thus, BFT merits attention for application in clinical practice.

  3. Preventive effects of benfotiamine in chronic diabetic complications.

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    Chakrabarti, Rana; Chen, Megan; Liu, Weihua; Chen, Shali

    2011-04-07

    Aims/Introduction:  In diabetes, increased oxidative stress as a result of damage to the electron transport chain can lead to tissue injury through upregulation of multiple vasoactive factors and extracellular matrix proteins. Benfotiamine, a lipid soluble thiamine derivative, through reducing mitochondrial superoxide production, blocks multiple pathways leading to tissue damage in hyperglycemia. We investigated if treatment with benfotiamine can prevent diabetes-induced production of vasoactive factors and extracellular matrix proteins, and whether such effects are tissue-specific. We also examined whether effects of benfotiamine are mediated through a nuclear mechanism.   Retinal, renal and cardiac tissues from the streptozotocin-induced diabetic rats were examined after 4 months of follow up. mRNA levels were quantified using real-time RT-PCR. Protein levels were quantified using western blot and ELISA. Cellular expressions of 8-Hydroxy-2'-deoxyguanosine, a marker of nuclear DNA damage and Phospho-H2AX were also examined.   Diabetic animals showed hyperglycemia, glucosuria, increased urinary albumin/creatine ratio and loss of bodyweight. In the kidneys, heart and retina, diabetes caused increased production of endothelin-1, transforming growth factor-β1, vascular endothelial growth factor and augmented extracellular matrix proteins (collagen, fibronectin [FN] and its splice variant extradomain B containing FN), along with evidence of structural alterations, characteristic of diabetes-induced tissue damage. Such changes were prevented by benfotiamine. Furthermore, benfotiamine prevented diabetes-induced oxidative DNA damage and upregulation of p300, a histone acetylator and a transcription coactivator.   Data from the present study suggest that benfotiamine is effective in preventing tissue damage in diabetes and at the transcriptional level such effects are mediated through prevention of p300 upregulation. (J Diabetes Invest, doi: 10.1111/j.2040

  4. Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro.

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    Schmid, Ursula; Stopper, Helga; Heidland, August; Schupp, Nicole

    2008-01-01

    Complications in diabetes mellitus are partially mediated by enhanced formation of reactive oxygen species. Among the factors involved in reactive oxygen species formation, advanced glycation end products play a key role. Owing to a reduced activity of the enzyme transketolase, which requires diphosphorylated thiamine (vitamin B(1)) as cofactor, an accumulation of those deleterious glucose metabolites especially in diabetic patients can be observed. Benfotiamine, a lipophilic thiamine diphosphate prodrug, prevented early renal and retinal changes in animal studies, and reduced neuropathic pain in clinical studies. Several mechanisms for these activities have been described. We investigated for the first time direct antioxidant abilities of benfotiamine. Additionally, a potential DNA protective effect of benfotiamine was analysed. Oxidative stress was detected by flow cytometry, antioxidative capacity was measured with the ferric reducing ability of plasma (FRAP) assay, two endpoints for genomic damage were assessed: the comet assay and the micronucleus test, and the expression and activity of transketolase was quantified. Benfotiamine prevented oxidative stress induced by the mutagen 4-nitroquinoline-1-oxide (NQO), the uremic toxin indoxyl sulfate, and the peptide hormone angiotensin II in three different kidney cell lines. Cell-free experiments showed a direct antioxidant effect of benfotiamine, which might account for the protective effect. Oxidative DNA damage, induced by angiotensin II, was completely prevented by benfotiamine. Incubation with benfotiamine increased transketolase expression and activity in the cells. Benfotiamine shows a direct antioxidant action. This effect of benfotiamine may be involved in the improvement of diabetic late complications, including peripheral neuropathy.

  5. Paraptosis Cell Death Induction by the Thiamine Analog Benfotiamine in Leukemia Cells

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    Sugimori, Naomi; Espinoza, J. Luis; Trung, Ly Quoc; Takami, Akiyoshi; Kondo, Yukio; An, Dao Thi; Sasaki, Motoko; Wakayama, Tomohiko; Nakao, Shinji

    2015-01-01

    Benfotiamine is a synthetic thiamine analogue that stimulates transketolase, a cellular enzyme essential for glucose metabolism. Currently, benfotiamine is used to treat diabetic neuropathy. We recently reported that oral benfotiamine induced a temporary but remarkable recovery from acute myeloid leukemia in an elderly patient who was ineligible for standard chemotherapy due to dementia and renal failure. In the present study we present evidences that benfotiamine possess antitumor activity a...

  6. Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia cells.

    Directory of Open Access Journals (Sweden)

    Naomi Sugimori

    Full Text Available Benfotiamine is a synthetic thiamine analogue that stimulates transketolase, a cellular enzyme essential for glucose metabolism. Currently, benfotiamine is used to treat diabetic neuropathy. We recently reported that oral benfotiamine induced a temporary but remarkable recovery from acute myeloid leukemia in an elderly patient who was ineligible for standard chemotherapy due to dementia and renal failure. In the present study we present evidences that benfotiamine possess antitumor activity against leukemia cells. In a panel of nine myeloid leukemia cell lines benfotiamine impaired the viability of HL-60, NB4, K562 and KG1 cells and also inhibited the growing of primary leukemic blasts. The antitumor activity of benfotiamine is not mediated by apoptosis, necrosis or autophagy, but rather occurs though paraptosis cell death induction. Mechanistic studies revealed that benfotiamine inhibited the activity of constitutively active ERK1/2 and concomitantly increased the phosphorylation of JNK1/2 kinase in leukemic cells. In addition, benfotiamine induced the down regulation of the cell cycle regulator CDK3 which resulted in G1 cell cycle arrest in the sensitive leukemic cells. Moreover, combination index studies showed that benfotiamine enhanced the antiproliferative activities of cytarabine against leukemia cells. These findings suggest that benfotiamine has antitumor therapeutic potential.

  7. Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia cells.

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    Sugimori, Naomi; Espinoza, J Luis; Trung, Ly Quoc; Takami, Akiyoshi; Kondo, Yukio; An, Dao Thi; Sasaki, Motoko; Wakayama, Tomohiko; Nakao, Shinji

    2015-01-01

    Benfotiamine is a synthetic thiamine analogue that stimulates transketolase, a cellular enzyme essential for glucose metabolism. Currently, benfotiamine is used to treat diabetic neuropathy. We recently reported that oral benfotiamine induced a temporary but remarkable recovery from acute myeloid leukemia in an elderly patient who was ineligible for standard chemotherapy due to dementia and renal failure. In the present study we present evidences that benfotiamine possess antitumor activity against leukemia cells. In a panel of nine myeloid leukemia cell lines benfotiamine impaired the viability of HL-60, NB4, K562 and KG1 cells and also inhibited the growing of primary leukemic blasts. The antitumor activity of benfotiamine is not mediated by apoptosis, necrosis or autophagy, but rather occurs though paraptosis cell death induction. Mechanistic studies revealed that benfotiamine inhibited the activity of constitutively active ERK1/2 and concomitantly increased the phosphorylation of JNK1/2 kinase in leukemic cells. In addition, benfotiamine induced the down regulation of the cell cycle regulator CDK3 which resulted in G1 cell cycle arrest in the sensitive leukemic cells. Moreover, combination index studies showed that benfotiamine enhanced the antiproliferative activities of cytarabine against leukemia cells. These findings suggest that benfotiamine has antitumor therapeutic potential.

  8. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.

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    Hammes, Hans-Peter; Du, Xueliang; Edelstein, Diane; Taguchi, Tetsuya; Matsumura, Takeshi; Ju, Qida; Lin, Jihong; Bierhaus, Angelika; Nawroth, Peter; Hannak, Dieter; Neumaier, Michael; Bergfeld, Regine; Giardino, Ida; Brownlee, Michael

    2003-03-01

    Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-kappaB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars. In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy. The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications.

  9. Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose.

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    Beltramo, E; Berrone, E; Buttiglieri, S; Porta, M

    2004-01-01

    High glucose induces pathological alterations in small and large vessels, possibly through increased formation of AGE, activation of aldose reductase and protein kinase C, and increased flux through the hexosamine pathway. We showed previously that thiamine and benfotiamine correct delayed replication and increase lactate production in endothelial cells subjected to high glucose. We now aim at verifying the effects of thiamine and benfotiamine on cell cycle, apoptosis, and expression of adhesion molecules in endothelial cells and pericytes, under high ambient glucose. Human umbilical vein endothelial cells and bovine retinal pericytes were cultured in normal (5.6 mmol/L) or high (28 mmol/L) glucose, with or without thiamine or benfotiamine, 50 or 100 micro mol/L. Apoptosis was determined by two separate ELISA methods, measuring DNA fragmentation and caspase-3 activity, respectively. Cell cycle and integrin subunits alpha3, alpha5, and beta1 concentration were measured by flow cytometry. Apoptosis was increased in high glucose after 3 days of culture, both in endothelium and pericytes. Thiamine and benfotiamine reversed such effects. Neither cell cycle traversal nor integrin concentrations were modified in these experimental conditions. Thiamine and benfotiamine correct increased apoptosis due to high glucose in cultured vascular cells. Further elucidations of the mechanisms through which they work could help set the basis for clinical use of this vitamin in the prevention and/or treatment of diabetic microangiopathy. Copyright 2004 John Wiley & Sons, Ltd.

  10. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.

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    Babaei-Jadidi, Roya; Karachalias, Nikolaos; Ahmed, Naila; Battah, Sinan; Thornalley, Paul J

    2003-08-01

    Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy. High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. This was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.

  11. Benfotiamine prevents increased β-amyloid production in HEK cells induced by high glucose.

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    Sun, Xiao-Jing; Zhao, Lei; Zhao, Na; Pan, Xiao-Li; Fei, Guo-Qiang; Jin, Li-Rong; Zhong, Chun-Jiu

    2012-10-01

    To determine whether high glucose enhances β-amyloid (Aβ) production in HEK293 Swedish mutant (APPsw) cells with Aβ precursor protein (APP) overexpression, and whether under this condition benfotiamine reduces the increased Aβ production. HEK293 APPsw cells were cultured with different concentrations of glucose for different times. The Aβ content in the supernatant was determined by ELISA. To investigate the mechanism by which benfotiamine reduced Aβ production, glycogen synthase kinase-3 (GSK-3) activity and expression were measured after the cells were cultured with 5.5 g/L glucose for 12 h. With 1.0, 3.0, 4.5, 5.5, 6.5, 7.5, 8.5, or 10.5 g/L glucose, Aβ production by HEK293 APPsw cells was highest in the presence of 5.5 g/L glucose for 6 and 12 h. The difference in Aβ content between 5.5 and 1.0 g/L was most marked after incubation for 12 h. Benfotiamine at 20 and 40 μg/mL significantly reduced Aβ production in cells incubated with 5.5 g/L glucose for 12 h. Moreover, 40 μg/mL benfotiamine significantly enhanced the ratio of phosphorylated GSK-3 to total GSK-3, together with consistent down-regulation of GSK-3 activity. High glucose increases Aβ production by HEK293 APPsw cells while benfotiamine prevents this increase. This is correlated with the modulation of GSK-3 activity.

  12. Thiamine and benfotiamine prevent apoptosis induced by high glucose-conditioned extracellular matrix in human retinal pericytes.

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    Beltramo, Elena; Nizheradze, Konstantin; Berrone, Elena; Tarallo, Sonia; Porta, Massimo

    2009-10-01

    Early and selective loss of pericytes and thickening of the basement membrane are hallmarks of diabetic retinopathy. We reported reduced adhesion, but no changes in apoptosis, of bovine retinal pericytes cultured on extracellular matrix (ECM) produced by endothelial cells in high glucose (HG). Since human and bovine pericytes may behave differently in conditions mimicking the diabetic milieu, we verified the behaviour of human retinal pericytes cultured on HG-conditioned ECM. Pericytes were cultured in physiological/HG on ECM produced by human umbilical vein endothelial cells in physiological/HG, alone or in the presence of thiamine and benfotiamine. Adhesion, proliferation, apoptosis, p53 and Bcl-2/Bax ratio (mRNA levels and protein concentrations) were measured in wild-type and immortalized human pericytes. Both types of pericytes adhered less to HG-conditioned ECM and plastic than to physiological glucose-conditioned ECM. DNA synthesis was impaired in pericytes cultured in HG on the three different surfaces but there were no differences in proliferation. DNA fragmentation and Bcl-2/Bax ratio were greatly enhanced by HG-conditioned ECM in pericytes kept in both physiological and HG. Addition of thiamine and benfotiamine to HG during ECM production completely prevented these damaging effects. Apoptosis is strongly increased in pericytes cultured on ECM produced by endothelium in HG, probably due to impairment of the Bcl-2/Bax ratio. Thiamine and benfotiamine completely revert this effect. This behaviour is therefore completely different from that of bovine pericytes, underlining the importance of establishing species-specific cell models to study the mechanisms of diabetic retinopathy. (c) 2009 John Wiley & Sons, Ltd.

  13. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes.

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    Stirban, Alin; Negrean, Monica; Stratmann, Bernd; Gawlowski, Thomas; Horstmann, Tina; Götting, Christian; Kleesiek, Knut; Mueller-Roesel, Michaela; Koschinsky, Theodor; Uribarri, Jaime; Vlassara, Helen; Tschoepe, Diethelm

    2006-09-01

    Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now. Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially. The HAGE induced a maximum reactive hyperemia decrease of -60.0% after 2 h and a maximum FMD impairment of -35.1% after 4 h, without affecting endothelium-independent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine. Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.

  14. Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications.

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    Beltramo, Elena; Berrone, Elena; Tarallo, Sonia; Porta, Massimo

    2008-09-01

    Thiamine (vitamin B1) is an essential cofactor in most organisms and is required at several stages of anabolic and catabolic intermediary metabolism, such as intracellular glucose metabolism, and is also a modulator of neuronal and neuro-muscular transmission. Lack of thiamine or defects in its intracellular transport can cause a number of severe disorders. Thiamine acts as a coenzyme for transketolase (TK) and for the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism. In particular, TK is able to shift excess fructose-6-phosphate and glycerhaldeyde-3-phosphate from glycolysis into the pentose-phosphate shunt, thus eliminating these potentially damaging metabolites from the cytosol. Diabetes might be considered a thiamine-deficient state, if not in absolute terms at least relative to the increased requirements deriving from accelerated and amplified glucose metabolism in non-insulin dependent tissues that, like the vessel wall, are prone to complications. A thiamine/TK activity deficiency has been described in diabetic patients, the correction of which by thiamine and/or its lipophilic derivative, benfotiamine, has been demonstrated in vitro to counteract the damaging effects of hyperglycaemia on vascular cells. Little is known, however, on the positive effects of thiamine/benfotiamine administration in diabetic patients, apart from the possible amelioration of neuropathic symptoms. Clinical trials on diabetic patients would be necessary to test this vitamin as a potential and inexpensive approach to the prevention and/or treatment of diabetic vascular complications.

  15. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes.

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    Karachalias, N; Babaei-Jadidi, R; Rabbani, N; Thornalley, P J

    2010-07-01

    The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy. Diabetes was induced in male Sprague-Dawley rats by 55 mg/kg streptozotocin and moderated by insulin (2 U twice daily). Diabetic and control rats were given thiamine or benfotiamine (7 or 70 mg kg(-1) day(-1)) over 24 weeks. Plasma, urine and tissues were collected and analysed for protein damage by stable isotopic dilution analysis MS. There were two- to fourfold increases in fructosyl-lysine and AGE content of glomerular, retinal, sciatic nerve and plasma protein in diabetes. Increases in AGEs were reversed by thiamine and benfotiamine therapy but increases in fructosyl-lysine were not. Methionine sulfoxide content of plasma protein and 3-nitrotyrosine content of sciatic nerve protein were increased in diabetes. Plasma glycation free adducts were increased up to twofold in diabetes; the increases were reversed by thiamine. Urinary excretion of glycation, oxidation and nitration free adducts was increased by seven- to 27-fold in diabetes. These increases were reversed by thiamine and benfotiamine therapy. AGEs, particularly arginine-derived hydroimidazolones, accumulate at sites of microvascular complication development and have markedly increased urinary excretion rates in experimental diabetes. Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine.

  16. Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels.

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    Vignisse, Julie; Sambon, Margaux; Gorlova, Anna; Pavlov, Dmitrii; Caron, Nicolas; Malgrange, Brigitte; Shevtsova, Elena; Svistunov, Andrey; Anthony, Daniel C; Markova, Natalyia; Bazhenova, Natalyia; Coumans, Bernard; Lakaye, Bernard; Wins, Pierre; Strekalova, Tatyana; Bettendorff, Lucien

    2017-07-01

    Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This reduction was prevented when the mice were treated (200mg/kg/day in drinking water for 20days) with thiamine or benfotiamine, that were recently found to prevent stress-induced behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS. Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP) remained unchanged, suggesting that the beneficial effects observed are not linked to the role of this coenzyme in energy metabolism. Predator stress increased hippocampal protein carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in particular benfotiamine protects against paraquat-induced oxidative stress. We therefore hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that thiamine and benfotiamine prevent

  17. Prevention of endotoxin-induced uveitis in rats by benfotiamine, a lipophilic analogue of vitamin B1.

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    Yadav, Umesh C S; Subramanyam, Sumitra; Ramana, Kota V

    2009-05-01

    To study the amelioration of ocular inflammation in endotoxin-induced uveitis (EIU) in rats by benfotiamine, a lipid-soluble analogue of thiamine. EIU in Lewis rats was induced by subcutaneous injection of lipopolysaccharide (LPS) followed by treatment with benfotiamine. The rats were killed 3 or 24 hours after LPS injection, eyes were enucleated, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. Immunohistochemical analysis of eye sections was performed to determine the expression of inducible-nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, protein kinase C (PKC), and transcription factor NF-kappaB. Infiltrating leukocytes, protein concentrations, and inflammatory cytokines and chemokines were significantly elevated in the AqH of EIU rats compared with control rats, and benfotiamine treatment suppressed these increases. Similarly increased expression of inflammatory markers iNOS and Cox-2 in ciliary body and retinal wall was also significantly inhibited by benfotiamine. The increased phosphorylation of PKC and the activation of NF-kappaB in the ciliary body and in the retinal wall of EIU rat eyes were suppressed by benfotiamine. These results suggest that benfotiamine suppresses oxidative stress-induced NF-kappaB-dependent inflammatory signaling leading to uveitis. Therefore, benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.

  18. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

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    Iva eBozic

    2015-09-01

    Full Text Available Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes – catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and •O2- production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

  19. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells.

    Science.gov (United States)

    Bozic, Iva; Savic, Danijela; Stevanovic, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate) possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes-catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and (·)O(-) 2 production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

  20. Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers.

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    Stirban, Alin; Nandrean, Simona; Kirana, Stanley; Götting, Christian; Veresiu, Ioan Andrei; Tschoepe, Diethelm

    2012-01-01

    Background. Smoking induces endothelial dysfunction (ED) mainly by exacerbating oxidative stress (OS) and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years) were investigated twice, 7-10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM)-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day). Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM). Smoking acutely induced a decrease in FMD by 50% ((∗∗)P benfotiamine treatment to 25%(∗§) ((∗)P benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

  1. Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

    OpenAIRE

    Shoeb, Mohammad; Ramana, Kota V

    2011-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of...

  2. Benfotiamine Counteracts Smoking-Induced Vascular Dysfunction in Healthy Smokers

    Directory of Open Access Journals (Sweden)

    Alin Stirban

    2012-01-01

    Full Text Available Background. Smoking induces endothelial dysfunction (ED mainly by exacerbating oxidative stress (OS and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years were investigated twice, 7–10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day. Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM. Smoking acutely induced a decrease in FMD by 50% (∗∗P<0.001 versus baseline an effect significantly reduced by benfotiamine treatment to 25%∗§ (∗P<0.05 versus baseline, §P<0.05 versus smoking alone. Smoking-induced elevation in sVCAM-1 was also prevented by benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

  3. Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis.

    Science.gov (United States)

    Gadau, S; Emanueli, C; Van Linthout, S; Graiani, G; Todaro, M; Meloni, M; Campesi, I; Invernici, G; Spillmann, F; Ward, K; Madeddu, P

    2006-02-01

    Benfotiamine, a vitamin B1 analogue, reportedly prevents diabetic microangiopathy. The aim of this study was to evaluate whether benfotiamine is of benefit in reparative neovascularisation using a type I diabetes model of hindlimb ischaemia. We also investigated the involvement of protein kinase B (PKB)/Akt in the therapeutic effects of benfotiamine. Streptozotocin-induced diabetic mice, given oral benfotiamine or vehicle, were subjected to unilateral limb ischaemia. Reparative neovascularisation was analysed by histology. The expression of Nos3 and Casp3 was evaluated by real-time PCR, and the activation state of PKB/Akt was assessed by western blot analysis and immunohistochemistry. The functional importance of PKB/Akt in benfotiamine-induced effects was investigated using a dominant-negative construct. Diabetic muscles showed reduced transketolase activity, which was corrected by benfotiamine. Importantly, benfotiamine prevented ischaemia-induced toe necrosis, improved hindlimb perfusion and oxygenation, and restored endothelium-dependent vasodilation. Histological studies revealed the improvement of reparative neovascularisation and the inhibition of endothelial and skeletal muscle cell apoptosis. In addition, benfotiamine prevented the vascular accumulation of advanced glycation end products and the induction of pro-apoptotic caspase-3, while restoring proper expression of Nos3 and Akt in ischaemic muscles. The benefits of benfotiamine were nullified by dominant-negative PKB/Akt. In vitro, benfotiamine stimulated the proliferation of human EPCs, while inhibiting apoptosis induced by high glucose. In diabetic mice, the number of circulating EPCs was reduced, with the deficit being corrected by benfotiamine. We have demonstrated, for the first time, that benfotiamine aids the post-ischaemic healing of diabetic animals via PKB/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. In addition, benfotiamine combats the diabetes-induced deficit in

  4. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2012-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2011-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating the arachidonic acid (AA) pathway generated inflammatory lipid mediators in RAW 264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes (LTB4), prostaglandin E2 (PGE2), thromboxanes 2 (TXB2) and prostacyclin (PGI2) in macrophages. Further, LPS-induced expressions of AA metabolizing enzymes such as COX-2, LOX-5, TXB synthase and PGI2 synthase were significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-kB, and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adducts formation. Most importantly, as compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented the LPS-induced macrophage death and monocytes adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. PMID:22067901

  6. Pharmacokinetics of thiamine derivatives especially of benfotiamine.

    Science.gov (United States)

    Loew, D

    1996-02-01

    Pharmacokinetic data of orally administered lipid-soluble thiamine analogues like benfotiamine are reviewed and assessed. It is quite clear that benfotiamine is absorbed much more better than water-soluble thiamine salts: maximum plasma levels of thiamine are about 5 times higher after benfotiamine, the bioavailability is at maximum about 3.6 times as high as that of thiamine hydrochloride and better than other lipophilic thiamine derivates. The physiological activity (alphaETK) increased only after benfotiamine was given. Due to its excellent pharmacokinetic profile benfotiamine should be preferred in treatment of relevant indications.

  7. Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats.

    Science.gov (United States)

    Stracke, H; Hammes, H P; Werkmann, D; Mavrakis, K; Bitsch, I; Netzel, M; Geyer, J; Köpcke, W; Sauerland, C; Bretzel, R G; Federlin, K F

    2001-01-01

    In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble) thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function (motor nerve conduction velocity) as well as on the formation of advanced glycation end-products in peripheral nerve tissue was studied. In one group of animals drug administration was started immediately after diabetes induction (prevention study) and in another group two months after diabetes induction (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration, deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with controls. After three months preventive administration of both vitamin B(1) preparations NCV had increased substantially compared with results in diabetic controls. It was nearly normal after six months with benfotiamine, while the administration of thiamine nitrate resulted in no further amelioration. NCV was nearly normalized after six months of benfotiamine application but not with thiamine. Furthermore, benfotiamine induced a major inhibition of neural imidazole-type AGE formation and completely prevented diabetes induced glycoxidation products (CML). Treatment with thiamine did not significantly affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate timely administration of liposoluble prodrug benfotiamine was effective in the prevention of functional damage and of AGE and cmL formation in nerves of diabetic rats.

  8. Using Analogies to Prevent Misconceptions about Chemical Equilibrium

    Science.gov (United States)

    Sahin Pekmez, Esin

    2010-01-01

    The main purpose of this study was to find the effectiveness of using analogies to prevent misconceptions about chemical equilibrium. Nineteen analogies, which were based on dynamic aspects of chemical equilibrium and application of Le Chatelier's principle, were developed. The participations of this study consisted of 11th grade students (n: 151)…

  9. The multifaceted therapeutic potential of benfotiamine.

    Science.gov (United States)

    Balakumar, Pitchai; Rohilla, Ankur; Krishan, Pawan; Solairaj, Ponnu; Thangathirupathi, Arunachalam

    2010-06-01

    Thiamine, known as vitamin B(1), plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of benfotiamine. (c) 2010 Elsevier Ltd. All rights reserved.

  10. Detection of transketolase in bone marrow-derived insulin-producing cells: benfotiamine enhances insulin synthesis and glucose metabolism.

    Science.gov (United States)

    Oh, Seh-Hoon; Witek, Rafal P; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E

    2009-01-01

    Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the proliferation of insulinoma cell line, INS-1; however, when INS-1 cells were cultured with oxythiamine, an inhibitor of TK, cell proliferation was suppressed. Treatment with benfotiamine activated glucose metabolism in INS-1 cells in high-glucose culture conditions, and appeared to maximize the BM-derived IPCs ability to synthesize insulin. Benfotiamine was not shown to induce the glucose receptor Glut-2, however it was shown to activate glucokinase, the enzyme responsible for conversion of glucose to glucose-6-phosphate. Furthermore, benfotiamine-treated groups showed upregulation of the downstream glycolytic enzyme, glyceraldehyde phosphate dehydrogenase (GAPDH). However, in cells where the pentose phosphate pathway was blocked by oxythiamine treatment, there was a clear downregulation of Glut-2, glucokinase, insulin, and GAPDH. When benfotiamine was used to treat mice transplanted with BM-derived IPCs transplanted, their glucose level was brought to a normal range. The glucose challenge of normal mice treated with benfotiamine lead to rapidly normalized blood glucose levels. These results indicate that benfotiamine activates glucose metabolism and insulin synthesis to prevent glucose toxicity caused by high concentrations of blood glucose in diabetes mellitus.

  11. Detection of Transketolase in Bone Marrow—Derived Insulin-Producing Cells: Benfotiamine Enhances Insulin Synthesis and Glucose Metabolism

    Science.gov (United States)

    Witek, Rafal P.; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E.

    2009-01-01

    Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the proliferation of insulinoma cell line, INS-1; however, when INS-1 cells were cultured with oxythiamine, an inhibitor of TK, cell proliferation was suppressed. Treatment with benfotiamine activated glucose metabolism in INS-1 cells in high-glucose culture conditions, and appeared to maximize the BM-derived IPCs ability to synthesize insulin. Benfotiamine was not shown to induce the glucose receptor Glut-2, however it was shown to activate glucokinase, the enzyme responsible for conversion of glucose to glucose-6-phosphate. Furthermore, benfotiamine-treated groups showed upregulation of the downstream glycolytic enzyme, glyceraldehyde phosphate dehydrogenase (GAPDH). However, in cells where the pentose phosphate pathway was blocked by oxythiamine treatment, there was a clear downregulation of Glut-2, glucokinase, insulin, and GAPDH. When benfotiamine was used to treat mice transplanted with BM-derived IPCs transplanted, their glucose level was brought to a normal range. The glucose challenge of normal mice treated with benfotiamine lead to rapidly normalized blood glucose levels. These results indicate that benfotiamine activates glucose metabolism and insulin synthesis to prevent glucose toxicity caused by high concentrations of blood glucose in diabetes mellitus. PMID:18393672

  12. Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose.

    Science.gov (United States)

    Pomero, F; Molinar Min, A; La Selva, M; Allione, A; Molinatti, G M; Porta, M

    2001-01-01

    We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation end-products (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 microM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3%+/-5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%+/-2.4%, p=0.005) or benfotiamine (87.5%+/-8.9%, p=0.006), although it not was completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%+/-38.9% of fluorescence in physiological glucose, p=0.003) was reduced by thiamine (113.2%+/-16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%+/-49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation.

  13. Benfotiamine and Alpha-Lipoic Acid in the Treatment of Diabetic Cardiovascular Autonomic Neuropathy (Review of Literature and Own Researches

    Directory of Open Access Journals (Sweden)

    V.O. Sergiyenko

    2014-04-01

    Full Text Available The analysis of current views on the mechanisms of fat-soluble form of vitamin B1 (benfotiamine and α-lipoic acid action, in particular features of their impact on carbohydrate and lipid metabolism, endothelial function, hemodynamics, vessel stiffness in cardiovascular diseases, cardiovascular autonomic neuropathy in type 2 diabetes mellitus, was perfomed. The results of experimental, randomized and own studies confirmed the value of the combined administration of benfotiamine and α-lipoic acid for the prevention and treatment of cardiovascular diseases, in particular cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus.

  14. Ameliorative effect of combination of benfotiamine and fenofibrate in diabetes-induced vascular endothelial dysfunction and nephropathy in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Chakkarwar, Vishal Arvind; Singh, Manjeet

    2009-01-01

    The study has been designed to investigate the effect of benfotiamine and fenofibrate in diabetes-induced experimental vascular endothelial dysfunction (VED) and nephropathy. The single administration of streptozotocin (STZ) (50 mg/kg, i.p.) produced diabetes, which was noted to develop VED and nephropathy in 8 weeks. The diabetes produced VED by attenuating acetylcholine-induced endothelium dependent relaxation, impairing the integrity of vascular endothelium, decreasing serum nitrite/nitrate concentration and increasing serum TBARS and aortic superoxide anion generation. Further, diabetes altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. The nephropathy was noted to be developed in the diabetic rat that was assessed in terms of increase in serum creatinine, blood urea, proteinuria, and glomerular damage. The benfotiamine (70 mg/kg, p.o.) and fenofibrate (32 mg/kg, p.o.) or lisinopril (1 mg/kg, p.o., a standard agent) treatments were started in diabetic rats after 1 week of STZ administration and continued for 7 weeks. The treatment with benfotiamine and fenofibrate either alone or in combination attenuated diabetes-induced VED and nephropathy. In addition, the combination of benfotiamine and fenofibrate was noted to be more effective in attenuating the diabetes-induced VED and nephropathy when compared to treatment with either drug alone or lisinopril. Treatment with fenofibrate normalizes the altered lipid profile in diabetic rats, whereas benfotiamine treatment has no effect on lipid alteration in diabetic rats. It may be concluded that diabetes-induced oxidative stress, lipids alteration, and consequent development of VED may be responsible for the induction of nephropathy in diabetic rats. Concurrent administration of benfotiamine and fenofibrate may provide synergistic benefits in preventing the development of diabetes-induced nephropathy by reducing the oxidative stress and lipid

  15. The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai

    2010-10-01

    The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

  16. Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives.

    Science.gov (United States)

    Volvert, Marie-Laure; Seyen, Sandrine; Piette, Marie; Evrard, Brigitte; Gangolf, Marjorie; Plumier, Jean-Christophe; Bettendorff, Lucien

    2008-06-12

    Lipid-soluble thiamine precursors have a much higher bioavailability than genuine thiamine and therefore are more suitable for therapeutic purposes. Benfotiamine (S-benzoylthiamine O-monophosphate), an amphiphilic S-acyl thiamine derivative, prevents the progression of diabetic complications, probably by increasing tissue levels of thiamine diphosphate and so enhancing transketolase activity. As the brain is particularly sensitive to thiamine deficiency, we wanted to test whether intracellular thiamine and thiamine phosphate levels are increased in the brain after oral benfotiamine administration. Benfotiamine that is practically insoluble in water, organic solvents or oil was solubilized in 200 mM hydroxypropyl-beta-cyclodextrin and the mice received a single oral administration of 100 mg/kg. Though thiamine levels rapidly increased in blood and liver to reach a maximum after one or two hours, no significant increase was observed in the brain. When mice received a daily oral administration of benfotiamine for 14 days, thiamine derivatives were increased significantly in the liver but not in the brain, compared to control mice. In addition, incubation of cultured neuroblastoma cells with 10 muM benfotiamine did not lead to increased intracellular thiamine levels. Moreover, in thiamine-depleted neuroblastoma cells, intracellular thiamine contents increased more rapidly after addition of thiamine to the culture medium than after addition of benfotiamine for which a lag period was observed. Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells

  17. Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages.

    Science.gov (United States)

    Yadav, Umesh C S; Kalariya, Nilesh M; Srivastava, Satish K; Ramana, Kota V

    2010-05-15

    This study was designed to investigate the molecular mechanisms by which benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory kappaB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-kappaB were significantly prevented by benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE(2) was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-kappaB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Protective role of benfotiamine, a fat soluble vitamin B1 analogue, in the lipopolysaccharide–induced cytotoxic signals in murine macrophages

    Science.gov (United States)

    Yadav, Umesh C S; Kalariya, Nilesh M; Srivastava, Satish K; Ramana, Kota V

    2010-01-01

    The study has been designed to investigate the molecular mechanisms by which benfotiamine, a lipid-soluble analogue of Vitamin B1 effects lipopolysaccharide (LPS) – induced inflammatory signals leading to cytotoxicity in mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of Bcl-2 family of pro-apoptotic proteins, caspase-3 activation and PARP cleavage, altered mitochondrial membrane potential and release of cytochrome-c and apoptosis inducing factor (AIF), phosphorylation and subsequent activation of p38-MAPK, stress activated kinases (SAPK/JNK), Protein kinase C, and cytoplasmic-phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory kappa B (IκB) and consequent activation and nuclear translocation of redox-sensitive transcription factor NF-κB was significantly prevented by benfotiamine. The LPS-induced increased expression of cytokines and chemokines and other inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 were also blocked significantly. Thus, our results elucidate the molecular mechanism of anti-inflammatory action of benfotiamine in LPS-induced inflammation in murine macrophage. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents the bacterial endotoxin-induced inflammation indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases. PMID:20219672

  19. Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats.

    Science.gov (United States)

    Harisa, Gamaleldin I

    2013-08-01

    The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin-induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin-induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc.

  20. Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients.

    Science.gov (United States)

    Schupp, Nicole; Dette, Eva Maria; Schmid, Ursula; Bahner, Udo; Winkler, Michaela; Heidland, August; Stopper, Helga

    2008-09-01

    Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfotiamine supplementation. AGE-associated fluorescence in plasma, and in the second study additionally, the antioxidative capacity of plasma was analyzed. Benfotiamine significantly lowered the genomic damage of PBLs in hemodialysis patients of both studies independent of changes in plasma AGE levels. The second study gave a hint to the mechanism, as the antioxidative capacity of the plasma of the treated patients clearly increased, which might ameliorate the DNA damage.

  1. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    OpenAIRE

    Varadi, Gyula; Zhu, Zhen; G. Carter, Stephen

    2015-01-01

    We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-...

  2. Benfotiamine Protects against Peritoneal and Kidney Damage in Peritoneal Dialysis

    OpenAIRE

    Kihm, Lars P.; Müller-Krebs, Sandra; Klein, Julia; Ehrlich, Gregory; Mertes, Laura; Gross, Marie-Luise; Adaikalakoteswari, Antonysunil; Thornalley, Paul J.; Hammes, Hans-Peter; Nawroth, Peter P.; Zeier, Martin; Schwenger, Vedat

    2011-01-01

    Residual renal function and the integrity of the peritoneal membrane contribute to morbidity and mortality among patients treated with peritoneal dialysis. Glucose and its degradation products likely contribute to the deterioration of the remnant kidney and damage to the peritoneum. Benfotiamine decreases glucose-induced tissue damage, suggesting the potential for benefit in peritoneal dialysis. Here, in a model of peritoneal dialysis in uremic rats, treatment with benfotiamine decreased peri...

  3. Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia.

    Science.gov (United States)

    Bozic, Iva; Savic, Danijela; Laketa, Danijela; Bjelobaba, Ivana; Milenkovic, Ivan; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may

  4. Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis.

    Science.gov (United States)

    Kihm, Lars P; Müller-Krebs, Sandra; Klein, Julia; Ehrlich, Gregory; Mertes, Laura; Gross, Marie-Luise; Adaikalakoteswari, Antonysunil; Thornalley, Paul J; Hammes, Hans-Peter; Nawroth, Peter P; Zeier, Martin; Schwenger, Vedat

    2011-05-01

    Residual renal function and the integrity of the peritoneal membrane contribute to morbidity and mortality among patients treated with peritoneal dialysis. Glucose and its degradation products likely contribute to the deterioration of the remnant kidney and damage to the peritoneum. Benfotiamine decreases glucose-induced tissue damage, suggesting the potential for benefit in peritoneal dialysis. Here, in a model of peritoneal dialysis in uremic rats, treatment with benfotiamine decreased peritoneal fibrosis, markers of inflammation, and neovascularization, resulting in improved characteristics of peritoneal transport. Furthermore, rats treated with benfotiamine exhibited lower expression of advanced glycation endproducts and their receptor in the peritoneum and the kidney, reduced glomerular and tubulointerstitial damage, and less albuminuria. Increased activity of transketolase in tissue and blood contributed to the protective effects of benfotiamine. In primary human peritoneal mesothelial cells, the addition of benfotiamine led to enhanced transketolase activity and decreased expression of advanced glycation endproducts and their receptor. Taken together, these data suggest that benfotiamine protects the peritoneal membrane and remnant kidney in a rat model of peritoneal dialysis and uremia. Copyright © 2011 by the American Society of Nephrology

  5. Diverse amide analogs of sulindac for cancer treatment and prevention.

    Science.gov (United States)

    Mathew, Bini; Hobrath, Judith V; Connelly, Michele C; Kiplin Guy, R; Reynolds, Robert C

    2017-10-15

    Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivo antitumor activity that was comparable to sulindac in a human colon tumor xenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good activity relative to the parent (1), including five analogs that also possess nanomolar inhibitory potencies against acute lymphoblastic leukemia cells. Several new analogs identified may serve as anticancer lead candidates for further development. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

  7. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    Directory of Open Access Journals (Sweden)

    Gyula Varadi

    2015-01-01

    Full Text Available We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers.  In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg or a microcrystalline suspension form (25 mg resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals.  The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis and dermis tissue of the test animals gives a strong indication that the topical treatment with benfotiamine works very well for the desired outcome of producing an intracellular increase of the activating cofactor pool for transketolase enzyme, which is implicated in the pathophysiology of diabetic neuropathy.

  8. Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose.

    Science.gov (United States)

    Berrone, Elena; Beltramo, Elena; Solimine, Carmela; Ape, Alessandro Ubertalli; Porta, Massimo

    2006-04-07

    Hyperglycemia is a causal factor in the development of the vascular complications of diabetes. One of the biochemical mechanisms activated by excess glucose is the polyol pathway, the key enzyme of which, aldose reductase, transforms d-glucose into d-sorbitol, leading to imbalances of intracellular homeostasis. We aimed at verifying the effects of thiamine and benfotiamine on the polyol pathway, transketolase activity, and intracellular glucose in endothelial cells and pericytes under high ambient glucose. Human umbilical vein endothelial cells and bovine retinal pericytes were cultured in normal (5.6 mmol/liter) or high (28 mmol/liter) glucose, with or without thiamine or benfotiamine 50 or 100 mumol/liter. Transketolase and aldose reductase mRNA expression was determined by reverse transcription-PCR, and their activity was measured spectrophotometrically; sorbitol concentrations were quantified by gas chromatography-mass spectrometry and intracellular glucose concentrations by fluorescent enzyme-linked immunosorbent assay method. Thiamine and benfotiamine reduce aldose reductase mRNA expression, activity, sorbitol concentrations, and intracellular glucose while increasing the expression and activity of transketolase, for which it is a coenzyme, in human endothelial cells and bovine retinal pericytes cultured in high glucose. Thiamine and benfotiamine correct polyol pathway activation induced by high glucose in vascular cells. Activation of transketolase may shift excess glycolytic metabolites into the pentose phosphate cycle, accelerate the glycolytic flux, and reduce intracellular free glucose, thereby preventing its conversion to sorbitol. This effect on the polyol pathway, together with other beneficial effects reported for thiamine in high glucose, could justify testing thiamine as a potential approach to the prevention and/or treatment of diabetic complications.

  9. Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia.

    Directory of Open Access Journals (Sweden)

    Iva Bozic

    Full Text Available Microglial cells are resident immune cells of the central nervous system (CNS, recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS and NO; cyclooxygenase-2 (COX-2, heat-shock protein 70 (Hsp70, tumor necrosis factor alpha α (TNF-α, interleukin-6 (IL-6, whereas it increased anti-inflammatory interleukin-10 (IL-10 production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2, c-Jun N-terminal kinases (JNK and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB in the nucleus. Therefore

  10. Pharmacokinetics of the transdermal delivery of benfotiamine.

    Science.gov (United States)

    Zhu, Zhen; Varadi, Gyula; Carter, Stephen G

    2016-04-01

    Accumulation of advanced glycation endpoints is a trigger to the development of diabetic peripheral neuropathy, which is a common complication of diabetes. Oral administration of benfotiamine (BFT) has shown some preclinical and clinical promise as a treatment for diabetic peripheral neuropathy. The purpose of this study was to evaluate the method of transdermal delivery of BFT as a possible, viable route of administration for the treatment of diabetic peripheral neuropathy. A single application of 10 mg of BFT was given to guinea pigs topically. The levels of thiamine (T), thiamine monophosphate, thiamine diphosphate, S-benzoylthiamine and BFT were measured in the blood, skin and muscle at different time points within 24 h. At the 24-h time point, following the single BFT dose, the T level was increased 10× in the blood, more than 7× in the skin and almost 4× in the muscle compared to the untreated animals. The total T content (total) was increased 7× in the blood, 17× in the skin and 3× in the muscle compared to the untreated animals. This strong increase in the tissue levels of T and the associated metabolic derivatives levels found in the blood and local tissues following a single dose indicate that topically applied BFT may be a viable and advantageous delivery method for the treatment of diabetic peripheral neuropathy.

  11. Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.

    Science.gov (United States)

    Winkler, G; Pál, B; Nagybéganyi, E; Ory, I; Porochnavec, M; Kempler, P

    1999-03-01

    The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c benfotiamine (p benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.

  12. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

    OpenAIRE

    Bozic, Iva; Savic, Danijela; Stevanovic, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate) possesses anti-inflammat...

  13. Benfotiamine relieves inflammatory and neuropathic pain in rats.

    Science.gov (United States)

    Sánchez-Ramírez, Gabriela M; Caram-Salas, Nadia L; Rocha-González, Héctor I; Vidal-Cantú, Guadalupe C; Medina-Santillán, Roberto; Reyes-García, Gerardo; Granados-Soto, Vinicio

    2006-01-13

    Benfotiamine has shown therapeutic efficacy in the treatment of painful diabetic neuropathy in human beings. However, so far there is no evidence about the efficacy of this drug in preclinical models of pain. The purpose of this study was to assess the possible antinociceptive and antiallodynic effect of benfotiamine in inflammatory and neuropathic pain models in the rat. Inflammatory pain was induced by injection of formalin in non-diabetic and diabetic (2 weeks) rats. Reduction of flinching behavior was considered as antinociception. Neuropathic pain was induced by either ligation of left L5/L6 spinal nerves or administration of streptozotocin (50 mg/kg, i.p.) in Wistar rats. Benfotiamine significantly reduced inflammatory (10-300 mg/kg) and neuropathic (75-300 mg/kg) nociception in non-diabetic and diabetic rats. Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans.

  14. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism

    DEFF Research Database (Denmark)

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke

    2016-01-01

    In animal models, the incretin hormone GLP-1 affects Alzheimer's disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients...... with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe...

  15. Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride.

    Science.gov (United States)

    Xie, Feifan; Cheng, Zeneng; Li, Sanwang; Liu, Xingling; Guo, Xin; Yu, Peng; Gu, Zhenkun

    2014-06-01

    Benfotiamine is a lipid-soluble thiamine precursor which can transform to thiamine in vivo and subsequently be metabolized to thiamine monophosphate (TMP) and thiamine diphosphate (TDP). This study investigated the pharmacokinetic profiles of thiamine and its phosphorylated metabolites after single- and multiple-dose administration of benfotiamine in healthy Chinese volunteers, and assessed the bioavailability of orally benfotiamine administration compared to thiamine hydrochloride. In addition, concentration of hippuric acid in urine which is produced in the transformation process of benfotiamine was determined. The results showed that thiamine and its phosphorylated metabolites exhibited different pharmacokinetic characteristics in plasma, blood and erythrocyte, and one-compartment model provided the best fit for pharmacokinetic profiles of thiamine. The transformation process of benfotiamine to thiamine produced large amount of hippuric acid. No accumulation of hippuric acid was observed after multiple-dose of benfotiamine. Compared to thiamine hydrochloride, the bioavailability of thiamine in plasma and TDP in erythrocyte after oral administration of benfotiamine were 1147.3 ± 490.3% and 195.8 ± 33.8%, respectively. The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride. © 2014, The American College of Clinical Pharmacology.

  16. The effect of benfotiamine on mu-opioid receptor mediated antinociception in experimental diabetes.

    Science.gov (United States)

    Nacitarhan, C; Minareci, E; Sadan, G

    2014-03-01

    Diabetic neuropathy is a prevalent, disabling disorder. Currently, the only treatments available to patients with diabetic neuropathy are glucose control and pain management. B vitamin present neuroprotective effects, which are suggested to be related to their analgesic action in various models of neuropathic pain. According to our literature knowledge there is no report about antinociceptive effects of thiamine as benfotiamine and opioids together in diabetic mice. The purpose of this study was to determine the effects of benfotiamine on the antinociception produced by mu-opioid receptor agonist fentanyl in diabetic mice. The effects of benfotiamine on antinociception produced by fentanyl in diabetic mice were studied in 4 groups. Antinociceptive effect was determined with tail flick, hot plate and formalin test. Our results showed that, mu-opioid agonist fentanyl in benfotiamine applied diabetic group caused more potent antinociceptive effect than in diabetic group without benfotiamine treatment. In brief benfotiamine supplement in diet did not bring out antinociceptive effect itself, but during development of STZ diabetes, benfotiamine replacement increased the antinociceptive effect of fentanyl in mice tail-flick test. This effect is probably due to the replacement of benfotiamine efficiency occurring in diabetes mellitus. Finally, we suppose that oral benfotiamine replacement therapy may be useful to ameliorate analgesic effect of mu-opioid agonists on neuropathic pain in diabetic case. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  17. Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence.

    Science.gov (United States)

    Manzardo, Ann M; He, Jianghua; Poje, Albert; Penick, Elizabeth C; Campbell, Jan; Butler, Merlin G

    2013-12-01

    Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analog, benfotiamine (BF), and BF's effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria for current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, -611 ± 380 standard drinks; PL: N=11, -159 ± 562 standard drinks, p-value=0.02). BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Chemoreactomic analysis of thiamine disulfide, thiamine hydrochloride, and benfotiamine molecules

    OpenAIRE

    O. A. Gromova; I. Yu. Torshin; L. V. Stakhovskaya; L. E. Fedotova

    2017-01-01

    Objective: to analyze the interactions that could indicate the potential pharmacological properties of the molecules of thiamin, thiamine disulfide, and others.Material and methods. The investigators simulated the properties of thiamine disulfide (bistiamin) versus those of the reference molecules of thiamin hydrochloride and benfotiamine. The study was performed using chemoreactomic simulation that is the newest area in post-genome pharmacology.Results and discussion. Chemoreactomic analysis...

  19. [The immunometaboic effects of benfotiamine and riboxine on hemolytic anemia].

    Science.gov (United States)

    Uteshev, B S; Lazareva, G A; Prokopenko, L G

    2002-01-01

    Single (80 mg/kg) or multiply repeated (30 mg/kg) intramuscular injections of phenylhydrazine decrease the functional activity of mononuclear blood cells and the reduces immunological reactivity of the organism. Benfotiamine and riboxin decrease the extent of changes in the immunological response to a single administration of phenylhydrazine but do not significantly influence the immunological functions impaired by repeated injections of the hemolytic toxin.

  20. Chemoreactomic analysis of thiamine disulfide, thiamine hydrochloride, and benfotiamine molecules

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2017-01-01

    Full Text Available Objective: to analyze the interactions that could indicate the potential pharmacological properties of the molecules of thiamin, thiamine disulfide, and others.Material and methods. The investigators simulated the properties of thiamine disulfide (bistiamin versus those of the reference molecules of thiamin hydrochloride and benfotiamine. The study was performed using chemoreactomic simulation that is the newest area in post-genome pharmacology.Results and discussion. Chemoreactomic analysis has shown that thiamine disulfide can inhibit the molecular receptors involved in blood pressure regulation: adrenoceptors, vasopressin receptor, and angiotensin receptor. Thiamine disulfide can inhibit the reuptake of serotonin, increase its levels, inhibit benzodiazepine receptor and dopamine reuptake, and enhance neuronal acetylcholine release to a large extent than benfotiamine. These molecular effects are consistent with the sedative and anticonvulsant action profile of thiamine disulfide. Simulation has indicated that thiamine disulfide has neuroprotective, anti-inflammatory, normolipidemic, and antitumor activities.Conclusion. The simulation results are confirmed by the available clinical and experimental findings and indicate the virtually unstudied molecular mechanisms of action of thiamine disulfide, benfotiamine, and thiamin hydrochloride. 

  1. A randomized, double-blind, crossover, placebo-controlled trial of 6 weeks benfotiamine treatment on postprandial vascular function and variables of autonomic nerve function in Type 2 diabetes.

    Science.gov (United States)

    Stirban, A; Pop, A; Tschoepe, D

    2013-10-01

    In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population. In a double-blind, placebo-controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal. Participants had an impaired baseline flow-mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow-mediated dilatation, following placebo treatment there was a significant postprandial flow-mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment. In people with Type 2 diabetes and markedly impaired fasting flow-mediated dilatation, a mixed test meal does not further deteriorate flow-mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow-mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  2. Effectiveness and retention of thiamine and its analogs administered to steelhead and landlocked Atlantic salmon

    Science.gov (United States)

    Ketola, H.G.; Isaacs, G.R.; Robins, J.S.; Lloyd, R.C.

    2008-01-01

    We investigated the feasibility of enhancing the reproduction of steelhead Oncorhynchus mykiss and landlocked Atlantic salmon Salmo salar in lakes where the consumption of alewives Alosa pseudoharengus and other forage fishes containing thiaminase can cause them to become thiamine deficient and thereby reduce the survival of their fry. We evaluated feeding fingerling steelhead excess thiamine hydrochloride (THCl) for 1 or 2 weeks or equimolar amounts of thiamine mononitrate, thiamine-tetrahydrofurfuryl-disulfide, benfotiamine, or dibenzoyl thiamine (DBT). We found minimal internal reserves of thiamine after 6 months. We also compared the ability of injections of thiamine and its analogs to prevent mortality in thiamine-deficient steelhead and Atlantic salmon sac fry and found all forms to be effective, although benfotiamine was the least effective on an equimolar basis. Further, we injected yearling steelhead and found that DBT was tolerated at approximately 11,200 nmol/g of body weight, about 10 times more than thiamine in any other form. When yearling steelhead were injected with near-maximal doses of thiamine hydrochloride and several analogs and then fed a thiamine-deficient diet, DBT was retained for approximately 2 years - in contrast to other forms, which were retained for less than about 6 months. Therefore, these results suggest that neither feeding nor injecting young hatchery salmonids with DBT is likely to enhance their reproduction for more than 2 years after stocking. However, injecting DBT in nearly mature fish (either cultured fish from hatcheries or wild fish captured in lakes) may provide them with enough thiamine to successfully spawn within 2 years even though they consume mainly thiaminase-containing forage fishes. ?? Copyright by the American Fisheries Society 2008.

  3. Benfotiamine in treatment of alcoholic polyneuropathy: an 8-week randomized controlled study (BAP I Study).

    Science.gov (United States)

    Woelk, H; Lehrl, S; Bitsch, R; Köpcke, W

    1998-01-01

    A three-armed, randomized, multicentre, placebo-controlled double-blind study was used to examine the efficacy of benfotiamine vs a combination containing benfotiamine and vitamins B6 and B12 in out-patients with severe symptoms of alcoholic polyneuropathy (Benfotiamine in treatment of Alcoholic Polyneuropathy, BAP I). The study period was 8 weeks and 84 patients fulfilled all the prerequisite criteria and completed the study as planned. Benfotiamine led to significant improvement of alcoholic polyneuropathy. Vibration perception (measured at the tip of the great toe) significantly improved in the course of the study, as did motor function. and the overall score reflecting the entire range of symptoms of alcoholic polyneuropathy. A tendency toward improvement was evident for pain and co-ordination; no therapy-specific adverse effects were seen.

  4. Change in psychiatric symptomatology after benfotiamine treatment in males is related to lifetime alcoholism severity.

    Science.gov (United States)

    Manzardo, Ann M; Pendleton, Tiffany; Poje, Albert; Penick, Elizabeth C; Butler, Merlin G

    2015-07-01

    Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with neurological deficits impacting mood and cognition. Alcohol consumption was reduced among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). We examined the relationship between lifetime alcoholism severity, psychiatric symptoms and response to BF among the alcohol dependent men from this cohort. Eighty-five adult men (mean age=48±8 years) meeting DSM-IV-TR criteria for a current alcohol use disorder who were abstinent Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months. Baseline SCL-90-R scale scores for men with high alcoholism severity (AS≥24; N=46 HAS) were significantly greater than for men with low alcoholism severity (ASalcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, palcohol use disorder and should be considered for adjuvant therapy in alcohol rehabilitation. #NCT00680121 High Dose Vitamin B1 to Reduce Abusive Alcohol Use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.

    Science.gov (United States)

    Hurt, Julie K; Coleman, Jennifer L; Fitzpatrick, Brendan J; Taylor-Blake, Bonnie; Bridges, Arlene S; Vihko, Pirkko; Zylka, Mark J

    2012-01-01

    Thiamine (Vitamin B1) is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT)-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although how these compounds inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP, ACPP) can dephosphorylate BT in vitro, in dorsal root ganglia (DRG) neurons and in primary-afferent axon terminals in the dorsal spinal cord. The dephosphorylated product S-benzoylthiamine (S-BT) then decomposes to O-benzoylthiamine (O-BT) and to thiamine in a pH-dependent manner, independent of additional enzymes. This unique reaction mechanism reveals that BT only requires a phosphatase for conversion to thiamine. However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP) and thiamine-a compound that is not phosphorylated-were entirely dependent on PAP at the spinal level. Moreover, pharmacokinetic studies with wild-type and Pap(-/-) mice revealed that PAP is not required for the conversion of BT to thiamine in vivo. Taken together, our study highlights an obligatory role for PAP in the antinociceptive effects of thiamine and phosphorylated thiamine analogs, and suggests a novel phosphatase-independent function for PAP.

  6. Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.

    Directory of Open Access Journals (Sweden)

    Julie K Hurt

    Full Text Available Thiamine (Vitamin B1 is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although how these compounds inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP, ACPP can dephosphorylate BT in vitro, in dorsal root ganglia (DRG neurons and in primary-afferent axon terminals in the dorsal spinal cord. The dephosphorylated product S-benzoylthiamine (S-BT then decomposes to O-benzoylthiamine (O-BT and to thiamine in a pH-dependent manner, independent of additional enzymes. This unique reaction mechanism reveals that BT only requires a phosphatase for conversion to thiamine. However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP and thiamine-a compound that is not phosphorylated-were entirely dependent on PAP at the spinal level. Moreover, pharmacokinetic studies with wild-type and Pap(-/- mice revealed that PAP is not required for the conversion of BT to thiamine in vivo. Taken together, our study highlights an obligatory role for PAP in the antinociceptive effects of thiamine and phosphorylated thiamine analogs, and suggests a novel phosphatase-independent function for PAP.

  7. Protective effect of treatment with thiamine or benfotiamine on liver oxidative damage in rat model of acute ethanol intoxication.

    Science.gov (United States)

    Portari, Guilherme Vannucchi; Ovidio, Paula Payão; Deminice, Rafael; Jordão, Alceu Afonso

    2016-10-01

    The aim of this study was to evaluate possible beneficial effects of treatment with thiamine or benfotiamine in an animal model of acute ethanol intoxication. Thirty male Wistar rats were separated at random into three groups of 10 animals each: Ethanol (E), Ethanol treated with thiamine (T) and Ethanol treated with benfotiamine (BE). Rats were gavaged with single dose of ethanol (5g/kg, 40% v:v). After 30min of ethanol gavage the animals were treated with thiamine or benfotiamine. Six hours after first gavage, the animals were euthanized and blood and liver samples were collected for ethanol and oxidative stress biomarkers quantification. Serum ethanol levels were higher in animals treated with thiamine or benfotiamine while hepatic alcohol levels were higher in animals of the group treated with benfotiamine comparing to controls or thiamine treated groups. The lipid peroxidation biomarkers were diminished for the groups treated with thiamine or benfotiamine comparing to E animals. Concerning protein oxidative damage parameters, they were enhanced for animals treated with benfotiamine in relation to other groups. In conclusion, the treatment with thiamine or benfotiamine even 30min after the massive dose of ethanol has proven to be beneficial against liver damage. Improved results were obtained with benfotiamine in relation to oxidative damage from aqueous compartments. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Effect of benfotiamine in podocyte damage induced by peritoneal dialysis fluid

    Directory of Open Access Journals (Sweden)

    Sandra eMüller-Krebs

    2015-03-01

    Full Text Available Background:In peritoneal dialysis (PD residual renal function (RRF fundamentally contributes to improved quality of life and patient survival. High glucose and advanced glycation end-products (AGE contribute locally to peritoneal and systemically to renal damage. Integrity of podocyte structure and function is of special importance to preserve RRF. Benfotiamine could counteract the glucose and AGE mediated toxicity by blocking hyperglycemia associated podocyte damage via the pentose phosphate pathway.Methods: A human differentiated podocyte cell line was incubated with control solution (Control, 2.5% glucose solution (Glucose and 2.5% PD fluid (PDF for 48 h either ± 50 μM benfotiamine.Podocyte damage and potential benefit of benfotiamine were analyzed using immunofluorescence, western blot analysis, and a functional migration assay. For quantitation, a semiquantitative score was used. Results:When incubating podocytes with benfotiamine, Glucose and PDF mediated damage was reduced resulting in lower expression of AGE and intact podocin and ZO-1 localization. The reorganization of the actin cytoskeleton was restored in the presence of benfotiamine as functional podocyte motility reached Control level. Decreased level of inflammation could be shown as well as reduced podocyte apoptosis.Conclusions:These data suggest that benfotiamine protects podocytes from Glucose and PDF mediated dysfunction and damage, in particular with regard to cytoskeletal reorganization, motility, inflammation and podocyte survival.

  9. Antinociceptive interaction between benfotiamine and resveratrol in capsaicin-induced licking.

    Science.gov (United States)

    Montiel-Ruiz, Rosa Mariana; Reyes-García, Gerardo; Flores-Murrieta, Francisco; Déciga-Campos, Myrna

    2009-01-01

    In an attempt to provide more direct evidence concerning the possible antinociceptive effect of resveratrol-benfotiamine combination on neurogenic pain, we investigated whether resveratrol and benfotiamine administered alone or in combination decrease capsaicin induced nociception in mice. Before testing, the animals were placed individually in transparent glass cylinders, 20 cm in diameter, serving as observation chambers. After the adaptation period, 20 microL of capsaicin (1.6 microg/paw) were injected under the skin of the dorsal of the right hind paw. Animals were observed individually for 5 min after capsaicin injection. The amount of time spent licking the injected paw was timed with a chronometer and was considered as indicative of nociception. Animals were pretreated with resveratrol (56.2-177 mg/kg, i.p.), benfotiamine (100-1000 mg/kg, p.o.) and their combinations (11:1, 22:2, 44:4; 88:8 mg/kg benfotiamine:resveratrol). It was observed that resveratrol (ED50 = 104 +/- 8.2 mg/kg) was able to produce more important decrement of capsaicin-induced licking than benfotiamine (ED50 = 529.4 +/- 85.2 mg/kg). In addition, a synergistic interaction was observed between benfotiamine and resveratrol, suggesting that this combination could be useful in neurogenic nociception.

  10. Effect of benfotiamine in podocyte damage induced by peritoneal dialysis fluid.

    Science.gov (United States)

    Müller-Krebs, Sandra; Nissle, Katharina; Tsobaneli, Julia; Zeier, Martin; Kihm, Lars Philipp; Kender, Zoltan; Fleming, Thomas; Nawroth, Peter Paul; Reiser, Jochen; Schwenger, Vedat

    2015-01-01

    In peritoneal dialysis (PD), residual renal function (RRF) fundamentally contributes to improved quality of life and patient survival. High glucose and advanced glycation end-products (AGE) contribute locally to peritoneal and systemically to renal damage. Integrity of podocyte structure and function is of special importance to preserve RRF. Benfotiamine could counteract the glucose and AGE-mediated toxicity by blocking hyperglycemia-associated podocyte damage via the pentose-phosphate pathway. A human differentiated podocyte cell line was incubated with control solution (control), 2.5% glucose solution (glucose), and 2.5% peritoneal dialysis fluid (PDF) for 48 h either ±50 μM benfotiamine. Podocyte damage and potential benefit of benfotiamine were analyzed using immunofluorescence, western blot analysis, and a functional migration assay. For quantitation, a semiquantitative score was used. When incubating podocytes with benfotiamine, glucose, and PDF-mediated damage was reduced, resulting in lower expression of AGE and intact podocin and ZO-1 localization. The reorganization of the actin cytoskeleton was restored in the presence of benfotiamine as functional podocyte motility reached control level. Decreased level of inflammation could be shown as well as reduced podocyte apoptosis. These data suggest that benfotiamine protects podocytes from glucose and PDF-mediated dysfunction and damage, in particular, with regard to cytoskeletal reorganization, motility, inflammation, and podocyte survival.

  11. Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats.

    Science.gov (United States)

    Mixcoatl-Zecuatl, Teresa; Quinonez-Bastidas, Geovanna N; Caram-Salas, Nadia L; Ambriz-Tututi, Monica; Araiza-Saldana, Claudia I; Rocha-Gonzalez, Hector I; Medina-Santillan, Roberto; Reyes-Garcia, Gerardo; Granados-Soto, Vinicio

    2008-01-01

    Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

  12. A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy.

    Science.gov (United States)

    Alkhalaf, Alaa; Klooster, Astrid; van Oeveren, Willem; Achenbach, Ulrike; Kleefstra, Nanne; Slingerland, Robbert J; Mijnhout, G Sophie; Bilo, Henk J G; Gans, Reinold O B; Navis, Gerjan J; Bakker, Stephan J L

    2010-07-01

    To investigate the effect of benfotiamine on urinary albumin excretion (UAE) and the tubular damage marker kidney injury molecule-1 (KIM-1) in patients with type 2 diabetes and nephropathy. Patients with type 2 diabetes and UAE equivalent to 15-300 mg/24 h, despite ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), were randomly assigned to 12 weeks of benfotiamine (900 mg/day) (n = 39) or placebo (n = 43). Compared with placebo, benfotiamine treatment resulted in significant improvement of thiamine status (P Benfotiamine treatment did not significantly decrease 24-h UAE or 24-h KIM-1 excretion. In patients with type 2 diabetes and nephropathy, high-dose benfotiamine treatment for 12 weeks in addition to ACE-Is or ARBs did not reduce UAE or KIM-1 excretion, despite improvement of thiamine status.

  13. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.

    Science.gov (United States)

    Stracke, H; Gaus, W; Achenbach, U; Federlin, K; Bretzel, R G

    2008-11-01

    Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.

  14. Change in Psychiatric Symptomatology after Benfotiamine Treatment in Males is a Function of Lifetime Alcoholism Severity

    Science.gov (United States)

    Manzardo, Ann M.; Pendleton, Tiffany; Poje, Albert; Penick, Elizabeth C.; Butler, Merlin G.

    2015-01-01

    Background Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with serious illness and neurological deficits that influence mood and cognition. We previously reported reduced alcohol consumption among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). As a follow-up, we have examined the relationship between lifetime alcoholism severity and psychiatric symptoms among the alcohol dependent men from this cohort and their response to BF treatment. Methods Eighty-five adult men (mean age = 48 ± 8 yrs) meeting DSM-IV-TR criteria for current alcohol dependence participated in a randomized, double-blind, placebo-controlled trial of 600 mg BF vs placebo (PL) for 6 months. Psychometric testing included a derived Lifetime Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months with data analyzed using ANOVA and MANOVA modeling. Results Baseline SCL-90-R scale scores for men with high alcoholism severity (AS ≥ 24; N=46 HAS) were significantly greater than for men with low alcoholism severity (AS < 24; N=39 LAS), but BIS scores did not differ. MANOVA modeling identified a significant treatment effect (F=2.5, df=10, p<0.03) and treatment x alcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, p<0.03) with SCL-90-R scores showing a reduction in symptoms among BF treated, high severity males. Conclustion BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with lifetime alcohol dependence and should be considered for adjuvant therapy in alcohol rehabilitation. PMID:25908323

  15. Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique.

    Science.gov (United States)

    Patel, S M; Patel, R P; Prajapati, B G

    2012-03-01

    The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4). Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

  16. Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique

    Directory of Open Access Journals (Sweden)

    S M Patel

    2012-01-01

    Full Text Available The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4. Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

  17. Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative.

    Science.gov (United States)

    Bitsch, R; Wolf, M; Möller, J; Heuzeroth, L; Grüneklee, D

    1991-01-01

    The bioequivalence of thiamin in 2 therapeutically used preparations was tested in 10 healthy young men. Thiamin was orally administered either as lipophilic benfotiamine or as water-soluble thiamin mononitrate. Biokinetic data, measured as area under the curve and maximal concentration in plasma and hemolysate after ingestion, demonstrated a significantly improved bioavailability from the lipophilic derivative despite an ingested dose of only 40% as compared with the water-soluble salt. A superior cellular efficacy of benfotiamine was also concluded from the short-term stimulation of the thiamin-dependent transketolase activity in erythrocytes.

  18. Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer's Disease.

    Science.gov (United States)

    Pan, Xiaoli; Chen, Zhichun; Fei, Guoqiang; Pan, Shumei; Bao, Weiqi; Ren, Shuhua; Guan, Yihui; Zhong, Chunjiu

    2016-12-01

    To date, we still lack disease-modifying therapies for Alzheimer's disease (AD). Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine (300 mg daily) over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B (PiB-PET) and exhibited positive imaging with β-amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improvement as assayed by the Mini-Mental Status Examination (MMSE) with an average increase of 3.2 points at month 18 of benfotiamine administration. The three patients who received follow-up PiB-PET had a 36.7% increase in the average standardized uptake value ratio in the brain compared with that in the first scan. Importantly, the MMSE scores of these three had an average increase of 3 points during the same period. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation. Our study provides new insight to the development of disease-modifying therapy.

  19. High-dose benfotiamine rescues cardiomyocyte contractile dysfunction in streptozotocin-induced diabetes mellitus.

    Science.gov (United States)

    Ceylan-Isik, Asli F; Wu, Shan; Li, Qun; Li, Shi-Yan; Ren, Jun

    2006-01-01

    Diabetic cardiomyopathy is characterized by cardiac dysfunction. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cardiac contractile dysfunction in mouse cardiomyocytes. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg ip). Fourteen days later, control and diabetic (fasting plasma glucose > 13.9 mM) mice were put on benfotiamine therapy (100 mg.kg(-1).day(-1) ip) for another 14 days. Mechanical and intracellular Ca2+ properties were evaluated in left ventricular myocytes using an IonOptix MyoCam system. The following indexes were evaluated: peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90), maximal velocity of shortening/relengthening, resting and rise of intracellular Ca2+ in response to electrical stimulus, sarcoplasmic reticulum (SR) Ca2+ load, and intracellular Ca2+ decay rate (tau). Two- or four-week STZ treatment led to hyperglycemia, prolonged TPS and TR90, reduced SR Ca2+ load, elevated resting intracellular Ca2+ level and prolonged tau associated with normal PS, maximal velocity of shortening/relengthening, and intracellular Ca2+ rise in response to electrical stimulus. Benfotiamine treatment abolished prolongation in TPS, TR90, and tau, as well as reduction in SR Ca2+ load without affecting hyperglycemia and elevated resting intracellular Ca2+. Diabetes triggered oxidative stress, measured by GSH-to-GSSG ratio and formation of advanced glycation end product (AGE) in the hearts. Benfotiamine treatment alleviated oxidative stress without affecting AGE or protein carbonyl formation. Collectively, our results indicated that benfotiamine may rescue STZ-induced cardiomyocyte dysfunction but not AGE formation in short-term diabetes.

  20. Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations.

    Science.gov (United States)

    Fraser, D A; Hessvik, N P; Nikolić, N; Aas, V; Hanssen, K F; Bøhn, S K; Thoresen, G H; Rustan, A C

    2012-07-01

    The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measured using real-time polymerase chain reaction (qPCR) and microarray technology. Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 μM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 μM benfotiamine). Benfotiamine also increased glucose uptake. In comparison, thiamine (200 μM) increased overall glucose metabolism but did not change glucose oxidation. In contrast to glucose, mitochondrial lipid oxidation and overall lipid metabolism were unchanged by benfotiamine. The expression of NADPH oxidase 4 (NOX4) was significantly downregulated by benfotiamine treatment under both normo- and hyperglycemic conditions. Gene set enrichment analysis (GSEA) showed that befotiamine increased peroxisomal lipid oxidation and organelle (mitochondrial) membrane function. In conclusion, benfotiamine increases mitochondrial glucose oxidation in myotubes and downregulates NOX4 expression. These findings may be of relevance to type 2 diabetes where reversal of reduced glucose oxidation and mitochondrial capacity is a desirable goal.

  1. A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy.

    Science.gov (United States)

    Stracke, H; Lindemann, A; Federlin, K

    1996-01-01

    In a double-blind, randomized, controlled study, the effectiveness of treatment with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy. The results showed a significant improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold. Long-term observation of 9 patients with verum over a period of 9 months support the results. Therapy-specific adverse effects were not seen. The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.

  2. Variability of skin autofluorescence measurement over 6 and 12 weeks and the influence of benfotiamine treatment.

    Science.gov (United States)

    Stirban, Alin; Pop, Alexandra; Fischer, Annelie; Heckermann, Sascha; Tschoepe, Diethelm

    2013-09-01

    Measurements of skin autofluorescence (SAF) allow for a simple and noninvasive quantification of tissue advanced glycation end-products (AGEs), a marker linked to the risk of diabetes complications. The aim of this study was to test the repeatability of SAF over 6 and 12 weeks and to test whether benfotiamine, a thiamine prodrug suggested to reduce AGEs formation under hyperglycemic conditions, is able to attenuate SAF when administered over 6 weeks. In a double-blind, placebo-controlled, randomized, crossover study, 22 patients with type 2 diabetes mellitus (T2DM) received 900 mg/day benfotiamine or placebo for 6 weeks (washout period of 6 weeks between). At the beginning and at the end of each treatment period, SAF was assessed in the fasting state, as well as 2, 4, and 6 h following a mixed test meal. The respective intra-individual and inter-individual variability of fasting SAF was 6.9% and 24.5% within 6 weeks and 10.9% and 23.1% within 12 weeks. The respective variability calculated for triplicate comparisons was 9.9% and 27.7%. A short-term therapy with benfotiamine did not influence SAF significantly, nor did we find a significant postprandial SAF increase. In patients with T2DM, repeated, timely spaced SAF measurements have an intra-subject variability of below 11%. Using these data, sample sizes were calculated for interventional studies aiming at reducing SAF. Benfotiamine treatment for 6 weeks did not significantly influence SAF; for this, a longer-term therapy is probably needed.

  3. Effect of Benfotiamine in Podocyte Damage Induced by Peritoneal Dialysis Fluid

    OpenAIRE

    M?ller-Krebs, Sandra; Nissle, Katharina; Tsobaneli, Julia; Zeier, Martin; Kihm, Lars Philipp; Kender, Zoltan; Fleming, Thomas; Nawroth, Peter Paul; Reiser, Jochen; Schwenger, Vedat

    2015-01-01

    Background: In peritoneal dialysis (PD), residual renal function (RRF) fundamentally contributes to improved quality of life and patient survival. High glucose and advanced glycation end-products (AGE) contribute locally to peritoneal and systemically to renal damage. Integrity of podocyte structure and function is of special importance to preserve RRF. Benfotiamine could counteract the glucose and AGE-mediated toxicity by blocking hyperglycemia-associated podocyte damage via the pentose-phos...

  4. Comparative autoradiographic investigations on the tissue distribution of benfotiamine versus thiamine in mice.

    Science.gov (United States)

    Hilbig, R; Rahmann, H

    1998-05-01

    The tissue distribution of two therapeutically applied preparations of B-vitamins were investigated in blood and selected organs (liver, brain, muscle, kidney) of laboratory mice using autoradiographic techniques. Incorporation of lipid-soluble 3H-benfotiamine (CAS 22457-89-2) and water-soluble 3H-thiaminehydrochloride (CAS 67-03-8) (200 microCi, equivalent to 105 mg vitamin/kg body weight) was monitored between 0.75 and 168 h after an oral or subcutaneous administration. The labelled tissue slices were autoradiographically analysed after a differential histochemical extraction procedure to evaluate the respective total radioactivity, the uptake into lipid-soluble, water-soluble and residual macromolecular compounds. Evaluation of these autoradiographic data (given as mumol vitamin preparation/mg tissue equivalent) proved that benfotiamine is incorporated much better than thiaminehydrochloride independent of the administration mode. In muscle and brain tissue a 5 to 25 fold higher amount of tracer incorporation was registered following benfotiamine as compared with the thiamine application, whereas in all other organs the difference in the label was mostly between 10 and 40%. Concerning the organ specific distribution, liver and kidney were the structures labelled highest by both substances and administration procedures. In the liver, concerning all incorporation times, a higher proportion of residual macromolecular compounds was found, whereas in the kidney the proportions of lipid- as well as of water-soluble materials prevailed. These data should be clinically relevant.

  5. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    International Nuclear Information System (INIS)

    Rancourt, Raymond C.; Veress, Livia A.; Ahmad, Aftab; Hendry-Hofer, Tara B.; Rioux, Jacqueline S.; Garlick, Rhonda B.; White, Carl W.

    2013-01-01

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O 2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: • TFPI administration to rats after mustard inhalation reduces airway cast formation. • Inhibition of thrombin activation is the likely mechanism for limiting casts. • Rats given TFPI had

  6. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Rancourt, Raymond C., E-mail: raymond.rancourt@ucdenver.edu; Veress, Livia A., E-mail: livia.veress@ucdenver.edu; Ahmad, Aftab, E-mail: aftab.ahmad@ucdenver.edu; Hendry-Hofer, Tara B., E-mail: tara.hendry-hofer@ucdenver.edu; Rioux, Jacqueline S., E-mail: jacqueline.rioux@ucdenver.edu; Garlick, Rhonda B., E-mail: rhonda.garlick@ucdenver.edu; White, Carl W., E-mail: carl.w.white@ucdenver.edu

    2013-10-01

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O{sub 2} saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: • TFPI administration to rats after mustard inhalation reduces airway cast formation. • Inhibition of thrombin activation is the likely mechanism for limiting casts. • Rats given TFPI

  7. Benfotiamine in the treatment of diabetic polyneuropathy--a three-week randomized, controlled pilot study (BEDIP study).

    Science.gov (United States)

    Haupt, E; Ledermann, H; Köpcke, W

    2005-02-01

    The aim of the study was to evaluate the efficacy of benfotiamine administered over three weeks (allithiamine; a lipid-soluble vitamin B1 prodrug with high bioavailability) to patients with diabetic polyneuropathy in a randomized, placebo-controlled, double-blind, two-center pilot study. Forty inpatients (23 male, 18 female, age range 18 - 70 years) with a history of type 1 or 2 diabetes and polyneuropathy of not longer than two years, were included in the study. Twenty Patients received two 50 mg benfotiamine tablets four times daily and 20 patients received placebo over the three-week study period. Two clinical units were involved with 10 patients receiving placebo and 10 patients benfotiamine in each. The neuropathy score according to Katzenwadel et al. [1987] was used to evaluate symptoms of polyneuropathy, vibration perception threshold and both the physician's and the patient's own assessment were documented. A statistically significant (p = 0.0287) improvement in the neuropathy score was observed in the group given active drug when compared to the placebo-treated controls. There was no statistically significant change observed in the tuning fork test. The most pronounced effect on complaints was a decrease in pain (p = 0.0414). More patients in the benfotiamine-treated group than in the placebo group considered their clinical condition to have improved (p = 0.052). No side effects attributable to benfotiamine were observed. The differences between the groups cannot be attributed to a change in metabolic parameters since there were no significant alterations in the HbA1 levels and blood sugar profiles. The body mass index of the two groups did not differ. This pilot investigation (BEDIP Study) has confirmed the results of two earlier randomized controlled trials and has provided further evidence for the beneficial effects of benfotiamine in patients with diabetic neuropathy.

  8. Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin.

    Science.gov (United States)

    Ustuner, Mehmet Alperen; Kaman, Dilara; Colakoglu, Neriman

    2017-12-01

    Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats. Rats were divided into five groups. Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group 4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats were euthanized by cervical decapitation and then blood samples and kidneys were collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant and antioxidant parameters, as well as histopathological examination of kidney tissues were assessed. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM-1 level as compared with the controls. Moreover, a significant increase in serum malondialdehyde, reduced glutathione. Histopathological examination of renal tissue in gentamisin administered group, there were extremly pronounced necrotic tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli. BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment was significantly decreased necrotic tubuli and hyalen deposition in gentamisin plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically significant alterations in these nephrotoxicity parameters when compared with GM group but histopathological examination of renal tissue in GM+CoQ10 administered group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation in tubuli. The results from our study indicate that BFT supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. PP2A contributes to endothelial death in high glucose: inhibition by benfotiamine.

    Science.gov (United States)

    Du, Y; Kowluru, A; Kern, T S

    2010-12-01

    Endothelial death is critical in diabetic vascular diseases, but regulating factors have been only partially elucidated. Phosphatases play important regulatory roles in cell metabolism, but have not previously been implicated in hyperglycemia-induced cell death. We investigated the role of the phosphatase, type 2A protein phosphatase (PP2A), in hyperglycemia-induced changes in signaling and death in bovine aortic endothelial cells (BAEC). We explored also the influence of benfotiamine on this phosphatase. Activation of PP2A was assessed in BAEC by the extent of methylation and measurement of activity, and the enzyme was inhibited using selective pharmacological (okadaic acid, sodium fostriecin) and molecular (small interfering RNA) approaches. BAECs cultured in 30 mM glucose significantly increased PP2A methylation and activity, and PP2A inhibitors blocked these abnormalities. PP2A activity was increased also in aorta and retina from diabetic rats. NF-κB activity and cell death in BAEC were significantly increased in 30 mM glucose and inhibited by PP2A inhibition. NF-κB played a role in the hyperglycemia-induced death of BAEC, since blocking its translocation with SN50 also inhibited cell death. Inhibition of PP2A blocked the hyperglycemia-induced dephosphorylation of NF-κB and Bad, thus favoring cell survival. Incubation of benfotiamine with BAEC inhibited the high glucose-induced activation of PP2A and NF-κB and cell death, as well as several other metabolic defects, which likewise were inhibited by inhibitors of PP2A. Activation of PP2A contributes to endothelial cell death in high glucose, and beneficial actions of benfotiamine are due, at least in part, to inhibition of PP2A activation.

  10. New oral dosage form for elderly patients. II. Release behavior of benfotiamine from silk fibroin gel.

    Science.gov (United States)

    Hanawa, T; Watanabe, A; Tsuchiya, T; Ikoma, R; Hidaka, M; Sugihara, M

    1995-05-01

    Silk fibroin gel (SFG) containing benfotiamine (BTMP) was prepared. The release behavior of BTMP from SFG was studied as a function of silk fibroin (SF) content and glycerol content, and the influence of the existence of beta-cyclodextrin (beta-CD) on the physicochemical properties of SFG were investigated. The release rate of BTMP from SFG was retarded by an increase in SF concentration. The addition of beta-CD affected both the release properties and rheological properties of the SFG. It was found from the results of the "paddle-bead method" that the release profiles of BTMP from SFG were inversely proportional to the SFG firmness.

  11. Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Alaa Alkhalaf

    Full Text Available Formation of advanced glycation endproducts (AGEs, endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy.Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15-300 mg/24h were randomized to receive benfotiamine (n = 39 or placebo (n = 43. Plasma and urinary AGEs (N(ε-(carboxymethyl lysine [CML], N(ε-(Carboxyethyl lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1] and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO] were measured at baseline and after 6 and 12 weeks.Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation.Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications. TRIAL REGRISTRATION: ClinicalTrials.gov NCT00565318.

  12. Effect of Benfotiamine on Advanced Glycation Endproducts and Markers of Endothelial Dysfunction and Inflammation in Diabetic Nephropathy

    NARCIS (Netherlands)

    Alkhalaf, Alaa; Kleefstra, Nanne; Groenier, Klaas H.; Bilo, Henk J. G.; Gans, Reinold O. B.; Heeringa, Peter; Scheijen, Jean L.; Schalkwijk, Casper G.; Navis, Gerjan J.; Bakker, Stephan J. L.

    2012-01-01

    Background: Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and

  13. Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy.

    Science.gov (United States)

    Alkhalaf, Alaa; Kleefstra, Nanne; Groenier, Klaas H; Bilo, Henk J G; Gans, Reinold O B; Heeringa, Peter; Scheijen, Jean L; Schalkwijk, Casper G; Navis, Gerjan J; Bakker, Stephan J L

    2012-01-01

    Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy. Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15-300 mg/24h) were randomized to receive benfotiamine (n = 39) or placebo (n = 43). Plasma and urinary AGEs (N(ε)-(carboxymethyl) lysine [CML], N(ε)-(Carboxyethyl) lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1]) and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin) and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO]) were measured at baseline and after 6 and 12 weeks. Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation. Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications. TRIAL REGRISTRATION: ClinicalTrials.gov NCT00565318.

  14. A Double-Blind, Randomized, Placebo-Controlled Clinical Trial on Benfotiamine Treatment in Patients With Diabetic Nephropathy

    NARCIS (Netherlands)

    Alkhalaf, Alaa; Klooster, Astrid; van Oeveren, Willem; Achenbach, Ulrike; Kleefstra, Nanne; Slingerland, Robbert J.; Mijnhout, G. Sophie; Bilo, Henk J. G.; Gans, Reinold O. B.; Navis, Gerjan J.; Bakker, Stephan J. L.

    OBJECTIVE - To investigate the effect of benfotiamine on urinary albumin excretion (UAE) and the tubular damage marker kidney injury molecule-1 (KIM-1) in patients with type 2 diabetes and nephropathy. RESEARCH DESIGN AND METHODS - Patients with type 2 diabetes and UAE equivalent to 15-300 mg/24 h,

  15. The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes

    Science.gov (United States)

    Fraser, David A.; Diep, Lien M.; Hovden, Inger Anette; Nilsen, Kristian B.; Sveen, Kari Anne; Seljeflot, Ingebjørg; Hanssen, Kristian F.

    2012-01-01

    OBJECTIVE To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. RESULTS Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes. PMID:22446172

  16. Thiamine and benfotiamine improve cognition and ameliorate GSK-3β-associated stress-induced behaviours in mice.

    Science.gov (United States)

    Markova, Nataliia; Bazhenova, Nataliia; Anthony, Daniel C; Vignisse, Julie; Svistunov, Andrey; Lesch, Klaus-Peter; Bettendorff, Lucien; Strekalova, Tatyana

    2017-04-03

    Thiamine (vitamin B1) deficiency in the brain has been implicated in the development of dementia and symptoms of depression. Indirect evidence suggests that thiamine may contribute to these pathologies by controlling the activities of glycogen synthase kinase (GSK)-3β. While decreased GSK-3β activity appears to impair memory, increased GSK-3β activity is associated with the distressed/depressed state. However, hitherto direct evidence for the effects of thiamine on GSK-3β function has not been reported. Here, we administered thiamine or, the more bioavailable precursor, benfotiamine at 200mg/kg/day for 2weeks to C57BL/6J mice, to determine whether treatment might affect behaviours that are known to be sensitive to GSK-3β activity and whether such administration impacts on GSK-3β expression within the brain. The mice were tested in models of contextual conditioning and extinction, a 5-day rat exposure stress test, and a modified swim test with repeated testing. The tricyclic antidepressant imipramine (7.5mg/kg/day), was administered as a positive control for the effects of thiamine or benfotiamine. As for imipramine, both compounds inhibited the upregulation of GSK-3β induced by predator stress or repeated swimming, and reduced floating scores and the predator stress-induced behavioural changes in anxiety and exploration. Coincident, thiamine and benfotiamine improved learning and extinction of contextual fear, and the acquisition of the step-down avoidance task. Our data indicate that thiamine and benfotiamine have antidepressant/anti-stress effects in naïve animals that are associated with reduced GSK-3β expression and conditioning of adverse memories. Thus thiamine and benfotiamine may modulate GSK-3β functions in a manner that is dependent on whether the contextual conditioning is adaptive or maladaptive. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations

    OpenAIRE

    Fraser, D. A.; Hessvik, N. P.; Nikolić, N.; Aas, V.; Hanssen, K. F.; Bøhn, S. K.; Thoresen, G. H.; Rustan, A. C.

    2011-01-01

    The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measu...

  18. Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling.

    Science.gov (United States)

    Marchetti, Valentina; Menghini, Rossella; Rizza, Stefano; Vivanti, Alessia; Feccia, Tiziana; Lauro, Davide; Fukamizu, Akiyoshi; Lauro, Renato; Federici, Massimo

    2006-08-01

    Dysfunction of mature endothelial cells is thought to play a major role in both micro- and macrovascular complications of diabetes. However, recent advances in biology of endothelial progenitor cells (EPCs) have highlighted their involvement in diabetes complications. To determine the effect of glucotoxicity on EPCs, human EPCs have been isolated from peripheral blood mononuclear cells of healthy donors and cultured in the presence or absence of high glucose (33 mmol/l) or high glucose plus benfotiamine to scavenge glucotoxicity. Morphological analysis revealed that high glucose significantly affected the number of endothelial cell colony forming units, uptake and binding of acLDL and Lectin-1, and the ability to differentiate into CD31- and vascular endothelial growth factor receptor 2-positive cells. Functional analysis outlined a reduced EPC involvement in de novo tube formation, when cocultured with mature endothelial cells (human umbilical vein endothelial cells) on matrigel. To explain the observed phenotypes, we have investigated the signal transduction pathways known to be involved in EPC growth and differentiation. Our results indicate that hyperglycemia impairs EPC differentiation and that the process can be restored by benfotiamine administration, via the modulation of Akt/FoxO1 activity.

  19. Antiglycation activity of thiamin-HCl and benfotiamine in diabetic condition.

    Science.gov (United States)

    Kousar, Samina; Sheikh, Munir Ahmad; Asghar, Muhammad

    2012-10-01

    To observe the antiglycation effect of water-soluble vitamin, thiamin-hydrochloride (B1) and its fat-soluble derivative benfotiamine and their comparison with two different glycation assays in diabetics. Plasma of both the normal's and diabetic persons was taken for this experimental study which was conducted in the Department of Chemistry and Biochemistry, University of Agriculture, Faisalabad in 2008. Varying concentrations of both the glycation inhibitors and glucose were incubated for 5 weeks at 37 degrees C. Thiobarbituric acid and periodate borohydride assays were used to measure the antiglycation activity. The increase in glycation was observed from 1st to 3rd week of incubation, while it decreased after the 5th week due to the formation of advanced glycation end products. It was observed that 10mM concentration of benfotiamine and 5mM and 1mM concentrations of thiamine-hydrochloride produced fairly good response to decreased glycation. Comparison between two assays proved periodate borohydride to be more reliable and sensitive than thiobarbituric acid.

  20. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes.

    Science.gov (United States)

    Du, X; Edelstein, D; Brownlee, M

    2008-10-01

    We determined whether fixed doses of benfotiamine in combination with slow-release alpha-lipoic acid normalise markers of reactive oxygen species-induced pathways of complications in humans. Male participants with and without type 1 diabetes were studied in the General Clinical Research Centre of the Albert Einstein College of Medicine. Glycaemic status was assessed by measuring baseline values of three different indicators of hyperglycaemia. Intracellular AGE formation, hexosamine pathway activity and prostacyclin synthase activity were measured initially, and after 2 and 4 weeks of treatment. In the nine participants with type 1 diabetes, treatment had no effect on any of the three indicators used to assess hyperglycaemia. However, treatment with benfotiamine plus alpha-lipoic acid completely normalised increased AGE formation, reduced increased monocyte hexosamine-modified proteins by 40% and normalised the 70% decrease in prostacyclin synthase activity from 1,709 +/- 586 pg/ml 6-keto-prostaglandin F(1alpha) to 4,696 +/- 533 pg/ml. These results show that the previously demonstrated beneficial effects of these agents on complication-causing pathways in rodent models of diabetic complications also occur in humans with type 1 diabetes.

  1. Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice.

    Science.gov (United States)

    Pan, Xiaoli; Gong, Neng; Zhao, Jing; Yu, Zhe; Gu, Fenghua; Chen, Jia; Sun, Xiaojing; Zhao, Lei; Yu, Meijing; Xu, Zhiru; Dong, Wenxin; Qin, Yan; Fei, Guoqiang; Zhong, Chunjiu; Xu, Tian-Le

    2010-05-01

    Reduction of glucose metabolism in brain is one of the main features of Alzheimer's disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3alpha and -3beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment.

  2. Detection of Transketolase in Bone Marrow—Derived Insulin-Producing Cells: Benfotiamine Enhances Insulin Synthesis and Glucose Metabolism

    OpenAIRE

    Oh, Seh-Hoon; Witek, Rafal P.; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E.

    2009-01-01

    Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the prolife...

  3. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  4. Liver, plasma and erythrocyte levels of thiamine and its phosphate esters in rats with acute ethanol intoxication: a comparison of thiamine and benfotiamine administration.

    Science.gov (United States)

    Portari, Guilherme Vannucchi; Vannucchi, Helio; Jordao, Alceu Afonso

    2013-03-12

    Thiamine and benfotiamine are vitamin B1 and pro-vitamin B1 substances, respectively. Vitamin B1 plays an essential role in energy metabolism, and its deficiency leads to neurologic and cardiovascular pathologies, as seen in alcoholics. This study presents new data about the effects of thiamine hydrochloride or benfotiamine treatment given to rats with acute alcohol intoxication, on the distribution of thiamine and its phosphate esters in liver, plasma and erythrocytes. The treatments were effective in increasing thiamine levels in plasma, erythrocytes and liver cells. The benfotiamine-treated group had its total plasma thiamine increased by 100%. In erythrocytes, thiamine levels were 4- and 25-fold higher in the groups treated with thiamine and benfotiamine, respectively, compared with the untreated groups. Liver thiamine was increased by 60% in the treated groups compared with the untreated groups. Thus, we verified the high bioavailability especially of benfotiamine within 6h of ethanol administration. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

    Science.gov (United States)

    Hammad, Ayat S; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar

    2017-05-01

    Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect

  6. ATLa, an aspirin-triggered lipoxin A4 synthetic analog, prevents the inflammatory and fibrotic effects of bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Martins, Vanessa; Valença, Samuel S; Farias-Filho, Francisco A; Molinaro, Raphael; Simões, Rafael L; Ferreira, Tatiana P T; e Silva, Patrícia M R; Hogaboam, Cory M; Kunkel, Steven L; Fierro, Iolanda M; Canetti, Claudio; Benjamim, Claudia F

    2009-05-01

    Despite an increase in the knowledge of mechanisms and mediators involved in pulmonary fibrosis, there are no successful therapeutics available. Lipoxins (LX) and their 15-epimers, aspirin-triggered LX (ATL), are endogenously produced eicosanoids with potent anti-inflammatory and proresolution effects. To date, few studies have been performed regarding their effect on pulmonary fibrosis. In the present study, using C57BL/6 mice, we report that bleomycin (BLM)-induced lung fibrosis was prevented by the concomitant treatment with an ATL synthetic analog, ATLa, which reduced inflammation and matrix deposition. ATLa inhibited BLM-induced leukocyte accumulation and alveolar collapse as evaluated by histology and morphometrical analysis. Moreover, Sirius red staining and lung hydroxyproline content showed an increased collagen deposition in mice receiving BLM alone that was decreased upon treatment with the analog. These effects resulted in benefits to pulmonary mechanics, as ATLa brought to normal levels both lung resistance and compliance. Furthermore, the analog improved mouse survival, suggesting an important role for the LX pathway in the control of disease establishment and progression. One possible mechanism by which ATLa restrained fibrosis was suggested by the finding that BLM-induced myofibroblast accumulation/differentiation in the lung parenchyma was also reduced by both simultaneous and posttreatment with the analog (alpha-actin immunohistochemistry). Interestingly, ATLa posttreatment (4 days after BLM) showed similar inhibitory effects on inflammation and matrix deposition, besides the TGF-beta level reduction in the lung, reinforcing an antifibrotic effect. In conclusion, our findings show that LX and ATL can be considered as promising therapeutic approaches to lung fibrotic diseases.

  7. Analog computing

    CERN Document Server

    Ulmann, Bernd

    2013-01-01

    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  8. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy

    Directory of Open Access Journals (Sweden)

    Batra Surinder K

    2011-08-01

    Full Text Available Abstract Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2, sonic hedgehog (SHH/GLIs and Wnt/β-catenin and downstream signaling elements such as Akt, nuclear factor-kappa B (NF-κB and signal transducers and activators of transcription (STATs. In counterbalance, the high metabolic instability and poor systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of great therapeutic interest, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors, alone or in combination with other anticancer drugs, may improve their chemopreventive and chemotherapeutic efficacies against cancer progression and relapse. Novel curcumin formulations may also be used to reverse drug resistance, eradicate the total cancer cell mass and improve the anticarcinogenic efficacy of the current anti-hormonal and chemotherapeutic treatments for patients with various aggressive and lethal cancers.

  9. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

    Energy Technology Data Exchange (ETDEWEB)

    Abel, E.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Boulware, S. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, T.; McIvor, E.; Powell, K.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); DiGiovanni, J.; Vasquez, K.M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, M.C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    2013-02-01

    Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

  10. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha.

    Science.gov (United States)

    Wu, Shan; Ren, Jun

    2006-02-13

    Diabetes mellitus leads to thiamine deficiency and multiple organ damage including diabetic neuropathy. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cerebral oxidative stress. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg, i.p.). Fourteen days later, control and diabetic (fasting blood glucose >13.9 mM) mice received benfotiamine (100 mg/kg/day, i.p.) for 14 days. Oxidative stress and protein damage were evaluated by glutathione/glutathione disulfide (GSH/GSSG) assay and protein carbonyl formation, respectively. Pro-oxidative or pro-inflammatory factors including advanced glycation end-product (AGE), tissue factor and tumor necrosis factor-alpha (TNF-alpha) were evaluated by immunoblot analysis. Four weeks STZ treatment led to hyperglycemia, enhanced cerebral oxidative stress (reduced GSH/GSSG ratio), elevated TNF-alpha and AGE levels without changes in protein carbonyl or tissue factor. Benfotiamine alleviated diabetes-induced cerebral oxidative stress without affecting levels of AGE, protein carbonyl, tissue factor and TNF-alpha. Collectively, our results indicated benfotiamine may antagonize diabetes-induced cerebral oxidative stress through a mechanism unrelated to AGE, tissue factor and TNF-alpha.

  11. The effects of long-term oral benfotiamine supplementation on peripheral nerve function and inflammatory markers in patients with type 1 diabetes: a 24-month, double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Fraser, David A; Diep, Lien M; Hovden, Inger Anette; Nilsen, Kristian B; Sveen, Kari Anne; Seljeflot, Ingebjørg; Hanssen, Kristian F

    2012-05-01

    To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes.

  12. Effectiveness of egg immersion in aqueous solutions of thiamine and thiamine analogs for reducing early mortality syndrome

    Science.gov (United States)

    Brown, S.B.; Brown, L.R.; Brown, M.; Moore, K.; Villella, M.; Fitzsimons, J.D.; Williston, B.; Honeyfield, D.C.; Hinterkopf, J.P.; Tillitt, D.E.; Zajicek, J.L.; Wolgamood, M.

    2005-01-01

    Protocols used for therapeutic thiamine treatments in salmonine early mortality syndrome (EMS) were investigated in lake trout Salvelinus namaycush and coho salmon Oncorhynchus kisutch to assess their efficacy. At least 500 mg of thiamine HCl/L added to egg baths was required to produce a sustained elevation of thiamine content in lake trout eggs. Thiamine uptake from egg baths was not influenced by a pH ranging from 5.5 to 7.5 or by a water hardness between 2 and 200 mg CaCO3/L. There was poorer thiamine uptake when initial thiamine levels were low, suggesting that current treatment regimes may not be as effective when thiamine levels are severely depressed and that higher treatment doses are necessary. Exposure of eggs to the more lipid-soluble thiamine analog allithiamine (1,000 mg/L) during water hardening increased egg thiamine levels by 1.5-2.5 nmol/g and was completely effective at reversing EMS. Another more lipid-soluble thiamine analog, benfotiamine (100 mg/L), reduced EMS but did not produce detectable increases in egg thiamine content. Although benfotiamine may be more effective than thiamine at mitigating EMS, it is more expensive than thiamine HCl or allithiamine. In addition, there still needs to be a more thorough examination of dose-response relationships. We conclude that allithiamine is an alternative to the use of thiamine in egg baths as a therapeutic treatment for salmonid EMS. ?? Copyright by the American Fisheries Society 2005.

  13. Analog earthquakes

    International Nuclear Information System (INIS)

    Hofmann, R.B.

    1995-01-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository

  14. Inhibition of macrophage oxidative stress prevents the reduction of ABCA-1 transporter induced by advanced glycated albumin.

    Science.gov (United States)

    de Souza Pinto, Raphael; Castilho, Gabriela; Paim, Bruno Alves; Machado-Lima, Adriana; Inada, Natalia M; Nakandakare, Edna Regina; Vercesi, Aníbal Eugênio; Passarelli, Marisa

    2012-05-01

    We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free albumin with 10 mM glycolaldehyde. ROS production and ABCA-1 protein level were determined by flow cytometry in J774 macrophages treated along time with control (C) or AGE-albumin alone or in the presence of aminoguanidine or benfotiamine. Mitochondrial function was evaluated by oxygraphy. Compared to C-albumin, AGE-albumin increased ROS production in macrophages, which was ascribed to the activities of NADPH oxidase and of the mitochondrial system. Mitochondrial respiratory chain activity was reduced in cells incubated with AGE-albumin. ROS generation along time was associated with the reduction in macrophage ABCA-1 protein level. Aminoguanidine prevented ROS elevation and restored the ABCA-1 content in macrophages; on the other hand, benfotiamine that promoted a lesser reduction in ROS generation was not able to restore ABCA-1 levels. Inhibition of oxidative stress induced by AGE-albumin prevents disturbances in reverse cholesterol transport by curbing the reduction of ABCA-1 elicited by advanced glycation in macrophages and therefore may contribute to the prevention of atherosclerosis in diabetes mellitus.

  15. Annexin V Imaging Detects Diabetes-Accelerated Apoptosis and Monitors the Efficacy of Benfotiamine Treatment in Ischemic Limbs of Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Ho Jung

    2014-05-01

    Full Text Available The role of apoptosis imaging for monitoring treatment response in ischemic limbs has not been properly explored. In this study, we investigated the ability of annexin V (AnxV imaging to assess the efficacy of antiapoptotic treatment in ischemic limbs of diabetic mice. Normal C57BL/6 mice and streptozotocin-induced diabetic mice were subject to hindlimb ischemia. AnxV-conjugated fluorescent streptavidin probes were intravenously injected, and optical imaging was performed. Tissue apoptosis was quantified by histochemistry and Western blotting. The AnxV probes showed specific targeting to apoptotic cells on confocal microscopy and flow cytometry. Intravenous AnxV probes displayed substantially greater accumulation in ischemic limbs of diabetic mice. Benfotiamine (BFT treatment of diabetic mice led to better perfusion recovery on laser Doppler imaging and reduced AnxV binding on optical imaging. TUNEL staining and cleaved caspase-3 Western blots confirmed accelerated apoptosis by diabetes and its suppression by BFT treatment. Furthermore, AnxV-SAv-PEcy5.5 uptake in the ischemic limbs closely correlated to cleaved caspase-3 expression. Thus, AnxV imaging may be useful for monitoring the efficacy of therapeutic agents designed to suppress ischemia-induced apoptosis.

  16. Annexin V imaging detects diabetes-accelerated apoptosis and monitors the efficacy of benfotiamine treatment in ischemic limbs of mice.

    Science.gov (United States)

    Jung, Kyung-Ho; Lee, Jin Hee; Park, Jin Won; Paik, Jin Young; Quach, Cung Hoa Thien; Lee, Eun Jeong; Lee, Kyung-Han

    2014-01-01

    The role of apoptosis imaging for monitoring treatment response in ischemic limbs has not been properly explored. In this study, we investigated the ability of annexin V (AnxV) imaging to assess the efficacy of antiapoptotic treatment in ischemic limbs of diabetic mice. Normal C57BL/6 mice and streptozotocin-induced diabetic mice were subject to hindlimb ischemia. AnxV-conjugated fluorescent streptavidin probes were intravenously injected, and optical imaging was performed. Tissue apoptosis was quantified by histochemistry and Western blotting. The AnxV probes showed specific targeting to apoptotic cells on confocal microscopy and flow cytometry. Intravenous AnxV probes displayed substantially greater accumulation in ischemic limbs of diabetic mice. Benfotiamine (BFT) treatment of diabetic mice led to better perfusion recovery on laser Doppler imaging and reduced AnxV binding on optical imaging. TUNEL staining and cleaved caspase-3 Western blots confirmed accelerated apoptosis by diabetes and its suppression by BFT treatment. Furthermore, AnxV-SAv-PEcy5.5 uptake in the ischemic limbs closely correlated to cleaved caspase-3 expression. Thus, AnxV imaging may be useful for monitoring the efficacy of therapeutic agents designed to suppress ischemia-induced apoptosis.

  17. Use of α-Lipoic Acid and Benfotiamine for Correction of Disturbance of Gastric Motor-Evacuation Function in Type 1 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    I.O. Kostitska

    2015-09-01

    Full Text Available The therapeutic effectiveness of α-lipoic acid and benfotiamine in treating symptoms of gastroparesis in type 1 diabetic patients was evaluated. Pathogenetic correlations between increased concentration of peripheral myelin protein and a decrease in the gastric motor-evacuation function were determined. The results of a three-month course of pathogenetic therapy demonstrate the effectiveness of combination therapy which is not associated with an improved compensation of carbohydrate and lipid metabolism. It is a result of the direct effect of preparations on the investigated metabolic processes and restoration of myelination of the nerve fibers.

  18. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-08-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to introduce analogies in their lessons. Both aspects have been discussed in the literature in the last few decades. However, almost nothing is known about how teachers draw their own analogies for instructional purposes or, in other words, about how they reason analogically when planning and conducting teaching. This is the focus of this paper. Six secondary teachers were individually interviewed; the aim was to characterize how they perform each of the analogical reasoning subprocesses, as well as to identify their views on analogies and their use in science teaching. The results were analyzed by considering elements of both theories about analogical reasoning: the structural mapping proposed by Gentner and the analogical mechanism described by Vosniadou. A comprehensive discussion of our results makes it evident that teachers' content knowledge on scientific topics and on analogies as well as their pedagogical content knowledge on the use of analogies influence all their analogical reasoning subprocesses. Our results also point to the need for improving teachers' knowledge about analogies and their ability to perform analogical reasoning.

  19. The antiarrhythmic peptide analog rotigaptide (ZP123) stimulates gap junction intercellular communication in human osteoblasts and prevents decrease in femoral trabecular bone strength in ovariectomized rats

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne

    2005-01-01

    Gap junctions play an important role in bone development and function, but the lack of pharmacological tools has hampered the gap junction research. The antiarrhythmic peptides stimulate gap junction communication between cardiomyocytes, but effects in noncardiac tissue are unknown. The purpose...... of this study was to examine whether antiarrhythmic peptides, which are small peptides increasing gap junctional conductivity, show specific binding to osteoblasts and investigate the effect of the stable analog rotigaptide (ZP123) on gap junctional intercellular communication in vitro and on bone mass...... and strength in vivo. Cell coupling and calcium signaling were assessed in vitro on human, primary, osteoblastic cells. In vivo effects of rotigaptide on bone strength and density were determined 4 wk after ovariectomy in rats treated with either vehicle, sc injection twice daily (300 nmol per kilogram body...

  20. How to prevent mind-wandering during an EVA ? Presentation of a mind-wandering detection method using ECG technology in a Mars-analog environment

    Science.gov (United States)

    Gontier, Camille

    2017-11-01

    The purpose of this study is to detect mind-wandering in an Extra-Vehicular Activity (EVA) context during a long supervision task. Detection is realized using an electro-cardiogram and measures of heart rate variability. Experienced by everyone, mind-wandering depicts the state of mind where thoughts are not related to the current action. Its deleterious aspect regarding performance suggests a need to take mind-wandering seriously as an impediment to manned space missions' safety. Previous research confirmed the hypothesis according to which several physiological responses can be used to track down mind-wandering. ECG recordings are both easy to obtain and analyze, statistically related to mind-wandering, and easy to record during extra-vehicular activities. Data analyzed in this paper have been recorded during a Mars-analog mission (MDRS 164), from February 20 to March 6, 2016 at the Mars Desert Research Station (Utah). During various cognitive tasks, the subject had his ECG and awareness levels monitored at the same time to see if a correlation between these two measures can be used in a Mars-mission environment. At different time intervals, the subject was interrupted using the thought probe method to inquire about his thoughts. Heart Rate Variability (HRV, which power in high frequencies is related to the parasympathetic system and is expected to vary with mind-wandering) was then computed from recorded data, and its statistical changes during on-task and off-task thoughts were assessed. Although data revealed no significant differences nor coherent trends in HRV-related metrics between the two conditions, results are paving the way towards a better understanding of ECG-recordings and their use during space-analog missions.

  1. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  2. Rhetoric and analogies

    OpenAIRE

    Aragonès, Enriqueta; Gilboa, Itzhak; Postlewaite, Andrew; Schmeidler, David; Universitat Autònoma de Barcelona. Unitat de Fonaments de l'Anàlisi Econòmica; Universitat Autònoma de Barcelona. Institut d'Anàlisi Econòmica

    2013-01-01

    The art of rhetoric may be defined as changing other people's minds (opinions, beliefs) without providing them new information. One tech- nique heavily used by rhetoric employs analogies. Using analogies, one may draw the listener's attention to similarities between cases and to re-organize existing information in a way that highlights certain reg- ularities. In this paper we offer two models of analogies, discuss their theoretical equivalence, and show that finding good analogies is a com- p...

  3. Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

    Science.gov (United States)

    Pacini, Stefania; Morucci, Gabriele; Branca, Jacopo J. V.; Aterini, Stefano; Amato, Marcello; Gulisano, Massimo; Ruggiero, Marco

    2013-01-01

    Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification. PMID:23749205

  4. Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Marco Ruggiero

    2013-06-01

    Full Text Available Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification.

  5. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E

    2013-01-01

    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  6. Structured Analog CMOS Design

    CERN Document Server

    Stefanovic, Danica

    2008-01-01

    Structured Analog CMOS Design describes a structured analog design approach that makes it possible to simplify complex analog design problems and develop a design strategy that can be used for the design of large number of analog cells. It intentionally avoids treating the analog design as a mathematical problem, developing a design procedure based on the understanding of device physics and approximations that give insight into parameter interdependences. The proposed transistor-level design procedure is based on the EKV modeling approach and relies on the device inversion level as a fundament

  7. Detecting analogies unconsciously

    Directory of Open Access Journals (Sweden)

    Thomas Peter Reber

    2014-01-01

    Full Text Available Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested whether young volunteers would detect analogies unconsciously between a current supraliminal (visible and a past subliminal (invisible situation. The subliminal encoding of the past situation precludes awareness of analogy detection in the current situation. First, participants encoded subliminal pairs of unrelated words in either one or nine encoding trials. Later, they judged the semantic fit of supraliminally presented new words that either retained a previously encoded semantic relation (‘analog’ or not (‘broken analog’. Words in analogs versus broken analogs were judged closer semantically, which reflects unconscious analogy detection. Hippocampal activity associated with subliminal encoding correlated with the behavioral measure of unconscious analogy detection. Analogs versus broken analogs were processed with reduced prefrontal but enhanced medial temporal activity. We conclude that analogous episodes can be detected even unconsciously drawing on the episodic memory network.

  8. [The effect of long-chain polyunsaturated higher ω-3 fatty acids, benfotiamine and α-lipoic acid on the lipid metabolism in patients with diabetes mellitus type 2 and cardiovascular autonomic neuropathy].

    Science.gov (United States)

    Sergienko, V A; Segin, V B; Samir, A; Sergienko, A A

    2013-01-01

    Eighty-one patients with diabetes mellitus type 2 (DM) and cardiovascular autonomic neuropathy were studied. The combined treatment with ω-3 PUFA, benfotiamine, and α-lipoic acid resulted in significant positive changes in total cholesterol, triacylglycerol, LDL and HDL cholesterol levels. The efficacy of this treatment was not associated with the improved compensation of DM but was a result of the direct influence of pharmacological agents on the metabolic rate studied.

  9. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  10. Analog synthetic biology.

    Science.gov (United States)

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  11. A novel spectral resolution and simultaneous determination of multicomponent mixture of Vitamins B1, B6, B12, Benfotiamine and Diclofenac in tablets and capsules by derivative and MCR-ALS

    Science.gov (United States)

    Hegazy, Maha A.; Abdelwahab, Nada S.; Fayed, Ahmed S.

    2015-04-01

    A novel method was developed for spectral resolution and further determination of five-component mixture including Vitamin B complex (B1, B6, B12 and Benfotiamine) along with the commonly co-formulated Diclofenac. The method is simple, sensitive, precise and could efficiently determine the five components by a complementary application of two different techniques. The first is univariate second derivative method that was successfully applied for determination of Vitamin B12. The second is Multivariate Curve Resolution using the Alternating Least Squares method (MCR-ALS) by which an efficient resolution and quantitation of the quaternary spectrally overlapped Vitamin B1, Vitamin B6, Benfotiamine and Diclofenac sodium were achieved. The effect of different constraints was studied and the correlation between the true spectra and the estimated spectral profiles were found to be 0.9998, 0.9983, 0.9993 and 0.9933 for B1, B6, Benfotiamine and Diclofenac, respectively. All components were successfully determined in tablets and capsules and the results were compared to HPLC methods and they were found to be statistically non-significant.

  12. Challenges in Using Analogies

    Science.gov (United States)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  13. Hydraulic Capacitor Analogy

    Science.gov (United States)

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  14. Optical analogy. Synthesis report

    International Nuclear Information System (INIS)

    1965-01-01

    The authors report the study of conditions under which light attenuation (reflection, diffusion, absorption) and the attenuation of some radiations (notably thermal neutrons) can be described with analogical calculations. The analogy between light physical properties and neutron properties is not searched for, but the analogy between their attenuation characteristics. After having discussed this possible analogy, they propose a mathematical formulation of neutron and optical phenomena which could theoretically justify the optical analogy. The second part reports a more practical study of optics problems such as the study of simple optics materials and illumination measurements, or more precisely the study of angular distributions of optical reflections, a determination of such angular distributions, and an experimental determination of the albedo

  15. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  16. Meat analog: a review.

    Science.gov (United States)

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  17. Selective termination, fetal reduction and analogical reasoning.

    Science.gov (United States)

    Pennings, G

    2013-06-01

    Analogical reasoning is a basic method in bioethics. Its main purpose is to transfer the rule from an existing or known situation to a new and problematic situation. This commentary applies the lifeboat analogy to the context of selective termination and fetal reduction. It turns out that the analogy is only partially helpful as the main principle in the case of selective termination is the procreative beneficence principle. However, the wide person-affecting form of this principle doubly justifies selective termination: i.e. one prevents the harm caused by the birth of an affected child and one increases the life chances of the remaining fetuses. I conclude, however, that all analogies are basically flawed since they assume that fetuses as such have interests. I argue that fetuses only have interests to the extent that they are potential future persons. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  19. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  20. Electrical Circuits and Water Analogies

    Science.gov (United States)

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  1. CMOS analog circuit design

    CERN Document Server

    Allen, Phillip E

    1987-01-01

    This text presents the principles and techniques for designing analog circuits to be implemented in a CMOS technology. The level is appropriate for seniors and graduate students familiar with basic electronics, including biasing, modeling, circuit analysis, and some familiarity with frequency response. Students learn the methodology of analog integrated circuit design through a hierarchically-oriented approach to the subject that provides thorough background and practical guidance for designing CMOS analog circuits, including modeling, simulation, and testing. The authors' vast industrial experience and knowledge is reflected in the circuits, techniques, and principles presented. They even identify the many common pitfalls that lie in the path of the beginning designer--expert advice from veteran designers. The text mixes the academic and practical viewpoints in a treatment that is neither superficial nor overly detailed, providing the perfect balance.

  2. Analogical Reasoning in Geometry Education

    Science.gov (United States)

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  3. Digital and analog communication systems

    Science.gov (United States)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  4. Analogs for transuranic elements

    International Nuclear Information System (INIS)

    Weimer, W.C.; Laul, J.C.; Kutt, J.C.

    1981-01-01

    A combined theoretical and experimental approach is being used to estimate the long-term environmental and biogeochemical behaviors of selected transuranic elements. The objective of this research is to estimate the effect that long-term (hundreds of years) environmental weathering has on the behavior of the transuranic elements americium and curium. This is achieved by investigating the actual behavior of naturally occurring rare earth elements, especially neodymium, that serve as transuranic analogs. Determination of the analog element behavior provides data that can be used to estimate the ultimate availability to man of transuranic materials released into the environment

  5. Terrestrial Analogs to Mars

    Science.gov (United States)

    Farr, T. G.; Arcone, S.; Arvidson, R. W.; Baker, V.; Barlow, N. G.; Beaty, D.; Bell, M. S.; Blankenship, D. D.; Bridges, N.; Briggs, G.; Bulmer, M.; Carsey, F.; Clifford, S. M.; Craddock, R. A.; Dickerson, P. W.; Duxbury, N.; Galford, G. L.; Garvin, J.; Grant, J.; Green, J. R.; Gregg, T. K. P.; Guinness, E.; Hansen, V. L.; Hecht, M. H.; Holt, J.; Howard, A.; Keszthelyi, L. P.; Lee, P.; Lanagan, P. D.; Lentz, R. C. F.; Leverington, D. W.; Marinangeli, L.; Moersch, J. E.; Morris-Smith, P. A.; Mouginis-Mark, P.; Olhoeft, G. R.; Ori, G. G.; Paillou, P.; Reilly, J. F., II; Rice, J. W., Jr.; Robinson, C. A.; Sheridan, M.; Snook, K.; Thomson, B. J.; Watson, K.; Williams, K.; Yoshikawa, K.

    2002-08-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing. These studies include field workshops, characterization of terrestrial analog sites, instrument tests, laboratory measurements (including analysis of Martian meteorites), and computer and laboratory modeling. The combination of all these activities allows scientists to constrain the processes operating in specific terrestrial environments and extrapolate how similar processes could affect Mars. The Terrestrial Analogs for Mars Community Panel has considered the following two key questions: (1) How do terrestrial analog studies tie in to the Mars Exploration Payload Assessment Group science questions about life, past climate, and geologic evolution of Mars, and (2) How can future instrumentation be used to address these questions. The panel has considered the issues of data collection, value of field workshops, data archiving, laboratory measurements and modeling, human exploration issues, association with other areas of solar system exploration, and education and public outreach activities.

  6. Reasoning through Instructional Analogies

    Science.gov (United States)

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  7. The Paradox of Analogy

    Directory of Open Access Journals (Sweden)

    David Botting

    2012-03-01

    Full Text Available I will show that there is a type of analogical reasoning that instantiates a pattern of reasoning in confirmation theory that is considered at best paradoxical and at worst fatal to the entire syntactical approach to confirmation and explanation. However, I hope to elaborate conditions under which this is a sound (although not necessarily strong method of reasoning.

  8. Analogy, explanation, and proof

    Science.gov (United States)

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  9. How Analogy Drives Physics

    International Nuclear Information System (INIS)

    Hofstadter, Doug

    2004-01-01

    Many new ideas in theoretical physics come from analogies to older ideas in physics. For instance, the abstract notion of 'isospin' (or isotopic spin) originated in the prior concept of 'spin' (quantized angular momentum); likewise, the concept of 'phonon' (quantum of sound, or quantized collective excitation of a crystal) was based on the prior concept of 'photon' (quantum of light, or quantized element of the electromagnetic field). But these two examples, far from being exceptions, in fact represent the bread and butter of inventive thinking in physics. In a nutshell, intraphysics analogy-making -- borrowing by analogy with something already known in another area of physics -- is central to the progress of physics. The aim of this talk is to reveal the pervasiveness -- indeed, the indispensability -- of this kind of semi-irrational, wholly intuitive type of thinking (as opposed to more deductive mathematical inference) in the mental activity known as 'doing physics'. Speculations as to why wild analogical leaps are so crucial to the act of discovery in physics (as opposed to other disciplines) will be offered.

  10. Quantum Analog Computing

    Science.gov (United States)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  11. Synthetic Biology: A Unifying View and Review Using Analog Circuits.

    Science.gov (United States)

    Teo, Jonathan J Y; Woo, Sung Sik; Sarpeshkar, Rahul

    2015-08-01

    We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.

  12. Terrestrial Spaceflight Analogs: Antarctica

    Science.gov (United States)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  13. Analog storage integrated circuit

    Science.gov (United States)

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  14. Analogy, Explanation, and Proof

    Directory of Open Access Journals (Sweden)

    John eHummel

    2014-11-01

    Full Text Available People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic whose truth was not even known prior to the existence of the explanation (proof. What do the cognitive operations underlying the (inductive inference that the milk is sour have in common with the (deductive proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This small-seeming difference poses a challenge to the task of marshaling our understanding of analogical reasoning in the service of understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence.

  15. Component Processes in Analogical Reasoning

    Science.gov (United States)

    Sternberg, Robert J.

    1977-01-01

    Describes alternative theoretical positions regarding (a) the component information processes used in analogical reasoning and (b) strategies for combining these processes. Also presents results from three experiments on analogical reasoning. (Author/RK)

  16. Benfotiamine improves functional recovery of the infarcted heart via activation of pro-survival G6PD/Akt signaling pathway and modulation of neurohormonal response.

    Science.gov (United States)

    Katare, Rajesh; Caporali, Andrea; Emanueli, Costanza; Madeddu, Paolo

    2010-10-01

    Benfotiamine (BFT) is a transketolase activator that directs glucose to the pentose phosphate pathway. The present study investigated whether BFT improves the recovery after myocardial infarction (MI) and explored underlying mechanisms of protection. Non-diabetic and streptozotocin-induced type 1 diabetic mice were supplemented with BFT (70 mg/kg/day in drinking water) for 4 weeks and then subjected to MI or sham operation. Cardiac function was monitored by echocardiography. At two weeks post-MI, intra-ventricular pressure was measured by Millar tip-catheter and hearts were collected for biochemical, immunohistochemical and expressional analyses. No treatment effect was observed in sham-operated mice. Post-MI mortality was higher in diabetic mice and hemodynamic studies confirmed the worsening effect of diabetes on functional recovery. Furthermore, diabetic mice demonstrated increased cardiomyocyte apoptosis, reduced reparative angiogenesis, larger scars, enhanced oxidative stress, and blunted activation of the pro-survival VEGF receptor-2/Akt/Pim-1 signaling pathway. BFT improved post-MI survival, functional recovery and neovascularization and reduced cardiomyocyte apoptosis and neurohormonal activation in diabetic as well as in non-diabetic mice. In addition, BFT stimulated the activity of pentose phosphate pathway enzymes, leading to reduction of oxidative stress, phosphorylation/activation of VEGF receptor-2 and Akt and increased Pim-1, pBad and Bcl-2 levels. These effects were contrasted on silencing glucose-6-phosphate dehydrogenase, the key enzyme in pentose phosphate pathway, or inhibiting Akt. BFT benefits post-MI recovery through stimulation of pro-survival mechanisms and containment of neurohormonal response. These results may have implications for the treatment of myocardial ischemia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Inductive, Analogical, and Communicative Generalization

    Directory of Open Access Journals (Sweden)

    Adri Smaling

    2003-03-01

    Full Text Available Three forms of inductive generalization - statistical generalization, variation-based generalization and theory-carried generalization - are insufficient concerning case-to-case generalization, which is a form of analogical generalization. The quality of case-to-case generalization needs to be reinforced by setting up explicit analogical argumentation. To evaluate analogical argumentation six criteria are discussed. Good analogical reasoning is an indispensable support to forms of communicative generalization - receptive and responsive (participative generalization — as well as exemplary generalization.

  18. Analogical Reasoning and Computer Programming.

    Science.gov (United States)

    Clement, Catherine A.; And Others

    1986-01-01

    A study of correlations between analogical reasoning and Logo programming mastery among female high school students related the results of pretests of analogical reasoning to posttests of programming mastery. A significant correlation was found between analogical reasoning and the ability to write subprocedures for use in several different…

  19. Analogical scaffolding: Making meaning in physics through representation and analogy

    Science.gov (United States)

    Podolefsky, Noah Solomon

    This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

  20. Anti-Plasmodium activity of ceramide analogs

    Directory of Open Access Journals (Sweden)

    Gatt Shimon

    2004-12-01

    Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the

  1. Discrete Calculus by Analogy

    CERN Document Server

    Izadi, F A; Bagirov, G

    2009-01-01

    With its origins stretching back several centuries, discrete calculus is now an increasingly central methodology for many problems related to discrete systems and algorithms. The topics covered here usually arise in many branches of science and technology, especially in discrete mathematics, numerical analysis, statistics and probability theory as well as in electrical engineering, but our viewpoint here is that these topics belong to a much more general realm of mathematics; namely calculus and differential equations because of the remarkable analogy of the subject to this branch of mathemati

  2. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H

    2014-01-01

    A comprehensive and in-depth review of analog circuit layout, schematic architecture, device, power network and ESD design This book will provide a balanced overview of analog circuit design layout, analog circuit schematic development, architecture of chips, and ESD design.  It will start at an introductory level and will bring the reader right up to the state-of-the-art. Two critical design aspects for analog and power integrated circuits are combined. The first design aspect covers analog circuit design techniques to achieve the desired circuit performance. The second and main aspect pres

  3. Albert Einstein, Analogizer Extraordinaire

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    Where does deep insight in physics come from? It is tempting to think that it comes from the purest and most precise of reasoning, following ironclad laws of thought that compel the clear mind completely rigidly. And yet the truth is quite otherwise. One finds, when one looks closely at any major discovery, that the greatest of physicists are, in some sense, the most crazily daring and irrational of all physicists. Albert Einstein exemplifies this thesis in spades. In this talk I will describe the key role, throughout Albert Einstein's fabulously creative life, played by wild guesses made by analogy lacking any basis whatsoever in pure reasoning. In particular, in this year of 2007, the centenary of 1907, I will describe how over the course of two years (1905 through 1907) of pondering, Einstein slowly came, via analogy, to understand the full, radical consequences of the equation that he had first discovered and published in 1905, arguably the most famous equation of all time: E = mc2.

  4. Detecting analogical resemblance without retrieving the source analogy.

    Science.gov (United States)

    Kostic, Bogdan; Cleary, Anne M; Severin, Kaye; Miller, Samuel W

    2010-06-01

    We examined whether people can detect analogical resemblance to an earlier experimental episode without being able to recall the experimental source of the analogical resemblance. We used four-word analogies (e.g., robin-nest/beaver-dam), in a variation of the recognition-without-cued-recall method (Cleary, 2004). Participants studied word pairs (e.g., robin-nest) and were shown new word pairs at test, half of which analogically related to studied word pairs (e.g., beaver-dam) and half of which did not. For each test pair, participants first attempted to recall an analogically similar pair from the study list. Then, regardless of whether successful recall occurred, participants were prompted to rate the familiarity of the test pair, which was said to indicate the likelihood that a pair that was analogically similar to the test pair had been studied. Across three experiments, participants demonstrated an ability to detect analogical resemblance without recalling the source analogy. Findings are discussed in terms of their potential relevance to the study of analogical reasoning and insight, as well as to the study of familiarity and recognition memory.

  5. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  6. Beginning analog electronics through projects

    CERN Document Server

    Singmin, Andrew

    2001-01-01

    Analog electronics is the simplest way to start a fun, informative, learning program. Beginning Analog Electronics Through Projects, Second Edition was written with the needs of beginning hobbyists and students in mind. This revision of Andrew Singmin's popular Beginning Electronics Through Projects provides practical exercises, building techniques, and ideas for useful electronics projects. Additionally, it features new material on analog and digital electronics, and new projects for troubleshooting test equipment.Published in the tradition of Beginning Electronics Through Projects an

  7. Children's Development of Analogical Reasoning: Insights from Scene Analogy Problems

    Science.gov (United States)

    Richland, Lindsey E.; Morrison, Robert G.; Holyoak, Keith J.

    2006-01-01

    We explored how relational complexity and featural distraction, as varied in scene analogy problems, affect children's analogical reasoning performance. Results with 3- and 4-year-olds, 6- and 7-year-olds, 9- to 11-year-olds, and 13- and 14-year-olds indicate that when children can identify the critical structural relations in a scene analogy…

  8. Optical analog transmission device

    International Nuclear Information System (INIS)

    Ikawa, Shinji.

    1994-01-01

    The present invention concerns a device such as electro-optical conversion elements, optoelectric-electric elements and optical transmission channel, not undergoing deleterious effects on the efficiency of conversion and transmission due to temperature, and aging change. That is, a sine wave superposing means superposes, on a detector signal to be transmitted, a sine-wave signal having a predetermined amplitude and at a frequency lower than that of the detector signal. An optoelectric conversion means converts the electric signal as the signal of the sine-wave signal superposing means into an optical signal and outputs the same to an optical transmitting channel. The optoelectric conversion means converts the transmitted signal to an electric signal. A discriminating means discriminates the electric signal into a detector signal and a sine-wave signal. A calculating means calculates an optical transmitting efficiency of the transmitting channel based on the amplitude of the discriminated sine-wave signal. A processing means compensates an amplitude value of the detector signals discriminated by the discriminating means based on the optical transmission efficiency. As a result, an optical analog transmission device can be attained, which conducts optical transmission at a high accuracy without undergoing the defective effects of the optical transmission efficiency. (I.S.)

  9. Conjecturing via Reconceived Classical Analogy

    Science.gov (United States)

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  10. Musik som analogi og metafor

    DEFF Research Database (Denmark)

    Bonde, Lars Ole

    2014-01-01

    Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser......Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser...

  11. Drawing Analogies in Environmental Education

    Science.gov (United States)

    Affifi, Ramsey

    2014-01-01

    Reconsidering the origin, process, and outcomes of analogy-making suggests practices for environmental educators who strive to disengage humans from the isolating illusions of dichotomizing frameworks. We can view analogies as outcomes of developmental processes within which human subjectivity is but an element, threading our sense of self back…

  12. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J M

    2010-01-01

    The design of an analog-to-digital converter or digital-to-analog converter is one of the most fascinating tasks in micro-electronics. In a converter the analog world with all its intricacies meets the realm of the formal digital abstraction. Both disciplines must be understood for an optimum conversion solution. In a converter also system challenges meet technology opportunities. Modern systems rely on analog-to-digital converters as an essential part of the complex chain to access the physical world. And processors need the ultimate performance of digital-to-analog converters to present the results of their complex algorithms. The same progress in CMOS technology that enables these VLSI digital systems creates new challenges for analog-to-digital converters: lower signal swings, less power and variability issues. Last but not least, the analog-to-digital converter must follow the cost reduction trend. These changing boundary conditions require micro-electronics engineers to consider their design choices for...

  13. Analog fourier transform channelizer and OFDM receiver

    OpenAIRE

    2007-01-01

    An OFDM receiver having an analog multiplier based I-Q channelizing filter, samples and holds consecutive analog I-Q samples of an I-Q baseband, the I-Q basebands having OFDM sub-channels. A lattice of analog I-Q multipliers and analog I-Q summers concurrently receives the held analog I-Q samples, performs analog I-Q multiplications and analog I-Q additions to concurrently generate a plurality of analog I-Q output signals, representing an N-point discrete Fourier transform of the held analog ...

  14. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  15. Gemini analogs of vitamin D.

    Science.gov (United States)

    Pazos, Gonzalo; Rivadulla, Marcos L; Pérez-García, Xenxo; Gandara, Zoila; Pérez, Manuel

    2014-01-01

    The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. This progression was possible due to improvements in the synthetic methods for the preparation of these derivatives, which allowed for increasing molecular complexity and complete diastereoselective control at C-20 and the substituted sidechains.

  16. Analog filters in nanometer CMOS

    CERN Document Server

    Uhrmann, Heimo; Zimmermann, Horst

    2014-01-01

    Starting from the basics of analog filters and the poor transistor characteristics in nanometer CMOS 10 high-performance analog filters developed by the authors in 120 nm and 65 nm CMOS are described extensively. Among them are gm-C filters, current-mode filters, and active filters for system-on-chip realization for Bluetooth, WCDMA, UWB, DVB-H, and LTE applications. For the active filters several operational amplifier designs are described. The book, furthermore, contains a review of the newest state of research on low-voltage low-power analog filters. To cover the topic of the book comprehensively, linearization issues and measurement methods for the characterization of advanced analog filters are introduced in addition. Numerous elaborate illustrations promote an easy comprehension. This book will be of value to engineers and researchers in industry as well as scientists and Ph.D students at universities. The book is also recommendable to graduate students specializing on nanoelectronics, microelectronics ...

  17. Analog elements for transuranic chemistries

    International Nuclear Information System (INIS)

    Weimer, W.C.

    1982-01-01

    The analytical technique for measuring trace concentrations of the analog rare earth elements has been refined for optimal detection. The technique has been used to determine the rare earth concentrations in a series of geological and biological materials, including samples harvested from controlled lysimeter investigations. These studies have demonstrated that any of the trivalent rare earth elements may be used as analog elements for the trivalent transuranics, americium and curium

  18. CMOS Analog IC Design: Fundamentals

    OpenAIRE

    Bruun, Erik

    2018-01-01

    This book is intended for use as the main textbook for an introductory course in CMOS analog integrated circuit design. It is aimed at electronics engineering students who have followed basic courses in mathematics, physics, circuit theory, electronics and signal processing. It takes the students directly from a basic level to a level where they can start working on simple analog IC design projects or continue their studies using more advanced textbooks in the field. A distinct feature of thi...

  19. Analogical proportions: another logical view

    Science.gov (United States)

    Prade, Henri; Richard, Gilles

    This paper investigates the logical formalization of a restricted form of analogical reasoning based on analogical proportions, i.e. statements of the form a is to b as c is to d. Starting from a naive set theoretic interpretation, we highlight the existence of two noticeable companion proportions: one states that a is to b the converse of what c is to d (reverse analogy), while the other called paralogical proportion expresses that what a and b have in common, c and d have it also. We identify the characteristic postulates of the three types of proportions and examine their consequences from an abstract viewpoint. We further study the properties of the set theoretic interpretation and of the Boolean logic interpretation, and we provide another light on the understanding of the role of permutations in the modeling of the three types of proportions. Finally, we address the use of these proportions as a basis for inference in a propositional setting, and relate it to more general schemes of analogical reasoning. The differences between analogy, reverse-analogy, and paralogy is still emphasized in a three-valued setting, which is also briefly presented.

  20. Antiangiogenic effects of synthetic analogs of curcumin in vivo ...

    African Journals Online (AJOL)

    The active compound curcumin is isolated from the spice turmeric. Curcumin, curcuminoids and their synthetic analogs have been shown to inhibit the progression of cancer in animal models. In colon and skin carcinogenesis the genetic changes engross different genes, but curcumin is effective in preventing ...

  1. Producing and Recognizing Analogical Relations

    Science.gov (United States)

    Lipkens, Regina; Hayes, Steven C

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  2. Fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1982-11-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. = 11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  3. Analog electronics for radiation detection

    CERN Document Server

    2016-01-01

    Analog Electronics for Radiation Detection showcases the latest advances in readout electronics for particle, or radiation, detectors. Featuring chapters written by international experts in their respective fields, this authoritative text: Defines the main design parameters of front-end circuitry developed in microelectronics technologies Explains the basis for the use of complementary metal oxide semiconductor (CMOS) image sensors for the detection of charged particles and other non-consumer applications Delivers an in-depth review of analog-to-digital converters (ADCs), evaluating the pros and cons of ADCs integrated at the pixel, column, and per-chip levels Describes incremental sigma delta ADCs, time-to-digital converter (TDC) architectures, and digital pulse-processing techniques complementary to analog processing Examines the fundamental parameters and front-end types associated with silicon photomultipliers used for single visible-light photon detection Discusses pixel sensors ...

  4. Natural analogs for Yucca Mountain

    International Nuclear Information System (INIS)

    Murphy, W.M.

    1995-01-01

    High-level radioactive waste in the US, spent fuels from commercial reactors and nuclear materials generated by defense activities, will remain potentially hazardous for thousands of years. Demonstrable long-term stability of certain geologic and geochemical systems motivates and sustains the concept that high-level waste can be safely isolated in geologic repositories for requisite periods of time. Each geologic repository is unique in its properties and performance with reguard to isolation of nuclear wastes. Studies of processes analogous to waste-form alteration and radioelement transport in environments analogous to Yucca Mountain are being conducted at two sites, described in this article to illustrate uses of natural analog data: the Nopal I uranium deposit in the Sierra Pena Blanca, Mexico, and the Akrotiri archaeological site on the island of Santorini, Greece

  5. Synthetic Analogs of Phospholipid Metabolites as Antimalarials.

    Science.gov (United States)

    1979-07-01

    phosphatidic acid analogs containing ether and phosphonate groups; completely non- hydrolyzable lecithin analogs containing phosphinate and ether groups...substance is a completely non- hydrolyzable analog of lecithin containing ether and phosphonate moieties instead of the normally labile carboxylic and...and also ant-i-phospholipase C (clostridial enzyme) activity. This substance Is a completely non- hydrolyzable analog of lecithin containing ether

  6. Multichannel analog temperature sensing system

    International Nuclear Information System (INIS)

    Gribble, R.

    1985-08-01

    A multichannel system that protects the numerous and costly water-cooled magnet coils on the translation section of the FRX-C/T magnetic fusion experiment is described. The system comprises a thermistor for each coil, a constant current circuit for each thermistor, and a multichannel analog-to-digital converter interfaced to the computer

  7. 49205 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1997-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course 49205 Analog and Digital Filters...

  8. Drawing Analogies to Deepen Learning

    Science.gov (United States)

    Fava, Michelle

    2017-01-01

    This article offers examples of how drawing can facilitate thinking skills that promote analogical reasoning to enable deeper learning. The instructional design applies cognitive principles, briefly described here. The workshops were developed iteratively, through feedback from student and teacher participants. Elements of the UK National…

  9. Bayesian analogy with relational transformations.

    Science.gov (United States)

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

  10. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Chromatographic Analysis of a Multicomponent Mixture of B1, B6, B12, Benfotiamine, and Diclofenac; Part I: HPLC and UPLC Methods for the Simultaneous Quantification of These Five Components in Tablets and Capsules.

    Science.gov (United States)

    Fayed, Ahmed Salah; Hegazy, Maha Abdel-Monem; Wahab, Nada Sayed Abdel

    2016-11-01

    New, simple, highly sensitive, precise, and accurate gradient reversed-phase chromatographic methods were developed using HPLC and ultra-HPLC (UPLC) systems for the determination of five components, namely thiamine, pyridoxine, cyanocobalamin, benfotiamine, and diclofenac in tablets and capsules. The methods were compared for their efficiency in the separation and determination of these five compounds using two different C18 columns (250 × 4.6 mm, 5 μm; and 100 × 4.6 mm, 2.6 μm) for HPLC and UPLC, respectively. Chromatographic separation was performed with a mobile phase containing acetonitrile and 0.025 M phosphate buffer (pH 3.5), with a gradient program and a flow rate of 1.5 and 1.0 mL/min for both methods, respectively. The methods were validated according to International Conference on Harmonization guidelines. Linearity was achieved in the range of 5.00 to 150.00 μg/mL for each of the five compounds. Ruggedness and intermediate precision were confirmed by different analysts on different columns on different days. Moreover, the components were subjected to an accelerated stability study under acidic, alkaline, and oxidative stress conditions and no interfering peaks were observed. The five compounds were efficiently separated in <20 min by HPLC, whereas for UPLC, separation was achieved in <8 min, which dramatically decreased the consumption of organic solvents.

  12. Analog circuit design art, science and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    This book is far more than just another tutorial or reference guide - it's a tour through the world of analog design, combining theory and applications with the philosophies behind the design process. Readers will learn how leading analog circuit designers approach problems and how they think about solutions to those problems. They'll also learn about the `analog way' - a broad, flexible method of thinking about analog design tasks.A comprehensive and useful guide to analog theory and applications. Covers visualizing the operation of analog circuits. Looks at how to rap

  13. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel

    2017-01-01

    This textbook is appropriate for use in graduate-level curricula in analog-to-digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters. It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation. This book presents an overview of the state of the art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, third edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 22-nm technology and the need for a more statistical approach to accuracy. Pedagogical enhancements to this edition include additional, new exercises, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate. Considerable background information and practical tips, from designing a PCB, to lay-o...

  14. Analogies between antiferromagnets and antiferroelectrics

    International Nuclear Information System (INIS)

    Enz, C.P.; Matthias, B.T.

    1980-01-01

    Ferro- and antiferromagnetism in the Laves phase TiBesub(2-x) Cusub(x) occurs for 0.1 4 H 2 PO 4 and its solid solutions with TlH 2 PO 4 and with the ferroelectric KH 2 PO 4 are discussed as function of deuteration and of pressure. Another analogy as function of pressure is established with the antiferroelectric perovskite PbZrO 3 . (author)

  15. Novel phosphanucleoside analogs of dideoxynucleosides

    Czech Academy of Sciences Publication Activity Database

    Páv, Ondřej; Buděšínský, Miloš; Rosenberg, Ivan

    2017-01-01

    Roč. 73, č. 34 (2017), s. 5220-5228 ISSN 0040-4020 R&D Projects: GA ČR(CZ) GA17-12703S; GA ČR GA13-26526S; GA MZd NV15-31604A Institutional support: RVO:61388963 Keywords : phosphanucleoside * nucleoside analog * ring-closing metathesis * stereoselective hydroboration * chiral resolution Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.651, year: 2016

  16. Electrostatic analogy for symmetron gravity

    Science.gov (United States)

    Ogden, Lillie; Brown, Katherine; Mathur, Harsh; Rovelli, Kevin

    2017-12-01

    The symmetron model is a scalar-tensor theory of gravity with a screening mechanism that suppresses the effect of the symmetron field at high densities characteristic of the Solar System and laboratory scales but allows it to act with gravitational strength at low density on the cosmological scale. We elucidate the screening mechanism by showing that in the quasistatic Newtonian limit there are precise analogies between symmetron gravity and electrostatics for both strong and weak screening. For strong screening we find that large dense bodies behave in a manner analogous to perfect conductors in electrostatics. Based on this analogy we find that the symmetron field exhibits a lightning rod effect wherein the field gradients are enhanced near the ends of pointed or elongated objects. An ellipsoid placed in a uniform symmetron gradient is shown to experience a torque. By symmetry there is no gravitational torque in this case. Hence this effect unmasks the symmetron and might serve as the basis for future laboratory experiments. The symmetron force between a point mass and a large dense body includes a component corresponding to the interaction of the point mass with its image in the larger body. None of these effects have counterparts in the Newtonian limit of Einstein gravity. We discuss the similarities between symmetron gravity and the chameleon model as well as the differences between the two.

  17. The Development of Analogical Reasoning Processes.

    Science.gov (United States)

    Sternberg, Robert J.; Rifkin, Bathsheva

    1979-01-01

    Two experiments were conducted to test the generalizability to children of a theory of analogical reasoning processes, originally proposed for adults, and to examine the development of analogical reasoning processes in terms of five proposed sources of cognitive development. (MP)

  18. 16-channel analog store and multiplexer unit

    Energy Technology Data Exchange (ETDEWEB)

    Brossard, M; Kulka, Z [Clermont-Ferrand-2 Univ., 63 - Aubiere (France). Lab. de Physique Corpusculaire

    1979-03-15

    A 16-channel analog store and multiplexer unit is described. The unit enables storing and selection of analog information which is then digitally encoded by single ADC. This solution becomes economically attractive particularly in multidetector pulse height analysis systems.

  19. Atheism and Analogy: Aquinas Against the Atheists

    OpenAIRE

    Linford, Daniel J.

    2014-01-01

    In the 13th century, Thomas Aquinas developed two models for how humans may speak of God - either by the analogy of proportion or by the analogy of proportionality. Aquinas's doctrines initiated a theological debate concerning analogy that spanned several centuries. In the 18th century, there appeared two closely related arguments for atheism which both utilized analogy for their own purposes. In this thesis, I show that one argument, articulated by the French materialist Paul-Henri Thiry Bar...

  20. Enhancing programming logic thinking using analogy mapping

    Science.gov (United States)

    Sukamto, R. A.; Megasari, R.

    2018-05-01

    Programming logic thinking is the most important competence for computer science students. However, programming is one of the difficult subject in computer science program. This paper reports our work about enhancing students' programming logic thinking using Analogy Mapping for basic programming subject. Analogy Mapping is a computer application which converts source code into analogies images. This research used time series evaluation and the result showed that Analogy Mapping can enhance students' programming logic thinking.

  1. Analogies and the 5E Model

    Science.gov (United States)

    Orgill, Mary Kay; Thomas, Megan

    2007-01-01

    Science classes are full of abstract or challenging concepts that are easier to understand if an analogy is used to illustrate the points. Effective analogies motivate students, clarify students' thinking, help students overcome misconceptions, and give students ways to visualize abstract concepts. When they are used appropriately, analogies can…

  2. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-01-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to…

  3. The Micro-Category Account of Analogy

    Science.gov (United States)

    Green, Adam E.; Fugelsang, Jonathan A.; Kraemer, David J. M.; Dunbar, Kevin N.

    2008-01-01

    Here, we investigate how activation of mental representations of categories during analogical reasoning influences subsequent cognitive processing. Specifically, we present and test the central predictions of the "Micro-Category" account of analogy. This account emphasizes the role of categories in aligning terms for analogical mapping. In a…

  4. Thinking by analogy, systematic risk, and option prices

    OpenAIRE

    Siddiqi, Hammad

    2011-01-01

    People tend to think by analogies and comparisons. Such way of thinking, termed coarse thinking by Mullainathan et al [Quarterly Journal of Economics, May 2008] is intuitively very appealing. We develop a new option pricing model based on the idea that the market consists of coarse thinkers as well as rational investors when limits to arbitrage (transaction costs) prevent rational investors from profiting at the expense of coarse thinkers. The new formula, which is a closed form solution to t...

  5. High Dynamic Range Nonlinear Measurement using Analog Cancellation

    Science.gov (United States)

    2012-10-01

    shield around sensitive areas. The target may also be sensitive to radiated coupling from the system and will benefit from a shield box or Faraday ... cage , if it is not already enclosed. On the shared measurement path and through the target, cross-channel coupling cannot be prevented, so low-PIM...testing is desired, traditional filtering is recommended, as the primary benefits of the analog canceller are effectively nullified. 2.4 Wideband

  6. Are all analogies created equal? Prefrontal cortical functioning may predict types of analogical reasoning.

    Science.gov (United States)

    Chrysikou, Evangelia G; Thompson-Schill, Sharon L

    2010-06-01

    Abstract The proposed theory can account for analogies based on learned relationships between elements in the source and target domains. However, its explanatory power regarding the discovery of new relationships during analogical reasoning is limited. We offer an alternative perspective for the role of PFC in analogical thought that may better address different types of analogical mappings.

  7. Practical analog electronics for technicians

    CERN Document Server

    Kimber, W A

    2013-01-01

    'Practical Analog Electronics for Technicians' not only provides an accessible introduction to electronics, but also supplies all the problems and practical activities needed to gain hands-on knowledge and experience. This emphasis on practice is surprisingly unusual in electronics texts, and has already gained Will Kimber popularity through the companion volume, 'Practical Digital Electronics for Technicians'. Written to cover the Advanced GNVQ optional unit in electronics, this book is also ideal for BTEC National, A-level electronics and City & Guilds courses. Together with 'Practical Digit

  8. Resistive RAMs as analog trimming elements

    Science.gov (United States)

    Aziza, H.; Perez, A.; Portal, J. M.

    2018-04-01

    This work investigates the use of Resistive Random Access Memory (RRAM) as an analog trimming device. The analog storage feature of the RRAM cell is evaluated and the ability of the RRAM to hold several resistance states is exploited to propose analog trim elements. To modulate the memory cell resistance, a series of short programming pulses are applied across the RRAM cell allowing a fine calibration of the RRAM resistance. The RRAM non volatility feature makes the analog device powers up already calibrated for the system in which the analog trimmed structure is embedded. To validate the concept, a test structure consisting of a voltage reference is evaluated.

  9. Analog and mixed-signal electronics

    CERN Document Server

    Stephan, Karl

    2015-01-01

    A practical guide to analog and mixed-signal electronics, with an emphasis on design problems and applications This book provides an in-depth coverage of essential analog and mixed-signal topics such as power amplifiers, active filters, noise and dynamic range, analog-to-digital and digital-to-analog conversion techniques, phase-locked loops, and switching power supplies. Readers will learn the basics of linear systems, types of nonlinearities and their effects, op-amp circuits, the high-gain analog filter-amplifier, and signal generation. The author uses system design examples to motivate

  10. Analog circuit design art, science, and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    Analog Circuit Design: Art, Science, and Personalities discusses the many approaches and styles in the practice of analog circuit design. The book is written in an informal yet informative manner, making it easily understandable to those new in the field. The selection covers the definition, history, current practice, and future direction of analog design; the practice proper; and the styles in analog circuit design. The book also includes the problems usually encountered in analog circuit design; approach to feedback loop design; and other different techniques and applications. The text is

  11. Analogical reasoning in schizophrenic delusions.

    Science.gov (United States)

    Simpson, Jane; Done, D John

    2004-09-01

    Reasoning ability has often been argued to be impaired in people with schizophrenic delusions, although evidence for this is far from convincing. This experiment examined the analogical reasoning abilities of several groups of patients, including non-deluded and deluded schizophrenics, to test the hypothesis that performance by the deluded schizophrenic group would be impaired. Eleven deluded schizophrenics, 10 depressed subjects, seven non-deluded schizophrenics and 16 matched non-psychiatric controls, who were matched on a number of key variables, were asked to solve an analogical reasoning task. Performance by the deluded schizophrenic group was certainly impaired when compared with the depressed and non-psychiatric control groups though less convincingly so when compared with the non-deluded schizophrenic group. The impairment shown by the deluded schizophrenic group seemed to occur at the initial stage of the reasoning task. The particular type of impairment shown by the deluded subjects was assessed in relation to other cognitive problems already researched and the implications of these problems on reasoning tasks and theories of delusions was discussed.

  12. Reliability of analog quantum simulation

    Energy Technology Data Exchange (ETDEWEB)

    Sarovar, Mohan [Sandia National Laboratories, Digital and Quantum Information Systems, Livermore, CA (United States); Zhang, Jun; Zeng, Lishan [Shanghai Jiao Tong University, Joint Institute of UMich-SJTU, Key Laboratory of System Control and Information Processing (MOE), Shanghai (China)

    2017-12-15

    Analog quantum simulators (AQS) will likely be the first nontrivial application of quantum technology for predictive simulation. However, there remain questions regarding the degree of confidence that can be placed in the results of AQS since they do not naturally incorporate error correction. Specifically, how do we know whether an analog simulation of a quantum model will produce predictions that agree with the ideal model in the presence of inevitable imperfections? At the same time there is a widely held expectation that certain quantum simulation questions will be robust to errors and perturbations in the underlying hardware. Resolving these two points of view is a critical step in making the most of this promising technology. In this work we formalize the notion of AQS reliability by determining sensitivity of AQS outputs to underlying parameters, and formulate conditions for robust simulation. Our approach naturally reveals the importance of model symmetries in dictating the robust properties. To demonstrate the approach, we characterize the robust features of a variety of quantum many-body models. (orig.)

  13. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J. M

    2013-01-01

    This textbook is appropriate for use in graduate-level curricula in analog to digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters.  It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation.  This book presents an overview of the state-of-the-art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, second edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 45-nm technology and the need for a more statistical approach to accuracy.  Pedagogical enhancements to this edition include more than twice the exercises available in the first edition, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate.  Considerable background information and pr...

  14. Automatic activation of categorical and abstract analogical relations in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Dunbar, Kevin N

    2006-10-01

    We examined activation of concepts during analogical reasoning. Subjects made either analogical judgments or categorical judgments about four-word sets. After each four-word set, they named the ink color of a single word in a modified Stroop task. Words that referred to category relations were primed (as indicated by longer response times on Stroop color naming) subsequent to analogical judgments and categorical judgments. This finding suggests that activation of category concepts plays a fundamental role in analogical thinking. When colored words referred to analogical relations, priming occurred subsequent to analogical judgments, but not to categorical judgments, even though identical four-word stimuli were used for both types of judgments. This finding lends empirical support to the hypothesis that, when people comprehend the analogy between two items, they activate an abstract analogical relation that is distinct from the specific content items that compose the analogy.

  15. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Fuller, V.; Kahvaz, Y.; Lambert, R.; Newsome, I.; Seeds, M.

    2013-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using facilities at the Dark Sky Observatory (DSO - Appalachian State University) and the Vatican Advanced Technology Telescope (VATT). These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in the 6th year of spectroscopic measurements of these stars: these data include Ca II H & K chromospheric flux measurements, and narrow-band measurements in the photospheric G-band, both obtained with the G/M spectrograph on the DSO 32-inch telescope. We will present evidence of activity cycles in a number of our stars, as well as periods determined from rotational modulation of the spectroscopic indices. The relationship between the Ca II activity index and the G-band index will be explored. NSF support for our project has provided funds for the construction of a robotic photometric telescope to monitor the program stars in a 5-passband system (Strömgren-v, Johnson-Cousins B, V, and R, and a 3-nm wide Hα filter). The robotic telescope has been functional since April 2012 and observes the program stars on every clear night; combined with the Piggy-back telescope attached to the DSO 32-inch, we now have photometric observations on over 130 nights stretching over nearly 2 years. We will examine the relationships between variations in the Ca II H & K index, the G-band index and the photometric bands. This project is supported by the National Science Foundation, grant AST-1109158.

  16. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Seeds, M. F.; Morrison, S. S.

    2012-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using the Dark Sky Observatory (DSO -- Appalachian State University) 32-inch telescope and the G/M spectrograph. These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in our 5th year of obtaining Ca II K & H chromospheric flux measurements, and are beginning to see signs of long-term activity cycles in a number of our stars. In addition, rotational modulation of the chromospheric fluxes is detectable in our data, and we have determined rotational periods for many of our stars. Short timescale increases in the K & H fluxes have been observed in a number of our stars; these events may be related to stellar flares. VATTSpec, a new moderate-resolution spectrograph on the 1.8-m Vatican Telescope in Arizona, has recently become involved with the project. This spectrograph will increase our ability to detect short-term changes in stellar activity on timescales of hours to minutes. We have been monitoring the program stars for one year in a multi-band photometric system consisting of Stromgren-v, and Johnson B, V, and R filters. We will soon add a narrow-band H-alpha filter to the system. Photometry is being carried out with a small piggy-back telescope on the 32-inch, but a robotic photometric telescope is currently being installed at DSO for this purpose. This project is supported by the National Science Foundation.

  17. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  18. Neural correlates of creativity in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Kraemer, David J M; Fugelsang, Jonathan A; Gray, Jeremy R; Dunbar, Kevin N

    2012-03-01

    Brain-based evidence has implicated the frontal pole of the brain as important for analogical mapping. Separately, cognitive research has identified semantic distance as a key determinant of the creativity of analogical mapping (i.e., more distant analogies are generally more creative). Here, we used functional magnetic resonance imaging to assess brain activity during an analogy generation task in which we varied the semantic distance of analogical mapping (as derived quantitatively from a latent semantic analysis). Data indicated that activity within an a priori region of interest in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. Results implicate increased recruitment of frontopolar cortex as a mechanism for integrating semantically distant information to generate solutions in creative analogical reasoning. 2012 APA, all rights reserved

  19. An emergent approach to analogical inference

    Science.gov (United States)

    Thibodeau, Paul H.; Flusberg, Stephen J.; Glick, Jeremy J.; Sternberg, Daniel A.

    2013-03-01

    In recent years, a growing number of researchers have proposed that analogy is a core component of human cognition. According to the dominant theoretical viewpoint, analogical reasoning requires a specific suite of cognitive machinery, including explicitly coded symbolic representations and a mapping or binding mechanism that operates over these representations. Here we offer an alternative approach: we find that analogical inference can emerge naturally and spontaneously from a relatively simple, error-driven learning mechanism without the need to posit any additional analogy-specific machinery. The results also parallel findings from the developmental literature on analogy, demonstrating a shift from an initial reliance on surface feature similarity to the use of relational similarity later in training. Variants of the model allow us to consider and rule out alternative accounts of its performance. We conclude by discussing how these findings can potentially refine our understanding of the processes that are required to perform analogical inference.

  20. Analog techniques in CEBAF's RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    Recent developments in high-speed analog technology have progressed into the areas of traditional RF technology. Diode related devices are being replaced by analog IC's in the CEBAF RF control system. Complex phase modulators and attenuators have been successfully tested at 70 MHz. They have three advantages over existing technology: lower cost, less temperature sensitivity, and more linearity. RF signal conditioning components and how to implement the new analog IC's will be covered in this paper. 4 refs., 5 figs

  1. Analog techniques in CEBAF'S RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    Recent developments in high-speed analog technology have progressed into the areas of traditional rf technology. Diode-related devices are being replaced by analog IC's in the CEBAF rf control system. Complex phase modulators and attenuators have been successfully tested at 70 MHz. They have three advantages over existing technology: lower cost, less temperature sensitivity, and more linearity. Rf signal conditioning components and how to implement the new analog IC's will be covered in this paper. 4 refs., 5 figs

  2. Design and Analysis of Reconfigurable Analog System

    Science.gov (United States)

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  3. Fermilab accelerator control system: Analog monitoring facilities

    International Nuclear Information System (INIS)

    Seino, K.; Anderson, L.; Smedinghoff, J.

    1987-10-01

    Thousands of analog signals are monitored in different areas of the Fermilab accelerator complex. For general purposes, analog signals are sent over coaxial or twinaxial cables with varying lengths, collected at fan-in boxes and digitized with 12 bit multiplexed ADCs. For higher resolution requirements, analog signals are digitized at sources and are serially sent to the control system. This paper surveys ADC subsystems that are used with the accelerator control systems and discusses practical problems and solutions, and it describes how analog data are presented on the console system

  4. Relations as transformations: implications for analogical reasoning.

    Science.gov (United States)

    Leech, Robert; Mareschal, Denis; Cooper, Richard P

    2007-07-01

    We present two experiments assessing whether the size of a transformation instantiating a relation between two states of the world (e.g., shrinks) is a performance factor affecting analogical reasoning. The first experiment finds evidence of transformation size as a significant factor in adolescent analogical problem solving while the second experiment finds a similar effect on adult analogical reasoning using a markedly different analogical completion paradigm. The results are interpreted as providing evidence for the more general framework that cognitive representations of relations are best understood as mental transformations.

  5. Epistemology of analogy: Knowledge, society and expression

    Directory of Open Access Journals (Sweden)

    Mauricio Beuchot

    2017-06-01

    Full Text Available In this article we expose the bases of analog epistemology. This theory of knowledge is between an extreme subjectivism and an extreme objectivism. Analog hermeneutics is a realistic hermeneutics. She seeks the truth, but incorporates the meaning and emotion. We have separated the reason from the experience, the praxis theory, the mind or the soul of the body. We have to get them back together, if we do not get lost in the rational (which says little of the human being, or we lose ourselves in the emotional (without logical consistency. The analogical hermeneutic realism is able, thanks to the analogy itself, to mediate in this way of union.

  6. Synthesis of tritium-labeled vitamin A and its analogs

    International Nuclear Information System (INIS)

    Rhee, S.W.; Bubb, J.E.

    1985-01-01

    Metabolic and pharmacologic studies of Vitamin A and its analogs related to the prevention of lung cancer and other epithelial cancers required tritium-labeled Vitamin A analogs and β-carotene at high specific activity. Syntheses of some of the isomers were therefore developed in the laboratory, as described in the paper. The advantages of the scheme shown are that : 1. Tritiums are introduced into the molecule by catalytic hydrogenation, thus affording high specific activity. 2. It uses an allylic rearrangement of tritiated vinyl-β-ionol to C 15 -phosphonium salt, which is condensed with C 5 -nitrile to give C 20 -skeleton of retinonitrile. 3. It permits the development of milder methods to convert tritium-labeled retinaldehyde, as a common intermediate, to the other retinoids (i.e., retinoic acid, retinol, and retinyl acetate). Furthermore, tritium-labeled all-trans-β-carotene, an important carotenoid, has been obtained from the retinaldehyde

  7. Expert analogy use in a naturalistic setting

    Science.gov (United States)

    Kretz, Donald R.; Krawczyk, Daniel C.

    2014-01-01

    The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker's goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption) of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance. PMID:25505437

  8. Expert Analogy Use in a Naturalistic Setting

    Directory of Open Access Journals (Sweden)

    Donald R Kretz

    2014-11-01

    Full Text Available The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker’s goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance.

  9. Young Children's Analogical Reasoning in Science Domains

    Science.gov (United States)

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

    This exploratory study in a classroom setting investigates first graders' (age 7-8 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at…

  10. Children's Use of Analogy during Collaborative Reasoning

    Science.gov (United States)

    Lin, Tzu-Jung; Anderson, Richard C.; Hummel, John E.; Jadallah, May; Miller, Brian W.; Nguyen-Jahiel, Kim; Morris, Joshua A.; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age…

  11. Patterns of Analogical Reasoning among Beginning Readers

    Science.gov (United States)

    Farrington-Flint, Lee; Wood, Clare; Canobi, Katherine H.; Faulkner, Dorothy

    2004-01-01

    Despite compelling evidence that analogy skills are available to beginning readers, few studies have actually explored the possibility of identifying individual differences in young children's analogy skills in early reading. The present study examined individual differences in children's use of orthographic and phonological relations between…

  12. ANALOGICAL REASONING USING TRANSFORMATIONS OF RULES

    OpenAIRE

    Haraguchi, Makoto; 原口, 誠

    1986-01-01

    A formalism of analogical reasoning is presented. The analogical reasoning can be considered as a deduction with a function of transforming logical rules. From this viewpoint, the reasoning is defined in terms of deduction, and is therefore realized in a logic programming system. The reasoning system is described as an extension of Prolog interpreter.

  13. Analogies in high school Brazilian chemistry textbooks

    Directory of Open Access Journals (Sweden)

    Rosária Justi

    2000-05-01

    Full Text Available This paper presents and discusses an analysis of the analogies presented by Brazilian chemistry textbooks for the medium level. The main aim of the analysis is to discuss whether such analogies can be said good teaching models. From the results, some aspects concerning with teachers' role are discussed. Finally, some new research questions are emphasised.

  14. Spectrometric analog-to-digital converter

    International Nuclear Information System (INIS)

    Ormandzhiev, S.I.; Jordanov, V.T.

    1988-01-01

    Converter of digit-by-digit counterbalancing with slipping dial with number of channels equal to total number of states of the main digital-to-analog converter of digit-by-digit counterbalancing systems is presented. Algorithm for selection of digital-to-analog converters, which must be used by means of computer is suggested

  15. An Analog Computer for Electronic Engineering Education

    Science.gov (United States)

    Fitch, A. L.; Iu, H. H. C.; Lu, D. D. C.

    2011-01-01

    This paper describes a compact analog computer and proposes its use in electronic engineering teaching laboratories to develop student understanding of applications in analog electronics, electronic components, engineering mathematics, control engineering, safe laboratory and workshop practices, circuit construction, testing, and maintenance. The…

  16. PEMETAAN ANALOGI PADA KONSEP ABSTRAK FISIKA

    Directory of Open Access Journals (Sweden)

    Nyoto Suseno

    2014-11-01

    Full Text Available The research of any where founded majority students have common difficulties in abstract physics concept. The result of observation, lecturers have problem  in teaching implementation of abstract concepts on physics learning. The objective of this research is to find out the ways how to overcome this problem. The research place of  physics education programs and senior high school. The data are colected by quetionere, observation and interview. The lecturer behavior to making out this case is use of analogy to make concrete a abstract concept. This action is true, because the analogies are dynamic tools that facilitate understanding, rather than representations of the correct and static explanations. Using analogies not only promoted profound understanding of abstract concept, but also helped students overcome their misconceptions. However used analogy in teaching not yet planed with seriousness, analogy used spontanously with the result that less optimal. By planing and selecting right analogy, the role of analogy can be achieved the optimal result. Therefore, it is important to maping analogies of abstract consepts on physics learning.

  17. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  18. Structure problems in the analog computation

    International Nuclear Information System (INIS)

    Braffort, P.L.

    1957-01-01

    The recent mathematical development showed the importance of elementary structures (algebraic, topological, etc.) in abeyance under the great domains of classical analysis. Such structures in analog computation are put in evidence and possible development of applied mathematics are discussed. It also studied the topological structures of the standard representation of analog schemes such as additional triangles, integrators, phase inverters and functions generators. The analog method gives only the function of the variable: time, as results of its computations. But the course of computation, for systems including reactive circuits, introduces order structures which are called 'chronological'. Finally, it showed that the approximation methods of ordinary numerical and digital computation present the same structure as these analog computation. The structure analysis permits fruitful comparisons between the several domains of applied mathematics and suggests new important domains of application for analog method. (M.P.)

  19. Generating explanations via analogical comparison.

    Science.gov (United States)

    Hoyos, Christian; Gentner, Dedre

    2017-10-01

    Generating explanations can be highly effective in promoting learning in both adults and children. Our interest is in the mechanisms that underlie this effect and in whether and how they operate in early learning. In adult reasoning, explanation may call on many subprocesses-including comparison, counterfactual reasoning, and reasoning by exclusion; but it is unlikely that all these processes are available to young children. We propose that one process that may serve both children and adults is comparison. In this study, we asked whether children would use the results of a comparison experience when asked to explain why a model skyscraper was stable. We focused on a challenging principle-that diagonal cross-bracing lends stability to physical structures (Gentner et al., Cognitive Science, 40, 224-240, 2016). Six-year-olds either received no training or interacted with model skyscrapers in one of three different conditions, designed to vary in their potential to invite and support comparison. In the Single Model condition, children interacted with a single braced model. In the comparison conditions (Low Alignability and High Alignability), children compared braced and unbraced models. Following experience with the models, children were asked to explain why the braced model was stable. They then received two transfer tasks. We found that children who received highly alignable pairs were most likely to (a) produce brace-based explanations and (b) transfer the brace principle to a dissimilar context. This provides evidence that children can benefit from analogical comparison in generating explanations and also suggests limitations on this ability.

  20. Frontopolar cortex mediates abstract integration in analogy.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Kraemer, David J M; Shamosh, Noah A; Dunbar, Kevin N

    2006-06-22

    Integration of abstractly similar relations during analogical reasoning was investigated using functional magnetic resonance imaging. Activation elicited by an analogical reasoning task that required both complex working memory and integration of abstractly similar relations was compared to activation elicited by a non-analogical task that required complex working memory in the absence of abstract relational integration. A left-sided region of the frontal pole of the brain (BA 9/10) was selectively active for the abstract relational integration component of analogical reasoning. Analogical reasoning also engaged a left-sided network of parieto-frontal regions. Activity in this network during analogical reasoning is hypothesized to reflect categorical alignment of individual component terms that make up analogies. This parieto-frontal network was also engaged by the complex control task, which involved explicit categorization, but not by a simpler control task, which did not involve categorization. We hypothesize that frontopolar cortex mediates abstract relational integration in complex reasoning while parieto-frontal regions mediate working memory processes, including manipulation of terms for the purpose of categorical alignment, that facilitate this integration.

  1. Advances in Analog Circuit Design 2015

    CERN Document Server

    Baschirotto, Andrea; Harpe, Pieter

    2016-01-01

    This book is based on the 18 tutorials presented during the 24th workshop on Advances in Analog Circuit Design. Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including low-power and energy-efficient analog electronics, with specific contributions focusing on the design of efficient sensor interfaces and low-power RF systems. This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development. ·         Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; ·         Presents material in a tutorial-based format; ·         Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing.

  2. The force of dissimilar analogies in bioethics.

    Science.gov (United States)

    Mertes, Heidi; Pennings, Guido

    2011-04-01

    Although analogical reasoning has long been a popular method of reasoning in bioethics, current literature does not sufficiently grasp its variety. We assert that the main shortcoming is the fact that an analogy's value is often judged on the extent of similarity between the source situation and the target situation, while in (bio)ethics, analogies are often used because of certain dissimilarities rather than in spite of them. We make a clear distinction between dissimilarities that aim to reinforce a similar approach in the source situation and the target situation and dissimilarities that aim to undermine or denounce a similar approach. The former kind of dissimilarity offers the analogy more normative force than if there were no dissimilarities present; this is often overlooked by authors who regard all relevant dissimilarities as detrimental to the analogy's strength. Another observation is that an evaluation of the normative force of an analogy cannot be made independently of moral principles or theories. Without these, one cannot select which elements in an analogy are morally relevant nor determine how they should be interpreted.

  3. Kidney sales and the analogy with dangerous employment.

    Science.gov (United States)

    Malmqvist, Erik

    2015-06-01

    Proponents of permitting living kidney sales often argue as follows. Many jobs involve significant risks; people are and should be free to take these risks in exchange for money; the risks involved in giving up a kidney are no greater than the risks involved in acceptable hazardous jobs; so people should be free to give up a kidney for money, too. This paper examines this frequently invoked but rarely analysed analogy. Two objections are raised. First, it is far from clear that kidney sales and dangerous jobs involve comparable risks on an appropriately broad comparison. Second, and more importantly, even if they do involve comparable risks it does not follow that kidney sales must be permitted because dangerous jobs are. The analogy assumes that kidney sales are banned for paternalistic reasons. But there may be other, non-paternalistic reasons for the ban. And paternalists, too, can consistently defend the ban even if kidney sales are no riskier than occupations that they find acceptable. Soft paternalists may want to protect would-be vendors from harms that they have not voluntarily chosen. Egalitarian hard paternalists may want to protect already badly off vendors from further worsening their situation. For neither species of paternalist is the size of the risk prevented decisive. I conclude that the analogy with dangerous jobs, while rhetorically powerful, pulls little real argumentative weight. Future debates on living kidney sales should therefore proceed without it.

  4. An Electrical Analog Computer for Poets

    Science.gov (United States)

    Bruels, Mark C.

    1972-01-01

    Nonphysics majors are presented with a direct current experiment beyond Ohms law and series and parallel laws. This involves construction of an analog computer from common rheostats and student-assembled voltmeters. (Author/TS)

  5. Pentagastrin analogs containing α-aminooxy acids

    International Nuclear Information System (INIS)

    Balaspiri, L.; Kovacs, L.; Kovacs, K.; Varga, L.; Varro, V.; Schoen, I.; Kisfaludy, L.

    1982-01-01

    Two 14 C-labelled pentagastrin analogs of different specific radioactivities, containing α-aminooxy acids, have been synthesised to study their biological effects in the gastro-intestinal tract. (U.K.)

  6. Quantum States Transfer by Analogous Bell States

    International Nuclear Information System (INIS)

    Mei Di; Li Chong; Yang Guohui; Song Heshan

    2008-01-01

    Transmitting quantum states by channels of analogous Bell states is studied in this paper. We analyze the transmitting process, constructed the probabilitic unitary operator, and gain the largest successful transfer quantum state probability.

  7. High-frequency analog integrated circuit design

    CERN Document Server

    1995-01-01

    To learn more about designing analog integrated circuits (ICs) at microwave frequencies using GaAs materials, turn to this text and reference. It addresses GaAs MESFET-based IC processing. Describes the newfound ability to apply silicon analog design techniques to reliable GaAs materials and devices which, until now, was only available through technical papers scattered throughout hundred of articles in dozens of professional journals.

  8. Emergent Explorations: Analog and Digital Scripting

    OpenAIRE

    Worden, Alexander

    2011-01-01

    This book documents an exploration of emergent and linear modes of defining space, form, and structure. The thesis highlights a dialog between analog and digital modeling techniques, in concept and project development. It identifies that analog modeling techniques, coupled with judgment, can be used to develop complex forms. The thesis project employs critical judgment and the textile techniques of crochet as a vehicle generate form. Crochet lends itself to this investigation because it ...

  9. An analog integrated circuit design laboratory

    OpenAIRE

    Mondragon-Torres, A.F.; Mayhugh, Jr.; Pineda de Gyvez, J.; Silva-Martinez, J.; Sanchez-Sinencio, E.

    2003-01-01

    We present the structure of an analog integrated circuit design laboratory to instruct at both, senior undergraduate and entry graduate levels. The teaching material includes: a laboratory manual with analog circuit design theory, pre-laboratory exercises and circuit design specifications; a reference web page with step by step instructions and examples; the use of mathematical tools for automation and analysis; and state of the art CAD design tools in use by industry. Upon completion of the ...

  10. HAPS, a Handy Analog Programming System

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe

    1975-01-01

    HAPS (Hybrid Analog Programming System) is an analog compiler that can be run on a minicomputer in an interactive mode. Essentially HAPS is written in FORTRAN. The equations to be programmed for an ana log computer are read in by using a FORTRAN-like notation. The input must contain maximum...... and emphasizes the limitations HAPS puts on equation structure, types of computing circuit, scaling, and static testing....

  11. Children's analogical reasoning about natural phenomena.

    Science.gov (United States)

    Pauen, S; Wilkening, F

    1997-10-01

    This report investigates children's analogical reasoning in a physics task, using an analogy generated by the children rather than by the experimenter. A total of 127 elementary school children took part in three related studies. Children learned to predict the behavior of a balance scale. Later, they were asked to solve a force interaction problem. Two versions of the balance scale training were devised: version A suggested an incorrect solution to the target problem (negative analogy), and version B suggested a correct solution to the target problem (positive analogy). In Study 1, 9- to 10-year-olds showed spontaneous transfer in both training conditions. In Study 2, 7-year-olds did not show any transfer in the positive analogy condition. Study 3 revealed that the lack of transfer in younger children was not due to a failure either to notice the analogy or to perform the mapping. Instead, 7-year-olds transferred only selected aspects of the correct solution. Copyright 1997 Academic Press.

  12. Working memory predicts children's analogical reasoning.

    Science.gov (United States)

    Simms, Nina K; Frausel, Rebecca R; Richland, Lindsey E

    2018-02-01

    Analogical reasoning is the cognitive skill of drawing relationships between representations, often between prior knowledge and new representations, that allows for bootstrapping cognitive and language development. Analogical reasoning proficiency develops substantially during childhood, although the mechanisms underlying this development have been debated, with developing cognitive resources as one proposed mechanism. We explored the role of executive function (EF) in supporting children's analogical reasoning development, with the goal of determining whether predicted aspects of EF were related to analogical development at the level of individual differences. We assessed 5- to 11-year-old children's working memory, inhibitory control, and cognitive flexibility using measures from the National Institutes of Health Toolbox Cognition battery. Individual differences in children's working memory best predicted performance on an analogical mapping task, even when controlling for age, suggesting a fundamental interrelationship between analogical reasoning and working memory development. These findings underscore the need to consider cognitive capacities in comprehensive theories of children's reasoning development. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The future of vitamin D analogs

    Directory of Open Access Journals (Sweden)

    Carlien eLeyssens

    2014-04-01

    Full Text Available The active form of vitamin D3, 1,25-dihydroxyvitamin D3, is a major regulator of bone and calcium homeostasis. In addition, this hormone also inhibits the proliferation and stimulates the differentiation of normal as well as malignant cells. Supraphysiological doses of 1,25-dihydroxyvitamin D3 are required to reduce cancer cell proliferation. However, these doses will lead in vivo to calcemic side effects such as hypercalcemia and hypercalciuria. During the last 25 years, many structural analogs of 1,25-dihydroxyvitamin D3 have been synthesized by the introduction of chemical modifications in the A-ring, central CD-ring region or side chain of 1,25-dihydroxyvitamin D3 in the hope to find molecules with a clear dissociation between the beneficial antiproliferative effects and adverse calcemic side effects. One example of such an analog with a good dissociation ratio is calcipotriol (DaivonexR, which is clinically used to treat the hyperproliferative skin disease psoriasis. Other vitamin D analogs were clinically approved for the treatment of osteoporosis or secondary hyperparathyroidism. No vitamin D analog is currently used in the clinic for the treatment of cancer although several analogs have been shown to be potent drugs in animal models of cancer. Omics studies as well as in vitro cell biological experiments unraveled basic mechanisms involved in the antineoplastic effects of vitamin D and its analogs. 1,25-dihydroxyvitamin D3 and analogs act in a cell type- and tissue-specific manner. Moreover, a blockade in the transition of the G0/1 towards S phase of the cell cycle, induction of apoptosis, inhibition of migration and invasion of tumor cells together with effects on angiogenesis and inflammation have been implicated in the pleiotropic effects of 1,25-dihydroxyvitamin D3 and its analogs. In this review we will give an overview of the action of vitamin D analogs in tumor cells and look forward how these compounds could be introduced in the

  14. NaturAnalogs for the Unsaturated Zone

    Energy Technology Data Exchange (ETDEWEB)

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  15. Analog forecasting with dynamics-adapted kernels

    Science.gov (United States)

    Zhao, Zhizhen; Giannakis, Dimitrios

    2016-09-01

    Analog forecasting is a nonparametric technique introduced by Lorenz in 1969 which predicts the evolution of states of a dynamical system (or observables defined on the states) by following the evolution of the sample in a historical record of observations which most closely resembles the current initial data. Here, we introduce a suite of forecasting methods which improve traditional analog forecasting by combining ideas from kernel methods developed in harmonic analysis and machine learning and state-space reconstruction for dynamical systems. A key ingredient of our approach is to replace single-analog forecasting with weighted ensembles of analogs constructed using local similarity kernels. The kernels used here employ a number of dynamics-dependent features designed to improve forecast skill, including Takens’ delay-coordinate maps (to recover information in the initial data lost through partial observations) and a directional dependence on the dynamical vector field generating the data. Mathematically, our approach is closely related to kernel methods for out-of-sample extension of functions, and we discuss alternative strategies based on the Nyström method and the multiscale Laplacian pyramids technique. We illustrate these techniques in applications to forecasting in a low-order deterministic model for atmospheric dynamics with chaotic metastability, and interannual-scale forecasting in the North Pacific sector of a comprehensive climate model. We find that forecasts based on kernel-weighted ensembles have significantly higher skill than the conventional approach following a single analog.

  16. Analogy, higher order thinking, and education.

    Science.gov (United States)

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. © 2015 John Wiley & Sons, Ltd.

  17. An analog silicon retina with multichip configuration.

    Science.gov (United States)

    Kameda, Seiji; Yagi, Tetsuya

    2006-01-01

    The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

  18. A fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1983-01-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. =11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  19. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  20. Natural Analogs for the Unsaturated Zone

    International Nuclear Information System (INIS)

    Simmons, A.; Unger, A.; Murrell, M.

    2000-01-01

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model

  1. Students' Pre- and Post-Teaching Analogical Reasoning when They Draw Their Analogies

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosaria

    2012-01-01

    Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in…

  2. Changes in analogical reasoning in adulthood.

    Science.gov (United States)

    Clark, E; Gardner, M K; Brown, G; Howell, R J

    1990-01-01

    This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill).

  3. Electronic devices for analog signal processing

    CERN Document Server

    Rybin, Yu K

    2012-01-01

    Electronic Devices for Analog Signal Processing is intended for engineers and post graduates and considers electronic devices applied to process analog signals in instrument making, automation, measurements, and other branches of technology. They perform various transformations of electrical signals: scaling, integration, logarithming, etc. The need in their deeper study is caused, on the one hand, by the extension of the forms of the input signal and increasing accuracy and performance of such devices, and on the other hand, new devices constantly emerge and are already widely used in practice, but no information about them are written in books on electronics. The basic approach of presenting the material in Electronic Devices for Analog Signal Processing can be formulated as follows: the study with help from self-education. While divided into seven chapters, each chapter contains theoretical material, examples of practical problems, questions and tests. The most difficult questions are marked by a diamon...

  4. Electrical analog of a Josephson junction

    International Nuclear Information System (INIS)

    Goldman, A.M.

    1979-01-01

    It is noted that a mathematical description of the phase-coupling of two oscillators synchronized by a phase-lock-loop under the influence of thermal white noise is analogous to that of the phase coupling of two superconductors in a Josephson junction also under the influence of noise. This analogy may be useful in studying threshold instabilities of the Josephson junction in regimes not restricted to the case of large damping. This is of interest because the behavior of the mean voltage near the threshold current can be characterized by critical exponents which resemble those exhibited by an order parameter of a continuous phase transition. As it is possible to couple a collection of oscillators together in a chain, the oscillator analogy may also be useful in exploring the dynamics and statistical mechanics of coupled junctions

  5. On Lovelock analogs of the Riemann tensor

    Science.gov (United States)

    Camanho, Xián O.; Dadhich, Naresh

    2016-03-01

    It is possible to define an analog of the Riemann tensor for Nth order Lovelock gravity, its characterizing property being that the trace of its Bianchi derivative yields the corresponding analog of the Einstein tensor. Interestingly there exist two parallel but distinct such analogs and the main purpose of this note is to reconcile both formulations. In addition we will introduce a simple tensor identity and use it to show that any pure Lovelock vacuum in odd d=2N+1 dimensions is Lovelock flat, i.e. any vacuum solution of the theory has vanishing Lovelock-Riemann tensor. Further, in the presence of cosmological constant it is the Lovelock-Weyl tensor that vanishes.

  6. Analogical reasoning for reliability analysis based on generic data

    Energy Technology Data Exchange (ETDEWEB)

    Kozin, Igor O

    1996-10-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects.

  7. Analogical reasoning for reliability analysis based on generic data

    International Nuclear Information System (INIS)

    Kozin, Igor O.

    1996-01-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects

  8. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science

    Science.gov (United States)

    Remigio, Krisette B.; Yangco, Rosanelia T.; Espinosa, Allen A.

    2014-01-01

    The study examined the reasoning skills of first year high school students after learning general science concepts through analogies. Two intact heterogeneous sections were randomly assigned to Analogy-Enhanced Instruction (AEI) group and Non Analogy-Enhanced (NAEI) group. Various analogies were incorporated in the lessons of the AEI group for…

  9. Perceptions of Rebuttal Analogy: Politeness and Implications for Persuasion.

    Science.gov (United States)

    Whaley, Bryan B.

    1997-01-01

    States that recent theorizing about the role of analogy in persuasion suggests that "rebuttal" analogy addresses two communicative functions by serving as argument and a method of social attack. Examines message receivers' perceptions of rebuttal analogy and rebuttal analogy users. Finds that participants perceived the communicator using…

  10. Words, Concepts, and the Geometry of Analogy

    Directory of Open Access Journals (Sweden)

    Stephen McGregor

    2016-08-01

    Full Text Available This paper presents a geometric approach to the problem of modelling the relationship between words and concepts, focusing in particular on analogical phenomena in language and cognition. Grounded in recent theories regarding geometric conceptual spaces, we begin with an analysis of existing static distributional semantic models and move on to an exploration of a dynamic approach to using high dimensional spaces of word meaning to project subspaces where analogies can potentially be solved in an online, contextualised way. The crucial element of this analysis is the positioning of statistics in a geometric environment replete with opportunities for interpretation.

  11. Analogical reasoning abilities of recovering alcoholics.

    Science.gov (United States)

    Gardner, M K; Clark, E; Bowman, M A; Miller, P J

    1989-08-01

    This study investigated analogical reasoning abilities of alcoholics who had been abstinent from alcohol for at least 1 year. Their performance was compared to that of nonalcoholic controls matched as a group for education, age, and gender. Solution times and error rates were modeled using a regression model. Results showed a nonsignificant trend for alcoholics to be faster, but more error prone, than controls. The same componential model applied to both groups, and fit them equally well. Although differences have been found in analogical reasoning ability between controls and alcoholics immediately following detoxification, we find no evidence of differences after extended periods of sobriety.

  12. Analogy in systems management: a theoretical inquiry

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, B.G.

    1983-11-01

    This theoretical analysis of the intuitive and diffuse characteristics of analogical reasoning processes is the first step in a research effort intended to lead to: understanding of common (and possibly costly) errors, pitfalls, travails, and problem-solving impediments; possible recommendations for improvements to organizational structures, control and coordination processes, and management information flows, and guidelines for a generalized analogical reasoning support framework (e.g., a handbook, a knowledge bank design, and/or even a software package/artificial intelligence program). 233 references.

  13. Analysis of Recurrent Analog Neural Networks

    Directory of Open Access Journals (Sweden)

    Z. Raida

    1998-06-01

    Full Text Available In this paper, an original rigorous analysis of recurrent analog neural networks, which are built from opamp neurons, is presented. The analysis, which comes from the approximate model of the operational amplifier, reveals causes of possible non-stable states and enables to determine convergence properties of the network. Results of the analysis are discussed in order to enable development of original robust and fast analog networks. In the analysis, the special attention is turned to the examination of the influence of real circuit elements and of the statistical parameters of processed signals to the parameters of the network.

  14. Analogy Mapping Development for Learning Programming

    Science.gov (United States)

    Sukamto, R. A.; Prabawa, H. W.; Kurniawati, S.

    2017-02-01

    Programming skill is an important skill for computer science students, whereas nowadays, there many computer science students are lack of skills and information technology knowledges in Indonesia. This is contrary with the implementation of the ASEAN Economic Community (AEC) since the end of 2015 which is the qualified worker needed. This study provided an effort for nailing programming skills by mapping program code to visual analogies as learning media. The developed media was based on state machine and compiler principle and was implemented in C programming language. The state of every basic condition in programming were successful determined as analogy visualization.

  15. Design of analog integrated circuits and systems

    CERN Document Server

    Laker, Kenneth R

    1994-01-01

    This text is designed for senior or graduate level courses in analog integrated circuits or design of analog integrated circuits. This book combines consideration of CMOS and bipolar circuits into a unified treatment. Also included are CMOS-bipolar circuits made possible by BiCMOS technology. The text progresses from MOS and bipolar device modelling to simple one and two transistor building block circuits. The final two chapters present a unified coverage of sample-data and continuous-time signal processing systems.

  16. High-speed and high-resolution analog-to-digital and digital-to-analog converters

    NARCIS (Netherlands)

    van de Plassche, R.J.

    1989-01-01

    Analog-to-digital and digital-to-analog converters are important building blocks connecting the analog world of transducers with the digital world of computing, signal processing and data acquisition systems. In chapter two the converter as part of a system is described. Requirements of analog

  17. Process and circuiting arrangement for the conversion of analog signals to digital signals and digital signals to analog signals

    International Nuclear Information System (INIS)

    Wintzer, K.

    1977-01-01

    Process for analog-to-digital and digital-to-analog conversion in telecommunication systems whose outstations each have an analog transmitter and an analog receiver. The invention illustrates a method of reducing the power demand of the converters at times when no conversion processes take place. (RW) [de

  18. Methane. [biosynthesis from manure or analogous substance

    Energy Technology Data Exchange (ETDEWEB)

    Ducellier, G L.R.; Isman, M A

    1949-04-19

    CH/sub 4/ is produced by the fermentation of manure or analogous substances in a vat having a dome covering the vat, the lower edge of the dome being immersed in a liquid seal, and the dome being arranged to rise vertically in order to hold the CH/sub 4/ produced.

  19. Analog voicing detector responds to pitch

    Science.gov (United States)

    Abel, R. S.; Watkins, H. E.

    1967-01-01

    Modified electronic voice encoder /Vocoder/ includes an independent analog mode of operation in addition to the conventional digital mode. The Vocoder is a bandwidth compression equipment that permits voice transmission over channels, having only a fraction of the bandwidth required for conventional telephone-quality speech transmission.

  20. Invention through Form and Function Analogy

    Science.gov (United States)

    Rule, Audrey C.

    2015-01-01

    "Invention through Form and Function Analogy" is an invention book for teachers and other leaders working with youth who are involving students in the invention process. The book consists of an introduction and set of nine learning cycle formatted lessons for teaching the principles of invention through the science and engineering design…

  1. Formal analogies in physics teacher education

    DEFF Research Database (Denmark)

    Avelar Sotomaior Karam, Ricardo; Ricardo, Elio

    2012-01-01

    the exact same appearance. Coulomb’s law’s similarity with Newton’s, Maxwell’s application of fluid theory to electromagnetism and Hamilton’s optical mechanical analogy are some among many other examples. These cases illustrate the power of mathematics in providing unifying structures for physics. Despite...

  2. An iconic, analogical approach to grammaticalization

    NARCIS (Netherlands)

    Fischer, O.; Conradie, C.J.; Johl, R.; Beukes, M.; Fischer, O.; Ljungberg, C.

    2010-01-01

    This paper addresses a number of problems connected with the ‘apparatus’ used in grammaticalization theory. It will be argued that we get a better grip on what happens in processes of grammaticalization (and its ‘opposite’, lexicalization) if the process is viewed in terms of analogical processes,

  3. Analog and digital dividers for mass spectrometers

    International Nuclear Information System (INIS)

    Osipov, A.K.

    1980-01-01

    Errors of four different types of stress dividers used in statical mass-spectrometers for determination of mass number by accelerating stress are analyzed. The simplest flowsheet of the analog divider comprises operation amplifier, in the chain of the negative feedback of which a multiplication device on differential cascade is switched- in. This analog divider has high sensitivity to temperature and high error approximately 5%. Application of the multiplier on differential cascade with normalization permits to increase temperature stability and decrease the error up to 1%. Another type of the analog divider is a logarithmic divider the error of which is constant within the whole operation range and it constitutes 1-5%. The digital divider with a digital-analog transformer (DAT) has the error of +-0.015% which is determined by the error of detectors and resistance of keys in the locked state. Considered is the design of a divider based on transformation of the inlet stress into the time period. The error of the divider is determined in this case mainly by stress of the zero shift of the operation amplifier (it should be compensated) and relative threshold stability of the comparator triggering which equals (2-3)x10 -4 . It is noted that the divider with DAT application and the divider with the use of stress transformation within the time period are most perspective ones for statical mass-spectrometers [ru

  4. Analog Experiment for rootless cone eruption

    Science.gov (United States)

    Noguchi, R.; Hamada, A.; Suzuki, A.; Kurita, K.

    2017-09-01

    Rootless cone is a unique geomorphological landmark to specify igneous origin of investigated terrane, which is formed by magma-water interaction. To understand its formation mechanism we conducted analog experiment for heat-induced vesiculation by using hot syrup and sodium bicarbonate solution.

  5. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    Minafra, J.; Schmidt, G. K.

    2016-12-01

    SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers. The SSERVI Analog Regolith Simulant Testbed provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment. The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area. SSERVI provides a bridge between several groups, joining together researchers from: 1) scientific and exploration communities, 2) multiple disciplines across a wide range of planetary sciences, and 3) domestic and international communities and partnerships. This testbed provides a means of consolidating the tasks of acquisition, storage and safety mitigation in handling large quantities of regolith simulant Facility hardware and environment testing scenarios include, but are not limited to the following; Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, and Surface features (i.e. grades and rocks) Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and planetary exploration activities at NASA Research Park, to academia and expanded commercial opportunities in California's Silicon Valley, as well as public outreach and education opportunities.

  6. A physical analogy to fuzzy clustering

    DEFF Research Database (Denmark)

    Jantzen, Jan

    2004-01-01

    This tutorial paper provides an interpretation of the membership assignment in the fuzzy clustering algorithm fuzzy c-means. The membership of a data point to several clusters is shown to be analogous to the gravitational forces between bodies of mass. This provides an alternative way to explain...

  7. A high-speed analog neural processor

    NARCIS (Netherlands)

    Masa, P.; Masa, Peter; Hoen, Klaas; Hoen, Klaas; Wallinga, Hans

    1994-01-01

    Targeted at high-energy physics research applications, our special-purpose analog neural processor can classify up to 70 dimensional vectors within 50 nanoseconds. The decision-making process of the implemented feedforward neural network enables this type of computation to tolerate weight

  8. C4913 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1996-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course C4913 Analog and Digital Filters...

  9. Analog circuit design automation for performance

    NARCIS (Netherlands)

    Ning, Zhen-Qiu; Ning, Zhen-Qiu; Kole, Marq; Kole, M.E.; Mouthaan, A.J.; Wallinga, Hans

    1992-01-01

    This paper describes an improved version of the program SEAS (a Simulated Evolution approach for Analog circuit Synthesis), in which an approach for selection of alternatives based on the evaluation of mutation values is developed, and design automafion for high performance comparators is covered.

  10. Hands Together! An Analog Clock Problem

    Science.gov (United States)

    Earnest, Darrell; Radtke, Susan; Scott, Siri

    2017-01-01

    In this article, the authors first present the Hands Together! task. The mathematics in this problem concerns the relationship of hour and minute durations as reflected in the oft-overlooked proportional movements of the two hands of an analog clock. The authors go on to discuss the importance of problem solving in general. They then consider…

  11. Analog subsystem for the plutonium protection system

    International Nuclear Information System (INIS)

    Arlowe, H.D.

    1978-12-01

    An analog subsystem is described which monitors certain functions in the Plutonium Protection System. Rotary and linear potentiometer output signals are digitized, as are the outputs from thermistors and container ''bulge'' sensors. This work was sponsored by the Department of Energy/Office of Safeguards and Security (DOE/OSS) as part of the overall Sandia Fixed Facility Physical Protection Program

  12. The GMO-Nanotech (Dis)Analogy?

    Science.gov (United States)

    Sandler, Ronald; Kay, W. D.

    2006-01-01

    The genetically-modified-organism (GMO) experience has been prominent in motivating science, industry, and regulatory communities to address the social and ethical dimensions of nanotechnology. However, there are some significant problems with the GMO-nanotech analogy. First, it overstates the likelihood of a GMO-like backlash against…

  13. A Mechanical Analogy for Ohm's Law.

    Science.gov (United States)

    do Couto Tavares, Milton; And Others

    1991-01-01

    A mechanical analogy between the microscopic motion of a charged carrier in an ordinary resistor and the macroscopic motion of a ball falling along a slanted board covered with a lattice of nails is introduced. The Drude model is also introduced to include the case of inelastic collisions. Computer simulation of the motion is described. (KR)

  14. Plasma analog of particle-pair production

    International Nuclear Information System (INIS)

    Tsidulko, Yu.A.; Berk, H.L.

    1996-09-01

    It is shown that the plasma axial shear flow instability satisfies the Klein-Gordon equation. The plasma instability is then shown to be analogous to spontaneous particle-pair production when a potential energy is present that is greater than twice the particle rest mass energy. Stability criteria can be inferred based on field theoretical conservation laws

  15. Performance of the Analog Moving Window Detector

    DEFF Research Database (Denmark)

    Hansen, V. Gregers

    1970-01-01

    A type of analog integrating moving window detector for use with a scanning pulse radar is examined. A performance analysis is carried out, which takes into account both the radiation pattern of the antenna and the dynamic character of the detection process due to the angular scanning...

  16. Insulin analogs with improved pharmacokinetic profiles.

    Science.gov (United States)

    Brange; Vølund

    1999-02-01

    The aim of insulin replacement therapy is to normalize blood glucose in order to reduce the complications of diabetes. The pharmacokinetics of the traditional insulin preparations, however, do not match the profiles of physiological insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties. Fast-acting analogs are based on the idea that an insulin with less tendency to self-association than human insulin would be more readily absorbed into the systemic circulation. Protracted-acting analogs have been created to mimic the slow, steady rate of insulin secretion in the fasting state. The present paper provides a historical review of the efforts to change the physicochemical and pharmacological properties of insulin in order to improve insulin therapy. The available clinical studies of the new insulins are surveyed and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs.

  17. Bootstrapped Low-Voltage Analog Switches

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1999-01-01

    Novel low-voltage constant-impedance analog switch circuits are proposed. The switch element is a single MOSFET, and constant-impedance operation is obtained using simple circuits to adjust the gate and bulk voltages relative to the switched signal. Low-voltage (1-volt) operation is made feasible...

  18. Military Importance of Natural Toxins and Their Analogs.

    Science.gov (United States)

    Pitschmann, Vladimír; Hon, Zdeněk

    2016-04-28

    Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots); it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.

  19. Analog-to-digital conversion using custom CMOS analog memory for the EOS time projection chamber

    International Nuclear Information System (INIS)

    Lee, K.L.; Arthur, A.A.; Jones, R.W.; Matis, H.S.; Nakamura, M.; Kleinfelder, S.A.; Ritter, H.G.; Wienman, H.H.

    1990-01-01

    This paper describes the multiplexing scheme of custom CMOS analog memory integrated circuits, 16 channels x 256 cells, into analog to digital converters (ADC's) to handle 15,360 signal channels of a time projection, chamber detector system. Primary requirements of this system are high density, low power and large dynamic range. The analog memory device multiplexing scheme was designed to digitize the information stored in the memory cells. The digitization time of the ADC's and the settling times for the memory unit were carefully interleaved to optimize the performance and timing during the multiplexing operation. This kept the total number of ADC's, a costly and power dissipative component, to an acceptable minimum

  20. Multi-targeting Andrographolide and its Natural Analogs as Potential Therapeutic Agents.

    Science.gov (United States)

    Kishore, V; Yarla, Nagendra Sastry; Bishayee, Anupam; Putta, Swathi; Malla, Ramarao; Neelapu, Nageswara Rao Reddy; Challa, Surekha; Das, Subhasish; Shiralgi, Yallappa; Hegde, Gurumurthy; Dhananjaya, Bhadrapura Lakkappa

    2017-01-01

    Andrographis paniculata (A. paniculata) is a medicinal plant used in the Indian and Chinese traditional medicinal systems for its various beneficial properties of therapeutics. This is due to the presence of a diterpene lactone called 'andrographolide'. Several biological activities like antiinflammatory, antitumour, anti-hyperglycaemic, anti-fertility, antiviral, cardio protective and hepatoprotective properties are attributed to andrographolide and its natural analogs. The studies have shown that not only this diterpene lactone (andrographolide), but also other related terpenoid analogs from A. paniculata could be exploited for disease prevention due to their structural similarity with diverse pharmacological activities. Several scientific groups are trying to unveil the underlying mechanisms involved in these biological actions brough aout by andrographolide and its analogs. This review aims at giving an overview on the therapeutical and/or pharmacological activities of andrographolide and its derivatives and also exemplify the underlying mechanisms involved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Multilateral Research Opportunities in Ground Analogs

    Science.gov (United States)

    Corbin, Barbara J.

    2015-01-01

    The global economy forces many nations to consider their national investments and make difficult decisions regarding their investment in future exploration. International collaboration provides an opportunity to leverage other nations' investments to meet common goals. The Humans In Space Community shares a common goal to enable safe, reliable, and productive human space exploration within and beyond Low Earth Orbit. Meeting this goal requires efficient use of limited resources and International capabilities. The International Space Station (ISS) is our primary platform to conduct microgravity research targeted at reducing human health and performance risks for exploration missions. Access to ISS resources, however, is becoming more and more constrained and will only be available through 2020 or 2024. NASA's Human Research Program (HRP) is actively pursuing methods to effectively utilize the ISS and appropriate ground analogs to understand and mitigate human health and performance risks prior to embarking on human exploration of deep space destinations. HRP developed a plan to use ground analogs of increasing fidelity to address questions related to exploration missions and is inviting International participation in these planned campaigns. Using established working groups and multilateral panels, the HRP is working with multiple Space Agencies to invite International participation in a series of 30- day missions that HRP will conduct in the US owned and operated Human Exploration Research Analog (HERA) during 2016. In addition, the HRP is negotiating access to Antarctic stations (both US and non-US), the German :envihab and Russian NEK facilities. These facilities provide unique capabilities to address critical research questions requiring longer duration simulation or isolation. We are negotiating release of international research opportunities to ensure a multilateral approach to future analog research campaigns, hoping to begin multilateral campaigns in the

  2. Using Visual Analogies To Teach Introductory Statistical Concepts

    Directory of Open Access Journals (Sweden)

    Jessica S. Ancker

    2017-07-01

    Full Text Available Introductory statistical concepts are some of the most challenging to convey in quantitative literacy courses. Analogies supplemented by visual illustrations can be highly effective teaching tools. This literature review shows that to exploit the power of analogies, teachers must select analogies familiar to the audience, explicitly link the analog with the target concept, and avert misconceptions by explaining where the analogy fails. We provide guidance for instructors and a series of visual analogies for use in teaching medical and health statistics.

  3. Analogical reasoning in children with specific language impairment: Evidence from a scene analogy task.

    Science.gov (United States)

    Krzemien, Magali; Jemel, Boutheina; Maillart, Christelle

    2017-01-01

    Analogical reasoning is a human ability that maps systems of relations. It develops along with relational knowledge, working memory and executive functions such as inhibition. It also maintains a mutual influence on language development. Some authors have taken a greater interest in the analogical reasoning ability of children with language disorders, specifically those with specific language impairment (SLI). These children apparently have weaker analogical reasoning abilities than their aged-matched peers without language disorders. Following cognitive theories of language acquisition, this deficit could be one of the causes of language disorders in SLI, especially those concerning productivity. To confirm this deficit and its link to language disorders, we use a scene analogy task to evaluate the analogical performance of SLI children and compare them to controls of the same age and linguistic abilities. Results show that children with SLI perform worse than age-matched peers, but similar to language-matched peers. They are more influenced by increased task difficulty. The association between language disorders and analogical reasoning in SLI can be confirmed. The hypothesis of limited processing capacity in SLI is also being considered.

  4. Analog data transmission via fiber optics

    International Nuclear Information System (INIS)

    Cisneros, E.L.; Burgueno, G.F.

    1986-10-01

    In the SLAC Linear Collider Detector (SLD), as in most high-energy particle detectors, the electromagnetic noise environment is the limiting factor in electronic readout performance. Front-end electronics are particulary susceptible to electromagnetic interference (EMI), and great care has been taken to minimize its effects. The transfer of preprocessed analog signals from the detector environs, to the remote digital processing electronics, by conventional means (via metal conductors), may ultimately limit the performance of the system. Because it is highly impervious to EMI and ground loops, a fiber-optic medium has been chosen for the transmission of these signals. This paper describes several fiber-optic transmission schemes which satisfy the requirements of the SLD analog data transmission

  5. Analog data transmission via fiber optics

    International Nuclear Information System (INIS)

    Cisneros, E.L.; Burgueno, G.F.

    1987-01-01

    In the SLAC Linear Collider Detector (SLD), as in most high-energy particle detectors, the electromagnetic noise environment is the limiting factor in electronic readout performance. Front-end electronics are particularly susceptible to electromagnetic interference (EMI), and great care has been taken to minimize its effects. The transfer of preprocessed analog signals from the detector environs, to the remote digital processing electronics, by conventional means (via metal conductors), may ultimately limit the performance of the system. Because it is highly impervious to EMI and ground loops, a fiber-optic medium has been chosen for the transmission of these signals. This paper describes several fiber-optic transmission schemes which satisfy the requirements of the SLD analog data transmission

  6. An analogy strategy for transformation optics

    International Nuclear Information System (INIS)

    Yao, Kan; Liu, Yongmin; Chen, Huanyang; Jiang, Xunya

    2014-01-01

    We introduce an analogy strategy to design transformation optical devices. Based on the similarities between field lines in different physical systems, the trajectories of light can be intuitively determined to curve in a gentle manner, and the resulting materials are isotropic and nonmagnetic. Furthermore, the physical meaning of the analogue problems plays a key role in the removal of dielectric singularities. We illustrate this approach by creating two designs of carpet cloak and a collimating lens as representative examples in two- and three-dimensional spaces, respectively. The analogy strategy not only reveals the intimate connections between different physical disciplines, such as optics, fluid mechanics and electrostatics, but also provides a heuristic pathway to designing advanced photonic systems

  7. The optical analogy for vector fields

    Science.gov (United States)

    Parker, E. N. (Editor)

    1991-01-01

    This paper develops the optical analogy for a general vector field. The optical analogy allows the examination of certain aspects of a vector field that are not otherwise readily accessible. In particular, in the cases of a stationary Eulerian flow v of an ideal fluid and a magnetostatic field B, the vectors v and B have surface loci in common with their curls. The intrinsic discontinuities around local maxima in absolute values of v and B take the form of vortex sheets and current sheets, respectively, the former playing a fundamental role in the development of hydrodyamic turbulence and the latter playing a major role in heating the X-ray coronas of stars and galaxies.

  8. High resolution tomography using analog coding

    International Nuclear Information System (INIS)

    Brownell, G.L.; Burnham, C.A.; Chesler, D.A.

    1985-01-01

    As part of a 30-year program in the development of positron instrumentation, the authors have developed a high resolution bismuth germanate (BGO) ring tomography (PCR) employing 360 detectors and 90 photomultiplier tubes for one plane. The detectors are shaped as trapezoid and are 4 mm wide at the front end. When assembled, they form an essentially continuous cylindrical detector. Light from a scintillation in the detector is viewed through a cylindrical light pipe by the photomultiplier tubes. By use of an analog coding scheme, the detector emitting light is identified from the phototube signals. In effect, each phototube can identify four crystals. PCR is designed as a static device and does not use interpolative motion. This results in considerable advantage when performing dynamic studies. PCR is the positron tomography analog of the γ-camera widely used in nuclear medicine

  9. Analog fault diagnosis by inverse problem technique

    KAUST Repository

    Ahmed, Rania F.

    2011-12-01

    A novel algorithm for detecting soft faults in linear analog circuits based on the inverse problem concept is proposed. The proposed approach utilizes optimization techniques with the aid of sensitivity analysis. The main contribution of this work is to apply the inverse problem technique to estimate the actual parameter values of the tested circuit and so, to detect and diagnose single fault in analog circuits. The validation of the algorithm is illustrated through applying it to Sallen-Key second order band pass filter and the results show that the detecting percentage efficiency was 100% and also, the maximum error percentage of estimating the parameter values is 0.7%. This technique can be applied to any other linear circuit and it also can be extended to be applied to non-linear circuits. © 2011 IEEE.

  10. Optimal neural computations require analog processors

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.

    1998-12-31

    This paper discusses some of the limitations of hardware implementations of neural networks. The authors start by presenting neural structures and their biological inspirations, while mentioning the simplifications leading to artificial neural networks. Further, the focus will be on hardware imposed constraints. They will present recent results for three different alternatives of parallel implementations of neural networks: digital circuits, threshold gate circuits, and analog circuits. The area and the delay will be related to the neurons` fan-in and to the precision of their synaptic weights. The main conclusion is that hardware-efficient solutions require analog computations, and suggests the following two alternatives: (i) cope with the limitations imposed by silicon, by speeding up the computation of the elementary silicon neurons; (2) investigate solutions which would allow the use of the third dimension (e.g. using optical interconnections).

  11. An introduction to analog and digital communications

    CERN Document Server

    Haykin, Simon

    2012-01-01

    The second edition of this accessible book provides readers with an introductory treatment of communication theory as applied to the transmission of information-bearing signals. While it covers analog communications, the emphasis is placed on digital technology. It begins by presenting the functional blocks that constitute the transmitter and receiver of a communication system. Readers will next learn about electrical noise and then progress to multiplexing and multiple access techniques.

  12. Pyrrolidine nucleotide analogs with a tunable conformation

    Czech Academy of Sciences Publication Activity Database

    Poštová Slavětínská, Lenka; Rejman, Dominik; Pohl, Radek

    2014-01-01

    Roč. 10, Aug 22 (2014), s. 1967-1980 ISSN 1860-5397 R&D Projects: GA ČR GA13-24880S Institutional support: RVO:61388963 Keywords : conformation * NMR * nucleic acids * nucleotide analog * phosphonic acid * pseudorotation * pyrrolidine Subject RIV: CC - Organic Chemistry Impact factor: 2.762, year: 2014 http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-10-205

  13. Combined analog-to-digital converter

    International Nuclear Information System (INIS)

    Zhukov, A.V.; Rzhendinskaya, S.N.

    1983-01-01

    A 10-bit analog-to-digital converter (ADC) designed for operating in spectrometers with time-dependent filters is described. The ADC operation is based on combining the parallel reading and sequential counting methods. At maximum conversion time of 12 μs, timing series frequency of 25 MHz and foUr reference levels the differential nonlinearity withoUt statistical smoothing (maximum relative channel width deviation from average value) is not more than 4%

  14. Performance of MSGC with analog pipeline readout

    International Nuclear Information System (INIS)

    Gomez, F.; Adeva, B.; Gracia, G.; Lopez, M.A.; Nunez, T.; Pazos, A.; Plo, M.; Rodriguez, A.; Santamarina, C.; Vazquez, P.

    1997-01-01

    We analyse some of the performance characteristics of a chromium MSGC operated with Ar-DME 50%-50% in a test beam at CERN. Excellent signal-to-noise ratio and efficiency has been achieved with this gas mixture using cathode analog pipeline readout. We also determine optimal parameters for the sampling algorithm in order to work in a random trigger experiment (fixed target). (orig.)

  15. Biomedical sensor design using analog compressed sensing

    Science.gov (United States)

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2015-05-01

    The main drawback of current healthcare systems is the location-specific nature of the system due to the use of fixed/wired biomedical sensors. Since biomedical sensors are usually driven by a battery, power consumption is the most important factor determining the life of a biomedical sensor. They are also restricted by size, cost, and transmission capacity. Therefore, it is important to reduce the load of sampling by merging the sampling and compression steps to reduce the storage usage, transmission times, and power consumption in order to expand the current healthcare systems to Wireless Healthcare Systems (WHSs). In this work, we present an implementation of a low-power biomedical sensor using analog Compressed Sensing (CS) framework for sparse biomedical signals that addresses both the energy and telemetry bandwidth constraints of wearable and wireless Body-Area Networks (BANs). This architecture enables continuous data acquisition and compression of biomedical signals that are suitable for a variety of diagnostic and treatment purposes. At the transmitter side, an analog-CS framework is applied at the sensing step before Analog to Digital Converter (ADC) in order to generate the compressed version of the input analog bio-signal. At the receiver side, a reconstruction algorithm based on Restricted Isometry Property (RIP) condition is applied in order to reconstruct the original bio-signals form the compressed bio-signals with high probability and enough accuracy. We examine the proposed algorithm with healthy and neuropathy surface Electromyography (sEMG) signals. The proposed algorithm achieves a good level for Average Recognition Rate (ARR) at 93% and reconstruction accuracy at 98.9%. In addition, The proposed architecture reduces total computation time from 32 to 11.5 seconds at sampling-rate=29 % of Nyquist rate, Percentage Residual Difference (PRD)=26 %, Root Mean Squared Error (RMSE)=3 %.

  16. Biophysical and lipofection studies of DOTAP analogs.

    Science.gov (United States)

    Regelin, A E; Fankhaenel, S; Gürtesch, L; Prinz, C; von Kiedrowski, G; Massing, U

    2000-03-15

    In order to investigate the relationship between lipid structure and liposome-mediated gene transfer, we have studied biophysical parameters and transfection properties of monocationic DOTAP analogs, systematically modified in their non-polar hydrocarbon chains. Stability, size and (by means of anisotropy profiles) membrane fluidity of liposomes and lipoplexes were determined, and lipofection efficiency was tested in a luciferase reporter gene assay. DOTAP analogs were used as single components or combined with a helper lipid, either DOPE or cholesterol. Stability of liposomes was a precondition for formation of temporarily stable lipoplexes. Addition of DOPE or cholesterol improved liposome and lipoplex stability. Transfection efficiencies of lipoplexes based on pure DOTAP analogs could be correlated with stability data and membrane fluidity at transfection temperature. Inclusion of DOPE led to rather uniform transfection and anisotropy profiles, corresponding to lipoplex stability. Cholesterol-containing lipoplexes were generally stable, showing high transfection efficiency at low relative fluidity. Our results demonstrate that the efficiency of gene transfer mediated by monocationic lipids is greatly influenced by lipoplex biophysics due to lipid composition. The measurement of fluorescence anisotropy is an appropriate method to characterize membrane fluidity within a defined system of liposomes or lipoplexes and may be helpful to elucidate structure-activity relationships.

  17. Targeting thyroid diseases with TSH receptor analogs.

    Science.gov (United States)

    Galofré, Juan C; Chacón, Ana M; Latif, Rauf

    2013-12-01

    The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  18. Synthetic analog computation in living cells.

    Science.gov (United States)

    Daniel, Ramiz; Rubens, Jacob R; Sarpeshkar, Rahul; Lu, Timothy K

    2013-05-30

    A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

  19. Theory of analogous force on number sets

    Energy Technology Data Exchange (ETDEWEB)

    Canessa, Enrique [Abdus Salam International Centre for Theoretical Physics, Trieste (Italy)

    2003-08-01

    A general statistical thermodynamic theory that considers given sequences of x-integers to play the role of particles of known type in an isolated elastic system is proposed. By also considering some explicit discrete probability distributions p{sub x} for natural numbers, we claim that they lead to a better understanding of probabilistic laws associated with number theory. Sequences of numbers are treated as the size measure of finite sets. By considering p{sub x} to describe complex phenomena, the theory leads to derive a distinct analogous force f{sub x} on number sets proportional to ({partial_derivative}p{sub x}/{partial_derivative}x){sub T} at an analogous system temperature T. In particular, this yields to an understanding of the uneven distribution of integers of random sets in terms of analogous scale invariance and a screened inverse square force acting on the significant digits. The theory also allows to establish recursion relations to predict sequences of Fibonacci numbers and to give an answer to the interesting theoretical question of the appearance of the Benford's law in Fibonacci numbers. A possible relevance to prime numbers is also analyzed. (author)

  20. Periglacial and glacial analogs for Martian landforms

    Science.gov (United States)

    Rossbacher, Lisa A.

    1992-01-01

    The list of useful terrestrial analogs for Martian landforms has been expanded to include: features developed by desiccation processes; catastrophic flood features associated with boulder-sized materials; and sorted ground developed at a density boundary. Quantitative analytical techniques developed for physical geography have been adapted and applied to planetary studies, including: quantification of the patterns of polygonally fractured ground to describe pattern randomness independent of pattern size, with possible correlation to the mechanism of origin and quantification of the relative area of a geomorphic feature or region in comparison to planetary scale. Information about Martian geomorphology studied in this project was presented at professional meetings world-wide, at seven colleges and universities, in two interactive televised courses, and as part of two books. Overall, this project has expanded the understanding of the range of terrestrial analogs for Martian landforms, including identifying several new analogs. The processes that created these terrestrial features are characterized by both cold temperatures and low humidity, and therefore both freeze-thaw and desiccation processes are important. All these results support the conclusion that water has played a significant role in the geomorphic history of Mars.

  1. Sensing Methods for Detecting Analog Television Signals

    Science.gov (United States)

    Rahman, Mohammad Azizur; Song, Chunyi; Harada, Hiroshi

    This paper introduces a unified method of spectrum sensing for all existing analog television (TV) signals including NTSC, PAL and SECAM. We propose a correlation based method (CBM) with a single reference signal for sensing any analog TV signals. In addition we also propose an improved energy detection method. The CBM approach has been implemented in a hardware prototype specially designed for participating in Singapore TV white space (WS) test trial conducted by Infocomm Development Authority (IDA) of the Singapore government. Analytical and simulation results of the CBM method will be presented in the paper, as well as hardware testing results for sensing various analog TV signals. Both AWGN and fading channels will be considered. It is shown that the theoretical results closely match with those from simulations. Sensing performance of the hardware prototype will also be presented in fading environment by using a fading simulator. We present performance of the proposed techniques in terms of probability of false alarm, probability of detection, sensing time etc. We also present a comparative study of the various techniques.

  2. Creative Analogy Use in a Heterogeneous Design Team

    DEFF Research Database (Denmark)

    Christensen, Bo; Ball, Linden J.

    2016-01-01

    the design dialogue derived from team members with highly disparate educational backgrounds. Our analyses revealed that analogies that matched (versus mismatched) educational backgrounds were generated and revisited more frequently, presumably because they were more accessible. Matching analogies were also...

  3. Scientific Analogies and Their Use in Teaching Science

    Science.gov (United States)

    Kipnis, Nahum

    Analogy in science knew its successes and failures, as illustrated by examples from the eighteenth-century physics. At times, some scientists abstained from using a certain analogy on the ground that it had not yet been demonstrated. Several false discoveries in the 18th and early 19th centuries appeared to support their caution. It is now clear that such a position reflected a methodological confusion that resulted from a failure to distinguish between particular and general analogies. Considering analogy as a hierarchical structure provides a new insight into "testing an analogy". While warning science teachers of dangers associated with use of analogy, historical cases and their analysis provided here may encourage them to use analogy more extensively while avoiding misconceptions. An argument is made that the history of science may be a better guide than philosophy of science and cognitive psychology when it concerns the role of analogy in science and in teaching science for understanding.

  4. When Reasoning Modifies Memory: Schematic Assimilation Triggered by Analogical Mapping

    Science.gov (United States)

    Vendetti, Michael S.; Wu, Aaron; Rowshanshad, Ebi; Knowlton, Barbara J.; Holyoak, Keith J.

    2014-01-01

    Analogical mapping highlights shared relations that link 2 situations, potentially at the expense of information that does not fit the dominant pattern of correspondences. To investigate whether analogical mapping can alter subsequent recognition memory for features of a source analog, we performed 2 experiments with 4-term proportional analogies…

  5. Analogies in Medicine: Valuable for Learning, Reasoning, Remembering and Naming

    Science.gov (United States)

    Pena, Gil Patrus; Andrade-Filho, Jose de Souza

    2010-01-01

    Analogies are important tools in human reasoning and learning, for resolving problems and providing arguments, and are extensively used in medicine. Analogy and similarity involve a structural alignment or mapping between domains. This cognitive mechanism can be used to make inferences and learn new abstractions. Through analogies, we try to…

  6. Modern Communication: Exploring Physiological Transmission through Tech-Savvy Analogies

    Science.gov (United States)

    Hollabaugh, Christopher R.; Milanick, Mark A.

    2014-01-01

    Analogies are often helpful for students to grasp key physiological concepts; sometimes the technical jargon makes the concept seem more complex than it actually is. In this article the authors provide several analogies for information transfer processes that sometimes confuse students. For an analogy to be useful, of course, it needs to be…

  7. The design analogy : a model for moral problem solving

    NARCIS (Netherlands)

    Dorst, C.H.; Royakkers, L.M.M.

    2006-01-01

    In this paper we explore an analogy between design and ethics, first drawn by Whitbeck. We investigate her claim that such an analogy can help to understand moral problems and aid us in dealing with them by suggesting strategies for addressing moral problems. We explore the nature of analogies, and

  8. Functional DNA: Teaching Infinite Series through Genetic Analogy

    Science.gov (United States)

    Kowalski, R. Travis

    2011-01-01

    This article presents an extended analogy that connects infinite sequences and series to the science of genetics, by identifying power series as "DNA for a function." This analogy allows standard topics such as convergence tests or Taylor approximations to be recast in a "forensic" light as mathematical analogs of genetic concepts such as DNA…

  9. Circuit with a successive approximation analog to digital converter

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    During successive approximation analog to digital conversion a series of successive digital reference values is selected that converges towards a digital representation of an analog input signal. An analog reference signal is generated dependent on the successive digital reference values and

  10. Circuit with a successive approximation analog to digital converter

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    During successive approximation analog to digital conversion a series of successive digital reference values is selected that converges towards a digital representation of an analog input signal. An analog reference signal is generated dependent on the successive digital reference values and

  11. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    Minafra, Joseph; Schmidt, Gregory; Bailey, Brad; Gibbs, Kristina

    2016-10-01

    The Solar System Exploration Research Virtual Institute (SSERVI) at NASA's Ames Research Center in California's Silicon Valley was founded in 2013 to act as a virtual institute that provides interdisciplinary research centered on the goals of its supporting directorates: NASA Science Mission Directorate (SMD) and the Human Exploration & Operations Mission Directorate (HEOMD).Primary research goals of the Institute revolve around the integration of science and exploration to gain knowledge required for the future of human space exploration beyond low Earth orbit. SSERVI intends to leverage existing JSC1A regolith simulant resources into the creation of a regolith simulant testbed facility. The purpose of this testbed concept is to provide the planetary exploration community with a readily available capability to test hardware and conduct research in a large simulant environment.SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers.SSERVI provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment.The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area, including dust mitigation and safety oversight.Facility hardware and environment testing scenarios could include, Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, Surface features (i.e. grades and rocks)Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and

  12. Military Importance of Natural Toxins and Their Analogs

    Directory of Open Access Journals (Sweden)

    Vladimír Pitschmann

    2016-04-01

    Full Text Available Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots; it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.

  13. Image magnification based on similarity analogy

    International Nuclear Information System (INIS)

    Chen Zuoping; Ye Zhenglin; Wang Shuxun; Peng Guohua

    2009-01-01

    Aiming at the high time complexity of the decoding phase in the traditional image enlargement methods based on fractal coding, a novel image magnification algorithm is proposed in this paper, which has the advantage of iteration-free decoding, by using the similarity analogy between an image and its zoom-out and zoom-in. A new pixel selection technique is also presented to further improve the performance of the proposed method. Furthermore, by combining some existing fractal zooming techniques, an efficient image magnification algorithm is obtained, which can provides the image quality as good as the state of the art while greatly decrease the time complexity of the decoding phase.

  14. Probleme bei der Digitalisierung analoger Messwerte

    Science.gov (United States)

    Plaßmann, Wilfried

    Messwerte liegen häufig in analoger Form als Spannungswerte vor. Sie werden in eine digital kodierte Form umgesetzt, wenn eine (nahezu) fehlerfreie Übertragung erforderlich ist, wenn Signalverläufe gespeichert werden sollen, wenn eine Weiterverarbeitung erfolgen soll oder wenn Messungen mit sehr geringem Messfehler notwendig sind. Hier soll auf einige Probleme, die durch die Umsetzung entstehen, aus messtechnischer Sicht eingegangen werden. Stichworte: Fehler bei der Digitalisierung; Signal-Quantisierungsgeräusch-Abstand; Verbesserung des Signal-Rausch-Verhältnisses; Abtast-Halte-Glied; Aliasing; Erfassung von Momentanwerten.

  15. Bosonic analog of the Klein paradox

    International Nuclear Information System (INIS)

    Wagner, R. E.; Ware, M. R.; Su, Q.; Grobe, R.

    2010-01-01

    The standard Klein paradox describes how an incoming electron scatters off a supercritical electrostatic barrier that is so strong that it can generate electron-positron pairs. This fermionic system has been widely discussed in textbooks to illustrate some of the discrepancies between quantum mechanical and quantum field theoretical descriptions for the pair creation process. We compare the fermionic dynamics with that of the corresponding bosonic system. We point out that the direct counterpart of the Pauli exclusion principle (the central mechanism to resolve the fermionic Klein paradox) is stimulated emission, which leads to the resolution of the analogous bosonic paradox.

  16. Novel Gemini vitamin D3 analogs

    DEFF Research Database (Denmark)

    Okamoto, Ryoko; Gery, Sigal; Kuwayama, Yoshio

    2014-01-01

    anticancer potency, but similar toxicity causing hypercalcemia. We focused on the effect of these compounds on the stimulation of expression of human cathelicidin antimicrobial peptide (CAMP) whose gene has a vitamin D response element in its promoter. Expression of CAMP mRNA and protein increased in a dose......-response fashion after exposure of acute myeloid leukemia (AML) cells to the Gemini analog, BXL-01-126, in vitro. A xenograft model of AML was developed using U937 AML cells injected into NSG-immunodeficient mice. Administration of vitamin D3 compounds to these mice resulted in substantial levels of CAMP...

  17. Development of analog watch with minute repeater

    Science.gov (United States)

    Okigami, Tomio; Aoyama, Shigeru; Osa, Takashi; Igarashi, Kiyotaka; Ikegami, Tomomi

    A complementary metal oxide semiconductor with large scale integration was developed for an electronic minute repeater. It is equipped with the synthetic struck sound circuit to generate natural struck sound necessary for the minute repeater. This circuit consists of an envelope curve drawing circuit, frequency mixer, polyphonic mixer, and booster circuit made by using analog circuit technology. This large scale integration is a single chip microcomputer with motor drivers and input ports in addition to the synthetic struck sound circuit, and it is possible to make an electronic system of minute repeater at a very low cost in comparison with the conventional type.

  18. Analog to digital conversion for nuclear spectrometry

    International Nuclear Information System (INIS)

    Carvalho, P.V.R. de.

    1982-04-01

    A study of the analog to digital conversion techniques for nuclear spectrometry is presented and the main design philosophies of nuclear ADC's are compared. Among them, the most suitable for the current Brazilian conditions, concerning the specifications and components avaiability is the one that employs a statistical correction of successive approximation converters. This technique is described in full detail. A prototype has been developed an tested for the practical demonstration of the theoretical conclusions. These tests was carried on nuclear spectrometry data aquisition system whose implementation is also described. (Author) [pt

  19. A bilateral frontoparietal network underlies visuospatial analogical reasoning.

    Science.gov (United States)

    Watson, Christine E; Chatterjee, Anjan

    2012-02-01

    Our ability to reason by analogy facilitates problem solving and allows us to communicate ideas efficiently. In this study, we examined the neural correlates of analogical reasoning and, more specifically, the contribution of rostrolateral prefrontal cortex (RLPFC) to reasoning. This area of the brain has been hypothesized to integrate relational information, as in analogy, or the outcomes of subgoals, as in multi-tasking and complex problem solving. Using fMRI, we compared visuospatial analogical reasoning to a control task that was as complex and difficult as the analogies and required the coordination of subgoals but not the integration of relations. We found that analogical reasoning more strongly activated bilateral RLPFC, suggesting that anterior prefrontal cortex is preferentially recruited by the integration of relational knowledge. Consistent with the need for inhibition during analogy, bilateral, and particularly right, inferior frontal gyri were also more active during analogy. Finally, greater activity in bilateral inferior parietal cortex during the analogy task is consistent with recent evidence for the neural basis of spatial relation knowledge. Together, these findings indicate that a network of frontoparietal areas underlies analogical reasoning; we also suggest that hemispheric differences may emerge depending on the visuospatial or verbal/semantic nature of the analogies. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Elucidating the neurotoxic effects of MDMA and its analogs.

    Science.gov (United States)

    Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Deruiter, Jack; Clark, Randall; Dhanasekaran, Muralikrishnan

    2014-04-17

    There is a rapid increase in the use of methylenedioxymethamphetamine (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have been synthesized illegally in furtive dwellings and are abused due to its addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have induced several adverse effects. Hence, understanding the mechanisms mediating this neurotoxic insult of MDMA-analogs is of immense importance for the public health in the world. We synthesized and investigated the neurotoxic effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned animal model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species generation. MDMA and MDMA-analogs exhibited stimulatory activity as compared to amphetamines and also induced several behavioral changes in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and inhibited mitochondrial complex-I activity which can lead to neurodegeneration. Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the release of monoamines, alter the monoaminergic neurotransmission, and augment oxidative stress and mitochondrial abnormalities leading to neurotoxicity. Thus, our study will help in developing effective pharmacological and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. How the creative use of analogies can shape medical practice.

    Science.gov (United States)

    Prasad, G V Ramesh

    2015-06-01

    Analogical reasoning is central to medical progress, and is either creative or conservative. According to Hofmann et al., conservative analogy relates concepts from old technology to new technologies with emphasis on preservation of comprehension and conduct. Creative analogy however brings new understanding to new technology, brings similarities existing in the source domain to a target domain where they previously had no bearing, and imports something entirely different from the content of the analogy itself. I defend the claim that while conservative analogies are useful by virtue of being comfortable to use from familiarity and experience, and are more easily accepted by society, they only lead to incremental advances in medicine. However, creative analogies are more exciting and productive because they generate previously unexpected associations across widely separated domains, emphasize relations over physical similarities, and structure over superficiality. I use kidney transplantation and anti-rejection medication development as an exemplar of analogical reasoning used to improve medical practice. Anti-rejection medication has not helped highly sensitized patients because of their propensity to rejecting most organs. I outline how conservative analogical reasoning led to anti-rejection medication development, but creative analogical reasoning helped highly sensitized and blood type incompatible patients through domino transplants, by which they obtain a kidney to which they are not sensitized. Creative analogical reasoning is more likely than conservative analogical reasoning to lead to revolutionary progress. While these analogies overlap and creative analogies eventually become conservative, progress is best facilitated by combining conservative and creative analogical reasoning. © 2015 John Wiley & Sons, Ltd.

  2. Discrete stochastic analogs of Erlang epidemic models.

    Science.gov (United States)

    Getz, Wayne M; Dougherty, Eric R

    2018-12-01

    Erlang differential equation models of epidemic processes provide more realistic disease-class transition dynamics from susceptible (S) to exposed (E) to infectious (I) and removed (R) categories than the ubiquitous SEIR model. The latter is itself is at one end of the spectrum of Erlang SE[Formula: see text]I[Formula: see text]R models with [Formula: see text] concatenated E compartments and [Formula: see text] concatenated I compartments. Discrete-time models, however, are computationally much simpler to simulate and fit to epidemic outbreak data than continuous-time differential equations, and are also much more readily extended to include demographic and other types of stochasticity. Here we formulate discrete-time deterministic analogs of the Erlang models, and their stochastic extension, based on a time-to-go distributional principle. Depending on which distributions are used (e.g. discretized Erlang, Gamma, Beta, or Uniform distributions), we demonstrate that our formulation represents both a discretization of Erlang epidemic models and generalizations thereof. We consider the challenges of fitting SE[Formula: see text]I[Formula: see text]R models and our discrete-time analog to data (the recent outbreak of Ebola in Liberia). We demonstrate that the latter performs much better than the former; although confining fits to strict SEIR formulations reduces the numerical challenges, but sacrifices best-fit likelihood scores by at least 7%.

  3. Endpoint distinctiveness facilitates analogical mapping in pigeons.

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G

    2015-03-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Endpoint Distinctiveness Facilitates Analogical Mapping in Pigeons

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G.

    2015-01-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, reassignment, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal map of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons’ capacity for more advanced types of analogical reasoning. PMID:25447511

  5. Merging Galaxy Clusters: Analysis of Simulated Analogs

    Science.gov (United States)

    Nguyen, Jayke; Wittman, David; Cornell, Hunter

    2018-01-01

    The nature of dark matter can be better constrained by observing merging galaxy clusters. However, uncertainty in the viewing angle leads to uncertainty in dynamical quantities such as 3-d velocities, 3-d separations, and time since pericenter. The classic timing argument links these quantities via equations of motion, but neglects effects of nonzero impact parameter (i.e. it assumes velocities are parallel to the separation vector), dynamical friction, substructure, and larger-scale environment. We present a new approach using n-body cosmological simulations that naturally incorporate these effects. By uniformly sampling viewing angles about simulated cluster analogs, we see projected merger parameters in the many possible configurations of a given cluster. We select comparable simulated analogs and evaluate the likelihood of particular merger parameters as a function of viewing angle. We present viewing angle constraints for a sample of observed mergers including the Bullet cluster and El Gordo, and show that the separation vectors are closer to the plane of the sky than previously reported.

  6. The gravitational analog of Faraday's induction law

    Science.gov (United States)

    Zile, Daniel; Overduin, James

    2015-04-01

    Michael Faraday, the discoverer of electromagnetic induction, was convinced that there must also be a gravitational analog of this law, and he carried out drop-tower experiments in 1849 to look for the electric current induced in a coil by changes in gravitational flux through the coil. This work, now little remembered, was in some ways the first investigation of what we would now call a unified-field theory. We revisit Faraday's experiments in the light of current knowledge and ask what might be learned if they were to be performed today. We then review the gravitational analog for Faraday's law that arises within the vector (or gravito-electromagnetic) approximation to Einstein's theory of general relativity in the weak-field, low-velocity limit. This law relates spinning masses and induced ``mass currents'' rather than spinning charges and electric currents, but is otherwise remarkably similar to its electromagnetic counterpart. The predicted effects are completely unobservable in everyday settings like those envisioned by Faraday, but are thought to be relevant in astrophysical contexts like the accretion disks around collapsed stars, thus bearing out Faraday's remarkable intuition. Undergraduate student.

  7. Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

    Science.gov (United States)

    Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

    2007-12-01

    Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.

  8. READ - Remote Analog ASIC Design System

    Directory of Open Access Journals (Sweden)

    Michael E. Auer

    2006-11-01

    Full Text Available The scope of this work is to present a solution to implement a remote electronic laboratory for testing and designing analog ASICs (ispPAC10. The application allows users to create circuit schematics, upload the design to the device and perform measurements. The software used for designing circuits is the PAC-Designer and it runs on a Citrix server. The signals are generated and the responses are acquired by a data acquisition board controlled by LabView. The virtual instruments interact with some ActiveX controls specially designed to look like real oscilloscope and function generator devices and represent the user interface of the lab. These ActiveX give users the control over the LabView VIs and the access to its facilities in order to perform electronic exercises.

  9. Nilpotent Quantum Mechanics: Analogs and Applications

    Directory of Open Access Journals (Sweden)

    Peter Marcer

    2017-07-01

    Full Text Available The most significant characteristic of nilpotent quantum mechanics is that the quantum system (fermion state and its environment (vacuum are, in mathematical terms, mirror images of each other. So a change in one automatically leads to corresponding changes in the other. We have used this characteristic as a model for self-organization, which has applications well beyond quantum physics. The nilpotent structure has also been identified as being constructed from two commutative vector spaces. This zero square-root construction has a number of identifiable characteristics which we can expect to find in systems where self-organization is dominant, and a case presented after the publication of a paper by us on “The ‘Logic’ of Self-Organizing Systems” [1], in the organization of the neurons in the visual cortex. We expect to find many more complex systems where our general principles, based, by analogy, on nilpotent quantum mechanics, will apply.

  10. Atwood and Poggendorff: an insightful analogy

    DEFF Research Database (Denmark)

    Coelho, Ricardo; Borges, Paulo; Avelar Sotomaior Karam, Ricardo

    2016-01-01

    - librium provide us with the solution for a compound Atwood machine with the same bodies. This analogy is pedagogically useful because it illustrates a common strategy to transform a dynamic in a static situation improving stu- dents’ comprehension of Newton’s laws and equilibrium.......Atwood’s treatise, in which the Atwood machine appears, was published in 1784. About 70 years later, Poggendorff showed experimentally that the weight of an Atwood machine is reduced when it is brought to motion. In the present paper, a twofold connection between this experiment and the Atwood...... machine is established. Firstly, if the Poggendorff apparatus is taken as an ideal one, the equations of motion of the apparatus coincide with the equations of motion of the compound Atwood machine. Secondly, if the Poggendorff apparatus, which works as a lever, is rebalanced, the equations of this equi...

  11. Atwood and Poggendorff: an insightful analogy

    Science.gov (United States)

    Coelho, R. L.; Borges, P. F.; Karam, R.

    2016-11-01

    Atwood’s treatise, in which the Atwood machine appears, was published in 1784. About 70 years later, Poggendorff showed experimentally that the weight of an Atwood machine is reduced when it is brought to motion. In the present paper, a twofold connection between this experiment and the Atwood machine is established. Firstly, if the Poggendorff apparatus is taken as an ideal one, the equations of motion of the apparatus coincide with the equations of motion of the compound Atwood machine. Secondly, if the Poggendorff apparatus, which works as a lever, is rebalanced, the equations of this equilibrium provide us with the solution for a compound Atwood machine with the same bodies. This analogy is pedagogically useful because it illustrates a common strategy to transform a dynamic in a static situation improving students’ comprehension of Newton’s laws and equilibrium.

  12. Analog Electronic Filters Theory, Design and Synthesis

    CERN Document Server

    Dimopoulos, Hercules G

    2012-01-01

    Filters are essential subsystems in a huge variety of electronic systems. Filter applications are innumerable; they are used for noise reduction, demodulation, signal detection, multiplexing, sampling, sound and speech processing, transmission line equalization and image processing, to name just a few. In practice, no electronic system can exist without filters. They can be found in everything from power supplies to mobile phones and hard disk drives and from loudspeakers and MP3 players to home cinema systems and broadband Internet connections. This textbook introduces basic concepts and methods and the associated mathematical and computational tools employed in electronic filter theory, synthesis and design.  This book can be used as an integral part of undergraduate courses on analog electronic filters. Includes numerous, solved examples, applied examples and exercises for each chapter. Includes detailed coverage of active and passive filters in an independent but correlated manner. Emphasizes real filter...

  13. Large-scale digitizer system, analog converters

    International Nuclear Information System (INIS)

    Althaus, R.F.; Lee, K.L.; Kirsten, F.A.; Wagner, L.J.

    1976-10-01

    Analog to digital converter circuits that are based on the sharing of common resources, including those which are critical to the linearity and stability of the individual channels, are described. Simplicity of circuit composition is valued over other more costly approaches. These are intended to be applied in a large-scale processing and digitizing system for use with high-energy physics detectors such as drift-chambers or phototube-scintillator arrays. Signal distribution techniques are of paramount importance in maintaining adequate signal-to-noise ratio. Noise in both amplitude and time-jitter senses is held sufficiently low so that conversions with 10-bit charge resolution and 12-bit time resolution are achieved

  14. Test signal generation for analog circuits

    Directory of Open Access Journals (Sweden)

    B. Burdiek

    2003-01-01

    Full Text Available In this paper a new test signal generation approach for general analog circuits based on the variational calculus and modern control theory methods is presented. The computed transient test signals also called test stimuli are optimal with respect to the detection of a given fault set by means of a predefined merit functional representing a fault detection criterion. The test signal generation problem of finding optimal test stimuli detecting all faults form the fault set is formulated as an optimal control problem. The solution of the optimal control problem representing the test stimuli is computed using an optimization procedure. The optimization procedure is based on the necessary conditions for optimality like the maximum principle of Pontryagin and adjoint circuit equations.

  15. Principles of digital and analog communications

    CERN Document Server

    Gibson, Jerry D

    1993-01-01

    This textbook for the first course in communications covers analog and digital systems and emphasizes digital communications. It covers data transmission, signal space, optimal receivers, and pulse code modulation, and includes readable treatments of coded modulation and continuous phase modulation. Advanced mathematics is kept to a minimum-Fourier series, Fourier transforms, linear systems, random variables, and stochastic process are described thoroughly. It includes data compression of speech and images and a full chapter coverage of information theory, rate distortion theory and coded modulation. It relates digital communications theory to current practice and covers digital communications over band-width constrained channels, including pulse shaping and equilization. -- Dieser Text bezieht sich auf eine vergriffene oder nicht verfügbare Ausgabe dieses Titels.

  16. Integrated Circuits for Analog Signal Processing

    CERN Document Server

    2013-01-01

      This book presents theory, design methods and novel applications for integrated circuits for analog signal processing.  The discussion covers a wide variety of active devices, active elements and amplifiers, working in voltage mode, current mode and mixed mode.  This includes voltage operational amplifiers, current operational amplifiers, operational transconductance amplifiers, operational transresistance amplifiers, current conveyors, current differencing transconductance amplifiers, etc.  Design methods and challenges posed by nanometer technology are discussed and applications described, including signal amplification, filtering, data acquisition systems such as neural recording, sensor conditioning such as biomedical implants, actuator conditioning, noise generators, oscillators, mixers, etc.   Presents analysis and synthesis methods to generate all circuit topologies from which the designer can select the best one for the desired application; Includes design guidelines for active devices/elements...

  17. Four-gate transistor analog multiplier circuit

    Science.gov (United States)

    Mojarradi, Mohammad M. (Inventor); Blalock, Benjamin (Inventor); Cristoloveanu, Sorin (Inventor); Chen, Suheng (Inventor); Akarvardar, Kerem (Inventor)

    2011-01-01

    A differential output analog multiplier circuit utilizing four G.sup.4-FETs, each source connected to a current source. The four G.sup.4-FETs may be grouped into two pairs of two G.sup.4-FETs each, where one pair has its drains connected to a load, and the other par has its drains connected to another load. The differential output voltage is taken at the two loads. In one embodiment, for each G.sup.4-FET, the first and second junction gates are each connected together, where a first input voltage is applied to the front gates of each pair, and a second input voltage is applied to the first junction gates of each pair. Other embodiments are described and claimed.

  18. HIGH RESOLUTION ANALOG / DIGITAL POWER SUPPLY CONTROLLER

    International Nuclear Information System (INIS)

    Medvedko, Evgeny A

    2003-01-01

    Corrector magnets for the SPEAR-3 synchrotron radiation source require precision, high-speed control for use with beam-based orbit feedback. A new Controller Analog/Digital Interface card (CANDI) has been developed for these purposes. The CANDI has a 24-bit DAC for current control and three 24-bit Δ-Σ ADCs to monitor current and voltages. The ADCs can be read and the DAC updated at the 4 kHz rate needed for feedback control. A precision 16-bit DAC provides on-board calibration. Programmable multiplexers control internal signal routing for calibration, testing, and measurement. Feedback can be closed internally on current setpoint, externally on supply current, or beam position. Prototype and production tests are reported in this paper. Noise is better than 17 effective bits in a 10 mHz to 2 kHz bandwidth. Linearity and temperature stability are excellent

  19. Quantum walks based on an interferometric analogy

    International Nuclear Information System (INIS)

    Hillery, Mark; Bergou, Janos; Feldman, Edgar

    2003-01-01

    There are presently two models for quantum walks on graphs. The ''coined'' walk uses discrete-time steps, and contains, besides the particle making the walk, a second quantum system, the coin, that determines the direction in which the particle will move. The continuous walk operates with continuous time. Here a third model for quantum walks is proposed, which is based on an analogy to optical interferometers. It is a discrete-time model, and the unitary operator that advances the walk one step depends only on the local structure of the graph on which the walk is taking place. This type of walk also allows us to introduce elements, such as phase shifters, that have no counterpart in classical random walks. Several examples are discussed

  20. Automating analog design: Taming the shrew

    Science.gov (United States)

    Barlow, A.

    1990-01-01

    The pace of progress in the design of integrated circuits continues to amaze observers inside and outside of the industry. Three decades ago, a 50 transistor chip was a technological wonder. Fifteen year later, a 5000 transistor device would 'wow' the crowds. Today, 50,000 transistor chips will earn a 'not too bad' assessment, but it takes 500,000 to really leave an impression. In 1975 a typical ASIC device had 1000 transistors, took one year to first samples (and two years to production) and sold for about 5 cents per transistor. Today's 50,000 transistor gate array takes about 4 months from spec to silicon, works the first time, and sells for about 0.02 cents per transistor. Fifteen years ago, the single most laborious and error prone step in IC design was the physical layout. Today, most IC's never see the hand of a layout designer: and automatic place and route tool converts the engineer's computer captured schematic to a complete physical design using a gate array or a library of standard cells also created by software rather than by designers. CAD has also been a generous benefactor to the digital design process. The architect of today's digital systems creates the design using an RTL or other high level simulator. Then the designer pushes a button to invoke the logic synthesizer-optimizer tool. A fault analyzer checks the result for testability and suggests where scan based cells will improve test coverage. One obstinate holdout amidst this parade of progress is the automation of analog design and its reduction to semi-custom techniques. This paper investigates the application of CAD techniques to analog design.

  1. 23rd workshop on Advances in Analog Circuit Design

    CERN Document Server

    Baschirotto, Andrea; Makinwa, Kofi

    2015-01-01

    This book is based on the 18 tutorials presented during the 23rd workshop on Advances in Analog Circuit Design.  Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, serving as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development.    • Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing; • Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; • Presents material in a tutorial-based format.

  2. Analog circuit design a tutorial guide to applications and solutions

    CERN Document Server

    Williams, Jim

    2011-01-01

    * Covers the fundamentals of linear/analog circuit and system design to guide engineers with their design challenges. * Based on the Application Notes of Linear Technology, the foremost designer of high performance analog products, readers will gain practical insights into design techniques and practice. * Broad range of topics, including power management tutorials, switching regulator design, linear regulator design, data conversion, signal conditioning, and high frequency/RF design. * Contributors include the leading lights in analog design, Robert Dobkin, Jim Willia

  3. Synthesis and anti-inflammatory activity of phenylbutenoid dimer analogs

    International Nuclear Information System (INIS)

    Kim, Sung Soo; Fang, Yuan Ying; Park, Hae Eil

    2015-01-01

    Several phenylbutenoid dimer (PBD) analogs were synthesized and evaluated for their inhibitory activities against nitric oxide (NO) production and TNF-α release. The PBD analogs were synthesized via Diels–Alder and subsequent Schlosser reactions as key steps. Among the tested compounds, two analogs (8c, 8f) exhibited much stronger inhibitory activity against LPS-stimulated NO production and TNF-α release in RAW 264.7 cells than that of wogonin

  4. Fluorinated analogs of malachite green: synthesis and toxicity.

    Science.gov (United States)

    Kraus, George A; Jeon, Insik; Nilsen-Hamilton, Marit; Awad, Ahmed M; Banerjee, Jayeeta; Parvin, Bahram

    2008-04-27

    A series of fluorinated analogs of malachite green (MG) have been synthesized and their toxicity to Saccharomyces cerevisiae and a human ovarian epithelial cell line examined. The toxicity profiles were found to be different for these two species. Two analogs, one with 2,4-difluoro substitution and the other with 2-fluoro substitution seem to be the most promising analogs because they showed the lowest toxicity to the human cells.

  5. Analogies between classical statistical mechanics and quantum mechanics

    International Nuclear Information System (INIS)

    Uehara, M.

    1986-01-01

    Some analogies between nonequilibrium classical statistical mechanics and quantum mechanics, at the level of the Liouville equation and at the kinetic level, are commented on. A theorem, related to the Vlasov equation applied to a plasma, is proved. The theorem presents an analogy with Ehrenfest's theorem of quantum mechanics. An analogy between the plasma kinetic theory and Bohm's quantum theory with 'hidden variables' is also shown. (Author) [pt

  6. The analogic model ''RIC'' of thermal behaviour of mass concrete

    International Nuclear Information System (INIS)

    Gonzalez Redondo, M.; Gonzalez de Posada, F.; Plana Claver, J.

    1997-01-01

    In order to study the thermal field and calorific flows in heat sources (i.e. mass concrete during setting) we have conceived, built and experimented with an analogical electric model. This model, named RIC, consists of resistors (R) and capacitors (C) in which nodes an electric current (I) has been injected. Several analogical constants were used for the mathematical approximation. Thus, this paper describes the analogical RIC model, simulating heat generation, boundary and initial conditions and concreting. (Author) 4 refs

  7. Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

    Science.gov (United States)

    Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

    2016-03-15

    L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Observations of Crew Dynamics During Mars Analog Simulations

    Science.gov (United States)

    Cusack, Stacy L.

    2009-01-01

    Crewmembers on Mars missions will face new and unique challenges compared to those in close communications proximity to Mission Control centers. Crews on Mars will likely become more autonomous and responsible for their day-to-day planning. These explorers will need to make frequent real time decisions without the assistance of large ground support teams. Ground-centric control will no longer be an option due to the communications delays. As a result of the new decision making model, crew dynamics and leadership styles of future astronauts may become significantly different from the demands of today. As a volunteer for the Mars Society on two Mars analog missions, this presenter will discuss observations made during isolated, surface exploration simulations. The need for careful crew selections, not just based on individual skill sets, but on overall team interactions becomes apparent very quickly when the crew is planning their own days and deciding their own priorities. Even more important is the selection of a Mission Commander who can lead a team of highly skilled individuals with strong and varied opinions in a way that promotes crew consensus, maintains fairness, and prevents unnecessary crew fatigue.

  9. Children's analogical reasoning in a third-grade science discussion

    Science.gov (United States)

    May, David B.; Hammer, David; Roy, Patricia

    2006-03-01

    Expert scientific inquiry involves the generation and use of analogies. How and when students might develop this aspect of expertise has implications for understanding how and when instruction might facilitate that development. In a study of K-8 student inquiry in physical science, we are examining cases of spontaneous analogy generation. In the case we present here, a third-grader generates an analogy and modifies it to reconcile his classmates' counterarguments, allowing us to identify in these third-graders specific aspects of nascent expertise in analogy use. Promoting abilities and inclinations such as these children display requires that educators recognize and respond to them.

  10. 25th workshop on Advances in Analog Circuit Design

    CERN Document Server

    Harpe, Pieter; Makinwa, Kofi

    2017-01-01

    This book is based on the 18 tutorials presented during the 25th workshop on Advances in Analog Circuit Design. Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including low-power and energy-efficient analog electronics, with specific contributions focusing on the design of continuous-time sigma-delta modulators, automotive electronics, and power management. This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development.

  11. Reynolds analogy for the Rayleigh problem at various flow modes.

    Science.gov (United States)

    Abramov, A A; Butkovskii, A V

    2016-07-01

    The Reynolds analogy and the extended Reynolds analogy for the Rayleigh problem are considered. For a viscous incompressible fluid we derive the Reynolds analogy as a function of the Prandtl number and the Eckert number. We show that for any positive Eckert number, the Reynolds analogy as a function of the Prandtl number has a maximum. For a monatomic gas in the transitional flow regime, using the direct simulation Monte Carlo method, we investigate the extended Reynolds analogy, i.e., the relation between the shear stress and the energy flux transferred to the boundary surface, at different velocities and temperatures. We find that the extended Reynolds analogy for a rarefied monatomic gas flow with the temperature of the undisturbed gas equal to the surface temperature depends weakly on time and is close to 0.5. We show that at any fixed dimensionless time the extended Reynolds analogy depends on the plate velocity and temperature and undisturbed gas temperature mainly via the Eckert number. For Eckert numbers of the order of unity or less we generalize an extended Reynolds analogy. The generalized Reynolds analogy depends mainly only on dimensionless time for all considered Eckert numbers of the order of unity or less.

  12. Non-analog Monte Carlo estimators for radiation momentum deposition

    International Nuclear Information System (INIS)

    Hykes, Joshua M.; Densmore, Jeffery D.

    2009-01-01

    The standard method for calculating radiation momentum deposition in Monte Carlo simulations is the analog estimator, which tallies the change in a particle's momentum at each interaction with the matter. Unfortunately, the analog estimator can suffer from large amounts of statistical error. In this paper, we present three new non-analog techniques for estimating momentum deposition. Specifically, we use absorption, collision, and track-length estimators to evaluate a simple integral expression for momentum deposition that does not contain terms that can cause large amounts of statistical error in the analog scheme. We compare our new non-analog estimators to the analog estimator with a set of test problems that encompass a wide range of material properties and both isotropic and anisotropic scattering. In nearly all cases, the new non-analog estimators outperform the analog estimator. The track-length estimator consistently yields the highest performance gains, improving upon the analog-estimator figure of merit by factors of up to two orders of magnitude.

  13. Two analogy strategies: the cases of mind metaphors and introspection

    Science.gov (United States)

    Fischer, Eugen

    2018-04-01

    Analogical reasoning is often employed in problem-solving and metaphor interpretation. This paper submits that, as a default, analogical reasoning addressing these different tasks employs different mapping strategies. In problem-solving, it employs analogy-maximising strategies (like structure mapping, Gentner, D., & Markman, A. B. (1997). Structure mapping in analogy and similarity. American Psychologist, 52, 45-56); in metaphor interpretation, analogy-minimising strategies (like ATT-Meta, Barnden, J. A. (2015). Open-ended elaborations in creative metaphor. In T. R. Besold, M. Schorlemmer, & A. Smaill (Eds.), Computational creativity research: Towards creative machines (pp. 217-242). Berlin: Springer). The two strategies interact in analogical reasoning with conceptual metaphors. This interaction leads to predictable fallacies. The paper supports these hypotheses through case-studies on "mind" metaphors from ordinary discourse, and abstract problem-solving in the philosophy of mind, respectively. It shows that (1) default metaphorical interpretations for vision- and space-cognition metaphors can be derived with a variant of the analogy-minimising ATT-Meta approach, (2) philosophically influential introspective conceptions of the mind can be derived with conceptual metaphors only through an analogy-maximising strategy, and (3) the interaction of these strategies leads to hitherto unrecognised fallacies in analogical reasoning with metaphors. This yields a debunking explanation of introspective conceptions.

  14. Is the Link from Working Memory to Analogy Causal? No Analogy Improvements following Working Memory Training Gains

    Science.gov (United States)

    Richey, J. Elizabeth; Phillips, Jeffrey S.; Schunn, Christian D.; Schneider, Walter

    2014-01-01

    Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data [1], but less work has tested this relationship through experimental manipulation [2]. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working memory tasks. This study investigated whether working memory improvements, if replicated, would increase analogical reasoning ability. We assessed participants’ performance on verbal and visual analogy tasks after a complex working memory training program incorporating verbal and spatial tasks [3], [4]. Participants’ improvements on the working memory training tasks transferred to other short-term and working memory tasks, supporting the possibility of broad effects of working memory training. However, we found no effects on analogical reasoning. We propose several possible explanations for the lack of an impact of working memory improvements on analogical reasoning. PMID:25188356

  15. Is the link from working memory to analogy causal? No analogy improvements following working memory training gains.

    Directory of Open Access Journals (Sweden)

    J Elizabeth Richey

    Full Text Available Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data, but less work has tested this relationship through experimental manipulation. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working memory tasks. This study investigated whether working memory improvements, if replicated, would increase analogical reasoning ability. We assessed participants' performance on verbal and visual analogy tasks after a complex working memory training program incorporating verbal and spatial tasks. Participants' improvements on the working memory training tasks transferred to other short-term and working memory tasks, supporting the possibility of broad effects of working memory training. However, we found no effects on analogical reasoning. We propose several possible explanations for the lack of an impact of working memory improvements on analogical reasoning.

  16. Is the link from working memory to analogy causal? No analogy improvements following working memory training gains.

    Science.gov (United States)

    Richey, J Elizabeth; Phillips, Jeffrey S; Schunn, Christian D; Schneider, Walter

    2014-01-01

    Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data, but less work has tested this relationship through experimental manipulation. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working memory tasks. This study investigated whether working memory improvements, if replicated, would increase analogical reasoning ability. We assessed participants' performance on verbal and visual analogy tasks after a complex working memory training program incorporating verbal and spatial tasks. Participants' improvements on the working memory training tasks transferred to other short-term and working memory tasks, supporting the possibility of broad effects of working memory training. However, we found no effects on analogical reasoning. We propose several possible explanations for the lack of an impact of working memory improvements on analogical reasoning.

  17. Insulin analog with additional disulfide bond has increased stability and preserved activity

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Ribel, Ulla

    2013-01-01

    Insulin is a key hormone controlling glucose homeostasis. All known vertebrate insulin analogs have a classical structure with three 100% conserved disulfide bonds that are essential for structural stability and thus the function of insulin. It might be hypothesized that an additional disulfide...... bond may enhance insulin structural stability which would be highly desirable in a pharmaceutical use. To address this hypothesis, we designed insulin with an additional interchain disulfide bond in positions A10/B4 based on Cα-Cα distances, solvent exposure, and side-chain orientation in human insulin...... (HI) structure. This insulin analog had increased affinity for the insulin receptor and apparently augmented glucodynamic potency in a normal rat model compared with HI. Addition of the disulfide bond also resulted in a 34.6°C increase in melting temperature and prevented insulin fibril formation...

  18. Salmonella Prevention

    Science.gov (United States)

    ... and in vegetable and fruit harvesting and packing operations may help prevent salmonellosis caused by contaminated foods. Better education of food industry workers in basic food safety and restaurant inspection procedures may prevent cross-contamination and other ...

  19. Modeling visual problem solving as analogical reasoning.

    Science.gov (United States)

    Lovett, Andrew; Forbus, Kenneth

    2017-01-01

    We present a computational model of visual problem solving, designed to solve problems from the Raven's Progressive Matrices intelligence test. The model builds on the claim that analogical reasoning lies at the heart of visual problem solving, and intelligence more broadly. Images are compared via structure mapping, aligning the common relational structure in 2 images to identify commonalities and differences. These commonalities or differences can themselves be reified and used as the input for future comparisons. When images fail to align, the model dynamically rerepresents them to facilitate the comparison. In our analysis, we find that the model matches adult human performance on the Standard Progressive Matrices test, and that problems which are difficult for the model are also difficult for people. Furthermore, we show that model operations involving abstraction and rerepresentation are particularly difficult for people, suggesting that these operations may be critical for performing visual problem solving, and reasoning more generally, at the highest level. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. NMR analog of Bell's inequalities violation test

    International Nuclear Information System (INIS)

    Souza, A M; Oliveira, I S; Sarthour, R S; Magalhaes, A; Teles, J; Azevedo, E R de; Bonagamba, T J

    2008-01-01

    In this paper, we present an analog of Bell's inequalities violation test for N qubits to be performed in a nuclear magnetic resonance (NMR) quantum computer. This can be used to simulate or predict the results for different Bell's inequality tests, with distinct configurations and a larger number of qubits. To demonstrate our scheme, we implemented a simulation of the violation of the Clauser, Horne, Shimony and Holt (CHSH) inequality using a two-qubit NMR system and compared the results to those of a photon experiment. The experimental results are well described by the quantum mechanics theory and a local realistic hidden variables model (LRHVM) that was specifically developed for NMR. That is why we refer to this experiment as a simulation of Bell's inequality violation. Our result shows explicitly how the two theories can be compatible with each other due to the detection loophole. In the last part of this work, we discuss the possibility of testing some fundamental features of quantum mechanics using NMR with highly polarized spins, where a strong discrepancy between quantum mechanics and hidden variables models can be expected

  1. Natural Analog Studies at Pena Blanca, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    A.M. Simmons

    2005-07-11

    The significance of the Pena Blanca uranium deposits in the State of Chihuahua, Mexico as potential natural analogs for a nuclear waste repository in unsaturated welded tuff was first recognized in the 1980s. In the 1970s, the Pena Blanca region was a major target of uranium exploration and exploitation by the Mexican government. Since then the Nopal I uranium deposit has been studied extensively by researchers in the U.S., Mexico, and Europe. The Nopal I deposit represents an environment similar to that of the proposed high-level radioactive waste repository at Yucca Mountain in many ways. Both are located in semi-arid regions. Both are located in Tertiary rhyolitic tuffs overlying carbonate rocks that have been subjected to basin and range-style tectonic deformation. Both are located in a chemically oxidizing, unsaturated zone 200 m or more above the water table. The alteration of uraninite to secondary minerals at Nopal I may be similar to the alteration of uranium fuel rods in this type of setting. Investigations at Nopal I and in the surrounding Sierra Pena Blanca have included detailed outcrop mapping, hydrologic and isotopic studies of flow and transport, studies of mineral alteration, modeling, and performance assessment.

  2. Natural Analog Studies at Pena Blanca, Mexico

    International Nuclear Information System (INIS)

    A.M. Simmons

    2005-01-01

    The significance of the Pena Blanca uranium deposits in the State of Chihuahua, Mexico as potential natural analogs for a nuclear waste repository in unsaturated welded tuff was first recognized in the 1980s. In the 1970s, the Pena Blanca region was a major target of uranium exploration and exploitation by the Mexican government. Since then the Nopal I uranium deposit has been studied extensively by researchers in the U.S., Mexico, and Europe. The Nopal I deposit represents an environment similar to that of the proposed high-level radioactive waste repository at Yucca Mountain in many ways. Both are located in semi-arid regions. Both are located in Tertiary rhyolitic tuffs overlying carbonate rocks that have been subjected to basin and range-style tectonic deformation. Both are located in a chemically oxidizing, unsaturated zone 200 m or more above the water table. The alteration of uraninite to secondary minerals at Nopal I may be similar to the alteration of uranium fuel rods in this type of setting. Investigations at Nopal I and in the surrounding Sierra Pena Blanca have included detailed outcrop mapping, hydrologic and isotopic studies of flow and transport, studies of mineral alteration, modeling, and performance assessment

  3. Natural CO2 Analogs for Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Scott H. Stevens; B. Scott Tye

    2005-07-31

    The report summarizes research conducted at three naturally occurring geologic CO{sub 2} fields in the US. The fields are natural analogs useful for the design of engineered long-term storage of anthropogenic CO{sub 2} in geologic formations. Geologic, engineering, and operational databases were developed for McElmo Dome in Colorado; St. Johns Dome in Arizona and New Mexico; and Jackson Dome in Mississippi. The three study sites stored a total of 2.4 billion t (46 Tcf) of CO{sub 2} equivalent to 1.5 years of power plant emissions in the US and comparable in size with the largest proposed sequestration projects. The three CO{sub 2} fields offer a scientifically useful range of contrasting geologic settings (carbonate vs. sandstone reservoir; supercritical vs. free gas state; normally pressured vs. overpressured), as well as different stages of commercial development (mostly undeveloped to mature). The current study relied mainly on existing data provided by the CO{sub 2} field operator partners, augmented with new geochemical data. Additional study at these unique natural CO{sub 2} accumulations could further help guide the development of safe and cost-effective design and operation methods for engineered CO{sub 2} storage sites.

  4. Heavy ion irradiation of astrophysical ice analogs

    International Nuclear Information System (INIS)

    Duarte, Eduardo Seperuelo; Domaracka, Alicja; Boduch, Philippe; Rothard, Hermann; Balanzat, Emmanuel; Dartois, Emmanuel; Pilling, Sergio; Farenzena, Lucio; Frota da Silveira, Enio

    2009-01-01

    Icy grain mantles consist of small molecules containing hydrogen, carbon, oxygen and nitrogen atoms (e.g. H 2 O, GO, CO 2 , NH 3 ). Such ices, present in different astrophysical environments (giant planets satellites, comets, dense clouds, and protoplanetary disks), are subjected to irradiation of different energetic particles: UV radiation, ion bombardment (solar and stellar wind as well as galactic cosmic rays), and secondary electrons due to cosmic ray ionization of H 2 . The interaction of these particles with astrophysical ice analogs has been the object of research over the last decades. However, there is a lack of information on the effects induced by the heavy ion component of cosmic rays in the electronic energy loss regime. The aim of the present work is to simulate of the astrophysical environment where ice mantles are exposed to the heavy ion cosmic ray irradiation. Sample ice films at 13 K were irradiated by nickel ions with energies in the 1-10 MeV/u range and analyzed by means of FTIR spectrometry. Nickel ions were used because their energy deposition is similar to that deposited by iron ions, which are particularly abundant cosmic rays amongst the heaviest ones. In this work the effects caused by nickel ions on condensed gases are studied (destruction and production of molecules as well as associated cross sections, sputtering yields) and compared with respective values for light ions and UV photons. (authors)

  5. Photometric properties of Mars soils analogs

    Science.gov (United States)

    Pommerol, A.; Thomas, N.; Jost, B.; Beck, P.; Okubo, C.; McEwen, A.S.

    2013-01-01

    We have measured the bidirectional reflectance of analogs of dry, wet, and frozen Martian soils over a wide range of phase angles in the visible spectral range. All samples were produced from two geologic samples: the standard JSC Mars-1 soil simulant and Hawaiian basaltic sand. In a first step, experiments were conducted with the dry samples to investigate the effects of surface texture. Comparisons with results independently obtained by different teams with similar samples showed a satisfying reproducibility of the photometric measurements as well as a noticeable influence of surface textures resulting from different sample preparation procedures. In a second step, water was introduced to produce wet and frozen samples and their photometry investigated. Optical microscope images of the samples provided information about their microtexture. Liquid water, even in relatively low amount, resulted in the disappearance of the backscattering peak and the appearance of a forward-scattering peak whose intensity increases with the amount of water. Specular reflections only appeared when water was present in an amount large enough to allow water to form a film at the surface of the sample. Icy samples showed a wide variability of photometric properties depending on the physical properties of the water ice. We discuss the implications of these measurements in terms of the expected photometric behavior of the Martian surface, from equatorial to circum-polar regions. In particular, we propose some simple photometric criteria to improve the identification of wet and/or icy soils from multiple observations under different geometries.

  6. MEDIA PEMBELAJARAN ANALOG OSCILLATOR VIRTUAL LABOLATORY

    Directory of Open Access Journals (Sweden)

    Aji Widhi Wibowo

    2016-01-01

    Full Text Available The purpose of this research is to design and implement a Virtual Labolatory Materials Signal Processing Sub discussion 'Oscillator' Analog as Newspapers. Developers using the model Sutopo Ariesto Hadi (2003 as a method to produce the product. Consists of six stages: concept, design, material collecting, assembly, testing and distribution. This results in the development of Virtual media Labolatory with material 'Oscillator' with the results of 4 (four practicum digital oscillator, namely (1 Oscillator Wien Bridge, (2 Colpitts oscillator, (3 Oscillator Hartley and (4 astable multivibrator. Another result is that a user be jobsheet practicum. There are two types, namely: (1 jobsheet grip lecturers and (2 jobsheet for students. In Jobsheet there is a short book that contains the Manual on procedures for the use of virtual labolatory when practical and anatomical description of the product. Virtual Labolatory consists of the initial page (flash scren, the main page (home, pages and pages about the developer's lab referring to the story board. There are four (4 test are: (1 the truth polarity capacitor, (2 the connection (wiring, (3 mode frequency and time in the meter frequency

  7. The MARS2013 Mars analog mission.

    Science.gov (United States)

    Groemer, Gernot; Soucek, Alexander; Frischauf, Norbert; Stumptner, Willibald; Ragonig, Christoph; Sams, Sebastian; Bartenstein, Thomas; Häuplik-Meusburger, Sandra; Petrova, Polina; Evetts, Simon; Sivenesan, Chan; Bothe, Claudia; Boyd, Andrea; Dinkelaker, Aline; Dissertori, Markus; Fasching, David; Fischer, Monika; Föger, Daniel; Foresta, Luca; Fritsch, Lukas; Fuchs, Harald; Gautsch, Christoph; Gerard, Stephan; Goetzloff, Linda; Gołebiowska, Izabella; Gorur, Paavan; Groemer, Gerhard; Groll, Petra; Haider, Christian; Haider, Olivia; Hauth, Eva; Hauth, Stefan; Hettrich, Sebastian; Jais, Wolfgang; Jones, Natalie; Taj-Eddine, Kamal; Karl, Alexander; Kauerhoff, Tilo; Khan, Muhammad Shadab; Kjeldsen, Andreas; Klauck, Jan; Losiak, Anna; Luger, Markus; Luger, Thomas; Luger, Ulrich; McArthur, Jane; Moser, Linda; Neuner, Julia; Orgel, Csilla; Ori, Gian Gabriele; Paternesi, Roberta; Peschier, Jarno; Pfeil, Isabella; Prock, Silvia; Radinger, Josef; Ramirez, Barbara; Ramo, Wissam; Rampey, Mike; Sams, Arnold; Sams, Elisabeth; Sandu, Oana; Sans, Alejandra; Sansone, Petra; Scheer, Daniela; Schildhammer, Daniel; Scornet, Quentin; Sejkora, Nina; Stadler, Andrea; Stummer, Florian; Taraba, Michael; Tlustos, Reinhard; Toferer, Ernst; Turetschek, Thomas; Winter, Egon; Zanella-Kux, Katja

    2014-05-01

    We report on the MARS2013 mission, a 4-week Mars analog field test in the northern Sahara. Nineteen experiments were conducted by a field crew in Morocco under simulated martian surface exploration conditions, supervised by a Mission Support Center in Innsbruck, Austria. A Remote Science Support team analyzed field data in near real time, providing planning input for the management of a complex system of field assets; two advanced space suit simulators, four robotic vehicles, an emergency shelter, and a stationary sensor platform in a realistic work flow were coordinated by a Flight Control Team. A dedicated flight planning group, external control centers for rover tele-operations, and a biomedical monitoring team supported the field operations. A 10 min satellite communication delay and other limitations pertinent to human planetary surface activities were introduced. The fields of research for the experiments were geology, human factors, astrobiology, robotics, tele-science, exploration, and operations research. This paper provides an overview of the geological context and environmental conditions of the test site and the mission architecture, in particular the communication infrastructure emulating the signal travel time between Earth and Mars. We report on the operational work flows and the experiments conducted, including a deployable shelter prototype for multiple-day extravehicular activities and contingency situations.

  8. Amino acid analogs for tumor imaging

    International Nuclear Information System (INIS)

    Goodman, M.M.; Shoup, T.

    1998-01-01

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [ 18 F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an α-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of α-aminoisobutyric acid

  9. Semantics by analogy for illustrative volume visualization☆

    Science.gov (United States)

    Gerl, Moritz; Rautek, Peter; Isenberg, Tobias; Gröller, Eduard

    2012-01-01

    We present an interactive graphical approach for the explicit specification of semantics for volume visualization. This explicit and graphical specification of semantics for volumetric features allows us to visually assign meaning to both input and output parameters of the visualization mapping. This is in contrast to the implicit way of specifying semantics using transfer functions. In particular, we demonstrate how to realize a dynamic specification of semantics which allows to flexibly explore a wide range of mappings. Our approach is based on three concepts. First, we use semantic shader augmentation to automatically add rule-based rendering functionality to static visualization mappings in a shader program, while preserving the visual abstraction that the initial shader encodes. With this technique we extend recent developments that define a mapping between data attributes and visual attributes with rules, which are evaluated using fuzzy logic. Second, we let users define the semantics by analogy through brushing on renderings of the data attributes of interest. Third, the rules are specified graphically in an interface that provides visual clues for potential modifications. Together, the presented methods offer a high degree of freedom in the specification and exploration of rule-based mappings and avoid the limitations of a linguistic rule formulation. PMID:23576827

  10. Intracranial Fluid Redistribution During a Spaceflight Analog

    Science.gov (United States)

    Koppelmans, Vincent; Pasternak, Ofer; Bloomberg, Jacob J.; De Dios, Yiri E.; Wood, Scott J.; Riascos, Roy; Reuter-Lorenz, Patrica A.; Kofman, Igor S.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2017-01-01

    The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and limb unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6 deg HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n=12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging, derived from diffusion MRI, was used to quantify the distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreased in the post-central gyrus and precuneus. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

  11. Resonant Tunneling Analog-To-Digital Converter

    Science.gov (United States)

    Broekaert, T. P. E.; Seabaugh, A. C.; Hellums, J.; Taddiken, A.; Tang, H.; Teng, J.; vanderWagt, J. P. A.

    1995-01-01

    As sampling rates continue to increase, current analog-to-digital converter (ADC) device technologies will soon reach a practical resolution limit. This limit will most profoundly effect satellite and military systems used, for example, for electronic countermeasures, electronic and signal intelligence, and phased array radar. New device and circuit concepts will be essential for continued progress. We describe a novel, folded architecture ADC which could enable a technological discontinuity in ADC performance. The converter technology is based on the integration of multiple resonant tunneling diodes (RTD) and hetero-junction transistors on an indium phosphide substrate. The RTD consists of a layered semiconductor hetero-structure AlAs/InGaAs/AlAs(2/4/2 nm) clad on either side by heavily doped InGaAs contact layers. Compact quantizers based around the RTD offer a reduction in the number of components and a reduction in the input capacitance Because the component count and capacitance scale with the number of bits N, rather than by 2 (exp n) as in the flash ADC, speed can be significantly increased, A 4-bit 2-GSps quantizer circuit is under development to evaluate the performance potential. Circuit designs for ADC conversion with a resolution of 6-bits at 25GSps may be enabled by the resonant tunneling approach.

  12. Young Children's Analogical Problem Solving: Gaining Insights from Video Displays

    Science.gov (United States)

    Chen, Zhe; Siegler, Robert S.

    2013-01-01

    This study examined how toddlers gain insights from source video displays and use the insights to solve analogous problems. Two- to 2.5-year-olds viewed a source video illustrating a problem-solving strategy and then attempted to solve analogous problems. Older but not younger toddlers extracted the problem-solving strategy depicted in the video…

  13. 47 CFR 74.705 - TV broadcast analog station protection.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false TV broadcast analog station protection. 74.705... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.705 TV broadcast analog station protection. (a) The TV broadcast...

  14. The interplay of conflict and analogy in multidisciplinary teams.

    Science.gov (United States)

    Paletz, Susannah B F; Schunn, Christian D; Kim, Kevin H

    2013-01-01

    Creative teamwork in multidisciplinary teams is a topic of interest to cognitive psychologists on the one hand, and to both social and organizational psychologists on the other. However, the interconnections between cognitive and social layers have been rarely explored. Drawing on mental models and dissonance theories, the current study takes a central variable studied by cognitive psychologists-analogy-and examines its relationship to a central variable examined by social psychologists-conflict. In an observational, field study, over 11h of audio-video data from conversations of the Mars Exploration Rover scientists were coded for different types of analogy and micro-conflicts that reveal the character of underlying psychological mechanisms. Two different types of time-lagged logistic models applied to these data revealed asymmetric patterns of associations between analogy and conflict. Within-domain analogies, but not within-discipline or outside-discipline analogies, preceded science and work process conflicts, suggesting that in multidisciplinary teams, representational gaps in very close domains will be more likely to spark conflict. But analogies also occurred in reaction to conflict: Process and negative conflicts, but not task conflicts, preceded within-discipline analogies, but not to within-domain or outside-discipline analogies. This study demonstrates ways in which cognition can be bidirectionally tied to social processes and discourse. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Neuroscientific Insights into the Development of Analogical Reasoning

    Science.gov (United States)

    Whitaker, Kirstie J.; Vendetti, Michael S.; Wendelken, Carter; Bunge, Silvia A.

    2018-01-01

    Analogical reasoning, or the ability to find correspondences between entities based on shared relationships, supports knowledge acquisition. As such, the development of this ability during childhood is thought to promote learning. Here, we sought to better understand the mechanisms by which analogical reasoning about semantic relations improves…

  16. Analogical reasoning and aging: the processing speed and inhibition hypothesis.

    Science.gov (United States)

    Bugaiska, Aurélia; Thibaut, Jean-Pierre

    2015-01-01

    This study was designed to investigate the effect of aging on analogical reasoning by manipulating the strength of semantic association (LowAssoc or HighAssoc) and the number of distracters' semantic analogies of the A:B::C:D type and to determine which factors might be responsible for the age-related differences on analogical reasoning by testing two different theoretical frameworks: the inhibition hypothesis and the speed mediation hypothesis. We compared young adults and two groups of aging people (old and old-old) with word analogies of the A:B::C:D format. Results indicate an age-related effect on analogical reasoning, this effect being greatest with LowAssoc analogies. It was not associated with the presence of semantic distractors. Moreover, the results show that the variance part of the analogy task due to age was mainly explained by processing speed (rather than by inhibition) in the case of old participants and by both processing speed and inhibition in the old-old group. These results are discussed in relation to current models of aging and their interaction with the processes involved in analogical reasoning.

  17. Young Children's Analogical Reasoning: The Role of Immediate Feedback

    Science.gov (United States)

    Chiu, Shuhui; Alexander, Patricia A.

    2014-01-01

    In this study, a computerized measure, Interactive Analogical Measure (IAM), was developed and used to assess young children's ability to reason analogically. The IAM was equipped to provide corrective feedback and the effects of that feedback were tested for experimental and control groups. A group of 5-year-olds (N = 80) participated in the…

  18. Analogical Reasoning in Children with Specific Language Impairment

    Science.gov (United States)

    Leroy, Sandrine; Parisse, Christophe; Maillart, Christelle

    2012-01-01

    Usage-based theory considers analogical reasoning as a cognitive process required in language development. We hypothesized that difficulties with analogical reasoning could hinder the abstraction of construction schemas, thus slowing down morphosyntactic development for children with specific language impairment (SLI). We also hypothesized, in…

  19. Analysis of Attention and Analogical Reasoning in Children of Poverty

    Science.gov (United States)

    Weatherholt, Tara N.; Harris, Ruby C.; Burns, Barbara M.; Clement, Catherine

    2006-01-01

    This study examined the relationship between specific attentional aspects of processing capacity and analogical reasoning in children from low-income families. 77 children aged 48-77 (M = 56.7) months were assessed on an analogical reasoning task (matrices subtest of the Kaufman Brief Intelligence Test) and on computerized attention tasks designed…

  20. Analogical Reasoning in the Classroom: Insights from Cognitive Science

    Science.gov (United States)

    Vendetti, Michael S.; Matlen, Bryan J.; Richland, Lindsey E.; Bunge, Silvia A.

    2015-01-01

    Applying knowledge from one context to another is a notoriously difficult problem, both for children and adults, but lies at the heart of educational endeavors. Analogical reasoning is a cognitive underpinning of the ability to notice and draw similarities across contexts. Reasoning by analogy is especially challenging for students, who must…

  1. Some aspects of analogical reasoning in mathematical creativity

    OpenAIRE

    Pease, Alison; Guhe, Markus; Smaill, Alan

    2010-01-01

    Analogical reasoning can shed light on both of the two key processes of creativity– generation and evaluation. Hence, it is a powerful tool for creativity. We illustrate this with three historical case studies of creative mathematical conjectures which were either found or evaluated via analogies. We conclude by describing our ongoing efforts to build computational realisations of these ideas.

  2. SEAS: A simulated evolution approach for analog circuit synthesis

    NARCIS (Netherlands)

    Ning, Zhen-Qiu; Ning, Zhen-Qiu; Mouthaan, A.J.; Wallinga, Hans

    1991-01-01

    The authors present a simulated evolution approach for analog circuit synthesis based on an analogy with the natural selection process in biological environments and on the iterative improvements in solving engineering problems. A prototype framework based on this idea, called SEAS, has been

  3. New Synthetic Routes to Furocoumarins and Their Analogs: A Review

    Directory of Open Access Journals (Sweden)

    Valery F. Traven

    2004-02-01

    Full Text Available Many furocoumarins and their analogs possess a prominent photobiological activity. Some of them are successfully used as drugs in phototherapy of skin diseases. Fries rearrangement of acyloxyheteroarenes, condensation of acylhydroxyheteroarenes with α-carbonyl compounds under base catalysis and transformations of dihydrofurocoumarinones are new trends in synthesis of furocoumarins and their analogs.

  4. Young Children's Analogical Reasoning across Cultures: Similarities and Differences

    Science.gov (United States)

    Richland, Lindsey Engle; Chan, Tsz-Kit; Morrison, Robert G.; Au, Terry Kit-Fong

    2010-01-01

    A cross-cultural comparison between U.S. and Hong Kong preschoolers examined factors responsible for young children's analogical reasoning errors. On a scene analogy task, both groups had adequate prerequisite knowledge of the key relations, were the same age, and showed similar baseline performance, yet Chinese children outperformed U.S. children…

  5. Analogy as a means of theoretical adoption of pedagogical disciplines

    Directory of Open Access Journals (Sweden)

    Solovcova Irina A.

    2006-01-01

    Full Text Available The paper considers an application of analogy in the initial-teacher training as a tool of approaching pedagogical disciplines. The author proposes a classification of pedagogical analogies which provides choices of the most efficient model for a specific didactic situation. The article clarifies the model of the theoretical approach to pedagogical disciplines through active use of analogy, which contributes to a higher efficiency in a teacher and student interaction. The model consists of three stages: training (the stage of acquiring analogy model, the analytical stage (acquisition of pedagogical concepts, phenomena and systems through the application of analogy, and the stage of self-realization (the application of analogy method in students’ scientific-research activities considering external and internal didactic conditions which transform analogy from a teaching method into a tool for the acquisition of pedagogical disciplines. The author demonstrates that the application of analogy has a positive effect not only on the acquisition of pedagogical knowledge (especially methodic and the development of heuristic skills in students, but also on motivation for the study of pedagogical disciplines (cognitive aspect and professional pedagogical activity (formation of an individual-pedagogical attitude. .

  6. Verbal Analogical Reasoning in Children with Language-Learning Disabilities.

    Science.gov (United States)

    Masterson, Julie J.; And Others

    1993-01-01

    Children (ages 9-13) with language-learning disabilities were administered 5 types of verbal analogies: synonyms, antonyms, linear order, category membership, and functional relationship. Subjects performed worse than mental age-matched children on all types of analogies and performed worse than language age-matched children on all types except…

  7. The Development of Verbal Relations in Analogical Reasonings.

    Science.gov (United States)

    Sternberg, Robert J.; Nigro, Georgia

    A six-process theory of analogical reasoning was tested by administering verbal analogy items to students in grades 3 through college. The items were classified according to five verbal relations: synonyms, antonyms, functional, linear ordering, and class membership. A new method of componential analysis that does not require precueing was used to…

  8. Analog capacitance ROM with IGFET bucket-brigade shift register

    DEFF Research Database (Denmark)

    Bruun, Erik; Olesen, Ole

    1975-01-01

    A new type of monolithic analog read-out memory is described. It consists of a memory element and associated on-chip readout circuitry. The memory can be used for storing sample values of time-varying analog signals. The memory element is a matrix of MOS capacitors, preprogrammed in size...

  9. Molecular interactions between (--epigallocatechin gallate analogs and pancreatic lipase.

    Directory of Open Access Journals (Sweden)

    Shihui Wang

    Full Text Available The molecular interactions between pancreatic lipase (PL and four tea polyphenols (EGCG analogs, like (--epigallocatechin gallate (EGCG, (--gallocatechin gallate (GCG, (--epicatechin gallate (ECG, and (--epigallocatechin (EC, were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent.

  10. The making of analog module for gamma camera interface

    International Nuclear Information System (INIS)

    Yulinarsari, Leli; Rl, Tjutju; Susila, Atang; Sukandar

    2003-01-01

    The making of an analog module for gamma camera has been conducted. For computerization of planar gamma camera 37 PMT it has been developed interface hardware technology and software between the planar gamma camera with PC. With this interface gamma camera image information (Originally analog signal) was changed to digital single, therefore processes of data acquisition, image quality increase and data analysis as well as data base processing can be conducted with the help of computers, there are three gamma camera main signals, i.e. X, Y and Z . This analog module makes digitation of analog signal X and Y from the gamma camera that conveys position information coming from the gamma camera crystal. Analog conversion to digital was conducted by 2 converters ADC 12 bit with conversion time 800 ns each, conversion procedure for each coordinate X and Y was synchronized using suitable strobe signal Z for information acceptance

  11. Learning Plate Tectonics Using a Pre-Analogy Step

    Science.gov (United States)

    Glesener, G. B.; Sandoval, W. A.

    2011-12-01

    Previous research has shown that children tend to demonstrate lower performance on analogical reasoning tasks at a causal relations level compared to most adults (Gentner & Toupin, 1986). This tendency is an obstacle that geoscience educators must overcome because of the high frequency of analogies used in geoscience pedagogy. In particular, analog models are used to convey complex systems of non-everyday/non-observable events found in nature, such as plate tectonics. Key factors in successful analogical reasoning that have been suggested by researchers include knowledge of the causal relations in the base analog (Brown & Kane, 1988; Gentner, 1988; Gentner & Toupin, 1986), and development of learning strategies and metaconceptual competence(Brown & Kane, 1988). External factors, such as guiding cues and hints have been useful cognitive supports that help students reason through analogical problems (Gick & Holyoak, 1980). Cognitive supports have been seen by researchers to decrease processing demands on retrieval and working memory (Richland, Zur, & Holyoak, 2007). We observed third and fourth graders learning about plate tectonics beginning with a pre-analogy step-a cognitive support activity a student can do before working with an analogy to understand the target. This activity was designed to aid students in developing their understanding of object attributes and relations within an analog model so that more focus can be placed on mapping the corresponding higher-order relations between the base and target. Students learned targeted concepts of plate tectonics, as measured by pre to post gains on items adapted from the Geosciences Concept Inventory. Analyses of classroom interaction showed that students used the object attributes and higher-order relations highlighted in the pre-analogy activity as resources to reason about plate boundaries and plate movement during earthquakes.

  12. NASA HRP Immunology Discipline - Use of Terrestrial Analogs

    Science.gov (United States)

    Crucian, Brian

    2014-01-01

    Due to the cost and operational constraints, as well as technical implementation limitations, it is desirous to perform relevant space physiology investigations first in terrestrial 'space analogs'. This is particularly true for initial investigations, which may then provide appropriate focus for subsequent flight investigations, or for mechanistic investigations that simply cannot be performed during spaceflight. Appropriate analog choice is extremely important. There are a wide variety of terrestrial space analogs, each relevant to a particular physiological discipline (or disciplines) and each with a particular fidelity (or lack thereof) to spaceflight, and each with unique operational constraints. The HRP Immunology Discipline is tasked with managing the HRP Risk concerning clinical risk for Astronaut crews related to spaceflight-associated immune dysregulation. Such dysregulation has been documented to occur during spaceflight, and found to persist for the duration of a 6-month ISS mission. Studies continue to characterize the onorbit phenomenon, but it generally consists of diminished immunocyte function, dysregulated cytokine profiles, and persistent herpesvirus reactivation. Causes are thought to synergistically include microgravity, psychological or physiological stress, radiation, and/or circadian misalignment. An appropriate terrestrial analog for immune dysregulation would replicate as many of these influences as possible. Such analogs may include clinostat or bioreactor cell culture (microgravity), hindlimb suspension (stress, fluid shifts, hypokinesis), or human deployment to remote or extreme environments (isolation, stress, circadian). Also, the laboratory setting may be used as an analog, or to augment analogs, such as sleep deprivation/misalignment or human centrifugation to replicate gravitational stress. As an appropriate example of a NASA Disciplines use of Terrestrial space analogs, this talk will discuss spaceflight associated immune

  13. Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2.

    Science.gov (United States)

    Lister, M D; Hancock, A J

    1988-10-01

    Six isomers of dipalmitoylcyclopentanetriol phosphocholine (cyclopentano-lecithin) were tested as potential substrates for phospholipase A2. Since each of these analogs possesses a configuration that mimics a narrow range of conformations of a glycerophospholipid molecule, the analogs were used to assess the enzyme's conformational requirements. Studies showed that all of the analogs containing the phosphocholine at the C-1 (or C-3) position could be hydrolyzed, while only one of the three analogs that contains the polar head group at the C-2 position was susceptible. Kinetic studies, however, revealed that only the all-trans-(1,3/2-1P)-cyclopentano-lecithin gave initial rates of hydrolysis that were measurable by pH-stat. Acyl group specificity of the enzyme towards the all-trans isomer was determined with an analog was acyl groups were distinguishable. The synthesis of this mixed-acid-cyclopentano-PC is described herein. When this analog was enzymatically assayed, results unequivocally showed the enzyme to be specific for C-2 acyl hydrolysis. This specificity, and data showing that the all-trans analog is stereospecifically hydrolyzed, indicate that it is acted on in an analogous manner to dipalmitoylphosphatidylcholine. These studies indicate that although the configuration of the analog is not necessarily a prerequisite for hydrolysis, there does appear to be an optimal spatial orientation for enzymatic activity. The analogy between the susceptibilities of all-trans-(1,3/2-1P)-cyclopentano-lecithin and glycero-lecithin suggests that the conformation of the glycero-lecithin during phospholipase A2-mediated hydrolysis may be best simulated by the all-trans orientation of C-O bonds in the artificial substrate.

  14. Analogical Matrices in Young Children and Students with Intellectual Disability: Reasoning by Analogy or Reasoning by Association?

    Science.gov (United States)

    Denaes, Caroline

    2012-01-01

    Background: Analogical reasoning (AR) is renowned for being a complex activity. Young children tend to reason by association, rather by analogy, and people with intellectual disability present problems of memorization. Both these populations usually show low performances in AR. The present author investigated whether familiar material and external…

  15. Frozen orbit realization using LQR analogy

    Science.gov (United States)

    Nagarajan, N.; Rayan, H. Reno

    In the case of remote sensing orbits, the Frozen Orbit concept minimizes altitude variations over a given region using passive means. This is achieved by establishing the mean eccentricity vector at the orbital poles i.e., by fixing the mean argument of perigee at 90 deg with an appropriate eccentricity to balance the perturbations due to zonal harmonics J2 and J3 of the Earth's potential. Eccentricity vector is a vector whose magnitude is the eccentricity and direction is the argument of perigee. The launcher dispersions result in an eccentricity vector which is away from the frozen orbit values. The objective is then to formulate an orbit maneuver strategy to optimize the fuel required to achieve the frozen orbit in the presence of visibility and impulse constraints. It is shown that the motion of the eccentricity vector around the frozen perigee can be approximated as a circle. Combining the circular motion of the eccentricity vector around the frozen point and the maneuver equation, the following discrete equation is obtained. X(k+1) = AX(k) + Bu(k), where X is the state (i.e. eccentricity vector components), A the state transition matrix, u the scalar control force (i.e. dV in this case) and B the control matrix which transforms dV into eccentricity vector change. Based on this, it is shown that the problem of optimizing the fuel can be treated as a Linear Quadratic Regulator (LQR) problem in which the maneuver can be solved by using control system design tools like MATLAB by deriving an analogy LQR design.

  16. Remote Sensing and Quantization of Analog Sensors

    Science.gov (United States)

    Strauss, Karl F.

    2011-01-01

    This method enables sensing and quantization of analog strain gauges. By manufacturing a piezoelectric sensor stack in parallel (physical) with a piezoelectric actuator stack, the capacitance of the sensor stack varies in exact proportion to the exertion applied by the actuator stack. This, in turn, varies the output frequency of the local sensor oscillator. The output, F(sub out), is fed to a phase detector, which is driven by a stable reference, F(sub ref). The output of the phase detector is a square waveform, D(sub out), whose duty cycle, t(sub W), varies in exact proportion according to whether F(sub out) is higher or lower than F(sub ref). In this design, should F(sub out) be precisely equal to F(sub ref), then the waveform has an exact 50/50 duty cycle. The waveform, D(sub out), is of generally very low frequency suitable for safe transmission over long distances without corruption. The active portion of the waveform, t(sub W), gates a remotely located counter, which is driven by a stable oscillator (source) of such frequency as to give sufficient digitization of t(sub W) to the resolution required by the application. The advantage to this scheme is that it negates the most-common, present method of sending either very low level signals (viz. direct output from the sensors) across great distances (anything over one-half meter) or the need to transmit widely varying higher frequencies over significant distances thereby eliminating interference [both in terms of beat frequency generation and in-situ EMI (electromagnetic interference)] caused by ineffective shielding. It also results in a significant reduction in shielding mass.

  17. De Analogía a Digitalia

    Directory of Open Access Journals (Sweden)

    Dr. Xaime Fandiño Alonso

    2001-01-01

    ía, creatividad y contenidos.ABSTRACTThe transition towards binary-based technology has unleashed dramatic changes that in the last decade have affected the different stages involved in an audiovisual production: from scripting and creating a project, through the various technological procedures of the actual production process to its final distribution.The remains of the analogical era are finally sinking under a seemingly unstoppable wave of constantly evolving new digital environments.The new hardware devices used in this field are mainly prototypes. An ever evolving market, the constant arising of new competitors, newborn joint-ventures and a myriad of related facts force technology providers to keep a pace of constant updating in a mad race of fierce competition.The old system which implied one machine for each process is increasingly becoming a memory of the past. Today new devices are being launched at such a speed that the old technological approach which dealt with mechanical appliances like magnetoscopes, closed platforms and linear recording are already bound for extinction.It’s only natural then that the sacred cows of the industry fear for their position. Big and small are elusive concepts in this new audiovisual frenzy. Its almost daily routine to read about big audiovisual corporations announcing mergers, buy-outs or the acquisition of a stake in new and small creativity and development firms built from scratch by young entrepreneurs out of the blue.The digital era is drawing a heavy curtain that luckily leaves behind an analogical era in which the ownership of the costly means of production was the most important card in the game. The artist could only exercise its art if access to the professional team and technical equipment required for an audiovisual work was granted by its proprietors.Today, digital means new systems with far more productive environments which besides are user-friendly and cost only a small fraction of the old hardware.Right now, with

  18. GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, M.; Brock, B.; Egefjord, L.

    2017-01-01

    transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P cerebral cortex as a whole compared...... and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here...

  19. Eye Movements Reveal Optimal Strategies for Analogical Reasoning.

    Science.gov (United States)

    Vendetti, Michael S; Starr, Ariel; Johnson, Elizabeth L; Modavi, Kiana; Bunge, Silvia A

    2017-01-01

    Analogical reasoning refers to the process of drawing inferences on the basis of the relational similarity between two domains. Although this complex cognitive ability has been the focus of inquiry for many years, most models rely on measures that cannot capture individuals' thought processes moment by moment. In the present study, we used participants' eye movements to investigate reasoning strategies in real time while solving visual propositional analogy problems (A:B::C:D). We included both a semantic and a perceptual lure on every trial to determine how these types of distracting information influence reasoning strategies. Participants spent more time fixating the analogy terms and the target relative to the other response choices, and made more saccades between the A and B items than between any other items. Participants' eyes were initially drawn to perceptual lures when looking at response choices, but they nonetheless performed the task accurately. We used participants' gaze sequences to classify each trial as representing one of three classic analogy problem solving strategies and related strategy usage to analogical reasoning performance. A project-first strategy, in which participants first extrapolate the relation between the AB pair and then generalize that relation for the C item, was both the most commonly used strategy as well as the optimal strategy for solving visual analogy problems. These findings provide new insight into the role of strategic processing in analogical problem solving.

  20. Eye Movements Reveal Optimal Strategies for Analogical Reasoning

    Directory of Open Access Journals (Sweden)

    Michael S. Vendetti

    2017-06-01

    Full Text Available Analogical reasoning refers to the process of drawing inferences on the basis of the relational similarity between two domains. Although this complex cognitive ability has been the focus of inquiry for many years, most models rely on measures that cannot capture individuals' thought processes moment by moment. In the present study, we used participants' eye movements to investigate reasoning strategies in real time while solving visual propositional analogy problems (A:B::C:D. We included both a semantic and a perceptual lure on every trial to determine how these types of distracting information influence reasoning strategies. Participants spent more time fixating the analogy terms and the target relative to the other response choices, and made more saccades between the A and B items than between any other items. Participants' eyes were initially drawn to perceptual lures when looking at response choices, but they nonetheless performed the task accurately. We used participants' gaze sequences to classify each trial as representing one of three classic analogy problem solving strategies and related strategy usage to analogical reasoning performance. A project-first strategy, in which participants first extrapolate the relation between the AB pair and then generalize that relation for the C item, was both the most commonly used strategy as well as the optimal strategy for solving visual analogy problems. These findings provide new insight into the role of strategic processing in analogical problem solving.

  1. A hierarchical spatiotemporal analog forecasting model for count data.

    Science.gov (United States)

    McDermott, Patrick L; Wikle, Christopher K; Millspaugh, Joshua

    2018-01-01

    Analog forecasting is a mechanism-free nonlinear method that forecasts a system forward in time by examining how past states deemed similar to the current state moved forward. Previous applications of analog forecasting has been successful at producing robust forecasts for a variety of ecological and physical processes, but it has typically been presented in an empirical or heuristic procedure, rather than as a formal statistical model. The methodology presented here extends the model-based analog method of McDermott and Wikle (Environmetrics, 27, 2016, 70) by placing analog forecasting within a fully hierarchical statistical framework that can accommodate count observations. Using a Bayesian approach, the hierarchical analog model is able to quantify rigorously the uncertainty associated with forecasts. Forecasting waterfowl settling patterns in the northwestern United States and Canada is conducted by applying the hierarchical analog model to a breeding population survey dataset. Sea surface temperature (SST) in the Pacific Ocean is used to help identify potential analogs for the waterfowl settling patterns.

  2. Design rules for superconducting analog-digital transducers; Entwurfsregeln fuer Supraleitende Analog-Digital-Wandler

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Taghrid

    2015-05-29

    This Thesis is a contribution for dimensioning aspects of circuits designs in superconductor electronics. Mainly superconductor comparators inclusive Josephson comparators as well as QOJS-Comparators are investigated. Both types were investigated in terms of speed and sensitivity. The influence of the thermal noise on the decision process of the comparators represent in so called gray zone, which is analysed in this thesis. Thereby, different relations between design parameters were derived. A circuit model of the Josephson comparator was verified by experiments. Concepts of superconductor analog-to-digital converters, which are based on above called comparators, were investigated in detail. From the comparator design rules, new rules for AD-converters were derived. Because of the reduced switching energy, the signal to noise ratio (SNR) of the circuits is affected and therefore the reliability of the decision-process is affected. For special applications with very demanding requirements in terms of the speed and accuracy superconductor analog-to-digital converters offer an excellent performance. This thesis provides relations between different design paramenters and shows resulting trade-offs, This method is transparent and easy to transfer to other circuit topologies. As a main result, a highly predictive tool for dimensioning of superconducting ADC's is proved.

  3. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

    Science.gov (United States)

    2012-01-01

    Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted. PMID:22891821

  4. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

    Directory of Open Access Journals (Sweden)

    Ebdrup Bjørn H

    2012-08-01

    Full Text Available Abstract Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1. Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted.

  5. A Computer-Based Visual Analog Scale,

    Science.gov (United States)

    1992-06-01

    34 keys on the computer keyboard or other input device. The initial position of the arrow is always in the center of the scale to prevent biasing the...3 REFERENCES 1. Gift, A.G., "Visual Analogue Scales: Measurement of Subjective Phenomena." Nursing Research, Vol. 38, pp. 286-288, 1989. 2. Ltmdberg...3. Menkes, D.B., Howard, R.C., Spears, G.F., and Cairns, E.R., "Salivary THC Following Cannabis Smoking Correlates With Subjective Intoxication and

  6. Symmetry energy II: Isobaric analog states

    Science.gov (United States)

    Danielewicz, Pawel; Lee, Jenny

    2014-02-01

    Using excitation energies to isobaric analog states (IAS) and charge invariance, we extract nuclear symmetry coefficients, representing a mass formula, on a nucleus-by-nucleus basis. Consistently with charge invariance, the coefficients vary weakly across an isobaric chain. However, they change strongly with nuclear mass and range from aa˜10 MeV at mass A˜10 to aa˜22 MeV at A˜240. Variation with mass can be understood in terms of dependence of nuclear symmetry energy on density and the rise in importance of low densities within nuclear surface in smaller systems. At A≳30, the dependence of coefficients on mass can be well described in terms of a macroscopic volume-surface competition formula with aaV≃33.2 MeV and aaS≃10.7 MeV. Our further investigation shows, though, that the fitted surface symmetry coefficient likely significantly underestimates that for the limit of half-infinite matter. Following the considerations of a Hohenberg-Kohn functional for nuclear systems, we determine how to find in practice the symmetry coefficient using neutron and proton densities, even when those densities are simultaneously affected by significant symmetry-energy and Coulomb effects. These results facilitate extracting the symmetry coefficients from Skyrme-Hartree-Fock (SHF) calculations, that we carry out using a variety of Skyrme parametrizations in the literature. For the parametrizations, we catalog novel short-wavelength instabilities. In our further analysis, we retain only those parametrizations which yield systems that are adequately stable both in the long- and short-wavelength limits. In comparing the SHF and IAS results for the symmetry coefficients, we arrive at narrow (±2.4 MeV) constraints on the symmetry-energy values S(ρ) at 0.04≲ρ≲0.13 fm. Towards normal density the constraints significantly widen, but the normal value of energy aaV and the slope parameter L are found to be strongly correlated. To narrow the constraints, we reach for the

  7. Analogical Arguments in Ethics and Law: A Defence of Deductivism

    Directory of Open Access Journals (Sweden)

    Fábio Perin Shecaira

    2013-09-01

    Full Text Available The paper provides a qualified defence of Bruce Waller’s deductivist schema for a priori analogical arguments in ethics and law. One crucial qualification is that the schema represents analogical arguments as complexes composed of one deductive inference (hence “deductivism” but also of one non-deductive subargument. Another important qualification is that the schema is informed by normative assumptions regarding the conditions that an analogical argument must satisfy in order for it to count as an optimal instance of its kind. Waller’s schema (in qualified form is defended from criticisms formulated by Trudy Govier, Marcello Guarini and Lilian Bermejo-Luque.

  8. Reasoning by analogy as an aid to heuristic theorem proving.

    Science.gov (United States)

    Kling, R. E.

    1972-01-01

    When heuristic problem-solving programs are faced with large data bases that contain numbers of facts far in excess of those needed to solve any particular problem, their performance rapidly deteriorates. In this paper, the correspondence between a new unsolved problem and a previously solved analogous problem is computed and invoked to tailor large data bases to manageable sizes. This paper outlines the design of an algorithm for generating and exploiting analogies between theorems posed to a resolution-logic system. These algorithms are believed to be the first computationally feasible development of reasoning by analogy to be applied to heuristic theorem proving.

  9. Source selection for analogical reasoning an empirical approach

    Energy Technology Data Exchange (ETDEWEB)

    Stubblefield, W.A. [Sandia National Labs., Albuquerque, NM (United States); Luger, G.F. [Univ. of New Mexico, Albuquerque, NM (United States)

    1996-12-31

    The effectiveness of an analogical reasoner depends upon its ability to select a relevant analogical source. In many problem domains, however, too little is known about target problems to support effective source selection. This paper describes the design and evaluation of SCAVENGER, an analogical reasoner that applies two techniques to this problem: (1) An assumption-based approach to matching that allows properties of candidate sources to match unknown target properties in the absence of evidence to the contrary. (2) The use of empirical learning to improve memory organization based on problem solving experience.

  10. Josephson junction analog and quasiparticle-pair current

    DEFF Research Database (Denmark)

    Bak, Christen Kjeldahl; Pedersen, Niels Falsig

    1973-01-01

    A close analogy exists between a Josephson junction and a phase-locked loop. A new type of electrical analog based on this principle is presented. It is shown that the inclusion in this analog of a low-pass filter gives rise to a current of the same form as the Josephson quasiparticle-pair current....... A simple picture of the quasiparticle-pair current, which gives the right dependences, is obtained by assuming a junction cutoff frequency to be at the energy gap. ©1973 American Institute of Physics...

  11. Single-event transients (SET) in analog circuits

    International Nuclear Information System (INIS)

    Chen Panxun; Zhou Kaiming

    2006-01-01

    A new phenomenon of single- event upset is introduced. The transient signal is produced in the output of analog circuits after a heavy ion strikes. The transient upset can influence the circuit connected with the output of analog circuits. For example, the output of operational amplifier can be connected with the input of a digital counter, and the pulse of sufficiently high transient output induced by an ion can increase counts of the counter. On the other hand, the transient voltage signal at the output of analog circuits can change the stage of other circuits. (authors)

  12. UV IRRADIATION OF AROMATIC NITROGEN HETEROCYCLES IN INTERSTELLAR ICE ANALOGS

    Science.gov (United States)

    Elsila, J. E.; Bernstein, M. P.; Sanford, S. A.

    2005-01-01

    Here, we present information on the properties of the ANH quinoline frozen in interstellar water-ice analogs. Quinoline is a two-ring compound structurally analogous to the PAH naphthalene. In this work, binary mixtures of water and quinoline were frozen to create interstellar ice analogs, which were then subjected to ultraviolet photolysis. We will present the infrared spectra of the resulting ices at various temperatures, as well as chromatographic analysis of the residues remaining upon warm-up of these ices to room temperature.

  13. Fast parallel-series analog-to-digital converter

    International Nuclear Information System (INIS)

    Pogosov, A.Yu.

    1987-01-01

    Fast analog-to-digital converters are used in systems for detection of rapid processes, nuclear spectroscopy. A 12-digit analog-to-digital converter with conversion time of 160 ns and conversion frequency of 8.3 MHz is described; a segmented digital-to-analog converter with differential non-linearity of < 0.01% and a differential amplifier-limiter with setting time of 80 ns at the error of 0.2% are utilized in the converter; a control device is based on the chain of flip-flop circuit

  14. Kinematics and age of 15 stars-photometric solar analogs

    Science.gov (United States)

    Galeev, A. I.; Shimansky, V. V.

    2008-03-01

    The radial and space velocities are inferred for 15 stars that are photometric analogs of the Sun. The space velocity components (U, V, W) of most of these stars lie within the 10-60 km/s interval. The star HD 225239, which in our previous papers we classified as a subgiant, has a space velocity exceeding 100 km/s, and belongs to the thick disk. The inferred fundamental parameters of the atmospheres of solar analogs are combined with published evolutionary tracks to estimate the masses and ages of the stars studied. The kinematics of photometric analogs is compared to the data for a large group of solar-type stars.

  15. Global orbit feedback utilizing analog and digital technologies

    International Nuclear Information System (INIS)

    Singh, O.; Tang, Y.; Ramamoorthy, S.; Krinsky, S.; Yu, L.H.

    1997-01-01

    At the NSLS, an analog global orbit feedback system is used in regular operations, and a digital global orbit feedback system is available in machine physics studies on the X-Ray Ring. Here, the authors discuss the relative merits of utilizing analog and digital technology in orbit feedback. Results of experiments are reported characterizing the performance of the analog and digital systems when operated individually or together. They give their thoughts on plans for future development of the orbit feedback systems at the NSLS

  16. Prevention: Exercise

    Medline Plus

    Full Text Available ... Steroid Injections Lumbar Zygapophysical (Facet) Joint Injections PREVENTION Lifestyle Choices 10 Tips for a Healthy Back Smoking Weight Patient Safety Exercise Strengthening Strengthen ...

  17. Technology under Moon and Mars Analog Missions Activities (MMAMA)

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA Analog Missions research addresses the need for integrated interdisciplinary field experiments as an integral part of preparation for planned human and robotic...

  18. AnalogRF and mixed-signal circuit systematic design

    CERN Document Server

    Tlelo-Cuautle, Esteban; Castro-Lopez, Rafael

    2013-01-01

    Despite the fact that in the digital domain, designers can take full benefits of IPs and design automation tools to synthesize and design very complex systems, the analog designers’ task is still considered as a ‘handcraft’, cumbersome and very time consuming process. Thus, tremendous efforts are being deployed  to develop new design methodologies in the analog/RF and mixed-signal domains. This book collects 16 state-of-the-art contributions devoted to the topic of systematic design of analog, RF and mixed signal circuits. Divided in the two parts Methodologies and Techniques recent theories, synthesis techniques and design methodologies, as well as new sizing approaches in the field of robust analog and mixed signal design automation are presented for researchers and R/D engineers.  

  19. Leibniz y el concepto de analogía

    Directory of Open Access Journals (Sweden)

    Oscar Miguel Esquisabel

    2008-11-01

    Full Text Available In this paper an analysis of the leibnizian applications of conceptof analogy as well as the analogical reasoning is approached. Thus, the analysis tries to show that the leibnizian concept of analogy is based on the idea of structural similarity. As a consequence of such consideration,two basic ways in which Leibniz applies analogical reasoning are examined. The first way has a conjectural character and is rather heuristic, whereas the second constitutes, at least in intention, a kind of demonstrative analogicalreasoning, since it tries to prove its conclusions for a determined theoreticaldomain by applying a transfer principle, which is itself founded on the identity of structural properties.This procedure is exemplified by outlining the leibnizian view on contingent truths. In this way, the paper concludesby pointing out the theoretical relevance of the concept of similarity in theleibnizian thought.

  20. Reference-Free CMOS Pipeline Analog-to-Digital Converters

    CERN Document Server

    Figueiredo, Michael; Evans, Guiomar

    2013-01-01

    This book shows that digitally assisted analog-to-digital converters are not the only way to cope with poor analog performance caused by technology scaling. It describes various analog design techniques that enhance the area and power efficiency without employing any type of digital calibration circuitry. These techniques consist of self-biasing for PVT enhancement, inverter-based design for improved speed/power ratio, gain-of-two obtained by voltage sum instead of charge redistribution, and current-mode reference shifting instead of voltage reference shifting. Together, these techniques allow enhancing the area and power efficiency of the main building blocks of a multiplying digital-to-analog converter (MDAC) based stage, namely, the flash quantizer, the amplifier, and the switched capacitor network of the MDAC. Complementing the theoretical analyses of the various techniques, a power efficient operational transconductance amplifier is implemented and experimentally characterized. Furthermore, a medium-low ...

  1. FXR agonist activity of conformationally constrained analogs of GW 4064.

    Science.gov (United States)

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

    2009-08-15

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  2. Associative memory in an analog iterated-map neural network

    Science.gov (United States)

    Marcus, C. M.; Waugh, F. R.; Westervelt, R. M.

    1990-03-01

    The behavior of an analog neural network with parallel dynamics is studied analytically and numerically for two associative-memory learning algorithms, the Hebb rule and the pseudoinverse rule. Phase diagrams in the parameter space of analog gain β and storage ratio α are presented. For both learning rules, the networks have large ``recall'' phases in which retrieval states exist and convergence to a fixed point is guaranteed by a global stability criterion. We also demonstrate numerically that using a reduced analog gain increases the probability of recall starting from a random initial state. This phenomenon is comparable to thermal annealing used to escape local minima but has the advantage of being deterministic, and therefore easily implemented in electronic hardware. Similarities and differences between analog neural networks and networks with two-state neurons at finite temperature are also discussed.

  3. Figure/ground analogy for integrated sustainability & planning

    CSIR Research Space (South Africa)

    Beyers, C

    2006-12-01

    Full Text Available This article proposes a figure ground analogy as alternative way of conceptually integrating sustainability and planning. Within this framework planners are challenged to creatively consider planning practice and thought against a background...

  4. The use of analogy in pro-life argumentation

    Directory of Open Access Journals (Sweden)

    Simona Mazilu

    2012-11-01

    Full Text Available The paper is concerned with how analogy is strategically used in pro-life argumentation on abortion. Pragma-dialectics (van Eemeren and Grootendorst 1992 offers a set of critical questions by means of which I will evaluate the use of the argumentation based on a relation of analogy in terms of dialectical soundness. Examining various pro-life texts, I have noticed that the analogies employed remain unexplained. Therefore, despite the apparent similarities between abortion and the German holocaust or slavery, for instance, there are essential differences which are not mentioned. I claim that these analogies mainly have a rhetorical function, to operate what has been called by Micheli (2007: 960 “a transfer of emotional consensus”.

  5. Nitrate analogs as attractants for soybean cyst nematode.

    Science.gov (United States)

    Hosoi, Akito; Katsuyama, Tsutomu; Sasaki, Yasuyuki; Kondo, Tatsuhiko; Yajima, Shunsuke; Ito, Shinsaku

    2017-08-01

    Soybean cyst nematode (SCN) Heterodera glycines Ichinohe, a plant parasite, is one of the most serious pests of soybean. In this paper, we report that SCN is attracted to nitrate and its analogs. We performed attraction assays to screen for novel attractants for SCN and found that nitrates were attractants for SCN and SCN recognized nitrate gradients. However, attraction of SCN to nitrates was not observed on agar containing nitrate. To further elucidate the attraction mechanism in SCN, we performed attraction assays using nitrate analogs ([Formula: see text], [Formula: see text], [Formula: see text]). SCN was attracted to all nitrate analogs; however, attraction of SCN to nitrate analogs was not observed on agar containing nitrate. In contrast, SCN was attracted to azuki root, irrespective of presence or absence of nitrate in agar media. Our results suggest that the attraction mechanisms differ between plant-derived attractant and nitrate.

  6. Analogy and differences between aluminium and titanium electrowinning

    CSIR Research Space (South Africa)

    Van Vuuren, DS

    2006-09-01

    Full Text Available larger market. The authors have tested this route experimentally, but could not produce pure titanium. The failure of electrowinning pure, molten titanium has been interpreted in terms of the analogy and differences between aluminium and titanium...

  7. Analogy of ISSR and RAPD markers for comparative analysis of ...

    African Journals Online (AJOL)

    Analogy of ISSR and RAPD markers for comparative analysis of genetic diversity among different Jatropha curcas genotypes. S Gupta, M Srivastava, GP Mishra, PK Naik, RS Chauhan, SK Tiwari, M Kumar, R Singh ...

  8. Software approach to automatic patching of analog computer

    Science.gov (United States)

    1973-01-01

    The Automatic Patching Verification program (APV) is described which provides the hybrid computer programmer with a convenient method of performing a static check of the analog portion of his study. The static check insures that the program is patched as specified, and that the computing components being used are operating correctly. The APV language the programmer uses to specify his conditions and interconnections is similar to the FORTRAN language in syntax. The APV control program reads APV source program statements from an assigned input device. Each source program statement is processed immediately after it is read. A statement may select an analog console, set an analog mode, set a potentiometer or DAC, or read from the analog console and perform a test. Statements are read and processed sequentially. If an error condition is detected, an output occurs on an assigned output device. When an end statement is read, the test is terminated.

  9. 22nd Workshop on Advances in Analog Circuit Design

    CERN Document Server

    Makinwa, Kofi; Harpe, Pieter

    2014-01-01

    This book is based on the 18 tutorials presented during the 22nd workshop on Advances in Analog Circuit Design.  Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including frequency reference, power management for systems-on-chip, and smart wireless interfaces.  This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development.    ·         Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; ·         Presents material in a tutorial-based format; ·         Includes coverage of frequency reference, power management for systems-on-chip, and smart wireless interfaces.

  10. Analog and digital signal analysis from basics to applications

    CERN Document Server

    Cohen Tenoudji, Frédéric

    2016-01-01

    This book provides comprehensive, graduate-level treatment of analog and digital signal analysis suitable for course use and self-guided learning. This expert text guides the reader from the basics of signal theory through a range of application tools for use in acoustic analysis, geophysics, and data compression. Each concept is introduced and explained step by step, and the necessary mathematical formulae are integrated in an accessible and intuitive way. The first part of the book explores how analog systems and signals form the basics of signal analysis. This section covers Fourier series and integral transforms of analog signals, Laplace and Hilbert transforms, the main analog filter classes, and signal modulations. Part II covers digital signals, demonstrating their key advantages. It presents z and Fourier transforms, digital filtering, inverse filters, deconvolution, and parametric modeling for deterministic signals. Wavelet decomposition and reconstruction of non-stationary signals are also discussed...

  11. Analog reactor simulator RAS; Reaktorski analogni simulator RAS

    Energy Technology Data Exchange (ETDEWEB)

    Radanovic, Lj; Bingulac, S; Popovic, D [The Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

    1961-07-01

    Analog computer RAS was designed as a nuclear reactor simulator, but it can be simultaneously used for solving a number of other problems. This paper contains a brief description of the simulator parts and their principal characteristics.

  12. Project Birdseye Aerial Photograph Collection: Digital and Analog Materials

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This collection consists of both analog and digital aerial photographs from Arctic areas in and around Baffin Bay, the Labrador Sea, the Arctic Ocean, the Beaufort...

  13. Project for a codable central unit for analog data acquisition

    International Nuclear Information System (INIS)

    Bouras, F.; Da Costa Vieira, D.; Sohier, B.

    1974-07-01

    The instrumentation for a 256 channel codable central processor intended for an operation in connection with a computer is presented. The computer indicates the adresses of the channels to be measured, orders the conversion, and acquires the results of measurements. The acquisition and computer coupling unit is located in a standard rock CAMAC (6 U 19inch., 25 positions); an example of configuration is given. The measurement velocity depends on the converter speed and dead time of analog circuits; for a ADC 1103 converter the total dead time is 6.5s min. The analog circuits are intended for +-10V range, the accuracy is 1/2n (2n is the number of bits). The result is acquired in words of 12 bits maximum. The information transfer and analog commutation (through integrated analog gates) are discussed [fr

  14. Analog Fiber Optic Link with DC-100 MHz Bandwidth

    National Research Council Canada - National Science Library

    Sullivan, C. A; Girardi, P. G; Lohrmann, Dieter R

    2008-01-01

    An analog fiber optic link covering the frequency range from DC to 100 MHz was designed, constructed, and tested, in order to connect a 10 kA pulse current probe to oscilloscopes for oscillographing...

  15. Preventative Maintenance.

    Science.gov (United States)

    Migliorino, James

    Boards of education must be convinced that spending money up front for preventive maintenance will, in the long run, save districts' tax dollars. A good program of preventive maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…

  16. BERAS ANALOG SEBAGAI PANGAN FUNGSIONAL DENGAN INDEKS GLIKEMIK RENDAH

    Directory of Open Access Journals (Sweden)

    Santi Noviasari

    2016-04-01

    Full Text Available ABSTRACTThe objective of this research was to produce rice analogue as functional food with low glycemic index. The rice was made from white corn and sorghum with additional soybean flour. The physicochemical properties of rice analogue being analysed were resistant starch content, total phenolic content, dietary fiber, color (L*, +a, +b values and whiteness (oHue. Rice analogue was potentially used as functional food indicated by high level of resistant starch 2.59%-3.31%, total phenolic content 0.18-0.25 mg GAE/g sample and dietary fiber 5.35%-6.14%. Rice analogue from white corn with and without soybean flour was further tested for glycemic index. Rice analogue from white corn has 69 GI value, while rice analogue from white corn with 10% soybean flour addition has 50 GI value.Keywords: functional food, glycemic index, rice analogueABSTRAKTujuan penelitian ini adalah untuk mendapatkan beras analog yang berpotensi sebagai pangan fungsional dan bernilai indeks glikemik rendah. Beras analog dibuat dari bahan baku jagung putih dan sorgum dengan penambahan tepung kedelai. Sifat fisiko kimia beras analog yang dianalisis adalah pati resisten, total fenol, serat pangan, warna (nilai L*, +a, +b dan derajat putih (oHue. Beras analog berpotensi sebagai pangan fungsional, yang ditunjukkan dengan tingginya kadar pati resisten yaitu sebanyak 2,59%-3,31%, total fenol sekitar 0,18-0,25 mg GAE/g sampel dan serat pangan antara 5,35%-6,14%. Beras analog berbahan baku jagung putih dengan dan tanpa penambahan kedelai dipilih untuk uji indeks glikemik. Beras analog dari jagung putih memiliki nilai IG 69 sedangkan beras analog dari jagung putih dengan penambahan tepung kedelai 10% memiliki nilai IG 50.Kata kunci: beras analog, indeks glikemik, pangan fungsional

  17. Analog Filter Design Rules for Multilevel Polybinary Signaling Generation

    DEFF Research Database (Denmark)

    Vegas Olmos, Juan José; Cavallero, Francisco javier Vaquero; Tafur Monroy, Idelfonso

    2014-01-01

    Polybinary signaling has gained attention lately due to its generation simplicity and reduced spectral usage. This paper presents a study on the requirements for analog filters for the generation of multilevel polybinary signals with three to nine levels.......Polybinary signaling has gained attention lately due to its generation simplicity and reduced spectral usage. This paper presents a study on the requirements for analog filters for the generation of multilevel polybinary signals with three to nine levels....

  18. Fluorinated Analogs of Malachite Green: Synthesis and Toxicity

    Directory of Open Access Journals (Sweden)

    Bahram Parvin

    2008-04-01

    Full Text Available A series of fluorinated analogs of malachite green (MG have been synthesizedand their toxicity to Saccharomyces cerevisiae and a human ovarian epithelial cell lineexamined. The toxicity profiles were found to be different for these two species. Twoanalogs, one with 2,4-difluoro substitution and the other with 2-fluoro substitution seem tobe the most promising analogs because they showed the lowest toxicity to the human cells.

  19. Benefit of Analog, Programmable and Digital Hearing Aids

    Directory of Open Access Journals (Sweden)

    Jamileh Fatahi

    2006-12-01

    Full Text Available Background and Aims: As the hearing aid technology progressively promotes toward replacing analog hearing aids with digital and programmable ones, comparison of the patient satisfaction of those kinds of hearing aids by means of a valuable tool seems so necessary. So, the aim of this study was to compare self-reported benefit of analog, digitally controlled programmable and digital hearing aids for reducing disability caused by hearing impairment in mild to severe sensorineural hearing impaired persons. Materials and Methods: This cross-sectional study was performed on 90 persons with mild to severe sensorineural hearing loss dividing into three groups: 43 subjects were fitted with digital, 15 with programmable, 32 with analog hearing aids. After pure tone audiometry, Abbreviated profile of hearing aid benefit (APHAB was completed before and one month after using hearing aids to determine the benefit of them. Results: Global APHAB mean scores for digital, programmable and analog hearing aids were 49.05, 33.19 and 39.53, respectively. Ease of Communication subscale mean scores were 53.46 for digitals, 37.66 for programmables and 39.09 for analogs. Background noise subscale mean scores for digital programmable and analog hearing aids were 46.36, 25.53 and 35.31, respectively. Global and also both subscale mean scores showed significant difference between digital hearing aids and programmable and analog ones. There was no significant difference between reverberation subscale mean scores of three groups. Conclusion: It seems digital hearing aids may be more beneficial to reduce disability caused by hearing loss than analog and programmable hearing aids are.

  20. Performance report for Stanford/SLAC Microstore Analog Memory Unit

    International Nuclear Information System (INIS)

    Freytag, D.R.; Walker, J.T.

    1984-09-01

    Tests of a newly developed Analog Memory Unit (AMU) are described. The device contains 256 analog storage cells consisting of pass transistors, a storage capacitor and a differential read out buffer. By addressing the storage cells sequentially, the shape of the signal present at the input can be recorded in time. Fast response and good amplitude resolution were the design goals for the development. Measurements on individual devices will be presented and the status of hybridized subsystems containing eight AMUs discussed

  1. Synthetic analogs of anoplin show improved antimicrobial activities

    DEFF Research Database (Denmark)

    Munk, Jens; Uggerhøj, Lars Erik; Poulsen, Tanja Juul

    2013-01-01

    We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC...... that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few...

  2. A heat exchanger analogy of automotive paint ovens

    International Nuclear Information System (INIS)

    Rao, Preetham P.

    2013-01-01

    Computational prediction of vehicle temperatures in an automotive paint oven is essential to predict paint quality and manufacturability. The complex geometry of vehicles, varying scales in the flow, transient nature of the process, and the tightly coupled conjugate heat transfer render the numerical models computationally very expensive. Here, a novel, simplified model of the oven is developed using an analogy to a three-stream cross flow heat exchanger that transfers heat from air to a series of moving bodies and supporting carriers. The analogous heat exchanger equations are developed and solved numerically. Steady state Computational Fluid Dynamics (CFD) simulations are carried out to model the flow field and to extract the heat transfer coefficients around the body and carriers. The air temperature distribution from the CFD models is used as a boundary condition in the analogous model. Correction coefficients are used in the analogy to take care of various assumptions. These are determined from existing test data. The same corrections are used to predict air temperatures for a modified configuration of the oven and a different vehicle. The method can be used to conduct control volume analysis of ovens to determine energy efficiency, and to study new vehicle or oven designs. -- Highlights: • Analogy of an automotive paint oven as a three stream cross flow heat exchanger. • The three streams are vehicle bodies, carriers and hot air. • Convection coefficients and inlet air stream temperatures from steady CFD simulations. • Analogy useful for overall energy efficiency analysis of conveyor ovens in general

  3. Fast event recorder utilizing a CCD analog shift register

    International Nuclear Information System (INIS)

    Ducar, R.J.; McIntyre, P.M.

    1978-01-01

    A system of electronics has been developed to allow the capture and recording of relatively fast, low-amplitude analog events. The heart of the system is a dual 455-cell analog shift register charge-coupled device, Fairchild CCD321ADC-3. The CCD is operated in a dual clock mode. The input is sampled at a selectable clock rate of .25-20 MHz. The stored analog data is then clocked out at a slower rate, typically about .25 MHz. The time base expansion of the analog data allows for analog-to-digital conversion and memory storage using conventional medium-speed devices. The digital data is sequentially loaded into a static RAM and may then be block transferred to a computer. The analog electronics are housed in a single-width NIM module, and the RAM memory in a single-width CAMAC module. Each pair of modules provides six parallel channels. Cost is about $200.00 per channel. Applications are described for ionization imaging (TPC, IRC) and long-drift calorimetry in liquid argon

  4. Analogical Reasoning in the Engineering Design Process and Technology Education Applications

    OpenAIRE

    2008-01-01

    This synthesis paper discusses the research exploring analogical reasoning, the role of analogies in the engineering design process, and educational applications for analogical reasoning. Researchers have discovered that analogical reasoning is often a fundamental cognitive tool in design problem solving. Regarding the possible role of analogical reasoning in the context of technology education; analogies may be a useful tool to develop student’s design skills, teach abstract or complex conce...

  5. Preventive analgesia

    DEFF Research Database (Denmark)

    Dahl, Jørgen B; Kehlet, Henrik

    2011-01-01

    This paper will discuss the concepts of pre-emptive and preventive analgesia in acute and persistent postsurgical pain, based on the most recent experimental and clinical literature, with a special focus on injury-induced central sensitization and the development from acute to chronic pain. Recent...... of preventive analgesia for persistent postoperative pain are promising. However, clinicians must be aware of the demands for improved design of their clinical studies in order to get more conclusive answers regarding the different avenues for intervention. Summary: The concept of preventive analgesia is still...

  6. Is the Link from Working Memory to Analogy Causal? No Analogy Improvements following Working Memory Training Gains

    OpenAIRE

    Richey, J. Elizabeth; Phillips, Jeffrey S.; Schunn, Christian D.; Schneider, Walter

    2014-01-01

    Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data [1], but less work has tested this relationship through experimental manipulation [2]. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working mem...

  7. Prevention: Exercise

    Medline Plus

    Full Text Available ... Tips for a Healthy Back Smoking Weight Patient Safety Exercise Strengthening Strengthen Your Core! Stretching/Flexibility Aerobic ... Strength Training for the Elderly Other Back Pack Safety Pregnancy and Back Pain Preventing Osteoporosis Back Pain ...

  8. Preventing Rejection

    Science.gov (United States)

    ... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

  9. Prevent Cyberbullying

    Science.gov (United States)

    ... Tips for Teachers Report Cyberbullying Print Share Prevent Cyberbullying Be Aware of What Your Kids are Doing ... Signs a Child is Being Cyberbullied or is Cyberbullying Others Many of the warning signs that cyberbullying ...

  10. Preventing Suicide

    Science.gov (United States)

    ... protective factors listed below: Skills in problem solving, conflict resolution, and nonviolent ways of handling disputes Effective ... 2017 Page last updated: August 9, 2017 Content source: National Center for Injury Prevention and Control, Division ...

  11. Prevention: Exercise

    Medline Plus

    Full Text Available ... A SPECIALIST Prevention Strengthening Exercise Committee Exercise Committee Core Strengthening Many popular forms of exercise focus on ... acute pain, you should stop doing it. Transverse Core Strengthening This strengthens the muscles that cross from ...

  12. Prevention: Exercise

    Medline Plus

    Full Text Available ... Training for the Elderly Other Back Pack Safety Pregnancy and Back Pain Preventing Osteoporosis Back Pain Basics ... increases your back pain after five repetitions, or causes acute pain, you should stop doing it. Transverse ...

  13. Preventing accidents

    Science.gov (United States)

    2005-08-01

    As the most effective strategy for improving safety is to prevent accidents from occurring at all, the Volpe Center applies a broad range of research techniques and capabilities to determine causes and consequences of accidents and to identify, asses...

  14. Prevention: Exercise

    Medline Plus

    Full Text Available ... 10 Tips for a Healthy Back Smoking Weight Patient Safety Exercise Strengthening Strengthen Your Core! Stretching/Flexibility ... Pain Preventing Osteoporosis Back Pain Basics Book RESOURCES Patient Information Feature Articles Patient Q&A Success Stories ...

  15. Prevention: Exercise

    Medline Plus

    Full Text Available ... Preventing Osteoporosis Back Pain Basics Book RESOURCES Patient Information Feature Articles Patient Q&A Success Stories Definitions Anatomy of the Spine Definitions A-Z Spine Specialists Videos 9 ...

  16. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  17. Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

    Directory of Open Access Journals (Sweden)

    Yu D

    2016-01-01

    Full Text Available Debin Yu,1 Mingzhi Zhao,2 Liwei Dong,1 Lu Zhao,1 Mingwei Zou,3 Hetong Sun,4 Mengying Zhang,4 Hongyu Liu,4 Zhihua Zou1 1National Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 2State Key Laboratory of Proteomics, National Engineering Research Center for Protein Drugs, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3Department of Psychology, College of Liberal Arts and Social Sciences, University of Houston, Houston, TX, USA; 4Prosit Sole Biotechnology, Co., Ltd., Beijing, People’s Republic of China Abstract: Type III interferons (IFNs (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4 are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the

  18. Analogy in causal inference: rethinking Austin Bradford Hill's neglected consideration.

    Science.gov (United States)

    Weed, Douglas L

    2018-05-01

    The purpose of this article was to rethink and resurrect Austin Bradford Hill's "criterion" of analogy as an important consideration in causal inference. In epidemiology today, analogy is either completely ignored (e.g., in many textbooks), or equated with biologic plausibility or coherence, or aligned with the scientist's imagination. None of these examples, however, captures Hill's description of analogy. His words suggest that there may be something gained by contrasting two bodies of evidence, one from an established causal relationship, the other not. Coupled with developments in the methods of systematic assessments of evidence-including but not limited to meta-analysis-analogy can be restructured as a key component in causal inference. This new approach will require that a collection-a library-of known cases of causal inference (i.e., bodies of evidence involving established causal relationships) be developed. This library would likely include causal assessments by organizations such as the International Agency for Research on Cancer, the National Toxicology Program, and the United States Environmental Protection Agency. In addition, a process for describing key features of a causal relationship would need to be developed along with what will be considered paradigm cases of causation. Finally, it will be important to develop ways to objectively compare a "new" body of evidence with the relevant paradigm case of causation. Analogy, along with all other existing methods and causal considerations, may improve our ability to identify causal relationships. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Analogical processes in children's understanding of spatial representations.

    Science.gov (United States)

    Yuan, Lei; Uttal, David; Gentner, Dedre

    2017-06-01

    We propose that map reading can be construed as a form of analogical mapping. We tested 2 predictions that follow from this claim: First, young children's patterns of performance in map reading tasks should parallel those found in analogical mapping tasks; and, second, children will benefit from guided alignment instructions that help them see the relational correspondences between the map and the space. In 4 experiments, 3-year-olds completed a map reading task in which they were asked to find hidden objects in a miniature room, using a corresponding map. We manipulated the availability of guided alignment (showing children the analogical mapping between maps and spaces; Experiments 1, 2, and 3a), the format of guided alignment (gesture or relational language; Experiment 2), and the iconicity of maps (Experiments 3a and 3b). We found that (a) young children's difficulties in map reading follow from known patterns of analogical development-for example, focusing on object similarity over relational similarity; and (b) guided alignment based on analogical reasoning led to substantially better performance. Results also indicated that children's map reading performance was affected by the format of guided alignment, the iconicity of the maps, and the order of tasks. The results bear on the developmental mechanisms underlying young children's learning of spatial representations and also suggest ways to support this learning. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Specialization of the Rostral Prefrontal Cortex for Distinct Analogy Processes

    Science.gov (United States)

    Gilbert, Sam J.; Benoit, Roland G.; Burgess, Paul W.

    2010-01-01

    Analogical reasoning is central to learning and abstract thinking. It involves using a more familiar situation (source) to make inferences about a less familiar situation (target). According to the predominant cognitive models, analogical reasoning includes 1) generation of structured mental representations and 2) mapping based on structural similarities between them. This study used functional magnetic resonance imaging to specify the role of rostral prefrontal cortex (PFC) in these distinct processes. An experimental paradigm was designed that enabled differentiation between these processes, by temporal separation of the presentation of the source and the target. Within rostral PFC, a lateral subregion was activated by analogy task both during study of the source (before the source could be compared with a target) and when the target appeared. This may suggest that this subregion supports fundamental analogy processes such as generating structured representations of stimuli but is not specific to one particular processing stage. By contrast, a dorsomedial subregion of rostral PFC showed an interaction between task (analogy vs. control) and period (more activated when the target appeared). We propose that this region is involved in comparison or mapping processes. These results add to the growing evidence for functional differentiation between rostral PFC subregions. PMID:20156841

  1. IADE: a system for intelligent automatic design of bioisosteric analogs

    Science.gov (United States)

    Ertl, Peter; Lewis, Richard

    2012-11-01

    IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor—an analog that has won a recent "Design a Molecule" competition.

  2. Transistor analogs of emergent iono-neuronal dynamics.

    Science.gov (United States)

    Rachmuth, Guy; Poon, Chi-Sang

    2008-06-01

    Neuromorphic analog metal-oxide-silicon (MOS) transistor circuits promise compact, low-power, and high-speed emulations of iono-neuronal dynamics orders-of-magnitude faster than digital simulation. However, their inherently limited input voltage dynamic range vs power consumption and silicon die area tradeoffs makes them highly sensitive to transistor mismatch due to fabrication inaccuracy, device noise, and other nonidealities. This limitation precludes robust analog very-large-scale-integration (aVLSI) circuits implementation of emergent iono-neuronal dynamics computations beyond simple spiking with limited ion channel dynamics. Here we present versatile neuromorphic analog building-block circuits that afford near-maximum voltage dynamic range operating within the low-power MOS transistor weak-inversion regime which is ideal for aVLSI implementation or implantable biomimetic device applications. The fabricated microchip allowed robust realization of dynamic iono-neuronal computations such as coincidence detection of presynaptic spikes or pre- and postsynaptic activities. As a critical performance benchmark, the high-speed and highly interactive iono-neuronal simulation capability on-chip enabled our prompt discovery of a minimal model of chaotic pacemaker bursting, an emergent iono-neuronal behavior of fundamental biological significance which has hitherto defied experimental testing or computational exploration via conventional digital or analog simulations. These compact and power-efficient transistor analogs of emergent iono-neuronal dynamics open new avenues for next-generation neuromorphic, neuroprosthetic, and brain-machine interface applications.

  3. New insights into the synergism of nucleoside analogs with radiotherapy

    International Nuclear Information System (INIS)

    Lee, Michael W; Parker, William B; Xu, Bo

    2013-01-01

    Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells

  4. Membrane Affinity of Platensimycin and Its Dialkylamine Analogs

    Directory of Open Access Journals (Sweden)

    Ian Rowe

    2015-08-01

    Full Text Available Membrane permeability is a desired property in drug design, but there have been difficulties in quantifying the direct drug partitioning into native membranes. Platensimycin (PL is a new promising antibiotic whose biosynthetic production is costly. Six dialkylamine analogs of PL were synthesized with identical pharmacophores but different side chains; five of them were found inactive. To address the possibility that their activity is limited by the permeation step, we calculated polarity, measured surface activity and the ability to insert into the phospholipid monolayers. The partitioning of PL and the analogs into the cytoplasmic membrane of E. coli was assessed by activation curve shifts of a re-engineered mechanosensitive channel, MscS, in patch-clamp experiments. Despite predicted differences in polarity, the affinities to lipid monolayers and native membranes were comparable for most of the analogs. For PL and the di-myrtenyl analog QD-11, both carrying bulky sidechains, the affinity for the native membrane was lower than for monolayers (half-membranes, signifying that intercalation must overcome the lateral pressure of the bilayer. We conclude that the biological activity among the studied PL analogs is unlikely to be limited by their membrane permeability. We also discuss the capacity of endogenous tension-activated channels to detect asymmetric partitioning of exogenous substances into the native bacterial membrane and the different contributions to the thermodynamic force which drives permeation.

  5. Overview of the Human Exploration Research Analog (HERA)

    Science.gov (United States)

    Neigut, J.

    2015-01-01

    In 2013, the Human Research Program at NASA began developing a new confinement analog specifically for conducting research to investigate the effects of confinement on the human system. The HERA (Human Exploration Research Analog) habitat has been used for both 7 and 14 day missions to date to examine and mitigate exploration risks to enable safe, reliable and productive human space exploration. This presentation will describe how the Flight Analogs Project developed the HERA facility and the infrastructure to suit investigator requirements for confinement research and in the process developed a new approach to analog utilization and a new state of the art analog facility. Details regarding HERA operations will be discussed including specifics on the mission simulation utilized for the current 14-day campaign, the specifics of the facility (total volume, overall size, hardware), and the capabilities available to researchers. The overall operational philosophy, mission fidelity including timeline, schedule pressures and cadence, and development and implementation of mission stressors will be presented. Research conducted to date in the HERA has addressed risks associated with behavioral health and performance, human physiology, as well as human factors. This presentation will conclude with a discussion of future research plans for the HERA, including infrastructure improvements and additional research capabilities planned for the upcoming 30-day missions in 2016.

  6. Docking Simulation of the Binding Interactions of Saxitoxin Analogs Produced by the Marine Dinoflagellate Gymnodinium catenatum to the Voltage-Gated Sodium Channel Nav1.4

    Directory of Open Access Journals (Sweden)

    Lorena M. Durán-Riveroll

    2016-05-01

    Full Text Available Saxitoxin (STX and its analogs are paralytic alkaloid neurotoxins that block the voltage-gated sodium channel pore (Nav, impeding passage of Na+ ions into the intracellular space, and thereby preventing the action potential in the peripheral nervous system and skeletal muscle. The marine dinoflagellate Gymnodinium catenatum produces an array of such toxins, including the recently discovered benzoyl analogs, for which the mammalian toxicities are essentially unknown. We subjected STX and its analogs to a theoretical docking simulation based upon two alternative tri-dimensional models of the Nav1.4 to find a relationship between the binding properties and the known mammalian toxicity of selected STX analogs. We inferred hypothetical toxicities for the benzoyl analogs from the modeled values. We demonstrate that these toxins exhibit different binding modes with similar free binding energies and that these alternative binding modes are equally probable. We propose that the principal binding that governs ligand recognition is mediated by electrostatic interactions. Our simulation constitutes the first in silico modeling study on benzoyl-type paralytic toxins and provides an approach towards a better understanding of the mode of action of STX and its analogs.

  7. Docking Simulation of the Binding Interactions of Saxitoxin Analogs Produced by the Marine Dinoflagellate Gymnodinium catenatum to the Voltage-Gated Sodium Channel Nav1.4.

    Science.gov (United States)

    Durán-Riveroll, Lorena M; Cembella, Allan D; Band-Schmidt, Christine J; Bustillos-Guzmán, José J; Correa-Basurto, José

    2016-05-06

    Saxitoxin (STX) and its analogs are paralytic alkaloid neurotoxins that block the voltage-gated sodium channel pore (Nav), impeding passage of Na⁺ ions into the intracellular space, and thereby preventing the action potential in the peripheral nervous system and skeletal muscle. The marine dinoflagellate Gymnodinium catenatum produces an array of such toxins, including the recently discovered benzoyl analogs, for which the mammalian toxicities are essentially unknown. We subjected STX and its analogs to a theoretical docking simulation based upon two alternative tri-dimensional models of the Nav1.4 to find a relationship between the binding properties and the known mammalian toxicity of selected STX analogs. We inferred hypothetical toxicities for the benzoyl analogs from the modeled values. We demonstrate that these toxins exhibit different binding modes with similar free binding energies and that these alternative binding modes are equally probable. We propose that the principal binding that governs ligand recognition is mediated by electrostatic interactions. Our simulation constitutes the first in silico modeling study on benzoyl-type paralytic toxins and provides an approach towards a better understanding of the mode of action of STX and its analogs.

  8. Cancer prevention.

    Science.gov (United States)

    Tubiana, M

    1999-01-01

    Over 70% of human cancers are associated with lifestyle and about half of cancer deaths could be prevented by relatively simple individual actions: no smoking, moderate consumption of alcohol, increased consumption of fruit and vegetables, avoidance of sunbathing, obesity and a too high consumption of saturated lipids. Most of these efforts would also markedly decrease the incidence of cardiovascular and respiratory diseases. However, the concept of prevention is currently neither well accepted nor understood by the medical community and the general public. It is often felt that it restricts freedom, imposes a choice between pleasure and duty, and that passing judgement on lifestyle is a form of intolerance. The case of tobacco illustrates the difficulties encountered by prevention, notably among adolescents. The fight against smoking requires information, a societal approach (ban on advertising, increase in price), and a reduction of the example given by adult smoking (parents, peers, teachers, physicians, TV presenters, movie stars, have a great influence on adolescents), while tobacco cessation programs must be promoted. The various approaches should be integrated into a global program of health prevention, including health education at school from 5 to 12 years of age. The efficacy of each of the global program's components should be evaluated. Misconceptions such as overestimation of the impact of pollution on health should also be corrected. Health is created and experienced by people within the setting of their daily lives, in particular during childhood. Prevention is the responsibility of individual members of the community but also of the community as a whole.

  9. Analog implementation of an integral resonant control scheme

    International Nuclear Information System (INIS)

    Pereira, E; Moheimani, S O R; Aphale, S S

    2008-01-01

    Integral resonant control (IRC) has been introduced as a high performance controller design methodology for flexible structures with collocated actuator–sensor pairs. IRC has a simple structure and is capable of achieving significant damping, over several modes, while guaranteeing closed-loop stability of the system in the presence of unmodeled out-of-bandwidth dynamics. IRC can be an ideal controller for various industrial damping applications, if packaged in a simple easy-to-implement electronic module. This work proposes an analog implementation of the IRC scheme using a single Op-Amp circuit. The objective is to show that with simple analog realization of the modified IRC scheme, it is possible to damp a large number of vibration modes. A brief discussion about the modeling, circuit considerations, implementation and experimental results is presented in order to validate the usefulness and practicality of the proposed analog IRC implementation. (technical note)

  10. Analog to digital workflow improvement: a quantitative study.

    Science.gov (United States)

    Wideman, Catherine; Gallet, Jacqueline

    2006-01-01

    This study tracked a radiology department's conversion from utilization of a Kodak Amber analog system to a Kodak DirectView DR 5100 digital system. Through the use of ProModel Optimization Suite, a workflow simulation software package, significant quantitative information was derived from workflow process data measured before and after the change to a digital system. Once the digital room was fully operational and the radiology staff comfortable with the new system, average patient examination time was reduced from 9.24 to 5.28 min, indicating that a higher patient throughput could be achieved. Compared to the analog system, chest examination time for modality specific activities was reduced by 43%. The percentage of repeat examinations experienced with the digital system also decreased to 8% vs. the level of 9.5% experienced with the analog system. The study indicated that it is possible to quantitatively study clinical workflow and productivity by using commercially available software.

  11. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    Directory of Open Access Journals (Sweden)

    Nádia Rezende Barbosa Raposo

    2012-10-01

    Full Text Available Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL, two times more active than resveratrol (IC50 = 57.05 µg/mL, followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

  12. Analogical thinking in ecology: looking beyond disciplinary boundaries.

    Science.gov (United States)

    Colyvan, Mark; Ginzburg, Lev R

    2010-06-01

    We consider several ways in which a good understanding of modern techniques and principles in physics can elucidate ecology, and we focus on analogical reasoning between these two branches of science. Analogical reasoning requires an understanding of both sciences and an appreciation of the similarities and points of contact between the two. In the current ecological literature on the relationship between ecology and physics, there has been some misunderstanding about the nature of modern physics and its methods. Physics is seen as being much cleaner and tidier than ecology. When compared to this idealized, fictional version of physics, ecology looks very different, and the prospect of ecology and physics learning from one another is questionable. We argue that physics, once properly understood, is more like ecology than ecologists have thus far appreciated. Physicists and ecologists can and do learn from each other, and, in this paper, we outline how analogical reasoning can facilitate such exchanges.

  13. Spatial analogies pervade complex relational reasoning: Evidence from spontaneous gestures.

    Science.gov (United States)

    Cooperrider, Kensy; Gentner, Dedre; Goldin-Meadow, Susan

    2016-01-01

    How do people think about complex phenomena like the behavior of ecosystems? Here we hypothesize that people reason about such relational systems in part by creating spatial analogies, and we explore this possibility by examining spontaneous gestures. In two studies, participants read a written lesson describing positive and negative feedback systems and then explained the differences between them. Though the lesson was highly abstract and people were not instructed to gesture, people produced spatial gestures in abundance during their explanations. These gestures used space to represent simple abstract relations (e.g., increase ) and sometimes more complex relational structures (e.g., negative feedback ). Moreover, over the course of their explanations, participants' gestures often cohered into larger analogical models of relational structure. Importantly, the spatial ideas evident in the hands were largely unaccompanied by spatial words. Gesture thus suggests that spatial analogies are pervasive in complex relational reasoning, even when language does not.

  14. Indicators of Discontinuous Change in the Development of Analogical Reasoning

    Science.gov (United States)

    Hosenfeld; van der Maas HLJ; van den Boom DC

    1997-03-01

    In a longitudinal study, five indicators of a transition in the development of analogical reasoning were examined in young elementary school children, (a) bimodality and (b) inaccessibility in the frequency distributions of test performance, and in the responses of the transitional subjects, respectively, (c) sudden jumps, (d) anomalous variance, and (e) critical slowing down. An open-ended geometric-analogies test was administered eight times during a period of six months to eighty children in Grades 1 and 2 (six- to eight-year-olds). Strong evidence for bimodality was found in the distribution of the test scores and weaker evidence for inaccessibility. In the performance curves of the transitional subjects sudden jumps were demonstrated. Furthermore, the transitional subjects displayed a temporary increase of inconsistent solution behavior and solution time near the sudden jump. The characteristic changes in the analogy performance of the transitional subjects were interpreted as a strategy shift.

  15. Regulatory requirements for replacement of analog systems with digital upgrades

    International Nuclear Information System (INIS)

    Loeser, P.J.

    1993-01-01

    This paper reviews briefly the regulatory guidelines which must be met in order to replace analog systems in nuclear power plants with digital systems. There is a move to do such replacements for a number of reasons: analog systems are aging, and showing considerable drift; few vendors manufacture analog systems today; support and parts are hard to get; digital systems provide flexibility. There is a safety concern however about undesirable and unpredictable effects to digital safety equipment due to plant transients, accidents, post-accident condition, and EMI/RF environmental interferences. License holders must comply with the requirements of 10 C.F.R. 50.59, which deals with safety concerns with respect to any changes to operating plants which may have an impact on the safety of the plant. NRC staff is taking the position that all digital upgrades will require an evaluation under this regulation

  16. Therapy with radiolabelled somatostatin analogs in neuroendocrine tumors

    International Nuclear Information System (INIS)

    Kunikowska, J.; Krolicki, L.

    2007-01-01

    In the 80's the discovery of somatostatin receptors expression on NET cells enabled the application of somatostatin analogues in diagnosis and therapy. Initially, 'cold' somatostatin analogs were used for therapeutical purpose, with overall good clinical response, but with minimal anti-proliferation effect. Furthermore, radiolabelled receptor-binding peptides have been shown to be an important class of radiopharmaceuticals for tumor diagnosis and therapy with minimal side-effects. Specific binding between receptor on tumor cell and peptide with beta emitting radionuclide act not only on tumor related symptoms but also on tumor cell via radiotoxic effect of beta radiation. Discoveries of next receptor combinations, allow the work over synthesis and applications of next receptors' analogs both in diagnosis and in therapy. Due to complex characteristics of NET's, the use therapeutic 'cocktail' containing the variety analogs may be of great importance. (author)

  17. Using analogs to generate production forecasts in Faja

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Lugo, Rolando A. [Repsol (Canada)

    2011-07-01

    In the Carabobol Block, extra heavy oil will be produced by cold production from Miocene Morical Member sands. Many parameters such as pressure, temperature, solution gas oil ratio and viscosity variation significantly impact well productivity; unfortunately little information is available on the Carabobol Block. The aim of this paper is to provide a new methodology for using analog data to develop fluid properties correlations and a future production profile. Data from the analog neighbour field in the Orinoco oil belt was used. A methodology using scatter data was successfully applied for the Carabobol Block and fluid composition, a complete PVT and an analytical forecast were found and confirmed with actual laboratory data and a gross numerical model. This study showed that analog data can be used as a first approach to assess initial reservoir conditions and fluid properties and to generate production forecasts.

  18. Analog Circuit Design Optimization Based on Evolutionary Algorithms

    Directory of Open Access Journals (Sweden)

    Mansour Barari

    2014-01-01

    Full Text Available This paper investigates an evolutionary-based designing system for automated sizing of analog integrated circuits (ICs. Two evolutionary algorithms, genetic algorithm and PSO (Parswal particle swarm optimization algorithm, are proposed to design analog ICs with practical user-defined specifications. On the basis of the combination of HSPICE and MATLAB, the system links circuit performances, evaluated through specific electrical simulation, to the optimization system in the MATLAB environment, for the selected topology. The system has been tested by typical and hard-to-design cases, such as complex analog blocks with stringent design requirements. The results show that the design specifications are closely met. Comparisons with available methods like genetic algorithms show that the proposed algorithm offers important advantages in terms of optimization quality and robustness. Moreover, the algorithm is shown to be efficient.

  19. Acoustic analog of monolayer graphene and edge states

    International Nuclear Information System (INIS)

    Zhong, Wei; Zhang, Xiangdong

    2011-01-01

    Acoustic analog of monolayer graphene has been designed by using silicone rubber spheres of honeycomb lattices embedded in water. The dispersion of the structure has been studied theoretically using the rigorous multiple-scattering method. The energy spectra with the Dirac point have been verified and zigzag edge states have been found in ribbons of the structure, which are analogous to the electronic ones in graphene nanoribbons. The guided modes along the zigzag edge excited by a point source have been numerically demonstrated. The open cavity and 'Z' type edge waveguide with 60 o corners have also been realized by using such edge states. -- Highlights: → Acoustic analog of monolayer graphene has been designed. → The energy spectra with the Dirac point have been verified. → The zigzag edge states have been found in ribbons of the structure. → The guided modes excited by a point source have been demonstrated. → The open cavity and 'Z' type edge waveguide have been realized.

  20. Analogical Reasoning in the Engineering Design Process and Technology Education Applications

    Science.gov (United States)

    Daugherty, Jenny; Mentzer, Nathan

    2008-01-01

    This synthesis paper discusses the research exploring analogical reasoning, the role of analogies in the engineering design process, and educational applications for analogical reasoning. Researchers have discovered that analogical reasoning is often a fundamental cognitive tool in design problem solving. Regarding the possible role of analogical…