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

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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.

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

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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

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

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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 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.

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.

The multifaceted therapeutic potential of benfotiamine.

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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.

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

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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.

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

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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

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.

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

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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.

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

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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.

Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis.

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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

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

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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.

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

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

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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.

Benfotiamine relieves inflammatory and neuropathic pain in rats.

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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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

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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.

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

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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

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

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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.

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

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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.

Effect of benfotiamine in podocyte damage induced by peritoneal dialysis fluid

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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.

Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients.

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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.

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.

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

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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.

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

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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-...

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

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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

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

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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.

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

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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.

Benfotiamine Protects against Peritoneal and Kidney Damage in Peritoneal Dialysis

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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...

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

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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.

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

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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.

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

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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.

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.

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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.

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

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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.

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

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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.

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

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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.

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

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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. 

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

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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...

Using Analogies to Prevent Misconceptions about Chemical Equilibrium

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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)…

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...

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

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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.

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.

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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.

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

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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.

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...

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...

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.

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.

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.

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.

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

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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.

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

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,

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.

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.

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.

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.

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...

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

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.

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...

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

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.

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.

High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats.

Science.gov (United States)

Karachalias, Nikolaos; Babaei-Jadidi, Roya; Kupich, Christian; Ahmed, Naila; Thornalley, Paul J

2005-06-01

The streptozotocin-induced (STZ) diabetic rat experimental model of diabetes on insulin maintenance therapy exhibits dyslipidemia, mild thiamine deficiency, and increased plasma protein advanced glycation end products (AGEs). The reversal of thiamine deficiency by high-dose thiamine and S-benzoylthiamine monophosphate (benfotiamine) prevented the development of incipient nephropathy. Recently, we reported that high-dose thiamine (but not benfotiamine) countered diabetic dyslipidemia. To understand further the differences between the effects of thiamine and benfotiamine therapy, we quantified the levels of the AGEs in plasma protein. We found hydroimidazolone AGE residues derived from glyoxal and methylglyoxal, G-H1 and MG-H1, were increased 115% and 68% in STZ diabetic rats, with respect to normal controls, and were normalized by both thiamine and benfotiamine; whereas N-carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL) residues were increased 74% and 118% in STZ diabetic rats and were normalized by thiamine only. The lack of effect of benfotiamine on plasma CML and CEL residue concentrations suggests there may be important precursors of plasma protein CML and CEL residues other than glyoxal and methylglyoxal. These are probably lipid-derived aldehydes.

[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.

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.

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

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.

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.

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

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

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.

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.

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.

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

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.

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.

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.

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.

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.

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 ...

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.

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.

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...

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

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

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

Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine.

Science.gov (United States)

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

2009-09-01

Vascular cells in diabetes are subjected to daily fluctuations from high to low glucose. We aimed at investigating whether pulsed exposure to different glucose concentrations influences apoptosis in human retinal pericytes (HRP) versus bovine retinal pericytes (BRP), with consequences on the onset of diabetic retinopathy, and the possible protective role of thiamine. BRP and HRP (wild-type and immortalized) were grown in physiological/high glucose for 7 days, and then returned to physiological glucose for another 24, 48 or 72 h. Cells were also kept intermittently at 48-h intervals in high/normal glucose for 8 days, with/without thiamine/benfotiamine. Apoptosis was determined through ELISA, TUNEL, Bcl-2, Bax and p53 expression/concentration. Continuous exposure to high glucose increased apoptosis in BRP, but not HRP. BRP apoptosis normalized within 24 h of physiological glucose re-entry, while HRP apoptosis increased within 24-48 h of re-entry. Intermittent exposure to high glucose increased apoptosis in HRP and BRP. Bcl-2/Bax results were consistent with DNA fragmentation, while p53 was unchanged. Thiamine and benfotiamine countered intermittent high glucose-induced apoptosis. Human pericytes are less prone to apoptosis induced by persistently high glucose than bovine cells. However, while BRP recover after returning to physiological levels, HRP are more vulnerable to both downwardly fluctuating glucose levels and intermittent exposure. These findings reinforce the hypotheses that (1) glycaemic fluctuations play a role in the development of diabetic retinopathy and (2) species-specific models are needed. Thiamine and benfotiamine prevent human pericyte apoptosis, indicating this vitamin as an inexpensive approach to the prevention and/or treatment of diabetic complications.

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

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

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...

[The effect of benfothiamine in the therapy of diabetic polyneuropathy].

Science.gov (United States)

Nikolić, Ana; Kacar, Aleksandra; Lavrnić, Dragana; Basta, Ivana; Apostolski, Slobodan

2009-01-01

Diabetic polyneuropathy (DPN) is one of the most common diabetic complications, which can result in a significant functional impairment and reduction of the quality of life in affected individuals. It occurs due to alterations in different biochemical mechanisms which require the presence of thiamine, which is why this vitamin is used in the therapy of DPN. Due to the low bioavailability of the hydrosolubile forms of thiamine, its liposolubile preparations (benfotiamine) are preferentially used. The aim of this study was to determine the efficacy of benfotiamine in combination with vitamin B6 in the therapy of DPN. The study group comprised of 22 patients with DPN who were treated with the combination of benfotiamine and vitamin B6 during 45 days. The effect of the therapy was evaluated by the analysis of different clinical, laboratory and electrophysiological parameters before and after conducted treatment. After the treatment period, a statistically highly significant reduction of pain (p benfotiamine therapy only in 22.7% of patients, while hyperpathy was initially present in 90.9%, and after treatment in 31.8% of patients (p benfotiamine was good starting choice for the treatment of diabetic polyneuropathy.

Effects of high glucose and thiamine on the balance between matrix metalloproteinases and their tissue inhibitors in vascular cells.

Science.gov (United States)

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

2010-06-01

Pericyte survival in diabetic retinopathy depends also on interactions with extracellular matrix (ECM) proteins, which are degraded by matrix metalloproteinases (MMP). Elevated glucose influences ECM turnover, through expression of MMP and their tissue inhibitors, TIMP. We reported on reduced pericyte adhesion to high glucose-conditioned ECM and correction by thiamine. We aimed at verifying the effects of thiamine and benfotiamine on MMP-2, MMP-9 and TIMP expression and activity in human vascular cells with high glucose. In HRP, MMP-2 activity, though not expression, increased with high glucose and decreased with thiamine and benfotiamine; TIMP-1 expression increased with high glucose plus thiamine and benfotiamine; MMP-9 was not expressed. In EC, MMP-9 and MMP-2 expression and activity increased with high glucose, but thiamine and benfotiamine had no effects; TIMP-1 expression was unchanged. Neither glucose nor thiamine modified TIMP-2 and TIMP-3 expression. TIMP-1 concentrations did not change in either HRP or EC. High glucose imbalances MMP/TIMP regulation, leading to increased ECM turnover. Thiamine and benfotiamine correct the increase in MMP-2 activity due to high glucose in HRP, while increasing TIMP-1.

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

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. <

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

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.

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.

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…

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...

Advances in the management of diabetic neuropathy.

Science.gov (United States)

Várkonyi, Tamás; Körei, Anna; Putz, Zsuzsanna; Martos, Tímea; Keresztes, Katalin; Lengyel, Csaba; Nyiraty, Szabolcs; Stirban, Alin; Jermendy, György; Kempler, Péter

2017-10-01

The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.

Abnormal Thiamine-Dependent Processes in Alzheimer’s Disease. Lessons from Diabetes

Science.gov (United States)

Gibson, Gary E.; Hirsch, Joseph A.; Cirio, Rosanna T.; Jordan, Barry D.; Fonzetti, Pasquale; Elder, Jessica

2013-01-01

Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. PMID:22982063

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

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.

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.

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.

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…

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

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

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…

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 ...

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.

Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes.

Science.gov (United States)

Gibson, Gary E; Hirsch, Joseph A; Cirio, Rosanna T; Jordan, Barry D; Fonzetti, Pasquale; Elder, Jessica

2013-07-01

Reduced glucose metabolism is an invariant feature of Alzheimer's Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. Copyright © 2012 Elsevier Inc. All rights reserved.

High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine.

Science.gov (United States)

Frank, T; Bitsch, R; Maiwald, J; Stein, G

2000-06-01

The influence of either orally administered S-benzoylthiamine-O-monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was tested in a randomised, two-group comparison study in 20 end-stage renal disease (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its activation coefficient (alpha-ETK) and the TDP concentration in erythrocytes. After ingestion of a single dose of either 100 mg thiamine nitrate (corresponding to 305 micromol thiamine) or 100 mg benfotiamine (corresponding to 214 micromol thiamine), the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period. The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood. Erythrocyte transketolase activity and alpha-ETK were measured before and 10 h after administration. The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from database query. Regarding the blood concentrations of TDP, the patients with ESRD had a 4.3 times higher area under the concentration time curve after benfotiamine administration than after thiamine nitrate. After benfotiamine administration, the peak plasma concentration of TDP exceeded that in healthy subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0 ng/ml after thiamine nitrate administration. The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66+/-0.6 in the benfotiamine group and 1.44+/-0.2 in the group receiving thiamine nitrate (P benfotiamine intake (P = 0.02) and from 3.71+/-0.8 microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08). Likewise, alpha

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…

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.

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.

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.

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…

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.

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.

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…

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.

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

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.

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

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)

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

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…

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…

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.

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.

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.

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.

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

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…

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.

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)

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.

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.

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

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

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...

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

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

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.

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.)

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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

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.

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.

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

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

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.

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...

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 ...

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.

Human pericyte-endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment.

Science.gov (United States)

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

2012-12-01

Pericytes regulate vascular tone, perfusion pressure and endothelial cell (EC) proliferation in capillaries. Thiamine and benfotiamine counteract high glucose-induced damage in vascular cells. We standardized two human retinal pericyte (HRP)/EC co-culture models to mimic the diabetic retinal microvascular environment. We aimed at evaluating the interactions between co-cultured HRP and EC in terms of proliferation/apoptosis and the possible protective role of thiamine and benfotiamine against high glucose-induced damage. EC and HRP were co-cultured in physiological glucose and stable or intermittent high glucose, with or without thiamine/benfotiamine. No-contact model: EC were plated on a porous membrane suspended into the medium and HRP on the bottom of the same well. Cell-to-cell contact model: EC and HRP were plated on the opposite sides of the same membrane. Proliferation (cell counts and DNA synthesis), apoptosis and tubule formation in Matrigel were assessed. In the no-contact model, stable high glucose reduced proliferation of co-cultured EC/HRP and EC alone and increased co-cultured EC/HRP apoptosis. In the contact model, both stable and intermittent high glucose reduced co-cultured EC/HRP proliferation and increased apoptosis. Stable high glucose had no effects on HRP in separate cultures. Both EC and HRP proliferated better when co-cultured. Thiamine and benfotiamine reversed high glucose-induced damage in all cases. HRP are sensitive to soluble factors released by EC when cultured in high glucose conditions, as suggested by conditioned media assays. In the Matrigel models, addition of thiamine and benfotiamine re-established the high glucose-damaged interactions between EC/HRP and stabilized microtubules.

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…

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…

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

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.

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

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...

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.

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

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.

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

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)

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...

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

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.

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…

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.

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.

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

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…

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.

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

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

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.

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.

Los pasiegos. La analogía salvaje y lo salvaje de la analogía

Directory of Open Access Journals (Sweden)

JAIME DE LA CALLE VALVERDE

2007-01-01

-entendiendo salvaje como un pensamiento humano prístino-: por un lado en sus relaciones con el racionalismo (¿emerge la analogía desde el racionalismo?, ¿qué relación guarda con éste?, ¿su nacimiento es resultado de una función «natural»? y por otro sobre la naturaleza social de lo salvaje a partir de las bases sociales que lo producen. Es decir, se rastrea lo que de salvaje tiene la analogía, si la analogía es o no una función ahistórica y asocial del intelecto humano. No se examina todo el complejo analógico de los pasiegos, únicamente aquél que establece relaciones homólogas entre las vacas y el entorno.

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.

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

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.

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.

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.

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

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 ...

Pre-Steady State Kinetic Investigation of the Incorporation of Anti-Hepatitis B Nucleotide Analogs Catalyzed by Non-Canonical Human DNA Polymerases

Science.gov (United States)

Brown, Jessica A.; Pack, Lindsey R.; Fowler, Jason D.; Suo, Zucai

2011-01-01

Antiviral nucleoside analogs have been developed to inhibit the enzymatic activities of the hepatitis B virus (HBV) polymerase, thereby preventing the replication and production of HBV. However, the usage of these analogs can be limited by drug toxicity because the 5′-triphosphates of these nucleoside analogs (nucleotide analogs) are potential substrates for human DNA polymerases to incorporate into host DNA. Although they are poor substrates for human replicative DNA polymerases, it remains to be established whether these nucleotide analogs are substrates for the recently discovered human X- and Y-family DNA polymerases. Using pre-steady state kinetic techniques, we have measured the substrate specificity values for human DNA polymerases β, λ, η, ι, κ, and Rev1 incorporating the active forms of the following anti-HBV nucleoside analogs approved for clinical use: adefovir, tenofovir, lamivudine, telbivudine, and entecavir. Compared to the incorporation of a natural nucleotide, most of the nucleotide analogs were incorporated less efficiently (2 to >122,000) by the six human DNA polymerases. In addition, the potential for entecavir and telbivudine, two drugs which possess a 3′-hydroxyl, to become embedded into human DNA was examined by primer extension and DNA ligation assays. These results suggested that telbivudine functions as a chain terminator while entecavir was efficiently extended by the six enzymes and was a substrate for human DNA ligase I. Our findings suggested that incorporation of anti-HBV nucleotide analogs catalyzed by human X- and Y-family polymerases may contribute to clinical toxicity. PMID:22132702

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…

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.

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.

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.

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…

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

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

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.

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.

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...

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

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...

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.

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.

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.

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.

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

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

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

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.

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...

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.

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.

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.

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.

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…

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.

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.

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

Tracking cognitive phases in analogical reasoning with event-related potentials.

Science.gov (United States)

Maguire, Mandy J; McClelland, M Michelle; Donovan, Colin M; Tillman, Gail D; Krawczyk, Daniel C

2012-03-01

Analogical reasoning consists of multiple phases. Four-term analogies (A:B::C:D) have an encoding period in which the A:B pair is evaluated prior to a mapping phase. The electrophysiological timing associated with analogical reasoning has remained unclear. We used event-related potentials to identify neural timing related to analogical reasoning relative to perceptual and semantic control conditions. Spatiotemporal principal-components analyses revealed differences primarily in left frontal electrodes during encoding and mapping phases of analogies relative to the other conditions. The timing of the activity differed depending upon the phase of the problem. During the encoding of A:B terms, analogies elicited a positive deflection compared to the control conditions between 400 and 1,200 ms, but for the mapping phase analogical processing elicited a negative deflection that occurred earlier and for a shorter time period, between 350 and 625 ms. These results provide neural and behavioral evidence that 4-term analogy problems involve a highly active evaluation phase of the A:B pair. 2012 APA, all rights reserved

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.

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....

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”.

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…

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)

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.

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.

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.

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.

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.

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.

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...

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

Wafer-level chip-scale packaging analog and power semiconductor applications

CERN Document Server

Qu, Shichun

2015-01-01

This book presents a state-of-art and in-depth overview in analog and power WLCSP design, material characterization, reliability, and modeling. Recent advances in analog and power electronic WLCSP packaging are presented based on the development of analog technology and power device integration. The book covers in detail how advances in semiconductor content, analog and power advanced WLCSP design, assembly, materials, and reliability have co-enabled significant advances in fan-in and fan-out with redistributed layer (RDL) of analog and power device capability during recent years. Along with new analog and power WLCSP development, the role of modeling is a key to assure successful package design. An overview of the analog and power WLCSP modeling and typical thermal, electrical, and stress modeling methodologies is also provided. This book also: ·         Covers the development of wafer-level power discrete packaging with regular wafer-level design concepts and directly bumping technology ·    �...

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…

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.  

Proportional and functional analogical reasoning in normal and language-impaired children.

Science.gov (United States)

Nippold, M A; Erskine, B J; Freed, D B

1988-11-01

Teachers often use analogies in classroom settings to clarify new concepts for their students. However, analogies may inadvertently confuse the youngster who has difficulty identifying the one-to-one comparisons underlying them. Although analogical reasoning has been studied extensively in normal children, no information was available concerning this construct in children having a specific language impairment. Thus, it was unknown to what extent they might be deficient in analogical reasoning. Therefore, in the present study, 20 children ages 6-8 years (mean age = 7:6) having normal nonverbal intelligence but deficits in language comprehension were administered tasks of verbal and perceptual proportional analogical reasoning and a problem-solving task of functional analogical reasoning. Compared to a normal-language control group matched on the basis of chronological age and sex, the language-impaired group was deficient in all three tasks of analogical reasoning. However, when the factor of nonverbal intelligence was controlled statistically, the differences between the groups on each of the tasks were removed. Additional findings were that verbal proportional analogical reasoning was significantly correlated to perceptual proportional analogical reasoning and to functional analogical reasoning. Implications for assessment and intervention with young school-age language-impaired children are discussed.

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.

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. .

Abstract analogical reasoning in high-functioning children with autism spectrum disorders.

Science.gov (United States)

Green, Adam E; Kenworthy, Lauren; Mosner, Maya G; Gallagher, Natalie M; Fearon, Edward W; Balhana, Carlos D; Yerys, Benjamin E

2014-12-01

Children with autism spectrum disorders (ASD) exhibit a deficit in spontaneously recognizing abstract similarities that are crucial for generalizing learning to new situations. This may contribute to deficits in the development of appropriate schemas for navigating novel situations, including social interactions. Analogical reasoning is the central cognitive mechanism that enables typically developing children to understand abstract similarities between different situations. Intriguingly, studies of high-functioning children with ASD point to a relative cognitive strength in basic, nonabstract forms of analogical reasoning. If this analogical reasoning ability extends to abstract analogical reasoning (i.e., between superficially dissimilar situations), it may provide a bridge between a cognitive capability and core ASD deficits in areas such as generalization and categorization. This study tested whether preserved analogical reasoning abilities in ASD can be extended to abstract analogical reasoning, using photographs of real-world items and situations. Abstractness of the analogies was determined via a quantitative measure of semantic distance derived from latent semantic analysis. Children with ASD performed as well as typically developing children at identifying abstract analogical similarities when explicitly instructed to apply analogical reasoning. Individual differences in abstract analogical reasoning ability predicted individual differences in a measure of social function in the ASD group. Preliminary analyses indicated that children with ASD, but not typically developing children, showed an effect of age on abstract analogical reasoning. These results provide new evidence that children with ASD are capable of identifying abstract similarities through analogical reasoning, pointing to abstract analogical reasoning as a potential lever for improving generalization skills and social function in ASD. © 2014 International Society for Autism Research, Wiley

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.

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

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).

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

Understanding the generative capacity of analogies as a tool for explanation

Science.gov (United States)

Wong, E. David

1993-12-01

Psychological studies have typically portrayed analogical reasoning as a process of schema transfer from a familiar domain of understanding to a problem situation. These studies have usually examined analogical reasoning in contexts where (a) individuals possess or have been provided with appropriate, problem-specific schema, (b) the nature of the problem and/or solution is fairly well defined, and (c) ideal analogies are provided or suggested by an outside source. This study examines analogical reasoning in contexts where understanding is generated from loosely organized, incomplete prior knowledge rather than transferred from a well-structured domain of understanding. In addition, participants were asked to create, apply, and modify their own analogies - as opposed to applying a given analogy - as a heuristic for constructing, evaluating, and modifying their explanations for a particular scientific phenomena. The results provide empirical support for the generative properties of analogies; that is, analogies can stimulate new inferences and insight. Furthermore, under specific conditions, individuals can productively harness the generative capacity of their own analogies to advance their conceptual understanding of scientific phenomena.

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.

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 ...

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...

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…

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…

Comparison of digital selenium radiography with an analog screen-film system in the diagnostic process of pneumoconiosis according to ILO classification

International Nuclear Information System (INIS)

Zaehringer, M.; Winnekendonk, G.; Gossmann, A.; Krueger, K.; Krug, B.

2001-01-01

Purpose: The aim of the study was to determine the diagnostic value of digital selenium radiography in patients with pneumoconiosis. For this purpose chest X-rays by digital selenium radiography and analog screen-film system were compared according to the ILO classification of pneumoconiosis. Method: After approval of the study by the local ethic commission and the Federal German Office for Radiation Protection 50 patients were subjected to X-rays by digital selenium radiography (Thoravision; Philips Medical Systems, Hamburg, Germany) and analog screen-film system of the same day within the scope of an industrial medicine preventive checkup. Four investigators rated the chest X-rays according to the ILO classification of pneumoconiosis. Results: The findings demonstrated by chest X-rays according to ILO classification were rated similar by digital selenium radiography and analog screen film systems. Image quality of the digital pictures was rated significantly better. Conclusion: The use of digital selenium radiography in evaluating chest X-rays according to the ILO classification does not result in over- or underestimation of pulmonary pathologies. Hence, in the diagnosis of pneumoconiosis, digital selenium radiography can replace the tested analog screen-film system. (orig.) [de

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…

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

Effects of Multimedia and Schema Induced Analogical Reasoning on Science Learning

Science.gov (United States)

Zheng, R. Z.; Yang, W.; Garcia, D.; McCadden, E. P.

2008-01-01

The present study investigates the effects of multimedia and schema induced analogical reasoning on science learning. It involves 89 fourth grade elementary students in the north-east of the United States. Participants are randomly assigned into four conditions: (a) multimedia with analogy; (b) multimedia without analogy; (c) analogy without…

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 ...

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.

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.

Analogy, an Alternative Model.
 Critics to the standard model of analogical problems solving and proposals for an alternative one

Directory of Open Access Journals (Sweden)

Ricardo A. Minervino

2016-02-01

Full Text Available The authors made an extension of Hofstadter‘s criticisms against the standard approach in analogical thinking represented by the structure-mapping theory of Gentner and the multiconstraint theory of Holyoak and Thagard. Based on this extension, they proposed a non-serial model of analogical problem solving. Against the standard approach, the model postulates that: (a people detect and evaluate differences between mapped elements before the subprocess of inference generation and consider them in order to control it, and (b properties of an element that explain why the element could fill a certain role in the base problem resolution (PERs play a crucial role in these detection and evaluation operations, and also in post-inferences subprocesses. An experiment showed that: (a people detect and evaluate the relevance of differences between mapped elements before inference generation, (b that they inhibit the generation of literal inferences when they face relevant differences, and (c that they stop the subprocess when they recognize insuperable ones. The results also showed that base PERs are reactivated at different moments of analogical transfer. The data obtained are incompatible with the standard theories of analogical thinking, which treat inference generation as a syntactic mechanism and exclude contextual semantic analysis from the study of analogy. 

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

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.

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.

The Discourse on Printed and Electronic Books: Analogies, Oppositions, and Perspectives

Science.gov (United States)

Velagic, Zoran

2014-01-01

Introduction: The point of departure for this paper is the twofold analogy (analogy of content, analogy of medium) between printed and electronic books, the aim being to draw attention to the usual perception of their capacities and relationships, to provide a rather detailed analysis of the outcome and sustainability of such analogies and…

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.

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...

Aseptically Sampled Organics in Subsurface Rocks From the Mars Analog Rio Tinto Experiment: An Analog For The Search for Deep Subsurface Life on Mars.}

Science.gov (United States)

Bonaccorsi, R.; Stoker, C. R.

2005-12-01

The subsurface is the key environment for searching for life on planets lacking surface life. Subsurface ecosystems are of great relevance to astrobiology including the search for past/present life on Mars. The surface of Mars has conditions preventing current life but the subsurface might preserve organics and even host some life [1]. The Mars-Analog-Rio-Tinto-Experiment (MARTE) is performing a simulation of a Mars drilling experiment. This comprises conventional and robotic drilling of cores in a volcanically-hosted-massive-pyrite deposit [2] from the Iberian Pyritic Belt (IBP) and life detection experiments applying anti-contamination protocols (e.g., ATP Luminometry assay). The RT is considered an important analog of the Sinus Meridiani site on Mars and an ideal model analog for a deep subsurface Martian environment. Former results from MARTE suggest the existence of a relatively complex subsurface life including aerobic and anaerobic chemoautotrophs and strict anaerobic methanogens sustained by Fe and S minerals in anoxic conditions. A key requirement for the analysis of a subsurface sample on Mars is a set of simple tests that can help determine if the sample contains organic material of biological origin, and its potential for retaining definitive biosignatures. We report here on the presence of bulk organic matter Corg (0.03-0.05 Wt%), and Ntot (0.01-0.04 Wt%) and amount of measured ATP (Lightning MVP, Biocontrol) in weathered rocks (tuffs, gossan, pyrite stockwork from Borehole #8; >166m). This provides key insight on the type of trophic system sustaining the subsurface biosphere (i.e., heterotrophs vs. autotrophs) at RT. ATP data (Relative-Luminosity-Units, RLU) provide information on possible contamination and distribution of viable biomass with core depth (BH#8, and BH#7, ~3m). Avg. 153 RLU, i.e., surface vs. center of core, suggest that cleaness/sterility can be maintained when using a simple sterile protocol under field conditions. Results from this

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.

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...

Andrographolide, a New Hope in the Prevention and Treatment of Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Muhammad T. Islam

2017-08-01

Full Text Available Recently, the use of plant-derived medicines is increasing interest in the prevention and treatment of a variety of disorders including metabolic syndromes. Metabolic syndrome is one of the major risk factors for cardiovascular diseases (CVDs and incidence of mortality worldwide. Scientific evidence suggests that Andrographis paniculata and its derived components, especially andrographolide (AGL and its analogs/derivatives have a broad spectrum of biological activities. This review aims to sketch the activity of AGL and its analogs/derivatives against the components of metabolic syndromes such as diabetes, hyperlipidemia, hypertension, and obesity. Additionally, AGL activity against CVDs is also summarized. The finding suggests that AGL and its analogs/derivatives have a potential role in the management of metabolic syndrome; however, more studies should be conducted to evaluate their effectiveness.

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

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

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.

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 ...

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…

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

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…

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…

Spanish Velar-Insertion and Analogy: A Usage-Based Diachronic Analysis

Science.gov (United States)

Fondow, Steven Richard

2010-01-01

The theory of Analogical and Exemplar Modeling (AEM) suggests renewed discussion of the formalization of analogy and its possible incorporation in linguistic theory. AEM is a usage-based model founded upon Exemplar Modeling (Bybee 2007, Pierrehumbert 2001) that utilizes several principles of the Analogical Modeling of Language (Skousen 1992, 1995,…

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

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.

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…

Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

Science.gov (United States)

Ruiz, Francisco J; Luciano, Carmen

2011-01-01

Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning. PMID:21547072

MENUMBUHKAN DAYA NALAR ( POWER OF REASON SISWA MELALUI PEMBELAJARAN ANALOGI MATEMATIKA

Directory of Open Access Journals (Sweden)

Rahayu Kariadinata

2012-02-01

Full Text Available Learning mathematical analogy is one alternative learning that can be applied in order to cultivate the power of reason (power of reason students. Through mathematical analogy students are required to be able to look for similarities or relationship nature of the two concepts are the same or different by comparison, then draw a conclusion from the similitude. Thus the analogy can be used as an explanation or as the basis of reasoning. Before starting the analogy of learning mathematics, teachers should examine the ability of understanding mathematical concepts of students, because of the level of understanding of students will affect the power of reason. Tasks (problems mathematical analogy included non-routine matter, therefore the required readiness of teachers to make it. In each question contained mathematical analogy same or different concepts, so it takes quite a lot of material. Steps to make about the mathematical analogy, are: a assemble all the concepts in mathematics student has learned; b Similarly stacking properties / relationships contained in any concept, and c select materials that have a nature / relationship analogous. In this paper is given two forms of matter of mathematical analogy is the analogy of mathematical models and mathematical analogy 1 models 2. Learning mathematical analogy should be carried out after a number of concepts learned. It is better to be given in classes end for many of the concepts that have been learned by the students. Reasoning power (power of reason the student becomes an important part in the process of learning to drive them toward their future as citizens are intelligent, which will be led by the power of reason (the brain and not by the strength (muscle only. As noted by former US President Thomas Jefferson (in Copi, 1978: vii, which states: "In a republican nation, Whose citizens are to be led by reason and persuasion and not by force, the art of reasoning Becomes of first importance"

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.

An Experimentation Platform for On-Chip Integration of Analog Neural Networks: A Pathway to Trusted and Robust Analog/RF ICs.

Science.gov (United States)

Maliuk, Dzmitry; Makris, Yiorgos

2015-08-01

We discuss the design of an experimentation platform intended for prototyping low-cost analog neural networks for on-chip integration with analog/RF circuits. The objective of such integration is to support various tasks, such as self-test, self-tuning, and trust/aging monitoring, which require classification of analog measurements obtained from on-chip sensors. Particular emphasis is given to cost-efficient implementation reflected in: 1) low energy and area budgets of circuits dedicated to neural networks; 2) robust learning in presence of analog inaccuracies; and 3) long-term retention of learned functionality. Our chip consists of a reconfigurable array of synapses and neurons operating below threshold and featuring sub-μW power consumption. The synapse circuits employ dual-mode weight storage: 1) a dynamic mode, for fast bidirectional weight updates during training and 2) a nonvolatile mode, for permanent storage of learned functionality. We discuss a robust learning strategy, and we evaluate the system performance on several benchmark problems, such as the XOR2-6 and two-spirals classification tasks.

Synthesis and structure-distribution study of radioiodinated norepinephrine storage analogs

Energy Technology Data Exchange (ETDEWEB)

Wieland, D.M.; Inbasekaran, M.; Brown, L.E.; Marsh, D.D.; Beierwaltes, W.H. (Michigan Univ., Ann Arbor (USA). Medical Center)

Unlabelled analogs of norepinephrine have been synthesised and then labelled with /sup 125/I in an attempt to find an agent with heart uptake and neuronal specificity greater than metaiodobenzylguanidine (MIBG). The analogs of norepinephrine were injected intravenously into dogs and showed a heart concentration similar to MIBG. Neuronal specificity of some analogs is being evaluated in rat heart.

Beuchot’s formal analogism within Peter Singer’s philosophy

Directory of Open Access Journals (Sweden)

José Barrientos-Rastrojo

2015-01-01

Full Text Available This paper analyses an analogic reading of singerian ethics. Firstly, it studies Mauricio Beuchot’s analogical hermeneutics grounds. Then, it takes them to each of the Peter Singer’s ethical universes. Finally, it reveals the scheme of his ethic that will be followed in his future works. Therefore, this article has a prospective mission related to Professor Singer and it has an practical mission related to Mauricio Beuchot because it determines a practical performance to his analogical hermeneutics.

A dark business, full of shadows: analogy and theology in William Harvey.

Science.gov (United States)

Goldberg, Benjamin

2013-09-01

In a short work called De conceptione appended to the end of his Exercitationes de generatione animalium (1651), William Harvey developed a rather strange analogy. To explain how such marvelous productions as living beings were generated from the rather inauspicious ingredients of animal reproduction, Harvey argued that conception in the womb was like conception in the brain. It was mostly rejected at the time; it now seems a ludicrous theory based upon homonymy. However, this analogy offers insight into the structure and function of analogies in early modern natural philosophy. In this essay I hope to not only describe the complex nature of Harvey's analogy, but also offer a novel interpretation of his use of analogical reasoning, substantially revising the account offered by Guido Giglioni (1993). I discuss two points of conceptual change and negotiation in connection with Harvey's analogy, understanding it as both a confrontation between the border of the natural and the supernatural, as well as a moment in the history of psychology. My interpretation touches upon a number of important aspects, including why the analogy was rejected, how Harvey systematically deployed analogies according to his notions of natural philosophical method, how the analogy fits into contemporary discussions of analogies in science, and finally, how the analogy must be seen in the context of changing Renaissance notions of the science of the soul, ultimately confronting the problem of how to understand final causality in Aristotelian science. In connection with the last, I conclude the essay by turning to how Harvey embeds the analogy within a natural theological cosmology. Copyright © 2013. Published by Elsevier Ltd.

Membrane Affinity of Platensimycin and Its Dialkylamine Analogs

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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.

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.

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…

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.

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...

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...

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.

Synthesis and structure-distribution study of radioiodinated norepinephrine storage analogs

International Nuclear Information System (INIS)

Wieland, D.M.; Inbasekaran, M.; Brown, L.E.; Marsh, D.D.; Beierwaltes, W.H.

1982-01-01

Unlabelled analogs of norepinephrine have been synthesised and then labelled with 125 I in an attempt to find an agent with heart uptake and neuronal specificity greater than metaiodobenzylguanidine (MIBG). The analogs of norepinephrine were injected intravenously into dogs and showed a heart concentration similar to MIBG. Neuronal specificity of some analogs is being evaluated in rat heart. (U.K.)

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…

Kinetics of the transformation of n-propyl gallate and structural analogs in the perfused rat liver

International Nuclear Information System (INIS)

Eler, Gabrielle Jacklin; Santos, Israel Souza; Giaretta de Moraes, Amarilis; Mito, Márcio Shigueaki; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar

2013-01-01

n-Propyl gallate and its analogs are used in foods and other products to prevent oxidation. In the liver the compound exerts several harmful effects, especially gluconeogenesis inhibition. The mode of transport and distribution of n-propyl gallate and its kinetics of biotransformation have not yet been investigated. To fill this gap the transformation, transport and distribution of n-propyl gallate and two analogs were investigated in the rat liver. Isolated perfused rat liver was used. n-Propyl gallate, methyl gallate, n-octyl gallate and transformation products were quantified by high pressure-liquid chromatography coupled to fluorescence detection. The interactions of n-propyl gallate and analogs with the liver presented three main characteristics: (1) the hydrolytic release of gallic acid from n-propyl gallate and methyl gallate was very fast compared with the subsequent transformations of the gallic acid moiety; (2) transport of the esters was very fast and flow-limited in contrast to the slow and barrier-limited transport of gallic acid; (3) the apparent distribution volume of n-propyl gallate, but probably also of methyl gallate and n-octyl gallate, greatly exceeded the water space in the liver, contrary to the gallic acid space which is smaller than the water space. It can be concluded that at low portal concentrations (< 50 μM) the gallic acid esters are 100% extracted during a single passage through the liver, releasing mainly gallic acid into the systemic circulation. For the latter a considerable time is required until complete biotransformation. The exposure of the liver to the esters, however, is quite prolonged due to extensive intracellular binding. - Highlights: • The liver binds very strongly n-propyl gallate and releases basically gallic acid. • n-propyl gallate and analogs undergo concentrative flow-limited distribution. • Gallic acid undergoes barrier-limited distribution and is slowly transformed. • The long residence time of n

Kinetics of the transformation of n-propyl gallate and structural analogs in the perfused rat liver

Energy Technology Data Exchange (ETDEWEB)

Eler, Gabrielle Jacklin; Santos, Israel Souza; Giaretta de Moraes, Amarilis; Mito, Márcio Shigueaki; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar, E-mail: adebracht@uol.com.br

2013-11-15

n-Propyl gallate and its analogs are used in foods and other products to prevent oxidation. In the liver the compound exerts several harmful effects, especially gluconeogenesis inhibition. The mode of transport and distribution of n-propyl gallate and its kinetics of biotransformation have not yet been investigated. To fill this gap the transformation, transport and distribution of n-propyl gallate and two analogs were investigated in the rat liver. Isolated perfused rat liver was used. n-Propyl gallate, methyl gallate, n-octyl gallate and transformation products were quantified by high pressure-liquid chromatography coupled to fluorescence detection. The interactions of n-propyl gallate and analogs with the liver presented three main characteristics: (1) the hydrolytic release of gallic acid from n-propyl gallate and methyl gallate was very fast compared with the subsequent transformations of the gallic acid moiety; (2) transport of the esters was very fast and flow-limited in contrast to the slow and barrier-limited transport of gallic acid; (3) the apparent distribution volume of n-propyl gallate, but probably also of methyl gallate and n-octyl gallate, greatly exceeded the water space in the liver, contrary to the gallic acid space which is smaller than the water space. It can be concluded that at low portal concentrations (< 50 μM) the gallic acid esters are 100% extracted during a single passage through the liver, releasing mainly gallic acid into the systemic circulation. For the latter a considerable time is required until complete biotransformation. The exposure of the liver to the esters, however, is quite prolonged due to extensive intracellular binding. - Highlights: • The liver binds very strongly n-propyl gallate and releases basically gallic acid. • n-propyl gallate and analogs undergo concentrative flow-limited distribution. • Gallic acid undergoes barrier-limited distribution and is slowly transformed. • The long residence time of n

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.

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.

Analogical study of the servo-control of a reactivity modulator

International Nuclear Information System (INIS)

Le Bot, Michel

1969-03-01

In the context of the study of the transfer functions related to the Cabri reactor, this paper presents: the objective of the servo-control (reactivity modulator, reasons for the analogical study), the principles of the servo-control (description of the servo-controlled system, elaboration of the error signal, principles of the phase meter, critical analysis of different types of phase meters), the analogical formulation (transfer diagram of the process, analogical simulation of the process, analogical realization of the phase meter, simulation of the Low Frequency generator), study of the controlled system and results (system responses to echelon and ramp signals, responses of the controlled system with the phase meter in feedback)

VME Switch for CERN's PS Analog Video System

CERN Document Server

Acebes, I; Heinze, W; Lewis, J; Serrano, J

2003-01-01

Analog video signal switching is used in CERN's Proton Synchrotron (PS) complex to route the video signals coming from Beam Diagnostics systems to the Meyrin Control Room (MCR). Traditionally, this has been done with custom electromechanical relay-based cards controlled serially via CAMAC crates. In order to improve the robustness and maintainability of the system, while keeping it analog to preserve the low latency, a VME card based on Analog Devices' AD8116 analog matrix chip has been developed. Video signals go into the front panel and exit the switch through the P2 connector of the VME backplane. The module is a 16 input, 32 output matrix. Larger matrices can be built using more modules and bussing their outputs together, thanks to the high impedance feature of the AD8116. Another VME module takes the selected signals from the P2 connector and performs automatic gain to send them at nominal output level through its front panel. This paper discusses both designs and presents experimental test results.

Analogical reasoning in a capuchin monkey (Cebus apella).

Science.gov (United States)

Kennedy, Erica Hoy; Fragaszy, Dorothy M

2008-05-01

Previous evidence has suggested that analogical reasoning (recognizing similarities among object relations when the objects themselves are dissimilar) is limited to humans and apes. This study investigated whether capuchin monkeys (Cebus apella) can use analogical reasoning to solve a 3-dimensional search task. The task involved hiding a food item under 1 of 2 or 3 plastic cups of different sizes and then allowing subjects to search for food hidden under the cup of analogous size in their own set of cups. Four monkeys were exposed to a series of relational matching tasks. If subjects reached criterion on these tasks, they were exposed to relational transfer tasks involving novel stimuli. Three of the monkeys failed to reach criterion on the basic relational matching tasks and therefore were not tested further. One monkey, however, revealed above-chance performance on a series of transfer tasks with 3 novel stimuli. This evidence suggests that contrary to previous arguments, a member of a New World monkey species can solve an analogical problem. PsycINFO Database Record (c) 2008 APA, all rights reserved.

Community Decadal Panel for Terrestrial Analogs to Mars

Science.gov (United States)

Barlow, N. G.; Farr, T.; Baker, V. R.; Bridges, N.; Carsey, F.; Duxbury, N.; Gilmore, M. S.; Green, J. R.; Grin, E.; Hansen, V.; Keszthelyi, L.; Lanagan, P.; Lentz, R.; Marinangeli, L.; Morris, P. A.; Ori, G. G.; Paillou, P.; Robinson, C.; Thomson, B.

2001-11-01

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 for Mars, 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 is considering the following two key questions: (1) How do terrestrial analog studies tie in to the MEPAG 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 is considering 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.

Antimicrobial and cell-penetrating properties of penetratin analogs

DEFF Research Database (Denmark)

Bahnsen, Jesper Søborg; Franzyk, Henrik; Sandberg-Schaal, Anne

2013-01-01

Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) show great potential as drug delivery vectors and new antibiotic drug entities, respectively. The current study deals with the properties of a variety of peptide analogs derived from the well-known CPP penetratin as well as octaar......Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) show great potential as drug delivery vectors and new antibiotic drug entities, respectively. The current study deals with the properties of a variety of peptide analogs derived from the well-known CPP penetratin as well...... as octaarginine and different Tat sequences. The effects of peptide length, guanidinium content, and sequence of non-cationic residues were assessed in mammalian and bacterial cells. The arginine (Arg) content in the penetratin analogs was found to influence eukaryotic cell uptake efficiency, antimicrobial...... was similar, the eukaryotic cellular uptake of the shuffled analogs was noticeably lower than for native penetratin. Moreover, a point substitution of Met to Leu in native penetratin had no influence on eukaryotic cellular uptake and antimicrobial effect, and only a minor effect on cytotoxicity, in contrast...

The use of analogies in forecasting ecological and societal responses to global warming

Energy Technology Data Exchange (ETDEWEB)

Glantz, M.H. (National Center for Atmospheric Research, Boulder CO (USA). Environmental Research and Societal Impacts Group)

1991-06-01

Due to the limitations of general circulation models, researchers use analogies to look at future climatic change and its effects. Analogies used include the greenhouse, the Altithermal period, regional climates and summertime. Analogical reasoning is a prominent part of general circulation modeling of the atmosphere. Analogies are useful for generating hypotheses and improving understanding, but not as forecasts. The use of an analogy to develop specific policies related to global warming is risky. Historical analogies can provide a first approach to ascertaining the level of societal preparedness for the impacts of a global warming. Each analogy provides additional information about the target problem. 63 refs., 3 figs., 1 tab.

The use of analogies in forecasting ecological and societal responses to global warming

International Nuclear Information System (INIS)

Glantz, M.H.

1991-01-01

Due to the limitations of general circulation models, researchers use analogies to look at future climatic change and its effects. Analogies used include the greenhouse, the Altithermal period, regional climates and summertime. Analogical reasoning is a prominent part of general circulation modeling of the atmosphere. Analogies are useful for generating hypotheses and improving understanding, but not as forecasts. The use of an analogy to develop specific policies related to global warming is risky. Historical analogies can provide a first approach to ascertaining the level of societal preparedness for the impacts of a global warming. Each analogy provides additional information about the target problem. 63 refs., 3 figs., 1 tab

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.

Introduction to engineering a starter's guide with hands-on analog multimedia explorations

CERN Document Server

Karam, Lina

2008-01-01

This lecture provides a hands-on glimpse of the field of electrical engineering. The introduced applications utilize the NI ELVIS hardware and software platform to explore concepts such as circuits, power, analog sensing, and introductory analog signal processing such as signal generation, analog filtering, and audio and music processing. These principals and technologies are introduced in a very practical way and are fundamental to many of the electronic devices we use today. Some examples include photodetection, analog signal (audio, light, temperature) level meter, and analog music equalize

The Description of Problems Relating to Analogies Used in Science and Technology Textbooks

Directory of Open Access Journals (Sweden)

Rahmi YAĞBASAN

2008-01-01

Full Text Available The aim of this study was to determine the problems concerning the use of analogies ingeneral and analogies used in primary school science and technology lessons inparticular. In this study, descriptive method was used. 4th, 5th, and 8th classes Scienceand Technology course books; 7 th, 8 th classes Science Books were used as a source.Analogies in the course books were classified according to the literature and theproblems found related to the analogies are pointed out in the study. In this study itwas seen that eighty-nine analogies were used in Science and Technology and inScience course books. These analogies were used in descending order as 8, 4, 6, 7, 5class groups. Also it was seen that these analogies were generally at simple andpictorial analogies.

Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

Science.gov (United States)

Havermans, Remco C; Jansen, Anita T M

2003-07-01

Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

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.

Advances in analog and RF IC design for wireless communication systems

CERN Document Server

Manganaro, Gabriele

2013-01-01

Advances in Analog and RF IC Design for Wireless Communication Systems gives technical introductions to the latest and most significant topics in the area of circuit design of analog/RF ICs for wireless communication systems, emphasizing wireless infrastructure rather than handsets. The book ranges from very high performance circuits for complex wireless infrastructure systems to selected highly integrated systems for handsets and mobile devices. Coverage includes power amplifiers, low-noise amplifiers, modulators, analog-to-digital converters (ADCs) and digital-to-analog converters

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.

Analogies as Creative Inspiration Sources in the Design Studio : The Teamwork

NARCIS (Netherlands)

Casakin, H.; Van Timmeren, A.

2014-01-01

Analogical reasoning can be seen as an important aid in problem solving, and architectural design problem solving in particular. Analogical reasoning was found to be an important aid supporting architectural education. In this paper we explored the use of visual and verbal analogies in the early

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

Directory of Open Access Journals (Sweden)

Sebastian Rabe

2014-07-01

Full Text Available The chemical synthesis of carbacyclopamine analog 2, a cyclopamine analog with an all-carbon E-ring, is reported. The use of C–H-functionalization logic and further metal-catalyzed transformations allows for a concise entry to this new class of acid-stable cyclopamine analogs.

Analogy as a strategy for supporting complex problem solving under uncertainty.

Science.gov (United States)

Chan, Joel; Paletz, Susannah B F; Schunn, Christian D

2012-11-01

Complex problem solving in naturalistic environments is fraught with uncertainty, which has significant impacts on problem-solving behavior. Thus, theories of human problem solving should include accounts of the cognitive strategies people bring to bear to deal with uncertainty during problem solving. In this article, we present evidence that analogy is one such strategy. Using statistical analyses of the temporal dynamics between analogy and expressed uncertainty in the naturalistic problem-solving conversations among scientists on the Mars Rover Mission, we show that spikes in expressed uncertainty reliably predict analogy use (Study 1) and that expressed uncertainty reduces to baseline levels following analogy use (Study 2). In addition, in Study 3, we show with qualitative analyses that this relationship between uncertainty and analogy is not due to miscommunication-related uncertainty but, rather, is primarily concentrated on substantive problem-solving issues. Finally, we discuss a hypothesis about how analogy might serve as an uncertainty reduction strategy in naturalistic complex problem solving.

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).

Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.

Science.gov (United States)

Bukhari, Syed Nasir Abbas; Jantan, Ibrahim

2015-01-01

There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.

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.

Componential Analysis of Analogical-Reasoning Performance of High and Low Achievers.

Science.gov (United States)

Armour-Thomas, Eleanor; Allen, Brenda A.

1990-01-01

Assessed analogical reasoning in high- and low-achieving students at the high school level and determined whether analogical reasoning was related to academic achievement in ninth grade students (N=54). Results indicated that high achievers performed better than low achievers on all types of analogical-reasoning processes. (Author/ABL)

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

An fMRI investigation of cognitive stages in reasoning by analogy.

Science.gov (United States)

Krawczyk, Daniel C; McClelland, M Michelle; Donovan, Colin M; Tillman, Gail D; Maguire, Mandy J

2010-06-25

We compared reasoning about four-term analogy problems in the format (A:B::C: D) to semantic and perceptual control conditions that required matching without analogical mapping. We investigated distinct phases of the problem solving process divided into encoding, mapping/inference, and response. Using fMRI, we assessed the brain activation relevant to each of these phases with an emphasis on achieving a better understanding of analogical reasoning relative to these other matching conditions. We predicted that the analogical condition would involve the most cognitive effort in the encoding and mapping/inference phases, while the control conditions were expected to engage greater prefrontal cortex (PFC) activation at the response period. Results showed greater activation for the analogical condition relative to the control conditions at the encoding phase in several predominantly left lateralized and medial areas of the PFC. Similar results were observed for the mapping/inference phase, though this difference was limited to the left PFC and rostral PFC. The response phase resulted in the fastest and most accurate responses in the analogy condition relative to the control conditions. This was accompanied by greater processing within the left lateral and the medial PFC for the control conditions relative to the analogy condition, consistent with most of the cognitive processing of the analogy condition having occurred in the prior task phases. Overall we demonstrate that the left ventral and dorsal lateral, medial, and rostral PFC are important in both the encoding of relational information, mapping and inference processes, and verification of semantic and perceptual responses in four term analogical reasoning. Copyright 2010 Elsevier B.V. All rights reserved.

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

The neural substrate of analogical reasoning: an fMRI study.

Science.gov (United States)

Luo, Qian; Perry, Conrad; Peng, Danling; Jin, Zhen; Xu, Duo; Ding, Guosheng; Xu, Shiyong

2003-10-01

This study investigated the anatomical substrate of analogical reasoning using functional magnetic resonance imaging. In the study, subjects performed a verbal analogy task (e.g., soldier is to army as drummer is to band) and, to control for activation caused by purely semantic access, a semantic judgment task. Significant activation differences between the verbal analogy and the semantic judgment task were found bilaterally in the prefrontal cortex (right BA 11/BA 47 and left BA45), the fusiform gyrus, and the basal ganglia; left lateralized in the postero-superior temporal gyrus (BA 22) and the (para) hippocampal region; and right lateralized in the anterior cingulate. The role of these areas in analogical reasoning is discussed.

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

21 CFR 582.5477 - Methionine hydroxy analog and its calcium salts.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methionine hydroxy analog and its calcium salts... Nutrients and/or Dietary Supplements 1 § 582.5477 Methionine hydroxy analog and its calcium salts. (a) Product. Methionine hydroxy analog and its calcium salts. (b) [Reserved] (c) Limitations, restrictions, or...

Chimpanzee (Pan troglodytes) relational matching: playing by their own (analogical) rules.

Science.gov (United States)

Flemming, Timothy M; Kennedy, Erica Hoy

2011-05-01

Chimpanzees (Pan troglodytes) have been known to exhibit rudimentary abilities in analogical reasoning (Flemming, Beran, Thompson, Kleider, & Washburn, 2008; Gillian, Premack, & Woodruff, 1981; Haun & Call, 2009; Thompson & Oden, 2000; Thompson, Oden, & Boysen, 1997). With a wide array of individual differences, little can be concluded about the species' capacity for analogies, much less their strategies employed for solving such problems. In this study, we examined analogical strategies in 3 chimpanzees using a 3-dimensional search task (e.g., Kennedy & Fragaszy, 2008). Food items were hidden under 1 of 2 or 3 plastic cups of varying sizes. Subsequently, chimpanzees searched for food under the cup of the same relative size in their own set of cups--reasoning by analogy. Two chimpanzees initially appeared to fail the first relational phase of the task. Meta-analyses revealed, however, that they were instead using a secondary strategy not rewarded by the contingencies of the task--choosing on the basis of the same relative position in the sample. Although this was not the intended strategy of the task, it was nonetheless analogical. In subsequent phases of the task, chimpanzees eventually learned to shift their analogical reasoning strategy to match the reward contingencies of the task and successfully choose on the basis of relative size. This evidence not only provides support for the analogical ape hypothesis (Thompson & Oden, 2000), but also exemplifies how foundational conceptually mediated analogical behavior may be for the chimpanzee. 2011 APA, all rights reserved

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...

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.

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.

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.

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.

Terrestrial Analogs to Mars: NRC Community Panel Decadal Report

Science.gov (United States)

Farr, T. G.

2002-12-01

A report was completed recently by a Community Panel for the NRC Decadal Study of Solar System Exploration. The desire was for a review of the current state of knowledge and for recommendations for action over the next decade. The topic of this panel, Terrestrial Analogs to Mars, was chosen to bring attention to the need for an increase in analog studies in support of the increased pace of Mars exploration. 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 of 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 overarching 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 considered the issues of data collection and archiving, value of field workshops, laboratory measurements and modeling, human exploration issues, association with other areas of solar system exploration, and education and public outreach activities. Parts of this work were performed under contract to NASA.

Revealing the Raft Domain Organization in the Plasma Membrane by Single-Molecule Imaging of Fluorescent Ganglioside Analogs.

Science.gov (United States)

Suzuki, Kenichi G N; Ando, Hiromune; Komura, Naoko; Konishi, Miku; Imamura, Akihiro; Ishida, Hideharu; Kiso, Makoto; Fujiwara, Takahiro K; Kusumi, Akihiro

2018-01-01

Gangliosides have been implicated in a variety of physiological processes, particularly in the formation and function of raft domains in the plasma membrane. However, the scarcity of suitable fluorescent ganglioside analogs had long prevented us from determining exactly how gangliosides perform their functions in the live-cell plasma membrane. With the development of new fluorescent ganglioside analogs, as described by Komura et al. (2017), this barrier has been broken. We can now address the dynamic behaviors of gangliosides in the live-cell plasma membrane, using fluorescence microscopy, particularly by single-fluorescent molecule imaging and tracking. Single-molecule tracking of fluorescent GM1 and GM3 revealed that these molecules are transiently and dynamically recruited to monomers (monomer-associated rafts) and homodimer rafts of the raftophilic GPI-anchored protein CD59 in quiescent cells, with exponential residency times of 12 and 40ms, respectively, in a manner dependent on raft-lipid interactions. Upon CD59 stimulation, which induces CD59-cluster signaling rafts, the fluorescent GM1 and GM3 analogs were recruited to the signaling rafts, with a lifetime of 48ms. These results represent the first direct evidence that GPI-anchored receptors and gangliosides interact in a cholesterol-dependent manner. Furthermore, they show that gangliosides continually move in and out of rafts that contain CD59 in an extremely dynamic manner, with much higher frequency than expected previously. Such studies would not have been possible without fluorescent ganglioside probes, which exhibit native-like behavior and single-molecule tracking. In this chapter, we review the methods for single-molecule tracking of fluorescent ganglioside analogs and the results obtained by applying these methods. © 2018 Elsevier Inc. All rights reserved.

How do Analogizing and Mental Simulation Influence Team Dynamics in Innovative Product Design?

DEFF Research Database (Denmark)

Casakin, Hernan; Ball, Linden J.; Christensen, Bo T.

2015-01-01

association with team cohesion, whereas solution generation and function finding had a stronger association with team collaboration. We propose that analogizing and mental simulations are strategies that serve valuable functions in engendering enhanced cohesion and collaboration, which might be expected...... and team collaboration. Analogies were coded for “analogical distance” (i.e., within domain or between domain) and “analogical purpose” (i.e., problem identification, function finding, solution generation, and explanation). The results indicated that the presence of either analogizing or mental simulation...... was related to team cohesion and team collaboration, with mental simulation having an especially marked association with team collaboration. Within-domain analogizing was found to enhance team collaboration, but it did not influence team cohesion. Furthermore, all types of analogical purpose showed a similar...

PENALARAN ANALOGI SISWA DALAM MENYELESAIKAN MASALAH LUAS DAN KELILING SEGITIGA DAN SEGIEMPAT

Directory of Open Access Journals (Sweden)

Dyah Ayu Pramoda Wardhani

2016-09-01

Penalaran analogi adalah proses penarikan kesimpulan dengan menggunakan kesamaan sifat dan struktur hubungan dari permasalahan sumber untuk diaplikasikan pada permasalahan target. Penelitian ini bertujuan untuk mendeskripsikan penalaran analogi siswa kelas VIII dalam menyelesaikan masalah luas dan keliling segitiga dan segiempat. Pendekatan yang digunakan dalam penelitian ini adalah pendekatan kualitatif dengan jenis penelitian deskriptif. Hasil penelitian ini menunjukkan penalaran analogi siswa kemampuan tinggi terjadi dengan baik. Penalaran analogi siswa kelompok sedang cenderung terjadi cukup baik. Ada beberapa hambatan yang dialami siswa kelompok sedang, yaitu pada proses mapping. Penalaran analogi siswa kemampuan rendah menunjukkan bahwa subjek tidak dapat memahami masalah yang diberikan.

D-hormone analog alfacalcidol: an update on its role in post-menopausal osteoporosis and rheumatoid arthritis management.

Science.gov (United States)

Richy, Florent; Deroisy, Rita; Lecart, Marie-Paule; Hanssens, Linda; Mawet, Audrey; Reginster, Jean-Yves

2005-04-01

Alfacalcidol (1-alpha-hydroxyvitamin D3) is a non-endogenous analog of vitamin D which can bypass the renal and intestinal regulatory mechanisms that control the production of calcitriol (1,25-hydroxyvitamin D3, the active form of vitamin D, D-Hormone). Alfacalcidol may be metabolized into calcitriol with a limited risk of hypercalcemia. Alfacalcidol and calcitriol have been evaluated in animal and human studies assessing their effects on bone mineral density and fracture rates. More recently, they have been shown to produce beneficial effects in muscle, immune system, and autoimmune diseases, including rheumatoid arthritis. This paper discusses the therapeutic efficacy of alfacalcidol in reports in which it has been proposed as an interesting alternative to vitamin D or calcitriol. Some recent findings about general metabolism and regulation of vitamin D and its analogs are discussed. The biological and clinical effects of alfacalcidol in post-menopausal osteoporosis are reviewed, followed by critical appraisal of its efficacy in preventing bone loss and falls in the elderly. The last two sections discuss the role of D analogs in regulating the immune system, with particular regard to rheumatoid arthritis. The main results of this review show that alfacalcidol may have a wider range of therapeutic applicability, beyond simply restricting it to patients in hemodialysis or peritoneal dialysis with high serum levels of intact PTH.

Further evaluation of the tropane analogs of haloperidol.

Science.gov (United States)

Sampson, Dinithia; Bricker, Barbara; Zhu, Xue Y; Peprah, Kwakye; Lamango, Nazarius S; Setola, Vincent; Roth, Bryan L; Ablordeppey, Seth Y

2014-09-01

Previous work from our labs has indicated that a tropane analog of haloperidol with potent D2 binding but designed to avoid the formation of MPP(+)-like metabolites, such as 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)pyridin-1-ium (BCPP(+)) still produced catalepsy, suggesting a strong role for the D2 receptor in the production of catalepsy in rats, and hence EPS in humans. This study tested the hypothesis that further modifications of the tropane analog to produce compounds with less potent binding to the D2 receptor than haloperidol, would produce less catalepsy. These tests have now revealed that while haloperidol produced maximum catalepsy, these compounds produced moderate to low levels of catalepsy. Compound 9, with the least binding affinity to the D2R, produced the least catalepsy and highest Minimum Adverse Effective Dose (MAED) of the analogs tested regardless of their affinities at other receptors including the 5-HT1AR. These observations support the hypothesis that moderation of the D2 binding of the tropane analogs could reduce catalepsy potential in rats and consequently EPS in man. Published by Elsevier Ltd.

Varieties of noise: analogical reasoning in synthetic biology.

Science.gov (United States)

Knuuttila, Tarja; Loettgers, Andrea

2014-12-01

The picture of synthetic biology as a kind of engineering science has largely created the public understanding of this novel field, covering both its promises and risks. In this paper, we will argue that the actual situation is more nuanced and complex. Synthetic biology is a highly interdisciplinary field of research located at the interface of physics, chemistry, biology, and computational science. All of these fields provide concepts, metaphors, mathematical tools, and models, which are typically utilized by synthetic biologists by drawing analogies between the different fields of inquiry. We will study analogical reasoning in synthetic biology through the emergence of the functional meaning of noise, which marks an important shift in how engineering concepts are employed in this field. The notion of noise serves also to highlight the differences between the two branches of synthetic biology: the basic science-oriented branch and the engineering-oriented branch, which differ from each other in the way they draw analogies to various other fields of study. Moreover, we show that fixing the mapping between a source domain and the target domain seems not to be the goal of analogical reasoning in actual scientific practice.

Metabolomic Discovery of Novel Urinary Galabiosylceramide Analogs as Fabry Disease Biomarkers

Science.gov (United States)

Boutin, Michel; Auray-Blais, Christiane

2015-03-01

Fabry disease is an X-linked, complex, multisystemic lysosomal storage disorder presenting marked phenotypic and genotypic variability among affected male and female patients. Glycosphingolipids, mainly globotriaosylceramide (Gb3) isoforms/analogs, globotriaosylsphingosine (lyso-Gb3) and analogs, as well as galabiosylceramide (Ga2) isoforms/analogs accumulate in the vascular endothelium, nerves, cardiomyocytes, renal glomerular and tubular epithelial cells, and biological fluids. The search for biomarkers reflecting disease severity and progression is still on-going. A metabolomic study using quadrupole time-of-flight mass spectrometry has revealed 22 galabiosylceramide isoforms/analogs in urine of untreated Fabry patients classified in seven groups according to their chemical structure: (1) Saturated fatty acid; (2) one extra double bond; (3) two extra double bonds; (4) hydroxylated saturated fatty acid; (5) hydroxylated fatty acid and one extra double bond; (6) hydrated sphingosine and hydroxylated fatty acid; (7) methylated amide linkage. Relative quantification of both Ga2 and Gb3 isoforms/analogs was performed. All these biomarkers are significantly more abundant in urine samples from untreated Fabry males compared with healthy male controls. A significant amount of Ga2 isoforms/analogs, accounting for 18% of all glycosphingolipids analyzed (Ga2 + Gb3 and respective isoforms/analogs), were present in urine of Fabry patients. Gb3 isoforms containing saturated fatty acids are the most abundant (60.9%) compared with 26.3% for Ga2. A comparison between Ga2 isoforms/analogs and their Gb3 counterparts also showed that the proportion of analogs with hydroxylated fatty acids is significantly greater for Ga2 (35.8%) compared with Gb3 (1.9%). These results suggest different biological pathways involved in the synthesis and/or degradation of Gb3 and Ga2 metabolites.

Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

Science.gov (United States)

Vyas, Alok; Dandawate, Prasad; Padhye, Subhash; Ahmad, Aamir; Sarkar, Fazlul

2013-01-01

Curcumin is the active component of dried rhizome of Curcuma longa, a perennial herb belonging to ginger family, cultivated extensively in south and southeastern tropical Asia. It is widely consumed in the Indian subcontinent, south Asia and Japan in traditional food recipes. Extensive research over last few decades has shown that curcumin is a potent anti-inflammatory agent with powerful therapeutic potential against a variety of cancers. It suppresses proliferation and metastasis of human tumors through regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases and other enzymes. It induces apoptotic cell death and also inhibits proliferation of cancer cells by cell cycle arrest. Pharmacokinetic data has shown that curcumin undergoes rapid metabolism leading to glucuronidation and sulfation in the liver and excretion in the feces, which accounts for its poor systemic bioavailability. The compound has, therefore, been formulated and administered using different drug delivery systems such as liposomes, micelles, polysaccharides, phospholipid complexes and nanoparticles that can overcome the limitation of bioavailability to some extent. Attempts to avoid rapid metabolism of curcumin until now have been met with limited success. This has prompted researchers to look for new synthetic curcumin analogs in order to overcome the drawbacks of limited bioavailability and rapid metabolism, and gain efficacy with reduced toxicity. In this review we provide a summarized account of novel synthetic curcumin formulations and analogs, and the recent progress in the field of cancer prevention and treatment. PMID:23116312

Preventive effect of dexketoprofen on postoperative pain.

Science.gov (United States)

Gelir, İsmail Kerem; Güleç, Sacit; Ceyhan, Dilek

2016-04-01

Preventive analgesia has been defined as reduction in noxious stimuli during preoperative, intraoperative, and postoperative periods. The aim of the present study was to prevent central sensitization by administering ketamine infusion throughout the surgical procedure. In addition, possible preventive effects of dexketoprofen when administered before and after incision were evaluated. Fifty patients were included. Group I was administered 50 mg intravenous dexketoprofen prior to surgical incision, and Group II received the same amount 10 minutes after the incision had been made. Following induction of general anesthesia, all patients received a bolus of 0.50 mg/kg ketamine in 0.07 mg/kg/h intravenous infusion. When postoperative visual analog scale values were compared, values for Group I after 1 and 4 hours were significantly lower than those of Group II. In addition, morphine consumption at 4, 8, 12, and 24 hours was significantly lower in Group I. Combined with the prevention of central sensitization with ketamine, administration of dexketoprofen prior to incision led to a lower rate of morphine consumption and more effective analgesia than post-incision administration.

Analogy-Integrated e-Learning Module: Facilitating Students' Conceptual Understanding

Science.gov (United States)

Florida, Jennifer

2012-01-01

The study deals with the development of an analogy-integrated e-learning module on Cellular Respiration, which is intended to facilitate conceptual understanding of students with different brain hemisphere dominance and learning styles. The module includes eight analogies originally conceptualized following the specific steps used to prepare…

Real time event selection and flash analog-to-digital converters

International Nuclear Information System (INIS)

Imori, Masatosi

1983-01-01

In high-energy particle experiments, high-speed analog logic is employed to select events on a real-time basis. Flash analog-to-digital converters replace the high-speed analog logic with digital logic. The digital logic gives great flexibility to the scheme for real-time event selection. This paper proposes the use of flash A/D converters for the logic used to obtain the total sum of the energy deposited in individual counters in a shower detector. (author)

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

CMOS analog integrated circuits high-speed and power-efficient design

CERN Document Server

Ndjountche, Tertulien

2011-01-01

High-speed, power-efficient analog integrated circuits can be used as standalone devices or to interface modern digital signal processors and micro-controllers in various applications, including multimedia, communication, instrumentation, and control systems. New architectures and low device geometry of complementary metaloxidesemiconductor (CMOS) technologies have accelerated the movement toward system on a chip design, which merges analog circuits with digital, and radio-frequency components. CMOS: Analog Integrated Circuits: High-Speed and Power-Efficient Design describes the important tren

Programs for control of an analog-signal switching network

International Nuclear Information System (INIS)

D'Ottavio, T.; Enriquez, R.; Katz, R.; Skelly, J.

1989-01-01

A suite of programs has been developed to control the network of analog-signal switching multiplexers in the AGS complex. The software is driven by a relational database which describes the architecture of the multiplexer tree and the set of available analog signals. Signals are routed through a three-layer multiplexer tree, to be made available at four consoles each with three 4-trace oscilloscopes. A menu-structured operator interface program is available at each console, to accept requests to route any available analog signal to any of that console's 12 oscilloscope traces. A common routing-server program provides automatic routing-server program provides automatic routing of requested signals through the layers of multiplexers, maintaining a reservation database to denote free and in-use trunks. Expansion of the analog signal system is easily accommodated in software by adding new signals, trunks, multiplexers, or consoles to the database. Programmatic control of the triggering signals for each of the oscilloscopes is also provided. 3 refs., 4 figs., 3 tabs

Concept Confusion and Concept Discernment in Basic Magnetism Using Analogical Reasoning

Science.gov (United States)

Lemmer, Miriam; Morabe, Olebogeng Nicodimus

2017-01-01

Analogical reasoning is central to all learning, whether in daily life situations, in the classroom or while doing research. Although analogies can aid the learning process of making sense of phenomena and understanding new ideas in terms of known ideas, these should be used with care. This article reports a study of the use of analogies and the…

The Great Depression and the Great Recession: A Comparative Analysis of their Analogies

Directory of Open Access Journals (Sweden)

Cristina Peicuti

2014-06-01

Full Text Available The decades preceding the Great Depression and the U.S. subprime mortgage crisis have close similarities. Both decades were characterized by rapid growth without major contractions, by an increase in liquidity, a lack of inflation, and a generalized decrease in risk premiums. Additional similarities included significant changes in the financing of real estate by commercial banks along with a consolidation of the banking sector and high hopes that the efficiency of monetary policy would prevent financial crises. These decades were also characterized by the consolidation of the powers of young central banks (the Federal Reserve System in the 1920s and the European Central Bank in the 2000s, by unsuccessful attempts to control market speculation, by their international dimensions, and by the eruption of crises after the failure of a major American financial institution that could have been avoided. Understanding these analogies help us better identify the causes of the subprime mortgage crisis and prevent history from repeating itself to the extentof such large-scale devastating consequences.

Connecting long distance: semantic distance in analogical reasoning modulates frontopolar cortex activity.

Science.gov (United States)

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

2010-01-01

Solving problems often requires seeing new connections between concepts or events that seemed unrelated at first. Innovative solutions of this kind depend on analogical reasoning, a relational reasoning process that involves mapping similarities between concepts. 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 characteristic of the kind of analogical mapping that can support innovation (i.e., identifying similarities across greater semantic distance reveals connections that support more innovative solutions and models). However, the neural substrates of semantically distant analogical mapping are not well understood. Here, we used functional magnetic resonance imaging (fMRI) to measure brain activity during an analogical reasoning task, in which we parametrically varied the semantic distance between the items in the analogies. Semantic distance was derived quantitatively from latent semantic analysis. Across 23 participants, activity in an a priori region of interest (ROI) in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. This ROI was centered on a functional peak that we previously associated with analogical mapping. To our knowledge, these data represent a first empirical characterization of how the brain mediates semantically distant analogical mapping.

Barrier analogs: Long-term performance issues, preliminary studies, and recommendations

Energy Technology Data Exchange (ETDEWEB)

Waugh, W.J. [Rust Geotech, Inc., Grand Junction, CO (United States). Environmental Sciences Lab.; Chatters, J.C.; Last, G.V.; Bjornstad, B.N.; Link, S.O. [Pacific Northwest Lab., Richland, WA (United States); Hunter, C.R. [Cascade Earth Sciences, La Grande, OR (United States)

1994-02-01

The US Department of Energy`s Hanford Protective Barrier Development Program is funding studies of natural analogs of the long-term performance of waste site covers. Natural-analog studies examine past environments as evidence for projecting the future performance of engineered structures. The information generated by analog studies is needed to (1) evaluate the designs and results of short term experiments and demonstrations, (2) formulate performance-modeling problems that bound expected changes in waste site environments, and (3) understand emergent system attributes that cannot be evaluated with short-term experiments or computer models. Waste site covers will be part of dynamic environmental systems with attributes that transcend the traits of engineered components. This report discusses results of the previously unreported preliminary studies conducted in 1983 and 1984. These results indicate that analogs could play an important role in predicting the long-term behavior of engineered waste covers. Layered exposures of glacial-flood-deposited gravels mantled with silt or sand that resemble contemporary barrier designs were examined. Bergmounds, another anomaly left by cataclysmic glacial floods, were also examined as analogs of surface gravel.

Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

Science.gov (United States)

Jha, Narendra Nath; Ghosh, Dhiman; Das, Subhadeep; Anoop, Arunagiri; Jacob, Reeba S.; Singh, Pradeep K.; Ayyagari, Narasimham; Namboothiri, Irishi N. N.; Maji, Samir K.

2016-01-01

Alpha-synuclein (α-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson’s disease (PD) pathogenesis. Compounds that modulate α-Syn aggregation and interact with preformed fibrils/oligomers and convert them to less toxic species could have promising applications in the drug development efforts against PD. Curcumin is one of the Asian food ingredient which showed promising role as therapeutic agent against many neurological disorders including PD. However, the instability and low solubility makes it less attractive for the drug development. In this work, we selected various curcumin analogs and studied their toxicity, stability and efficacy to interact with different α-Syn species and modulation of their toxicity. We found a subset of curcumin analogs with higher stability and showed that curcumin and its various analogs interact with preformed fibrils and oligomers and accelerate α-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed α-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating α-Syn aggregation. PMID:27338805

Moving Toward Bioadjuvant Approaches to Head and Neck Cancer Prevention

International Nuclear Information System (INIS)

Saba, Nabil F.; Hammond, Anthea; Shin, Dong M.; Khuri, Fadlo R.

2007-01-01

Head and neck squamous cell carcinoma affects >45,000 Americans annually. Patients who are successfully treated for their primary tumor are at high risk of developing a second primary tumor, making effective preventive strategies highly desirable for this disease. Although a landmark study in 1990 suggested some benefit of high-dose retinoids in head and neck cancer prevention, subsequent trials using more tolerable doses have shown limited clinical success. Newer preventive strategies have included bioadjuvant therapy combining retinoids with interferon and α-tocopherol, combinations of molecularly targeted agents, and oncolytic viruses. Furthermore, considerable evidence has supported a cancer protective role for several nutrients, including green tea and curcumin analogs. Natural compounds such as these with favorable long-term safety profiles might be particularly suited to the cancer prevention setting, in which patients will usually tolerate only moderate risk and toxicity

Using Analogies in Teaching Physics: A Study on Latvian Teachers' Views and Experience

Science.gov (United States)

Jonane, Lolita

2015-01-01

The role of analogies as tools for teaching difficult science concepts has been widely discussed in science education. The application of analogies in the context of sustainable education involves richer potential. The purposeful use of appropriate analogies can facilitate analogical thinking and transfer skills, as well as develop abilities which…

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.

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...

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…

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...

Electrochemical deposition of magnesium from analogous ionic liquid based on dimethylformamide

International Nuclear Information System (INIS)

Wang, Huaiyou; Jia, Yongzhong; Wang, Xiaohua; Yao, Ying; Yue, Duyuan; Jing, Yan

2013-01-01

In this paper, a homogeneous, colorless analogous ionic liquid containing dimethylformamide (DMF) and magnesium chloride hexahydrate is synthesized. The conductivity of analogous ionic liquid is measured as a function of temperature and composition. Irreversible electrochemical behavior was generally observed by cyclic voltammetry (CV) in the analogous ionic liquid based electrolytes containing simple Mg salt. CV also shows that the reducing reaction of Mg 2+ is a diffusion control process. Electrochemical impedance spectroscopy (EIS) of analogous ionic liquid was measured at 20 °C, 40 °C and 60 °C. Electrodeposition of magnesium metal from analogous ionic liquid has been studied. The Mg deposits are also systematically characterized by the techniques of powder X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). Results showed that magnesium was found in the deposited film

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.

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

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

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

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

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.

On automatic synthesis of analog/digital circuits

Energy Technology Data Exchange (ETDEWEB)

Beiu, V.

1998-12-31

The paper builds on a recent explicit numerical algorithm for Kolmogorov`s superpositions, and will show that in order to synthesize minimum size (i.e., size-optimal) circuits for implementing any Boolean function, the nonlinear activation function of the gates has to be the identity function. Because classical and--or implementations, as well as threshold gate implementations require exponential size, it follows that size-optimal solutions for implementing arbitrary Boolean functions can be obtained using analog (or mixed analog/digital) circuits. Conclusions and several comments are ending the paper.

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.

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…

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…

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.

Analog Organic Electronics Building Blocks for Organic Smart Sensor Systems on Foil

CERN Document Server

Marien, Hagen; Heremans, Paul

2013-01-01

 This book provides insight into organic electronics technology and in analog circuit techniques that can be used to increase the performance of both analog and digital organic circuits. It explores the domain of organic electronics technology for analog circuit applications, specifically smart sensor systems.  It focuses on all the building blocks in the data path of an organic sensor system between the sensor and the digital processing block. Sensors, amplifiers, analog-to-digital converters and DC-DC converters are discussed in detail. Coverage includes circuit techniques, circuit implementation, design decisions and measurement results of the building blocks described. Offers readers the first book to focus on analog organic circuit design; Discusses organic electronics technology for analog circuit applications in the context of smart sensor systems; Describes all building blocks necessary for an organic sensor system between the sensor and the digital processing block; Includes circuit techniques, cir...

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.

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...

A Kolmogorov Complexity View of Analogy: From Logical Modeling to Experimentations

Science.gov (United States)

Bayoudh, Meriam; Prade, Henri; Richard, Gilles

Analogical reasoning is considered as one of the main mechanisms underlying human intelligence and creativity, allowing the paradigm shift essential to a creative process. More specific is the notion of analogical proportion like "2 is to 4 as 5 is to 10" or "read is to reader as lecture is to lecturer": such statements can be precisely described within an algebraic framework. When the proportion holds between concepts as in "engine is to car as heart is to human" or "wine is to France as beer is to England", applying an algebraic framework is less straightforward and a new way to understand analogical proportions on the basis of Kolmogorov complexity theory may seem more appropriate. This viewpoint has been used to develop a classifier detecting analogies in natural language. Despite their apparent difference, it is quite clear that the two viewpoints should be strongly related. In this paper, we investigate the link between a purely abstract view of analogical proportions and a definition based on Kolmogorov complexity theory. This theory is used as a backbone to experiment a classifier of natural language analogies whose results are consistent with the abstract setting.

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.

Toward a 62.5 MHz analog virtual pipeline integrated data acquisition system

International Nuclear Information System (INIS)

Kleinfelder, S.A.; Levi, M.; Milgrome, O.

1991-01-01

Requirements of analog pipeline memories at the SSC are reviewed and the concept of virtual pipelines is introduced. Design details and test results of several new custom analog and digital integrated circuits implementing sections of the virtual multiple pipeline (VMP) scheme are provied. These include serial, random access and simultaneous read and write random access analog storage and retrieval circuits, a 100 MHz systolic variable depth digital pipeline, and a prototye 32 μs, 12 bit serial analog to digital converter. (orig.)

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)

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.

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.

Verbal and perceptual analogical reasoning and proportional metaphor comprehension in young children.

Science.gov (United States)

Nippold, M A; Sullivan, M P

1987-09-01

In contrast to the common assumption that young children have little or no ability to reason by analogy or to comprehend proportional metaphors, the present study demonstrated that children as young as age 5 years have an emerging ability to solve both verbal and perceptual proportional analogy problems and to detect the meanings of proportional metaphoric sentences. These results were largely because the experimental tasks were designed to minimize the number of factors that would restrict the performance of young children. The results indicated that the years between 5 and 7 mark a steady improvement in analogical reasoning and proportional metaphor comprehension, but that children ages 5, 6, and 7 display a wide-ranging ability in these areas. It was also found that perceptual analogical reasoning was statistically related to verbal analogical reasoning and to proportional metaphor comprehension, and that perceptual analogical reasoning and proportional metaphor comprehension were both statistically related to receptive vocabulary development.

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.)

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

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…

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…

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

Configurable Analog-Digital Conversion Using the Neural EngineeringFramework

Directory of Open Access Journals (Sweden)

Christian G Mayr

2014-07-01

Full Text Available Efficient Analog-Digital Converters (ADC are one of the mainstays of mixed-signal integrated circuit design. Besides the conventional ADCs used in mainstream ICs, there have been various attempts in the past to utilize neuromorphic networks to accomplish an efficient crossing between analog and digital domains, i.e. to build neurally inspired ADCs. Generally, these have suffered from the same problems as conventional ADCs, that is they require high-precision, handcrafted analog circuits and are thus not technology portable. In this paper, we present an ADC based on the Neural Engineering Framework (NEF. It carries out a large fraction of the overall ADC process in the digital domain, i.e. it is easily portable across technologies. The analog-digital conversion takes full advantage of the high degree of parallelism inherent in neuromorphic networks, making for a very scalable ADC. In addition, it has a number of features not commonly found in conventional ADCs, such as a runtime reconfigurability of the ADC sampling rate, resolution and transfer characteristic.

The effect of benfothiamine in the therapy of diabetic polyneuropathy

Directory of Open Access Journals (Sweden)

Nikolić Ana

2009-01-01

Full Text Available Introduction. Diabetic polyneuropathy (DPN is one of the most common diabetic complications, which can result in a significant functional impairment and reduction of the quality of life in affected individuals. It occurs due to alterations in different biochemical mechanisms which require the presence of thiamine, which is why this vitamin is used in the therapy of DPN. Due to the low bioavailability of the hydrosolubile forms of thiamine, its liposolubile preparations (benfotiamine are preferentially used. Objective. The aim of this study was to determine the efficacy of benfotiamine in combination with vitamin B6 in the therapy of DPN. Methods. The study group comprised of 22 patients with DPN who were treated with the combination of benfotiamine and vitamin B6 during 45 days. The effect of the therapy was evaluated by the analysis of different clinical, laboratory and electrophysiological parameters before and after conducted treatment. Results. After the treatment period, a statistically highly significant reduction of pain (p<0.01 was noted with the reduction of pain score on visual analogue scale in 86.4% of patients. A significant reduction of subjective complaints was also noted, with decreased modified total symptom score in 95.5% of patients (p<0.01. The presence of alodynia was reported at the beginning of the study in 77.3%, and after the benfotiamine therapy only in 22.7% of patients, while hyperpathy was initially present in 90.9%, and after treatment in 31.8% of patients (p<0,01. Neurophysiological parameters of polyneuropathy also significantly improved, with the improvement of the compound muscle action potential amplitude in 68.2% (p<0.01 and motor conduction velocity of the peroneal nerve in 45.5% of patients (p<0.01. The improvement of the sensory nerve action potential amplitude (p<0.01 and sensory conduction velocity (p=0.05 of the sural nerve was found in 45.5% of patients. After the treatment period, there was a highly

Single-event effects in analog and mixed-signal integrated circuits

International Nuclear Information System (INIS)

Turflinger, T.L.

1996-01-01

Analog and mixed-signal integrated circuits are also susceptible to single-event effects, but they have rarely been tested. Analog circuit single-particle transients require modified test techniques and data analysis. Existing work is reviewed and future concerns are outlined

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.

Digital redesign of anti-wind-up controller for cascaded analog system.

Science.gov (United States)

Chen, Y S; Tsai, J S H; Shieh, L S; Moussighi, M M

2003-01-01

The cascaded conventional anti-wind-up (CAW) design method for integral controller is discussed. Then, the prediction-based digital redesign methodology is utilized to find the new pulse amplitude modulated (PAM) digital controller for effective digital control of the analog plant with input saturation constraint. The desired digital controller is determined from existing or pre-designed CAW analog controller. The proposed method provides a novel methodology for indirect digital design of a continuous-time unity output-feedback system with a cascaded analog controller as in the case of PID controllers for industrial control processes with the presence of actuator saturations. It enables us to implement an existing or pre-designed cascaded CAW analog controller via a digital controller effectively.

Analogies between Heavy Metal Music and the Symptoms of Mental Illness

Directory of Open Access Journals (Sweden)

David G. Angeler

2018-04-01

Full Text Available This paper builds a link between isolated domains within the arts and sciences, specifically between music and psychiatry. An analogous model is presented that associates heavy metal music with bipolar disorder, a form of mental illness. Metal music consists of a variety of subgenres with distinct manifestations of song, rhythm, instrumentation, and vocal structure. These manifestations are analogous to the symptomatology of bipolar disorder, specifically the recurrent episodes of (hypomania and depression. Examples of songs are given which show these analogies. Besides creating a subjective link between apparently unconnected knowledge domains, these analogies could play a heuristic role in clinical applications and education about the disorder and mental illnesses at large.

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…

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...

Morphometry of Left Frontal and Temporal Poles Predicts Analogical Reasoning Abilities.

Science.gov (United States)

Aichelburg, Clarisse; Urbanski, Marika; Thiebaut de Schotten, Michel; Humbert, Frederic; Levy, Richard; Volle, Emmanuelle

2016-03-01

Analogical reasoning is critical for making inferences and adapting to novelty. It can be studied experimentally using tasks that require creating similarities between situations or concepts, i.e., when their constituent elements share a similar organization or structure. Brain correlates of analogical reasoning have mostly been explored using functional imaging that has highlighted the involvement of the left rostrolateral prefrontal cortex (rlPFC) in healthy subjects. However, whether inter-individual variability in analogical reasoning ability in a healthy adult population is related to differences in brain architecture is unknown. We investigated this question by employing linear regression models of performance in analogy tasks and voxel-based morphometry in 54 healthy subjects. Our results revealed that the ability to reason by analogy was associated with structural variability in the left rlPFC and the anterior part of the inferolateral temporal cortex. Tractography of diffusion-weighted images suggested that these 2 regions have a different set of connections but may exchange information via the arcuate fasciculus. These results suggest that enhanced integrative and semantic abilities supported by structural variation in these areas (or their connectivity) may lead to more efficient analogical reasoning. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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)

Analogical reasoning and prefrontal cortex: evidence for separable retrieval and integration mechanisms.

Science.gov (United States)

Bunge, Silvia A; Wendelken, Carter; Badre, David; Wagner, Anthony D

2005-03-01

The present study examined the contributions of prefrontal cortex (PFC) subregions to two component processes underlying verbal analogical reasoning: semantic retrieval and integration. Event-related functional magnetic resonance imaging data were acquired while subjects performed propositional analogy and semantic decision tasks. On each trial, subjects viewed a pair of words (pair 1), followed by an instructional cue and a second word pair (pair 2). On analogy trials, subjects evaluated whether pair 2 was semantically analogous to pair 1. On semantic trials, subjects indicated whether the pair 2 words were semantically related to each other. Thus, analogy--but not semantic--trials required integration across multiple retrieved relations. To identify regions involved in semantic retrieval, we manipulated the associative strength of pair 1 words in both tasks. Anterior left inferior PFC (aLIPC) was modulated by associative strength, consistent with a role in controlled semantic retrieval. Left frontopolar cortex was insensitive to associative strength, but was more sensitive to integration demands than was aLIPC, consistent with a role in integrating the products of semantic retrieval to evaluate whether distinct representations are analogous. Right dorsolateral PFC exhibited a profile consistent with a role in response selection rather than retrieval or integration. These findings indicate that verbal analogical reasoning depends on multiple, PFC-mediated computations.

Population and particle decay of isobaric analog states in medium heavy nuclei

International Nuclear Information System (INIS)

Gales, S.

1980-05-01

The systematic features of proton stripping and neutron pick-up reactions to Isobaric Analog States in medium heavy nuclei are presented. The ( 3 He,d) reaction investigated at high incident energy is shown to selectively excite high-spin particle-analog states. Similarly the ( 3 He,α) reaction populates hole-analog states. The recent results related to such highly excited states in a wide range of nuclei ( 48 Ca to 208 Pb) are discussed in the framework of the DWBA theory of direct reactions with special emphasis on the treatment of unbound proton states or deeply-bound neutron hole states. The particle decay of Isobaric Analog States are investigated using the ( 3 He,d p) and ( 3 He, α p) sequential processes. The experimental method developed at Orsay (0 0 detection) for particle-particle angular correlations is presented. The advantage and the limits of such approach are illustrated by typical examples of particle decays: core-excited states, neutron particle-hole multiplets and the first observation of the proton emission of hole-analog levels. In conclusion new experimental approaches such as asymmetry measurements for analog states observed in transfer reactions or possible population of double analog states in heavy nuclei are discussed

Low-voltage current-mode CMOS building blocks for field programmable analog arrays and application

International Nuclear Information System (INIS)

Madian, A.H.K.

2007-01-01

The role of analog integrated circuits in modem electronic systems remains important, even though digital circuits dominate the market for VLSI solutions. Analog systems have always played an essential role in interfacing digital electronics to the real world in applications such as analog signal processing and signal conditioning .Industrial process and motion control and biomedical measurements . In addition, analog solutions are becoming increasingly competitive with digital circuits for dense, low-power, high-speed applications in low-precision signal-processing. Because of the wide variety of analog functions required in electronic systems and the complexity of the signals (frequency, time, signal levels, parasitic), analog system design is very specialized and supported by a diverse set of CAD tools that are more difficult to integrate than those required for digital design. The drive towards shorter design cycles for analog integrated circuits has demanded the development of high performance analog circuits that are re configurable and suitable for CAD methodologies. the researcher here try to contribute in this filed

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)

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.

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.

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

Low-power analog integrated circuits for wireless ECG acquisition systems.

Science.gov (United States)

Tsai, Tsung-Heng; Hong, Jia-Hua; Wang, Liang-Hung; Lee, Shuenn-Yuh

2012-09-01

This paper presents low-power analog ICs for wireless ECG acquisition systems. Considering the power-efficient communication in the body sensor network, the required low-power analog ICs are developed for a healthcare system through miniaturization and system integration. To acquire the ECG signal, a low-power analog front-end system, including an ECG signal acquisition board, an on-chip low-pass filter, and an on-chip successive-approximation analog-to-digital converter for portable ECG detection devices is presented. A quadrature CMOS voltage-controlled oscillator and a 2.4 GHz direct-conversion transmitter with a power amplifier and upconversion mixer are also developed to transmit the ECG signal through wireless communication. In the receiver, a 2.4 GHz fully integrated CMOS RF front end with a low-noise amplifier, differential power splitter, and quadrature mixer based on current-reused folded architecture is proposed. The circuits have been implemented to meet the specifications of the IEEE 802.15.4 2.4 GHz standard. The low-power ICs of the wireless ECG acquisition systems have been fabricated using a 0.18 μm Taiwan Semiconductor Manufacturing Company (TSMC) CMOS standard process. The measured results on the human body reveal that ECG signals can be acquired effectively by the proposed low-power analog front-end ICs.

Automatic Generation of Analogy Questions for Student Assessment: An Ontology-Based Approach

Science.gov (United States)

Alsubait, Tahani; Parsia, Bijan; Sattler, Uli

2012-01-01

Different computational models for generating analogies of the form "A is to B as C is to D" have been proposed over the past 35 years. However, analogy generation is a challenging problem that requires further research. In this article, we present a new approach for generating analogies in Multiple Choice Question (MCQ) format that can be used…

Synthesis of I-125 labeled photoaffinity rapamycin analogs

International Nuclear Information System (INIS)

Shu, A.Y.L.; Yamashita, D.S.; Holt, D.A.; Heys, J.R.

1996-01-01

Two no-carrier-added 125 I-labelled photoaffinity rapamycin analogs were prepared: 7-demethoxy-7-(4-azido-3- 125 I-benzyloxy) rapamycin and its C 28 -C 29 seco analog. The key reactions of the synthesis were substitution of the C 7 methoxyl of rapamycin with 4-azido-3-tributylstannylbenzyloxy group, exchange of tributyltin with 125 I using Na 125 I and Chloramine-T, and a ZnCl 2 mediated retro-Aldol cleavage of the C 28 -C 29 bond of rapamycin. (author)

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...

Two functions of analogical reasoning in design. A cognitive-psychology approach

OpenAIRE

Visser , Willemien

1996-01-01

International audience; On the basis of data collected in three empirical studies conducted on industrial designers, this paper identifies two different types of "spontaneous" use of analogy in design. Focus is on the first "stages" of analogical reasoning, i.e. construction of a target representation, and search and retrieval of a source. At the action-execution level, analogies are used in order to solve the current design problem; at the action-management level, in order to make the action...

Reasoning by analogy requires the left frontal pole: lesion-deficit mapping and clinical implications.

Science.gov (United States)

Urbanski, Marika; Bréchemier, Marie-Laure; Garcin, Béatrice; Bendetowicz, David; Thiebaut de Schotten, Michel; Foulon, Chris; Rosso, Charlotte; Clarençon, Frédéric; Dupont, Sophie; Pradat-Diehl, Pascale; Labeyrie, Marc-Antoine; Levy, Richard; Volle, Emmanuelle

2016-06-01

SEE BURGESS DOI101093/BRAIN/AWW092 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : Analogical reasoning is at the core of the generalization and abstraction processes that enable concept formation and creativity. The impact of neurological diseases on analogical reasoning is poorly known, despite its importance in everyday life and in society. Neuroimaging studies of healthy subjects and the few studies that have been performed on patients have highlighted the importance of the prefrontal cortex in analogical reasoning. However, the critical cerebral bases for analogical reasoning deficits remain elusive. In the current study, we examined analogical reasoning abilities in 27 patients with focal damage in the frontal lobes and performed voxel-based lesion-behaviour mapping and tractography analyses to investigate the structures critical for analogical reasoning. The findings revealed that damage to the left rostrolateral prefrontal region (or some of its long-range connections) specifically impaired the ability to reason by analogies. A short version of the analogy task predicted the existence of a left rostrolateral prefrontal lesion with good accuracy. Experimental manipulations of the analogy tasks suggested that this region plays a role in relational matching or integration. The current lesion approach demonstrated that the left rostrolateral prefrontal region is a critical node in the analogy network. Our results also suggested that analogy tasks should be translated to clinical practice to refine the neuropsychological assessment of patients with frontal lobe lesions. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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)

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.

Neural underpinnings of divergent production of rules in numerical analogical reasoning.

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Wu, Xiaofei; Jung, Rex E; Zhang, Hao

2016-05-01

Creativity plays an important role in numerical problem solving. Although the neural underpinnings of creativity have been studied over decades, very little is known about neural mechanisms of the creative process that relates to numerical problem solving. In the present study, we employed a numerical analogical reasoning task with functional Magnetic Resonance Imaging (fMRI) to investigate the neural correlates of divergent production of rules in numerical analogical reasoning. Participants performed two tasks: a multiple solution analogical reasoning task and a single solution analogical reasoning task. Results revealed that divergent production of rules involves significant activations at Brodmann area (BA) 10 in the right middle frontal cortex, BA 40 in the left inferior parietal lobule, and BA 8 in the superior frontal cortex. The results suggest that right BA 10 and left BA 40 are involved in the generation of novel rules, and BA 8 is associated with the inhibition of initial rules in numerical analogical reasoning. The findings shed light on the neural mechanisms of creativity in numerical processing. Copyright © 2016 Elsevier B.V. All rights reserved.

Analogical thinking in ecology: looking beyond disciplinary boundaries.

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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.

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.

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.

Analogical scaffolding and the learning of abstract ideas in physics: Empirical studies

Directory of Open Access Journals (Sweden)

Noah S. Podolefsky

2007-09-01

Full Text Available Previously, we proposed a model of student reasoning which combines the roles of representation, analogy, and layering of meaning—analogical scaffolding [Podolefsky and Finkelstein, Phys. Rev. ST Phys. Educ. Res. 3, 010109 (2007]. The present empirical studies build on this model to examine its utility and demonstrate the vital intertwining of representation, analogy, and conceptual learning in physics. In two studies of student reasoning using analogy, we show that representations couple to students’ existing prior knowledge and also lead to the dynamic formation of new knowledge. Students presented with abstract, concrete, or blended (both abstract and concrete representations produced markedly different response patterns. In the first study, using analogies to scaffold understanding of electromagnetic (EM waves, students in the blend group were more likely to reason productively about EM waves than students in the abstract group by as much as a factor of 3 (73% vs 24% correct, p=0.002. In the second study, examining representation use within one domain (sound waves, the blend group was more likely to reason productively about sound waves than the abstract group by as much as a factor of 2 (48% vs 23% correct, p=0.002. Using the analogical scaffolding model we examine when and why students succeed and fail to use analogies and interpret representations appropriately.

Analogical scaffolding and the learning of abstract ideas in physics: Empirical studies

Directory of Open Access Journals (Sweden)

Noah D. Finkelstein

2007-09-01

Full Text Available Previously, we proposed a model of student reasoning which combines the roles of representation, analogy, and layering of meaning—analogical scaffolding [Podolefsky and Finkelstein, Phys. Rev. ST Phys. Educ. Res. 3, 010109 (2007]. The present empirical studies build on this model to examine its utility and demonstrate the vital intertwining of representation, analogy, and conceptual learning in physics. In two studies of student reasoning using analogy, we show that representations couple to students’ existing prior knowledge and also lead to the dynamic formation of new knowledge. Students presented with abstract, concrete, or blended (both abstract and concrete representations produced markedly different response patterns. In the first study, using analogies to scaffold understanding of electromagnetic (EM waves, students in the blend group were more likely to reason productively about EM waves than students in the abstract group by as much as a factor of 3 (73% vs 24% correct, p=0.002 . In the second study, examining representation use within one domain (sound waves, the blend group was more likely to reason productively about sound waves than the abstract group by as much as a factor of 2 (48% vs 23% correct, p=0.002 . Using the analogical scaffolding model we examine when and why students succeed and fail to use analogies and interpret representations appropriately.

Use of the "Tree" Analogy in Evolution Teaching by Biology Teachers

Science.gov (United States)

Marcelos, Maria Fátima; Nagem, Ronaldo Luiz

2012-04-01

This work discusses the use of Darwin's `Tree of Life' as a didactic analogy and metaphor in teaching evolution. It investigates whether biology teachers of pupils from 17 to 18 years old know Darwin's text `Tree of Life'. In addition, it examines whether those teachers systematically employ either the analogies present in that text or other analogies between the tree and evolution, and whether they adopt a specific methodology for teaching with analogies and metaphors (A&M). The academic training of teachers regarding use of A&M is review briefly. A diagnostic study was carried out with biology teachers in a public school in the town of Contagem in the state of Minas Gerais in Brazil. The data were obtained through direct observation, questionnaires and a focus group. The teachers pointed out in the questionnaires that some details of Darwin's analogy are utilized as a resource. However, analysis of the data indicates that the `Tree of Life' text is not known or utilized in class. At the same time, the teachers state that they use aspects of the tree as a didactic resource to teach evolution and that its use facilitates the learning of content. The teachers have little knowledge of specific methodologies of teaching with analogies and metaphors, revealing that their training is incomplete in this area.

Categories children find easy and difficult to process in figural analogies

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Claire E Stevenson

2014-08-01

Full Text Available Analogical reasoning, the ability to learn about novel phenomena by relating it to structurally similar knowledge, develops with great variability in children. Furthermore, the development of analogical reasoning coincides with greater working memory efficiency and increasing knowledge of the objects and rules present in analogy problems. In figural matrices, a classical form of analogical reasoning assessment, some categories, such as color, appear easier for children to encode and infer than others, such as orientation. Yet, few studies have structurally examined differences in the difficulty of rule-types across different age-groups. This cross-sectional study of figural analogical reasoning examined which underlying rules in figural analogies were easier or more difficult for children to correctly process. School children (N=1422, M=7.0 years, SD=21 months, range 4.5-12.5 years were assessed in analogical reasoning using classical figural matrices and memory measures. The transformations the children had to induce and apply concerned the categories: animal, color, orientation, position, quantity and size. The role of age and memory span on the children’s ability to correctly process each type of transformation was examined using explanatory item response theory models. The results showed that with increasing age and/or greater memory span all transformations were processed more accurately. The what transformations animal, color, quantity and size were easiest, whereas the where transformations orientation and position were most difficult. However, animal, orientation and position became relatively easier with age and increased memory efficiency. The implications are discussed in terms of the development of visual processing in object recognition versus position and motion encoding, the ventral (what and dorsal (where pathways respectively.

Nyquist AD Converters, Sensor Interfaces, and Robustness Advances in Analog Circuit Design, 2012

CERN Document Server

Baschirotto, Andrea; Steyaert, Michiel

2013-01-01

This book is based on the presentations during the 21st workshop on Advances in Analog Circuit Design.  Expert designers provide readers with information about a variety of topics at the frontier of analog circuit design, including Nyquist analog-to-digital converters, capacitive sensor interfaces, reliability, variability, and connectivity.  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 Nyquist A/D converters, capacitive sensor interfaces, reliability, variability, and connectivity.

Developing a 300C Analog Tool for EGS

Energy Technology Data Exchange (ETDEWEB)

Normann, Randy

2015-03-23

This paper covers the development of a 300°C geothermal well monitoring tool for supporting future EGS (enhanced geothermal systems) power production. This is the first of 3 tools planed. This is an analog tool designed for monitoring well pressure and temperature. There is discussion on 3 different circuit topologies and the development of the supporting surface electronics and software. There is information on testing electronic circuits and component. One of the major components is the cable used to connect the analog tool to the surface.

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

PA03.05. Masha taila as a preventive measure in gulpha marma injuries.

Science.gov (United States)

Dhaded, Rajani; Kulkarni, BG

2013-01-01

Purpose: In Basketball game Gulpha Marma injuries are common. Wrong landing causes inflammation & tearing of ligament resulting into sprain. Prevention can be carried out by protective wears like Ankelet,crape bandge which gives temporary recovery. Assessment and evaluation of the application of Masha Taila as a Snehana and Avagaha Sweda as a preventive measure for Gulpha Marma injuries. Method: 30 players with Normal ankle joint (Group A) & 30 players with Ankle sprain (1st degree) of Basketball players (Group B) were taken with age group 13 to 25 yrs. Goniometer to measure Range of motion (R.O.M.), pain analog scale for pain gradation. Result: Group A and B were compared with their control groups. The statistical result for normal dorsiflexion was 0.0007 degree, plantar flexion 0.001 degree, dorsi flexion of ankle sprain players 0.002 degree, plantar flexion 0.03 degree. The measurement of ROM of all players increased by 510 times indicating increased joint flexibility, based on ROM Mash taila proved to be a preventive measure. Pain analog scale for group B players indicated moderate pain at 0 day,reduced by 50% on 15th day and completely reduced on 30th day. Conclusion: “Prevention is better than cure”. As a preventive aspect the application of Masha Taila in normal ankle joint as Snehan & Swedan with warm water increases flexibility of joint and muscle strength. In sprained joint the same Taila application relives pain and regains its movements, this recovery and strength of joints happens because of reduce adhesion & influence the direction of new collage fibres in the healing process. It eliminates toxic accumulation from secondary muscle spasm. These Marma being the vital points must be prevented by applying Snehan & Swedan before starting the game just as warm up.

Simulation of Rossi-α method with analog Monte-Carlo method

International Nuclear Information System (INIS)

Lu Yuzhao; Xie Qilin; Song Lingli; Liu Hangang

2012-01-01

The analog Monte-Carlo code for simulating Rossi-α method based on Geant4 was developed. The prompt neutron decay constant α of six metal uranium configurations in Oak Ridge National Laboratory were calculated. α was also calculated by Burst-Neutron method and the result was consistent with the result of Rossi-α method. There is the difference between results of analog Monte-Carlo simulation and experiment, and the reasons for the difference is the gaps between uranium layers. The influence of gaps decrease as the sub-criticality deepens. The relative difference between results of analog Monte-Carlo simulation and experiment changes from 19% to 0.19%. (authors)

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.

Toward Wireless Health Monitoring via an Analog Signal Compression-Based Biosensing Platform.

Science.gov (United States)

Zhao, Xueyuan; Sadhu, Vidyasagar; Le, Tuan; Pompili, Dario; Javanmard, Mehdi

2018-06-01

Wireless all-analog biosensor design for the concurrent microfluidic and physiological signal monitoring is presented in this paper. The key component is an all-analog circuit capable of compressing two analog sources into one analog signal by the analog joint source-channel coding (AJSCC). Two circuit designs are discussed, including the stacked-voltage-controlled voltage source (VCVS) design with the fixed number of levels, and an improved design, which supports a flexible number of AJSCC levels. Experimental results are presented on the wireless biosensor prototype, composed of printed circuit board realizations of the stacked-VCVS design. Furthermore, circuit simulation and wireless link simulation results are presented on the improved design. Results indicate that the proposed wireless biosensor is well suited for sensing two biological signals simultaneously with high accuracy, and can be applied to a wide variety of low-power and low-cost wireless continuous health monitoring applications.

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…

Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents