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Sample records for 6-keto pgf1 alpha

  1. Stimulation of the synthesis of 15-hydroxyeicosatetraenoic acid (15-HETE) and 6-keto-prostaglandin F/sub 1. cap alpha. / (6-keto-PGF/sub 1. cap alpha. /) by cultured human umbilical veins

    SciTech Connect

    Ibe, B.O.; Johnson, A.R.; Falck, J.R.; Campbell, W.B.

    1986-03-05

    These studies were designed to investigate the synthesis of 6-keto-PGF/sub 1..cap alpha../ and 15-HETE in cultured human endothelial cells. The identification of the 15-HETE in these cells was made by UV absorption and gas chromatography/mass spectrometry. Specific radioimmunoassays were developed to quantify the synthesized 6-keto-PGF/sub 1..cap alpha../ and 15-HETE. The release of 15-HETE and 6-keto-PGF/sub 1..cap alpha../ was stimulated by arachidonic acid, histamine or the calcium ionophore A23187. The release of 15-HETE paralleled the release of 6-keto-PGF/sub 1..cap alpha../ and was both concentration-related and time-dependent. Aspirin, ibuprofen and indomethacin inhibited both the formation of 6-keto-PGF/sub 1..cap alpha../ and 15-HETE in similar concentrations. These data indicate that agents which stimulate PGI/sub 2/ synthesis also stimulate the synthesis of 15-HETE. Also, they implicate the cyclooxygenase pathway in the synthesis of 6-keto PGF/sub 1..cap alpha../ and 15-HETE in human endothelial cells.

  2. Concentrations of prostaglandins E2, F2 alpha and 6-keto-prostaglandin F1 alpha in the utero-ovarian venous plasma of nonpregnant and early pregnant ewes.

    PubMed

    Silvia, W J; Ottobre, J S; Inskeep, E K

    1984-05-01

    The effect of pregnancy on concentrations of prostaglandins E2, F2 alpha and 6-keto-prostaglandin F1 alpha (PGE2, PGF2 alpha and 6-keto-PGF1 alpha) in utero-ovarian venous plasma was examined in ewes on Days 10 through 14 after estrus, an interval which includes the critical period for maternal recognition of pregnancy. The utero-ovarian vein ipsilateral to a corpus luteum was catheterized on Day 9 or 10 in 6 pregnant and 8 nonpregnant ewes. Five blood samples were collected at 30-min intervals for 2 h beginning at 0500 and 1700 h daily. Sampling began at 0500 h on the day after catheterization. The mean and variance within each 2-h collection period were calculated for each ewe. The natural logarithm of the variance in each collection period (ln variance) was used as an estimate of the fluctuations in secretory activity by the endometrial-conceptus complex. Patterns of the mean concentrations of PGE2 were different between pregnant and nonpregnant ewes (P less than 0.01); PGE2 being higher in the pregnant ewes beginning on Day 13. There was a trend for the patterns of ln variance in PGE2 to differ (P less than 0.1) with pregnancy status over the entire period; ln variance was greater in pregnant ewes beginning on Day 13. The patterns of the mean concentrations and ln variances for PGF2 alpha and 6-keto-PGF1 alpha did not differ between pregnant and nonpregnant ewes. There were significant increases in both of these prostaglandins over time, independent of pregnancy status (P less than 0.01). The association of higher concentrations of PGE2 in utero-ovarian venous plasma with early pregnancy is consistent with the hypothesis that PGE2, originating from the uterus and/or conceptus, is one factor involved in maintenance of the corpus luteum of pregnancy.

  3. Major urinary metabolites of 6-keto-prostaglandin F2α in mice.

    PubMed

    Kuklev, Dmitry V; Hankin, Joseph A; Uhlson, Charis L; Hong, Yu H; Murphy, Robert C; Smith, William L

    2013-07-01

    Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption. Quantification of appropriate urinary 3-series PG metabolites could be used for noninvasive measurement of omega-3 fatty acid tone. Here we describe the preparation of tritium- and deuterium-labeled 6-keto-PGF2α and their use in identifying urinary metabolites in mice using LC-MS/MS. The major 6-keto-PGF2α urinary metabolites included dinor-6-keto-PGF2α (~10%) and dinor-13,14-dihydro-6,15-diketo-PGF1α (~10%). These metabolites can arise only from the enzymatic conversion of EPA to the 3-series PGH endoperoxide by cyclooxygenases, then PGI3 by prostacyclin synthase and, finally, nonenzymatic hydrolysis to 6-keto-PGF2α. The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases.

  4. Production of prostaglandins by the pseudopregnant rat uterus, in vitro, and the effect of tamoxifen with the identification of 6-keto-prostaglandin F1alpha as a major product.

    PubMed Central

    Fenwick, L; Jones, R L; Naylor, B; Poyser, N L; Wilson, N H

    1977-01-01

    1 Prostaglandin production by rat uterus homogenates has been studied, in vitro, on days 2 to 13 of pseudopregnancy. 2 The highest production of prostaglandins occurred on day 5. 3 The amounts of prostaglandins F and D formed were higher than the amounts of prostaglandin E on every day studied. 4 The ratios of prostglandins F and D to prostaglandin E produced steadily decreased up to day 6. It then increased with the highest values occurring between days 10 and 13, 5 Progesterone levels in peripheral plasma increased rapidly from days 2 to 5, remained high up to day 9, then steadily decreased between days 10 and 13. 6 The anti-oestrogenic drug, tamoxifen administered on day 2, significantly inhibited the increase of prostaglandin production which occurred on day 5. Prostaglandin E production was inhibited more than the production of prostaglandins F and D. 7 Analysis of the uterine extracts by gas chromatography and mass spectrometry showed prostaglandin F2alpha, F1alpha (in trace amounts), E2 and D2 to be present. 8 The major product detected was 6-keto-prostaglandin F1alpha. Its identification forms an addendum to the paper. 9 Also present as a major product was 6(9)-oxy-11,15-dihydroxyprosta-7,13-dienoic acid. PMID:836998

  5. Changes in endogenous prostacyclin in the rat brain during clinical death and after resuscitation.

    PubMed

    Kapuściński, A

    1992-01-01

    By means of the radioimmunologic method changes of concentration of 6-keto-prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3-fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed.

  6. Effects of sulglycotide on endogenous prostaglandin synthesis in human antral mucosa.

    PubMed

    Calabrò, A; Orsini, B; Milani, S; Psilogenis, M; Surrenti, C

    1992-12-01

    The effect of sulglycotide, a polysulphated glycopeptide isolated from pig duodenum, on PGE2, 6-ketoPGF1 alpha and TxB2 production from isolated biopsy specimens of human antral mucosa was investigated in vitro, in comparison with carbenoxolone. In addition to a tendency toward increased PGE2 production just short of statistical significance, both sulglycotide and carbenoxolone significantly increased 6-ketoPGF1 alpha accumulation in the incubation medium. TxB2 levels were not significantly modified by the two drugs. Therefore, changes in the prostanoid production by human antral mucosa could, at least partially account for the cytoprotective effects of sulglycotide in man.

  7. Eicosanoid synthesis in cardiomyocytes: influence of hypoxia, reoxygenation, and polyunsaturated fatty acids.

    PubMed

    Oudot, F; Grynberg, A; Sergiel, J P

    1995-01-01

    The synthesis of eicosanoids was investigated in cultured rat ventricular myocytes. Under normoxia, the cardiomyocytes released 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin (PG) E2 and smaller amounts of PGF2 alpha and thromboxane B2. Hypoxia enhanced the production of PGE2 and PGF2 alpha, whereas the synthesis of 6-keto-PGF1 alpha was not affected. Conversely, posthypoxic reoxygenation greatly increased the synthesis of 6-keto-PGF1 alpha, whereas the synthesis of PGF2 alpha, was not affected and that of PGE2 was reduced. The cardiomyocyte polyunsaturated fatty acid (PUFA) profile was altered by arachidonic acid or eicosapentaenoic acid and docosahexaenoic acid. Under normoxia, the eicosanoid production appeared to be roughly related to the cell phospholipid arachidonic acid content. Conversely, during posthypoxic reoxygenation, the production of eicosanoids was related to the cell phospholipid n-3 PUFA content, with the n-3-rich cells displaying a marked inhibition of the synthesis. This inhibition was mainly attributed to eicosapentaenoic acid and/or docosapentaenoic acid. Whether this inhibition occurs in vivo during postischemic reperfusion, it may contribute to the beneficial effect of n-3 PUFA on the heart.

  8. Arachidonate metabolism in bovine gallbladder muscle

    SciTech Connect

    Nakano, M.; Hidaka, T.; Ueta, T.; Ogura, R.

    1983-04-01

    Incubation of (1-/sup 14/C)arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of (1-/sup 14/C)PGH2 was virtually identical to that of (1-/sup 14/C)AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid.

  9. Nitric oxide-mediated cyclooxygenase activation. A key event in the antiplatelet effects of nitrovasodilators.

    PubMed Central

    Salvemini, D; Currie, M G; Mollace, V

    1996-01-01

    We have evaluated the contributions of nitric oxide (NO) and prostacyclin (PGI2) in the in vivo antiplatelet effects of clinically useful nitrovasodilators. In rats, intravenous infusion of three NO donors, glyceryl trinitrate, sodium nitroprusside, or 3'-morpholinosydnonimine, the stable metabolite of molsidomine, released 6-keto PGF1alpha (the stable metabolite of PGI2) and inhibited ex vivo human platelet aggregation to adenosine diphosphate by at least 80%. In in vitro studies, glyceryl trinitrate, sodium nitroprusside, and 3'-morpholinosydnonimine, at clinically attainable concentrations, increased cyclooxygenase activity in endothelial cells (EC), which resulted in a four- to sixfold release of 6-keto PGF1alpha. Pretreatment of the EC with hemoglobin which binds to and inactivates the biological actions of NO, but not by methylene blue (MelB), attenuated the NO-mediated PGI2 from the EC by at least 70%. Release of 6-keto PGF1alpha by the NO donors increased the ability of these compounds to inhibit thrombin-induced human platelet aggregation by at least 10 times; this potentiation was inhibited by hemoglobin but not by MeB. MeB blocked the direct anti-platelet effect of the NO donors in the absence of EC. In summary, we have demonstrated that NO, directly as well as together with an NO-driven cyclooxygenase activation (and hence PGI2), release contributes to the marked anti-platelet effects observed after the in vivo administration of clinically used nitrovasodilators. PMID:8647949

  10. [Image and quantity analysis of prostaglandin in rats' blood plasma and Na(+)-K(+)-ATPase in their cerebellum during the prevention of motion sickness by cinnarizine].

    PubMed

    Dong, W; Tian, D; Zhang, M

    1998-06-01

    To study the mechanism of cinnarizine in preventing motion sickness, TXB2, 6-Keto-PGF1 alpha in rats' blood plasma and Na(+)-K(+)-ATPase activity in the endothelial cells of their cerebellar capillary were measured and analysed by a radioactive immunity analyser and a computer image system. The results showed that TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in the cinnarizine preventing group (CPG) decreased remarkably, compared with those in the motion sickness group(MSG) (p < 0.05). The activity of Na(+)-K(+)-ATPase in the endothelial cells of rats' cerebellar capillary in CPG was higher than that in MSG (p < 0.01). The authors suggest that the lower concentration of TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in CPG is closely related to cinnarizine which prevents Ca2+ from entering into the platelets and into the endothelial cells of blood vessels. The higher activity of Na(+)-K(+)-ATPase in the cerebellum may be caused by cinnarizene which dilates the blood vessels in the brain, increases the blood flow therein, and hinders Ca2+ from getting into the cerebellum cells. These change are believed to be the important mechanism of how cinnarizine prevents motion sickness.

  11. Role of renal prostaglandins in the action of ramipril (HOE-498) in normotensive rats.

    PubMed

    Lahera, V; Durán, F; Cachofeiro, V; Cañizo, F J; Cantón, J J; Rodriguez, F J; Tresguerres, J A

    1989-01-01

    Changes in blood pressure, plasma renin activity, urine volume, urinary PGE2, 6-keto-PGF1 alpha and kinins, were studied after the administration of the angiotensin converting enzyme inhibitor ramipril (100 mu/kg/day), for one week in concomitantly indomethacin (1 mg/kg/day) treated and untreated rats. Measurements were made basally, before Ramipril administration and on days 1 and 7 during the treatment. Ramipril given alone induced a decrease in urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) on day 1, together with an increase in urinary kinins on day 7 (p less than 0.01) and in urine volume on days 1 and 7 (p less than 0.05). Increased urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) were observed in indomethacin pretreated rats after ramipril administration. No modifications in BP levels were observed either with indomethacin or with ramipril given alone or with ramipril plus indomethacin. Ramipril increased plasma renin activity levels both in indomethacin treated and untreated rats on days 1 (p less than 0.01) and 7 (p less than 0.05). The diuretic effect of ramipril and the stimulation of kinins were blunted when concomitant indomethacin was administered. Although a stimulatory effect of ramipril on urinary PGS was only observed during indomethacin administration, the present results would suggest that a non-inhibited PGS synthesis would be required for the renal actions of Ramipril.

  12. Prostacyclin: its pathogenic role in essential hypertension and the class effect of ACE inhibitors on prostaglandin metabolism.

    PubMed

    Rodríguez-García, J L; Villa, E; Serrano, M; Gallardo, J; García-Robles, R

    1999-01-01

    Angiotensin-converting enzyme inhibitors (ACEI) block degradation of bradykinin, and bradykinin stimulates prostacyclin synthesis. Therefore, we set out to determine whether the effects of ACE inhibitors on prostaglandin production in essential hypertensive patients are class effects or are dependent on ACE inhibitor structure. In addition, we studied whether hypertensives show an impaired capacity to synthesize vasodilator prostaglandins. To address these questions, we compared the effects of captopril (sulfhydryl-containing inhibitor), enalapril and ramipril (carboxyl-containing inhibitors) and fosinopril (phosphoryl-containing inhibitor) on blood pressure and urinary excretion of 6-keto-prostaglandin (PG) F1-alpha (the breakdown product of prostacyclin) in 44 mild-to-moderate essential hypertensive subjects before and 8 weeks after administration of an ACEI. We also studied prostacyclin excretion in 15 normotensive healthy controls. Levels of urinary 6-keto-PGF1-alpha (pg/ml) were measured by specific radioimmunoassay. Hypertensive subjects showed a lower excretion of 6-keto-PGF1-alpha than normotensive controls (212+/-147 vs 353+/-98 pg/ml, p < 0.001). All ACEI induced a significant decrease in MAP and increased the rate of excretion of the prostacyclin metabolite: C, 211+/-200 to 338+/-250 pg/ml, p < 0.05; E, 202+/-133 to 296+/-207 pg/ml, p < 0.05; R, 205+/-127 to 342+/-211 pg/ml, p < 0.05; F, 235+/-128 to 347+/-241 pg/ml, p < 0.05. In hypertensives (n = 44) the decrease in blood pressure correlated negatively with the rise in 6-keto-PGF1-alpha excretion (r = -0.51, p < 0.001). These data suggest that impaired prostacyclin biosynthesis in hypertensive patients could account for haemodynamic changes leading to the hypertensive state. Moreover, the hypotensive mechanisms of ACEI may be mediated by an increase in prostacyclin production; this effect seems to be class-dependent.

  13. Synthetic pathways of gallbladder mucosal prostanoids: the role of cyclooxygenase-1 and 2.

    PubMed

    Longo, W E; Panesar, N; Mazuski, J E; Kaminski, D

    1999-02-01

    Acute cholecystitis is associated with increased gallbladder prostanoid formation and the inflammatory changes and prostanoid increases can be inhibited by nonsteroidal anti-inflammatory agents. Recent information indicates that prostanoids are produced by two cyclooxygenase (COX) enzymes, COX-1 and COX-2. The purpose of this study was to determine the COX enzymatic pathway in gallbladder mucosal cells involved in the production of prostanoids stimulated by inflammatory agents. Human gallbladder mucosal cells were isolated from cholecystectomy specimens and maintained in cell culture and studied in comparison with cells from a well differentiated gallbladder mucosal carcinoma cell line. COX enzymes were evaluated by Western immunoblotting and prostanoids were measured by ELISA. Unstimulated and stimulated cells were exposed to specific COX-1 and COX-2 inhibitors. In both normal and transformed cells constitutive COX-1 was evident and in gallbladder cancer cells lysophosphatidyl choline (LPC) induced the formation of constitutive COX-1 enzyme. While not detected in unstimulated normal mucosal cells and cancer cells, COX-2 protein was induced by both lipopolysaccharide (LPS) and LPC. Unstimulated gallbladder mucosal cells and cancer cells produced prostaglandin E2 (PGE2) and prostacyclin (6-keto prostaglandin F1alpha, 6-keto PGF1alpha) continuously. In freshly isolated normal gallbladder mucosal cells, continuously produced 6 keto PGF1alpha was inhibited by both COX-1 and COX-2 inhibitors while PGE2 levels were not affected. Both LPS and LPC stimulated PGE2 and 6 keto PGF1alpha formation were blocked by COX-2 inhibitors in freshly isolated, normal human gallbladder mucosal cells and in the gallbladder cancer cells. The prostanoid response of gallbladder cells stimulated by proinflammatory agents is inhibited by COX-2 inhibitors suggesting that these agents may be effective in treating the pain and inflammation of gallbladder disease.

  14. Alteration of cyclosporine (CsA)-induced nephrotoxicity by gamma linolenic acid (GLA) and eicosapentaenoic acid (EPA) in Wistar rats.

    PubMed

    Morphake, P; Bariety, J; Darlametsos, I; Tsipas, G; Gkikas, G; Hornysh, A; Papanikolaou, N

    1994-01-01

    Administration of cyclosporine (CsA), 37.4 microM (45 mg)/Kg, per day for 7 days, to Wistar rats, induced decreased creatinine clearance (Ccr) and body weight loss (BWL), but it did not induce proteinuria. These changes were associated with enhanced urinary thromboxane B2 (TXB2) and diminished 6-keto-PGF1 alpha (6kPGF1 alpha) and prostaglandin E2 (PGE2) excretions. The augmentation in TXB2 and the decrease in PGs highly diminished the ratios of 6kPGF1 alpha/TXB2 and PGE2/TXB2. In microscopic sections all of the kidneys were affected to variable degrees. When CsA was administered to animals fed for 70 days, prior to the experiment, on standard chow (SC) containing evening primrose oil (EPO) or fish oil (FO), 1% and 10% respectively (EPO contained 9% gamma-linolenic acid (GLA) and FO 5.6% eicosapentaenoic acid (EPA)), the nephrotoxic effect of CsA was partially prevented. These changes were accompanied by increased ratios of urinary 6kPGF1 alpha/TXB2 and PGE2/TXB2 excretions. Light microscopic (LM) studies showed that rats' kidneys fed on SC containing EPO or FO were not always affected and the lesions were of minor importance. In conclusion, these results suggest that EPO (GLA) and FO (EPA) could play a beneficial role in the development or the modulation of the renal syndrome induced by CsA.

  15. Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats

    PubMed Central

    Mao, Shumei; Li, Chengde

    2015-01-01

    Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE) and its possible mechanisms in spontaneously hypertensive rats (SHR rats). Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats) were used in this study. Rats were, respectively, given EFE (EFE group), captopril (captopril group), or phosphate-buffered saline (PBS) (normal control group and SHR group) for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II), aldosterone (Ald), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) in plasma were determined by radioimmunoassay, and serum nitric oxide (NO) concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL). After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity. PMID:26798397

  16. Stimulation of renin release by intrarenal calcium infusion.

    PubMed

    Lahera, V; Fiksen-Olsen, M J; Romero, J C

    1990-02-01

    The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca/kg/min) on renin secretion were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 minutes each (1 ml/min). In a second group, the same doses were administered 30 minutes after the start of infusion of prostaglandin synthesis inhibitors (indomethacin 10 micrograms/kg/min intrarenal or injection of meclofenamate 5 mg/kg i.v. bolus). Mean arterial pressure, renal blood flow, and glomerular filtration rate remained unchanged during the infusion of calcium in both groups. The infusion of 10 micrograms Ca/kg/min increased renin secretion 77% and sodium excretion 123%. During the infusion of 100 micrograms Ca/kg/min, renin secretion was not different from precalcium values, whereas urinary 6-keto-PGF1 alpha, urine flow, sodium, potassium, and calcium excretion rates were increased (p less than 0.05). During the administration of prostaglandin synthesis inhibitors, the urinary 6-keto-PGF1 alpha levels were reduced, and the infusion of 10 micrograms Ca/kg/min failed to increase renin secretion, sodium excretion, or 6-keto-PGF1 alpha excretion rates. The infusion of 100 micrograms Ca/kg/min during prostaglandin synthesis inhibition did not modify urine flow or sodium excretion; however, potassium and calcium excretions increased. It is concluded that 1) the intrarenal infusion of small doses of calcium gluconate is capable of stimulating renin secretion through a prostaglandin-mediated mechanism, and 2) the stimulation of renin secretion as well as the increase in sodium excretion induced by calcium are independent of hemodynamic alterations.

  17. The influence of mono- and divalent cations on the cardiac metabolism of arachidonic acid

    SciTech Connect

    Weis, M.T.; Malik, K.U. )

    1989-06-01

    Our previous study indicated that, in the isolated rabbit heart, perfusion with Ca2+ free Krebs Henseleit buffer (KHB) results in increased conversion of exogenous arachidonic acid to PGE2 and 6-keto-PGF1 alpha, probably as the result of increased availability of substrate to cyclooxygenase. Since perfusion with Ca2+ free buffer is known to cause alterations in the cardiac content of various mono- and divalent cations, the present study was performed to determine: (a) The relationship between the conversion of exogenous arachidonic acid to prostaglandins and cardiac content of Na+, K+, Ca2+ and Mg2+; and (b) Whether enhanced arachidonic acid conversion to prostaglandins during Ca2+ free perfusion is due to reduced incorporation of this fatty acid into tissue lipids. Perfusion of the rabbit heart with Ca2+ free buffer produced a significant reduction in the tissue content of Na+, K+, Ca2+ and Mg2+. However, the production of 6-keto-PGF1 alpha from exogenous arachidonic acid was linearly correlated with tissue Mg2+. These observations, together with our finding that perfusion with Ca2+ free KHB reduced the incorporation of (3H) arachidonic acid into tissue lipids, suggests that Ca2+ free perfusion may, by reducing the activity of arachidonyl CoA synthetase (a Mg2+ dependent enzyme), decrease the acylation of arachidonic acid into lipids, thus increasing the availability of arachidonic acid to cyclooxygenase.

  18. A single mechanism to explain the effect of calcium on renal function.

    PubMed

    Lahera, V; Ruilope, L M; Romero, J C

    1991-07-01

    It is known that calcium induces the formation of potent vasodilators in endothelial cells and vasoconstriction in smooth muscle cells, whereas in the renal parenchyma, it modulates sodium excretion through vascular and tubular mechanisms. Consequently, an increased concentration of calcium in renal circulation may induce a sequence of contrasting hemodynamics and excretory effects depending on the threshold of a particular mechanism that is first being stimulated. In order to identify this sequence of responses and their respective thresholds, we infused into the renal artery of anesthetized dogs progressively increasing doses of calcium gluconate that ranged from 1 to 400 micrograms/kg/min. The administration of 1, 10, and 100 micrograms/kg/min of calcium gluconate was followed by a significant increase in urinary excretion of PGE2 and 6-keto-PGF1 alpha and by a marked diuresis and natriuresis without altering renal blood flow (RBF) or glomerular filtration rate (GFR). Renin release was increased by 80% only during the infusion of the 10 micrograms/kg/min dose. The intrarenal infusion of a 400 micrograms/kg/min dose of calcium produced marked decreases in RBF and GFR, while urine sodium excretion (UNaV), UPGE2V, and U6-keto-PGF1 alpha V continued and were markedly elevated. During all these maneuvers, mean arterial pressure remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Prostaglandin F{sub 2{alpha}} regulates cytokine responses of mast cells through the receptors for prostaglandin E

    SciTech Connect

    Kaneko, Izumi; Hishinuma, Takanori; Suzuki, Kaori; Owada, Yuji; Kitanaka, Noriko; Kondo, Hisatake; Goto, Junichi; Furukawa, Hiroshi; Ono, Masao

    2008-03-14

    There is an increasing body of evidence that prostanoids modulate mast cell functions and contribute to the development of allergic inflammation. The present study aimed to identify an undetermined function of prostaglandin (PG) F{sub 2{alpha}} in mast cell activation and the signaling mechanism involved in it. Simultaneous quantification of prostanoids by liquid chromatography/tandem mass spectrometry revealed the constitutive release of PGF{sub 2{alpha}}, thromboxane B{sub 2}, and 6-keto-PGF{sub 1{alpha}} from bone marrow-derived mast cells (BMMCs). Upon activation of BMMCs by lipopolysaccharide, the cytokine production in BMMCs was enhanced when the culture was supplemented with PGF{sub 2{alpha}}. However, F prostanoid receptor-a selective receptor for PGF{sub 2{alpha}}-was not detected in BMMCs. Further investigations performed using prostanoid receptor antagonists revealed an alternative mechanism wherein the receptors for PGE species-E prostanoid receptors-mediated the PGF{sub 2{alpha}} signal in BMMCs. The present study provides an insight into a novel function of PGF{sub 2{alpha}}, i.e., an autocrine accelerator for mast cell activation.

  20. Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.; Hatfaludy, Sophia; Sohar, Istvan; Shansky, Janet

    1990-01-01

    The purpose of the study is to determine whether mechanical stimulation of cultured muscle cells influences prostaglandin efflux rates and whether they are related to stretch-induced alterations in protein turnover rates. The materials and methods of the experiment, including cell cultures, mechanical stimulation, protein synthesis, and degradation assays are outlined, and emphasis is placed on the effect of short-term mechanical stimulation in basal medium prostaglandin efflux from cultured skeletal muscle and stretch-induced alterations in prostaglandins efflux in complete medium. The major finding of the study is that mechanical stimulation of tissue-cultured skeletal-muscle cells under conditions inducing skeletal-muscle hypertropy increases the efflux of PGE(2) and PGE(2-alpha) but not 6-keto-PGF(1-alpha), the prostacyclin product.

  1. He-Ne laser treatment on menorrhagia

    NASA Astrophysics Data System (ADS)

    Ding, Ai-Hua

    1993-03-01

    By using He-Ne laser treatment, 84.7 - 91.1% of patients with menorrhagia, a common symptom of multiple gynecological diseases, are treated effectively. After laser irradiation, the amount of vaginal bleeding was reduced 47.1% on average. It has been proven that low-energy laser is an effective non-traumatic, painless, and easily acceptable new physical method in patients with menorrhagia. To study the mechanisms of efficiency, the quantitative determination of PGE2, PGF2(alpha ), 6-Keto-PGF1(alpha ), TXB2 in endometrium and blood flow before and after treatment were carried out. The results suggest that the effectiveness may be due to the recovery regulation of local uterine PGS level.

  2. Prostacyclin and pathogenesis of hemodynamic abnormalities of diabetic ketoacidosis in rats.

    PubMed

    Quyyumi, A A; Iaffaldano, R; Guerrero, J L; Ryan, C A; Powell, W J; Axelrod, L

    1989-12-01

    The pathogenesis of the hemodynamic abnormalities of diabetic ketoacidosis (DKA) is not well understood. Previous studies suggest that prostacyclin (PGI2) production by adipose tissue is increased in DKA. We investigated the role of PGI2 in the pathogenesis of the reduced vascular resistance in DKA. Rats with streptozocin-induced DKA were anesthetized with pentobarbital sodium, and flow was measured with an electromagnetic probe on the infradiaphragmatic aorta. The plasma level of 6-keto-PGF1 alpha (stable derivative of PGI2) was higher (mean +/- SE 0.91 +/- 0.05 ng/ml) and vascular resistance lower (4.9 +/- 0.2 mmHg.ml-1.min-1.100 g-1 [resistance units, RU]) in 67 rats with DKA than in 21 normal rats (0.34 +/- 0.03 ng/ml, P less than .01, and 9.0 +/- 0.7 RU, P less than .01, respectively). Inhibition of cyclooxygenase activity with either indomethacin or meclofenamic acid reduced the plasma 6-keto-PGF1 alpha level but failed to raise vascular resistance. Infusions of PGI2 in rats with DKA demonstrated that the vasculature was responsive to PGI2. Inhibition of cyclooxygenase activity not only reduced PGI2 production but also suppressed renin release. When the effects of the renin-angiotensin system were excluded by bilateral nephrectomy, indomethacin caused a significant increase (P less than .05) in vascular resistance. Thus, the failure of cyclooxygenase inhibitors to raise vascular resistance in DKA was a result of concurrent suppression of vasodilator (PGI2) and vasoconstrictor (renin-angiotensin system) mechanisms that are activated in DKA. Insulin administration increased vascular resistance (P less than .01) and decreased the level of plasma 6-keto-PGF1 alpha (P less than .01). Combined administration of PGI2 and insulin did not alter vascular resistance, suggesting that the increase in vascular resistance with insulin was predominantly due to the reduction of circulating PGI2. Thus, vascular resistance is decreased in DKA primarily as a result of the

  3. Aldosterone alters the participation of endothelial factors in noradrenaline vasoconstriction differently in resistance arteries from normotensive and hypertensive rats.

    PubMed

    Xavier, Fabiano E; Blanco-Rivero, Javier; Avendaño, María Soledad; Sastre, Esther; Yela, Rubén; Velázquez, Kyra; Salaíces, Mercedes; Balfagón, Gloria

    2011-03-11

    This study analyzed the effect of aldosterone (0.05mg/kg per day, 3 weeks) on vasoconstriction induced by noradrenaline in mesenteric resistance arteries from WKY rats and SHR. Contraction to noradrenaline was measured in mesenteric resistance arteries from untreated and aldosterone-treatedrats from both strains. Participation of nitric oxide (NO), superoxide anions, thromboxane A(2) (TxA(2)) and prostacyclin in this response was determined. 6-keto-prostaglandin (PG)F1alpha and thromboxane B(2) (TxB(2)) releases were determined by enzyme immunoassay. NO and superoxide anion release were also determined by fluorescence and chemiluminiscence, respectively. Aldosterone did not modify noradrenaline-induced contraction in either strain. In mesenteric resistance arteries from both aldosterone-treated groups, endothelium removal or preincubation with NO synthesis inhibitor L-NAME increased the noradrenaline-induced contraction, while incubation with the superoxide anion scavenger tempol decreased it. Preincubation with either the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively) decreased the noradrenaline contraction in aldosterone-treated animals, while this response was not modified by COX-1 inhibitor SC-560. TxA(2) synthesis inhibitor (furegrelate), or TxA2 receptor antagonist (SQ 29 548) also decreased the noradrenaline contraction in aldosterone-treated animals. In untreated SHR, but not WKY rats, this response was increased by L-NAME, and reduced by tempol, indomethacin, NS-398 or SQ 29 548. Aldosterone treatment did not modify NO or TxB(2) release, but it did increase superoxide anion and 6-keto-PGF(1alpha) release in mesenteric resistance arteries from both strains. In conclusion, chronic aldosterone treatment reduces smooth muscle contraction to alpha-adrenergic stimuli, producing a new balance in the release of endothelium-derived prostanoids and NO.

  4. Effect of lactate-buffered peritoneal dialysis fluids on human peritoneal mesothelial cell interleukin-6 and prostaglandin synthesis.

    PubMed

    Witowski, J; Topley, N; Jörres, A; Liberek, T; Coles, G A; Williams, J D

    1995-01-01

    The present study focused on the evaluation of constitutive and cytokine-stimulated human peritoneal mesothelial cell (HPMC) IL-6 and 6-keto-PGF1 alpha release following pre-exposure to peritoneal dialysis fluid (PDF). Exposure of HPMC to PDF pH 5.2 resulted in a time-dependent increase in cell cytotoxicity [as assessed by lactate dehydrogenase (LDH) release] and concomitant inhibition of constitutive and IL-1 beta stimulated IL-6 and 6-keto-PGF1 alpha synthesis. After 15 minutes of exposure to PDF constitutive and IL-1 beta stimulated IL-6 release were reduced by 32.0 +/- 9.7% and 76.0 +/- 7.4% (N = 6, P < 0.046 and P < 0.027, respectively). PCR amplification of reverse transcribed mRNA from HPMC pre-exposed to PDF pH 5.2 demonstrated suppression of IL-1 beta stimulated IL-6 and cyclooxygenase (Cox-1 and Cox-2) transcripts. In order to mimic the dialysis cycle in vivo, an in vitro dialysis system was established. HPMC were exposed first to control medium, PDF pH 5.2 or PDF 7.3 for 15 minutes and then sequentially to pooled spent peritoneal dialysis effluent for up to four hours. The cells were subsequently allowed to recover in control medium for 12 hours in the presence or absence of IL-1 beta or TNF-alpha (both at 1000 pg/ml). There was no evidence of significant cell toxicity as assessed by LDH release during either the 'in vitro dialysis' or 'recovery' phases. Under these conditions short term exposure to PDF pH 5.2 followed by 'in vitro dialysis' resulted in significant inhibition of cytokine stimulated IL-6 (69.6 +/- 18.2 vs. 96.7 +/- 27.9 pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF1 alpha (197.5 +/- 89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF1 alpha (197.5 +/- 89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P < 0.003) release when compared to cells incubated in control medium. Adjustment of the pH of PDF to 7.3 reversed its inhibitory effects. We conclude that short-term exposure to PDF pH 5

  5. Biosynthesis of prostaglandins in gingiva of patients with chronic periodontitis

    SciTech Connect

    Mendieta, C.F.; Reeve, C.M.; Romero, J.C.

    1985-01-01

    This study was undertaken to determine the ability of inflamed and normal gingival tissues to synthesize prostaglandins (PGs) from the precursor arachidonic acid. Thirteen samples of inflamed human gingival tissue and six samples of normal human gingival tissue were studied. The inflammation was characterized histologically. After incubation of the tissue with (/sup 14/C)arachidonate, PG metabolites were separated by thin-layer chromatography and identified by comparison with co-chromatographed standards. Inflamed gingival tissue synthesized significantly larger amounts, compared to normal tissue, of 6-keto-PGF1 alpha (P less than 0.05), thromboxane B2, PGD2, and PGA2. Some unidentified metabolites, possibly lipoxygenase products were detected in significantly larger amounts in inflamed than in normal tissue.

  6. Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins.

    PubMed

    Schalin-Karrila, M; Mattila, L; Jansen, C T; Uotila, P

    1987-07-01

    In a double-blind trial patients with atopic eczema received either oral evening primrose oil (EPO) (n = 14) or placebo (n = 11) for 12 weeks. In the EPO group a statistically significant improvement was observed in the overall severity and grade of inflammation and in the percentage of the body surface involved by eczema as well as in dryness and itch. Patients in the placebo group showed a significant reduction in inflammation. The patients receiving EPO showed a significantly greater reduction in inflammation than those receiving placebo. Evening primrose oil caused a significant rise in the amount of dihomogammalinolenic acid in the plasma phospholipid fatty acids. Plasma levels of TXB2, 6-keto-PGF1 alpha and PGE1, and the amount of TXB2 released into serum during clotting were not altered by evening primrose oil.

  7. The effect of trinitrobenzene sulfonic acid on gut-derived smooth muscle cell arachidonic acid metabolism: role of endogenous prostanoids.

    PubMed

    Longo, W E; Smith, G S; Deshpande, Y; Reickenberg, C; Kaminski, D L

    1997-01-01

    The contribution of smooth muscle cells as a potential source of eicosanoid production during inflammatory states remains to be elucidated. We investigated the effect of trinitrobenzene sulfonic acid (TNB), a known pro-inflammatory agent, on jejunal smooth muscle cell eicosanoid production. Human gut-derived smooth muscle cells (HISM) were incubated with TNB for 1 hour. Additionally, some cells were preincubated with either dimethylthiourea, or indomethacin for 1 hour before exposure to identical concentrations of TNB. Incubation with TNB led to significant increases in PGE(2) and 6-keto PGF-1(alpha) release, but not leukotriene B(4) release; responses which were both inhibited by dimethylthiourea and indomethacin treatment. Our results suggest that gutderived smooth muscle cells may represent an important source of proinflammatory prostanoids but not leukotrienes during inflammatory states of the intestine. The inhibition of prostanoid activity by thiourea may be mediated by suppression of cyclooxygenase activity in this cell line.

  8. Regulation of prostaglandin production by nitric oxide; an in vivo analysis.

    PubMed Central

    Salvemini, D; Settle, S L; Masferrer, J L; Seibert, K; Currie, M G; Needleman, P

    1995-01-01

    1. Endotoxin E. Coli lipopolysaccharide (LPS)-treatment in conscious, restrained rats increased plasma and urinary prostaglandin (PG) and nitric oxide (NO) production. Inducible cyclo-oxygenase (COX-2) and nitric oxide synthase (iNOS) expression accounted for the LPS-induced PG and NO release since the glucocorticoid, dexamethasone inhibited both effects. Thus, LPS (4 mg kg-1) increased the plasma levels of nitrite/nitrate from 14 +/- 1 to 84 +/- 7 microM within 3 h and this rise was inhibited to 35 +/- 1 microM by dexamethasone. Levels of 6-keto PGF1 alpha in the plasma were below the detection limit of the assay (< 0.2 ng ml-1). However, 3 h after the injection of LPS these levels rose to 2.6 +/- 0.2 ng ml-1 and to 0.7 +/- 0.01 ng ml-1 after LPS in rats that received dexamethasone. 2. The induced enzymes were inhibited in vivo with selective COX and NOS inhibitors. Furthermore, NOS inhibitors, that did not affect COX activity in vitro markedly suppressed PG production in the LPS-treated animals. For instance, the LPS-induced increased in plasma nitrite/nitrate and 6-keto PGF1 alpha at 3 h was decreased to 18 +/- 2 microM and 0.5 +/- 0.02 ng ml-1, 23 +/- 1 microM and 0.7 +/- 0.01 ng ml-1, 29 +/- 2 microM and 1 +/- 0.01 ng ml-1 in rats treated with LPS in the presence of the NOS inhibitors NG-monomethyl-L-arginine, NG-nitro arginine methyl ester and aminoguanidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7542531

  9. Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: antioxidant intervention and/or iron and copper sequestering ability.

    PubMed

    Maffei Facinó, R; Carini, M; Aldini, G; Berti, F; Rossoni, G; Bombardelli, E; Morazzoni, P

    1996-12-01

    An isolated rabbit heart Langendorff preparation paced electrically was used to evaluate the effects of a highly purified, high molecular weight fraction of oligomeric procyanidines isolated from Vitis vinifera seeds on myocardial reperfusion injury after 40 minutes of low flow (1 ml/min) ischemia. Infusion of the heart with 100 or 200 micrograms/ml procyanidines dose-dependently reduced ventricular contracture during ischemia (LVEDP values decreased by 28% and 51%), decreased coronary perfusion pressure (CPP), improved cardiac mechanical performance upon reperfusion, increased the release of 6-keto-PGF1 alpha into the perfusate in both the pre-ischemic and the reperfusion periods (by 68% at 200 micrograms/ml), and suppressed rhythm irregularity. This antiarrhythmogenic action was confirmed in a more severe model of ischemia (flow rate 0.2 ml/ min). The cardioprotective agent allopurinol infused at 20 micrograms/ml had effects on the contractility and on the release of 6-keto-PGF1 alpha comparable to those of 200 micrograms/ml procyanidines. The results of the second part of this study show that procyanidines are potent scavengers of several reactive oxygen species involved in the ischemia/reperfusion damage: the superoxide anion (IC50 = 5.64 microM: rate constant K = 7.55 x 10(5) M-1 s-1, determined by the phenazine methosulfate/NADH method); the hydroxyl radical (IC50 = 28 microM; rate constant K = 1.2 x 10(12) M-1 s-1, determined by the electron spin resonance spectroscopy); peroxyl radicals (IC50 = 0.025 microM and 0.35 microM, determined using two different lipid substrates, phosphatidylcholine liposomes and methyl linoleate micelles by UV spectroscopy at 233 nm). Finally, procyanidines interact with Fe2+ and Cu2+ ions (the catalysts of HO. radicals production) giving rise to strong complexes, with stability constants (log K) ranging from 9.35 to approximately 9.

  10. Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells.

    PubMed Central

    Schafer, A I; Crawford, D D; Gimbrone, M A

    1984-01-01

    An important determinant of platelet-vessel wall interactions is the local balance of production of endothelial prostacyclin (PGI2) and platelet thromboxane (TX) A2, labile eicosanoids with opposing effects on hemostasis. Disputed evidence suggests that platelet-derived prostaglandin endoperoxide intermediates may be utilized as substrates for vascular PGI2 synthesis. Using several different approaches, we have found that platelets can transfer endoperoxides to cultured endothelial cells for efficient conversion to PGI2, but a reciprocal transfer of endothelial endoperoxides for utilization by platelet thromboxane synthetase does not occur under the same experimental conditions. However, platelets can utilize arachidonic acid released by endothelial cells for lipoxygenase metabolism. We have directly demonstrated the production of [3H]6-keto-PGF1 alpha (the breakdown product of [3H]PGI2) by aspirin-treated endothelial cells in the presence of platelets stimulated with [3H]arachidonic acid. In coincubation experiments using either arachidonate or ionophore A23187 as a stimulus, radioimmunoassay of the net production of arachidonic acid metabolites showed that 6-keto-PGF1 alpha generation by aspirin-treated endothelial cells in the presence of platelets may actually exceed its generation by uninhibited endothelial cells alone. In functional assays, platelet aggregation was inhibited in the presence of aspirin-treated endothelial cells after stimulation with either arachidonate or ionophore A23187. In contrast, the inverse experiments, using aspirin-treated platelets and uninhibited endothelial cells, failed to demonstrate platelet utilization of endothelial endoperoxides for TXA2 production by any of the above methods. These studies thus provide evidence that efficient unidirectional transfer and utilization of platelet-derived endoperoxides for endothelial PGI2 production can occur. This process may serve to amplify PGI2 generation adjacent to areas of vascular

  11. Changes of plasma thromboxane level in subarachnoid haemorrhage. A study with 11-dehydro-TXB2 as measuring index.

    PubMed

    Suzuki, S; Nonogaki, Y; Ebina, K; Sekiya, T; Iwabuchi, T; Takiguchi, M

    1991-01-01

    Changes of plasma thromboxane level in subarachnoid haemorrhage (SAH) were studied clinically and experimentally using 11-dehydro-thromboxane B2 (11 DTX) as a measuring index. 11 DTX is a major long-lived metabolite formed from thromboxane (TX) B2, and is said to be a more reliable parameter for detecting TXA2 production in biological systems. In this clinical study, blood was sampled from the cubital vein of 10 SAH patients on the earliest possible day (day 0 or 1), during the vasospasm predilection period (day 7 approximately 11) and in the chronic stage (day 16 approximately 32). Plasma concentrations of 11 DTX and 6-keto-PGF 1 alpha were measured in clinical cases. A canine SAH model was produced by the two haemorrhage methods and blood was sampled from the superior sagittal sinus before and on day 4 of the first cisternal blood injection. 11 DTX, TXB2 and platelet function were examined in each sample. In the clinical studies, plasma 11 DTX levels tended to be higher in the early stage of SAH but decreased thereafter to the normal or lower level. Plasma concentrations of 6-keto-PGF1 alpha tended to decrease mildly during the vasospasm predilection period. In the experimental study, neither definite change of plasma 11 DTX level nor neurological deficit could be induced by the mimic SAH, while an increase in platelet aggregability and narrowing of the basilar artery were observed. 11 DTX was inferred to be a more reliable parameter of TX biosynthesis than TXB2.

  12. Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin treated man.

    PubMed Central

    Konturek, S J; Kwiecień, N; Obtułowicz, W; Kopp, B; Oleksy, J

    1986-01-01

    Two groups A and B each comprising 12 healthy young male subjects were used in a double blind, placebo controlled trial to assess the effects of 1.0 g sucralfate qid on prostaglandin (PG) generation and mucosal integrity in the intact and aspirin-treated stomach. Mucosal formation and luminal release of PGE2, 6-keto-PGE1 alpha and thromboxane B2, gastric microbleeding and DNA loss (integrity indicators) and basal and pentagastrin induced acid secretion were measured after placebo and sucralfate treatment in subjects without (group A) and with administration of 2.5 g aspirin (group B). Sucralfate significantly reduced spontaneous gastric microbleeding and DNA loss in group A and prevented blood loss but not DNA loss caused by aspirin in group B. The protective effects of sucralfate on spontaneous gastric microbleeding were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with a reduction in release of thromboxane B2. In aspirin treated subjects both mucosal generation and luminal release of prostaglandins and thromboxane B2 were greatly suppressed although sucralfate treatment did not influence these prostaglandins in spite of the reduction in mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and aspirin treated gastric microbleeding in man and that this protection may be partly because of the increased mucosal biosynthesis of prostaglandins. PMID:3492413

  13. Alpha Blockers

    MedlinePlus

    ... conditions such as high blood pressure and benign prostatic hyperplasia. Find out more about this class of medication. ... these conditions: High blood pressure Enlarged prostate (benign prostatic hyperplasia) Though alpha blockers are commonly used to treat ...

  14. Alpha fetoprotein

    MedlinePlus

    ... Alpha fetoprotein - series References Cunningham FG, Leveno KJ, Bloom SL, et al. Prenatal diagnosis and fetal therapy. In: Cunningham FG, Leveno KJ, Bloom SL, et al, eds. Williams Obstetrics . 23rd ed. ...

  15. Alpha Thalassemia

    MedlinePlus

    ... an apparently normal individual has a child with hemoglobin H disease or alpha thalassemia minor. It can ... gene on one chromosome 25% 25% 25% 25% hemoglobin H disease there is a 25% chance with ...

  16. Interactions between inducible isoforms of nitric oxide synthase and cyclo-oxygenase in vivo: investigations using the selective inhibitors, 1400W and celecoxib

    PubMed Central

    Hamilton, Lorna C; Warner, Timothy D

    1998-01-01

    Exposure of tissues to endotoxin (LPS) and/or cytokines leads to the induction of both inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). It has previously been reported that there is `cross-talk' between these two systems. However, such previous studies have been limited by the availability of highly selective inhibitors. Here we have investigated the interactions between iNOS and COX-2 in vivo using 1400W, an iNOS-selective inhibitor, and celecoxib, a COX-2-selective inhibitor.Infusion of LPS to rats for 6 h caused a time-dependent increase in the plasma concentrations of 6 keto-prostaglandin F1α (6 keto-PGF1α) and nitrite/nitrate (NO2/NO3), consistent with the induction of iNOS and COX-2. Bolus injection of arachidonic acid (AA) at t=6 h resulted in a further increase of circulating levels of 6 keto-PGF1α in LPS-treated animals.Treatment of rats with 1400W or the non-selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) inhibited the increase in plasma NO2/NO3 but were both without effect on the plasma concentration of 6 keto-PGF1α before or after AA.Treatment with the non-steroidal anti-inflammatory drugs (NSAIDs), A771726 or diclofenac, or with celecoxib significantly reduced the increase in circulating 6 keto-PGF1α caused by LPS, and the large increase in 6 keto-PGF1α following injection of AA. None of the COX inhibitors affected the increase in plasma NO2/NO3. Dexamethasone, however, significantly inhibited both the increase in 6 keto-PGF1α and the increase in NO2/NO3.In conclusion, the use of selective inhibitors does not support the concept of cross talk in vivo between iNOS and COX-2. PMID:9786506

  17. Nondeletional alpha-thalassemia: first description of alpha Hph alpha and alpha Nco alpha mutations in a Spanish population.

    PubMed

    Ayala, S; Colomer, D; Aymerich, M; Pujades, A; Vives-Corrons, J L

    1996-07-01

    Several different deletions underlie the molecular basis of alpha-thalassemia. The most common alpha-thalassemia determinant in Spain is the rightward deletion (-alpha 3.7). To our knowledge, however, no cases of alpha-thalassemia due to nondeletional mutations have so far been described in this particular Mediterranean area. Here, we report the existence of nondeletional forms of alpha-thalassemia in ten Spanish families. The alpha 2-globin gene was characterized in ten unrelated patients and their relatives only when the presence of deletional alpha-thalassemia was ruled out. The alpha 2-globin gene analysis was performed using the polymerase chain reaction (PCR) followed by restriction enzyme analysis or by allelespecific priming. This allowed the identification of a 5-base pair (bp) deletion at the donor site of IVS I (alpha Hph alpha) in 9 cases and the alpha 2 initiation codon mutation (alpha Nco alpha) in one case. Although these alpha 2-globin gene mutations are found in other mediterranean areas, our results demonstrate their presence in the Spanish population and suggest that the alpha Hph alpha/alpha alpha genotype is probably the most common nondeletional form of alpha-thalassemia in Spain.

  18. Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet-activating factor is mediated by leukotriene C4.

    PubMed Central

    Piper, P. J.; Stewart, A. G.

    1986-01-01

    Platelet-activating factor (Paf, 0.04-4.50 nmol) dose-dependently induced coronary vasoconstriction and decreased cardiac contractility in rat, isolated perfused hearts and concomitantly released leukotriene-like bioactivity into the cardiac effluent. Platelet-activating factor (0.9 nmol) induced an increase in 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), PGF2 alpha, PGE2 and thromboxane B2 (TXB2) measured by radioimmunoassay (RIA) of cardiac effluents following partial purification using C18 Sep-Paks. The leukotriene-like bioactivity released by Paf was identified as leukotriene C4 (LTC4) using a combination of isolation on reverse phase-h.p.l.c. (r.p.h.p.l.c.) and quantitation by RIA. In addition, LTB4 was also identified by r.p.h.p.l.c. and the levels, determined by RIA, were within the range having biological activity. The release of cyclo-oxygenase products by Paf was prevented by indomethacin (2.8 microM), markedly attenuated by diethylcarbamazine (7.7 mM) but unaffected by FPL 55712 (1.9 microM)-pretreatment. Furthermore, LTC4 (50 pmol) did not increase the release of the cyclo-oxygenase products measured. The release of LTB4 and LTC4 appeared to be unaffected by indomethacin pretreatment whereas diethylcarbamazine-pretreatment markedly inhibited release. The coronary vasoconstriction induced by Paf (0.9 nmol) was attenuated by pretreatment with indomethacin or diethylcarbamazine, whereas FPL 55712 caused a marked inhibition of the response. In contrast, the decrease in cardiac contractility was prevented by indomethacin or diethylcarbamazine and unaffected by FPL 55712 pretreatment. It is concluded that LTC4 may be largely responsible for the coronary vasoconstriction induced by Paf with cyclo-oxygenase products having a possible modulatory role whereas the latter appear to be involved in the Paf-induced decrease in cardiac contractility. PMID:3091131

  19. Ab initio alpha-alpha scattering.

    PubMed

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-12-03

    Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  20. Ab initio alpha-alpha scattering

    NASA Astrophysics Data System (ADS)

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A.; Luu, Thomas; Meißner, Ulf-G.

    2015-12-01

    Processes such as the scattering of alpha particles (4He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei—nuclei with even and equal numbers of protons and neutrons—is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the ‘adiabatic projection method’ to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  1. alpha-Hexachlorocyclohexane (alpha-HCH)

    Integrated Risk Information System (IRIS)

    alpha - Hexachlorocyclohexane ( alpha - HCH ) ; CASRN 319 - 84 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Ass

  2. Differences in responsiveness of intrapulmonary artery and vein to arachidonic acid: mechanism of arterial relaxation involves cyclic guanosine 3':5'-monophosphate and cyclic adenosine 3':5'-monophosphate

    SciTech Connect

    Ignarro, L.J.; Harbison, R.G.; Wood, K.S.; Wolin, M.S.; McNamara, D.B.; Hyman, A.L.; Kadowitz, P.J.

    1985-06-01

    The objective of this study was to examine the relationship between responses of bovine intrapulmonary artery and vein to arachidonic acid and cyclic nucleotide levels in order to better understand the mechanism of relaxation elicited by arachidonic acid and acetylcholine. Arachidonic acid relaxed phenylephrine-precontracted arterial rings and elevated both cyclic GMP and cyclic AMP levels in arteries with intact endothelium. In contrast, endothelium-damaged arterial rings contracted to arachidonic acid without demonstrating significant changes in cyclic nucleotide levels. Indomethacin partially inhibited endothelium-dependent relaxation and abolished cyclic AMP accumulation whereas methylene blue, a guanylate cyclase inhibitor, partially inhibited relaxation and abolished cyclic GMP accumulation in response to arachidonic acid. All vessel responses were blocked by a combination of the two inhibitors. Prostaglandin (PG) I2 relaxed arterial rings and elevated cyclic AMP levels whereas PGE2 and PGF2 alpha caused contraction, suggesting that the indomethacin-sensitive component of arachidonic acid-elicited relaxation is due to PGI2 formation and cyclic AMP accumulation. The methylene blue-sensitive component is attributed to an endothelium-dependent but cyclooxygenase-independent generation of a substance causing cyclic GMP accumulation. Intrapulmonary veins contracted to arachidonic acid with no changes in cyclic nucleotide levels and PGI2 was without effect. Homogenates of intrapulmonary artery and vein formed 6-keto-PGF1 alpha, PGF2 alpha and PGE2 from (/sup 14/C)arachidonic acid, which was inhibited by indomethacin. Thus, bovine intrapulmonary vein may not possess receptors for PGI2.

  3. Alpha Hydroxy Acids

    MedlinePlus

    ... Cosmetics Home Cosmetics Products & Ingredients Ingredients Alpha Hydroxy Acids Share Tweet Linkedin Pin it More sharing options ... for Industry: Labeling for Cosmetics Containing Alpha Hydroxy Acids The following information is intended to answer questions ...

  4. The Alpha Centauri System.

    ERIC Educational Resources Information Center

    Soderblom, David R.

    1987-01-01

    Describes the Alpha Centauri star system, which is the closest star system to the sun. Discusses the difficulties associated with measurements involving Alpha Centauri, along with some of the recent advances in stellar seismology. Raises questions about the possibilities of planets around Alpha Centauri. (TW)

  5. Angiotensin II and renal prostaglandin release in the dog. Interactions in controlling renal blood flow and glomerular filtration rate.

    PubMed

    Bugge, J F; Stokke, E S

    1994-04-01

    The relationship between angiotensin II and renal prostaglandins, and their interactions in controlling renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in 18 anaesthetized dogs with acutely denervated kidneys. Intrarenal angiotensin II infusion increased renal PGE2 release (veno-arterial concentration difference times renal plasma flow) from 1.7 +/- 0.9 to 9.1 +/- 0.4 and 6-keto-PGF1 alpha release from 0.1 +/- 0.1 to 5.3 +/- 2.1 pmol min-1. An angiotensin II induced reduction in RBF of 20% did not measurably change GFR whereas a 30% reduction reduced GFR by 18 +/- 8%. Blockade of prostaglandin synthesis approximately doubled the vasoconstrictory action of angiotensin II, and all reductions in RBF were accompanied by parallel reductions in GFR. When prostaglandin release was stimulated by infusion of arachidonic acid (46.8 +/- 13.3 and 15.9 +/- 5.4 pmol min-1 for PGE2, and 6-keto-PGF1 alpha, respectively), angiotensin II did not change prostaglandin release, but had similar effects on the relationship between RBF and GFR as during control. In an ureteral occlusion model with stopped glomerular filtration measurements of ureteral pressure and intrarenal venous pressure permitted calculations of afferent and efferent vascular resistances. Until RBF was reduced by 25-30% angiotensin II increased both afferent and efferent resistances almost equally, keeping the ureteral pressure constant. At greater reductions in RBF, afferent resistance increased more than the efferent leading to reductions in ureteral pressure. This pattern was not changed by blockade of prostaglandin synthesis indicating no influence of prostaglandins on the distribution of afferent and efferent vascular resistances during angiotensin II infusion. In this ureteral occlusion model glomerular effects of angiotensin II will not be detected, and it might well be that the shift from an effect predominantly on RBF to a combined effect on both RBF and GFR induced by inhibition

  6. Endogenous prostaglandin endoperoxides and prostacyclin modulate the thrombolytic activity of tissue plasminogen activator. Effects of simultaneous inhibition of thromboxane A2 synthase and blockade of thromboxane A2/prostaglandin H2 receptors in a canine model of coronary thrombosis.

    PubMed Central

    Golino, P; Rosolowsky, M; Yao, S K; McNatt, J; De Clerck, F; Buja, L M; Willerson, J T

    1990-01-01

    We tested the hypothesis that simultaneous inhibition of TxA2 synthase and blockade of TxA2/PHG2 receptors is more effective in enhancing thrombolysis and preventing reocclusion after discontinuation of tissue plasminogen activator (t-PA) than either intervention alone. Coronary thrombosis was induced in 35 dogs by placing a copper coil into the left anterior descending coronary artery. Coronary flow was measured with a Doppler flow probe. 30 min after thrombus formation, the animals received saline (controls, n = 10); SQ 29548 (0.4 mg/kg bolus + 0.4 mg/kg per h infusion), a TxA2/PGH2 receptor antagonist (n = 8); dazoxiben (5 mg/kg bolus + 5 mg/kg per h infusion), a TxA2 synthase inhibitor (n = 9); or R 68070 (5 mg/kg bolus + 5 mg/kg per h infusion), a drug that blocks TxA2/PGH2 receptors and inhibits TxA2 synthase (n = 8). Then, all dogs received heparin (200 U/kg) and a bolus of t-PA (80 micrograms/kg) followed by a continuous infusion (8 micrograms/kg per min) for up to 90 min or until reperfusion was achieved. The time to thrombolysis did not change significantly in SQ 29548-treated dogs as compared with controls (42 +/- 5 vs. 56 +/- 7 min, respectively, P = NS), but it was significantly shortened by R 68070 and dazoxiben (11 +/- 2 and 25 +/- 6 min, respectively, P less than 0.001 vs. controls and SQ 29548-treated dogs). R 68070 administration resulted in a lysis time significantly shorter than that observed in the dazoxiben-treated group (P less than 0.01). Reocclusion was observed in eight of eight control dogs, five of seven SQ 29548-treated dogs, seven of nine dazoxiben-treated dogs, and zero of eight R 68070-treated animals (P less than 0.001). TxB2 and 6-keto-PGF1 alpha, measured in blood samples obtained from the coronary artery distal to the thrombus, were significantly increased at reperfusion and at reocclusion in control animals and in dogs receiving SQ 29548. R 68070 and dazoxiben prevented the increase in plasma TxB2 levels, whereas 6-keto-PGF1

  7. Lipoxygenase- and cyclooxygenase-reaction products and incorporation into glycerolipids or radiolabeled arachidonic acid in the bovine retina

    SciTech Connect

    Birkle, D.L.; Bazan, N.G.

    1984-02-01

    The metabolism of radiolabeled arachidonic acid (AA) by the intact bovine retina in vitro has been studied. Synthesis of prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs), and incorporation of AA into glycerolipids has been measured by reverse-phase and straight-phase high performance liquid chromatography with flow scintillation detection, and by thin-layer chromatography. AA was actively acylated into glycerolipids, particularly triglycerides, phosphatidylcholine and phosphatidylinositol. AA was also converted to the major PGs, PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha and TXB2, and to the lipoxygenase reaction products, 12-HETE, 5-HETE, and other monohydroxy isomers. Approximately 6% of the radiolabeled AA was converted to eicosanoids. The synthesis of HETEs was inhibited in a concentration-dependent manner (IC50 . 8.3 nM) by nordihydroguaiaretic acid (NDGA). PG synthesis was inhibited by aspirin (10 microM), indomethacin (1 microM) and NDGA (IC50 . 380 nM). Metabolism of AA via lipoxygenase, cyclooxygenase and activation-acylation was inhibited by boiling retinal tissue prior to incubation. These studies demonstrate an active system for the uptake and utilization of AA in the bovine retina, and provide the first evidence of lipoxygenase-mediated metabolism of AA, resulting in the synthesis of mono-hydroxyeicosatetraenoic acids, in the retina.

  8. Histamine stimulation of prostaglandin and HETE synthesis in human endothelial cells

    SciTech Connect

    Revtyak, G.E.; Hughes, M.J.; Johnson, A.R.; Campbell, W.B.

    1988-08-01

    Endothelial cells (EC) cultured from human umbilical artery (UA) and vein (UV) metabolized (/sup 14/C)arachidonic acid to prostaglandins (PGs), monohydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs). Major radioactive products were identified as 6-keto-PGF1 alpha, PGE2, PGF2 alpha, 12-hydroxy heptadecatrienoic acid, 15-HETE, and 11-HETE. In addition, extracts from UV ECs contained 12-HETE, 5-HETE, 14,15-EET, and 5,6-EET as minor products, whereas extracts from UA ECs contained only 12-HETE as a minor product. UA ECs also produced metabolites comigrating with 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET. Histamine increased the release of (/sup 14/C)PGs and (/sup 14/C)HETEs from (/sup 14/C)arachidonic acid-labeled ECs. Indomethacin, aspirin, and nordihydroguauretic acid completely inhibited synthesis of both (/sup 14/C)PGs and (/sup 14/C)HETEs from exogenous (/sup 14/C)arachidonic acid in these cells. Microsomes metabolized (/sup 14/C)arachidonic acid to the same (/sup 14/C)PGs and (/sup 14/C)HETEs as intact cells. Pretreatment of microsomes with indomethacin completely inhibited formation of these products. These data indicate that UA ECs and UV ECs metabolize endogenous and exogenous arachidonic acid to both PGs and HETEs. Also 15-HETE and 11-HETE appear to be synthesized by a microsomal enzyme with the properties of cyclooxygenase.

  9. Evening primose oil and fish oil are ineffective as supplementary treatment of bronchial asthma.

    PubMed

    Stenius-Aarniala, B; Aro, A; Hakulinen, A; Ahola, I; Seppälä, E; Vapaatalo, H

    1989-06-01

    The effect of daily dietary supplementation with 15 to 20 mL of evening primrose seed oil or fish oil was assessed by comparison with olive oil as placebo in a cross-over study in 29 asthmatics. During 10 weeks of each regimen, the patients kept record of symptoms, peak expiratory flow rates and medication. Plasma and urine TxB2, PGE2, PGF2 alpha and 6 keto-PGF1 alpha and plasma fatty acid composition of plasma cholesterol esters were measured at the end of each treatment period. There were no differences between regimes with regard to peak flow rates, symptoms, or drug consumption. Plasma PGE2 levels increased during the fish oil treatment but there were no changes in other prostanoids in plasma or urine. The fatty acid pattern of plasma cholesterol esters showed significant differences between the supplementation periods. We conclude that moderate doses of evening primrose oil or fish oil are ineffective as a supplementary treatment of bronchial asthma.

  10. Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat kidneys.

    PubMed

    Hasan, Jamal; Beharry, Kay D; Gharraee, Zahra; Stavitsky, Yuri; Abad-Santos, Patricia; Abad-Santos, Matthew; Aranda, Jacob V; Modanlou, Houchang D

    2008-03-01

    The use of indomethacin in preterm newborn infants with symptomatic patent ductus arteriosus is associated with compromised renal function. Ibuprofen has been shown to be as effective as indomethacin with fewer renal side effects. We examined the hypothesis that early postnatal ibuprofen has less adverse effects on neonatal rat renal prostanoids, COX-2 expression, and angiotensin II than indomethacin. Newborn rats received IP injections of human therapeutic doses of ibuprofen or indomethacin on the first 3 days of life. Control rats were treated with equivalent volume saline. Kidneys were assessed in suckling and weanling rats for prostanoids, COX-2 expression, and angiotensin II. In suckling rats, indomethacin suppressed PGE(2) and COX-2 expression, and increased PGF(2alpha), whereas ibuprofen increased COX-2 and angiotensin II. Although both NSAIDs suppressed 6-ketoPGF(1alpha) and TxB(2) levels in suckling rats, the effect was sustained in weanling rats with indomethacin. Our findings demonstrate that indomethacin exhibits more potent suppressive effects on renal COX-2 and vasodilator prostanoids which are important regulators of renal development and function. These long-term, sustained effects may explain in part, why indomethacin exerts more severe adverse renal effects than ibuprofen, when administered during early postnatal life.

  11. Interpreting EEG alpha activity.

    PubMed

    Bazanova, O M; Vernon, D

    2014-07-01

    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  12. ALPHA CONTAMINATION MONITORING

    DTIC Science & Technology

    This project was conducted to determine the alpha hazard existing in the vicinity of the missile launch pad following the destruction of a missile ...were used for plutonium particle collection. Because all warhead-carrying missiles were properly launched after Project 2.3 was approved, no alpha contamination data was obtained.

  13. Imaging alpha particle detector

    DOEpatents

    Anderson, David F.

    1985-01-01

    A method and apparatus for detecting and imaging alpha particles sources is described. A conducting coated high voltage electrode (1) and a tungsten wire grid (2) constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source (3) to be quantitatively or qualitatively analyzed. A thin polyester film window (4) allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  14. Imaging alpha particle detector

    DOEpatents

    Anderson, D.F.

    1980-10-29

    A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  15. Event counting alpha detector

    DOEpatents

    Bolton, Richard D.; MacArthur, Duncan W.

    1996-01-01

    An electrostatic detector for atmospheric radon or other weak sources of alpha radiation. In one embodiment, nested enclosures are insulated from one another, open at the top, and have a high voltage pin inside and insulated from the inside enclosure. An electric field is produced between the pin and the inside enclosure. Air ions produced by collision with alpha particles inside the decay volume defined by the inside enclosure are attracted to the pin and the inner enclosure. With low alpha concentrations, individual alpha events can be measured to indicate the presence of radon or other alpha radiation. In another embodiment, an electrical field is produced between parallel plates which are insulated from a single decay cavity enclosure.

  16. Event counting alpha detector

    DOEpatents

    Bolton, R.D.; MacArthur, D.W.

    1996-08-27

    An electrostatic detector is disclosed for atmospheric radon or other weak sources of alpha radiation. In one embodiment, nested enclosures are insulated from one another, open at the top, and have a high voltage pin inside and insulated from the inside enclosure. An electric field is produced between the pin and the inside enclosure. Air ions produced by collision with alpha particles inside the decay volume defined by the inside enclosure are attracted to the pin and the inner enclosure. With low alpha concentrations, individual alpha events can be measured to indicate the presence of radon or other alpha radiation. In another embodiment, an electrical field is produced between parallel plates which are insulated from a single decay cavity enclosure. 6 figs.

  17. Alpha-particle diagnostics

    SciTech Connect

    Young, K.M.

    1991-01-01

    This paper will focus on the state of development of diagnostics which are expected to provide the information needed for {alpha}- physics studies in the future. Conventional measurement of detailed temporal and spatial profiles of background plasma properties in DT will be essential for such aspects as determining heating effectiveness, shaping of the plasma profiles and effects of MHD, but will not be addressed here. This paper will address (1) the measurement of the neutron source, and hence {alpha}-particle birth profile, (2) measurement of the escaping {alpha}-particles and (3) measurement of the confined {alpha}-particles over their full energy range. There will also be a brief discussion of (4) the concerns about instabilities being generated by {alpha}-particles and the methods necessary for measuring these effects. 51 refs., 10 figs.

  18. Reexamination of the {alpha}-{alpha}''fishbone'' potential

    SciTech Connect

    Day, J. P.; McEwen, J. E.; Elhanafy, M.; Smith, E.; Woodhouse, R.; Papp, Z.

    2011-09-15

    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the {alpha}-{alpha} fishbone potential by simultaneously fitting to two-{alpha} resonance energies, experimental phase shifts, and three-{alpha} binding energies. We found that, essentially, a simple Gaussian can provide a good description of two-{alpha} and three-{alpha} experimental data without invoking three-body potentials.

  19. The alpha channeling effect

    SciTech Connect

    Fisch, N. J.

    2015-12-10

    Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

  20. Thromboxane and prostacyclin synthesis following whole body irradiation in rats

    SciTech Connect

    Schneidkraut, M.J.; Kot, P.A.; Ramwell, P.W.; Rose, J.C.

    1984-01-01

    The effect of radiation on the mechanism and source of in vivo thromboxane B/sub 2/ (TxB/sub 2/) and 6-keto-prostaglandin F/sub 1..cap alpha../ (6-keto-PGF/sub 1..cap alpha..) synthesis was evaluated. Rats were irradiated with 2, 10, or 20 gray (Gy) whole body gamma irradiation and showed an increase in urine TxB/sup 2/ after either 10 or 20 Gy. Urine 6-keto-PGF/sub 1..cap alpha../ was elevated only after exposure to 20 Gy. Irradiation did not alter urine volume and osmolarity, nor was there a correlation between urine osmolarity and the urinary concentration of TxB/sup 2/ or 6-keto-PGF/sub 1..cap alpha../. Rats were pretreated with indomethacin to determine if radiation-induced alterations in urine TxB/sup 2/ and 6-keto-PGF/sub 1..cap alpha../ could be suppressed. Pretreatment with indomethacin significantly decreased urine TxB..cap alpha.. and 6-keto-PFG/sub 1..cap alpha../ in both irradiated and nonirradiated animals. Finally, the sources of urinary cyclooxygenase products were investigated using an isogravitometric cross-perfusion system. These experiments demonstrated that urine TxB..cap alpha.. is derived from extrarenal sources, whereas 6-keto-PGF/sub 1..cap alpha.. is synthesized primarily by the kidney. It may be concluded that radiation exposure increases in vivo cyclooxygenase pathway activity by both renal and ultrarenal tissues.

  1. Alpha One Foundation

    MedlinePlus

    Languages French (Francais) German (Deutsch) Italian (Italiano) Spanish (Español) Portuguese (Portugues) Swedish (Svenska) Donate One Time Monthly Keep In Touch | About Us | Contact Us | What is the Alpha-1 ...

  2. Coaching the alpha male.

    PubMed

    Ludeman, Kate; Erlandson, Eddie

    2004-05-01

    Highly intelligent, confident, and successful, alpha males represent about 70% of all senior executives. Natural leaders, they willingly take on levels of responsibility most rational people would find overwhelming. But many of their quintessential strengths can also make alphas difficult to work with. Their self-confidence can appear domineering. Their high expectations can make them excessively critical. Their unemotional style can keep them from inspiring their teams. That's why alphas need coaching to broaden their interpersonal tool kits while preserving their strengths. Drawing from their experience coaching more than 1,000 senior executives, the authors outline an approach tailored specifically for the alpha. Coaches get the alpha's attention by inundating him with data from 360-degree feedback presented in ways he will find compelling--both hard-boiled metrics and vivid verbatim comments from colleagues about his strengths and weaknesses. A 360-degree assessment is a wake-up call for most alphas, providing undeniable proof that their behavior doesn't work nearly as well as they think it does. That paves the way for a genuine commitment to change. In order to change, the alpha must venture into unfamiliar--and often uncomfortable--psychological territory. He must admit vulnerability, accept accountability not just for his own work for others', connect with his underlying emotions, learn to motivate through a balance of criticism and validation, and become aware of unproductive behavior patterns. The goal of executive coaching is not simply to treat the alpha as an individual problem but to improve the entire team dynamic. Initial success creates an incentive to persevere, and the virtuous cycle reverberates throughout the entire organization.

  3. alpha2-Adrenoreceptor antagonists.

    PubMed

    Mayer, P; Imbert, T

    2001-06-01

    A review of the literature relating to the therapeutic potential of alpha2-adrenoceptor antagonists published between 1990 and 2000 is presented. Although extensively studied since the early 1970s in a wide spectrum of therapeutic applications, the distinction of alpha2-adrenoceptor subtypes and some emerging evidence concerning new applications in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, obesity and schizophrenia, have refreshed an interest in this class of agents.

  4. Alpha Particle Diagnostic

    SciTech Connect

    Fisher, Ray, K.

    2009-05-13

    The study of burning plasmas is the next frontier in fusion energy research, and will be a major objective of the U.S. fusion program through U.S. collaboration with our international partners on the ITER Project. For DT magnetic fusion to be useful for energy production, it is essential that the energetic alpha particles produced by the fusion reactions be confined long enough to deposit a significant fraction of their initial ~3.5 MeV energy in the plasma before they are lost. Development of diagnostics to study the behavior of energetic confined alpha particles is a very important if not essential part of burning plasma research. Despite the clear need for these measurements, development of diagnostics to study confined the fast confined alphas to date has proven extremely difficult, and the available techniques remain for the most part unproven and with significant uncertainties. Research under this grant had the goal of developing diagnostics of fast confined alphas, primarily based on measurements of the neutron and ion tails resulting from alpha particle knock-on collisions with the plasma deuterium and tritium fuel ions. One of the strengths of this approach is the ability to measure the alphas in the hot plasma core where the interesting ignition physics will occur.

  5. Manipulation of pulmonary prostacyclin synthase expression prevents murine lung cancer.

    PubMed

    Keith, Robert L; Miller, York E; Hoshikawa, Yasushi; Moore, Mark D; Gesell, Tracy L; Gao, Bifeng; Malkinson, Alvin M; Golpon, Heiko A; Nemenoff, Raphael A; Geraci, Mark W

    2002-02-01

    Inhibition of cyclooxygenase (COX) activity decreases eicosanoid production and prevents lung cancer in animal models. Prostaglandin (PG) I(2) (PGI(2), prostacyclin) is a PGH(2) metabolite with anti-inflammatory, antiproliferative, and antimetastatic properties. The instability of PGI(2) has limited its evaluation in animal models of cancer. We hypothesized that pulmonary overexpression of prostacyclin synthase may prevent the development of murine lung tumors. Transgenic mice with selective pulmonary prostacyclin synthase overexpression were exposed to two distinct carcinogenesis protocols: an initiation/promotion model and a simple carcinogen model. The transgenic mice exhibited significantly reduced lung tumor multiplicity (tumor number) in proportion to transgene expression, a dose-response effect. Moreover, the highest expressing mice demonstrated reduced tumor incidence. To investigate the mechanism for protection, we evaluated PG levels and inflammatory responses. At the time of sacrifice following one carcinogenesis model, the transgenics exhibited only an increase in 6-keto-PGF(1alpha), not a decrease in PGE(2). Thus, elevated PGI(2) levels and not decreased PGE(2) levels appear to be necessary for the chemopreventive effects. When exposed to a single dose of butylated hydroxytoluene, transgenic mice exhibited a survival advantage; however, reduction in alveolar inflammatory response was not observed. These studies demonstrate that manipulation of PG metabolism downstream from COX produces even more profound lung cancer reduction than COX inhibition alone and could be the basis for new approaches to understanding the pathogenesis and prevention of lung cancer.

  6. Endothelial cell functions in vitro cultured on poly(L-lactic acid) membranes modified with different methods.

    PubMed

    Zhu, Yabin; Gao, Changyou; Liu, Yunxiao; Shen, Jiacong

    2004-06-01

    We recently developed several methods to enhance the cell-polymer interactions. Optimal conditions for each method have been revealed separately by in vitro cell culture. As a practical consideration for construction of tissue-engineered organs, it is necessary to consider which is the most suitable and convenient in clinical applications. To compare the efficiency of these methods with respect to cell functions, poly-L-lactic acid (PLLA) was selected as matrix being modified by 1) aminolysis (PLLA-NH(2)), 2) collagen immobilization with GA (PLLA-GA-Col), 3) chondroitin sulfate (CS)/collagen layer-by-layer (LBL) assembly (PLLA-CS/Col), 4) photo-induced grafting copolymerization of hydrophilic methacrylic acid (MAA) (PLLA-g-PMAA), and 5) further immobilization of collagen with 1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride (EDAC) (PLLA-g-PMAA-Col). The surface wettability of the modified PLLA was determined by water contact angle measurements. The cell response to the modified PLLA was quantitatively assessed and compared by using human umbilical endothelial cells (HUVECs) culture. Our results indicate that all the modifications can improve the cytocompatibility of PLLA (e.g., cells can attach with spreading morphology, proliferate and secret vWF and 6-keto-PGF(1 alpha)). All the collagen-modified PLLA showed more positive cell response than those purely aminolyzed or PMAA grafted. Among all the methods, collagen immobilization by LBL assembly or GA bridging after aminolysis is more acceptable for the convenience and applicability to scaffolds.

  7. Effect of radiation on prostacyclin (PGI2) production by cultured endothelial cells

    SciTech Connect

    Eldor, A.; Vlodavsky, I.; Hyam, E.; Atzmon, R.; Fuks, Z.

    1983-02-01

    The effect of ionizing irradiation on the synthesis of prostacyclin (PGI2) by cultured bovine aortic endothelial cells was determined. PGI2 was measured in the culture medium by a radioimmunoassay for 6-Keto PGF1 alpha. Two phenomena were observed following irradiation: a) Cells which suffered an immediate radiation damage (1000-5000 rads) released high quantities of PGI2 to the culture medium. This was due to a de novo synthesis of PGI2 stimulated by radiation induced cellular damage, since pretreatment with aspirin of the endothelial cell monolayers resulted in a marked inhibition of PGI2 release following irradiation. b) Metabolically active cells which remained confluent and firmly attached to the culture dish following single, low and intermediate doses (200-1200 rads) radiation, exhibited a marked decrease in their capacity to synthesize PGI2 upon exposure to various stimuli of the arachidonic acid cascade. Similar results were observed with cells treated with fractionated radiation. The quantities of PGI2 produced by the endothelial cells decreased as a function of the dose of radiation and time interval between irradiation and subsequent stimulation. The effect of radiation on PGI2 production by the vascular endothelium may be relevant to the development of radiation induced capillary occlusions, and the enhancement of atherosclerotic lesions in large vessels.

  8. Lipoxygenase products mediate the attachment of rat macrophages to glomeruli in vitro

    SciTech Connect

    Baud, L.; Sraer, J.; Delarue, F.; Bens, M.; Balavoine, F.; Schlondorff, D.; Ardaillou, R.; Sraer, J.D.

    1985-06-01

    Because there is an accumulation of macrophages in the Bowman's space during human and experimental glomerulonephritis, the authors have studied the binding of (/sup 3/H)-uridine labeled macrophages to isolated glomeruli. Binding was related to the glomerular protein and macrophage concentrations, temperature, time of incubation, and was a saturable process. Macrophage adherence depended on glomerular lipoxygenase activity but not on glomerular cyclooxygenase activity since preincubation of glomeruli with nordihydroguaiaretic acid (NDGA) inhibited this phenomenon whereas preincubation with indomethacin was ineffective. Glomeruli interacted with macrophages in converting arachidonic acid (C20:4) to prostaglandins (PG) since productions of 6 keto-PGF1 alpha, TXB2, and PGD2 by glomeruli and macrophages incubated in combination were much greater than the sums of their respective productions by glomeruli and macrophages incubated separately. Macrophages were the source of the supplementary synthesis of PG which was abolished when these cells were pretreated with aspirin. Stimulation of macrophages by glomeruli was blunted by pretreatment of glomeruli with NDGA. Production of PG and of 12-HETE by macrophages was stimulated by a lipid extract of glomeruli containing the oxygenated metabolites of C20:4. Direct addition of 12-HPETE also stimulated macrophage functions. These data suggest that macrophage attachment to glomeruli and macrophage stimulation in the presence of glomeruli depend on glomerular lipoxygenase activity.

  9. Role of eicosanoids and white blood cells in the beneficial effects of limited reperfusion after ischemia-reperfusion injury in skeletal muscle

    SciTech Connect

    Anderson, R.J.; Cambria, R.A.; Dikdan, G.; Lysz, T.W.; Hobson, R.W. II )

    1990-08-01

    Limiting the rate of reperfusion blood flow has been shown to be beneficial locally in models of ischemia-reperfusion injury. We investigated the effects of this on eicosanoids (thromboxane B2, 6-keto-PGF1 alpha, and leukotriene B4), white blood cell activation, and skeletal muscle injury as quantitated by triphenyltetrazolium chloride and technetium-99m pyrophosphate after ischemia-reperfusion injury in an isolated gracilis muscle model in 16 anesthetized dogs. One gracilis muscle in each dog was subjected to 6 hours of ischemia followed by 1 hour of limited reperfusion and then by a second hour of normal reperfusion. The other muscle was subjected to 6 hours of ischemia followed by 2 hours of normal reperfusion. Six dogs each were used as normal reperfusion controls (NR) and limited reperfusion controls (LR), with 5 dogs being treated with a thromboxane synthetase inhibitor (LR/TSI) and another five with a leukotriene inhibitor (LR/LI). LR in all three groups (LR, LR/TSI, and LR/LI) showed a benefit in skeletal muscle injury as measured by triphenyltetrazolim chloride and technetium-99m pyrophosphate when compared with NR. However, there was no significant difference between the groups with LR regarding eicosanoid levels and white blood cell activation when compared with NR. These results demonstrate that LR produces benefits by mechanisms other than those dependent upon thromboxane A2, prostacyclin, or white blood cell activation.

  10. Biochemical and pharmacological consequences of the interaction between methotrexate and ketoprofen in the rabbit.

    PubMed Central

    Perrin, A.; Milano, G.; Thyss, A.; Cambon, P.; Schneider, M.

    1990-01-01

    Severe methotrexate (MTX) toxicity is a proven complication of associations of MTX and non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated the interaction between MTX (50 or 100 mg kg-1) and ketoprofen (KP) (3 mg kg-1 day-1, pretreatment for 8 days) in the rabbit. The drug association induced a reversible increase in blood urea and creatinine. The severity degree of renal dysfunction was significantly related to the MTX dose; it was not modified by prolonged exposure to KP after MTX administration. The biological markers of haematopoietic and hepatic functions were unchanged. Pretreatment by KP induced a marked reduction (70%) in the urinary excretion of the prostaglandin 6-keto-PGF1 alpha. MTX dose-related alterations in MTX pharmacokinetics were also observed with the drug association: at a MTX dose of 100 mg kg-1, the presence of KP significantly reduced the total body clearance, the renal clearance and the fraction of MTX eliminated in urine as compared to controls. An appreciable reduction in the plasma binding of MTX was also noted in vivo when KP was associated. This experimental study confirms the existence of an interaction between MTX and KP and demonstrates its renal origin. PMID:2245165

  11. Prostacyclin production by arterialized autogenous venous grafts in dogs.

    PubMed

    Eldor, A; Hoover, E L; Pett, S B; Gay, W A; Alonso, D R; Weksler, B B

    1981-09-01

    Arteries are capable of producing significantly larger quantities of prostacyclin than are veins. To test the hypothesis, whether prostacyclin production by the vessel wall is related to blood pressure and flow, we measured the amounts of PGI2 released and synthesized by venous segments transplanted for 6 weeks into the arterial circulation. These results were compared with the production of prostacyclin by normal veins and arteries. In 20 dogs a segment of jugular vein was interposed into the carotid system; a sham dissection was done on the opposite side. "Arterialized" vein grafts showed prominent intima lined by endothelium, medial smooth muscle cell proliferation and fibrotic proliferation in adventitia. Spontaneous and arachidonic acid-stimulated prostacyclin production (measured by radioimmunoassay for 6-keto-PGF1 alpha) was not significantly different between arterialized venous autografts and jugular veins. Significantly larger amounts of prostacyclin were synthesized by the carotid artery. Thus, histologic changes and rheologic effects occurring in vein grafts transposed to the arterial site do not affect prostacyclin production.

  12. A diet containing n-3 and n-6 fatty acids favorably alters the renal phospholipids, eicosanoid synthesis and plasma lipids in nephrotic rats.

    PubMed

    Barcelli, U O; Beach, D C; Thompson, B; Weiss, M; Pollak, V E

    1988-11-01

    The nephrotic syndrome was induced in rats by intravenous adriamycin (3 mg/kg). The rats were then divided into four groups which, for six weeks, were pair-fed diets containing beef tallow (BT), fish oil (FO), a source of n-3 fatty acids, evening primrose oil (EPO), a source of n-6 fatty acids, or a combination of evening primrose oil and fish oil, 75:25 (EPO:FO). The fat content of the diets was 15%. Significant incorporation of the fatty acids into kidney phospholipids was demonstrated. Diets containing FO, EPO and EPO:FO lowered plasma triglycerides and total cholesterol levels as compared with diets containing BT. Only EPO:FO raised high density lipoprotein (HDL) cholesterol levels, as compared with BT. The combination EPO:FO prevented the tenfold suppression of aortic 6-keto-PGF1 alpha caused by FO. These changes in plasma lipids and eicosanoid production are potentially antiatherogenic and may prevent glomerular sclerosis. The combination of EPO and FO, containing n-6 and n-3 fatty acids may offer advantages over either family of fatty acids in this model of nephrotic syndrome.

  13. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    SciTech Connect

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.

  14. Decreased arachidonic acid content and metabolism in tissues of NZB/W F1 females fed a diet containing 0. 45% dehydroisoandrosterone (DHA)

    SciTech Connect

    Matsunaga, A.; Cottam, G.L.

    1987-05-01

    A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous (1-/sup 14/C)arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1..cap alpha.. were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet.

  15. Cyclooxygenase-2-derived prostanoids reduce inward arterial remodeling induced by blood flow reduction in old obese Zucker rat mesenteric arteries.

    PubMed

    Vessières, Emilie; Belin de Chantemèle, Eric J; Guihot, Anne-Laure; Jardel, Alain; Toutain, Bertrand; Loufrani, Laurent; Henrion, Daniel

    2013-01-01

    Obesity is associated with altered arterial structure and function leading to arterial narrowing in most vascular beds, especially when associated with aging. Nevertheless, mesenteric blood flow remains elevated in obese rats, although the effect of aging remains unknown. We investigated mesenteric artery narrowing following blood flow reduction in vivo in 3- and 12-month-old obese Zucker rats. After 21 days, inward remodeling occurred in low flow (LF) arteries in young and old lean rats and in young obese rats (30% diameter reduction). Diameter did not significantly decrease in old obese rats. Phenylephrine-mediated contraction was reduced by approximately 20% in LF arteries in all groups but in old obese rat arteries in which the decrease reached 80%. LF arteries expressed cyclooxygenase-2 and blood 6-keto-PGF1alpha (prostacyclin metabolite) was elevated in old obese rats. In old obese rats, acute cyclooxygenase-2 blockade restored phenylephrine-mediated contraction in LF arteries and chronic cyclooxygenase-2 blockade restored inward remodeling and contractility to control level. Thus, in old obese rats, cyclooxygenase-2-derived prostacyclin prevented the diameter reduction induced by a chronic decrease in blood flow. This adaptation is in favor of a preserved perfusion of the mesentery by contrast with other vascular territories, possibly amplifying the vascular disorders occurring in obesity.

  16. C5a-induced hemodynamic and hematologic changes in the rabbit. Role of cyclooxygenase products and polymorphonuclear leukocytes.

    PubMed Central

    Lundberg, C.; Marceau, F.; Hugli, T. E.

    1987-01-01

    Hemodynamic and hematologic changes occurring after intravascular complement activation have implicated the anaphylatoxins in this response. In this study, the hemodynamic and hematologic effects of purified C5a were investigated in rabbits; and involvement of prostanoids, histamine, and polymorphonuclear leukocytes (PMNs) were examined. The anaphylatoxin C5a induces a reversible systemic arterial hypotension which coincides with an increase in central venous pressure (CVP), decreased cardiac output (CO), increased plasma prostanoid levels, as well as neutropenia. Total peripheral resistance (TPR) remained unchanged. The cyclooxygenase inhibitor indomethacin abolished the C5a-induced hypotension and normalized plasma prostanoid levels without altering the C5a-induced neutropenia. The thromboxane (Tx) A2 synthetase inhibitor dazoxiben reduced TxB2 plasma levels and increased 6-keto-prostaglandin PGF1 alpha and PGE2 levels without altering the hypotensive response. However, with dazoxiben treatment both TPR and CVP decreased. The H2-receptor antagonist cimetidine reduced C5a-induced hypotension and diminished prostanoid release. Both the hypotensive response and elevated prostanoid release were observed after C5a challenge in animals rendered neutropenic prior to challenge. It is concluded that C5a-induced arterial hypotension in the rabbit is a PMN-independent reaction, mediated through cyclooxygenase products and, to some degree, by histamine. The mechanism producing systemic arterial hypotension does not seem to involve peripheral vasodilation but appears to be a secondary effect of pulmonary vasoconstriction, possibly mediated by TxA2. PMID:3115110

  17. Alpha irradiation modeling

    SciTech Connect

    Keeton, S C; Mount, M E

    1999-03-26

    With the end of the Cold War and the associated limitations imposed on the nuclear weapons stockpile by strategic arms treaties, much has changed in the stockpile stewardship program. Weapons that were originally designed for stockpile lives on the order of 15 to 20 years are now being evaluated for much longer periods: in some cases as much as 60 years. As such, issues that were once considered to be of no consequence are being reexamined. Among these is the extent of the radiation dose received by secondary organics over time that results from the intrinsic alpha source of the weapon components. This report describes the results of work performed to estimate the alpha radiation deposition in the organic components of an LLNL system at specific points in its stockpile life. Included are discussions of the development of the intrinsic time- and energy-dependent alpha source term per unit mass, estimation of the effective source and absorber material thicknesses, development of a simplified model for the total intrinsic alpha source term and energy deposition in the absorber, and the alpha radiation deposition in the organic components of a selected LLNL weapon.

  18. ALPHA MIS: Reference manual

    SciTech Connect

    Lovin, J.K.; Haese, R.L.; Heatherly, R.D.; Hughes, S.E.; Ishee, J.S.; Pratt, S.M.; Smith, D.W.

    1992-02-01

    ALPHA is a powerful and versatile management information system (MIS) initiated and sponsored and by the Finance and Business Management Division of Oak Ridge National Laboratory, who maintain and develop it in concert with the Business Systems Division for its Information Center. A general-purpose MIS, ALPHA allows users to access System 1022 and System 1032 databases to obtain and manage information. From a personal computer or a data terminal, Energy Systems employees can use ALPHA to control their own report reprocessing. Using four general commands (Database, Select, Sort, and Report) they can (1) choose a mainframe database, (2) define subsets within it, (3) sequentially order a subset by one or more variables, and (4) generate a report with their own or a canned format.

  19. The Apollo Alpha Spectrometer.

    NASA Technical Reports Server (NTRS)

    Jagoda, N.; Kubierschky, K.; Frank, R.; Carroll, J.

    1973-01-01

    Located in the Science Instrument Module of Apollo 15 and 16, the Alpha Particle Spectrometer was designed to detect and measure the energy of alpha particles emitted by the radon isotopes and their daughter products. The spectrometer sensor consisted of an array of totally depleted silicon surface barrier detectors. Biased amplifier and linear gate techniques were utilized to reduce resolution degradation, thereby permitting the use of a single 512 channel PHA. Sensor identification and in-flight radioactive calibration were incorporated to enhance data reduction.

  20. From Alpha to Omega

    ERIC Educational Resources Information Center

    Czaja, Paul Clement

    2006-01-01

    The Alpha point of the authors' life as a Montessori educator began in 1959, when he was a graduate student studying philosophy at Fordham University in the Bronx, New York. While studying the works of the great American philosopher William James, the author came across the writings of Maria Montessori and immediately became captivated by her…

  1. [alpha]-Oxocarboxylic Acids

    ERIC Educational Resources Information Center

    Kerber, Robert C.; Fernando, Marian S.

    2010-01-01

    Several [alpha]-oxocarboxylic acids play key roles in metabolism in plants and animals. However, there are inconsistencies between the structures as commonly portrayed and the reported acid ionization constants, which result because the acids are predominantly hydrated in aqueous solution; that is, the predominant form is RC(OH)[subscript 2]COOH…

  2. Radial-velocity variations in Alpha Ori, Alpha Sco, and Alpha Her

    SciTech Connect

    Smith, M.A.; Patten, B.M.; Goldberg, L. Computer Sciences Corp., Seabrook, MD Iowa State Univ., Ames )

    1989-12-01

    Radial-velocity observations of Alpha Ori, Alpha Sco A, and Alpha Her A are used to study radial-velocity periodicities in M supergiants. The data refer to several metallic lines in the H-alpha region and to H-alpha itself. It is shown that Alpha Ori and Alpha Sco A have cycle lengths of about 1 yr and semiamplitudes of 2 km/s. It is suggested that many semiregular red supergiant varibles such as Alpha Ori may be heading toward chaos. All three stars show short-term stochastic flucutations with an amplitude of 1-2 km/s. It is found that the long-term variability of H-alpha velocities may be a consequence of intermittent failed ejections. 58 refs.

  3. Effects of ozone on cyclooxygenase metabolites in the baboon tracheobronchial tree

    SciTech Connect

    Fouke, J.M.; DeLemos, R.A.; Dunn, M.J.; McFadden, E.R. Jr. )

    1990-07-01

    Short-term exposure to 0.5 parts per million (ppm) ozone has been shown to cause an increase in respiratory resistance in primates that can be diminished by 50% with pretreatment with cromolyn sodium. Because of the known membrane-stabilizing effects of cromolyn and the resultant inhibition of mediator production, we hypothesized a role for the products of arachidonic acid (AA) metabolism in these events. We exposed five adult male baboons to 0.5 ppm ozone on two occasions, once with cromolyn pretreatment and once without. Pulmonary resistance (RL) was monitored and bronchoalveolar lavage (BAL) was performed before and after each exposure. The BAL was analyzed for a stable hydrolysis product of prostacyclin, 6-keto-prostaglandin (PG) F1 alpha, PGE2, a stable hydrolysis product of thromboxane (Tx) A2, TxB2, and PGF2 alpha. RL increased after ozone exposure (1.62 +/- 0.23 to 3.77 +/- 0.51 cmH2O.l-1.s, difference 2.15; P less than 0.02), and this effect was partially blocked by cromolyn (1.93 +/- 0.09 to 3.18 +/- 0.40 cmH2O.l-1.s, difference 1.25; P less than 0.02). The base-line levels of the metabolites of AA in the BAL were as follows (in pg/ml): 6-keto-PGF1 alpha 72.78 +/- 12.6, PGE2 145.92 +/- 30.52, TxB2 52.52 +/- 9.56, and PGF2 alpha 22.28 +/- 5.42. Ozone exposure had no effect on the level of any of these prostanoids (P = NS). These studies quantify the magnitude of cyclooxygenase products of AA metabolism in BAL from baboon lungs and demonstrate that changes in the levels of these mediators in BAL are not prerequisites for ozone-induced increases in respiratory resistance.

  4. Summary of Alpha Particle Transport

    SciTech Connect

    Medley, S.S.; White, R.B.; Zweben, S.J.

    1998-08-19

    This paper summarizes the talks on alpha particle transport which were presented at the 5th International Atomic Energy Agency's Technical Committee Meeting on "Alpha Particles in Fusion Research" held at the Joint European Torus, England in September 1997.

  5. HB Hillingdon [alpha46(CE4)Phe-->Val (alpha1 Or alpha2)]: a new alpha chain hemoglobin variant.

    PubMed

    Babb, Anna; Solaiman, Susannah; Green, Brian N; Mantio, Debbie; Patel, Ketan

    2009-01-01

    Routine antenatal hemoglobinopathy screening detected a new alpha chain variant that eluted with Hb A(2) on cation exchange high performance liquid chromatography (HPLC) in a lady of Sri Lankan origin who had normal hematological indices. The mutation was identified by electrospray ionization mass spectrometry (ESI-MS) as alpha46(CE4)Phe-->Val, inferring that the variant was due to a single base change at codon 46 (TTC>GTC) of the alpha1- or alpha2-globin genes.

  6. Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum.

    PubMed

    Porcu, Patrizia; O'Buckley, Todd K; Alward, Sarah E; Marx, Christine E; Shampine, Lawrence J; Girdler, Susan S; Morrow, A Leslie

    2009-01-01

    The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, p<0.001), (3alpha,5alpha)-3,21-dihydroxypregnan-20-one (3alpha,5alpha-THDOC, +205%, p<0.01), (3alpha,5alpha)-3-hydroxyandrostan-17-one (3alpha,5alpha-A, +216%, p<0.001), (3alpha,5alpha,17beta)-androstane-3,17-diol (3alpha,5alpha-A-diol, +190%, p<0.01). (3alpha,5beta)-3-hydroxypregnan-20-one (3alpha,5beta-THP) and (3alpha,5beta)-3-hydroxyandrostan-17-one (3alpha,5beta-A) were not altered, while (3alpha,5beta)-3,21-dihydroxypregnan-20-one (3alpha,5beta-THDOC) and (3alpha,5beta,17beta)-androstane-3,17-diol (3alpha,5beta-A-diol) were increased from undetectable levels to 271+/-100 and 2.4+/-0.9 pg+/-SEM, respectively (5/8 rats). Progesterone administration increased serum levels of 3alpha,5alpha-THP (+1806%, p<0.0001), 3alpha,5beta-THP (+575%, p<0.001), 3alpha,5alpha

  7. The ALPHA Magnetic Spectrometer

    NASA Astrophysics Data System (ADS)

    Viertel, G. M.; Capell, M.

    1998-12-01

    The ALPHA Magnetic Spectrometer (AMS) will be the first large magnetic spectrometer in space. It is scheduled to be installed on the future International Space Station ALPHA (ISSA) in the year 2002 to perform measurements of the charged particle composition to answer fundamental questions in particle physics and astrophysics. Before installation on ISSA, AMS will fly on the shuttle DISCOVERY for a period of 10 days starting in May 1998. This will enable AMS to perform a test of the apparatus and first measurements. The AMS detector has five major components: A permanent NdFeB magnet, six planes of Silicon double-sided microstrip detectors, a plastic scintillator time of flight hodoscope, a plastic scintillator anticoincidence counter and an Aerogel Cherenkov threshold counter. In addition, there are electronics, support infrastructure and interfaces.

  8. Influence of ShuJinHuoXue tablets on ischemia reperfusion injury of animals' skeletal muscle.

    PubMed

    Tong, Zhihong; Yu, Fang; Liu, Zhonghua; Liang, Haidong

    2012-07-16

    Ischemia-reperfusion (IR) can lead to serious tissue oxidative injury in animals. ShuJinHuoXue tablet (SJHXT) is a Chinese Traditional Medicine which can relax the muscles and stimulate the blood circulation and has been used as a clinical medicine. In the present study, we investigated the effects of SJHXT pretreatment on oxidative injury using an animal model of acute limb IR. Results showed that SJHXT pre-treatment (200, 300 and 400 mg/kg/day) markedly reduced serum endothelin-1 (ET-1), thromboxane B2 (TXB₂) levels and thromboxane B2/6-keto- prostaglandin F1α (TXB₂/6-Keto-PGF(1α)), wet weight/dried weight (W/D) ratio, myeloperoxidase (MPO), creatine kinase (CK), lactate dehydrogenase (LDH) activities, and increased serum nitric oxide (NO), 6-Keto-PGF(1α) levels and NO/ET-1 ratio in the IR+SJHXT groups. In addition, the SJHXT pre-treatment (200, 300 and 400 mg/kg/day) markedly reduced skeletal muscle Ca²⁺, malondialdehyde (MDA) levels, increased Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. Our results suggest that SJHXT pre-treatment may improve skeletal muscle blood vessel microcirculation, decrease skeletal muscle oxidative injury and enhance antioxidant enzymes activities in IR animals.

  9. Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats.

    PubMed

    Muñoz-Marín, Javier; De la Cruz, José Pedro; Reyes, José Julio; López-Villodres, Juan Antonio; Guerrero, Ana; López-Leiva, Inmaculada; Espartero, José Luis; Labajos, María Teresa; González-Correa, José Antonio

    2013-08-01

    The low lipophilicity of hydroxytyrosol (HT) has motivated efforts to synthesize homologous series with better lipid solubility, such as the ethers, which are more lipophilic than HT. Because HT inhibits platelet aggregation, the aim of the study was to assess the possible anti-platelet effect of five HT ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl) after oral administration to rats. Whole blood collagen-induced platelet aggregation and calcium-induced thromboxane B2 (TxB2), aortic 6-keto-prostaglandin F1α (6-keto-PGF1α) and nitrites+nitrates, plasma concentration of lipid peroxides (TBARS) and red blood cell content of reduced glutathione (GSH) were measured. The administration of 20 mg/kg/day inhibited platelet aggregation, TxB2 and TBARS in a non-linear manner related to the length of the carbon chain, with a cut-off effect in the hexyl derivative. Aortic nitrite and red blood cell GSH production were also increased. The aortic production of 6-keto-PGF1α was unaltered except in the group treated with the dodecyl derivative. The administration of 50 mg/kg/day showed a similar pharmacodynamic profile but without the non-linear effect. In conclusion, HT ethers, especially the hexyl derivative, are a potential alternative to hydroxytyrosol, and their effect merits additional research to determine their role in the prophylaxis of vascular disease.

  10. Relative contributions of direct and indirect mechanisms mediating endothelin-induced contraction of guinea-pig trachea.

    PubMed Central

    Hay, D. W.; Hubbard, W. C.; Undem, B. J.

    1993-01-01

    1. The present study was undertaken to determine the mechanism of action of endothelin-1 (ET-1)-induced contraction of the guinea-pig isolated trachea. 2. ET-1 (1 nM-0.3 microM) produces a concentration-dependent contraction of guinea-pig trachea with an EC50 of approximately 25 nM. The combination of the peptidoleukotriene receptor antagonist, SK&F 104353 (10 microM) and the H1-histamine receptor antagonist, mepyramine (10 microM), which abolishes antigen-induced contraction in guinea-pig trachea, was without effect on ET-1 concentration-response curves. Furthermore, the platelet-activating factor (PAF) receptor antagonist, WEB 2086, (1 or 10 microM) did not inhibit ET-induced contraction. 3. ET-1 (0.3 microM) did not stimulate histamine or immunoreactive peptidoleukotriene release from guinea-pig isolated trachea. 4. The release of various prostanoids from guinea-pig trachea was increased significantly by ET-1 (0.3 microM); the profile of release was prostaglandin D2 (PGD2) = PGE2 = 6-keto PGF1 alpha (PGI2 metabolite) > thromboxane B2 = PGF2 alpha >> 9 alpha, 11 beta PGF2 (PGD2 metabolite). ET-1-induced release of prostaglandins, which was about 30% of that elicited by antigen in sensitized tissues, was not affected by epithelium removal and was observed in tissues from which the smooth muscle had been removed. Previous studies in our laboratory indicated that indomethacin potentiated contraction produced by high concentrations of ET-1, whereas a thromboxane receptor antagonist was without appreciable effect on ET-1 concentration-response curves. 5. Pretreatment of tissues for 1 h with capsaicin (10 microM), which depletes different sensory neurones, produced a small, but significant, inhibitory effect on ET-1 concentration-response curves in the presence but not the absence of the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7507780

  11. Background canceling surface alpha detector

    DOEpatents

    MacArthur, D.W.; Allander, K.S.; Bounds, J.A.

    1996-06-11

    A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone. 5 figs.

  12. Background canceling surface alpha detector

    DOEpatents

    MacArthur, Duncan W.; Allander, Krag S.; Bounds, John A.

    1996-01-01

    A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone.

  13. Are alpha-gliadins glycosylated?

    PubMed

    Turner, J B; Garner, G V; Gordon, D B; Brookes, S J; Smith, C A

    2002-02-01

    Alpha-gliadins isolated by carboxymethylcellulose chromatography contain noncovalently bound glucose probably due to contaminating proteoglycans and to material shed from the column. Traces of carbohydrate remain strongly bound to alpha-gliadins even after harsh denaturation, but our results indicate alpha-gliadins are not glycoproteins. Suggestions that gliadins are glycoproteins are probably due to contamination with this glucose and the presence of these proteoglycans.

  14. Long range alpha particle detector

    DOEpatents

    MacArthur, D.W.; Wolf, M.A.; McAtee, J.L.; Unruh, W.P.; Cucchiara, A.L.; Huchton, R.L.

    1993-02-02

    An alpha particle detector capable of detecting alpha radiation from distant sources. In one embodiment, a high voltage is generated in a first electrically conductive mesh while a fan draws air containing air molecules ionized by alpha particles through an air passage and across a second electrically conductive mesh. The current in the second electrically conductive mesh can be detected and used for measurement or alarm. The detector can be used for area, personnel and equipment monitoring.

  15. Modeling Solar Lyman Alpha Irradiance

    NASA Technical Reports Server (NTRS)

    Pap, J.; Hudson, H. S.; Rottman, G. J.; Willson, R. C.; Donnelly, R. F.; London, J.

    1990-01-01

    Solar Lyman alpha irradiance is estimated from various solar indices using linear regression analyses. Models developed with multiple linear regression analysis, including daily values and 81-day running means of solar indices, predict reasonably well both the short- and long-term variations observed in Lyman alpha. It is shown that the full disk equivalent width of the He line at 1083 nm offers the best proxy for Lyman alpha, and that the total irradiance corrected for sunspot effect also has a high correlation with Lyman alpha.

  16. Alpha Kappa Alpha Sorority's Reading Improvement Program for Minorities.

    ERIC Educational Resources Information Center

    Marable, June Morehead

    This document discusses the founding and establishment of Alpha Kappa Alpha Sorority's reading experience pilot project. The efforts of this project were aligned with those of Right to Read and Reading Is Fundamental (RIF). Because of the response from parents and children, plans are being made to increase present operations within the next…

  17. Molecular characterization of alpha 1- and alpha 2-adrenoceptors.

    PubMed

    Harrison, J K; Pearson, W R; Lynch, K R

    1991-02-01

    Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin Lynch and his colleagues discuss these questions in this review.

  18. Microscopic cluster model of {alpha}+n, {alpha}+p, {alpha}+ {sup 3}He, and {alpha}+{alpha} elastic scattering from a realistic effective nuclear interaction

    SciTech Connect

    Dohet-Eraly, J.; Baye, D.

    2011-07-15

    An effective nucleon-nucleon interaction adapted to cluster-model calculations of collisions is derived from the realistic Argonne potential AV18 with the unitary correlation operator method. The unitary correlation is determined from the {alpha}+{alpha} elastic phase shifts calculated in a cluster approach by the generator coordinate method coupled with the microscopic R-matrix method. With this interaction, the elastic phase shifts for the {alpha}+n, {alpha}+p, and {alpha}+{sup 3}He collisions are calculated within the same model. Without further adjustment, a good agreement with experimental data is obtained with a small model space.

  19. Alpha-particle microdosimetry.

    PubMed

    Chouin, Nicolas; Bardies, Manuel

    2011-07-01

    With the increasing availability of alpha emitters, targeted α-particle therapy has emerged as a solution of choice to treat haematological cancers and micrometastatic and minimal residual diseases. Alpha-particles are highly cytotoxic because of their high linear energy transfer (LET) and have a short range of a few cell diameters in tissue, assuring good treatment specificity. These radiologic features make conventional dosimetry less relevant for that context. Stochastic variations in the energy deposited in cell nuclei are important because of the microscopic target size, low number of α- particle traversals, and variation in LET along the α-particle track. Microdosimetry provides a conceptual framework that aims at a systematic analysis of the stochastic distribution of energy deposits in irradiated matter. The different quantities of microdosimetry and the different methods of microdosimetric calculations were described in the early eighties. Since then, numerous models have been published through the years and applied to analyse experimental data or to model realistic therapeutic situations. Major results have been an accurate description of the high toxicity of α-particles, and the description of the predominant effect of activity distribution at the cellular scale on toxicity or efficacy of potential targeted α-particle therapies. This last factor represents a major limitation to the use of microdosimetry in vivo because determination of the source - target distribution is complicated. The future contributions of microdosimetry in targeted α-particle therapy research will certainly depend on the ability to develop high-resolution detectors and on the implementation of pharmaco-kinetic models at the tumour microenvironment scale.

  20. DFT CONFORMATIONAL STUDIES OF ALPHA-MALTOTRIOSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent DFT optimization studies on alpha-maltose improved our understanding of the preferred conformations of alpha-maltose and the present study extends these studies to alpha-maltotriose with three alpha-D-glucopyranose residues linked by two alpha-[1-4] bridges, denoted herein as DP-3's. Combina...

  1. Prothymosin alpha in human blood.

    PubMed Central

    Panneerselvam, C; Haritos, A A; Caldarella, J; Horecker, B L

    1987-01-01

    The major cross-reacting peptide in human plasma detected with a radioimmunoassay (RIA) for thymosin alpha 1 was identified as prothymosin alpha, based on its elution properties in gel-filtration chromatography and its amino acid composition after purification by HPLC. A small quantity (less than 10%) of the total cross-reacting material was recovered in fractions corresponding to lower molecular weight thymosin alpha 1-like peptides. The total quantity of cross-reacting material detected in human blood, expressed as thymosin alpha 1 equivalents, was 11-14 pmol/ml (approximately 90% was recovered in the leukocyte fraction, approximately 10% was in the plasma fraction, and 1-2% was in the erythrocyte fraction). The peptide present in leukocytes was also identified as prothymosin alpha. After correction for the 5-times lower molar reactivity of prothymosin alpha in the thymosin alpha 1 RIA employed in these experiments, we estimate that the content of prothymosin alpha in human blood is 55-70 pmol/ml (0.6-0.8 microgram/ml). The relatively small quantities recovered in the erythrocyte and plasma fractions may be attributed to contamination of the former by leukocytes or to leakage from leukocytes into the plasma. PMID:3474615

  2. EEG Alpha Power and Intelligence.

    ERIC Educational Resources Information Center

    Doppelmayr, M.; Klimesch, W.; Stadler, W.; Pollhuber, D.; Heine, C.

    2002-01-01

    Tested whether alpha power in different sub-bands is selectively related to intelligence. For 74 Austrian subjects, the EEG was recorded during a resting session and 2 different intelligence tests were performed. Findings show a strong positive correlation between intelligence and alpha power. (SLD)

  3. Alpha particle emitters in medicine

    SciTech Connect

    Fisher, D.R.

    1989-09-01

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ({sup 211}At) and natural bismuth-212 ({sup 212}Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ({sup 223}Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs.

  4. Prevalence of -alpha(3.7) and alpha alpha alpha(anti3.7) alleles in sickle cell trait and beta-thalassemia patients in Mexico.

    PubMed

    Nava, María Paulina; Ibarra, Bertha; Magaña, María Teresa; de la Luz Chávez, María; Perea, F Javier

    2006-01-01

    The aim of this study was to determine the frequency of alpha-globin gene mutations in three groups of Mexican unrelated individuals. The first two groups were normal and sickle cell trait individuals from the Costa Chica region, a place with a 12.8% frequency of HbS carriers, and the third group comprised of Mexican mestizo patients with beta-thalassemia. We searched for -alpha(3.7) and -alpha(4.2) alpha(+)-thalassemia deletion alleles, as well as the alpha alpha alpha(anti3.7) triplication through long-gap PCR. The alleles -alpha(3.7) and alpha alpha alpha(anti3.7) were found in the heterozygote state only; 19% of the normal subjects had the -alpha(3.7) allele, and 2% showed the alpha alpha alpha(anti3.7) allele. In individuals with the sickle cell trait, 17% had the -alpha(3.7) deletion, and the alpha alpha alpha(anti3.7) triplication was observed in 3% of these individuals. We revealed that 16% of the subjects with beta-thalassemia showed the -alpha(3.7) deletion and 28% the alpha alpha alpha(anti3.7) triplication. The -alpha(4.2) deletion was not detected in any individual. The frequency of the -alpha(3.7) allele was roughly the same in the three groups studied; this can be explained by the fact that the three groups have common genes from Africa and the Mediterranean, where a high prevalence of alpha(+)-thalassemia has been observed. To our knowledge, the frequency of alpha alpha alpha(anti3.7) triplication observed in the Mexican beta-thalassemia patients is the highest reported. As the -alpha(3.7) and alpha alpha alpha(anti3.7) alleles are very common in our selected populations, we believe that there is a need to investigate systematically the alpha-globin gene mutations in all hemoglobinopathies in the Mexican population.

  5. Identifying diagnostic endocrine markers and changes in endometrial gene expressions during pyometra in cats.

    PubMed

    Jursza-Piotrowska, Ewelina; Siemieniuch, Marta J

    2016-06-01

    Pyometra is a significant reproductive problem in cats. The aims of this study were to evaluate (i) the immunological profile of queens by studying plasma concentrations of metabolites of prostacyclin I2 (6-keto-PGF1α), leukotriene B4 (LTB4) and leukotriene C4 (LTC4); and (ii) the gene transcription profiles of Toll-like receptors (TLRs) 2 and 4 (TLR2/4), PGE2-synthase (PGES), PGF2α-synthase (PGFS) and prostaglandin-endoperoxide synthase 2 (PTGS2) in the feline endometrium throughout the estrous cycle, after medroxyprogesterone acetate (MPA) treatment and during pyometra. The concentration of plasma 6-keto-PGF1α in pyometra was increased in comparison to other groups studied (p<0.01). Endometrial mRNA coding for TLR2 was up-regulated in cats suffering from pyometra compared to other groups (p<0.001). Expression of mRNA for TLR4 was up-regulated in endometria originating from MPA-treated cats, pyometra and late diestrus cats, compared with tissues from cats during estrus and anestrus (p<0.05). As expected, endometrial mRNA for PTGS2 was up-regulated only in pyometra, compared with other groups (p<0.001). Similarly, endometrial mRNA for PGFS was up-regulated in pyometra, compared with endometria from anestrus, late diestrus and from MPA-treated cats (p<0.05), or from cats during estrus (p<0.01). Overall, these results indicate that plasma concentrations of LTB4 and LTC4 are not useful diagnostic markers since they were not increased in queens with pyometra, in contrast to 6-keto-PGF1α. In addition, treatment with MPA evoked neither endocrine nor molecular changes in endometria of cats.

  6. Stimulation of arachidonic acid metabolism in primary cultures of osteoblast-like cells by hormones and drugs

    SciTech Connect

    Feyen, J.H.; van der Wilt, G.; Moonen, P.; Di Bon, A.; Nijweide, P.J.

    1984-12-01

    The effects of parathyroid hormone (PTH), dihydroxycholecalciferol (1,25-(OH)2 D3), thrombin, epidermal growth factor (EGF) and 12-o-tetradecanoylphorbol-13-acetate (PMA) on the biosynthesis and release of arachidonic acid metabolites were studied in primary cultures of osteoblast-like cells isolated from 18-day-old chick embryo calvaria. Cells were labelled with (/sup 14/C)-arachidonic acid for 30 h. The radioactive eicosanoids were extracted from the cell culture media after a further 30 h stimulation period and analysed on a PRP-1 column by HPLC. The radioactive products were characterized by co-elution of (/sup 3/H) standard prostanoids. Osteoblasts showed a basal release of the prostanoids 6-keto-PGF1 alpha, TXB2, PGF2 alpha, PGE2, PGD2 and PGB2, the latter being the most abundant one. Indomethacin (10(-5) M) effectively inhibited the basal release, but not that of an as yet unidentified compound. The release of prostanoids was stimulated by PTH (2 U/ml), thrombin (0.4 NIH/ml), EGF (50 ng/ml) and PMA (25 ng/ml), the latter being by far the most potent one. 1,25-(OH)2D3 was found to slightly inhibit the prostanoid release. These results indicate: (1) primary cultures of osteoblasts synthesize several prostaglandins, thromboxane B2 and one unidentified product. (2) the action on bone of PTH and the various drugs tested may be, at least partly, mediated by an increased prostaglandin production by osteoblasts. Clearly this does not apply to 1,25-(OH)2D3.

  7. Venus - Alpha Regio

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The eastern edge of Alpha Regio is shown in this image centered at 30 degrees south latitude and 11.8 degrees east longitude (longitude on Venus is measured from 0 degrees to 360 degrees east). Seven circular, dome-like hills, averaging 25 kilometers (15 miles) in diameter with maximum heights of 750 meters (2,475 feet) dominate the scene. These features are interpreted as very thick lava flows that came from an opening on the relatively level ground, which allowed the lava to flow in an even pattern outward from the opening. The complex fractures on top of the domes suggest that if the domes were created by lava flows, a cooled outer layer formed and then further lava flowing in the interior stretched the surface. The domes may be similar to volcanic domes on Earth. Another interpretation is that the domes are the result of molten rock or magma in the interior that pushed the surface layer upward. The near-surface magma then withdrew to deeper levels, causing the collapse and fracturing of the dome surface. The bright margins possibly indicate the presence of rock debris on the slopes of the domes. Some of the fractures on the plains cut through the domes, while others appear to be covered by the domes. This indicates that active processes pre date and post date the dome-like hills. The prominent black area in the northeast corner of the image is a data gap. North is at the top of the image.

  8. Synthesis of a precursor for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha,17 beta-diol 17-glucuronide

    SciTech Connect

    Rao, P.N.; Damodaran, K.M.

    1984-03-01

    Starting from 11 beta-hydroxytestosterone, the synthesis of a strategic precursor, C-9 (11) unsaturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (9a), for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide has been achieved. The authors optimized the reaction conditions for catalytic reduction employing hydrogen and subsequent base hydrolysis followed by purification on Amberlite XAD-2 resin to obtain the saturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide.

  9. Alpha-particle spectrometer experiment

    NASA Technical Reports Server (NTRS)

    Gorenstein, P.; Bjorkholm, P.

    1972-01-01

    Mapping the radon emanation of the moon was studied to find potential areas of high activity by detection of radon isotopes and their daughter products. It was felt that based on observation of regions overflown by Apollo spacecraft and within the field of view of the alpha-particle spectrometer, a radon map could be constructed, identifying and locating lunar areas of outgassing. The basic theory of radon migration from natural concentrations of uranium and thorium is discussed in terms of radon decay and the production of alpha particles. The preliminary analysis of the results indicates no significant alpha emission.

  10. Effect of exogenous 5,8,11,14,17-eicosapentaenoic acid on cardiac anaphylaxis.

    PubMed Central

    Juan, H.; Peskar, B. A.; Simmet, T.

    1987-01-01

    The effects of infusions of eicosapentaenoic acid (EPA) (6 X 10(-8) mol min-1 and 15 X 10(-8) mol min-1) on the coronary constriction and the release of immunoreactive sulphidopeptide-leukotrienes (SP-LT), thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) from perfused anaphylactic guinea-pig hearts were investigated. EPA dose-dependently inhibited the profound early coronary flow reduction after antigen injection. The less pronounced late phase of anaphylactic coronary flow reduction was, however, not significantly affected. EPA (15 X 10(-8) mol min-1) significantly shortened the average duration of antigen-induced arrhythmias. EPA dose-dependently decreased release of immunoreactive TXB2 and 6-keto-PGF1 alpha from anaphylactic guinea-pig hearts. Release of immunoreactive SP-LT was dose-dependently increased after antigen challenge in the presence of EPA. Inhibiton of the release of SP-LT by the lipoxygenase inhibitor esculetin (1 X 10(-7) mol min-1) was accompanied by a significant attenuation of flow reduction during the late phase of anaphylactic vasoconstriction. Reversed phase h.p.l.c. of perfusates from anaphylactic guinea-pig hearts revealed immunoreactivity comigrating with authentic leukotriene C4 (LTC4), LTD4, and LTE4. In perfusates from hearts treated with EPA infusions, additional immunoreactivity was detected comigrating with LTC5, LTD5 and LTE5. In addition to immunoreactivity migrating with LTB4, as observed in control heart perfusates, in perfusates from EPA-treated hearts, a second peak was observed, which coincides with the retention time described for LTB5. Exogenous LTC5 (1 X 10(-12) mol min-1 and 20 X 10(-12) mol min-1) induced dose-dependent reductions of coronary flow and was found to be a slightly weaker constrictor than LTC4, but no significant differences were observed. Coronary vasoconstriction elicited by infusion of exogenous LTC4 (20 X 10(-12) mol min-1) was dose-dependently inhibited by infusions of EPA. However

  11. Alpha Magnetic Spectrometer (AMS) Overview

    NASA Video Gallery

    The Alpha Magnetic Spectrometer (AMS) is flying to the station on STS-134. The AMS experiment is a state-of-the-art particle physics detector being operated by an international team composed of 60 ...

  12. Genetics Home Reference: alpha thalassemia

    MedlinePlus

    ... a blood disorder that reduces the production of hemoglobin . Hemoglobin is the protein in red blood cells that ... alpha thalassemia , a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. ...

  13. Progesterone's 5 alpha-reduced metabolite, 3 alpha,5 alpha-THP, mediates lateral displacement of hamsters.

    PubMed

    Frye, Cheryl A; Rhodes, Madeline E

    2005-03-15

    5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), progesterone (P4)'s 5 alpha-reduced, 3 alpha-hydroxysteroid oxidoreduced product, facilitates lordosis of rodents in part via agonist-like actions at GABA(A)/benzodiazepine receptor complexes in the ventral tegmental area (VTA). Whether 3 alpha,5 alpha-THP influences another reproductively-relevant behavior, lateral displacement, of hamsters was investigated. Lateral displacement is the movement that female hamsters make with their perineum towards male-like tactile stimulation. This behavior facilitates, and is essential for, successful mating. Hamsters in behavioral estrus had greater lateral displacement responses when endogenous progestin levels were elevated compared to when progestin levels were lower. Administration of P4, a prohormone for 3 alpha,5 alpha-THP, dose-dependently (500 > 200 > 100, 50, or 0 microg) enhanced lateral displacement of ovariectomized hamsters that had been primed with SC estradiol benzoate (5 or 10 microg). Inhibiting P4's metabolism to 3 alpha,5 alpha-THP by co-administering finasteride, a 5 alpha-reductase inhibitor, or indomethacin, a 3 alpha-hydroxysteroid oxidoreductase inhibitor, either systemically or to the VTA, significantly decreased lateral displacement and midbrain progestin levels of naturally receptive or hormone-primed hamsters compared to controls. These data suggest that lateral displacement is progestin-sensitive and requires the formation of 3 alpha,5 alpha-THP in the midbrain VTA.

  14. Mechanism of alpha-tocopheryl-phosphate (alpha-TP) transport across the cell membrane

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have reported that alpha-TP is synthesized and hydrolyzed in animal cells and tissues; it modulates also several cell functions (FRBM 39:970, and UBMB Life, 57:23, 2005). While it is similar to alpha-tocopherol (alpha-T), alpha-TP appears to be more potent than alpha-T in inhibiting cell prolifer...

  15. Workshop on Precision Measurements of $\\alpha_s$

    SciTech Connect

    Bethke, Siegfried; Hoang, Andre H.; Kluth, Stefan; Schieck, Jochen; Stewart, Iain W.; Aoki, S.; Beneke, M.; Bethke, S.; Blumlein, J.; Brambilla, N.; Brodsky, S.; /MIT, LNS

    2011-10-01

    These are the proceedings of the Workshop on Precision Measurements of {alpha}{sub s} held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of {alpha}{sub s}(m{sub Z}) in the {ovr MS} scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, {tau}-decays, electro-weak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

  16. Immunodiagnosis of alpha chain disease.

    PubMed Central

    Doe, W F; Danon, F; Seligmann, M

    1979-01-01

    Since the early diagnosis of alpha chain disease (alphaCD)) is essential to successful treatment and to epidemiological studies, the available immunodiagnostic techniques were compared for their sensitivity, specificity and ease of performance on a panel of sixteen sera, comprising ten alphaCD sera and six control sera containing either IgA myeloma protein or high levels of polyclonal IgA. Immunoselection by immunoelectrophoresis into gel containing a specially developed anti-Fabalpha antiserum provided the most sensitive and specific detection system for alphaCD protein. The same technique using anti-light chain antiserum for immunoselection was also highly sensitive, but proved less specific, being prone to false positives with difficult IgA myeloma proteins. Somewhat less sensitive, but specific and simple to perform, was immunoelectrophoresis using an antiserum recognizing the conformational specificities of Fabalpha as well as those of the constant region of alpha chains. Immunoselection using the Ouchterlony or rocket techniques proved to be less sensitive and prone to false positives when some IgA myeloma sera were tested. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 PMID:113152

  17. Bioisosteric phentolamine analogs as selective human alpha(2)- versus alpha(1)-adrenoceptor ligands.

    PubMed

    Bavadekar, Supriya A; Hong, Seoung-Soo; Lee, Sang-Ii; Miller, Duane D; Feller, Dennis R

    2008-08-20

    Phentolamine is known to act as a competitive, non-subtype-selective alpha-adrenoceptor antagonist. In an attempt to improve alpha(2)- versus alpha(1)-adrenoceptor selectivity and alpha(2)-adrenoceptor subtype-selectivity, two new chemical series of bioisosteric phentolamine analogs were prepared and evaluated. These compounds were evaluated for binding affinities on alpha(1)- (alpha(1A)-, alpha(1B)-, alpha(1D)-) and alpha(2)- (alpha(2A)-, alpha(2B)-, alpha(2C)-) adrenoceptor subtypes that had been stably expressed in human embryonic kidney and Chinese hamster ovary cell lines, respectively. Methylation of the phenolic hydroxy group and replacement of the 4-methyl group of phentolamine with varying lipophilic substituents yielded bioisosteric analogs selective for the alpha(2)- versus alpha(1)-adrenoceptors. Within the alpha(2)-adrenoceptors, these analogs bound with higher affinity at the alpha(2A)- and alpha(2C)-subtypes as compared to the alpha(2B)-subtype. In particular, the t-butyl analog was found to be the most selective, its binding at the alpha(2C)-adrenoceptor (Ki=3.6 nM) being 37- to 173-fold higher than that at the alpha(1)-adrenoceptors, and around 2- and 19-fold higher than at the alpha(2A)- and alpha(2B)-adrenoceptors, respectively. Data from luciferase reporter gene assays confirmed the functional antagonist activities of selected compounds from the bioisosteric series on human alpha(1A)- and alpha(2C)-adrenoceptors. Thus, the results with these bioisosteric analogs of phentolamine provide a lead to the rational design of potent and selective alpha(2)-adrenoceptor ligands that may be useful in improving the therapeutic profile of this drug class for human disorders.

  18. Space Station alpha joint bearing

    NASA Technical Reports Server (NTRS)

    Everman, Michael R.; Jones, P. Alan; Spencer, Porter A.

    1987-01-01

    Perhaps the most critical structural system aboard the Space Station is the Solar Alpha Rotary Joint which helps align the power generation system with the sun. The joint must provide structural support and controlled rotation to the outboard transverse booms as well as power and data transfer across the joint. The Solar Alpha Rotary Joint is composed of two transition sections and an integral, large diameter bearing. Alpha joint bearing design presents a particularly interesting problem because of its large size and need for high reliability, stiffness, and on orbit maintability. The discrete roller bearing developed is a novel refinement to cam follower technology. It offers thermal compensation and ease of on-orbit maintenance that are not found in conventional rolling element bearings. How the bearing design evolved is summarized. Driving requirements are reviewed, alternative concepts assessed, and the selected design is described.

  19. Prostaglandin synthesis in human T cells: its partial inhibition by lectins and anti-CD3 antibodies as a possible step in T cell activation.

    PubMed

    Aussel, C; Mary, D; Fehlmann, M

    1987-05-15

    The human leukemic T cell line Jurkat was used to study arachidonic acid (AA) metabolism. We demonstrated that Jurkat cells are able to convert AA into prostaglandins (PG) and thromboxanes. The presence of tritiated 6-keto-PGF1 alpha, PGE2, PGA2 (B2), and thromboxane B2 in the culture medium was shown either by thin-layer chromatography after a 4-hr incubation period of [3H]AA-prelabeled Jurkat cells or by using specific radioimmuno assays. PG synthesis was inhibited by both indomethacin and niflumic acid, two cyclooxygenase inhibitors. AA metabolism through the cyclooxygenase pathway was followed during T cell activation. T cells were activated by lectins or anti-CD3 monoclonal antibodies (mAb) to trigger the T3-Ti complex and by 12-0-tetradecanoylphorbol 13-acetate (TPA) to mimic IL 1-dependent pathways. Our results show that lectins and anti-CD3 mAb both reduce the amount of PG released by the cells, whereas TPA did not. We confirmed that a combination of TPA and lectins or TPA and anti-CD3 mAb is necessary to obtain full activation of Jurkat cells if this event is monitored by using measurement of IL 2 synthesis. In addition, lectins and anti-CD3 mAb can be replaced by the cyclooxygenase inhibitors indomethacin or niflumic acid. Indeed, a combination of TPA and one of these two drugs induced maximal IL 2 synthesis. These results thus suggest that a reduction in PG synthesis might be a prerequisite to allow the cascade of events involved in T cell activation.

  20. Diet enriched with procyanidins enhances antioxidant activity and reduces myocardial post-ischaemic damage in rats.

    PubMed

    Facino, R M; Carini, M; Aldini, G; Berti, F; Rossoni, G; Bombardelli, E; Morazzoni, P

    1999-01-01

    Aim of this work was to study the efficacy of procyanidins from Vitis vinifera seeds, a standardized mixture of polyphenol antioxidants, on cardiac mechanics following ischemia/reperfusion stunning in the rat, after 3 weeks supplementation. Young and aged male rats were fed a diet enriched with procyanidins complexed (1:3 w/w) with soybean lecithin (2.4%); control animals (CTR-young and CTR-aged) received an equal amount of lecithin and 2 additional groups of animals the standard diet. At the end of the treatment, the total plasma antioxidant defense (TRAP), vitamin E, ascorbic acid and uric acid were determined in plasma and the hearts from all groups of animals subjected to moderate ischemia (flow reduction to 1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min). In both young and aged rats supplemented with procyanidins the recovery of left ventricular developed pressure (LVDP) at the end of reperfusion was 93% (p < 0.01) and 74% (p < 0.01) of the preischemic values and the values of coronary perfusion pressure (CPP) were maintained close to those of the preischemic period. Also creatine kinase (CK) outflow was restrained to baseline levels, while a 2-fold increase in prostacyclin (6-keto-PGF1alpha) in the perfusate from hearts of young and aged rats was elicited during both ischemia and reperfusion. In parallel, procyanidins significantly increased the total antioxidant plasma capacity (by 40% in young and by 30% in aged rats) and the plasma levels of ascorbic acid, while tend to reduce vitamin E levels; no significant differences were observed in uric acid levels. The results of this study demonstrate that procyanidins supplementation in the rat (young and aged) makes the heart less susceptible to ischemia/reperfusion damage and that this is positively associated to an increase in plasma antioxidant activity.

  1. Evaluation of platelets and hemostasis during hemodialysis with six different membranes.

    PubMed

    Verbeelen, D; Jochmans, K; Herman, A G; Van der Niepen, P; Sennesael, J; De Waele, M

    1991-01-01

    Hemodialysis induces thrombocytopenia and activation of coagulation. The severity of this reaction depends on the kind of membrane. In this study, we present the results of determination of platelet count, and of different factors of coagulation in 10 stable dialysis patients. Measurements were performed at the start and after 15 and 45 min of dialysis. Samples were taken before and after the dialyzer. All 10 patients were treated consecutively and in a random order during 14 days with the following membranes: polyacrylonitrile (Filtral 12, Hospal), hemophan (GFS 120 Plus, Gambro, and Bio-Nephros HF Andante, Organon), polysulfone (F6, Fresenius), cuprammonium (AM50-BIO, Asahi) and cellulose acetate (Duo-Flux, Cordis-Dow). The cellulose acetate membrane induced a small but significant drop of mean platelet count [results are mean (SEM)]: from 245,000 (17,000) to 224,000 (16,000)/microliters after 15 min. With the same membrane a dramatic increase after 15 min was noted of 6-keto-PGF1 alpha from 56.3 (9) to 146.7 (35.7) pg/ml. The other membranes did not influence significantly prostanoid levels and platelet count. During dialysis no significant changes of fibrinopeptide A (FPA) and von Willebrand factor (VWF) were observed. Nevertheless, predialysis FPA and beta-thromboglobulin (beta TG) concentrations were lowest after 14 days of treatment with cellulose acetate and polyacrylonitrile membranes. It is concluded that the activation of coagulation depends on the membrane used. The activation may be dominated by one single system (e.g. prostanoids). The different predialysis concentration of some of the factors suggests interference of the dialysis membrane with the activation of coagulation during the interdialytic period.

  2. Endotoxic shock after long-term resuscitation of hemorrhage/reperfusion injury decreased splanchnic blood flow and eicosanoid release.

    PubMed Central

    Myers, S I; Tumage, R H; Kadesky, K M; Seelig, A R; Bartula, L

    1996-01-01

    OBJECTIVE: The authors examine the hypothesis that hemorrhage/reperfusion injury predisposes the splanchnic bed to decreased prostacyclin (PGl2) release and blood flow after subsequent endotoxin challenge. SUMMARY BACKGROUND DATA: Prostacyclin is a potent vasodilator that has been demonstrated to be an important regulator of splanchnic blood flow. Previous studies have demonstrated that during resuscitation from severe hemorrhage, there is a marked reduction in intestinal PGl2 levels, which is associated with reduced splanchnic perfusion. METHODS: Anesthetized Sprague-Dawley rats underwent hemorrhage to a mean arterial pressure of 30 mmHg for 30 minutes followed by the reinfusion of shed blood. Then the animals were maintained on total parenteral nutrition (TPN) for 10 days, after which time they received 20 mg/kg Escherichia coli endotoxin intraperitoneally. Aortic and superior mesenteric artery (SMA) blood flow was monitored with a Doppler flow probe. The splanchnic bed was excised and perfused in vitro for measurement of venous effluent eicosanoid concentrations. Controls consisted of animals that received TPN and endotoxin but did not undergo hemorrhage and resuscitation (sham). RESULTS: Total parenteral nutrition support of sham animals followed by endotoxin challenge did not alter splanchnic eicosanoid release or blood flow. Hemorrhage/reperfusion animals supported by long-term TPN and challenged with endotoxin demonstrated a threefold decrease in splanchnic prostacyclin metabolite (6-keto-PGF1 alpha) release and a 50% decrease in SMA blood flow. CONCLUSIONS: Hemorrhage/reperfusion injury predisposes the splanchnic bed from rats sustained with long-term TPN to decreased release of PGl2 and SMA blood flow when challenged with endotoxin as a second injury. PMID:8757386

  3. Effects of a novel Hungarian antacid containing Al and Mg (Tisacid) on mucosal prostaglandin generation and oxygen free radicals in normal rats.

    PubMed

    Nagy, L; Mózsik, G; Vincze, A; Süto G; Hunyady, B; Rinfel, J; Past, T; Jávor, T

    1990-01-01

    A new patented chemical agent (Al-Mg-hydroxy-carbonate; acid-binding capacity greater than 30 mmol/g) was produced by our work-team. After our preliminary pharmacological and some prospective, randomized, multicentre, controlled clinical studies, this antacid was registered (Tisacid tablet and suspension; Alkaloida, Hungary). A cumulative ulcer healing rate of 80-85% was proved by Tisacid monotherapy applied in low doses (from 80 to 160 mmol/day) in patients with duodenal ulcer. The aims of this study were: (i) to determine the role of different antacids on the genesis of mucosal prostaglandins (PGs) (PGE2 and 6-keto-PGF1 alpha) in normal rats; (ii) to evaluate the effects of indomethacin pre-treatment (20 mg/kg b.w.,s.c.) on the Tisacid-induced alterations of gastric mucosal PG-contents; (iii) to analyse the generation of oxygen free radicals and lipid peroxidation in the rat oxyntic mucosa by the application of different doses of Tisacid (activities of CAT, GSH-px and SOD, contents of MDA and red. GSH). It was found that: Tisacid has a potent gastroproprotective effect in gastric mucosa, via (a) an increase in the mucosal levels of PGs, and (b) a scavenging-like effect in normal rat gastric mucosa. It is concluded that the gastroprotective effect of Tisacid appears because of the following: (i) excellent acid-neutralizing capacity; (ii) mucosal generation of PGs (PGE2 and PGI2); (iii) free radical scavenging; (iv) its possible activity as a Ca-antagonist (Mg-containing compound).

  4. Role of prostaglandins in the renal response to calcium infusion.

    PubMed

    Lahera, V; Fiksen-Olsen, M J; Romero, J C

    1990-04-01

    The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg-1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1.

  5. NACA Physicist Studying Alpha Rays

    NASA Technical Reports Server (NTRS)

    1957-01-01

    NACA Physicits studying Alpha Rays in a continuous cloud chamber. A cloud chamber is used by Lewis scientists to obtain information aimed at minimizing undesirable effects of radiation on nuclear-powered aircraft components. Here, alpha particles from a polonium source emit in a flower-like pattern at the cloud chamber's center. The particles are made visible by means of alcohol vapor diffusing from an area at room temperature to an area at minus -78 deg. Centigrade. Nuclear-powered aircraft were never developed and aircraft nuclear propulsion systems were canceled in the early 1960s.

  6. Bremsstrahlung in {alpha} Decay Reexamined

    SciTech Connect

    Boie, H.; Scheit, H.; Jentschura, U. D.; Koeck, F.; Lauer, M.; Schwalm, D.; Milstein, A. I.; Terekhov, I. S.

    2007-07-13

    A high-statistics measurement of bremsstrahlung emitted in the {alpha} decay of {sup 210}Po has been performed, which allows us to follow the photon spectra up to energies of {approx}500 keV. The measured differential emission probability is in good agreement with our theoretical results obtained within the quasiclassical approximation as well as with the exact quantum mechanical calculation. It is shown that, due to the small effective electric dipole charge of the radiating system, a significant interference between the electric dipole and quadrupole contributions occurs, which is altering substantially the angular correlation between the {alpha} particle and the emitted photon.

  7. Alpha Channeling in Mirror Machines

    SciTech Connect

    Fisch, Nathaniel J.

    2014-07-16

    This Final Report for DE-FG02-06ER54851, Alpha Channeling in Mirror Machines, was in fact submitted on April 9, 2010. Some confusion arose because it was submitted as an initial progress report on a related grant, Alpha Channeling in Open- System Magnetic Devices. The original text is reproduced below, except that the publication record is undated. Note that the articles published in 2009 and 2010 reflect work in fact done under DE-FG02-06ER54851.

  8. Test chamber for alpha spectrometry

    DOEpatents

    Larsen, Robert P.

    1977-01-01

    Alpha emitters for low-level radiochemical analysis by measurement of alpha spectra are positioned precisely with respect to the location of a surface-barrier detector by means of a chamber having a removable threaded planchet holder. A pedestal on the planchet holder holds a specimen in fixed engagement close to the detector. Insertion of the planchet holder establishes an O-ring seal that permits the chamber to be pumped to a desired vacuum. The detector is protected against accidental contact and resulting damage.

  9. The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1

    PubMed Central

    1995-01-01

    The heterodimeric alpha 4 integrins alpha 4 beta 7 lymphocyte Peyer's patch adhesion molecule ([LPAM]-1) and alpha 4 beta 1 (very late antigen-4) are cell surface adhesion molecules involved in lymphocyte trafficking and lymphocyte-cell and matrix interactions. Known cellular ligands include vascular cell adhesion molecule (VCAM)-1, which binds to alpha 4 beta 1 and alpha 4 beta 7, and the mucosal addressin cell adhesion molecule (MAdCAM)-1, which binds to alpha 4 beta 7. Here we show that the alpha 4 chain of these integrins can itself serve as a ligand. The alpha 4 chain, immunoaffinity purified and immobilized on glass slides, binds thymocytes and T lymphocytes. Binding exhibits divalent cation requirements and temperature sensitivity which are characteristic of integrin-mediated interactions, and is specifically inhibited by anti-alpha 4 integrin antibodies, which exert their effect at the cell surface. Cells expressing exclusively alpha 4 beta 7 (TK-1) or alpha 4 beta 1 (L1-2) both bound avidly, whereas alpha 4-negative cells did not. A soluble 34-kD alpha 4 chain fragment retained binding activity, and it inhibited lymphocyte adhesion to alpha 4 ligands. It has been shown that alpha 4 integrin binding to fibronectin involves an leucine-aspartic acid-valine (LDV) motif in the HepII/IIICS region of fibronectin (CS-1 peptide), and homologous sequences are important in binding to VCAM-1 and MAdCAM-1. Three conserved LDV motifs occur in the extracellular sequence of alpha 4. A synthetic LDV-containing alpha 4- derived oligopeptide supports alpha 4-integrin-dependent lymphocyte adhesion and blocks binding to the 34-kD alpha 4 chain fragment. Our results suggest that alpha 4 beta 7 and alpha 4 beta 1 integrins may be able to bind to the alpha 4 subunit on adjacent cells, providing a novel mechanism for alpha 4 integrin-mediated and activation-regulated lymphocyte interactions during immune responses. PMID:7629498

  10. Alpha proton x ray spectrometer

    NASA Technical Reports Server (NTRS)

    Rieder, Rudi; Waeke, H.; Economou, T.

    1994-01-01

    Mars Pathfinder will carry an alpha-proton x ray spectrometer (APX) for the determination of the elemental chemical composition of Martian rocks and soils. The instrument will measure the concentration of all major and some minor elements, including C, N, and O at levels above typically 1 percent.

  11. Sparse Coding for Alpha Matting.

    PubMed

    Johnson, Jubin; Varnousfaderani, Ehsan Shahrian; Cholakkal, Hisham; Rajan, Deepu

    2016-07-01

    Existing color sampling-based alpha matting methods use the compositing equation to estimate alpha at a pixel from the pairs of foreground ( F ) and background ( B ) samples. The quality of the matte depends on the selected ( F,B ) pairs. In this paper, the matting problem is reinterpreted as a sparse coding of pixel features, wherein the sum of the codes gives the estimate of the alpha matte from a set of unpaired F and B samples. A non-parametric probabilistic segmentation provides a certainty measure on the pixel belonging to foreground or background, based on which a dictionary is formed for use in sparse coding. By removing the restriction to conform to ( F,B ) pairs, this method allows for better alpha estimation from multiple F and B samples. The same framework is extended to videos, where the requirement of temporal coherence is handled effectively. Here, the dictionary is formed by samples from multiple frames. A multi-frame graph model, as opposed to a single image as for image matting, is proposed that can be solved efficiently in closed form. Quantitative and qualitative evaluations on a benchmark dataset are provided to show that the proposed method outperforms the current stateoftheart in image and video matting.

  12. Sparse Coding for Alpha Matting.

    PubMed

    Johnson, Jubin; Varnousfaderani, Ehsan; Cholakkal, Hisham; Rajan, Deepu

    2016-04-21

    Existing color sampling based alpha matting methods use the compositing equation to estimate alpha at a pixel from pairs of foreground (F) and background (B) samples. The quality of the matte depends on the selected (F,B) pairs. In this paper, the matting problem is reinterpreted as a sparse coding of pixel features, wherein the sum of the codes gives the estimate of the alpha matte from a set of unpaired F and B samples. A non-parametric probabilistic segmentation provides a certainty measure on the pixel belonging to foreground or background, based on which a dictionary is formed for use in sparse coding. By removing the restriction to conform to (F,B) pairs, this method allows for better alpha estimation from multiple F and B samples. The same framework is extended to videos, where the requirement of temporal coherence is handled effectively. Here, the dictionary is formed by samples from multiple frames. A multi-frame graph model, as opposed to a single image as for image matting, is proposed that can be solved efficiently in closed form. Quantitative and qualitative evaluations on a benchmark dataset are provided to show that the proposed method outperforms current state-of-the-art in image and video matting.

  13. Alcoholism, Alpha Production, and Biofeedback

    ERIC Educational Resources Information Center

    Jones, Frances W.; Holmes, David S.

    1976-01-01

    Electroencephalograms of 20 alcoholics and 20 nonalcoholics were obtained. Data indicated that alcoholics produced less alpha than nonalcoholics. In one training condition subjects were given accurate biofeedback, whereas in the other condition subjects were given random (noncontingent) feedback. Accurate biofeedback did not result in greater…

  14. Coexistence of {alpha}+{alpha}+n+n and {alpha}+t+t cluster structures in {sup 10}Be

    SciTech Connect

    Itagaki, N.; Ito, M.; Milin, M.; Hashimoto, T.; Ishiyama, H.; Miyatake, H.

    2008-06-15

    The coexistence of the {alpha}+{alpha}+n+n and {alpha}+t+t cluster structures in the excited states of {sup 10}Be has been discussed. In the previous analysis, all the low-lying states of {sup 10}Be were found to be well described by the motion of the two valence neutrons around two {alpha} clusters. However, the {alpha}+t+t cluster structure was found to coexist with the {alpha}+{alpha}+n+n structure around E{sub x}=15 MeV, close to the corresponding threshold. We have introduced a microscopic model to solve the coupling effect between these two configurations. The K=0 and K=1 states are generated from the {alpha}+t+t configurations due to the spin coupling of two triton clusters. The present case of {sup 10}Be is one of the few examples in which completely different configurations of triton-type ({alpha}+t+t three-center) and {alpha}-type ({alpha}+{alpha}+n+n two-center) clusters coexist in a single nucleus in the same energy region.

  15. A synopsis of collective alpha effects and implications for ITER

    SciTech Connect

    Sigmar, D.J.

    1990-10-01

    This paper discusses the following: Alpha Interaction with Toroidal Alfven Eigenmodes; Alpha Interaction with Ballooning Modes; Alpha Interaction with Fishbone Oscillations; and Implications for ITER.

  16. What Causes Alpha-1 Antitrypsin Deficiency?

    MedlinePlus

    ... Causes Alpha-1 Antitrypsin Deficiency? Alpha-1 antitrypsin (AAT) deficiency is an inherited disease. "Inherited" means it's ... parents to children through genes. Children who have AAT deficiency inherit two faulty AAT genes, one from ...

  17. How Is Alpha-1 Antitrypsin Deficiency Treated?

    MedlinePlus

    ... Alpha-1 Antitrypsin Deficiency Treated? Alpha-1 antitrypsin (AAT) deficiency has no cure, but its related lung ... pulmonary disease). If you have symptoms related to AAT deficiency, your doctor may recommend: Medicines called inhaled ...

  18. The ultraviolet spectra of Alpha Aquilae and Alpha Canis Minoris

    NASA Technical Reports Server (NTRS)

    Morton, D. C.; Bruzual A., G.; Kurucz, R. L.; Spinrad, H.

    1977-01-01

    Scans of Alpha Aql (A7 IV, V) and Alpha CMi (F5 IV-V) obtained with the Copernicus satellite spectrometer over the wavelength range from 2100 to 3200 A are presented along with a spectrum of the integrated solar disk over the same range procured during a calibrated rocket flight. About 1500 fairly strong absorption lines in the Alpha CMi spectrum between 2400 and 2961 A are identified by comparison with a solar atlas and by using a theoretical spectrum synthesized from a blanketed LTE model with an effective temperature of 6500 K and a surface gravity of 10,000 cm/sec per sec. The Mg II resonance doublet at 2795.528 and 2802.704 A is found to be present in all three stars together with a discontinuity at 2635 A due to Fe II, Fe I, Cr I, and Mn II. It is concluded that the Mg II resonance lines and the 2635-A continuum break would be the best spectral features for estimating the redshift of a galaxy observed at low resolution provided the redshift is not less than about 0.75.

  19. Recent Results on the CKM Angle Alpha

    SciTech Connect

    Mihalyi, A.; /Wisconsin U., Madison

    2005-10-18

    The method to measure the CKM angle {alpha} and the modes sensitive to it are discussed. It is shown that the B {yields} {rho}{rho} decays provide the most stringent constraint on {alpha}, which is found to be {alpha} = 96{sup o} {+-} 10{sup o}(stat) {+-} 4{sup o}(syst){+-} 13{sup o}(penguin).

  20. Genetics Home Reference: alpha-mannosidosis

    MedlinePlus

    ... infantile form Orphanet: Alpha-mannosidosis The MPS Society (UK): Guide to Alpha-Mannosidosis (PDF) Patient Support and ... Organization for Rare Disorders (NORD) The MPS Society (UK) GeneReviews (1 link) Alpha-Mannosidosis ClinicalTrials.gov (1 ...

  1. Effectiveness of Alpha Biofeedback Therapy: Negative Results.

    ERIC Educational Resources Information Center

    Watson, Charles G.; Herder, Joseph

    1980-01-01

    Assessed the utility of alpha biofeedback training in the treatment of patients (N=66). Biofeedback and placebo biofeedback groups were given alpha or mock-alpha training sessions. Improvement on 54 variables was compared to that of no-treatment controls. Only a chance number of significant changes appeared among the groups. (Author)

  2. Effect of Diethylcarbamazine (DEC) on prostaglandin levels in Wuchereria bancrofti infected microfilaraemics.

    PubMed

    Sankari, T; Hoti, S L; Das, L K; Govindaraj, V; Das, P K

    2013-06-01

    Diethylcarbamazine (DEC) interferes with arachidonic acid metabolism for the clearance of microfilariae in Wuchereria bancrofti infected individuals. In this study, we have quantified the plasma concentrations of prostaglandin E2 (PGE2) and 6-keto-PGF1α, the end products of arachidonic acid metabolic pathway in microfilaraemics (DEC treated and untreated), and normal healthy individuals at pre- and 3,9,12,36, and 72 h of post-DEC treatment. We have also determined the microfilariae counts at pre and post day 2 (36 h) and day 3 (72 h) of DEC treatment by membrane filtration technique. Significant reduction in PGE2 and 6-keto-PGF1α concentrations was found at 12 h of DEC treatment. Rapid reduction in microfilarial counts was observed at 36 h of post-DEC treatment. Higher levels of prostaglandins were found at pre-treatment hours in microfilaraemics compared to normal healthy individuals (P < 0.05). Our findings indicate that DEC inhibits prostaglandins for the clearance of microfilariae, and increased levels of prostaglandins in microfilaraemics may be contributed by the parasite or host upon stimulation.

  3. Brassinolide activities of 2alpha,3alpha-diols versus 3alpha,4alpha-diols in the bean second internode bioassay: explanation by molecular modeling methods.

    PubMed

    Sísa, Miroslav; Vilaplana-Polo, Marc; Ballesteros, Carme Brosa; Kohout, Ladislav

    2007-10-01

    In general, the structural requirements postulated for a high brassinolide activity are: 2alpha,3alpha-diol, 6-ketone or better 7-oxalactone in B-ring, A/B trans fused ring junction, a cis C-22,C-23-diol preferentially with RR configurations, and a C-24 methyl or ethyl substituent [Takatsuto S, Yazawa N, Ikekawa N, Takematsu T, Takeuchi Y, Koguchi M. Structure-activity relationship of brassinosteroids. Phytochemistry 1983;22:2437-41; Thompson MJ, Meudt WJ, Mandava NB, Dutky SR, Lusby WR, Spaulding DW. Synthesis of brassinosteroids and relationship of structure to plant growth-promoting effects. Steroids 1982;39:89-105]. We found that the 3alpha,4alpha-diols 4, 6 and 8 are more active than the 2alpha,3alpha-diols 3, 5 and 7 [Sísa M, Budesínský M, Kohout L. Synthesis of 7a-homo and 7a,7b-dihomo-5alpha-cholestane analogues of brassinolide. Collect Czech Chem Commun 2003;68:2171-89]. This fact is in strong contrast with the structure requirements mentioned above. Our hypothesis suggests that the lower activity of 2alpha,3alpha-diols and/or the higher activity of 3alpha,4alpha-diols could be explained by twisting and distortion of the molecule due to the seven- or eight-membered B-ring and also by the position of a carbonyl group relative to the A-ring diol. 3D-SAR computer methodologies as alignments and overlaps of GRID maps and 3D-QSAR analysis GRID-GOLPE (CoMFA-like) were used as an effort to explain the higher bioactivity of 3alpha,4alpha-diols 4, 6 and 8 in comparison with the 2alpha,3alpha-diols 3, 5 and 7 of B-ring enlarged brassinosteroids.

  4. Voglibose: An Alpha Glucosidase Inhibitor

    PubMed Central

    Dabhi, Ajay S.; Bhatt, Nikita R.; Shah, Mohit J.

    2013-01-01

    Diabetes Mellitus (DM) is a morbid disease worldwide, with increasing incidence as time passes. It has macro-vascular and micro-vascular complications. The main cause of these complications is poorly controlled postprandial hyperglycaemia. Alpha glucosidase inhibitors, namely acarbose, voglibose and miglitol, are available for therapy. Voglibose is well tolerated and effective in comparable doses among these drugs. This article highlights the important features of voglibose. PMID:24551718

  5. Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics.

    PubMed

    Liebhaber, S A; Kan, Y W

    1981-08-01

    The alpha-globin polypeptide is encoded by two adjacent genes, alpha 1 and alpha 2. In the normal diploid state (alpha alpha/alpha alpha) all four alpha-globin genes are expressed. Loss or dysfunction of one or more of these genes leads to deficient alpha-globin production and results in alpha-thalassemia. We present a technique to differentially assess the steady-state levels of the alpha 1- and alpha-2-globin messenger RNA (mRNA) transcripts and thus delineate the relative level of expression of the two alpha-globin loci in a variety of alpha-thalassemia states. Only alpha 1 mRNA was produced in the alpha-thalassemia-2 haplotype (-alpha) (one of the two alpha-globin genes deleted from chromosome 16). This confirms previous gene mapping data which demonstrate deletion of the alpha 2 gene. The triple alpha-globin gene haplotype (alpha alpha alpha) is the reciprocal of the alpha-thalassemia-2 haplotype and thus contains an extra alpha 2-globin gene. RNA from this haplotype contained a greater than normal level of alpha 2-relative to alpha 1-globin mRNA. This data implies that the extra alpha 2 gene in the triple alpha-globin haplotype is functional. We detected a relative instability of the alpha 2-globin mRNA encoding the alpha-globin structural mutant Constant Spring. This instability may contribute to the low level of expression of the alpha-Constant Spring protein. In a Chinese patient with nondeletion hemoglobin-H disease (- -/alpha alpha T) (both alpha-globin genes are present but not fully functional) a normal ratio was maintained between the levels of alpha 1- and alpha 2-globin mRNA, implying that mRNA production from both alpha-globin genes is suppressed in a balanced manner. These observations extended previous findings concerning the structural rearrangements in the deletion types of alpha-thalassemia and the pathophysiology of two nondeletion variants.

  6. Formation of varanic acid, 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acid from 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid in Bombina orientalis.

    PubMed

    Une, M; Inoue, A; Hoshita, T

    1996-11-01

    Varanic acid (3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acid; 24-OH-THCA) is almost the sole component of bile acids in the bile of Bombina orientalis. To examine in the mechanism of the formation of 24-OH-THCA, radiolabeled (25R)- and (25S)-3 alpha, 7 alpha, 12 alpha-trihdroxy-5 beta-cholestanoic acids [(25R)- and (25S)-THCA] and (24E)-3 alpha, 7 alpha, 12 alpha-trihdroxy-5 beta-cholest-24-enoic acid (delta 24-THCA) were administered intraperitoneally to B. orientalis, gallbladder bile was collected after 24 h, and bile acids were subsequently extracted. Then the bile acids were analyzed by means of radio thin-layer chromatography and radio high-performance liquid chromatography after conversion to p-bromophenacyl ester derivatives. Although delta 24-THCA was not converted to 24-OH-THCA, (25R)-THCA and (25S)-THCA were transformed to (24R,25R)-24-OH-THCA and (24R,25S)-24-OH-THCA, respectively. These results strongly suggest that 24-OH-THCA was transformed via direct hydroxylation of the saturated side chain of THCA, not via hydration to an alpha, beta-unsaturated acid, delta 24-THCA, in B. orientalis.

  7. Alpha voltaic batteries and methods thereof

    NASA Technical Reports Server (NTRS)

    Raffaelle, Ryne P. (Inventor); Jenkins, Phillip (Inventor); Wilt, David (Inventor); Scheiman, David (Inventor); Chubb, Donald (Inventor); Castro, Stephanie (Inventor)

    2011-01-01

    An alpha voltaic battery includes at least one layer of a semiconductor material comprising at least one p/n junction, at least one absorption and conversion layer on the at least one layer of semiconductor layer, and at least one alpha particle emitter. The absorption and conversion layer prevents at least a portion of alpha particles from the alpha particle emitter from damaging the p/n junction in the layer of semiconductor material. The absorption and conversion layer also converts at least a portion of energy from the alpha particles into electron-hole pairs for collection by the one p/n junction in the layer of semiconductor material.

  8. THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

    SciTech Connect

    Hayes, Matthew; Oestlin, Goeran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas; Schaerer, Daniel; Verhamme, Anne; Orlitova, Ivana; Mas-Hesse, J. Miguel; Oti-Floranes, Hector; Adamo, Angela; Atek, Hakim; Cannon, John M.; Herenz, E. Christian; Kunth, Daniel; Laursen, Peter

    2013-03-10

    We report on new imaging observations of the Lyman alpha emission line (Ly{alpha}), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly{alpha}, H{alpha}, and the far ultraviolet continuum. We show that Ly{alpha} is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, R{sub P20}, Ly{alpha} radii are larger than those of H{alpha} by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Ly{alpha}-to-FUV radii is 2.9. This suggests that much of the Ly{alpha} light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly{alpha} compared to H{alpha}, {xi}{sub Ly{alpha}} = R {sup Ly{alpha}}{sub P20}/R {sup H{alpha}}{sub P20}, we find {xi}{sub Ly{alpha}} to be uncorrelated with total Ly{alpha} luminosity. However, {xi}{sub Ly{alpha}} is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly{alpha} photons throughout the interstellar medium and drive a large extended Ly{alpha} halo.

  9. Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats.

    PubMed

    Ikeda, Saiko; Tohyama, Tomoko; Yoshimura, Hiroyuki; Hamamura, Kimio; Abe, Kouichi; Yamashita, Kanae

    2003-02-01

    We previously showed that alpha- and gamma-tocotrienols accumulate in adipose tissue and skin but not in plasma or other tissues of rats fed a tocotrienol-rich fraction extracted from palm oil containing alpha-tocopherol and alpha- and gamma-tocotrienols. To clarify the nature of tocotrienol metabolism, we studied the distribution of alpha- or gamma-tocotrienol in rats fed alpha- or gamma-tocotrienol without alpha-tocopherol, and the effect of alpha-tocopherol on their distribution. Wistar rats (4-wk-old) were fed a diet with 50 mg alpha-tocotrienol/kg alone or with 50 mg alpha-tocopherol/kg in expt. 1, and a diet with 50 mg gamma-tocotrienol/kg alone or with 50 mg alpha-tocopherol/kg in expt. 2, for 8 wk. alpha-Tocotrienol was detected in various tissues and plasma of the rats fed alpha-tocotrienol alone, and the alpha-tocotrienol concentrations in those tissues and plasma decreased (P < 0.05) by the dietary alpha-tocopherol in the rats fed alpha-tocotrienol with alpha-tocopherol. However, gamma-tocotrienol preferentially accumulated in the adipose tissue and skin of the rats fed gamma-tocotrienol alone, and the dietary alpha-tocopherol failed either to decrease (P >/= 0.05) gamma-tocotrienol concentrations in the adipose tissue and skin or to increase (P >/= 0.05) in the urinary excretion of 2,7,8-trimethyl-2(2'-carboxymethyl)-6-hydroxycroman, a metabolite of gamma-tocotrienol, in the rats fed gamma-tocotrienol with alpha-tocopherol. These data suggest that alpha-tocopherol enhances the alpha-tocotrienol metabolism but not the gamma-tocotrienol metabolism in rats.

  10. PPAR-alpha in cutaneous inflammation

    PubMed Central

    Schmuth, Matthias

    2011-01-01

    Peroxisome proliferator-activated receptor (PPAR)-alpha is a fatty acid activated transcription factors that belongs to the nuclear hormone receptor family. Primarily PPAR-alpha serves as a lipid sensor. While PPAR-alpha controls enzymes from the lipid and glucose metabolism in the liver, heart and muscles, PPAR-alpha is also involved in skin homeostasis. PPAR-alpha controls keratinocyte proliferation/differentiation, contributes to wound healing and regulates skin inflammation. PPAR-alpha activation exerts anti-inflammatory effects in various skin conditions such as irritant and allergic contact dermatitis, atopic dermatitis and UV-induced erythema, rendering investigations into the functions of PPAR-alpha necessary to provide better understandings to treat many inflammatory skin disorders. PMID:21519405

  11. 8alpha-hydroxyflavinmononucleotide and related compounds.

    PubMed

    Zhilina, T A; Berezoyski, V M

    1977-01-01

    2', 3', 4'-Triacetyl-FMN has been transformed by selective radical bromination into 2', 3', 4'-triacetyl-8alpha-bromo-FMN, and the following hydrolysis of the latter has afforded 8alpha-hydroxy-FMN. The presence of the hydroxy group in the 8alpha position of 8alpha-hydroxy-FMN is confirmed by its acetylation into 2', 3'-diacetyl-8alpha-acetoxyriboflavin-4', 5'-cyclophosphate. The absorption spectra of the synthesized compounds have shown the reduction of the extinction ratios of the first and second absorption maxima in comparison with the extinction of the same maxima for 8alpha-hydroxyriboflavin. Unlike FMN, fluorescence quenching for 8alpha-hydroxy-FMN has been found.

  12. Physiologic and prognostic significance of "alpha coma".

    PubMed Central

    Iragui, V J; McCutchen, C B

    1983-01-01

    A patient with posthypoxic "alpha coma" is described whose EEGs were recorded before coma, within two hours following the onset of coma and after recovery. The differences observed between the alpha activity during coma and that seen before and after suggest that the alpha activity during coma and the physiologic alpha rhythm are different phenomena. This case, as well as others reported, also suggests that "alpha coma" resolving in the first 24 hours following hypoxia may have a better prognosis than "alpha coma" detected after the first day, and stresses the need for EEG monitoring begun in the immediate period following hypoxia in order to assess accurately the prognostic significance of this EEG pattern in the early stages of postanoxic encephalopathy. The aetiology of "alpha coma" also affects outcome. The survival rate appears higher in patients with respiratory arrest than in those with combined cardiopulmonary arrest. PMID:6886700

  13. alpha-Tocopheryl phosphate – an active lipid mediator?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The vitamin E (alpha-tocopherol, alphaT) derivative, alpha-tocopheryl phosphate (alphaTP), is detectable in small amounts in plasma, tissues, and cultured cells. Studies done in vitro and in vivo suggest that alphaT can become phosphorylated and alphaTP dephosphorylated, suggesting the existence of ...

  14. Is Hb A2 elevated in adults with sickle-alpha-thalassemia (beta(S)/beta(S); -alpha/-alpha)?

    PubMed

    Ballas, S K; Gay, R N; Chehab, F F

    1997-09-01

    Thirteen patients with sickle cell anemia (SS) were found to have two alpha gene deletions with a presumptive genotype of beta(S)/beta(S); -alpha/-alpha. Hematological data showed that this group of patients had elevated Hb A2 level. In order to determine whether the elevation of Hb A2 is typical of SS with a two alpha gene deletion or is due to undiagnosed S-beta(O)-thalassemia with a two alpha gene deletion we looked for the presence or absence of beta(O)-thalassemia by molecular techniques. The latter included reverse dot-blot hybridization to rule out a beta-thalassemia mutation, digestion with CvnI endonuclease followed by Southern blotting and hybridization with a beta genomic probe, and, in selected patients, determination of the synthetic alpha/beta ratio. One of the 13 patients had S-beta(O)-thalassemia with a G-->A mutation at IVS-II-1 indicating that her genotype was beta(S)/beta(O) thalassemia; -alpha/-alpha. The remaining 12 patients were homozygous for the sickle gene, had relatively elevated Hb levels, increased Hb A2 values, and Hb F levels similar to those in patients with SS and four or three alpha genes. At the clinical level, the 12 patients with SS and a two alpha gene deletion had increased prevalence of avascular necrosis, retinopathy, and splenomegaly, but decreased prevalence of leg ulcers and cerebrovascular accidents. Together, the data indicate that SS with a two alpha gene deletion (beta(S)/beta(S); -alpha/-alpha) is a unique subset of patients with SS characterised by distinct hematological and clinical features.

  15. Anti-ischemic activity and endothelium-dependent vasorelaxant effect of hydrolysable tannins from the leaves of Rhus coriaria (Sumac) in isolated rabbit heart and thoracic aorta.

    PubMed

    Beretta, Giangiacomo; Rossoni, Giuseppe; Santagati, Natale Alfredo; Facino, Roberto Maffei

    2009-11-01

    The aim of this work was to investigate the cardioprotective activity of hydrolysable gallotannins from Rhus coriaria L. leaves extract (RCLE) in isolated rabbit heart preparations, submitted to low-flow ischemia/reperfusion damage. RCLE induces a dose-dependent normalization of coronary perfusion pressure (CPP), reducing left ventricular contracture during ischemia, and improving left ventricular developed pressure and the maximum rate of rise and fall of left ventricular pressure at reperfusion. Creatinine kinase (CK) and lactate dehydrogenase (LDH) outflow were significantly reduced during reperfusion. In parallel there was a rise in the release of the cytoprotective 6-ketoprostaglandin F (1alpha) (6-keto-PGF (1alpha)) and a decrease of tumor necrosis factor-alpha (TNF-alpha), both significant only at the highest RCLE concentrations (150-500 microg/mL). The vasorelaxant activity of RCLE was studied in isolated rabbit aorta rings precontracted with norepinephrine (NE) with and without endothelium. The vasorelaxation induced by RCLE was predominantly endothelium-dependent as demonstrated by the loss of RCLE vasorelaxant ability in i) de-endothelized rings and ii) in intact aortic rings after pretreatment with NG-monomethyl- L-arginine (L-NMMA) and 1 H-[1.2.4]oxadiazolo[4.3- A]quinoxalin-1-one (ODQ). The inhibition of vasorelaxation in intact rings by indomethacin (INDO) demonstrates the ability of RCLE to modulate the coronary endothelium cyclooxygenase (COX) pathway. The K-ATP channel antagonist glibenclamide (GLIB) was ineffective. The antioxidant activity of RCLE, investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model and in living cell systems (rat erythrocytes), was stronger than that of gallic acid, ascorbic acid and trolox. The structure of its main bioactive constituents, profiled by HPLC-ESI-HR-S, comprised a mixture of polygalloylated D-glucopyranose with different degrees of galloylation and 3- O-methylgallic acid. The cardiovascular protective

  16. The mongoose acetylcholine receptor alpha-subunit: analysis of glycosylation and alpha-bungarotoxin binding.

    PubMed

    Asher, O; Jensen, B S; Lupu-Meiri, M; Oron, Y; Fuchs, S

    1998-04-17

    The mongoose AChR alpha-subunit has been cloned and shown to be highly homologous to other AChR alpha-subunits, with only six differences in amino acid residues at positions that are conserved in animal species that bind alpha-bungarotoxin (alpha-BTX). Four of these six substitutions cluster in the ligand binding site, and one of them, Asn-187, forms a consensus N-glycosylation site. The mongoose glycosylated alpha-subunit has a higher apparent molecular mass than that of the rat glycosylated alpha-subunit, probably resulting from the additional glycosylation at Asn-187 of the mongoose subunit. The in vitro translated mongoose alpha-subunit, in a glycosylated or non-glycosylated form, does not bind alpha-BTX, indicating that lack of alpha-BTX binding can be achieved also in the absence of glycosylation.

  17. Alpha 2-adrenoceptor agonists potentiate responses mediated by alpha 1-adrenoceptors in the cat nictitating membrane.

    PubMed Central

    Shepperson, N. B.

    1984-01-01

    Alpha 1 but not alpha 2-adrenoceptors mediate contractions of the cat nictitating membrane. The contractions of this tissue evoked by alpha 1-adrenoceptor agonists, but not those evoked by angiotensin II, are potentiated by pre-dosing with alpha 2-adrenoceptor agonists. This potentiation is reversed by the alpha 2-adrenoceptor antagonist, WY 26392. Pressor responses evoked by alpha 1-adrenoceptor agonists or angiotensin II were not affected by alpha 2-adrenoceptor agonists. Contractions of the nictitating membrane evoked by noradrenaline were reduced by pretreatment with WY 26392. These results suggest that in some tissues the role of alpha 2-adrenoceptors may be to modulate responses to alpha 1-adrenoceptors, rather than to evoke a discrete response themselves. PMID:6148985

  18. Lymphatic transport of alpha-, gamma- and delta-tocotrienols and alpha-tocopherol in rats.

    PubMed

    Ikeda, I; Imasato, Y; Sasaki, E; Sugano, M

    1996-01-01

    Lymphatic transport of alpha-, gamma- and delta-tocotrienols and alpha-tocopherol was measured in thoracic duct-cannulated rats. Animals were administered 3 ml of a test emulsion containing 200 mg sodium taurocholate, 50 mg fatty acid free-albumin, 200 mg fat and 100 mg of a mixture of tocotrienols and alpha-tocopherol (Exp. 1) or 10 mg of purified alpha-, gamma- or delta-tocotrienol or alpha-tocopherol (Exp. 2) through a gastric tube. Quantitative lymphatic recovery of oleic acid given as triolein was obtained in these experimental conditions. The 24-hours recovery of tocotrienols and alpha-tocopherol were 10-20% of the administered dose in Exp. 1. The recovery of alpha-tocotrienol was about 2-times higher than that of alpha-tocopherol, while that of gamma- and delta-tocotrienols was intermediate between these two alpha-forms. In Exp. 2, where these compounds were administered individually, the 24 hours recovery ranged from 22 to 37% of the administered dose. Again, the recovery of alpha-tocotrienol was significantly higher than that of the other tocotrienols and alpha-tocopherol, while that of gamma- and delta-tocotrienols and alpha-tocopherol was comparable. Thus, the results show the preferential absorption of alpha-tocotrienol compared to gamma- and delta-tocotrienols and alpha-tocopherol.

  19. Targeted alpha therapy for cancer

    NASA Astrophysics Data System (ADS)

    Allen, Barry J.; Raja, Chand; Rizvi, Syed; Li, Yong; Tsui, Wendy; Zhang, David; Song, Emma; Qu, Chang Fa; Kearsley, John; Graham, Peter; Thompson, John

    2004-08-01

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The 213Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 µCi in human

  20. Salicylic acid retention impairs aspirin reactivity in type 2 diabetes.

    PubMed

    Zhang, Haowen; Xie, Hao; Zheng, Xiao; Chai, Yingying; Tang, Zhiyuan; Chen, Hanyu; Li, Feiyan; Christoph, Heier; Chen, Jiandong; Sun, Weixin; Ye, Hui; Wang, Shiguang; Hao, Haiping; Chen, Xiaohu

    2017-01-05

    High on-aspirin platelet reactivity (HAPR) has been associated with compromised aspirin efficacy in patients with diabetes suffering from acute cardiovascular events, but the key mechanisms remain elusive. The objective of this study was to uncover the potential link between pathogenic accumulation of salicylic acid (SA), the major metabolite of aspirin, and HAPR in diabetic state. Aspirin failed to inhibit platelet CD62P expression and thromboxane (TX) B2/6-keto-prostaglandin(PG)F1α ratio in a type 2 diabetes mellitus (T2DM) mice model, particularly in the female, which were unanimously accompanied by significantly higher plasma SA concentrations. Pre-administration with SA increased both platelet CD62P expression and TXB2/6-keto-PGF1α ratio in female T2DM mice, while pretreatment with NaHCO3 caused the opposite effect. On the in vitro human umbilical vein endothelial cells (HUVECs)-platelet interaction assay, SA suppressed inflammation-induced cyclooxygenase-2 upregulation on HUVECs and attenuated their inhibitory effect on platelet aggregation in a dose-dependent manner. The prolonged retention of SA in diabetes may be partially explained by the downregulation of various SA efflux transporters in the kidney and the decreased urine pH. Importantly, in female aspirin non-responsive patients, the trough plasma concentration of SA are markedly increased with T2DM treated with long-term aspirin, and TXB2/6-keto-PGF1α ratio and uric acid level in plasma are positively correlated with SA concentration. Our findings support that the accumulation of SA represents an important factor in causing HAPR in diabetes, and that targeting impaired SA excretion may become a novel intervention strategy to diabetes-associated HAPR.

  1. Selective sorting of alpha-granule proteins.

    PubMed

    Italiano, J E; Battinelli, E M

    2009-07-01

    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. A majority of this vast array of secreted proteins are stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on the mechanisms of alpha-granule biogenesis and secretion, with a particular emphasis on recent findings that clearly demonstrate that platelets contain distinct subpopulations of alpha-granules that undergo differential release during activation. We consider the implications of this new paradigm of platelet secretion, discuss mechanisms of alpha-granule biogenesis, and review the molecular basis of transport and delivery of alpha-granules to assembling platelets.

  2. Alpha-1 antitrypsin augmentation therapy.

    PubMed

    Wewers, Mark D; Crystal, Ronald G

    2013-03-01

    The therapy of alpha-1 antitrypsin deficiency (AATD) is an example of a medical triumph over a common hereditary disease. Based on the understanding of the pathogens of the disease as a deficiency in liver production of alpha-1 antitrypsin (AAT) resulting from inherited genetic variation in both parental AAT genes, the knowledge that A1AT functions primarily to inhibit neutrophil elastase (NE), and the observation that NE instilled into the lung of experimental animals resulted in emphysema, the concept evolved that the pulmonary manifestations of the disease could be halted by intermittent intravenous infusions of AAT purified from pooled human plasma. Following preliminary clinical studies in the academic community, and then pharmaceutical company development of large scale purification of human AAT, the FDA approved the use of weekly AAT augmentation therapy for AATD following a clinical trial which demonstrated that weekly infusions would raise to normal plasma and lung epithelial fluid levels of AAT in AAT-deficient individuals. The therapy is now used worldwide to treat AATD, the only pulmonary genetic disease with effective therapy for all affected individuals.

  3. Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein metabolism.

    PubMed

    Rhee, James; Ge, Hongfei; Yang, Wenli; Fan, Melina; Handschin, Christoph; Cooper, Marcus; Lin, Jiandie; Li, Cai; Spiegelman, Bruce M

    2006-05-26

    Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator involved in several aspects of energy metabolism. It is induced or activated under different stimuli in a highly tissue-specific manner and subsequently partners with certain transcription factors in those tissues to execute various biological programs. In the fasted liver, PGC-1alpha is induced and interacts with hepatocyte nuclear factor 4alpha (HNF4alpha) and other transcription factors to activate gluconeogenesis and increase hepatic glucose output. Given the broad spectrum of liver genes responsive to HNF4alpha, we sought to determine those that were specifically targeted by the combination of PGC-1alpha and HNF4alpha. Coexpression of these two molecules in murine stem cells reveals a high induction of mRNA for apolipoproteins A-IV and C-II. Forced expression of PGC-1alpha in mouse and human hepatoma cells increases the mRNA of a subset of apolipoproteins implicated in very low density lipoprotein and triglyceride metabolism, including apolipoproteins A-IV, C-II, and C-III. Coactivation of the apoC-III/A-IV promoter region by PGC-1alpha occurs through a highly conserved HNF4alpha response element, the loss of which completely abolishes activation by PGC-1alpha and HNF4alpha. Adenoviral infusion of PGC-1alpha into live mice increases hepatic expression of apolipoproteins A-IV, C-II, and C-III and increases serum and very low density lipoprotein triglyceride levels. Conversely, knock down of PGC-1alpha in vivo causes a decrease in both apolipoprotein expression and serum triglyceride levels. These data point to a crucial role for the PGC-1alpha/HNF4alpha partnership in hepatic lipoprotein metabolism.

  4. Beta/alpha continuous air monitor

    DOEpatents

    Becker, Gregory K.; Martz, Dowell E.

    1989-01-01

    A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinguishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts.

  5. Beta/alpha continuous air monitor

    DOEpatents

    Becker, G.K.; Martz, D.E.

    1988-06-27

    A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinquishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts. 7 figs.

  6. Gene transfer mediated by alpha2-macroglobulin.

    PubMed Central

    Schneider, H; Huse, K; Birkenmeier, G; Otto, A; Scholz, G H

    1996-01-01

    alpha2-Macroglobulin covalently linked to poly(L)-lysine can be used as a vehicle for receptor-mediated gene transfer. This modified alpha2-macroglobulin maintains its ability to bind to the alpha2-macroglobulin receptor, and was shown to introduce a luciferase reporter gene plasmid into HepG2 human hepatoma cells in vitro. The alpha2-macroglobulin receptor is a very large and multifunctional cell surface receptor, whose rapid and efficient internalization rate makes it attractive for gene therapy, e.g. for hepatic gene targeting via injection into the portal vein. PMID:8871570

  7. Prospects for alpha particle studies on TFTR

    SciTech Connect

    Zweben, S.J.

    1987-05-01

    TFTR is expected to produce approximately 5 MW of alpha heating during the D/T Q approx. = 1 phase of operation in 1990. At that point the collective confinement properties and the heating effects of alpha particles become accessible for study for the first time. This paper outlines the potential performance of TFTR with respect to alpha particle production, the diagnostics which will be available for alpha particle measurements, and the physics issues which can be studied both before and during D/T operation.

  8. EEG, alpha waves and coherence

    NASA Astrophysics Data System (ADS)

    Ascolani, Gianluca

    This thesis addresses some theoretical issues generated by the results of recent analysis of EEG time series proving the brain dynamics are driven by abrupt changes making them depart from the ordinary Poisson condition. These changes are renewal, unpredictable and non-ergodic. We refer to them as crucial events. How is it possible that this form of randomness be compatible with the generation of waves, for instance alpha waves, whose observation seems to suggest the opposite view the brain is characterized by surprisingly extended coherence? To shed light into this apparently irretrievable contradiction we propose a model based on a generalized form of Langevin equation under the influence of a periodic stimulus. We assume that there exist two different forms of time, a subjective form compatible with Poisson statistical physical and an objective form that is accessible to experimental observation. The transition from the former to the latter form is determined by the brain dynamics interpreted as emerging from the cooperative interaction among many units that, in the absence of cooperation would generate Poisson fluctuations. We call natural time the brain internal time and we make the assumption that in the natural time representation the time evolution of the EEG variable y(t) is determined by a Langevin equation perturbed by a periodic process that in this time representation is hardly distinguishable from an erratic process. We show that the representation of this random process in the experimental time scale is characterized by a surprisingly extended coherence. We show that this model generates a sequence of damped oscillations with a time behavior that is remarkably similar to that derived from the analysis of real EEG's. The main result of this research work is that the existence of crucial events is not incompatible with the alpha wave coherence. In addition to this important result, we find another result that may help our group, or any other research

  9. Enzymatic synthesis of a selective inhibitor for alpha-glucosidases: alpha-acarviosinyl-(1-->9)-3-alpha-D-glucopyranosylpropen.

    PubMed

    Lee, Young-Su; Lee, Myoung-Hee; Lee, Hee-Seob; Lee, Seung-Jae; Kim, Young-Wan; Zhang, Ran; Withers, Stephen G; Kim, Kwan Soo; Lee, Sung-Joon; Park, Kwan-Hwa

    2008-07-09

    Here, we describe the enzymatic synthesis of novel inhibitors using acarviosine-glucose as a donor and 3-alpha-D-glucopyranosylpropen (alphaGP) as an acceptor. Maltogenic amylase from Thermus sp. (ThMA) catalyzed the transglycosylation of the acarviosine moiety to alphaGP. The two major reaction products were isolated using chromatographies. Structural analyses revealed that acarviosine was transferred to either C-7 or C-9 of the alphaGP, which correspond to C-4 and C-6 of glucose. Both inhibited rat intestine alpha-glucosidase competitively but displayed a mixed-type inhibition mode against human pancreatic alpha-amylase. The alpha-acarviosinyl-(1-->7)-3-alpha-D-glucopyranosylpropen showed weaker inhibition potency than acarbose against both alpha-glycosidases. In contrast, the alpha-acarviosinyl-(1-->9)-3-alpha-D-glucopyranosylpropen exhibited a 3.0-fold improved inhibition potency against rat intestine alpha-glucosidase with 0.3-fold inhibition potency against human pancreatic alpha-amylase relative to acarbose. In conclusion, alpha-acarviosinyl-(1-->9)-3-alpha-D-glucopyranosylpropen is a novel alpha-glucosidase-selective inhibitor with 10-fold enhanced selectivity toward alpha-glucosidase over alpha-amylase relative to acarbose, and it could be applied as a potent hypoglycemic agent.

  10. 40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-.alpha.-phenyl-, ethyl ester. 721.10300 Section 721.10300 Protection of Environment ENVIRONMENTAL....-phenyl-, ethyl ester. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester (PMN...

  11. 40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-.alpha.-phenyl-, ethyl ester. 721.10300 Section 721.10300 Protection of Environment ENVIRONMENTAL....-phenyl-, ethyl ester. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester (PMN...

  12. 40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-.alpha.-phenyl-, ethyl ester. 721.10300 Section 721.10300 Protection of Environment ENVIRONMENTAL....-phenyl-, ethyl ester. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester (PMN...

  13. Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume

    ERIC Educational Resources Information Center

    Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.

    2015-01-01

    Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…

  14. The murine alpha B-crystallin/small heat shock protein enhancer: identification of alpha BE-1, alpha BE-2, alpha BE-3, and MRF control elements.

    PubMed

    Gopal-Srivastava, R; Piatigorsky, J

    1993-11-01

    The murine alpha B-crystallin gene (a member of the small heat shock protein family) is expressed constitutively at high levels in the lens and at lower levels in many other tissues, including skeletal muscle. We have previously used the herpes simplex virus thymidine kinase promoter fused to the human growth hormone gene to identify an alpha B-crystallin enhancer at positions -427 to -259 that has high activity in muscle and low activity in lens cell lines. In the study reported here, we performed DNase I footprinting, transfection, mutagenesis, and electrophoretic mobility shift experiments using the murine C2C12 muscle and alpha TN4-1 lens cell lines and the rabbit N/N1003A lens cell line to identify sequences responsible for activity of this enhancer. Enhancer activity in both the muscle and lens cells was dependent on novel elements called alpha BE-1 (-407 to -397), alpha BE-2 (-360 to -327), and alpha BE-3 (-317 to -306). These elements were also weakly occupied by nuclear proteins in L929 cells, which appear to express the alpha B-crystallin gene at a very low level (detectable only by the polymerase chain reaction). A fourth element containing a consensus muscle regulatory factor-binding site called MRF (-300 to -288) was occupied and used only by the C2C12 muscle cells. Cotransfection in NIH 3T3 cells and antibody-gel shift experiments using C2C12 nuclear extracts indicated that MyoD, myogen, or a similar member of this family can activate the alpha B-crystallin enhancer by interaction with the MRF site. Taken together, we conclude that the alpha BE-1, alpha BE-2, and alpha BE-3 elements are shared by both lens and muscle cells, but the MRF element is used only in muscle cells, providing the first example of a muscle-specific control element in a crystallin gene.

  15. Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist {alpha}-conotoxin OmIA that discriminates {alpha}3 vs. {alpha}6 nAChR subtypes

    SciTech Connect

    Chi, Seung-Wook; Kim, Do-Hyoung; Olivera, Baldomero M.; McIntosh, J. Michael; Han, Kyou-Hoon . E-mail: khhan600@kribb.re.kr

    2006-06-23

    {alpha}-Conotoxin OmIA from Conus omaria is the only {alpha}-conotoxin that shows a {approx}20-fold higher affinity to the {alpha}3{beta}2 over the {alpha}6{beta}2 subtype of nicotinic acetylcholine receptor. We have determined a three-dimensional structure of {alpha}-conotoxin OmIA by nuclear magnetic resonance spectroscopy. {alpha}-Conotoxin OmIA has an '{omega}-shaped' overall topology with His{sup 5}-Asn{sup 12} forming an {alpha}-helix. Structural features of {alpha}-conotoxin OmIA responsible for its selectivity are suggested by comparing its surface characteristics with other functionally related {alpha}4/7 subfamily conotoxins. Reduced size of the hydrophilic area in {alpha}-conotoxin OmIA seems to be associated with the reduced affinity towards the {alpha}6{beta}2 nAChR subtype.

  16. Remote Associates Test and Alpha Brain Waves

    ERIC Educational Resources Information Center

    Haarmann, Henk J.; George, Timothy; Smaliy, Alexei; Dien, Joseph

    2012-01-01

    Previous studies found that performance on the remote associates test (RAT) improves after a period of incubation and that increased alpha brain waves over the right posterior brain predict the emergence of RAT insight solutions. We report an experiment that tested whether increased alpha brain waves during incubation improve RAT performance.…

  17. Alpha particle spectrometry using superconducting microcalorimeters

    NASA Astrophysics Data System (ADS)

    Horansky, Robert; Ullom, Joel; Beall, James; Hilton, Gene; Stiehl, Gregory; Irwin, Kent; Plionis, Alexander; Lamont, Stephen; Rudy, Clifford; Rabin, Michael

    2009-03-01

    Alpha spectrometry is the preferred technique for analyzing trace samples of radioactive material because the alpha particle flux can be significantly higher than the gamma-ray flux from nuclear materials of interest. Traditionally, alpha spectrometry is performed with Si detectors whose resolution is at best 8 keV FWHM. Here, we describe the design and operation of a microcalorimeter alpha detector with an energy resolution of 1.06 keV FWHM at 5 MeV. We demonstrate the ability of the microcalorimeter to clearly resolve the alpha particles from Pu-239 and Pu-240, whose ratio differentiates reactor-grade Pu from weapons-grade. We also show the first direct observation of the decay of Po-209 to the ground state of Pb-205 which has traditionally been obscured by a much stronger alpha line 2 keV away. Finally, the 1.06 keV resolution observed for alpha particles is far worse than the 0.12 keV resolution predicted from thermal fluctuations and measurement of gamma-rays. The cause of the resolution degradation may be ion damage in the tin. Hence, alpha particle microcalorimeters may provide a novel tool for studying ion damage and lattice displacement energies in bulk materials.

  18. Commentary on Coefficient Alpha: A Cautionary Tale

    ERIC Educational Resources Information Center

    Green, Samuel B.; Yang, Yanyun

    2009-01-01

    The general use of coefficient alpha to assess reliability should be discouraged on a number of grounds. The assumptions underlying coefficient alpha are unlikely to hold in practice, and violation of these assumptions can result in nontrivial negative or positive bias. Structural equation modeling was discussed as an informative process both to…

  19. 21 CFR 882.1610 - Alpha monitor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An...

  20. 21 CFR 882.1610 - Alpha monitor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An...

  1. 21 CFR 882.1610 - Alpha monitor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An...

  2. 21 CFR 882.1610 - Alpha monitor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An...

  3. 21 CFR 882.1610 - Alpha monitor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An...

  4. The Diffusion of Antimony of Alpha Iron.

    DTIC Science & Technology

    Diffusion coefficients of antimony in alpha iron were determined in the temperature range 700 to 900C using the residual activity method. Specimens...negligible effect on the diffusion of antomony in alpha iron . These results are discussed in relation to the phenomenon of temper brittleness in steels

  5. Coefficient Alpha Bootstrap Confidence Interval under Nonnormality

    ERIC Educational Resources Information Center

    Padilla, Miguel A.; Divers, Jasmin; Newton, Matthew

    2012-01-01

    Three different bootstrap methods for estimating confidence intervals (CIs) for coefficient alpha were investigated. In addition, the bootstrap methods were compared with the most promising coefficient alpha CI estimation methods reported in the literature. The CI methods were assessed through a Monte Carlo simulation utilizing conditions…

  6. Monitoring pipes for residual alpha contamination

    SciTech Connect

    MacArthur, D.; Rawool-Sullivan, M.; Dockray, T.

    1996-09-01

    The sensitivity and application of traditional alpha monitors is limited by the short range of alpha particles in air and in solid materials. Detecting small amounts of alpha-emitting contamination inside pipes presents particular problems. The alpha particle cannot penetrate the walls of the pipe. Associated gamma-ray detection and active neutron interrogation is often used to detect large amounts of radioactive material in pipes, but these methods are of limited use for detecting small amounts of contamination. Insertion of a traditional alpha probes works well in large diameter straight pipes, but is increasingly difficult as the pipe network becomes smaller in diameter and more complex. Monitors based on long-range alpha detection (LRAD) detect ionization of the ambient air rather than the alpha particles themselves. A small fan draws the ions into an externally mounted ion detector. Thus, the air in the pipe serves as both the detector gas and the mechanism for transporting the alpha-induced ions to a detection grid outside the pipe. All of the ions created by all of the contamination in the pipe can be measured in a single detector. Since ambient air serves as the probe, crushed or twisted sections of pipe can be monitored almost as effectively as straight sections. The pipe monitoring system described in the paper was tested both at LANL and BNFL`s Sellafield reprocessing facility in the UK. In this paper, we report on the first field tests of the pipe monitoring system.

  7. Bayesian Meta-Analysis of Coefficient Alpha

    ERIC Educational Resources Information Center

    Brannick, Michael T.; Zhang, Nanhua

    2013-01-01

    The current paper describes and illustrates a Bayesian approach to the meta-analysis of coefficient alpha. Alpha is the most commonly used estimate of the reliability or consistency (freedom from measurement error) for educational and psychological measures. The conventional approach to meta-analysis uses inverse variance weights to combine…

  8. 27 CFR 21.95 - Alpha terpineol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c)...

  9. 27 CFR 21.95 - Alpha terpineol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c)...

  10. 27 CFR 21.95 - Alpha terpineol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c)...

  11. 27 CFR 21.95 - Alpha terpineol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c)...

  12. Elementary Processes Underlying Alpha Channeling in Tokamaks

    SciTech Connect

    NM.J. Fisch

    2012-06-15

    Alpha channeling in tokamaks is speculative, but also extraordinarily attractive. Waves that can accomplish this effect have been identified. Key aspects of the theory now enjoy experimental confirmation. This paper will review the elementary processes of wave-particle interactions in plasma that underlie the alpha channeling effect

  13. Atypical Alpha Asymmetry in Adults with ADHD

    ERIC Educational Resources Information Center

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

    2009-01-01

    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  14. Meta-Analysis of Coefficient Alpha

    ERIC Educational Resources Information Center

    Rodriguez, Michael C.; Maeda, Yukiko

    2006-01-01

    The meta-analysis of coefficient alpha across many studies is becoming more common in psychology by a methodology labeled reliability generalization. Existing reliability generalization studies have not used the sampling distribution of coefficient alpha for precision weighting and other common meta-analytic procedures. A framework is provided for…

  15. Local Structure and Vibrational Properties of alpha-Pu, alpha-U, and the alpha-U Charge Density Wave

    SciTech Connect

    Nelson, E J; Allen, P G; Blobaum, K M; Wall, M A; Booth, C H

    2004-08-10

    The local atomic environment and vibrational properties of atoms in monoclinic pure {alpha}-plutonium as well as orthorhombic pure {alpha}-uranium and its low-temperature charge-density-wave (CDW) modulation are examined by extended x-ray absorption fine structure spectroscopy (EXAFS). Pu L{sub III}-edge and U L{sub III}-edge EXAFS data measured at low temperatures verify the crystal structures of {alpha}-U and {alpha}-Pu samples previously determined by x-ray diffraction and neutron scattering. Debye-Waller factors from temperature-dependent EXAFS measurements are fit with a correlated Debye model. The observed Pu-Pu bond correlated Debye temperature of {theta}{sub cD}({alpha}-Pu) = 162 {+-} 5 K for the pure {alpha}-Pu phase agrees with our previous measurement of the correlated Debye temperature of the gallium-containing {alpha}'-Pu phase in a mixed phase 1.9 at% Ga-doped {alpha}'-Pu/{delta}-Pu alloy. The temperature dependence of the U-U nearest neighbor Debye-Waller factor exhibits a sharp discontinuity in slope near T{sub CDW} = 43 K, the transition temperature at which the charge-density wave (CDW) in {alpha}-U condenses from a soft phonon mode along the (100) direction. Our measurement of the CDW using EXAFS is the first observation of the structure of the CDW in polycrystalline {alpha}-U. The different temperature dependence of the Debye-Waller factor for T < T{sub CDW} can be modeled by the change in bond length distributions resulting from condensation of the charge density wave. For T > T{sub CDW}, the observed correlated Debye temperature of {theta}{sub cD}({alpha}-U) = 199 {+-} 3 K is in good agreement with other measurements of the Debye temperature for polycrystalline {alpha}-U. CDW structural models fit to the {alpha}-U EXAFS data support a squared CDW at the lowest temperatures, with a displacement amplitude of {var_epsilon} = 0.05 {+-} 0.02 {angstrom}.

  16. Catalytic Mechanism of Human Alpha-galactosidase

    SciTech Connect

    Guce, A.; Clark, N; Salgado, E; Ivanen, D; Kulinskaya, A; Brumer, H; Garman, S

    2010-01-01

    The enzyme {alpha}-galactosidase ({alpha}-GAL, also known as {alpha}-GAL A; E.C. 3.2.1.22) is responsible for the breakdown of {alpha}-galactosides in the lysosome. Defects in human {alpha}-GAL lead to the development of Fabry disease, a lysosomal storage disorder characterized by the buildup of {alpha}-galactosylated substrates in the tissues. {alpha}-GAL is an active target of clinical research: there are currently two treatment options for Fabry disease, recombinant enzyme replacement therapy (approved in the United States in 2003) and pharmacological chaperone therapy (currently in clinical trials). Previously, we have reported the structure of human {alpha}-GAL, which revealed the overall structure of the enzyme and established the locations of hundreds of mutations that lead to the development of Fabry disease. Here, we describe the catalytic mechanism of the enzyme derived from x-ray crystal structures of each of the four stages of the double displacement reaction mechanism. Use of a difluoro-{alpha}-galactopyranoside allowed trapping of a covalent intermediate. The ensemble of structures reveals distortion of the ligand into a {sup 1}S{sub 3} skew (or twist) boat conformation in the middle of the reaction cycle. The high resolution structures of each step in the catalytic cycle will allow for improved drug design efforts on {alpha}-GAL and other glycoside hydrolase family 27 enzymes by developing ligands that specifically target different states of the catalytic cycle. Additionally, the structures revealed a second ligand-binding site suitable for targeting by novel pharmacological chaperones.

  17. Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology.

    PubMed

    Danzer, Karin M; Krebs, Simon K; Wolff, Michael; Birk, Gerald; Hengerer, Bastian

    2009-10-01

    Lewy bodies, alpha-synuclein (alpha-syn) immunopositive intracellular deposits, are the pathological hallmark of Parkinson's disease (PD). Interestingly, Lewybody-like structures have been identified in fetal tissue grafts about one decade after transplantation into the striatum of PD patients. One possible explanation for the accelerated deposition of alpha-syn in the graft is that the aggregation of alpha-syn from the host tissue to the graft is spread by a prion disease-like mechanism. We discuss here an in vitro model which might recapitulate some aspects of disease propagation in PD. We found here that in vitro-generated alpha-syn oligomers induce transmembrane seeding of alpha-syn aggregation in a dose- and time-dependent manner. This effect was observed in primary neuronal cultures as well as in neuronal cell lines. The seeding oligomers were characterized by a distinctive lithium dodecyl sulfate-stable oligomer pattern and could be generated in a dynamic process out of pore-forming oligomers. We propose that alpha-syn oligomers form as a dynamic mixture of oligomer types with different properties and that alpha-syn oligomers can be converted into different types depending on the brain milieu conditions. Our data indicate that extracellular alpha-syn oligomers can induce intracellular alpha-syn aggregation, therefore we hypothesize that a similar mechanism might lead to alpha-syn pathology propagation.

  18. Folate receptor {alpha} regulates cell proliferation in mouse gonadotroph {alpha}T3-1 cells

    SciTech Connect

    Yao, Congjun; Evans, Chheng-Orn; Stevens, Victoria L.; Owens, Timothy R.; Oyesiku, Nelson M.

    2009-11-01

    We have previously found that the mRNA and protein levels of the folate receptor alpha (FR{alpha}) are uniquely over-expressed in clinically human nonfunctional (NF) pituitary adenomas, but the mechanistic role of FR{alpha} has not fully been determined. We investigated the effect of FR{alpha} over-expression in the mouse gonadotroph {alpha}T3-1 cell line as a model for NF pituitary adenomas. We found that the expression and function of FR{alpha} were strongly up-regulated, by Western blotting and folic acid binding assay. Furthermore, we found a higher cell growth rate, an enhanced percentage of cells in S-phase by BrdU assay, and a higher PCNA staining. These observations indicate that over-expression of FR{alpha} promotes cell proliferation. These effects were abrogated in the same {alpha}T3-1 cells when transfected with a mutant FR{alpha} cDNA that confers a dominant-negative phenotype by inhibiting folic acid binding. Finally, by real-time quantitative PCR, we found that mRNA expression of NOTCH3 was up-regulated in FR{alpha} over-expressing cells. In summary, our data suggests that FR{alpha} regulates pituitary tumor cell proliferation and mechanistically may involve the NOTCH pathway. Potentially, this finding could be exploited to develop new, innovative molecular targeted treatment for human NF pituitary adenomas.

  19. Calcium: Alpha-Synuclein Interactions in Alpha-Synucleinopathies

    PubMed Central

    Rcom-H'cheo-Gauthier, Alexandre N.; Osborne, Samantha L.; Meedeniya, Adrian C. B.; Pountney, Dean L.

    2016-01-01

    Aggregation of the pre-synaptic protein, α-synuclein (α-syn), is the key etiological factor in Parkinson's disease (PD) and other alpha-synucleinopathies, such as multiple system atrophy (MSA) and Dementia with Lewy bodies (DLB). Various triggers for pathological α-syn aggregation have been elucidated, including post-translational modifications, oxidative stress, and binding of metal ions, such as calcium. Raised neuronal calcium levels in PD may occur due to mitochondrial dysfunction and/or may relate to calcium channel dysregulation or the reduced expression of the neuronal calcium buffering protein, calbindin-D28k. Recent results on human tissue and a mouse oxidative stress model show that neuronal calbindin-D28k expression excludes α-syn inclusion bodies. Previously, cell culture model studies have shown that transient increases of intracellular free Ca(II), such as by opening of the voltage-gated plasma calcium channels, could induce cytoplasmic aggregates of α-syn. Raised intracellular free calcium and oxidative stress also act cooperatively to promote α-syn aggregation. The association between raised neuronal calcium, α-syn aggregation, oxidative stress, and neurotoxicity is reviewed in the context of neurodegenerative α-syn disease and potential mechanism-based therapies. PMID:28066161

  20. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    SciTech Connect

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  1. G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits.

    PubMed Central

    Strathmann, M P; Simon, M I

    1991-01-01

    Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) are central to the signaling processes of multicellular organisms. We have explored the diversity of the G protein subunits in mammals and found evidence for a large family of genes that encode the alpha subunits. Amino acid sequence comparisons show that the different alpha subunits fall into at least three classes. These classes have been conserved in animals separated by considerable evolutionary distances; they are present in mammals, Drosophila, and nematodes. We have now obtained cDNA clones encoding two murine alpha subunits, G alpha 12 and G alpha 13, that define a fourth class. The translation products are predicted to have molecular masses of 44 kDa and to be insensitive to ADP-ribosylation by pertussis toxin. They share 67% amino acid sequence identity with each other and less than 45% identity with other alpha subunits. Their transcripts can be detected in every tissue examined, although the relative levels of the G alpha 13 message appear somewhat variable. Images PMID:1905812

  2. Mapping High-Velocity H-alpha and Lyman-alpha Emission from Supernova 1987A

    NASA Technical Reports Server (NTRS)

    France, Kevin; McCray, Richard; Fransson, Claes; Larsson, Josefin; Frank, Kari A.; Burrows, David N.; Challis, Peter; Kirshner, Robert P.; Chevalier, Roger A.; Garnavich, Peter; Heng, Kevin; Lawrence, Stephen S.; Lundqvist, Peter; Smith, Nathan; Sonneborn, George

    2015-01-01

    We present new Hubble Space Telescope images of high-velocity H-alpha and Lyman-alpha emission in the outer debris of SN 1987A. The H-alpha images are dominated by emission from hydrogen atoms crossing the reverse shock. For the first time we observe emission from the reverse shock surface well above and below the equatorial ring, suggesting a bipolar or conical structure perpendicular to the ring plane. Using the H-alpha imaging, we measure the mass flux of hydrogen atoms crossing the reverse shock front, in the velocity intervals (-7,500 < V(sub obs) < -2,800 km/s) and (1,000 < V(sub obs) < 7,500 km/s), ?M(sub H) = 1.2 × 10(exp -3) M/ y. We also present the first Lyman-alpha imaging of the whole remnant and new Chandra X-ray observations. Comparing the spatial distribution of the Lyman-alpha and X-ray emission, we observe that the majority of the high-velocity Lyman-alpha emission originates interior to the equatorial ring. The observed Lyman-alpha/H-alpha photon ratio, R(L-alpha/H-alpha) approx. = 17, is significantly higher than the theoretically predicted ratio of approx. = 5 for neutral atoms crossing the reverse shock front. We attribute this excess to Lyman-alpha emission produced by X-ray heating of the outer debris. The spatial orientation of the Lyman-alpha and X-ray emission suggests that X-ray heating of the outer debris is the dominant Lyman-alpha production mechanism in SN 1987A at this phase in its evolution.

  3. Involvement of central alpha1-adrenoceptors on renal responses to central moxonidine and alpha-methylnoradrenaline.

    PubMed

    de Andrade, Carina A F; de Andrade, Glaucia M F; De Paula, Patricia M; De Luca, Laurival A; Menani, José V

    2009-04-01

    Moxonidine (alpha2-adrenoceptor/imidazoline receptor agonist) injected into the lateral ventricle induces diuresis, natriuresis and renal vasodilation. Moxonidine-induced diuresis and natriuresis depend on central imidazoline receptors, while central alpha1-adrenoceptors are involved in renal vasodilation. However, the involvement of central alpha1-adrenoceptors on diuresis and natriuresis to central moxonidine was not investigated yet. In the present study, the effects of moxonidine, alpha-methylnoradrenaline (alpha2-adrenoceptor agonist) or phenylephrine (alpha1-adrenoceptor agonist) alone or combined with previous injections of prazosin (alpha1-adrenoceptor antagonist), yohimbine or RX 821002 (alpha2-adrenoceptor antagonists) intracerebroventricularly (i.c.v.) on urinary sodium, potassium and volume were investigated. Male Holtzman rats (n = 5-18/group) with stainless steel cannula implanted into the lateral ventricle and submitted to gastric water load (10% of body weight) were used. Injections of moxonidine (20 nmol) or alpha-methylnoradrenaline (80 nmol) i.c.v. induced natriuresis (196 +/- 25 and 171 +/- 30, respectively, vs. vehicle: 101 +/- 9 microEq/2 h) and diuresis (9.0 +/- 0.4 and 12.3 +/- 1.6, respectively, vs. vehicle: 5.2 +/- 0.5 ml/2 h). Pre-treatment with prazosin (320 nmol) i.c.v. abolished the natriuresis (23 +/- 4 and 76 +/- 11 microEq/2 h, respectively) and diuresis (5 +/- 1 and 7.6 +/- 0.8 ml/2 h, respectively) produced by i.c.v. moxonidine or alpha-methylnoradrenaline. RX 821002 (320 nmol) i.c.v. abolished the natriuretic effect of alpha-methylnoradrenaline, however, yohimbine (320 nmol) did not change renal responses to moxonidine. Phenylephrine (80 nmol) i.c.v. induced natriuresis and kaliuresis that were blocked by prazosin. Therefore, the present data suggest that moxonidine and alpha-methylnoradrenaline acting on central imidazoline receptors and alpha2-adrenoceptors, respectively, activate central alpha1-adrenergic mechanisms to

  4. [Contents and its change during storage of alpha-solanine and alpha-chaconine in potatoes].

    PubMed

    Shindo, Tetsuya; Ushiyama, Hirofumi; Kan, Kimiko; Yasuda, Kazuo; Saito, Kazuo

    2004-10-01

    Contents of alpha-solanine and alpha-chaconine in native species of potato (May Queen, Danshaku and Waseshiro), and in species (Jagakids Red '90 (Red) and Jagakids Purple '90 (Purple)) on the market, and their change during storage at room temparature were investigated. alpha-Solanine and alpha-chaconine were extracted from potatoes with methanol, cleaned up by using a Sep-Pak Plus C18 cartridge, and then subjected to HPLC. The recoveries of alpha-solanine and alpha-chaconine from potatoes were both more than 96%, and the quantitation limits were both 2 microg/g. alpha-Solanine and alpha-chaconine were detected in periderm in all samples at the levels of 260-320 microg/g in May Queen,190-240 microg/g in Danshaku, 43-63 microg/g in Waseshiro, 140-200 microg/g in Red and 84-130 microg/g in Purple, respectively. alpha-Solanine and alpha-chaconine were detected in the cortex in all samples of May Queen and Danshaku at the levels of 2.7-12 microg/g and 5.8-31 microg/g, respectively. Contents of alpha-solanine and alpha-chaconine in the cortex of May Queen and Danshaku were less than 10% of those in the periderm. When potatoes were stored for 90 days at room temparature in a dark place, no marked change in the contents of alpha-solanine and alpha-chaconine was observed in any of the potato samples.

  5. Local structure and vibrational properties of alpha-Pu, alpha-Uand the alpha-U charge density wave

    SciTech Connect

    Nelson, E.J.; Allen, P.G.; Blobaum, K.J.M.; Wall, W.A.; Booth, C.H.

    2004-08-10

    The local atomic environment and vibrational properties of atoms in monoclinic pure {alpha}-plutonium as well as orthorhombic pure a-uranium and its low-temperature charge-density-wave (CDW) modulation are examined by extended x-ray absorption fine structure spectroscopy (EXAFS). Pu L{sub III}-edge and U L{sub III}-edge EXAFS data measured at low temperatures verify the crystal structures of {alpha}-U and {alpha}-Pu samples previously determined by x-ray diffraction and neutron scattering. Debye-Waller factors from temperature-dependent EXAFS measurements are fit with a correlated Debye model. The observed Pu-Pu bond correlated Debye temperature of {theta}{sub cD}({alpha}-Pu) = 162 {+-} 5 K for the pure {alpha}-Pu phase agrees with our previous measurement of the correlated Debye temperature of the gallium-containing {alpha}{prime}-Pu phase in a mixed phase 1.9 at% Ga-doped {alpha}{prime}-Pu/{delta}-Pu alloy. The temperature dependence of the U-U nearest neighbor Debye-Waller factor exhibits a sharp discontinuity in slope near T{sub CDW} = 43 K, the transition temperature at which the charge-density wave (CDW) in {alpha}-U condenses from a soft phonon mode along the (100) direction. Our measurement of the CDW using EXAFS is the first observation of the structure of the CDW in polycrystalline {alpha}-U. The different temperature dependence of the Debye-Waller factor for T < T{sub CDW} can be modeled by the change in bond length distributions resulting from condensation of the charge density wave. For T > T{sub CDW}, the observed correlated Debye temperature of {theta}{sub cD}({alpha}-U) = 199 {+-} 3 K is in good agreement with other measurements of the Debye temperature for polycrystalline {alpha}-U. CDW structural models fit to the {alpha}-U EXAFS data support a squared CDW at the lowest temperatures, with a displacement amplitude of {var_epsilon} = 0.05 {+-} 0.02 {angstrom}.

  6. A new alpha chain hemoglobin variant: Hb Al-Hammadi Riyadh [alpha75(EF4)Asp-->Val (alpha2)].

    PubMed

    Burnichon, Nelly; Lacan, Philippe; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Mowafy, Mohammed; Couprie, Nicole; Francina, Alain

    2006-01-01

    A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC-->GTC); alpha75(EF4)Asp-->Val (alpha2)] corresponding to an A-->T transversion on the second exon of the alpha2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.

  7. Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.

    PubMed

    Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R

    2005-04-01

    The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

  8. Cloning and targeted mutations of G alpha 7 and G alpha 8, two developmentally regulated G protein alpha-subunit genes in Dictyostelium.

    PubMed Central

    Wu, L; Gaskins, C; Zhou, K; Firtel, R A; Devreotes, P N

    1994-01-01

    GTP-binding protein (G protein)-mediated signal transduction pathways play essential roles during the aggregation and differentiation process of Dictyostelium. In addition to the five known G protein alpha-subunit genes, we recently identified three novel alpha-subunit genes, G alpha 6, G alpha 7, and G alpha 8, using the polymerase chain reaction technique. We present here a more complete analysis of G alpha 7 and G alpha 8. The cDNAs of these two genes were cloned, and their complete nucleotide sequences were determined. Sequence analyses indicate that G alpha 8 possesses some unusual features. It lacks the "TCATDT" motif, a sequence of amino acids highly conserved among G alpha subunits, and has an additional 50 amino acids at its C-terminus consisting of long stretches of asparagine. Moreover, G alpha 8 is unusually resistant to protease digestion, which may indicate a slow GTP hydrolysis rate. The possible functions of these alpha-subunits were assessed by generating mutants lacking G alpha 7 or G alpha 8 by gene targeting through homologous recombination and by overexpressing G alpha 7 or G alpha 8 protein. Overexpression of G alpha 7 resulted in abnormal morphogenesis starting at the slug stage, whereas analysis of the other strains failed to reveal any obvious growth or developmental defects under either normal or stressful conditions. The implications of these results are discussed. Images PMID:7949425

  9. Lucid dreaming and alpha activity: a preliminary report.

    PubMed

    Ogilvie, R D; Hunt, H T; Tyson, P D; Lucescu, M L; Jeakins, D B

    1982-12-01

    10 good dream recallers spent 2 nights in the sleep lab during which they were awakened 4 times per night from REM sleep, twice during their highest alpha activity in REM, and twice during low REM alpha. 5 were given alpha feedback training prior to sleep onset. Arousals from high alpha REM sleep yielded significantly higher lucidity ratings. Alpha feedback had no effect upon lucidity or REM alpha levels. Similarities between lucid dreams and meditative phenomena are discussed.

  10. Lyman alpha emission in starburst galaxies

    NASA Astrophysics Data System (ADS)

    Kunth, Daniel

    1999-07-01

    We propose to perform a deep study of Ly-alpha emission and destruction in 3 star-forming galaxies. These objects have been already observed with the GHRS and exhibit a variety of situations, with Ly-alpha showing P Cyg profiles, secondary emissions or even a deep damped absorption line with no emission. They also span a range of intrinsic properties: IZW18 is a gas-rich, metal deficient dust free dwarf galaxy, Haro 2 has a simple morphology while IRAS 08339+6517 is a luminous IRAS starburst galaxy with more dust and complex Ly- alpha profile. The use of STIS will allow for the first time to study the geometrical/kinematical configuration of the ionized and neutral gas across the galaxies nuclear regions and pin point the effects of porosity and the kinematical structure of the ISM, that may play the key roles {in addition to dust} in the detectability of the line. This study will have important impact for cosmology since Ly-alpha emitters are nowaday found at high-re dshift. We strongly emphasize that since Ly-alpha is primarely a diagnostic of the ISM, a full understanding of how the ISM and Ly-alpha are related is a necessary step before we can hope to correlate Ly-alpha to the cosmic star-formation rate. Our results will be interpreted against the model of superbubble evolution developed with G. Tenorio Tagle.

  11. Lyman Alpha Spicule Observatory (LASO)

    NASA Astrophysics Data System (ADS)

    Chamberlin, P. C.; Allred, J. C.; Airapetian, V.; Gong, Q.; Mcintosh, S. W.; De Pontieu, B.; Fontenla, J. M.

    2011-12-01

    The Lyman Alpha Spicule Observatory (LASO) sounding rocket will observe small-scale eruptive events called "Rapid Blue-shifted Events" (RBEs) [Rouppe van der Voort et al., 2009], the on-disk equivalent of Type-II spicules, and extend observations that explore their role in the solar coronal heating problem [De Pontieu et al., 2011]. LASO utilizes a new and novel optical design to simultaneously observe two spatial dimensions at 4.2" spatial resolution (2.1" pixels) over a 2'x2' field of view with high spectral resolution of 66mÅ (33mÅ pixels) across a broad 20Å spectral window. This spectral window contains three strong chromospheric and transition region emissions and is centered on the strong Hydrogen Lyman-α emission at 1216Å. This instrument makes it possible to obtain new data crucial to the physical understanding of these phenomena and their role in the overall energy and momentum balance from the upper chromosphere to lower corona. LASO was submitted March 2011 in response to the ROSES SHP-LCAS call.

  12. Lyman Alpha Spicule Observatory (LASO)

    NASA Astrophysics Data System (ADS)

    Chamberlin, Phillip C.; Allred, J.; Airapetian, V.; Gong, Q.; Fontenla, J.; McIntosh, S.; de Pontieu, B.

    2011-05-01

    The Lyman Alpha Spicule Observatory (LASO) sounding rocket will observe small-scale eruptive events called "Rapid Blue-shifted Events” (RBEs), the on-disk equivalent of Type-II spicules, and extend observations that explore their role in the solar coronal heating problem. LASO utilizes a new and novel optical design to simultaneously observe two spatial dimensions at 4.2" spatial resolution (2.1” pixels) over a 2'x2' field of view with high spectral resolution of 66mÅ (33mÅ pixels) across a broad 20Å spectral window. This spectral window contains three strong chromospheric and transition region emissions and is centered on the strong Hydrogen Lyman-α emission at 1216Å. This instrument makes it possible to obtain new data crucial to the physical understanding of these phenomena and their role in the overall energy and momentum balance from the upper chromosphere to lower corona. LASO was submitted March 2011 in response to the ROSES SHP-LCAS call.

  13. Lyman Alpha Spicule Observatory (LASO)

    NASA Technical Reports Server (NTRS)

    Chamberlin, Phillip C.

    2011-01-01

    The Lyman Alpha Spicule Observatory (LASO) sounding rocket will observe smallscale eruptive events called "Rapid Blue-shifted Events" (RBEs) [Rouppe van der Voort et al., 2009], the on-disk equivalent of Type-II spicules, and extend observations that explore their role in the solar coronal heating problem [De Pontieu et al., 2011]. LASO utilizes a new and novel optical design to simultaneously observe two spatial dimensions at 4.2" spatial resolution (2.1" pixels) over a 2'x2' field of view with high spectral resolution of 66mAngstroms (33mAngstroms pixels) across a broad 20Angstrom spectral window. This spectral window contains three strong chromospheric and transition region emissions and is centered on the strong Hydrogen Lyman-a emission at 1216Angstroms. This instrument makes it possible to obtain new data crucial to the physical understanding of these phenomena and their role in the overall energy and momentum balance from the upper chromosphere to lower corona. LASO was submitted March 2011 in response to the ROSES SHP-LCAS call.

  14. Diabetes and Alpha Lipoic Acid

    PubMed Central

    Golbidi, Saeid; Badran, Mohammad; Laher, Ismail

    2011-01-01

    Diabetes mellitus is a multi-faceted metabolic disorder where there is increased oxidative stress that contributes to the pathogenesis of this debilitating disease. This has prompted several investigations into the use of antioxidants as a complementary therapeutic approach. Alpha lipoic acid, a naturally occurring dithiol compound which plays an essential role in mitochondrial bioenergetic reactions, has gained considerable attention as an antioxidant for use in managing diabetic complications. Lipoic acid quenches reactive oxygen species, chelates metal ions, and reduces the oxidized forms of other antioxidants such as vitamin C, vitamin E, and glutathione. It also boosts antioxidant defense system through Nrf-2-mediated antioxidant gene expression and by modulation of peroxisome proliferator activated receptors-regulated genes. ALA inhibits nuclear factor kappa B and activates AMPK in skeletal muscles, which in turn have a plethora of metabolic consequences. These diverse actions suggest that lipoic acid acts by multiple mechanisms, many of which have only been uncovered recently. In this review we briefly summarize the known biochemical properties of lipoic acid and then discussed the oxidative mechanisms implicated in diabetic complications and the mechanisms by which lipoic acid may ameliorate these reactions. The findings of some of the clinical trials in which lipoic acid administration has been tested in diabetic patients during the last 10 years are summarized. It appears that the clearest benefit of lipoic acid supplementation is in patients with diabetic neuropathy. PMID:22125537

  15. Targeted alpha therapy: part I.

    PubMed

    Elgqvist, Jorgen

    2011-07-01

    The possibility of pinpointing biological targets, and thereby potentially targeting and eradicating small tumors or even single cancer cells, is a tantalizing concept that has been discussed since the magic-bullet concept was first presented by Paul Erlich in the beginning of the 20th century in connection with his work on tissue staining for histological examinations and the work by Kohler and Milstein on antibody production published in 1975. This concept now seems feasible through the use of highly specific targeting constructs, chemical labeling of radioactive substances to these targeting constructs that results in high specific activities, radioimmunocomplexes with good stability even after injection, and the use of radionuclides emitting alpha( α)-particles having exceedingly high ionizing density and, therefore, a high probability of killing cells along its track in tissue. The short range of the emitted α-particles makes them even more interesting by minimizing unwanted irradiation of normal tissue surrounding the targeted cancer cells of interest, assuming high specificity of the targeting construct and good stability of the chemical bonds between the targeting construct and the α-particle emitter. Targeted Alpha Therapy (TAT), in which an α-particle emitting radionuclide is specifically directed to the biological target, is gaining more attention as new targets, targeting constructs, chemical labeling techniques, and α-particle emitters are, respectively, identified, constructed, developed, and made available. Results and improvements are now being published at an increasing rate and the number of conceivable applications is expanding, especially in the field of cancer treatment. Therefore, it is of utmost importance to provide an overview of the overall progress in the research field of TAT on a regular basis. However, problems such as limited or delayed diffusion of the α-radioimmunocomplex and inhomogeneous activity distributions in the

  16. Scalable encryption using alpha rooting

    NASA Astrophysics Data System (ADS)

    Wharton, Eric J.; Panetta, Karen A.; Agaian, Sos S.

    2008-04-01

    Full and partial encryption methods are important for subscription based content providers, such as internet and cable TV pay channels. Providers need to be able to protect their products while at the same time being able to provide demonstrations to attract new customers without giving away the full value of the content. If an algorithm were introduced which could provide any level of full or partial encryption in a fast and cost effective manner, the applications to real-time commercial implementation would be numerous. In this paper, we present a novel application of alpha rooting, using it to achieve fast and straightforward scalable encryption with a single algorithm. We further present use of the measure of enhancement, the Logarithmic AME, to select optimal parameters for the partial encryption. When parameters are selected using the measure, the output image achieves a balance between protecting the important data in the image while still containing a good overall representation of the image. We will show results for this encryption method on a number of images, using histograms to evaluate the effectiveness of the encryption.

  17. Diagnostics for PLX-alpha

    NASA Astrophysics Data System (ADS)

    Gilmore, Mark; Hsu, Scott

    2015-11-01

    The goal of the Plasma Liner eXperiment PLX-alpha at Los Alamos National Laboratory is to establish the viability of creating a spherically imploding plasma liner for MIF and HED applications, using a spherical array of supersonic plasma jets launched by innovative contoured-gap coaxial plasma guns. PLX- α experiments will focus in particular on establishing the ram pressure and uniformity scalings of partial and fully spherical plasma liners. In order to characterize these parameters experimentally, a suite of diagnostics is planned, including multi-camera fast imaging, a 16-channel visible interferometer (upgraded from 8 channels) with reconfigurable, fiber-coupled front end, and visible and VUV high-resolution and survey spectroscopy. Tomographic reconstruction and data fusion techniques will be used in conjunction with interferometry, imaging, and synthetic diagnostics from modeling to characterize liner uniformity in 3D. Diagnostic and data analysis design, implementation, and status will be presented. Supported by the Advanced Research Projects Agency - Energy - U.S. Department of Energy.

  18. SUMOylation of ROR{alpha} potentiates transcriptional activation function

    SciTech Connect

    Hwang, Eun Ju; Lee, Ji Min; Jeong, Jiyeong; Park, Joo Hyeon; Yang, Young; Lim, Jong-Seok; Kim, Jung Hwa; Baek, Sung Hee; Kim, Keun Il

    2009-01-16

    SUMOylation regulates a variety of cellular processes, including control of transcriptional activities of nuclear receptors. Here, we present SUMOylation of orphan nuclear receptor, ROR{alpha} by both SUMO-1 and SUMO-2. SUMOylation of ROR{alpha} occurred on the 240th lysine residue at the hinge region of human protein. PIAS family members, PIASx{alpha}, PIAS3, and PIASy, increased SUMOylation of ROR{alpha}, whereas SENP2 specifically removed SUMO from ROR{alpha}. SUMOylation-defective mutant form of ROR{alpha} exhibited decreased transcriptional activity on ROR{alpha}-responsive promoters indicating that SUMOylation may positively regulate transcriptional function of ROR{alpha}.

  19. Fibrinogen {alpha} genes: Conservation of bipartite transcripts and carboxy-terminal-extended {alpha} subunits in vertebrates

    SciTech Connect

    Fu, Y.; Cao, Y.; Hertzberg, K.M.; Grieninger, G.

    1995-11-01

    All three well-studied subunits of the clotting protein fibrinogen ({alpha}, {beta}, {gamma}) share N-terminal structural homologies, but until recently only the {beta} and {gamma} chains were recognized as having similar globular C-termini. With the discovery of an extra exon in the human fibrinogen {alpha} gene (exon VI), a minor form of the {alpha} subunit ({alpha}{sub E}) with an extended {beta}- and {gamma}-like C-terminus has been identified. In the present study, the polymerase chain reaction has been used to identify sequences that encode counterparts to {alpha}{sub E} in chicken, rabbit, rat, and baboon. The basic six-exon structure of the fibrinogen {alpha} genes is shown to be conserved among mammals and birds, as are the intron positions. Bipartite transcripts - still bearing an intron prior to the last exon - are found among the products of the various vertebrate fibrinogen {alpha} genes. The last exon represents the largest conserved segment of the gene and, in each species examined, encodes exactly 236 amino acids. The C-termini of these {alpha}{sub E} chains align without a single gap and are between 76 and 99% identical. Since the exon VI-encoded domain of {alpha}{sub E} is as well conserved as the corresponding regions of the {beta} and {gamma} chains, it follows that it is equally important and that {alpha}{sub E}-fibrinogen plays a vital, if as-yet unrecognized physiological role. 21 refs., 7 figs., 1 tab.

  20. Genetic variation of individual alpha frequency (IAF) and alpha power in a large adolescent twin sample.

    PubMed

    Smit, Christine M; Wright, Margaret J; Hansell, Narelle K; Geffen, Gina M; Martin, Nicholas G

    2006-08-01

    To further clarify the mode of genetic transmission on individual alpha frequency (IAF) and alpha power, the extent to which individual differences in these alpha indices are influenced by genetic factors were examined in a large sample of adolescent twins (237 MZ, 282 DZ pairs; aged 16). EEG was measured at rest (eyes closed) from the right occipital site, and a second EEG recording for 50 twin pairs obtained approximately 3 months after the initial collection, enabled an estimation of measurement error. Analyses confirmed a strong genetic influence on both IAF (h(2)=0.81) and alpha power (h(2)=0.82), and there was little support for non-additive genetic (dominance) variance. A small but significant negative correlation (-0.18) was found between IAF and alpha power, but genetic influences on IAF and alpha power were largely independent. All non-genetic variance was due to unreliability, with no significant variance attributed to unique environmental factors. Relationships between the alpha and IQ indices were also explored but were generally either non-significant or very low. The findings confirm the high heritability for both IAF and alpha power, they further suggest that the mode of genetic transmission is due to additive genetic factors, that genetic influences on the underlying neural mechanisms of alpha frequency and power are largely specific, and that individual differences in alpha activity are influenced little by developmental plasticity and individual experiences.

  1. Collagen alpha5 and alpha2(IV) chain coexpression: analysis of skin biopsies of Alport patients.

    PubMed

    Patey-Mariaud de Serre, N; Garfa, M; Bessiéres, B; Noël, L H; Knebelmann, B

    2007-08-01

    Alport syndrome is a collagen type IV disease caused by mutations in the COL4A5 gene with the X-linked form being most prevalent. The resultant alpha5(IV) collagen chain is a component of the glomerular and skin basement membranes (SBMs). Immunofluorescent determination of the alpha5(IV) chain in skin biopsies is the procedure of choice to identify patients. In 30% of patients, however, the mutant protein is still found in the SBM resulting in a normal staining pattern. In order to minimize or eliminate false results, we compared the distribution of the alpha2(IV) chain (another SBM component) and the alpha5(IV) chain by standard double label immunofluorescence (IF) and by confocal laser scanning microscopy. The study was performed on 55 skin biopsies of patients suspected of Alports and five normal control specimens. In normal skin, IF showed the classical linear pattern for both collagens along the basement membrane. Additionally, decreased alpha5(IV) was found in the bottom of the dermal papillary basement membrane. Confocal analysis confirmed the results and show alpha5(IV) focal interruptions. In suspected patients, both techniques showed the same rate of abnormal alpha5(IV) expression: segmental in women and absent in men. Our results show a physiological variation of alpha5(IV) location with focal interruptions and decreased expression in the bottom of the dermal basement membrane. Comparison of alpha5(IV) with alpha2(IV) expression is simple and eliminates technical artifacts.

  2. Variable displacement alpha-type Stirling engine

    NASA Astrophysics Data System (ADS)

    Homutescu, V. M.; Bălănescu, D. T.; Panaite, C. E.; Atanasiu, M. V.

    2016-08-01

    The basic design and construction of an alpha-type Stirling engine with on load variable displacement is presented. The variable displacement is obtained through a planar quadrilateral linkage with one on load movable ground link. The physico-mathematical model used for analyzing the variable displacement alpha-type Stirling engine behavior is an isothermal model that takes into account the real movement of the pistons. Performances and power adjustment capabilities of such alpha-type Stirling engine are calculated and analyzed. An exemplification through the use of the numerical simulation was performed in this regard.

  3. Synthesis of alpha-phosphorylated alpha,beta-unsaturated imines and their selective reduction to vinylogous and saturated alpha-aminophosphonates.

    PubMed

    Palacios, Francisco; Vicario, Javier; Maliszewska, Agnieszka; Aparicio, Domitila

    2007-03-30

    An efficient synthesis of alpha,beta-unsaturated imines derived from alpha-aminophosphonates is achieved through aza-Wittig reaction of P-trimethyl phosphazenes with beta,gamma-unsaturated alpha-ketophosphonates. Selective 1,2-reduction of such 1-azadienes affords beta,gamma-unsaturated alpha-aminophosphonates, phosphorylated analogs of vinylglycines, which are hydrogenated to yield saturated alpha-aminophosphonate derivatives.

  4. Potential bile acid metabolites. 19. The epimeric 3 alpha,6,7 beta-trihydroxy- and 3 alpha,6,7 beta,12 alpha-tetrahydroxy-5 alpha-cholanoic acids.

    PubMed

    Iida, T; Nishida, S; Chang, F C; Niwa, T; Goto, J; Nambara, T

    1993-04-01

    Syntheses by a new procedure of the known 3 alpha,6 alpha,7 beta- and 3 alpha,6 beta,7 beta-trihydroxy-5 alpha-cholanoic acids, and of the once-reported analog 3 alpha,6 alpha,7 beta,12 alpha-, as well as the new 3 alpha,6 beta,7 beta,12 alpha-tetrahydroxy-5 alpha-cholanoic acids, are described. Key intermediates of the syntheses are the 6-oxo-7 beta-ols of the respective 5 alpha-cholanoic acids (and their methyl esters) prepared by allomerization at C-5 of appropriate 6-bromo-7-oxo derivatives of the corresponding 5 beta-acids. Successful reduction of the 6,7-ketols to the desired products depended on the proper choice of reagents, either Zn(BH4)2 or Li/NH3/MeOH.

  5. Alpha-1 Antitrypsin Deficiency (Inherited Emphysema)

    MedlinePlus

    ... lung disease, • Physical exam, • Breathing tests and X-rays and • Oxygen levels. Two special blood tests determine the diagnosis of Alpha-1 Antitrypsin Deficiency. The first test measures the ...

  6. Nuclear diagnostic for fast alpha particles

    DOEpatents

    Grisham, L.R.; Post, D.E. Jr.; Dawson, J.M.

    1983-11-23

    This invention relates generally to high energy confined plasmas and more particularly is directed to measuring the velocity distribution of confined energetic alpha particles resulting from deuterium-tritium fusion reactions in a confined energetic plasma.

  7. Thorium isotopic analysis by alpha spectrometry.

    PubMed

    Gingell, T

    2001-01-01

    The technique of alpha spectrometry is used to detect alpha particles and to determine their energy. In this way the technique is able to provide simultaneously quantitative information (i.e. the activity) and qualitative information (the identity) on any radionuclide that emits an alpha particle. The longer-lived naturally occurring isotopes of thorium are all alpha emitters so the technique can be used to quantify them directly and this is extremely important if radiation doses due to intakes of these isotopes into the body are to be accurately assessed. The principle of the technique is discussed, its advantages and disadvantages, and the instrumentation that is commonly used today. The need for radiochemical separation is discussed and illustrated by reference to analysis procedures in current use for thorium isotopic analysis. Practical issues such as detection limits, quality control procedures. sample throughput and cost will be covered.

  8. Radioimmunotherapy with alpha-particle emitting radionuclides.

    PubMed

    Zalutsky, M R; Pozzi, O R

    2004-12-01

    An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides decaying by the emission of alpha-particles offer the possibility of matching the cell specific reactivity of monoclonal antibodies with radiation with a range of only a few cell diameters. Furthermore, alpha-particles have important biological advantages compared with external beam radiation and beta-particles including a higher biological effectiveness, which is nearly independent of oxygen concentration, dose rate and cell cycle position. In this review, the clinical settings most likely to benefit from alpha-particle radioimmunotherapy will be discussed. The current status of preclinical and clinical research with antibodies labeled with 3 promising alpha-particle emitting radionuclides - (213)Bi, (225)Ac, and (211)At - also will be summarized.

  9. Radioimmunotherapy with alpha-emitting nuclides.

    PubMed

    McDevitt, M R; Sgouros, G; Finn, R D; Humm, J L; Jurcic, J G; Larson, S M; Scheinberg, D A

    1998-09-01

    This review discusses the application of alpha particle-emitting radionuclides in targeted radioimmunotherapy. It will outline the production and chemistry of astatine-211, bismuth-212, lead-212, actinium-225, bismuth-213, fermium-255, radium-223 and terbium-149, which at present are the most promising alpha-emitting isotopes available for human clinical use. The selective cytotoxicity offered by alpha particle-emitting radioimmunoconstructs is due to the high linear energy transfer and short particle path length of these radionuclides. Based upon the pharmacokinetics of alpha particle-emitting radioimmunoconstructs, both stochastic and conventional dosimetric methodology is discussed, as is the preclinical and initial clinical use of these radionuclides conjugated to monoclonal antibodies for the treatment of human neoplasia.

  10. Genetics Home Reference: 5-alpha reductase deficiency

    MedlinePlus

    ... About half of these individuals adopt a male gender role in adolescence or early adulthood. Related Information ... 1730-5. Citation on PubMed Cohen-Kettenis PT. Gender change in 46,XY persons with 5alpha-reductase- ...

  11. Alpha Coincidence Spectroscopy studied with GEANT4

    SciTech Connect

    Dion, Michael P.; Miller, Brian W.; Tatishvili, Gocha; Warren, Glen A.

    2013-11-02

    Abstract The high-energy side of peaks in alpha spectra, e.g. 241Am, as measured with a silicon detector has structure caused mainly by alpha-conversion electron and to some extent alphagamma coincidences. We compare GEANT4 simulation results to 241Am alpha spectroscopy measurements with a passivated implanted planar silicon detector. A large discrepancy between the measurements and simulations suggest that the GEANT4 photon evaporation database for 237Np (daughter of 241Am decay) does not accurately describe the conversion electron spectrum and therefore was found to have large discrepancies with experimental measurements. We describe how to improve the agreement between GEANT4 and alpha spectroscopy for actinides of interest by including experimental measurements of conversion electron spectroscopy into the photon evaporation database.

  12. Frontal alpha asymmetry and sexually motivated states.

    PubMed

    Prause, Nicole; Staley, Cameron; Roberts, Verena

    2014-03-01

    Anterior alpha asymmetry of electroencephalographic (EEG) signals has been suggested to index state approach (or avoidance) motivation. This model has not yet been extended to high approach-motivation sexual stimuli, which may represent an important model of reward system function. Sixty-five participants viewed a neutral and a sexually motivating film while their EEG was recorded, and reported their sexual feelings after each film. Greater alpha power in the left hemisphere during sexually motivated states was evident. A positive relationship between self-reported mental sexual arousal and alpha asymmetry was identified, where coherence between these indicators was higher in women. Notably, coherence was stronger when mental versus physical sexual arousal was rated. Alpha asymmetry appears to offer a new method for further examining this novel coherence pattern across men and women.

  13. Nature of the pygmy dipole resonance in 140Ce studied in (alpha, alpha' gamma) experiments.

    PubMed

    Savran, D; Babilon, M; van den Berg, A M; Harakeh, M N; Hasper, J; Matic, A; Wörtche, H J; Zilges, A

    2006-10-27

    A concentration of electric-dipole excitations below the particle threshold, which is frequently denoted as the pygmy dipole resonance, has been studied in the semimagic nucleus 140Ce in (alpha, alpha' gamma) experiments at E alpha = 136 MeV. The technique of alpha-gamma coincidence experiments allows the separation of E1 excitations from states of other multipolarities in the same energy region and provides an excellent energy resolution to allow a detailed analysis for each state. The experimental results show that the PDR splits into two parts with different nuclear structure: one part which is excited in (alpha, alpha' gamma) as well as (gamma, gamma') experiments and one part which is excited only in (gamma, gamma').

  14. Alpha-emitters for medical therapy workshop

    SciTech Connect

    Feinendegen, L.E.; McClure, J.J.

    1996-12-31

    A workshop on ``Alpha-Emitters for Medical Therapy`` was held May 30-31, 1996 in Denver Colorado to identify research goals and potential clinical needs for applying alpha-particle emitters and to provide DOE with sufficient information for future planning. The workshop was attended by 36 participants representing radiooncology, nuclear medicine, immunotherapy, radiobiology, molecular biology, biochemistry, radiopharmaceutical chemistry, dosimetry, and physics. This report provides a summary of the key points and recommendations arrived at during the conference.

  15. Measurement of the angle alpha at BABAR

    SciTech Connect

    Perez, A.; /Orsay, LAL

    2009-06-25

    The authors present recent measurements of the CKM angle {alpha} using data collected by the BABAR detector at the PEP-II asymmetric-energy e{sup +}e{sup -} collider at the SLAC National Accelerator Laboratory, operating at the {Upsilon}(4S) resonance. They present constraints on {alpha} from B {yields} {pi}{pi}, B {yields} {rho}{rho} and B {yields} {rho}{pi} decays.

  16. [Studies on determination of alpha-amylase with p-nitrophenyl-alpha-D-maltotetraoside].

    PubMed

    Kruse-Jarres, J D; Schott, F J; Klein, B; Rastetter, N; Wallenfels, K

    1982-11-01

    Nitrophenylmaltodextrins are alpha-amylase substrates which allow a continuous determination with a zero order kinetics over a period of at least 10 min, without deviations from linearity. Only one auxiliary enzyme is necessary. Practicability and clinical evidence of alpha-amylase determinations by means of p-nitrophenyl-alpha-D-maltotetraoside are demonstrated. The interserial precision of 0.84% cannot conceal an only moderate correlation with previous methods. This fact, however, does not negate the advantages.

  17. Alpha-particles for targeted therapy.

    PubMed

    Sgouros, George

    2008-09-01

    Alpha-particles are helium nuclei that deposit DNA damaging energy along their track that is 100 to 1000 times greater than that of conventionally used beta-particle emitting radionuclides for targeted therapy; the damage caused by alpha-particles is predominately double-stranded DNA breaks severe enough so as to be almost completely irreparable. This means that a small number of tracks through a cell nucleus can sterilize a cell and that, because the damage is largely irreparable, alpha-particle radiation is not susceptible to resistance as seen with external radiotherapy (e.g., in hypoxic tissue). The ability of a single track to influence biological outcome and the stochastic nature of alpha-particle decay require statistical or microdosimetric techniques to properly reflect likely biological outcome when the biologically relevant target is small or when a low number of radionuclide decays have occurred. In therapeutic implementations, microdosimetry is typically not required and the average absorbed dose over a target volume is typically calculated. Animal and cell culture studies have shown that, per unit absorbed dose, the acute biological effects of alpha-particles are 3 to 7 times greater than the damage caused by external beam or beta-particle radiation. Over the past ten to 15 years, alpha-particle emitting radionuclides have been investigated as a possible new class of radionuclides for targeted therapy. Results from the small number of clinical trials reported to date have shown efficacy without significant toxicity.

  18. Is ALPHA the Odometer of the Universe?

    NASA Astrophysics Data System (ADS)

    Goradia, Shantilal

    2007-10-01

    The answer seems to be affirmative. ALPHA may be an odometer with sixty decimal points, the last digit moving up one integer every Planck time, displaying the information of the age of the universe. We can only measure it to the ninth decimal point. ALPHA is greater than or equal to the reciprocal of the natural logarithm of the age of the universe in Planck times, sixty orders of magnitude. Eddington spent good portion of his life trying to come up with a value of ALPHA based on multiplicity. Gamow had the insight about the four nucleotides of genetic tape. His deeper 1967 insight was a link between ALPHA and cosmology. Evolution mandates variation of ALPHA. In terms of the entropy equation on Boltzmann's tomb, ALPHA seems to be the Maxwell's demon, decreasing the entropy of invisible compartments within which electromagnetic interactions take place. Nature potentially knows only the Planck units. I will discuss the implications for the second law of thermodynamics drafted in physics/0210040 v3.

  19. Methods for the synthesis and polymerization of .alpha.,.alpha.'-dihalo-p-xylenes

    DOEpatents

    Ferraris, John P.; Neef, Charles J.

    2002-07-30

    The present invention describes an improved method for the polymerization of .alpha.,.alpha.-dihalo-p-xylene's such as the .alpha.,.alpha.'-dihalo-2-methoxy-5-(2-ethylhexyloxy)-xylene's. The procedure for synthesis is based on the specific order of addition of reagents and the use of an anionic initiator that allows control of the molecular weight of the polymer. The molecular weight control allows processability of the polymer which is important for its utility in applications including in light-emitting-diodes, field effect transistors and photovoltaic devices.

  20. Contribution from 3 alpha-Condensed States to the Triple-Alpha Reaction

    SciTech Connect

    Kato, Kiyoshi; Kurokawa, Chie; Arai, Koji

    2010-06-01

    The alpha-condensed state in nuclear systems has been proposed by Tohsaki et al. and has given rise to interesting discussions. The Hoyle state of {sup 12}C has been studied as the most typical example of such an alpha-condensed state. A new resonant 0{sub 3}{sup +} state (E{sub r} = 1.66 MeV, GAMMA = 1.48 MeV) is predicted as an excited alpha-condensed state in addition to the second 0{sup +} state of the Hoyle state by calculations of the 3 alpha orthogonality condition model (3 alpha OCM) using the complex scaling method. Based on this result, the breakup strengths of the inversion reaction for sequential ({sup 8}Be+alpha->{sup 12}C+gamma) and direct (alpha+alpha+alpha->{sup 12}C+gamma) processes are calculated. It is discussed that a large reaction strength calculated recently by Ogata et al. in non-resonant energies is considered as a contribution from the excited 0{sub 3}{sup +} state.

  1. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments.

    PubMed Central

    Baer, R; Boehm, T; Yssel, H; Spits, H; Rabbitts, T H

    1988-01-01

    We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one rearrangement within J delta-C delta and one or more J alpha rearrangements, and finally, cells with rearrangements within J alpha and consequential deletion of the delta locus. Further analysis by cloning of rearrangements within the J alpha locus show that, in addition to V alpha-J alpha joins, J alpha-J alpha aberrant recombinations occur and rearrangement data indicate that such events are frequent. A model is presented to account for such recombinations. Images PMID:2971534

  2. Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor knock out mice brain.

    PubMed

    Höcker, Jan; Weber, Bernd; Tonner, Peter H; Scholz, Jens; Brand, Philipp-Alexander; Ohnesorge, Henning; Bein, Berthold

    2008-03-17

    alpha(2)-adrenoceptor agonists like clonidine or dexmedetomidine increase the sedative and analgesic actions of opioids. Furthermore opioids like meperidine show potent anti-shivering effects like alpha(2)-adrenoceptor agonists. The underlying molecular mechanisms of these effects are still poorly defined. The authors therefore studied the ability of four different opioids (meperidine, remifentanil, sufentanil and tramadol) to interact with different alpha(2)-adrenoceptor subtypes in mice lacking individual alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptors (alpha(2)-adrenoceptor knock out (alpha(2)-AR KO) mice)). The interaction of opioids with alpha(2)-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor deficient mice. Displacement of the radiolabelled alpha(2)-adrenoceptor agonist [(125)I]-paraiodoclonidine ([(125)I]-PIC) from alpha(2)-adrenoceptors in different brain regions by increasing opioid concentrations was measured, and binding affinity of the analysed opioids to alpha(2)-adrenoceptor subtypes in different brain regions was quantified. Meperidine, remifentanil and tramadol but not sufentanil provoked dose dependent displacement of specifically bound [(125)I]-PIC from all alpha(2)-adrenoceptor subtypes in cortex, cerebellum, medulla oblongata, thalamus, hippocampus and pons. Required concentrations of meperidine and remifentanil for [(125)I]-PIC displacement from alpha(2B)- and alpha(2C)-adrenoceptors were lower than from alpha(2A)-adrenoceptors, indicating higher binding affinity for alpha(2B)- and alpha(2C)-adrenoceptors. In contrast, [(125)I]-PIC displacement by tramadol indicated higher binding affinity to alpha(2A)-adrenoceptors than to alpha(2B)- and alpha(2C)-adrenoceptors. Our results indicate that meperidine, remifentanil and tramadol interact with alpha(2)-adrenoceptors in mouse brain showing different affinity for alpha(2A)-, alpha(2B)- and alpha(2C

  3. Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane

    NASA Astrophysics Data System (ADS)

    Gyoneva, Lazarina

    The glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is alpha3(IV)alpha4(IV)alpha5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the alpha3(IV)alpha4(IV)alpha5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the alpha3(IV)alpha4(IV)alpha5(IV) chains present and missing. The experiments showed basement membranes containing alpha3(IV)alpha4(IV)alpha5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the alpha3(IV)alpha4(IV)alpha5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the alpha3(IV)alpha4(IV)alpha5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the alpha3(IV)alpha4(IV)alpha5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of alpha3(IV)alpha4(IV)alpha

  4. G alpha 16, a G protein alpha subunit specifically expressed in hematopoietic cells.

    PubMed Central

    Amatruda, T T; Steele, D A; Slepak, V Z; Simon, M I

    1991-01-01

    Signal-transduction pathways mediated by guanine nucleotide-binding regulatory proteins (G proteins) determine many of the responses of hematopoietic cells. A recently identified gene encoding a G protein alpha subunit, G alpha 16, is specifically expressed in human cells of the hematopoietic lineage. The G alpha 16 cDNA encodes a protein with predicted Mr of 43,500, which resembles the G q class of alpha subunits and does not include a pertussis toxin ADP-ribosylation site. In comparison with other G protein alpha subunits, the G alpha 16 predicted protein has distinctive amino acid sequences in the amino terminus, the region A guanine nucleotide-binding domain, and in the carboxyl-terminal third of the protein. Cell lines of myelomonocytic and T-cell phenotype express the G alpha 16 gene, but no expression is detectable in two B-cell lines or in nonhematopoietic cell lines. G alpha 16 gene expression is down-regulated in HL-60 cells induced to differentiate to neutrophils with dimethyl sulfoxide. Antisera generated from synthetic peptides that correspond to two regions of G alpha 16 specifically react with a protein of 42- to 43-kDa in bacterial strains that overexpress G alpha 16 and in HL-60 membranes. This protein is decreased in membranes from dimethyl sulfoxide-differentiated HL-60 cells and is not detectable in COS cell membranes. The restricted expression of this gene suggests that G alpha 16 regulates cell-type-specific signal-transduction pathways, which are not inhibited by pertussis toxin. Images PMID:1905813

  5. Overview Of Suborbital Human Transportation Concept Alpha

    NASA Astrophysics Data System (ADS)

    Adirim, H.; Pilz, N.; Marini, M.; Hendrick, P.; Schmid, M.; Behr, R.; Barth, T.; Tarfeld, F.; Wiegand, A.; Charbonnier, D.; Haya Ramos, R.; Steeland, J.; Mack, A.

    2011-05-01

    Within the EC co-funded project FAST20XX (Future high-Altitude high-Speed Transport 20XX), the European suborbital passenger transportation system concept ALPHA (Airplane Launched PHoenix Aircraft), which shall be based to a maximum extent on existing technologies and capabilities, is currently being investigated as collaborative project by a European consortium under coordination of ESA. The ALPHA concept incorporates an air-launch from a carrier aircraft, which shall be used as first stage. The ALPHA vehicle shall be capable of transporting up to four passengers plus one pilot to an altitude of at least 100 km. The ALPHA vehicle is a down-scaled version of the suborbital space transportation concept Hopper, which was already deeply investigated within the European FESTIP System Study and the German ASTRA program including the successfully flown experimental landing demonstrator Phoenix. This approach has allowed the use of existing aerodynamic vehicle data and has led to the adaptation of the external Hopper/Phoenix configuration for ALPHA. In FESTIP and ASTRA, the Hopper configuration showed sufficient stability margins. Due to the geometric similarity of the ALPHA and Hopper vehicles, a trimable and flyable configuration could be derived by means of ALPHA flight trajectory calculations. In its current configuration, the ALPHA vehicle has a length of ca. 9 m and a gross take-off mass of ca. 3.5 Mg. The launch, staging and separation of ALPHA shall be performed either as internal air-launch from the cargo bay of the carrier aircraft, as under-wing air-launch or as towed air-launch. After separation from the carrier aircraft, the ALPHA vehicle ignites its onboard rocket propulsion system. Since conventional liquid and solid propulsion did not seem suitable for ALPHA due to Their high cost, limited safety and toxicity, a low-cost, “green” and non-hazardous hybrid propulsion system based on liquid nitrous oxide in combination with a solid polymer fuel was

  6. Pharmacologic specificity of alpha-2 adrenergic receptor subtypes

    SciTech Connect

    Petrash, A.; Bylund, D.

    1986-03-01

    The authors have defined alpha-2 adrenergic receptor subtypes in human and rat tissues using prazosin as a subtype selective drug. Prazosin has a lower affinity (250 nM) at alpha-2A receptor and a higher affinity (5 nM) at alpha-2B receptors. In order to determine if other adrenergic drugs are selective for one or the other subtypes, the authors performed (/sup 3/H)yohimbine inhibition experiments with various adrenergic drugs in tissues containing alpha-2A, alpha-2B or both subtypes. Oxymetazoline, WB4101 and yohimbine were found to be 80-, 20- and 10-fold more potent at alpha-2A receptors than at alpha-2B receptors. Phentolamine, adazoxan, (+)- and (-)-mianserin, clonidine, (+)-butaclamol, (-)- and (+)-norepinephrine, epinephrine, dopamine and thioridazine were found to have equal affinities for the two subtypes. These results further validate the subdivision of alpha-2 adrenergic receptors into alpha-2A and alpha-2B subtypes.

  7. Targeted alpha-therapy: past, present, future?

    PubMed

    Brechbiel, Martin W

    2007-11-21

    Monoclonal antibodies have become a viable strategy for the delivery of therapeutic, particle emitting radionuclides specifically to tumor cells to either augment anti-tumor action of the native antibodies or to solely take advantage of their action as targeting vectors. Proper and rational selection of radionuclide and antibody combinations is critical to making radioimmunotherapy (RIT) a standard therapeutic modality due to the fundamental and significant differences in the emission of either alpha- and beta-particles. The alpha-particle has a short path length (50-80 microm) that is characterized by high linear energy transfer (100 keV microm(-1)). Actively targeted alpha-therapy potentially offers a more specific tumor cell killing action with less collateral damage to the surrounding normal tissues than beta-emitters. These properties make targeted alpha-therapy an appropriate therapy to eliminate minimal residual or micrometastatic disease. RIT using alpha-emitters such as (213)Bi, (211)At, (225)Ac, and others has demonstrated significant activity in both in vitro and in vivo model systems. Limited numbers of clinical trials have progressed to demonstrate safety, feasibility, and therapeutic activity of targeted alpha-therapy, despite having to traverse complex obstacles. Further advances may require more potent isotopes, additional sources and more efficient means of isotope production. Refinements in chelation and/or radiolabeling chemistry combined with rational improvements of isotope delivery, targeting vectors, molecular targets, and identification of appropriate clinical applications remain as active areas of research. Ultimately, randomized trials comparing targeted alpha-therapy combined with integration into existing standards of care treatment regimens will determine the clinical utility of this modality.

  8. Alpha-particle fluence in radiobiological experiments.

    PubMed

    Nikezic, Dragoslav; Yu, Kwan Ngok

    2016-11-03

    Two methods were proposed for determining alpha-particle fluence for radiobiological experiments. The first involved calculating the probabilities of hitting the target for alpha particles emitted from a source through Monte Carlo simulations, which when multiplied by the activity of the source gave the fluence at the target. The second relied on the number of chemically etched alpha-particle tracks developed on a solid-state nuclear track detector (SSNTD) that was irradiated by an alpha-particle source. The etching efficiencies (defined as percentages of latent tracks created by alpha particles from the source that could develop to become visible tracks upon chemical etching) were computed through Monte Carlo simulations, which when multiplied by the experimentally counted number of visible tracks would also give the fluence at the target. We studied alpha particles with an energy of 5.486 MeV emitted from an (241)Am source, and considered the alpha-particle tracks developed on polyallyldiglycol carbonate film, which is a common SSNTD. Our results showed that the etching efficiencies were equal to one for source-film distances of from 0.6 to 3.5 cm for a circular film of radius of 1 cm, and for source-film distances of from 1 to 3 cm for circular film of radius of 2 cm. For circular film with a radius of 3 cm, the etching efficiencies never reached 1. On the other hand, the hit probability decreased monotonically with increase in the source-target distance, and fell to zero when the source-target distance was larger than the particle range in air.

  9. Restoration of on-time embryo implantation corrects the timing of parturition in cytosolic phospholipase A2 group IVA deficient mice.

    PubMed

    Brown, Naoko; Morrow, Jason D; Slaughter, James C; Paria, Bibhash C; Reese, Jeff

    2009-12-01

    Cytosolic phospholipase A2 (cPLA2, PLA2G4A) catalyzes the release of arachidonic acid for prostaglandin synthesis by cyclooxygenase 1 (PTGS1) and cyclooxygenase 2 (PTGS2). Mice with Pla2g4a deficiency have parturition delay and other reproductive deficits, including deferred onset of implantation, crowding of implantation sites, and small litters. In this study, we examined the contribution of PLA2G4A to parturition in mice. Pla2g4a mRNA and protein expression were discretely localized in the term and preterm uterine luminal epithelium and colocalized with Ptgs1, but not Ptgs2, expression. The levels of PGE2, PGF2alpha, 6-keto-PGF1alpha, and TxB2 were significantly decreased in Pla2g4a-null uterine tissues, similar to Ptgs1-null uteri, consistent with predominance of PLA2G4A-PTGS1-mediated prostaglandin synthesis in preparation for murine parturition. Litter size was strongly associated with the timing of parturition in Pla2g4a-null mice but could not fully account for the parturition delay. Pla2g4a-null females that received PGE2 + carbaprostacyclin at the time of implantation delivered earlier (20.5 +/- 0.2 days vs. 21.6 +/- 0.2 days, P < 0.01), although litter size was not improved (4.6 vs. 4.4 pups per litter, P = 0.6). After correction for small litter size, multivariate analysis indicated that Pla2g4a-null mice given prostaglandin treatment to improve implantation timing had gestational length that was similar to wild-type and Pla2g4a heterozygous mice. These results indicate that, despite specific Pla2g4a expression and function in term gestation uteri, the delayed parturition phenotype in Pla2g4a-null mice is primarily due to deferral of implantation. The role of PLA2G4A in timely parturition appears to be critically related to its actions in early pregnancy.

  10. A chimera-like alpha-amylase inhibitor suggesting the evolution of Phaseolus vulgaris alpha-amylase inhibitor.

    PubMed

    Wato, S; Kamei, K; Arakawa, T; Philo, J S; Wen, J; Hara, S; Yamaguchi, H

    2000-07-01

    White kidney bean (Phaseolus vulgaris) contains two kinds of alpha-amylase inhibitors, one heat-stable (alpha AI-s) and one heat-labile (alpha AI-u). alpha AI-s has recently been revealed to be a tetrameric complex, alpha(2)beta(2), with two active sites [Kasahara et al. (1996) J. Biochem. 120, 177-183]. The present study was undertaken to reveal the molecular features of alpha AI-u, which is composed of three kinds of subunits, alpha, beta, and gamma. The gamma-subunit, in contrast to the alpha- and beta-subunits that are indistinguishable from the alpha- and beta-subunits of alpha AI-s, was found to correspond to a subunit of an alpha-amylase inhibitor-like protein, which has been identified as an inactive, evolutionary intermediate between arcelin and the alpha-amylase inhibitor in a P. vulgaris defense protein family. The polypeptide molecular weight of alpha AI-u determined by the light-scattering technique, together with the polypeptide molecular weights of the subunits, suggests that alpha AI-u is a trimeric complex, alpha beta gamma. The inhibition of alpha AI-u by increasing amounts of porcine pancreatic alpha-amylase (PPA) indicates that an inactive 1:1 complex is formed between alpha AI-u and PPA. Molecular weight estimation of the complex by the light-scattering technique confirmed that it is a complex of alpha AI-u with one PPA molecule. Thus it seems probable that alpha AI-u is an evolutionary intermediate of the P. vulgaris alpha-amylase inhibitor.

  11. Some aspects of the mechanism of complexation of red kidney bean alpha-amylase inhibitor and alpha-amylase.

    PubMed

    Wilcox, E R; Whitaker, J R

    1984-04-10

    Bovine pancreatic alpha-amylase binds 1 mol of acarbose (a carbohydrate alpha-amylase inhibitor) per mol at the active site and also binds acarbose nonspecifically. The red kidney bean alpha-amylase inhibitor-bovine pancreatic alpha-amylase complex retained nonspecific binding for acarbose only. Binding of p-nitrophenyl alpha-D-maltoside to the final complex of red kidney bean alpha-amylase inhibitor and bovine pancreatic alpha-amylase has a beta Ks (Ks') value that is 3.4-fold greater than the Ks (16 mM) of alpha-amylase for p-nitrophenyl alpha-D-maltoside alone. The initial complex of alpha-amylase and inhibitor apparently hydrolyzes this substrate as rapidly as alpha-amylase alone. The complex retains affinity for substrates and competitive inhibitors, which, when present in high concentrations, cause dissociation of the complex. Maltose (0.5 M), a competitive inhibitor of alpha-amylase, caused dissociation of the red kidney bean alpha-amylase inhibitor--alpha-amylase complex. Interaction between red kidney bean (Phaseolus vulgaris) alpha-amylase inhibitor and porcine pancreatic alpha-amylase proceeds through two steps. The first step has a Keq of 3.1 X 10(-5) M. The second step (unimolecular; first order) has a forward rate constant of 3.05 min-1 at pH 6.9 and 30 degrees C. alpha-Amylase inhibitor combines with alpha-amylase, in the presence of p-nitrophenyl alpha-D-maltoside, noncompetitively. On the basis of the data presented, it is likely that alpha-amylase is inactivated by the alpha-amylase inhibitor through a conformational change. A kinetic model, in the presence and absence of substrate, is described for noncompetitive, slow, tight-binding inhibitors that proceed through two steps.

  12. Endometrial receptivity: expression of alpha3beta1, alpha4beta1 and alphaVbeta1 endometrial integrins in women with impaired fertility.

    PubMed

    Skrzypczak, J; Mikołajczyk, M; Szymanowski, K

    2001-11-01

    Advances in immunohistochemical methods with the specificity of poly- and monoclonal antibodies allow the description of the endometrial receptivity, which is characterized by the ability of secretion of phase specific proteins and glikoproteins by epithelial and stromal cells. We studied the differences in the expression of alpha3beta1, alpha4beta1 and alphaVbeta1 integrins in endometrium of women with recurrent miscarriages and women with unexplained infertility. The endometrial tissue was collected during hysteroscopy performed between 7th and 9th day after ovulation. The immunohistochemical evaluation of alpha3beta1, alpha4beta1 and alphaVbeta1 integrin expression was determined in all endometrial biopsies. Staining intensity of alpha3beta1 in glandular epithelium and endometrial stroma was similar in both groups. In women with recurrent miscarriages we noted a lower concentrations of the alpha4beta1 and alphaVbeta1 integrins during the midluteal phase than in women with unexplained infertility. Moreover, integrins alpha4beta1 and alphaVbeta1 were expressed more frequently in glandular epithelium and endometrial stroma of women with unexplained infertility than those of women with recurrent miscarriages. However, alphaV(2)1 staining in endometrial stroma was stronger than that of alpha4beta1. It can be concluded, that these integrins may play an important role in the implantation process.

  13. Effect of alpha-tocopherol on bovine in vitro fertilization.

    PubMed

    Marques, A; Santos, P; Antunes, G; Chaveiro, A; Moreira da Silva, F

    2010-02-01

    The objectives of this work are to determine if exogenous supplementation with alpha-tocopherol increases the in vitro fertilization (IVF) rate of bovine oocytes and improves viability of selected spermatozoa after 'swim-up'. The percentage of fertilized oocytes was significantly but negatively correlated (r = -0.941, p < 0.01) with the concentration of alpha-tocopherol. The control resulted in 95% of fertilized oocytes, which decreased as follows: 25 microM alpha-tocopherol (alpha25) 86%, 50 microM alpha-tocopherol (alpha50) 74%, 100 microM alpha-tocopherol (alpha100) 66% and 200 microM alpha-tocopherol (alpha200) 56%. Relatively to sperm viability after 'swim-up' with alpha-tocopherol supplementation, this antioxidant proved to have a beneficial effect as its concentration increased up to alpha50, decreasing for the concentrations of alpha100 and alpha200. Control resulted in 83% of live cells and 16% of dead cells; alpha25 resulted in 88% of live cells and 12% of dead cells; alpha50 resulted in 91% of live cells and 9% of dead cells; alpha100 resulted in 67% of live cells and 33% of dead cells; and finally alpha200 resulted in 57% of live cells and 42% of dead cells. In summary, the present study allows to conclude that, in our conditions, supplementation with the antioxidant alpha-tocopherol in IVF of bovine oocytes has a detrimental effect on fertilization rates. Nevertheless, exogenous supplementation with alpha-tocopherol at a concentration of 50 mM in the sperm-TALP media during the 'swim-up' technique has a significant beneficial effect on the selected spermatozoa viability.

  14. The biological effects of five feline IFN-alpha subtypes.

    PubMed

    Baldwin, Susan L; Powell, Tim D; Sellins, Karen S; Radecki, Steven V; Cohen, J John; Milhausen, Michael J

    2004-06-01

    IFN-alpha has been shown to induce both antiviral and antiproliferative activities in animals. This report describes the biological activity of five recently identified feline IFN-alpha subtypes expressed in the Chinese hamster ovary (CHO) cell line (rfeIFN-alpha1[CHO], rfeIFN-alpha2[CHO], rfeIFN-alpha3[CHO], rfeIFN-alpha5[CHO] and rfeIFN-alpha6[CHO]) and the feIFN-alpha6 subtype expressed in and purified from Pichia pastoris (rfeIFN-alpha6[P. pastoris]). The rfeIFN-alpha[CHO] subtypes were tested for antiviral activity against either Vesicular stomatitis virus (VSV) or feline calicivirus (FCV) infected feline embryonic fibroblast cell line (AH927) or Crandell feline kidney cell line (CRFK). Antiviral activity was induced against both VSV and FCV infected AH927 cells and VSV infected CRFK cells by all five of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris]. In addition, the IFN-alpha inducible Mx gene (associated with antiviral activity) was upregulated in vivo 24 h following treatment with rfeIFN-alpha6[P. pastoris], compared to baseline levels seen prior to treatment. All of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris] exhibited antiproliferative activity in the FeT-J cell line (an IL-2 independent feline T-cell line). Both necrosis and apoptosis were observed in rfeIFN-alpha6[P. pastoris]-treated FeT-J cells. The rfeIFN-alpha3[CHO] subtype consistently exhibited lower antiviral and antiproliferative activity compared to that observed with the other four rfeIFN-alpha[CHO] subtypes. In summary, this paper demonstrates that five previously described feIFN-alpha subtypes induce both antiviral and antiproliferative activities in vitro and are capable of upregulating the feMx gene in vivo.

  15. Infusions of 3alpha,5alpha-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3alpha,5alpha-THP in midbrain, hippocampus, diencephalon, and cortex of female rats.

    PubMed

    Frye, Cheryl A; Rhodes, Madeline E

    2008-02-11

    17beta-Estradiol (E2) and progesterone (P4) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P4 metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), modulates lordosis of E2-primed rodents; 3alpha,5alpha-THP can also influence anxiety and social behaviors. To examine if 3alpha,5alpha-THP in the VTA mediates socio-sexual behaviors, we infused 3alpha,5alpha-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E2, P4, dihydroprogesterone (DHP), and 3alpha,5alpha-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3alpha,5alpha-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3alpha,5alpha-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3alpha,5alpha-THP, but neither E2 nor P4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3alpha,5alpha-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

  16. Alpha Channeling in Rotating Plasma with Stationary Waves

    SciTech Connect

    A. Fetterman and N.J. Fisch

    2010-02-15

    An extension of the alpha channeling effect to supersonically rotating mirrors shows that the rotation itself can be driven using alpha particle energy. Alpha channeling uses radiofrequency waves to remove alpha particles collisionlessly at low energy. We show that stationary magnetic fields with high nθ can be used for this purpose, and simulations show that a large fraction of the alpha energy can be converted to rotation energy.

  17. Experimental and Theoretical Electron Density Distribution of Alpha,Alpha-Trehalose Dihydrate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alpha,alpha-rehalose is of interest because of its cryoprotective and antidessicant properties, and because it possesses various technical anomalies such as 13C NMR spectra that give misleading indications of intramolecular structural symmetry. It is a non-reducing disaccharide, with the glycosidic...

  18. Solution structure of alpha t alpha, a helical hairpin peptide of de novo design.

    PubMed Central

    Fezoui, Y.; Connolly, P. J.; Osterhout, J. J.

    1997-01-01

    alpha t alpha is a 38-residue peptide designed to adopt a helical hairpin conformation in solution (Fezoui Y, Weaver DL Osterhout JJ, 1995, Protein Sci 4:286-295). A previous study of the carboxylate form of alpha t alpha by CD and two-dimensional NMR indicated that the peptide was highly helical and that the helices associated in approximately the intended orientation (Fezoui Y, Weaver DL, Osterhout JJ, 1994, Proc Natl Acad Sci USA 91:3675-3679). Here, the solution structure of alpha t alpha as determined by two-dimensional NMR is reported. A total of 266 experimentally derived distance restraints and 20 dihedral angle restraints derived from J-couplings were used. One-hundred initial structures were generated by distance geometry and refined by dynamical simulated annealing. Twenty-three of the lowest-energy structures consistent with the experimental restraints were analyzed. The results presented here show that alpha t alpha is comprised of two associating helices connected by a turn region. PMID:9300486

  19. Amyloid formation and disaggregation of {alpha}-synuclein and its tandem repeat ({alpha}-TR)

    SciTech Connect

    Bae, Song Yi; Kim, Seulgi; Hwang, Heejin; Kim, Hyun-Kyung; Yoon, Hyun C.; Kim, Jae Ho; Lee, SangYoon; Kim, T. Doohun

    2010-10-01

    Research highlights: {yields} Formation of the {alpha}-synuclein amyloid fibrils by [BIMbF{sub 3}Im]. {yields} Disaggregation of amyloid fibrils by epigallocatechin gallate (EGCG) and baicalein. {yields} Amyloid formation of {alpha}-synuclein tandem repeat ({alpha}-TR). -- Abstract: The aggregation of {alpha}-synuclein is clearly related to the pathogenesis of Parkinson's disease. Therefore, detailed understanding of the mechanism of fibril formation is highly valuable for the development of clinical treatment and also of the diagnostic tools. Here, we have investigated the interaction of {alpha}-synuclein with ionic liquids by using several biochemical techniques including Thioflavin T assays and transmission electron microscopy (TEM). Our data shows a rapid formation of {alpha}-synuclein amyloid fibrils was stimulated by 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BIMbF{sub 3}Im], and these fibrils could be disaggregated by polyphenols such as epigallocatechin gallate (EGCG) and baicalein. Furthermore, the effect of [BIMbF{sub 3}Im] on the {alpha}-synuclein tandem repeat ({alpha}-TR) in the aggregation process was studied.

  20. Cortical Alpha Oscillations Predict Speech Intelligibility

    PubMed Central

    Dimitrijevic, Andrew; Smith, Michael L.; Kadis, Darren S.; Moore, David R.

    2017-01-01

    Understanding speech in noise (SiN) is a complex task involving sensory encoding and cognitive resources including working memory and attention. Previous work has shown that brain oscillations, particularly alpha rhythms (8–12 Hz) play important roles in sensory processes involving working memory and attention. However, no previous study has examined brain oscillations during performance of a continuous speech perception test. The aim of this study was to measure cortical alpha during attentive listening in a commonly used SiN task (digits-in-noise, DiN) to better understand the neural processes associated with “top-down” cognitive processing in adverse listening environments. We recruited 14 normal hearing (NH) young adults. DiN speech reception threshold (SRT) was measured in an initial behavioral experiment. EEG activity was then collected: (i) while performing the DiN near SRT; and (ii) while attending to a silent, close-caption video during presentation of identical digit stimuli that the participant was instructed to ignore. Three main results were obtained: (1) during attentive (“active”) listening to the DiN, a number of distinct neural oscillations were observed (mainly alpha with some beta; 15–30 Hz). No oscillations were observed during attention to the video (“passive” listening); (2) overall, alpha event-related synchronization (ERS) of central/parietal sources were observed during active listening when data were grand averaged across all participants. In some participants, a smaller magnitude alpha event-related desynchronization (ERD), originating in temporal regions, was observed; and (3) when individual EEG trials were sorted according to correct and incorrect digit identification, the temporal alpha ERD was consistently greater on correctly identified trials. No such consistency was observed with the central/parietal alpha ERS. These data demonstrate that changes in alpha activity are specific to listening conditions. To our

  1. Cortical Alpha Oscillations Predict Speech Intelligibility.

    PubMed

    Dimitrijevic, Andrew; Smith, Michael L; Kadis, Darren S; Moore, David R

    2017-01-01

    Understanding speech in noise (SiN) is a complex task involving sensory encoding and cognitive resources including working memory and attention. Previous work has shown that brain oscillations, particularly alpha rhythms (8-12 Hz) play important roles in sensory processes involving working memory and attention. However, no previous study has examined brain oscillations during performance of a continuous speech perception test. The aim of this study was to measure cortical alpha during attentive listening in a commonly used SiN task (digits-in-noise, DiN) to better understand the neural processes associated with "top-down" cognitive processing in adverse listening environments. We recruited 14 normal hearing (NH) young adults. DiN speech reception threshold (SRT) was measured in an initial behavioral experiment. EEG activity was then collected: (i) while performing the DiN near SRT; and (ii) while attending to a silent, close-caption video during presentation of identical digit stimuli that the participant was instructed to ignore. Three main results were obtained: (1) during attentive ("active") listening to the DiN, a number of distinct neural oscillations were observed (mainly alpha with some beta; 15-30 Hz). No oscillations were observed during attention to the video ("passive" listening); (2) overall, alpha event-related synchronization (ERS) of central/parietal sources were observed during active listening when data were grand averaged across all participants. In some participants, a smaller magnitude alpha event-related desynchronization (ERD), originating in temporal regions, was observed; and (3) when individual EEG trials were sorted according to correct and incorrect digit identification, the temporal alpha ERD was consistently greater on correctly identified trials. No such consistency was observed with the central/parietal alpha ERS. These data demonstrate that changes in alpha activity are specific to listening conditions. To our knowledge, this is the

  2. Alpha-particle sensitive test SRAMs

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Blaes, B. R.

    1990-01-01

    A bench-level test is being developed to evaluate memory-cell upsets in a test SRAM designed with a cell offset voltage. This offset voltage controls the critical charge needed to upset the cell. The effect is demonstrated using a specially designed 2-micron n-well CMOS 4-kb test SRAM and a Po-208 5.1-MeV 0.61-LET alpha-particle source. This test SRAM has been made sensitive to alpha particles through the use of a cell offset voltage, and this has allowed a bench-level characterization in a laboratory setting. The experimental data are linked to a alpha-particle interaction physics and to SPICE circuit simulations through the alpha-particle collection depth. The collection depth is determined by two methods and found to be about 7 micron. In addition, alpha particles that struck outside the bloated drain were able to flip the SRAM cells. This lateral charge collection was observed to be more than 6 micron.

  3. Fate of Alpha Dynamos at Large Rm.

    PubMed

    Cameron, Alexandre; Alexakis, Alexandros

    2016-11-11

    At the heart of today's solar magnetic field evolution models lies the alpha dynamo description. In this work, we investigate the fate of alpha dynamos as the magnetic Reynolds number Rm is increased. Using Floquet theory, we are able to precisely quantify mean-field effects like the alpha and beta effect (i) by rigorously distinguishing dynamo modes that involve large-scale components from the ones that only involve small scales, and by (ii) providing a way to investigate arbitrary large-scale separations with minimal computational cost. We apply this framework to helical and nonhelical flows as well as to random flows with short correlation time. Our results determine that the alpha description is valid for Rm smaller than a critical value Rm_{c} at which small-scale dynamo instability starts. When Rm is above Rm_{c}, the dynamo ceases to follow the mean-field description and the growth rate of the large-scale modes becomes independent of the scale separation, while the energy in the large-scale modes is inversely proportional to the square of the scale separation. The results in this second regime do not depend on the presence of helicity. Thus, alpha-type modeling for solar and stellar models needs to be reevaluated and new directions for mean-field modeling are proposed.

  4. H-alpha Observations of MKW10

    NASA Astrophysics Data System (ADS)

    Johnson, Harold; Coble, Kimberly A.; Koopmann, Rebecca A.; Durbala, Adriana; Undergraduate ALFALFA Team

    2016-01-01

    As part of the Undergraduate ALFALFA Team project looking at clusters and groups of galaxies to investigate the effects of environment on star formation, we analyzed H-alpha and R-band observations of the group MKW10 from the WIYN 0.9-m telescope with MOSAIC camera at Kitt Peak. We continuum-subtract the H-alpha images by scaling and subtracting the broadband R images. This process includes: determining the seeing of each image by calculating the FWHM values of several stars in the image; convolving all images to the worst seeing; stacking images for each filter; subtracting sky background; scaling the R image to H-alpha; and subtracting the scaled R from H-alpha. We then use the H-alpha-continuum-subtracted image to perform surface photometry of individual galaxies in MKW10. The data will be used to determine star formation rates and distributions of galaxies in this group environment and will be compared to results for galaxies in other UAT group and cluster environments. Analysis is ongoing.This work has been supported by NSF grant AST-1211005 and the Illinois Space Grant Consortium.

  5. Benchmarking the External Surrogate Ratio Method using the (alpha,alpha' f) reaction at STARS

    SciTech Connect

    Lesher, S R; Bernstein, L A; Ai, H; Beausang, C W; Bleuel, D; Burke, J T; Clark, R M; Fallon, P; Gibelin, J; Lee, I Y; Lyles, B F; Macchiavelli, A O; McMahan, M A; Moody, K J; Norman, E B; Phair, L; Rodriguez-Vieitez, E; Wiedeking, M

    2008-01-09

    We measured the ratio of the fission probabilities of {sup 234}U* relative to {sup 236}U* formed via an ({alpha},{alpha}{prime}) direct reactions using the STARS array at the 88-inch cyclotron at the Lawrence Berkeley National Laboratory. This ratio has a shape similar to the ratio of neutron capture probabilities from {sup 233}U(n; f) and {sup 235}U(n; f), indicating the alpha reactions likely formed a compound nucleus. This result indicates that the ratios of fission exit channel probabilities for two actinide nuclei populated via ({alpha}, {alpha}{prime}) can be used to determine an unknown fission cross section relative to a known one. The validity of the External Surrogate Ratio Method (ESRM) is tested and the results support the conclusions of Burke et al. [1].

  6. A circularly permuted alpha-amylase-type alpha/beta-barrel structure in glucan-synthesizing glucosyltransferases.

    PubMed

    MacGregor, E A; Jespersen, H M; Svensson, B

    1996-01-15

    A motif of amino acid residues, located at the active site and specific beta-strands in alpha-amylases, is recognized in alpha-1,3- and alpha-1,6-glucan-synthesizing glucosyltransferases, leading to the conclusion that these enzymes contain an alpha/beta-barrel closely related to the (beta/alpha)8-fold of the alpha-amylase superfamily. The secondary structure elements of the transferase barrel, however, are circularly permuted to start with an alpha-helix equivalent to helix 3 in the alpha-amylases. Thus, the transferase counterpart of the long third beta-->alpha connection--constituting a domain in the alpha-amylases--is divided to precede and succeed the barrel. This architectural arrangement may be coupled to sucrose scission and glucosyl transfer. The involvement in the mechanism in glucosyltransferases of active site residues recurring in amylolytic enzymes is discussed.

  7. The alpha glycerophosphate cycle in Drosophila melanogaster V. molecular analysis of alpha glycerophosphate dehydrogenase and alpha glycerophosphate oxidase mutants.

    PubMed

    Carmon, Amber; Chien, Jeff; Sullivan, David; MacIntyre, Ross

    2010-01-01

    Two enzymes, alpha glycerophosphate dehydrogenase (GPDH-1) in the cytoplasm and alpha glycerophosphate oxidase (GPO-1) in the mitochondrion cooperate in Drosophila flight muscles to generate the ATP needed for muscle contraction. Null mutants for either enzyme cannot fly. Here, we characterize 15 ethyl methane sulfonate (EMS)-induced mutants in GPDH-1 at the molecular level and assess their effects on structural and evolutionarily conserved domains of this enzyme. In addition, we molecularly characterize 3 EMS-induced GPO-1 mutants and excisions of a P element insertion in the GPO-1 gene. The latter represent the best candidate for null or amorphic mutants in this gene.

  8. Levels of alpha-HCH, lindane, and enantiomeric ratios of alpha-HCH in marine mammals from the northern hemisphere.

    PubMed

    Hummert, K; Vetter, W; Luckas, B

    1995-09-01

    The enantiomeric ratios of alpha-HCH were determined by chiral gas chromatography in blubber of marine mammals from regions of the northern hemisphere (North Sea, Baltic Sea, Arctic and Iceland). Cetaceans (harbour porpoises and white-beaked dolphins) showed a preferential accumulation of (+)-alpha-HCH. In blubber of harbour seals, grey seals and harp seals (+)-alpha-HCH was also more abundant than (-)-alpha-HCH. Hooded seals formed an exception with a (+/-) enantiomeric ratio of alpha-HCH < 1.

  9. A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice.

    PubMed

    Heidet, Laurence; Borza, Dorin-Bogdan; Jouin, Mélanie; Sich, Mireille; Mattei, Marie-Geneviève; Sado, Yoshikazu; Hudson, Billy G; Hastie, Nicholas; Antignac, Corinne; Gubler, Marie-Claire

    2003-10-01

    Collagen IV is a major structural component of basement membranes. In the glomerular basement membrane (GBM) of the kidney, the alpha3, alpha4, and alpha5(IV) collagen chains form a distinct network that is essential for the long-term stability of the glomerular filtration barrier, and is absent in most patients affected with Alport syndrome, a progressive inherited nephropathy associated with mutation in COL4A3, COL4A4, or COL4A5 genes. To investigate, in vivo, the regulation of the expression, assembly, and function of the alpha3alpha4alpha5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4 locus. Transgenic mice expressed the human alpha3 and alpha4(IV) chains in a tissue-specific manner. In the kidney, when expressed onto a Col4a3(-/-) background, the human alpha3(IV) chain restored the expression of and co-assembled with the mouse alpha4 and alpha5(IV) chains specifically at sites where the human alpha3(IV) was expressed, demonstrating that the expression of all three chains is required for network assembly. The co-assembly of the human and mouse chains into a hybrid network in the GBM restores a functional GBM and rescues the Alport phenotype, providing further evidence that defective assembly of the alpha3-alpha4-alpha5(IV) protomer, caused by mutations in any of the three chains, is the pathogenic mechanism responsible for the disease. This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain.

  10. Efficient synthesis of 1-azadienes derived from alpha-aminoesters. Regioselective preparation of alpha-dehydroamino acids, vinylglycines, and alpha-amino acids.

    PubMed

    Palacios, Francisco; Vicario, Javier; Aparicio, Domitila

    2006-09-29

    An efficient synthesis of 1-azadienes derived from alpha-aminoesters is achieved through an aza-Wittig reaction of phosphazenes with beta,gamma-unsaturated alpha-ketoesters. Regioselective 1,2-reduction of these functionalized 1-azadienes affords vinylglycine derivatives, while conjugative 1,4-reduction gives alpha-dehydroamino acid compounds. Reduction of both the carbon-carbon and the imine-carbon-nitrogen double bonds leads to the formation of alpha-amino acid derivatives.

  11. Lyman-alpha imagery of Comet Kohoutek

    NASA Technical Reports Server (NTRS)

    Carruthers, G. R.; Opal, C. B.; Page, T. L.; Meier, R. R.; Prinz, D. K.

    1974-01-01

    Electrographic imagery of Comet Kohoutek in the 1100-1500 A wavelength range was obtained from a sounding rocket on Jan. 8, 1974, and from the Skylab space station on 13 occasions between Nov. 26, 1973 and Feb. 2, 1974. These images are predominantly due to Lyman-alpha (1216 A) emission from the hydrogen coma of the comet. The rocket pictures have been calibrated for absolute sensitivity and a hydrogen production rate has been determined. However, the Skylab camera suffered degradation of its sensitivity during the mission, and its absolute sensitivity for each observation can only be estimated by comparison of the comet images with those taken by the rocket camera, with imagery of the geocoronal Lyman-alpha glow, of the moon in reflected Lyman-alpha, and of ultraviolet-bright stars. The rocket and geocoronal comparisons are used to derive a preliminary, qualitative history of the development of the cometary hydrogen coma and the associated hydrogen production rate.

  12. Microdosimetry for targeted alpha therapy of cancer.

    PubMed

    Huang, Chen-Yu; Guatelli, Susanna; Oborn, Bradley M; Allen, Barry J

    2012-01-01

    Targeted alpha therapy (TAT) has the advantage of delivering therapeutic doses to individual cancer cells while reducing the dose to normal tissues. TAT applications relate to hematologic malignancies and now extend to solid tumors. Results from several clinical trials have shown efficacy with limited toxicity. However, the dosimetry for the labeled alpha particle is challenging because of the heterogeneous antigen expression among cancer cells and the nature of short-range, high-LET alpha radiation. This paper demonstrates that it is inappropriate to investigate the therapeutic efficacy of TAT by macrodosimetry. The objective of this work is to review the microdosimetry of TAT as a function of the cell geometry, source-target configuration, cell sensitivity, and biological factors. A detailed knowledge of each of these parameters is required for accurate microdosimetric calculations.

  13. The Story of Alpha - In Three Parts

    NASA Astrophysics Data System (ADS)

    Hautecoeur, Jean-Paul

    2001-09-01

    The article presents a retrospective history of the ALPHA series of publications. This action-research project (later called "cooperative research") on literacy and basic education is divided into three periods of seven years each. The first one, "Construction", involved assisting the nascent literacy movement in Québec and Canada by given it a theoretical, critical and ideological basis. In the second period, "Ruptures", the project distanced itself somewhat from the literacy movement, whose success, according to the author, was dubious. During the same period ALPHA systematised its critical function and internationalised its field of research. The third phase, "Wanderings", involved a different research paradigm, in which the project explored basic education at community level in connection with local development initiatives. This biographical/autobiographical account ends with the last publication ALPHA 2000, evincing an ecological vision for alternative education and sustainable communities, partly documented in the Arab countries.

  14. The status of alpha-particle diagnostics

    SciTech Connect

    Young, K.M.; Johnson, D.W.

    1992-08-01

    There is a flurry of activity to complete alpha-particle diagnostics so that they can undergo some experimental testing in DT plasmas on JET or TFTR prior to implementation on ITER. Successful measurements of escaping charged fusion products have been made in DD plasmas, and the {alpha}-particle source can be well characterized by neutron profile measurement. These methods can be extrapolated to DT plasmas. Measurement of the confined {alpha}-particles requires a new technique. Collective Thomson scattering, methods involving charge-exchange interactions and nuclear reactions with impurities will be discussed. Some assessment is given of the capabilities of these techniques, bearing in mind the potential for their use in the physics phase of the ITER program.

  15. Alternating current long range alpha particle detector

    DOEpatents

    MacArthur, Duncan W.; McAtee, James L.

    1993-01-01

    An alpha particle detector, utilizing alternating currents, whcih is capable of detecting alpha particles from distinct sources. The use of alternating currents allows use of simpler ac circuits which, in turn, are not susceptible to dc error components. It also allows the benefit of gas gain, if desired. In the invention, a voltage source creates an electric field between two conductive grids, and between the grids and a conductive enclosure. Air containing air ions created by collision with alpha particles is drawn into the enclosure and detected. In some embodiments, the air flow into the enclosure is interrupted, creating an alternating flow of ions. In another embodiment, a modulated voltage is applied to the grid, also modulating the detection of ions.

  16. Microdosimetry for Targeted Alpha Therapy of Cancer

    PubMed Central

    Huang, Chen-Yu; Guatelli, Susanna; Oborn, Bradley M.; Allen, Barry J.

    2012-01-01

    Targeted alpha therapy (TAT) has the advantage of delivering therapeutic doses to individual cancer cells while reducing the dose to normal tissues. TAT applications relate to hematologic malignancies and now extend to solid tumors. Results from several clinical trials have shown efficacy with limited toxicity. However, the dosimetry for the labeled alpha particle is challenging because of the heterogeneous antigen expression among cancer cells and the nature of short-range, high-LET alpha radiation. This paper demonstrates that it is inappropriate to investigate the therapeutic efficacy of TAT by macrodosimetry. The objective of this work is to review the microdosimetry of TAT as a function of the cell geometry, source-target configuration, cell sensitivity, and biological factors. A detailed knowledge of each of these parameters is required for accurate microdosimetric calculations. PMID:22988479

  17. Iron modulates the alpha chain of fibrinogen.

    PubMed

    Nielsen, Vance G; Jacobsen, Wayne K

    2016-04-01

    Iron-bound fibrinogen has been noted to accelerate plasmatic coagulation in patients with divergent conditions involving upregulation of heme oxygenase activity, including hemodialysis, Alzheimer's disease, sickle cell anemia, and chronic migraine. Our goal was to determine if a site of iron-fibrinogen interaction was on the alpha chain. Using thrombelastography, we compared the coagulation kinetic profiles of plasma exposed to 0-10 µM ferric chloride after activation of coagulation with thrombin generated by contact activation of plasma with the plastic sample cup or by exposure to 1 µg/ml of Calloselasma rhodostoma venom (rich in ancrod activity), which causes coagulation via polymerization of alpha chain monomers. Venom mediated coagulation always occurred before thrombin activated thrombus formation, and ferric chloride always diminished the time of onset of coagulation and increased the velocity of clot growth. Iron enhances plasmatic coagulation kinetics by modulating the alpha chain of fibrinogen.

  18. Nuclear diagnostic for fast alpha particles

    DOEpatents

    Grisham, Larry R.; Post Jr., Douglass E.; Dawson, John M.

    1986-06-03

    Measurement of the velocity distribution of confined energetic alpha particles resulting from deuterium-tritium fusion reactions in a magnetically contained plasma is provided. The fusion plasma is seeded with energetic boron neutrals for producing, by means of the reaction .sup.10 B (.alpha.,n) .sup.13 N reaction, radioactive nitrogen nuclei which are then collected by a probe. The radioactivity of the probe is then measured by conventional techniques in determining the energy distribution of the alpha particles in the plasma. In a preferred embodiment, diborane gas (B.sub.2 H.sub.6) is the source of the boron neutrals to produce .sup.13 N which decays almost exclusively by positron emission with a convenient half-life of 10 minutes.

  19. Nuclear diagnostic for fast alpha particles

    DOEpatents

    Grisham, Larry R.; Post, Jr., Douglass E.; Dawson, John M.

    1986-01-01

    Measurement of the velocity distribution of confined energetic alpha particles resulting from deuterium-tritium fusion reactions in a magnetically contained plasma is provided. The fusion plasma is seeded with energetic boron neutrals for producing, by means of the reaction .sup.10 B (.alpha.,n) .sup.13 N reaction, radioactive nitrogen nuclei which are then collected by a probe. The radioactivity of the probe is then measured by conventional techniques in determining the energy distribution of the alpha particles in the plasma. In a preferred embodiment, diborane gas (B.sub.2 H.sub.6) is the source of the boron neutrals to produce .sup.13 N which decays almost exclusively by positron emission with a convenient half-life of 10 minutes.

  20. Coefficient alpha and interculture test selection.

    PubMed

    Thurber, Steven; Kishi, Yasuhiro

    2014-04-01

    The internal consistency reliability of a measure can be a focal point in an evaluation of the potential adequacy of an instrument for adaptation to another cultural setting. Cronbach's alpha (α) coefficient is often used as the statistical index for such a determination. However, alpha presumes a tau-equivalent test and may constitute an inaccurate population estimate for multidimensional tests. These notions are expanded and examined with a Japanese version of a questionnaire on nursing attitudes toward suicidal patients, originally constructed in Sweden using the English language. The English measure was reported to have acceptable internal consistency (α) albeit the dimensionality of the questionnaire was not addressed. The Japanese scale was found to lack tau-equivalence. An alternative to alpha, "composite reliability," was computed and found to be below acceptable standards in magnitude and precision. Implications for research application of the Japanese instrument are discussed.

  1. Synthesis of peptide .alpha.-thioesters

    DOEpatents

    Camarero, Julio A.; Mitchell, Alexander R.; De Yoreo, James J.

    2008-08-19

    Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.

  2. Alpha-decay of light protactinium isotopes

    SciTech Connect

    Faestermann, T.; Gillitzer, A.; Hartel, K.; Henning, W.; Kienle, P.

    1987-12-10

    Light protactinium isotopes have been produced with /sup 204/Pb (/sup 19/F,xn) reactions. ..cap alpha..-activities with E/sub ..cap alpha../ = 9.90(5) MeV, T/sub 1/2/ = 53(10) ns and E/sub ..cap alpha../ = 9.65(5) MeV, T/sub 1/2/ = 0.78(16) ..mu..s could be attributed to the previously unobserved nuclei /sup 219/Pa and /sup 220/Pa with the help of excitation functions. The peak cross sections for the 4n and 3n evaporation channels are on the order of 10 ..mu..b. The decay energies as well as the halflives fit well into the systematics of these nuclei close to the magic neutron number N = 126. /sup 219/Pa is the shortest lived nuclide known with directly measured halflife.

  3. Alternating current long range alpha particle detector

    DOEpatents

    MacArthur, D.W.; McAtee, J.L.

    1993-02-16

    An alpha particle detector, utilizing alternating currents, which is capable of detecting alpha particles from distinct sources. The use of alternating currents allows use of simpler ac circuits which, in turn, are not susceptible to dc error components. It also allows the benefit of gas gain, if desired. In the invention, a voltage source creates an electric field between two conductive grids, and between the grids and a conductive enclosure. Air containing air ions created by collision with alpha particles is drawn into the enclosure and detected. In some embodiments, the air flow into the enclosure is interrupted, creating an alternating flow of ions. In another embodiment, a modulated voltage is applied to the grid, also modulating the detection of ions.

  4. [ALPHA-ACTININS AND SIGNAL TRANSDUCTION PATHWAYS].

    PubMed

    Panyushev, N V; Tentler, D G

    2015-01-01

    Involvement of actin cytoskeleton proteins in signal transduction from cell surface to the nucleus, including regulation of transcription factors activity, has now been supported by a lot of experimental data. Here-with, cytoskeletal proteins may have different functions than ones they execute in the cytoplasm. Particularly, alpha-actinin 4 stabilizing actin microfilaments in the cytoplasm can translocate to the nucleus and change the activity of several transcription factors. Despite the lack of nuclear import signal and DNA binding domain, alpha-actinin 4 can bind to promoter sequences, and co-activate NF-κB-dependent transcription. Selective regulation of NF-κB gene targets may indicate involvement of alpha-actinin 4 in determining the specificity of cell response to NF-κB activation in cells of different types.

  5. Solution structure of {alpha}-conotoxin PIA, a novel antagonist of {alpha}6 subunit containing nicotinic acetylcholine receptors

    SciTech Connect

    Chi, Seung-Wook; Lee, Si-Hyung; Kim, Do-Hyoung; Kim, Jae-Sung; Olivera, Baldomero M.; McIntosh, J. Michael; Han, Kyou-Hoon . E-mail: khhan600@kribb.re.kr

    2005-12-30

    {alpha}-Conotoxin PIA is a novel nicotinic acetylcholine receptor (nAChR) antagonist isolated from Conus purpurascens that targets nAChR subtypes containing {alpha}6 and {alpha}3 subunits. {alpha}-conotoxin PIA displays 75-fold higher affinity for rat {alpha}6/{alpha}3{beta}2{beta}3 nAChRs than for rat {alpha}3{beta}2 nAChRs. We have determined the three-dimensional structure of {alpha}-conotoxin PIA by nuclear magnetic resonance spectroscopy. The {alpha}-conotoxin PIA has an '{omega}-shaped' overall topology as other {alpha}4/7 subfamily conotoxins. Yet, unlike other neuronally targeted {alpha}4/7-conotoxins, its N-terminal tail Arg{sup 1}-Asp{sup 2}-Pro{sup 3} protrudes out of its main molecular body because Asp{sup 2}-Pro{sup 3}-Cys{sup 4}-Cys{sup 5} forms a stable type I {beta}-turn. In addition, a kink introduced by Pro{sup 15} in the second loop of this toxin provides a distinct steric and electrostatic environment from those in {alpha}-conotoxins MII and GIC. By comparing the structure of {alpha}-conotoxin PIA with other functionally related {alpha}-conotoxins we suggest structural features in {alpha}-conotoxin PIA that may be associated with its unique receptor recognition profile.

  6. Human eosinophils can express the cytokines tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha.

    PubMed Central

    Costa, J J; Matossian, K; Resnick, M B; Beil, W J; Wong, D T; Gordon, J R; Dvorak, A M; Weller, P F; Galli, S J

    1993-01-01

    By in situ hybridization, 44-100% of the blood eosinophils from five patients with hypereosinophilia and four normal subjects exhibited intense hybridization signals for TNF-alpha mRNA. TNF-alpha protein was detectable by immunohistochemistry in blood eosinophils of hypereosinophilic subjects, and purified blood eosinophils from three atopic donors exhibited cycloheximide-inhibitable spontaneous release of TNF-alpha in vitro. Many blood eosinophils (39-91%) from hypereosinophilic donors exhibited intense labeling for macrophage inflammatory protein-1 alpha (MIP-1 alpha) mRNA, whereas eosinophils of normal donors demonstrated only weak or undetectable hybridization signals for MIP-1 alpha mRNA. Most tissue eosinophils infiltrating nasal polyps were strongly positive for both TNF-alpha and MIP-1 alpha mRNA. By Northern blot analysis, highly enriched blood eosinophils from a patient with the idiopathic hypereosinophilic syndrome exhibited differential expression of TNF-alpha and MIP-1 alpha mRNA. These findings indicate that human eosinophils represent a potential source of TNF-alpha and MIP-1 alpha, that levels of expression of mRNA for both cytokines are high in the blood eosinophils of hypereosinophilic donors and in eosinophils infiltrating nasal polyps, that the eosinophils of normal subjects express higher levels of TNF-alpha than MIP-1 alpha mRNA, and that eosinophils purified from the blood of atopic donors can release TNF-alpha in vitro. Images PMID:8514874

  7. X-rays from Alpha Centauri

    NASA Technical Reports Server (NTRS)

    Nugent, J.; Garmire, G.

    1978-01-01

    HEAO 1 observations of soft X-ray emission from a point source in the vicinity of Alpha Cen are reported. The source, designated H1437-61, is tentatively identified with Alpha Cen, and an X-ray luminosity comparable to that of the sun in an active state is estimated. A temperature of about 500,000 K and an emission integral of 5 x 10 to the 50th per cu cm are obtained. Coronal emission is suggested as the X-ray-producing mechanism.

  8. Lunar surface outgassing and alpha particle measurements

    SciTech Connect

    Lawson, S. L.; Feldman, W. C.; Lawrence, David J. ,; Moore, K. R.; Elphic, R. C.; Maurice, S.; Belian, Richard D.; Binder, Alan B.

    2002-01-01

    The Lunar Prospector Alpha Particle Spectrometer (LP APS) searched for lunar surface gas release events and mapped their distribution by detecting alpha particle?; produced by the decay of gaseous radon-222 (5.5 MeV, 3.8 day half-life), solid polonium-2 18 (6.0 MeV, 3 minute half-life), and solid polonium-210 (5.3 MeV, 138 day half-life, but held up in production by the 21 year half-life of lead-210). These three nuclides are radioactive daughters from the decay of uranium-238.

  9. Defined solid angle alpha counting at NPL.

    PubMed

    Arinc, Arzu; Parfitt, Michael J; Keightley, John D; Wilson, Alan

    2016-03-01

    This paper describes the design of and first measurements with the new defined solid angle (DSA) alpha counter at the National Physical Laboratory, UK, with the aim of enabling high-precision radionuclide standardisations for alpha-emitting radionuclides and half-life measurements. The counter may be employed at three source-detector distances in order to monitor the measured activities with calculated geometrical efficiencies. Initial results are promising but further work is required to reduce the dominant uncertainty associated with the source activity distribution.

  10. Fan-less long range alpha detector

    DOEpatents

    MacArthur, D.W.; Bounds, J.A.

    1994-05-10

    A fan-less long range alpha detector is disclosed which operates by using an electrical field between a signal plane and the surface or substance to be monitored for air ions created by collisions with alpha radiation. Without a fan, the detector can operate without the possibility of spreading dust and potential contamination into the atmosphere. A guard plane between the signal plane and the electrically conductive enclosure and maintained at the same voltage as the signal plane, reduces leakage currents. The detector can easily monitor soil, or other solid or liquid surfaces. 2 figures.

  11. Alpha particles in effective field theory

    SciTech Connect

    Caniu, C.

    2014-11-11

    Using an effective field theory for alpha (α) particles at non-relativistic energies, we calculate the strong scattering amplitude modified by Coulomb corrections for a system of two αs. For the strong interaction, we consider a momentum-dependent interaction which, in contrast to an energy dependent interaction alone [1], could be more useful in extending the theory to systems with more than two α particles. We will present preliminary results of our EFT calculations for systems with two alpha particles.

  12. Monitoring airborne alpha-emitter contamination

    SciTech Connect

    Kerr, P.L.; Koster, J.E.; Conaway, J.G.; Bounds, J.A.; Whitley, C.W.; Steadman, P.A.

    1998-02-01

    Facilities that may produce airborne alpha emitter contamination require a continuous air monitoring (CAM) system. However, these traditional CAMs have difficulty in environments with large quantities of non-radioactive particulates such as dust and salt. Los Alamos has developed an airborne plutonium sensor (APS) for the REBOUND experiment at the Nevada Test Site which detects alpha contamination directly in the air, and so is less vulnerable to the problems associated with counting activity on a filter. In addition, radon compensation is built into the detector by the use of two measurement chambers.

  13. HETDEX: Diffuse Lyman-Alpha Emission

    NASA Astrophysics Data System (ADS)

    Tuttle, Sarah E.; Finkelstein, S.; Gebhardt, K.; HETDEX Collaboration

    2012-01-01

    The intermediate redshift universe probed by HETDEX, 1.8 < z < 3.0, holds a great deal of information about star formation and the evolution of galaxies. Although simulations reveal a regime active with gas accretion and feeding of galaxies via filaments, observational evidence for this accretion from the Intergalactic Medium (IGM) at any redshift has been very limited. Here we use data from VIRUS-P across several well-characterized fields to put limits on diffuse emission of Lyman-Alpha at the outskirts of galaxies. This work is done in preparation for a similar program with the full HETDEX sample of Lyman-Alpha Emitters (LAEs).

  14. Parallel Genetic Algorithm for Alpha Spectra Fitting

    NASA Astrophysics Data System (ADS)

    García-Orellana, Carlos J.; Rubio-Montero, Pilar; González-Velasco, Horacio

    2005-01-01

    We present a performance study of alpha-particle spectra fitting using parallel Genetic Algorithm (GA). The method uses a two-step approach. In the first step we run parallel GA to find an initial solution for the second step, in which we use Levenberg-Marquardt (LM) method for a precise final fit. GA is a high resources-demanding method, so we use a Beowulf cluster for parallel simulation. The relationship between simulation time (and parallel efficiency) and processors number is studied using several alpha spectra, with the aim of obtaining a method to estimate the optimal processors number that must be used in a simulation.

  15. Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling.

    PubMed Central

    Ruthardt, M; Testa, U; Nervi, C; Ferrucci, P F; Grignani, F; Puccetti, E; Grignani, F; Peschle, C; Pelicci, P G

    1997-01-01

    Fusion proteins involving the retinoic acid receptor alpha (RAR alpha) and the PML or PLZF nuclear protein are the genetic markers of acute promyelocytic leukemias (APLs). APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. We here report that (i) like PML-RAR alpha expression, PLZF-RAR alpha expression blocks terminal differentiation of hematopoietic precursor cell lines (U937 and HL-60) in response to different stimuli (vitamin D3, transforming growth factor beta1, and dimethyl sulfoxide); (ii) PML-RAR alpha, but not PLZF-RAR alpha, increases RA sensitivity of hematopoietic precursor cells and restores RA sensitivity of RA-resistant hematopoietic cells; (iii) PML-RAR alpha and PLZF-RAR alpha have similar RA binding affinities; and (iv) PML-RAR alpha enhances the RA response of RA target genes (those for RAR beta, RAR gamma, and transglutaminase type II [TGase]) in vivo, while PLZF-RAR alpha expression has either no effect (RAR beta) or an inhibitory activity (RAR gamma and type II TGase). These data demonstrate that PML-RAR alpha and PLZF-RAR alpha have similar (inhibitory) effects on RA-independent differentiation and opposite (stimulatory or inhibitory) effects on RA-dependent differentiation and that they behave in vivo as RA-dependent enhancers or inhibitors of RA-responsive genes, respectively. Their different activities on the RA signalling pathway might underlie the different responses of PML-RAR alpha and PLZF-RAR alpha APLs to RA treatment. The PLZF-RAR alpha fusion protein contains an approximately 120-amino-acid N-terminal motif (called the POZ domain), which is also found in a variety of zinc finger proteins and a group of poxvirus proteins and which mediates protein

  16. The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha.

    PubMed

    Yang, Qian; Nagano, Tomokazu; Shah, Yatrik; Cheung, Connie; Ito, Shinji; Gonzalez, Frank J

    2008-01-01

    To determine the impact of the species difference between rodents and humans in response to peroxisome proliferators (PPs) mediated by peroxisome proliferator-activated receptor (PPAR)alpha, PPAR alpha-humanized transgenic mice were generated using a P1 phage artificial chromosome (PAC) genomic clone bred onto a ppar alpha-null mouse background, designated hPPAR alpha PAC. In hPPAR alpha PAC mice, the human PPAR alpha gene is expressed in tissues with high fatty acid catabolism and induced upon fasting, similar to mouse PPAR alpha in wild-type (Wt) mice. Upon treatment with the PP fenofibrate, hPPAR alpha PAC mice exhibited responses similar to Wt mice, including peroxisome proliferation, lowering of serum triglycerides, and induction of PPAR alpha target genes encoding enzymes involved in fatty acid metabolism in liver, kidney, and heart, suggesting that human PPAR alpha (hPPAR alpha) functions in the same manner as mouse PPAR alpha in regulating fatty acid metabolism and lowering serum triglycerides. However, in contrast to Wt mice, treatment of hPPAR alpha PAC mice with fenofibrate did not cause significant hepatomegaly and hepatocyte proliferation, thus indicating that the mechanisms by which PPAR alpha affects lipid metabolism are distinct from the hepatocyte proliferation response, the latter of which is only induced by mouse PPAR alpha. In addition, a differential regulation of several genes, including the oncogenic let-7C miRNA by PPs, was observed between Wt and hPPAR alpha PAC mice that may contribute to the inherent difference between mouse and human PPAR alpha in activation of hepatocellular proliferation. The hPPAR alpha PAC mouse model provides an in vivo platform to investigate the species difference mediated by PPAR alpha and an ideal model for human risk assessment PPs exposure.

  17. alpha-Ketobutyrate metabolism in perfused rat liver: regulation of alpha-ketobutyrate decarboxylation and effects of alpha-ketobutyrate on pyruvate dehydrogenase.

    PubMed

    Lapointe, D S; Olson, M S

    1985-11-01

    The oxidative decarboxylation and subsequent production of glucose from alpha-ketobutyrate were studied using perfused livers from fasted rats. The production of 14CO2 from alpha-keto-[1-14C]butyrate increased monotonically while the production of glucose from alpha-ketobutyrate was biphasic as the perfusate concentration of alpha-ketobutyrate was increased. The biphasic gluconeogenic response using alpha-ketobutyrate as the gluconeogenic precursor was similar to that observed with propionate. The decarboxylation of alpha-ketobutyrate was found to be exquisitely sensitive to the effects of the monocarboxylate transport inhibitor, alpha-cyanocinnamate. Infusion of beta-hydroxybutyrate caused a substantial inhibition of alpha-ketobutyrate decarboxylation while dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, did not stimulate the metabolism of alpha-ketobutyrate but was inhibitory. The effects of alpha-ketobutyrate infusion on pyruvate decarboxylation were tested and it was found that at low perfusate pyruvate concentrations (ca. 0.25 mM) increasing alpha-ketobutyrate led to increasing inhibition of pyruvate decarboxylation, while at high perfusate pyruvate concentrations (ca. 2.5 mM) an initial inhibition was apparent which did not increase substantially with increasing alpha-ketobutyrate concentrations. The results obtained indicate that the regulation of alpha-ketobutyrate metabolism by oxidative decarboxylation differs significantly from that of pyruvate. In addition, while the rate of gluconeogenesis using alpha-ketobutyrate as a precursor was remarkably similar to that using propionate as a gluconeogenic precursor, the effects of alpha-ketobutyrate on the oxidative decarboxylation of pyruvate were qualitatively different from the effects of propionate on pyruvate metabolism.

  18. Determining the alpha dynamo parameter in incompressible homogeneous magnetohydrodynamic turbulence

    NASA Technical Reports Server (NTRS)

    Matthaeus, W. H.; Goldstein, M. L.; Lantz, S. R.

    1983-01-01

    Alpha, an important parameter in dynamo theory, is proportional to either the kinetic, current, magnetic, or velocity helicity of the fluctuating magnetic field and fluctuating velocity field. The particular helicity to which alpha is proportional depends on the assumptions used in deriving the first order smoothed equations that describe the alpha effect. In two cases, when alpha is proportional to either the magnetic helicity or velocity helicity, alpha is determined experimentally from two point measurements of the fluctuating fields in incompressible, homogeneous turbulence having arbitrary symmetry. For the other two possibilities, alpha is determined if the turbulence is isotropic.

  19. The alpha-form of the hydroxides of bivalent metals

    NASA Technical Reports Server (NTRS)

    Feitknecht, W.

    1984-01-01

    X-ray analyses were made of the hydroxides of the bivalent metals. The freshly pptd. hydroxide is usually in the alpha-form, which on standing is converted to another form or other forms. The alpha and c grating dimensions of the alpha-form and the C6-type of Co, Zn, C, Co-Zn and Ni-Zn hydroxides are tabulated. Ni hydroxide does not exhibit an alpha-form. The alpha-Co(OH)2, the blue form, is stabilized by sugar or by the higher alcohols: these compounds do not stabilize alpha-Zn(OH)2.

  20. alpha-Ketobutyrate metabolism in perfused rat liver: regulation of alpha-ketobutyrate decarboxylation and effects of alpha-ketobutyrate on pyruvate dehydrogenase

    SciTech Connect

    Lapointe, D.S.; Olson, M.S.

    1985-11-01

    The oxidative decarboxylation and subsequent production of glucose from alpha-ketobutyrate were studied using perfused livers from fasted rats. The production of /sup 14/CO/sub 2/ from alpha-keto-(1-/sup 14/C)butyrate increased monotonically while the production of glucose from alpha-ketobutyrate was biphasic as the perfusate concentration of alpha-ketobutyrate was increased. The biphasic gluconeogenic response using alpha-ketobutyrate as the gluconeogenic precursor was similar to that observed with propionate. The effects of alpha-ketobutyrate infusion on pyruvate decarboxylation were tested and it was found that at low perfusate pyruvate concentrations increasing alpha-ketobutyrate led to increasing inhibition of pyruvate decarboxylation, while at high perfusate pyruvate concentrations an initial inhibition was apparent which did not increase substantially with increasing alpha-ketobutyrate concentrations. The results obtained indicate that the regulation of alpha-ketobutyrate metabolism by oxidative decarboxylation differs significantly from that of pyruvate. In addition, while the rate of gluconeogenesis using alpha-ketobutyrate as a precursor was remarkably similar to that using propionate as a gluconeogenic precursor, the effects of alpha-ketobutyrate on the oxidative decarboxylation of pyruvate were qualitatively different from the effects of propionate on pyruvate metabolism.

  1. Transformer Recharging with Alpha Channeling in Tokamaks

    SciTech Connect

    N.J. Fisch

    2009-12-21

    Transformer recharging with lower hybrid waves in tokamaks can give low average auxiliary power if the resistivity is kept high enough during the radio frequency (rf) recharging stage. At the same time, operation in the hot ion mode via alpha channeling increases the effective fusion reactivity. This paper will address the extent to which these two large cost saving steps are compatible. __________________________________________________

  2. Production of alpha-amylase by yeast

    SciTech Connect

    Thomse, K.K.

    1987-01-01

    The enzyme alpha-amylase confers to an organism the enzymatic activity for the degradation of polyglucosides with alpha-1,4 glycosidic bonds such as starch and glycogen which are among the major storage compounds in plants and animals. Most alpha-amylases are single polypeptides of molecular weights around 50,000 dalton. They are generally found in the digestive tract of animals and in germinating seeds. Among the products released upon enzymatic degradation of polyglucosides maltose, a sugar that can be utilized as carbon source by yeast, is a major constituent. A cDNA segment complementary to mouse salivary amylase messenger RNA has been inserted into the yeast expression vector pMA56 behind the promoter of the gene encoding alcohol dehydrogenase I of yeast. Yeast transformants harboring plasmids with the normal orientation of the promoter and the mouse amylase cDNA gene produce amylase and release the enzyme in free form into the culture medium. Approximately 90% of the amylase activity is found in the medium. Yeast strains carrying MAL allele and transformed with a plasmid which directed the synthesis of mouse alpha-amylase were tested on plates containing starch and in batch fermentations using different high molecular weight sugars and oligosaccharides as carbon source. The results of these experiments will be discussed. (Refs. 21).

  3. Understanding a Widely Misunderstood Statistic: Cronbach's "Alpha"

    ERIC Educational Resources Information Center

    Ritter, Nicola L.

    2010-01-01

    It is important to explore score reliability in virtually all studies, because tests are not reliable. The present paper explains the most frequently used reliability estimate, coefficient alpha, so that the coefficient's conceptual underpinnings will be understood. Researchers need to understand score reliability because of the possible impact…

  4. Alpha Background Rejection in Bolometer Detectors

    NASA Astrophysics Data System (ADS)

    Deporzio, Nicholas

    2016-03-01

    This study presents the modification of bolometer detectors used in particle searches to veto or otherwise reject alpha radiation background and the statistical advantages of doing so. Several techniques are presented in detail - plastic film scintillator vetoes, metallic film ionization vetoes, and scintillating bolometer vetoes. Plastic scintillator films are cooled to bolometer temperatures and bombarded with 1.4MeV to 6.0MeV alpha particles representative of documented detector background. Photomultipliers detect this scintillation light and produce a veto signal. Layered metallic films of a primary metal, dielectric, and secondary metal, such as gold-polyethylene-gold films, are cooled to milli-kelvin temperatures and biased to produce a current signal veto when incident 1.4MeV to 6.0MeV alpha particles ionize conduction paths through the film. Modified Zinc Molybdate Bolometers are used to produce scintillation light when stimulated by alpha background. Calibration of veto signal to background energy is presented. Results are used to quantify the statistical impact of such modifications on bolometer searches.

  5. Alpha particles diffusion due to charge changes

    SciTech Connect

    Clauser, C. F. Farengo, R.

    2015-12-15

    Alpha particles diffusion due to charge changes in a magnetized plasma is studied. Analytical calculations and numerical simulations are employed to show that this process can be very important in the pedestal-edge-SOL regions. This is the first study that presents clear evidence of the importance of atomic processes on the diffusion of alpha particles. A simple 1D model that includes inelastic collisions with plasma species, “cold” neutrals, and partially ionized species was employed. The code, which follows the exact particle orbits and includes the effect of inelastic collisions via a Monte Carlo type random process, runs on a graphic processor unit (GPU). The analytical and numerical results show excellent agreement when a uniform background (plasma and cold species) is assumed. The simulations also show that the gradients in the density of the plasma and cold species, which are large and opposite in the edge region, produce an inward flux of alpha particles. Calculations of the alpha particles flux reaching the walls or divertor plates should include these processes.

  6. Synthesis of stabilized alpha-helical peptides.

    PubMed

    Bernal, Federico; Katz, Samuel G

    2014-01-01

    Stabilized alpha-helical (SAH) peptides are valuable laboratory tools to explore important protein-protein interactions. Whereas most peptides lose their secondary structure when isolated from the host protein, stapled peptides incorporate an all-hydrocarbon "staple" that reinforces their natural alpha-helical structure. Thus, stapled peptides retain their functional ability to bind their native protein targets and serve multiple experimental uses. First, they are useful for structural studies such as NMR or crystal structures that map and better define binding sites. Second, they can be used to identify small molecules that specifically target that interaction site. Third, stapled peptides can be used to test the importance of specific amino acid residues or posttranslational modifications to the binding. Fourth, they can serve as structurally competent bait to identify novel binding partners to specific alpha-helical motifs. In addition to markedly improved alpha-helicity, stapled peptides also display resistance to protease cleavage and enhanced cell permeability. Most importantly, they are useful for intracellular experiments that explore the functional consequences of blocking particular protein interactions. Because of their remarkable stability, stapled peptides can be applied to whole-animal, in vivo studies. Here we describe a protocol for the synthesis of a peptide that incorporates an all-hydrocarbon "staple" employing a ring-closing olefin metathesis reaction. With proper optimization, stapled peptides can be a fundamental, accurate laboratory tool in the modern chemical biologist's armory.

  7. Electron Screening Effects on {alpha}-decay

    SciTech Connect

    Musumarra, A.; Bonasera, A.; Del Zoppo, A.; Di Pietro, A.; Figuera, P.; Kimura, S.; Lattuada, M.; Pellegriti, M. G.; Scuderi, V.; Torresi, D.; Farinon, F.; Geissel, H.; Knoebel, R.; Prochazka, A.; Scheidenberger, C.; Nociforo, C.; Behr, K.-H.; Bosch, F.; Boutin, D.; Bruenle, A.

    2009-08-26

    An open problem in Nuclear Astrophysics concerns the understanding of electron-screening effects on nuclear reaction rates at stellar energies. In this framework, we have proposed to investigate the influence of the electron cloud on {alpha}-decay by measuring Q-values and {alpha}-decay half-lives of fully stripped, H-like and He-like ions. These kinds of measurements have been feasible just recently for highly-charged radioactive nuclides by fragmentation of {sup 238}U at relativistic energies at the FRS-ESR facility at GSI. In this way it is possible to produce, efficiently separate and store highly-charged {alpha}-emitters. Candidates for the proposed investigation were carefully selected and will be studied by using the Schottky Mass Spectroscopy technique. In order to establish a solid reference data set, lifetimes and Q{sub {alpha}}-value measurements of the corresponding neutrals have been performed directly at the FRS, by implanting the separated ions into an active Silicon stopper.

  8. 27 CFR 21.95 - Alpha terpineol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants §...

  9. Cytokine therapeutics: lessons from interferon alpha.

    PubMed Central

    Gutterman, J U

    1994-01-01

    Cytokines are soluble proteins that allow for communication between cells and the external environment. Interferon (IFN) alpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of growth and differentiation, affecting cellular communication and signal transduction pathways as well as immunological control. This review focuses on the biological and clinical activities of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-alpha in malignant, viral, immunological, angiogenic, inflammatory, and fibrotic diseases suggests a spectrum of interrelated pathophysiologies. The principles learned from in vivo studies will be discussed, particularly hairy cell leukemia, chronic myelogenous leukemia, certain angiogenic diseases, and hepatitis. After the surprising discovery of activity in a rare B-cell neoplasm, IFN-alpha emerged as a prototypic tumor suppressor protein that represses the clinical tumorigenic phenotype in some malignancies capable of differentiation. Regulatory agencies throughout the world have approved IFN-alpha for treatment of 13 malignant and viral disorders. The principles established with this cytokine serve as a paradigm for future development of natural proteins for human disease. PMID:8108387

  10. Coefficient Alpha and Reliability of Scale Scores

    ERIC Educational Resources Information Center

    Almehrizi, Rashid S.

    2013-01-01

    The majority of large-scale assessments develop various score scales that are either linear or nonlinear transformations of raw scores for better interpretations and uses of assessment results. The current formula for coefficient alpha (a; the commonly used reliability coefficient) only provides internal consistency reliability estimates of raw…

  11. EEG alpha power and creative ideation.

    PubMed

    Fink, Andreas; Benedek, Mathias

    2014-07-01

    Neuroscientific studies revealed first insights into neural mechanisms underlying creativity, but existing findings are highly variegated and often inconsistent. Despite the disappointing picture on the neuroscience of creativity drawn in recent reviews, there appears to be robust evidence that EEG alpha power is particularly sensitive to various creativity-related demands involved in creative ideation. Alpha power varies as a function of creativity-related task demands and the originality of ideas, is positively related to an individuals' creativity level, and has been observed to increase as a result of creativity interventions. Alpha increases during creative ideation could reflect more internally oriented attention that is characterized by the absence of external bottom-up stimulation and, thus, a form of top-down activity. Moreover, they could indicate the involvement of specific memory processes such as the efficient (re-)combination of unrelated semantic information. We conclude that increased alpha power during creative ideation is among the most consistent findings in neuroscientific research on creativity and discuss possible future directions to better understand the manifold brain mechanisms involved in creativity.

  12. EEG alpha power and creative ideation☆

    PubMed Central

    Fink, Andreas; Benedek, Mathias

    2014-01-01

    Neuroscientific studies revealed first insights into neural mechanisms underlying creativity, but existing findings are highly variegated and often inconsistent. Despite the disappointing picture on the neuroscience of creativity drawn in recent reviews, there appears to be robust evidence that EEG alpha power is particularly sensitive to various creativity-related demands involved in creative ideation. Alpha power varies as a function of creativity-related task demands and the originality of ideas, is positively related to an individuals’ creativity level, and has been observed to increase as a result of creativity interventions. Alpha increases during creative ideation could reflect more internally oriented attention that is characterized by the absence of external bottom-up stimulation and, thus, a form of top-down activity. Moreover, they could indicate the involvement of specific memory processes such as the efficient (re-)combination of unrelated semantic information. We conclude that increased alpha power during creative ideation is among the most consistent findings in neuroscientific research on creativity and discuss possible future directions to better understand the manifold brain mechanisms involved in creativity. PMID:23246442

  13. A Tutorial on Alpha-channelling

    SciTech Connect

    Fisch, N.J.; Herrmann, M.C.

    1998-11-01

    One of the more ambitious uses of intense microwaves in tokamaks or in other magnetic confinement deuterium-tritium (DT) fusion devices would be to divert power from energetic alpha-particles to waves. This so-called "alpha-channelling" would be a large step towards achieving economical fusion power. The intense waves, amplified by the substantial free energy in the alpha-particles, damp on fuel ions, resulting in a hot ion mode, doubling the fusion power of the reactor at the same confined pressure. If the waves damp preferentially on electrons or ions traveling in one direction, current can be driven. This tutorial explains the key concepts and recent advances that lead us to believe in the plausibility of such an effect, at the same time showing how experiments to date give us a measure of confidence in both the simulations themselves, the underlying physical assumptions, and ultimately the reasonableness of the application of these ideas to alpha-channelling in a tokamak reactor.

  14. Alpha thalassaemia-mental retardation, X linked

    PubMed Central

    Gibbons, Richard

    2006-01-01

    X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal. So far, 168 patients have been reported. Language is usually very limited. Seizures occur in about one third of the cases. While many patients are affectionate with their caregivers, some exhibit autistic-like behaviour. Patients present with facial hypotonia and a characteristic mouth. Genital abnormalities are observed in 80% of children and range from undescended testes to ambiguous genitalia. Alpha-thalassaemia is not always present. This syndrome is X-linked recessive and results from mutations in the ATRX gene. This gene encodes the widely expressed ATRX protein. ATRX mutations cause diverse changes in the pattern of DNA methylation at heterochromatic loci but it is not yet known whether this is responsible for the clinical phenotype. The diagnosis can be established by detection of alpha thalassaemia, identification of ATRX gene mutations, ATRX protein studies and X-inactivation studies. Genetic counselling can be offered to families. Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s. PMID:16722615

  15. Shedding Lyman Alpha Light on Cosmological Reionization

    NASA Astrophysics Data System (ADS)

    Rhoads, James E.; Malhotra, Sangeeta; Ammons, S. Mark; Dressler, Alan; Gonzalez, Alicia; Finkelstein, Steven; Hibon, Pascale; Jiang, Tianxing; Lee, Janice; Mobasher, Bahram; Monson, Andy; Persson, S. Eric; Probst, Ronald; Swaters, Rob; Tilvi, Vithal S.; Veilleux, Sylvain; Wang, Junxian; Zabludoff, Ann; Zheng, Zhenya

    2015-08-01

    Lyman alpha photons are a powerful tool for studying reionization. They interact strongly with neutral hydrogen, so that neutral intergalactic gas acts to hide Lyman alpha light from our instruments. I will discuss two ongoing narrowband surveys to study the Epoch of Reionization. The Deep And Wide Narrowband (DAWN) survey is a 40 night NOAO survey program to look for Lyman alpha emission at redshift 7.7, using the NEWFIRM camera on the 4m Mayall Telescope at Kitt Peak National Observatory. The First Light And Reionization Experiment (FLARE) is pursuing a corresponding survey at redshift 8.8, using the FourStar camera on the Magellan telescope. Both surveys are motivated by the application of Lyman alpha lines to the study of reionization. Reionization marked the first global impact that gravitationally bound objects (stars and/or black holes) had on the universe around them, and also the last time that most hydrogen atoms did anything noteworthy. I will present results from both the DAWN and FLARE surveys, which have identified candidate galaxies near redshifts 7.7 and 8.8 in multiple fields.

  16. E-PERM alpha surface monitor

    SciTech Connect

    Fricke, V.

    1999-12-16

    Innovative Technology Summary Reports are designed to provide potential users with the information they need to quickly determine if a technology would apply to a particular environmental management problem. They are also designed for readers who may recommend that a technology be considered by prospective users. Each report describes a technology, system, or process that has been developed and tested with funding from DOE's Office of Science and Technology (OST). The E-PERM{reg{underscore}sign} Alpha Surface Monitor is an integrating electret ion chamber innovative technology used to measure alpha radiation on surfaces of materials. The technology is best used on surfaces with low contamination levels such as areas with potential for free release, but can also be used in areas with higher levels of contamination. Measurement accuracy and production of the E-PERM {reg{underscore}sign} Alpha Surface Monitor compared favorably with the baseline technology. The innovative technology cost is approximately 28% higher than the baseline with an average unit cost per reading costing %6.04 vs. $4.36; however, the flexibility of the E-PERM{reg{underscore}sign} Alpha Surface Monitor may offer advantages in ALARA, reduction of operator error, waste minimization, and measurement accuracy.

  17. Alpha-actinin structure and regulation.

    PubMed

    Sjöblom, B; Salmazo, A; Djinović-Carugo, K

    2008-09-01

    Alpha-actinin is a cytoskeletal actin-binding protein and a member of the spectrin superfamily, which comprises spectrin, dystrophin and their homologues and isoforms. It forms an anti-parallel rod-shaped dimer with one actin-binding domain at each end of the rod and bundles actin filaments in multiple cell-type and cytoskeleton frameworks. In non-muscle cells, alpha-actinin is found along the actin filaments and in adhesion sites. In striated, cardiac and smooth muscle cells, it is localized at the Z-disk and analogous dense bodies, where it forms a lattice-like structure and stabilizes the muscle contractile apparatus. Besides binding to actin filaments alpha-actinin associates with a number of cytoskeletal and signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, rendering it important structural and regulatory roles in cytoskeleton organization and muscle contraction. This review reports on the current knowledge on structure and regulation of alpha-actinin.

  18. Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells.

    PubMed

    Vieira, Elaine; Marroquí, Laura; Figueroa, Ana Lucia C; Merino, Beatriz; Fernandez-Ruiz, Rebeca; Nadal, Angel; Burris, Thomas P; Gomis, Ramon; Quesada, Ivan

    2013-01-01

    Disruption of pancreatic clock genes impairs pancreatic beta-cell function, leading to the onset of diabetes. Despite the importance of pancreatic alpha-cells in the regulation of glucose homeostasis and in diabetes pathophysiology, nothing is known about the role of clock genes in these cells. Here, we identify the clock gene Rev-erb alpha as a new intracellular regulator of glucagon secretion. Rev-erb alpha down-regulation by siRNA (60-70% inhibition) in alphaTC1-9 cells inhibited low-glucose induced glucagon secretion (p<0.05) and led to a decrease in key genes of the exocytotic machinery. The Rev-erb alpha agonist GSK4112 increased glucagon secretion (1.6 fold) and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha-cells, whereas the Rev-erb alpha antagonist SR8278 produced the opposite effect. At 0.5 mM glucose, alphaTC1-9 cells exhibited intrinsic circadian Rev-erb alpha expression oscillations that were inhibited by 11 mM glucose. In mouse primary alpha-cells, glucose induced similar effects (p<0.001). High glucose inhibited key genes controlled by AMPK such as Nampt, Sirt1 and PGC-1 alpha in alphaTC1-9 cells (p<0.05). AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha. Nampt inhibition decreased Sirt1, PGC-1 alpha and Rev-erb alpha mRNA expression (p<0.01) and glucagon release (p<0.05). These findings identify Rev-erb alpha as a new intracellular regulator of glucagon secretion via AMPK/Nampt/Sirt1 pathway.

  19. Expression of cardiac alpha-actin spares extraocular muscles in skeletal muscle alpha-actin diseases--quantification of striated alpha-actins by MRM-mass spectrometry.

    PubMed

    Ravenscroft, Gianina; Colley, Stephen M J; Walker, Kendall R; Clement, Sophie; Bringans, Scott; Lipscombe, Richard; Fabian, Victoria A; Laing, Nigel G; Nowak, Kristen J

    2008-12-01

    As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle alpha-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac alpha-actin, the alpha-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac alpha-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle alpha-actin disease is thus probably due to greater levels of cardiac alpha-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle alpha-actin.

  20. Imaging of Damped Ly-alpha Absorbers

    NASA Astrophysics Data System (ADS)

    Jim, K. T. C.; Roth, K. C.

    1998-05-01

    Intervening H I gas clouds toward QSOs give rise to damped Ly-alpha absorption. Because of the high column density (N(H I)>= 2*E(20) cm(-2) ) these systems have been thought to be galactic disks in some stage of formation. However, because potential optical counterparts have not been identified for most damped Ly-alpha systems, it is possible that some of the absorbing systems could be dwarf irregular galaxies or low surface brightness galaxies, and are thus difficult to image. In any case, the absorbers are expected to have small angular separation from the QSOs, and so high resolution imaging is required to differentiate the absorbers from the QSOs. Because previous studies have not shown any dominant morphological form for the few candidate objects known, our images are obtained with the Hawaii tip-tilt system in order to achieve the best possible morphological classification. By imaging in the NIR and optical bands that bracket the 4000 Angstroms break of these Ly-alpha absorbers, we can more readily select candidate objects by photometrically constraining their redshifts. In our sample of 14 QSOs with abosorbers from 1alpha absorption systems which have no previously optically-identified counterparts, and for some of which we have Keck HIRES spectra. Companion papers in this session present the spectral analysis of two of these QSO's (Roth et al., Bauer et al.) and studies of M81 as a possible local analog of the Ly-alpha absorbers (Kolhatkar et al.)

  1. Alpha decay of {sup 181}Pb

    SciTech Connect

    Davids, C.N.; Henderson, D.J.; Hermann, R.

    1995-08-01

    The {alpha}-decay energy of {sup 181}Pb was measured as 7211(10) keV and 7044(15). In the first study the isotope was produced in {sup 90}Zr bombardments of {sup 94}Mo and, after traversing a velocity filter, implanted in a position-sensitive Si detector; no half life for {sup 181}Pb was reported. In the second study the isotope was produced in {sup 40}Ca bombardments of {sup 144}Sm and transported to a position in front of a Si(Au) surface barrier detector with a fast He-gas-jet capillary system; an estimate of 50 ms was determined for the {sup 181}Pb half life. Recently we investigated {sup 181}Pb {alpha} decay at ATLAS as part of a survey experiment in which a l-pnA beam of 400-MeV {sup 92}Mo was used to irradiate targets of {sup 89}Y, {sup 90,92,94}Zr, and {sup 92}Mo to examine yields for one- and two-nucleon evaporation products from symmetric cold-fusion reactions. Recoiling nuclei of interest were passed through the Fragment Mass Analyzer and implanted in a double-sided silicon strip detector for {alpha}-particle assay. With the {sup 90}Zr target we observed a group at 7065(20) keV which was correlated with A = 181 recoils and had a half life of 45(20) ms. Our new results for {sup 181}Pb therefore agreed with those of the second study. There was no indication in the {sup 90}Zr + {sup 92}Mo data of the 7211(10)-keV {alpha} particles seen by Keller et al. The interested reader is referred to the 1993 atomic mass evaluation wherein the input {alpha}-decay energies and resultant masses of the light Pb isotopes (including {sup 181}Pb) are discussed.

  2. Alpha-Alpha scattering, chiral symmetry and {sup 8}Be lifetime

    SciTech Connect

    Ruiz Arriola, E.

    2008-08-31

    Alpha-alpha scattering is discussed in terms of a chiral two pion exchange potential (TPE) which turns out to be attractive and singular at the origin, hence demanding renormalization. When {sup 8}Be is treated as a resonance state a model independent correlation between the Q-factor and lifetime 1/{gamma} for the decay into two alpha particles arises. For a wide range of parameters compatible with potential model analyses of low energy {pi}{alpha} scattering it is found {gamma} = 4.4(4)eV in fairly good agreement with the experimental value {gamma}{sub exp.} = 5.57(25)eV. The remaining discrepancy as well as the phase shift up to E{sub LAB} = 15 MeV could be accommodated by the leading nuclear peripheral contributions due to the {sup 3}H+p and {sup 3}He+n continuum.

  3. Degradation of the potato glycoalkaloids--alpha-solanine and alpha-chaconine in groundwater.

    PubMed

    Jensen, Pia H; Jacobsen, Ole S; Henriksen, Trine; Strobel, Bjarne W; Hansen, Hans Christian B

    2009-06-01

    The potato glycoalkaloids alpha-chaconine and alpha-solanine are produced in high amounts in potato plants from where release to soil takes place. Degradation of the compounds in groundwater was investigated, as their fate in the terrestrial environment is unknown. Abiotic and microbial degradation were followed in groundwater sampled from below a potato field and spiked with the glycoalkaloids (115 nmol/l). Degradation was primarily microbial and the glycoalkaloids were degraded within 21-42 days. The metabolites beta(1)-solanine, gamma-solanine, and solanidine were formed from alpha-solanine, while beta-chaconine, gamma-chaconine and solanidine were detected from alpha-chaconine. Thus, indigenous groundwater microorganisms are capable of degrading the glycoalkaloids.

  4. TFTR alpha extraction and measurement: Development and testing of advanced alpha detectors: Final report

    SciTech Connect

    Wehring, B.W.

    1988-02-15

    Advanced alpha-particle detectors made of heavy elements were investigated as alternatives to silicon surface-barrier detectors for the ''foil-neutralization technique'' of alpha-particle diagnostics in fusion reactors with high neutron backgrounds. From an extensive literature review, it was decided that HgI/sub 2/ would make a more suitable detector for alpha-particle diagnostics than other heavy element detectors such as CdTe. Thus, HgI/sub 2/ detectors were designed and fabricated. Experimental tests were performed to determine detector characteristics and detector responses to alpha particles. Radiation noise measurements were also performed using the North Carolina State University PULSTAR nuclear reactor for both the HgI/sub 2/ detectors and commercial Si(Au) surface barrier detectors. 15 refs., 1 fig.

  5. Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA.

    PubMed

    De Saint Jan, D; David-Watine, B; Korn, H; Bregestovski, P

    2001-09-15

    1. Two ligand binding alpha subunits, alpha1 and alpha2, of the human (H) glycine receptor (GlyR) are involved at inhibitory synapses in the adult and neonatal spinal cord, respectively. The ability of homomeric alphaH1 and alphaH2 GlyRs to be activated by glycine, taurine and GABA was studied in Xenopus oocytes or in the human embryonic kidney HEK-293 cell line. 2. In outside-out patches from HEK cells, glycine, taurine and GABA activated both GlyRs with the same main unitary conductance, i.e. 85 +/- 3 pS (n = 6) for alphaH1, and 95 +/- 5 pS (n = 4) for alphaH2. 3. The sensitivity of both alphaH1 and alphaH2 GlyRs to glycine was highly variable. In Xenopus oocytes the EC50 for glycine (EC50gly) was between 25 and 280 microM for alphaH1 (n = 44) and between 46 and 541 microM for alphaH2 (n = 52). For both receptors, the highest EC50gly values were found on cells with low maximal glycine responses. 4. The actions of taurine and GABA were dependent on the EC50gly: (i) their EC50 values were linearly correlated to EC50gly, with EC50tau approximately 10 EC50gly and EC50GABA approximately 500-800 EC50gly; (ii) they could act either as full or weak agonists depending on the EC50gly. 5. The Hill coefficient (n(H)) of glycine remained stable regardless of the EC50gly whereas n(H) for taurine decreased with increasing EC50tau. 6. The degree of desensitization, evaluated by fast application of saturating concentrations of agonist on outside-out patches from Xenopus oocytes, was similar for glycine and taurine on both GlyRs and did not exceed 50 %. 7. Our data concerning the variations of EC50gly and the subsequent behaviour of taurine and GABA could be qualitatively described by the simple del Castillo-Katz scheme, assuming that the agonist gating constant varies whereas the binding constants are stable. However, the stability of the Hill coefficient for glycine was not explained by this model, suggesting that other mechanisms are involved in the modulation of EC50.

  6. Enantioselective reactions of donor/acceptor carbenoids derived from alpha-aryl-alpha-diazoketones.

    PubMed

    Denton, Justin R; Davies, Huw M L

    2009-02-19

    The reaction of a variety of alpha-aryl-alpha-diazo ketones with activated olefins, catalyzed by the adamantyl glycine-derived dirhodium complex Rh(2)(S-PTAD)(4), generates cyclopropyl ketones with high diastereoselectivity (up to >95:5 dr) and enantioselectivity (up to 98% ee). Intermolecular C-H functionalization of 1,4-cyclohexadiene by means of carbenoid-induced C-H insertion was also possible with this type of carbenoid.

  7. Lipopolysaccharide-induced cytokine cascade and lethality in LT alpha/TNF alpha-deficient mice.

    PubMed Central

    Amiot, F.; Fitting, C.; Tracey, K. J.; Cavaillon, J. M.; Dautry, F.

    1997-01-01

    BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is often considered the main proinflammatory cytokine induced by lipopolysaccharide (LPS) and consequently the critical mediator of the lethality associated with septic shock. MATERIALS AND METHODS: We used mice carrying a deletion of both the lymphotoxin alpha (LT-alpha) and TNF-alpha genes to assess the role of TNF in the cytokine cascade and lethality induced by LPS. RESULTS: Initial production of IL-1 alpha, IL-1 beta, IL-6, and IL-10 is comparable in wild-type and mutant mice. However, at later times, expression of IL-1 alpha, IL-1 beta, and IL-10 is prolonged, whereas that of IL-6 decreases in mutant mice. Expression of IFN-gamma is almost completely abrogated in mutants, which is in agreement with a more significant alteration of the late phase of the cytokine cascade. We measured similar LD50 (600 micrograms) for the intravenous injection of LPS in mice of the three genotypes (+/+, +/-, -/-), demonstrating that the absence of TNF does not confer long-term protection from lethality. However, death occurred much more slowly in mutant mice, who were protected more efficiently from death by CNI 1493, an inhibitor of proinflammatory cytokine production, than were wild-type mice. DISCUSSION: Thus, while TNF-alpha is not required for the induction of these cytokines by LPS, it modulates the kinetics of their expression. The lethality studies simultaneously confirm a role for TNF as a mediator of early lethality and establish that, in the absence of these cytokines, other mediators take over, resulting in the absence of long-term protection from LPS toxicity. Images FIG. 1 FIG. 2 PMID:9440119

  8. Physical Properties of Lyman-alpha Forest and Damped Lyman-alpha Systems

    NASA Astrophysics Data System (ADS)

    Kulkarni, V. P.; Fall, S. M.

    1995-12-01

    We present a review of our results regarding various physical properties of quasar absorption line systems, in particular, the Lyman-alpha forest and the damped Lyman-alpha systems. We made the first detection of the quasar proximity effect at low redshifts, using HST Key Project data on the Ly-alpha forest for z < 1. This allowed the first empirical estimate of the intensity of the ionizing UV background at < z > ~ 0.5 and showed evidence for evolution of the ionizing UV background with redshift. We have also studied the implications of non-thermal motions inside Ly-alpha forest clouds for the statistics of these clouds. We showed that the distributions in H I column densities f(N) for systems with saturated Ly-alpha lines and the extent (and sign) of N-sigma correlations could differ from previous estimates, if the clouds possessed non-Maxwellian velocity distributions. We also present results of a study of the chemical properties of several damped Lyman-alpha systems, based on published high-sensitivity observations. In particular, we examine the total (gas + solid phase) metallicity and the dust content of these systems. Results will also be presented of an analysis of an 18 km s(-1) resolution spectrum of the Ly-alpha forest of the z = 2.1 quasar Q1331+170, performed in collaboration with Dr. D. G. York, Dr. D. E. Welty (U. Chicago), Dr. R. F. Green, Dr. K. Huang (NOAO) and Dr. J. Bechtold (U. Arizona). One of the main results is some evidence for small-scale clustering among the Ly-alpha forest clouds.

  9. Domino transformation of D-glucal to racemic alpha-substituted alpha-hydroxymethyl furfuryl derivatives.

    PubMed

    Mukherjee, Debaraj; Yousuf, Syed Khalid; Taneja, Subhash Chandra

    2008-11-06

    Lewis acid mediated one-pot transformation of D-glucal in the presence of nucleophiles leads to the formation of racemic alpha-substituted alpha-hydroxymethyl furfuryl derivatives, versatile synthons for biologically active molecules. Transformations using O-, S-, C-, and N-nucleophiles could be achieved readily under mild and scalable conditions. Indium triflate proved to be the catalyst of choice in terms of conversion and regioselectivity.

  10. Antibody-mediated reduction of .alpha.-ketoamides

    DOEpatents

    Schultz, Peter G.; Gallop, Mark A.

    1998-01-01

    Monoclonal antibodies raised against a 4-nitrophenyl phosphonate hapten catalyze the stereospecific reduction of an .alpha.-ketoamide to the corresponding .alpha.-hydroxyamide in the presence of an appropriate reducing agent.

  11. Antibody-mediated reduction of {alpha}-ketoamides

    DOEpatents

    Schultz, P.G.; Gallop, M.A.

    1998-06-09

    Monoclonal antibodies raised against a 4-nitrophenyl phosphonate hapten catalyze the stereospecific reduction of an {alpha}-ketoamide to the corresponding {alpha}-hydroxyamide in the presence of an appropriate reducing agent.

  12. Who Is at Risk for Alpha-1 Antitrypsin Deficiency?

    MedlinePlus

    ... for Alpha-1 Antitrypsin Deficiency? Alpha-1 antitrypsin (AAT) deficiency occurs in all ethnic groups. However, the ... most often in White people of European descent. AAT deficiency is an inherited condition. "Inherited" means the ...

  13. An assay for intermolecular exchange of alpha crystallin

    NASA Technical Reports Server (NTRS)

    Gopalakrishnan, S.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    An affinity column of alpha crystallin linked to cyanogen bromide-activated Sepharose was developed to study the exchange of alpha subunits. Alpha crystallin bound to the Sepharose-alpha complex was dissociated with 8 mol/l urea, followed by quantitation using high-performance reverse-phase liquid chromatography. The time course of binding at 37 degrees C showed a hyperbolic binding pattern reaching equilibrium between 6-18 hr. Under these conditions, binding of beta and gamma crystallins to the same matrix was less than 10% of the alpha values, as was binding of alpha to glycine-coupled Sepharose. This assay was used to demonstrate changes in the subunit exchange of alpha crystallins present in high molecular weight versus lower molecular weight aggregates of the human lens. These results show that this binding procedure was a specific reproducible assay that might be used to study intermolecular interactions of the alpha crystallins.

  14. Effects of tumor necrosis factor-alpha (TNF alpha) in epidermal keratinocytes revealed using global transcriptional profiling.

    PubMed

    Banno, Tomohiro; Gazel, Alix; Blumenberg, Miroslav

    2004-07-30

    Identification of tumor necrosis factor-alpha (TNF alpha) as the key agent in inflammatory disorders, e.g. rheumatoid arthritis, Crohn's disease, and psoriasis, led to TNF alpha-targeting therapies, which, although avoiding many of the side-effects of previous drugs, nonetheless causes other side-effects, including secondary infections and cancer. By controlling gene expression, TNF alpha orchestrates the cutaneous responses to environmental damage and inflammation. To define TNF alpha action in epidermis, we compared the transcriptional profiles of normal human keratinocytes untreated and treated with TNF alpha for 1, 4, 24, and 48 h by using oligonucleotide microarrays. We found that TNF alpha regulates not only immune and inflammatory responses but also tissue remodeling, cell motility, cell cycle, and apoptosis. Specifically, TNF alpha regulates innate immunity and inflammation by inducing a characteristic large set of chemokines, including newly identified TNF alpha targets, that attract neutrophils, macrophages, and skin-specific memory T-cells. This implicates TNF alpha in the pathogenesis of psoriasis, fixed drug eruption, atopic and allergic contact dermatitis. TNF alpha promotes tissue repair by inducing basement membrane components and collagen-degrading proteases. Unexpectedly, TNF alpha induces actin cytoskeleton regulators and integrins, enhancing keratinocyte motility and attachment, effects not previously associated with TNF alpha. Also unanticipated was the influence of TNF alpha upon keratinocyte cell fate by regulating cell-cycle and apoptosis-associated genes. Therefore, TNF alpha initiates not only the initiation of inflammation and responses to injury, but also the subsequent epidermal repair. The results provide new insights into the harmful and beneficial TNF alpha effects and define the mechanisms and genes that achieve these outcomes, both of which are important for TNF alpha-targeted therapies.

  15. Structural and electrochemical studies of alpha manganese dioxide ({alpha}-MnO{sub 2})

    SciTech Connect

    Johnson, C.S.; Dees, D.W.; Mansuetto, M.F.; Thackeray, M.M.; Vissers, D.R.; Argyriou, D.; Loong, C.-K.; Christensen, L.

    1996-08-01

    The structural and electrochemical properties of alpha-MnO[sub 2], prepared by acid digestion of Mn[sub 2]O[sub 3], and its lithiated derivatives xLi[sub 2] O . MnO[sub 2] (where x is greater than or equal to zero and less than or equal to 0.25) have been investigated as insertion compounds in the search for new and viable cathode materials for rechargeable 3-V batteries. The alpha-MnO[sub 2] product fabricated by this technique contains water within the large (2x2) channels of the structure; the water can be removed from the alpha-MnO[sub 2] framework without degradation of the structure, and then at least partially replaced by Li[sub 2]O. The lithia-doped alpha-MnO[sub 2] electrodes, described generically as xLi[sub 2]O . Mno[sub 2], stabilize the structure and provide higher capacities on cycling than the parent material. The structures of these alpha- MnO[sub 2]-type electrode materials are described. and electrochemical data are presented for both liquid electrolyte and polymer electrolyte Li/alpha-MnO[sub 2] and Li/xLi[sub 2]O . MnO[sub 2] cells.

  16. Alternative nonallelic deletion is constitutive of ruminant alpha(s1)-casein.

    PubMed

    Ferranti, P; Lilla, S; Chianese, L; Addeo, F

    1999-07-01

    Multiple forms of alpha(s1)-casein were identified in the four major ruminant species by structural characterization of the protein fraction. While alpha(s1)-casein phenotypes were constituted by a mixture of at least seven molecular forms in ovine and caprine species, there were only two forms in bovine and water buffalo species. In ovine and caprine forms the main component corresponded to the 199-residue-long form, and the deleted proteins differed from the complete one by the absence of peptides 141-148, 110-117, or Gln78, or a combination of such deletions. The deleted segments corresponded to the sequence regions encoded by exons 13 and 16, and by the first triplet of exon 11 (CAG), suggesting that the occurrence of the short protein forms is due to alternative skipping, as previously demonstrated for some caprine and ovine phenotypes. The alternative deletion of Gln78 in alpha(s1)-casein, the only form common to the milk of all the species examined and located in a sequence region joining the polar phosphorylation cluster and the hydrophobic C-terminal domain of the protein, may play a functional role in the stabilization of the milk micelle structure.

  17. Human GABAA receptor alpha 1 and alpha 3 subunits genes and alcoholism.

    PubMed

    Parsian, A; Cloninger, C R

    1997-05-01

    gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA effects are largely mediated by binding to the postsynaptic GABAA receptor, causing the opening of an integral chloride-ion channel. The GABAA antagonists picrotoxin and bicuculline reduce some ethanol-induced behaviors, such as motor impairment, sedation, and hypnosis. The role of this receptor in alcoholism is further supported by effective alleviation of alcohol withdrawal symptoms by GABAA agonists. To determine the role of the GABAA receptor (GABR) genes in the development of alcoholism, we have used alpha 1 and alpha 3 simple sequence repeat polymorphisms in a sample of unrelated alcoholics, alcoholic probands with both parents, and psychiatrically normal controls. For the GABR alpha 1 gene, the differences between allele frequencies, when all alleles were compared together, were not significant between total alcoholics, subtypes of alcoholics, and normal controls. However, for GABR alpha 3, the differences between total alcoholics and normal controls were significant when all alleles were compared together. The differences between subtypes of alcoholics and normal controls were not significant. The results of haplotype relative risk analysis for both genes, GABR alpha 1 and GABR alpha 3, were also negative. It is possible that the sample size in the haplotype relative risk is too small to have power to detect the differences in transmitted versus nontransmitted alleles. There is a need for a replication study in a large family sample that will allow haplotype relative risk or affected sib-pair analysis.

  18. Chaperone-like activities of {alpha}-synuclein: {alpha}-Synuclein assists enzyme activities of esterases

    SciTech Connect

    Ahn, Misun; Kim, SeungBum; Kang, Mira; Ryu, Yeonwoo . E-mail: ywryu@ajou.ac.kr; Doohun Kim, T. . E-mail: doohunkim@ajou.ac.kr

    2006-08-11

    {alpha}-Synuclein, a major constituent of Lewy bodies (LBs), has been implicated to play a critical role in the pathogenesis of Parkinson's disease (PD), although the physiological function of {alpha}-synuclein has not yet been known. Here we have shown that {alpha}-synuclein, which has no well-defined secondary or tertiary structure, can protect the enzyme activity of microbial esterases against stress conditions such as heat, pH, and organic solvents. In particular, the flexibility of {alpha}-synuclein and its C-terminal region seems to be important for complex formation, but the structural integrity of the C-terminal region may not be required for stabilization of enzyme activity. In addition, atomic force microscopy (AFM) and in vivo enzyme assays showed highly specific interactions of esterases with {alpha}-synuclein. Our results indicate that {alpha}-synuclein not only protects the enzyme activity of microbial esterases in vitro, but also can stabilize the active conformation of microbial esterases in vivo.

  19. Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1

    PubMed Central

    1994-01-01

    The plasma protein fibronectin is an important opsonin in wound repair and host defense. To better understand the process of fibronectin- mediated phagocytosis, we have transfected K562 cells, which endogenously express alpha 5 beta 1, with alpha v beta 3. In these transfectants, antibodies to alpha v beta 3 block phagocytosis of fibronectin-opsonized beads completely, even though half the ingestion occurs through endogenous alpha 5 beta 1 receptors. alpha 5 beta 1- mediated adhesion to fibronectin-coated surfaces is unaffected by alpha v beta 3 ligation. Neither alpha v beta 5 nor alpha M beta 2 ligation affects alpha 5 beta 1 phagocytic function in transfectants expressing these receptors. Pharmacologic data suggest that alpha v beta 3 ligation suppresses the phagocytic competence of high affinity alpha 5 beta 1 receptors through a signal transduction pathway, perhaps involving protein kinase C. In addition to its significance for phagocytosis, alpha v beta 3 regulation of alpha 5 beta 1 function may be significant for its roles in cell migration, metastasis, and angiogenesis. PMID:7525603

  20. Ovarian stimulation with human chorionic gonadotropin and equine chorionic gonadotropin affects prostacyclin and its receptor expression in the porcine oviduct.

    PubMed

    Małysz-Cymborska, I; Andronowska, A

    2015-10-01

    Prostaglandins are well-known mediators of crucial events in the female reproductive tract, eg, early embryo development and implantation. Prostacyclin (PGI2) is the most synthesized prostaglandin in the human oviduct during the postovulatory period, indicating its important role in supporting and regulating the oviductal environment. The present study was undertaken to determine the influence of insemination and ovarian stimulation with human chorionic gonadotropin (hCG)/equine chorionic gonadotropin (eCG) on PGI2 synthesis in the porcine oviduct on day 3 post coitus. Mature gilts (n = 25) were assigned into 2 experiments. In experiment I, gilts were divided into cyclic (control; n = 5) and inseminated (control; n = 5) groups. In experiment II, there were 3 groups of animals: inseminated (n = 5), induced ovulation/inseminated (750 IU eCG, 500 IU hCG; n = 5), and superovulated/inseminated (1,500 IU eCG, 1,000 IU hCG; n = 5) gilts. Parts of oviducts (isthmus and ampulla) were collected 3 days after phosphate-buffered saline treatment (cyclic gilts of experiment I) or insemination (all other groups). Expression of messenger RNA for PGI2 synthase (PGIS) and its receptor (IP) was measured by real-time reverse transcription polymerase chain reaction (real-time RT PCR) and protein levels using Western blots. Concentrations of the PGI2 metabolite 6-keto PGF1α were evaluated by enzyme immunoassay and localization of PGIS and IP in the oviductal tissues using immunohistochemical staining. Insemination by itself increased PGIS protein levels in the oviductal isthmus (P < 0.05) and IP protein expression in the ampulla (P < 0.05). The concentration of 6-keto PGF1α increased significantly in the oviductal ampulla after insemination (P < 0.05). Induction of ovulation decreased IP protein levels in the oviductal ampulla (P < 0.05), whereas superovulation reduced IP levels in both parts of the oviduct (P < 0.01). Synthesis of 6-keto PGF1α was reduced by induction of ovulation

  1. 2-Aminoresorcinol is a potent alpha-glucosidase inhibitor.

    PubMed

    Gao, Hong; Kawabata, Jun

    2008-01-15

    A series of aminoresorcinols and related compounds were tested for rat intestinal alpha-glucosidase inhibition and these results suggested that the 2-aminoresorcinol moiety of 6-amino-5,7-dihydroxyflavone (2) is important to exert the intestinal alpha-glucosidase inhibitory activity and 2-aminoresorcinol (4), itself, is a potent alpha-glucosidase inhibitor and inhibited sucrose-hydrolyzing activity of rat intestinal alpha-glucosidase uncompetitively.

  2. Studies on the receptors to 5alpha-androst-16-en-3-one and 5alpha-androst-16-en-3alpha-ol in sow nasal mucosa.

    PubMed

    Gennings, J N; Gower, D B; Bannister, L H

    1977-02-28

    The presence of receptors to the "boar taint" pheromones 5alpha-androst-16-en-3-one and 5alpha-androst-16-en-3alpha-ol has been demonstrated in sow olfactory mucosa. Binding studies indicated that a sufficiently low concentration of olfactory tissue homogenate exhibited saturation of binding of 5alpha-androst-16-en-3-one, and this was of high affinity compared with control tissues of non-olfactory and heated olfactory tissues. Analysis of receptor binding of 5alpha-androst-16-en-3-one gave a value for the affinity constant (Ka) of approx. 8.3-10(8) M-1 and the value for the molar concentration of binding sites (n[M]) was approx. 3.3 pmol/mg protein. Almost identical values of Ka and n [M] were obtained when receptor binding of 5alpha-[5alpha-3H]androst-16-en-3alpha-ol was investigated (Ka 8.4-10(8) M-1; n [M] 3.7 pmol/mg protein). This suggests that the same receptor binds both 5alpha-androst-16-en-3-one and 5alpha-androst-16-en-3alpha-ol with equally high affinity. In a preliminary investigation to establish the specificity of the receptor, the binding of 17beta-hydroxy-5alpha-androstan-3-one was assayed; this steroid is odourless but has a similar structure except in ring D to 5alpha-androst-16-en-3-one. Binding was of the low affinity, non-specific type only, indicating that the sow olfactory receptors are not sensitive to this androgen.

  3. Nicotine inhibits Fc epsilon RI-induced cysteinyl leukotrienes and cytokine production without affecting mast cell degranulation through alpha 7/alpha 9/alpha 10-nicotinic receptors.

    PubMed

    Mishra, Neerad C; Rir-sima-ah, Jules; Boyd, R Thomas; Singh, Shashi P; Gundavarapu, Sravanthi; Langley, Raymond J; Razani-Boroujerdi, Seddigheh; Sopori, Mohan L

    2010-07-01

    Smokers are less likely to develop some inflammatory and allergic diseases. In Brown-Norway rats, nicotine inhibits several parameters of allergic asthma, including the production of Th2 cytokines and the cysteinyl leukotriene LTC(4). Cysteinyl leukotrienes are primarily produced by mast cells, and these cells play a central role in allergic asthma. Mast cells express a high-affinity receptor for IgE (FcepsilonRI). Following its cross-linking, cells degranulate and release preformed inflammatory mediators (early phase) and synthesize and secrete cytokines/chemokines and leukotrienes (late phase). The mechanism by which nicotine modulates mast cell activation is unclear. Using alpha-bungarotoxin binding and quantitative PCR and PCR product sequencing, we showed that the rat mast/basophil cell line RBL-2H3 expresses nicotinic acetylcholine receptors (nAChRs) alpha7, alpha9, and alpha10; exposure to exceedingly low concentrations of nicotine (nanomolar), but not the biologically inactive metabolite cotinine, for > or = 8 h suppressed the late phase (leukotriene/cytokine production) but not degranulation (histamine and hexosaminidase release). These effects were unrelated to those of nicotine on intracellular free calcium concentration but were causally associated with the inhibition of cytosolic phospholipase A(2) activity and the PI3K/ERK/NF-kappaB pathway, including phosphorylation of Akt and ERK and nuclear translocation of NF-kappaB. The suppressive effect of nicotine on the late-phase response was blocked by the alpha7/alpha9-nAChR antagonists methyllycaconitine and alpha-bungarotoxin, as well as by small interfering RNA knockdown of alpha7-, alpha9-, or alpha10-nAChRs, suggesting a functional interaction between alpha7-, alpha9-, and alpha10-nAChRs that might explain the response of RBL cells to nanomolar concentrations of nicotine. This "hybrid" receptor might serve as a target for novel antiallergic/antiasthmatic therapies.

  4. Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.

    PubMed

    Tulppala, M; Marttunen, M; Söderstrom-Anttila, V; Foudila, T; Ailus, K; Palosuo, T; Ylikorkala, O

    1997-07-01

    Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three

  5. Identification of Dictyostelium G alpha genes expressed during multicellular development.

    PubMed Central

    Hadwiger, J A; Wilkie, T M; Strathmann, M; Firtel, R A

    1991-01-01

    Guanine nucleotide-binding protein (G protein)-mediated signal transduction constitutes a common mechanism by which cells receive and respond to a diverse set of environmental signals. Many of the signals involved in the developmental life cycle of the slime mold Dictyostelium have been postulated to be transduced by such pathways and, in some cases, these pathways have been demonstrated to be dependent on specific G proteins. Using the polymerase chain reaction, we have identified two additional Dictyostelium G alpha genes, G alpha 4 and G alpha 5, that are developmentally regulated. Transcripts from both of these genes are primarily expressed during the multicellular stages of development, suggesting possible roles in cell differentiation or morphogenesis. The entire G alpha 4 gene was sequenced and found to encode a protein consisting of 345 amino acids. The G alpha 4 subunit is homologous to other previously identified G alpha subunits, including the Dictyostelium G alpha 1 (43% identity) and G alpha 2 (41% identity) subunits. However, the G alpha 4 subunit contains some unusual sequence divergences in residues highly conserved among most eukaryotic G alpha subunits, suggesting that G alpha 4 may be a member of another class of G alpha subunits. Images PMID:1910174

  6. Physical and chemical properties of human plasma alpha2-macroglobulin.

    PubMed Central

    Hall, P K; Roberts, R C

    1978-01-01

    Alpha2-M (alpha2-macroglobulin) was purified from human plasma by two different procedures. As well as having no detectable impurities by the usual criteria for testing the homogeneity of protein preparations, these alpha2M preparations showed a single component, after reduction in urea, of 185000 daltons by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The molecular weight of the alpha2M was found to be 718000 by sedimentation equilibrium experiments using the gravimetrically determined -v of 0.731 ml/g. The interaction of several proteinases with alpha2M was studied by using a novel discontinuous polyacrylamide-gel system, which showed clear separation of the enzyme-complexed alpha2M from the free alpha2M. These studies indicated that urokinase, as well as trypsin, chymotrypsin, plasmin and thrombin forms complexes with alphaM. The cleavage of the 185000-dalton subunit to a 85000-dalton species on interaction of trypsin with alpha2M was demonstrated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis after reduction of the alpha2M-trypsin complex in urea. The amino acid composition, carbohydrate content, absorption coefficient at 280 nm, the specific refractive increment and the sedimentation coefficient for these alpha2M preparations were measured. The stability of the trypsin-binding activity of the alpha2M preparations was also studied under several storage situations. Images Fig. 1. Fig. 2. Fig. 3. Fig. 6. PMID:80217

  7. Human seminal alpha inhibins: isolation, characterization, and structure.

    PubMed Central

    Li, C H; Hammonds, R G; Ramasharma, K; Chung, D

    1985-01-01

    Two additional peptides with inhibin-like activity have been isolated from human seminal plasma. One consists of 52 amino acids and the other, 92 amino acids. They are designated alpha-inhibin-52 and alpha-inhibin-92. Sequence analyses show that the NH2-terminal 31 amino acids of alpha-inhibin-52 are identical to the structure of the inhibin-like peptide previously reported [ILP-(1-31), now designated alpha-inhibin-31], and the COOH-terminal 52 amino acids of alpha-inhibin-92 are identical to the structure of alpha-inhibin-52. The amino acid sequence of alpha-inhibin-92 is: (sequence in text) Bioassay data in mouse pituitaries in vitro show that alpha-inhibin-52 is 3.4 times more active and alpha-inhibin-92 is greater than 40 times more active than alpha-inhibin-31 in suppressing follitropin-release. Radioimmunoassay data indicate that alpha-inhibin-52 and alpha-inhibin-92 have only 60% immunoreactivity. PMID:3889920

  8. The serotonin aldehyde, 5-HIAL, oligomerizes alpha-synuclein.

    PubMed

    Jinsmaa, Yunden; Cooney, Adele; Sullivan, Patricia; Sharabi, Yehonatan; Goldstein, David S

    2015-03-17

    In Parkinson's disease (PD) alpha-synuclein oligomers are thought to be pathogenic, and 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate aldehyde intermediate in neuronal dopamine metabolism, potently oligomerizes alpha-synuclein. PD involves alpha-synuclein deposition in brainstem raphe nuclei; however, whether 5-hydroxyindoleacetaldehyde (5-HIAL), the aldehyde of serotonin, oligomerizes alpha-synuclein has been unknown. In this study we tested whether 5-HIAL oligomerizes alpha-synuclein in vitro and in PC12 cells conditionally over-expressing alpha-synuclein. Alpha-synuclein oligomers were quantified by western blotting after incubation of alpha-synuclein with serotonin and monoamine oxidase-A (MAO-A) to generate 5-HIAL or dopamine to generate DOPAL. Oligomerization of alpha-synuclein in PC12 cells over-expressing the protein was compared between vehicle-treated cells and cells incubated with levodopa to generate DOPAL or 5-hydroxytryptophan to generate 5-HIAL. Monoamine aldehyde mediation of the oligomerization was assessed using the MAO inhibitor, pargyline. Dopamine and serotonin incubated with MAO-A both strongly oligomerized alpha-synuclein (more than 10 times control); pargyline blocked the oligomerization. In synuclein overexpressing PC12 cells, levodopa and 5-hydroxytryptophan elicited pargyline-sensitive alpha-synuclein oligomerization. 5-HIAL oligomerizes alpha-synuclein both in vitro and in synuclein-overexpressing PC12 cells, in a manner similar to DOPAL. The findings may help explain loss of serotonergic neurons in PD.

  9. Bayesian Statistical Inference for Coefficient Alpha. ACT Research Report Series.

    ERIC Educational Resources Information Center

    Li, Jun Corser; Woodruff, David J.

    Coefficient alpha is a simple and very useful index of test reliability that is widely used in educational and psychological measurement. Classical statistical inference for coefficient alpha is well developed. This paper presents two methods for Bayesian statistical inference for a single sample alpha coefficient. An approximate analytic method…

  10. [Interferon alpha-2b modified with polyethylene glycol].

    PubMed

    Wu, Yingxin; Zhai, Yanqin; Lei, Jiandu; Ma, Guanghui; Su, Zhiguo

    2008-09-01

    In order to obtain a more stable PEGylated interferon alpha-2b, and prolong its half life, interferon alpha-2b (IFN alpha-2b) was modified with monomethoxy polyethylene glycol propionaldehyde (mPEG-ALD) 20000. It was found that the optimized reaction condition for the maximum bioactivity and highest PEGylation degree of the mono PEGylated interferon alpha-2b was as follows: in 20 mmol/L, pH 6.5, citric acid and sodium dihydrogen phosphate buffer, the concentration of IFN alpha-2b was 4 mg/mL, and the molar ratio of PEG/IFN alpha-2b was 8:1, and the reaction time was 20 h at 4 degrees C. Under the optimized reaction condition, the mono PEGylation degree reached to 55%. Ion exchange chromatography was used to separate and purify mono PEGylated interferon alpha-2b from the reaction mixture. The purity of mono PEGylated interferon alpha-2b was higher than 97% characterized by HPLC. The bioactivity of the mono PEGylated interferon alpha-2b was 13.4% of the native IFN alpha-2b, while its half life in SD rat is much longer than the native IFN alpha-2b. The mono PEGylated interferon alpha-2b is also stable in aqueous.

  11. Direct Measurement of {sup 21}Na+{alpha} Stellar Reaction

    SciTech Connect

    Binh, D. N.; Kubono, S.; Yamaguchi, H.; Hayakawa, S.; Hashimoto, T.; Kahl, D.; Teranishi, T.; Iwasa, N.; Kume, N.; Kato, S.; Khiem, L. H.; Tho, N. T.; Wakabayashi, Y.

    2010-08-12

    The measurement of the resonant alpha scattering and the {sup 21}Na({alpha}, p) reaction were performed for the first time in inverse kinematics with the thick target method using a {sup 21}Na radioisotope (RI) beam. This paper reports the current result of alpha scattering measurement and its astrophysics implication.

  12. The muscle-specific laminin receptor alpha7 beta1 integrin negatively regulates alpha5 beta1 fibronectin receptor function.

    PubMed

    Tomatis, D; Echtermayer, F; Schöber, S; Balzac, F; Retta, S F; Silengo, L; Tarone, G

    1999-02-01

    alpha7 beta1 is the major integrin complex expressed in differentiated muscle cells where it functions as a laminin receptor. In this work we have expressed the alpha7 integrin subunit in CHO cells to investigate the functional properties of this receptor. After transfection with alpha7 CHO cells acquired the ability to adhere and spread on laminin 1 consistent with the laminin receptor activity of the alpha7 beta1. alpha7 transfectants, however, showed a 70% reduction in the ability to adhere to fibronectin and were unable to assemble a fibronectin matrix. The degree of reduction was inversely related to the level of alpha7 expression. To define the mechanisms underlying this adhesive defect we analyzed surface expression and functional properties of the alpha5 beta1 fibronectin receptor. Although cell surface expression of alpha5 beta1 was reduced by a factor of 20-25% in alpha7 transfectants compared to control untransfected cells, this slight reduction was not sufficient to explain the dramatic reduction in cell adhesion (70%) and matrix assembly (close to 100%). Binding studies showed that the affinity of 125I-fibronectin for its surface receptor was decreased by 50% in alpha7 transfectants, indicating that the alpha5 beta1 integrin is partially inactivated in these cells. Inactivation can be reversed by Mn2+, a cation known to increase integrin affinity for their ligands. In fact, incubation of cells with Mn2+ restored fibronectin binding affinity, adhesion to fibronectin, and assembly of fibronectin matrix in alpha7 transfectants. These data indicate that alpha7 expression leads to the functional down regulation of alpha5beta1 integrin by decreasing ligand binding affinity and surface expression. In conclusion, the data reported establish the existence of a negative cooperativity between alpha7 and alpha5 integrins that may be important in determining functional regulation of integrins during myogenic differentiation.

  13. Fluoxetine may influence lordosis of rats through effects on midbrain 3 alpha,5 alpha-THP concentrations.

    PubMed

    Frye, Cheryl A; Petralia, Sandra M; Rhodes, Madeline E; Stein, Benjamin

    2003-12-01

    5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) in the ventral tegmental area (VTA) mediates lordosis of rodents. If fluoxetine's effects on lordosis are mediated in part by midbrain 3alpha,5alpha-THP, then fluoxetine regimens that decrease and increase lordosis would be expected to respectively lower and elevate midbrain 3alpha,5-THP levels. Experiment 1: Ovariectomized (ovx) rats received estradiol benzoate (EB; 5 micro g, SC) at 0 and 24 h and fluoxetine (20 mg/kg, IP) or vehicle 30 min before sex testing and tissue collection. Other rats received fluoxetine (10 mg/kg, IP) or vehicle for 15 days followed by EB-priming and testing. Systemic acute or chronic fluoxetine significantly decreased lordosis and midbrain 3alpha,5alpha-THP levels compared to vehicle. Experiment 2: Ovx rats with unilateral cannula to the VTA were primed with EB (5 micro g; 0, 24 h) and/or progesterone (0 or 100 micro g; 44 h, SC). At 47.5 h, fluoxetine (3.6 mM) or vehicle was infused to the VTA. At 48 h, rats were tested. Administering fluoxetine to the VTA significantly increased lordosis and midbrain 3alpha,5alpha-THP levels compared to vehicle infusions. Experiment 3: Ovx EB-primed rats were tested prior to, and 30 min after, treatmemt with acute fluoxetine (20 mg/kg, IP). Rats were then infused with 3alpha,5alpha-THP (100 ng) or vehicle to the VTA and were retested. 3alpha,5alpha-THP, but not vehicle, to the VTA reversed acute fluoxetine's inhibitory effects on lordosis. Together, these data suggest fluoxetine may alter lordosis in part through actions of 3alpha-THP in the midbrain.

  14. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol.

    PubMed

    Serbinova, E; Kagan, V; Han, D; Packer, L

    1991-01-01

    d-Alpha-tocopherol (2R,4'R,8'R-Alpha-tocopherol) and d-alpha-tocotrienol are two vitamin E constituents having the same aromatic chromanol "head" but differing in their hydrocarbon "tail": tocopherol with a saturated and toctrienol with an unsaturated isoprenoid chain. d-Alpha-tocopherol has the highest vitamin E activity, while d-alpha-tocotrienol manifests only about 30% of this activity. Since vitamin E is considered to be physiologically the most important lipid-soluble chain-breaking antioxidant of membranes, we studied alpha-tocotrienol as compared to alpha-tocopherol under conditions which are important for their antioxidant function. d-Alpha-tocotrienol possesses 40-60 times higher antioxidant activity against (Fe2+ + ascorbate)- and (Fe2+ + NADPH)-induced lipid peroxidation in rat liver microsomal membranes and 6.5 times better protection of cytochrome P-450 against oxidative damage than d-alpha-tocopherol. To clarify the mechanisms responsible for the much higher antioxidant potency of d-alpha-tocotrienol compared to d-alpha-tocopherol, ESR studies were performed of recycling efficiency of the chromanols from their chromanoxyl radicals. 1H-NMR measurements of lipid molecular mobility in liposomes containing chromanols, and fluorescence measurements which reveal the uniformity of distribution (clusterizations) of chromanols in the lipid bilayer. From the results, we concluded that this higher antioxidant potency of d-alpha-tocotrienol is due to the combined effects of three properties exhibited by d-alpha-tocotrienol as compared to d-alpha-tocopherol: (i) its higher recycling efficiency from chromanoxyl radicals, (ii) its more uniform distribution in membrane bilayer, and (iii) its stronger disordering of membrane lipids which makes interaction of chromanols with lipid radicals more efficient. The data presented show that there is a considerable discrepancy between the relative in vitro antioxidant activity of d-alpha-tocopherol and d-alpha

  15. Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

    SciTech Connect

    Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

    1986-03-05

    EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A/sub 4/ hydrolase activity, plasma renin activity (PRA), urinary levels of TxB/sub 2/ and 6-keto-PGF/sub 1..cap alpha../ and aortic conversion of (/sup 14/C)-AA to (/sup 14/C)-6-keto-PGF/sub 1..cap alpha../ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P < 0.001) and retarded the development of hypertension in young SHR rats (178 +/- 6 vs. 218 +/- 4 mmHg in controls, p < 0.001). Platelets showed decreased responsiveness to ADP (3 ..mu..M) and glomerular LTA/sub 4/ hydrolase activity was inhibited. PRA and urinary levels of TxB/sub 2/ and 6-keto-PGF/sub 1..cap alpha../ were not changed. Similarly, there was no change in aortic conversion of (/sup 14/C)-AA to (/sup 14/C)-6-keto-PGF/sub 1..cap alpha../ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function.

  16. PSYCHOPHYSICS OF EEG ALPHA STATE DISCRIMINATION

    PubMed Central

    Frederick, Jon A.

    2012-01-01

    Nearly all research in neurofeedback since the 1960s has focused on training voluntary control over EEG constructs. By contrast, EEG state discrimination training focuses on awareness of subjective correlates of EEG states. This study presents the first successful replication of EEG alpha state discrimination first reported by Kamiya (1962). A 150-second baseline was recorded in 106 participants. During the task, low (<30th percentile of the baseline) and high alpha events (>70th percentile) triggered a prompt. Participants indicated “high” or “low” with a keypress response and received immediate feedback. Seventy-five percent of participants achieved significant discrimination within nine sessions, with a significant learning curve effect. Performance was significantly related to physical properties of the EEG signal, including magnitude, duration, and absolute vs. relative amplitude. These results are consistent with a conceptualization of EEG state discrimination as a sensory modality, although it is also intricately related to voluntary control of these states. PMID:22800733

  17. The Ups and Downs of Alpha Centauri

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas

    2014-11-01

    Nearby Alpha Centauri is destined for a pivotal chapter in human history, as first stop of future starfarers from Earth: 3x closer than the next nearest star; three very different objects to visit -- Alpha Cen A (G2V), B (K1V), and C (M6V); and B hosts an Earth-mass companion, albeit in a hot, lifeless orbit. For its part, Chandra has been keeping intent watch on the high-energy starspot cycles of AB, with semi-annual pointings over the past decade. Only HRC-I can separate AB as they plunge toward a close approach of 4" in 2016; and LETGS has countered that an abrupt 50x drop in XMM count rate of sun-like A in early 2005, ominously reported as the "darkening of the solar twin," simply is a soft sensitivity issue, not an unprecedented, inexplicable case of corona interrupta.

  18. Automatically processed alpha-track radon monitor

    DOEpatents

    Langner, G.H. Jr.

    1993-01-12

    An automatically processed alpha-track radon monitor is provided which includes a housing having an aperture allowing radon entry, and a filter that excludes the entry of radon daughters into the housing. A flexible track registration material is located within the housing that records alpha-particle emissions from the decay of radon and radon daughters inside the housing. The flexible track registration material is capable of being spliced such that the registration material from a plurality of monitors can be spliced into a single strip to facilitate automatic processing of the registration material from the plurality of monitors. A process for the automatic counting of radon registered by a radon monitor is also provided.

  19. Automatically processed alpha-track radon monitor

    DOEpatents

    Langner, Jr., G. Harold

    1993-01-01

    An automatically processed alpha-track radon monitor is provided which includes a housing having an aperture allowing radon entry, and a filter that excludes the entry of radon daughters into the housing. A flexible track registration material is located within the housing that records alpha-particle emissions from the decay of radon and radon daughters inside the housing. The flexible track registration material is capable of being spliced such that the registration material from a plurality of monitors can be spliced into a single strip to facilitate automatic processing of the registration material from the plurality of monitors. A process for the automatic counting of radon registered by a radon monitor is also provided.

  20. Automatically processed alpha-track radon monitor

    SciTech Connect

    Langner, G.H. Jr.

    1991-05-02

    An automatically processed alpha-track radon monitor is provided which includes a housing having an aperture allowing radon entry, and a filter that excludes the entry of radon daughters into the housing. A flexible track registration material is located within the housing that records alpha-particle emissions from the decay of radon and radon daughters inside the housing. The flexible track registration material is capable of being spliced such that the registration material from a plurality of monitors can be spliced into a single strip to facilitate automatic processing of the registration material from the plurality of monitors. A process for the automatic counting of radon registered by a radon monitor is also provided.

  1. Radioimmunotherapy with alpha-particle-emitting immunoconjugates

    SciTech Connect

    Macklis, R.M.; Kinsey, B.M.; Kassis, A.L.; Ferrara, J.L.M.; Atcher, R.W.; Hines, J.J.; Coleman, C.N.; Adelstein, S.J.; Burakoff, S.J.

    1988-05-20

    Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An ..cap alpha..-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2/sup +/ EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of (/sup 3/H)thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy. 18 references, 3 figures.

  2. Optical conductivity of alpha-Mn

    NASA Technical Reports Server (NTRS)

    Scoles, K. J.; Christy, R. W.

    1982-01-01

    The optical constants were measured at room temperature in the photon-energy range 0.6 to 6.5 eV on evaporated thin films. Evaporation conditions were chosen that gave the alpha-Mn crystal structure with reasonably large grains. The optical conductivity was separated into intraband and interband contributions by fitting to the Drude formula at low energies. The results are anomalous in comparison to other 3d transition metals. The free-electron lifetime is exceptionally sort (in agreement with the large dc resistivity of Mn), and the interband transitions seem unusually weak at the lower energies. Possible explanations related to the complicated crystal structure of alpha-Mn are discussed.

  3. Bakers' asthma caused by alpha amylase.

    PubMed

    Valdivieso, R; Subiza, J; Subiza, J L; Hinojosa, M; de Carlos, E; Subiza, E

    1994-10-01

    Two bakers with bronchial asthma and two with rhinoconjunctivitis are described. Prick and RAST tests were positive with wheat flour in all of them, but the challenge test (nasal or bronchial) with wheat flour extract was positive only in one asthmatic baker. The prick test, RAST, and nasal or bronchial challenge done with alpha amylase extract (a glycolytic enzyme obtained from Aspergillus oryzae and used as a flour additive) were positive in all four patients. Our results support previous data indicating that alpha amylase used in bakeries is an important antigen that could cause respiratory allergy in bakers. It can function as sole causative allergen or in addition with other allergens used in the baking industry.

  4. The Alpha Magnetic Spectrometer Silicon Tracker

    NASA Astrophysics Data System (ADS)

    Burger, W. J.

    1999-10-01

    The Alpha Magnetic Spectrometer (AMS) is designed as a independent module for installation on the International Space Station Alpha (ISSA) in the year 2002 for an operational period of three years. The principal scientific objectives are the searches for antimatter and dark matter in cosmic rays. The AMS uses 5.5m2 of silicon microstrip sensors to reconstruct charged particle trajectories in the field of a permanent magnet. The detector design and construction covered a 3yr period which terminated with a test flight on the NASA space shuttle Discovery during June 2-12, 1988. In this contribution, we describe the shuttle version of the AMS silicon tracker, including preliminary results of the tracker performance during the flight.

  5. Project Longshot: A mission to Alpha Centauri

    NASA Technical Reports Server (NTRS)

    West, Curtis; Chamberlain, Sally; Pagan, Neftali; Stevens, Robert

    1989-01-01

    Project Longshot, an exercise in the Advanced Design Program for Space, had as its destination Alpha Centauri, the closest star system to our own solar system. Alpha Centauri, a trinary star system, is 4.34 light years from earth. Although Project Longshot is impossible based on existing technologies, areas that require further investigation in order to make this feat possible are identified. Three areas where advances in technology are needed are propulsion, data processing for autonomous command and control functions, and reliability. Propulsion, possibly by antimatter annihilation; navigation and navigation aids; reliable hardware and instruments; artificial intelligence to eliminate the need for command telemetry; laser communication; and a reliable, compact, and lightweight power system that converts energy efficiently and reliably present major challenges. Project Longshot promises exciting advances in science and technology and new information concerning the universe.

  6. Alpha ash transport and ash control

    SciTech Connect

    Miley, G.H.; Hu, S.C.; Varadarajan, V.

    1990-01-01

    This paper discusses: thermal {alpha}-particle transport is a crucial issue in ash buildup. The transport will determine if buildup prevents ignition and if external control is necessary. Due to uncertainties in the transport coefficients, 1-1/2-D sensitivity study of the influence on the fusion power density is done using the BALDUR code. The Baldur simulations with varying diffusion coefficients for ash plasma are performed. The results of ash transport in the presence of sawteeth and varying edge conditions are discussed. Also, the nature of the fishbone oscillation in the presence of two hot species consisting of hot alphas and beam injected ions is discussed. The sawteeth and fishbones can be potential mechanisms for enhanced ash transport; the latter will indirectly influence the ash transport.

  7. Celecoxib inhibits growth of human autosomal dominant polycystic kidney cyst-lining epithelial cells through the VEGF/Raf/MAPK/ERK signaling pathway.

    PubMed

    Xu, Tao; Wang, Nian-Song; Fu, Li-Li; Ye, Chao-Yang; Yu, Sheng-Qiang; Mei, Chang-Lin

    2012-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a progressive chronic kidney disease. To date there are no effective medicines to halt development and growth of cysts. In the present study, we explored novel effects of celecoxib (CXB), a COX-2 specific inhibitor, on primary cultures of human ADPKD cyst-lining epithelial cells. Primary cultures of ADPKD cyst-lining epithelial cells were obtained from five patients. Effects of CXB were measured by various assays to detect BrdU incorporation, apoptosis and proliferation in vitro. Additionally, effects of CXB on kidney weight, the cyst index, the fibrosis index, blood urea nitrogen (BUN), serum creatinine (SCr), serum 6-keto-PGF-1α, serum thromboxane-2 (TXB2) and renal PCNA expression were assessed in Han:SPRD rat, a well-characterized rodent model of PKD. CXB inhibited proliferation of ADPKD cyst-lining epithelial cells, blocked the release of VEGF from the cells and induced extensive apoptosis in a time- and dose-dependent manner. Moreover, CXB up-regulated the cell cycle negative regulator p21(CIP/WAF1) and the cell cycle positive regulator Cyclin A, blocked ERK1/2 phosphorylation, induced apoptotic factors (Bax and caspase-3) and reduced Bcl-2. Furthermore, CXB inhibited the expression of VEGFR-2 and Raf-1 in ADPKD cyst-lining epithelial cells. CXB markedly reduced the cyst index, the fibrosis index, leukocyte infiltration, BUN, SCr, serum 6-keto-PGF-1α, TXB2 and renal PCNA expression in Han:SPRD rat. We demonstrated for the first time that CXB could suppress renal cyst-lining growth both in vitro and in vivo in Han:SPRD rat. CXB can inhibit proliferation, suppress cell cycle progression, and induce apoptosis in ADPKD cyst-lining epithelial cells through the inhibition of the VEGF/VEGFR-2/Raf-1/MAPK/ERK signaling pathway.

  8. SUPPRESSION OF THE NITRIC OXIDE PATHWAY IN METASTATIC RENAL CELL CARCINOMA PATIENTS RECEIVING VEGF-SIGNALING INHIBITORS

    PubMed Central

    Robinson, Emily S.; Khankin, Eliyahu V.; Choueiri, Toni K.; Dhawan, Mallika D.; Rogers, Miranda J.; Karumanchi, S. Ananth; Humphreys, Benjamin D.

    2010-01-01

    Therapies that target the vascular endothelial growth factor (VEGF) pathway cause hypertension but the mechanism remains unknown. This cross-sectional study tested the hypothesis that VEGF inhibition causes hypertension by suppressing VEGF-mediated vasodilatory pathways. Urine was collected from 80 patients with metastatic renal cell carcinoma from 2002–2009, 40 at baseline and 40 while on VEGF inhibitors. Measured urinary biomarkers include albumin, metabolites of the nitric oxide pathway and its downstream effector, cGMP, and prostaglandin pathway biomarkers prostaglandin E2, 6-keto PGF 1α, and cAMP, all normalized to urinary creatinine. The mean age in both groups was 61.8 years, 76% were male, and urinary albumin was higher in patients receiving VEGF inhibitors (median 18.4mg/g vs. 4.6 mg/g; p=0.009). cGMP/Cr was suppressed in patients on VEGF inhibitors (0.28 pmol/ug vs. 0.39 pmol/ug; p=0.01), with a trend toward suppression of nitrate/Cr (0.46 umol/mg vs. 0.62 umol/mg; p=0.09). Both comparisons were strengthened when patients on bevacizumab were excluded and only those receiving small molecule tyrosine kinase inhibitors were analyzed (cGMP/Cr, p=0.003; Nitrate/Cr, p=0.01). Prostaglandin E2, 6-keto PGF1α, and cAMP did not differ between groups. These results suggest that hypertension induced by VEGF inhibitors is mediated by suppression of nitric oxide production. Prospective studies are needed to explore whether these biomarkers may be useful predictors of efficacy in patients receiving VEGF-targeted therapies. PMID:20956731

  9. Assessment of oxidative stress markers and prostaglandins after chronic training of triathletes.

    PubMed

    Medina, Sonia; Domínguez-Perles, Raul; Cejuela-Anta, Roberto; Villaño, Débora; Martínez-Sanz, José M; Gil, Pilar; García-Viguera, Cristina; Ferreres, Federico; Gil, José I; Gil-Izquierdo, Angel

    2012-12-01

    The present study established the pattern of isoprostanes (IsoPs) and prostaglandins metabolites (PGMs) in urine after triathlon training. Fifteen Caucasian triathletes - 5 women and 10 men - performed 793 and 1603 Objective Load Scales, respectively. The optimization of urine hydrolysis conditions, concerning to the type of buffer, the units of hydrolytic enzyme added, and the pH, allowed precise quantification of these metabolites by UPLC-MS/MS, avoiding the under-estimation of their concentrations that occurred in previous studies. Their rate of conjugation ranged between 36% and 100%. This implies significant importance since it supposes non-detection of some IsoPs and PGMs totally conjugated with glucuronic acid developed by other previous methodologies. Among the 13 compounds analyzed, this assay detected and characterized 4 IsoPs and 3 PGMs in the triathletes' urine. The PGMs tetranor-PGEM and 11β-PGF(2α) and the IsoP 8-iso-PGF(2α), showed lower concentrations after the training program, whereas the PGMs 6-keto-PGF(1α) increased (vascular PGI(2) metabolite). In fact, their pattern in the triathletes' urine indicated that their variation may have been related with the physical activity. Due to its high variation, 6-keto PGF(1α) stood out as a useful marker of the vasodilation and inhibition of the platelet aggregation of the PGI(2) linked to the physical exercise. The data obtained provided a global picture of changes in lipid peroxidation and vascular events as a consequence of chronic exercise.

  10. Potential protective effects of Clostridium butyricum on experimental gastric ulcers in mice

    PubMed Central

    Wang, Fang-Yan; Liu, Jia-Ming; Luo, Hai-Hua; Liu, Ai-Hua; Jiang, Yong

    2015-01-01

    AIM: To investigate the effects of Clostridium butyricum (C. butyricum) on experimental gastric ulcers (GUs) induced by alcohol, restraint cold stress, or pyloric ligation in mice, respectively. METHODS: One hundred and twenty mice were randomly allocated into three types of gastric ulcer models (n = 40 each), induced by alcohol, restraint cold stress, or pyloric ligation. In each GU model, 40 mice were allocated into four groups (n = 10 each): the sham control group; model group (GU induction without pretreatment); C. butyricum group (GU induction with C. butyricum pretreatment); and Omeprazole group (GU induction with Omeprazole pretreatment). The effects of C. butyricum were evaluated by examining the histological changes in the gastric mucosal erosion area, the activities of superoxide dismutase (SOD) and catalase (CAT), the level of malondialdehyde (MDA), and the contents of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, leukotriene B4 (LTB4) and 6-keto-PGF-1α (degradation product of PGI2) in the gastric tissue. RESULTS: Our data showed that C. butyricum significantly reduced the gastric mucosal injury area and ameliorated the pathological conditions of the gastric mucosa. C. butyricum not only minimized the decreases in activity of SOD and CAT, but also reduced the level of MDA in all three GU models used in this study. The accumulation of IL1-β, TNF-α and LBT4 decreased, while 6-keto-PGF-1α increased with pretreatment by C. butyricum in all three GU models. CONCLUSION: Our data demonstrated the protective effects of pretreatment with C. butyricum on anti-oxidation and anti-inflammation in different types of GU models in mice. Further studies are needed to explore its potential clinical benefits. PMID:26217085

  11. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages

    PubMed Central

    Rossi, A; Pergola, C; Koeberle, A; Hoffmann, M; Dehm, F; Bramanti, P; Cuzzocrea, S; Werz, O; Sautebin, L

    2010-01-01

    BACKGROUND AND PURPOSE Zileuton is the only 5-lipoxygenase (5-LOX) inhibitor marketed as a treatment for asthma, and is often utilized as a selective tool to evaluate the role of 5-LOX and leukotrienes. The aim of this study was to investigate the effect of zileuton on prostaglandin (PG) production in vitro and in vivo. EXPERIMENTAL APPROACH Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 macrophages and human whole blood stimulated with LPS were used as in vitro models and rat carrageenan-induced pleurisy as an in vivo model. KEY RESULTS Zileuton suppressed PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. We found that zileuton significantly reduced PGE2 and 6-keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. This effect was not related to 5-LOX inhibition, because it was also observed in macrophages from 5-LOX knockout mice. Notably, zileuton inhibited PGE2 production in LPS-stimulated human whole blood and suppressed PGE2 and 6-keto PGF1α pleural levels in rat carrageenan-induced pleurisy. Interestingly, zileuton failed to inhibit the activity of microsomal PGE2 synthase1 and of cyclooxygenase (COX)-2 and did not affect COX-2 expression. However, zileuton significantly decreased AA release in macrophages accompanied by inhibition of phospholipase A2 translocation to cellular membranes. CONCLUSIONS AND IMPLICATION Zileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed. PMID:20880396

  12. Proceedings, High-Precision $\\alpha_s$ Measurements from LHC to FCC-ee

    SciTech Connect

    d'Enterria, David; Skands, Peter Z.

    2015-01-01

    This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\\alpha_s(m_Z)$ = 0.1177 $\\pm$ 0.0013, is about 1\\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.

  13. Tumour necrosis factor-alpha (TNF-alpha) in patients who have asbestosis and develop cancer.

    PubMed Central

    Partanen, R; Koskinen, H; Hemminki, K

    1995-01-01

    OBJECTIVES--Concentrations of tumour necrosis factor-alpha (TNF-alpha) were assayed by radioimmunoassay in serum samples collected between 1981 and 1987 from 111 patients with asbestosis who were at a high risk of cancer. Follow up of these patients until 1993 showed that 38 had developed cancer (27 lung, three mesotheliomas, and eight diverse malignancies). RESULTS--The mean serum concentrations of TNF-alpha given in fmol/100 microliters serum in all the cases with cancer (14.1) and the cases with lung cancer (13.6) were significantly higher (P < 0.05) than the mean concentrations in the exposed controls (10.5). A positive increase was considered to be any value that was > 2 SDs above the mean of the exposed controls. 22% (six of 27) of the cases with lung cancer were positive compared with 4% (three of 73) of the exposed controls, a significant difference (P < 0.001). The serum concentrations of TNF-alpha correlated moderately with cancer (r = 0.3), lung cancer (r = 0.3), and Neu oncoproteins and epidermal growth factor receptor (EGFR) (r = 0.3, 0.5 respectively). Also, there was a significant correlation between development of cancer and severity or progression of asbestosis. There was no correlation between the concentrations of TNF-alpha and severity or progression of asbestosis. CONCLUSIONS--These results showed high concentrations of TNF-alpha in the patients who had cancer. TNF-alpha may offer an auxiliary method in early diagnosis of cancers related to asbestosis. PMID:7795753

  14. Diamond detector for alpha-particle spectrometry.

    PubMed

    Dueñas, J A; de la Torre Pérez, J; Martín Sánchez, A; Martel, I

    2014-08-01

    An artificially grown high purity diamond was used as a detector for alpha-particle spectrometry. Diamond detectors can match the performance of silicon detectors employed in standard continuous air monitoring systems. Its radiation hardness and electronic properties make them ideal to work under extreme condition such as high temperature and ambient lights. A 50 μm thickness single-crystal diamond detector has been compared with a 300 μm passivated implanted planar silicon detector, under ambient conditions.

  15. Lyman Alpha Photochemistry in the Solar Nebula

    NASA Technical Reports Server (NTRS)

    Fegley, Bruce, Jr.

    1997-01-01

    The purpose of the project "Lyman Alpha Photochemistry in the Solar Nebula" was to model photochemistry in the primitive solar nebula and the early solar systems. As part of the modeling, it was necessary to model the composition of the gas and dust accreted by the solar nebula. This final report contains a list of publications where the results of this project have been published.

  16. First Attempts at Antihydrogen Trapping in ALPHA

    SciTech Connect

    Andresen, G. B.; Bowe, P. D.; Hangst, J. S.; Bertsche, W.; Butler, E.; Charlton, M.; Humphries, A. J.; Jenkins, M. J.; Joergensen, L. V.; Madsen, N.; Werf, D. P. van der; Bray, C. C.; Chapman, S.; Fajans, J.; Povilus, A.; Wurtele, J. S.; Cesar, C. L.; Lambo, R.; Silveira, D. M.; Fujiwara, M. C.

    2008-08-08

    The ALPHA apparatus is designed to produce and trap antihydrogen atoms. The device comprises a multifunction Penning trap and a superconducting, neutral atom trap having a minimum-B configuration. The atom trap features an octupole magnet for transverse confinement and solenoidal mirror coils for longitudinal confinement. The magnetic trap employs a fast shutdown system to maximize the probability of detecting the annihilation of released antihydrogen. In this article we describe the first attempts to observe antihydrogen trapping.

  17. Adriamycin cardiotoxicity amelioration by alpha-tocopherol.

    PubMed

    Krivit, W

    1979-01-01

    Adriamycin has become a potent member of the cancer chemotherapeutic program. However, the full utilization of adriamycin is limited by its cardiotoxicity. In experimental animals, alpha-tocopherol has been shown by some to ameliorate or prevent cardiac dysfunction without impairing antitumor effectiveness. During adriamycin therapy, future clinical research should consist of biochemical measurements of vitamin E in plasma, lipoperoxidation in red cells and platelets, while cars to indicate deficiency, should be considered as one method of ameliorating toxicity.

  18. TGF-Alpha Expression During Breast Tumorigenesis

    DTIC Science & Technology

    1999-07-01

    constant during progression from benign to invasive disease . EGFR expression, however, was increased during the early hyperplastic phase of tumor progression...that TGFa was uniquely mitogenic. (200 words) 14. SUBJECT TERMS Breast Cancer 15. NUMBER OF PAGES oncogene pre-invasive breast disease 54 TGF-alpha...suggests EGFR is an important early event in the progression towards invasive disease . 7. Examine tissue as above for proliferation, estrogen

  19. Conformational restriction through C alpha i <--> C alpha i cyclization: Ac12c, the largest cycloaliphatic C alpha,alpha- disubstituted glycine known.

    PubMed

    Saviano, M; Iacovino, R; Menchise, V; Benedetti, E; Bonora, G M; Gatos, M; Graci, L; Formaggio, F; Crisma, M; Toniolo, C

    2000-02-01

    Two complete series of N-protected, monodispersed oligopeptide esters to the pentamer level from 1-aminocyclododecane-1-carboxylic acid (Ac(12)c), an alpha-amino acid conformationally constrained through C(alpha)(i) <--> C(alpha)(i) cyclization, and either L-Ala or Aib residues, along with the N-protected Ac(12)c homopeptide alkylamide series from monomer to trimer, have been synthesized by solution methods and fully characterized. The solution-preferred conformations of these peptides have been assessed by Fourier transform ir absorption and (1)H-nmr techniques. Moreover, the molecular structures of one derivative (Z-Ac(12)c-OH) and three peptides [the tripeptide ester Z-L-Ala-Ac(12)c-L-Ala-OMe, the tripeptide alkylamide Z-(Ac(12)c)(3)-NHiPr, and the tetrapeptide ester Z-(Aib)(2)-Ac(12)c-Aib-OtBu (Aib, alpha-aminoisobutyric acid)] have been determined in the crystal state by x-ray diffraction. The results obtained point to the conclusion that beta-bends and 3(10)-helices are preferentially adopted by peptides based on Ac(12)c, the largest cycloaliphatic C-disubstituted glycine known. A comparison with the structural tendencies extracted from published works on peptides from Aib, the prototype of C-disubstituted glycines, and the other extensively studied members of the class of 1-aminocycloalkane-1-carboxylic acids (Ac(n) c, with n = 3-9), is made and the implications for the use of the Ac(12)c residue in the Ac(n) c scan approach of conformationally restricted analogues of bioactive peptides are briefly discussed.

  20. Fourth High Alpha Conference, volume 1

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The goal of the Fourth High Alpha Conference was to focus on the flight validation of high angle-of-attack technologies and provide an in-depth review of the latest high angle-of-attack activities. Areas that were covered include: high angle-of-attack aerodynamics, propulsion and inlet dynamics, thrust vectoring, control laws and handling qualities, tactical utility, and forebody controls.

  1. Fourth High Alpha Conference, volume 2

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The goal of the Fourth High Alpha Conference, held at the NASA Dryden Flight Research Center on July 12-14, 1994, was to focus on the flight validation of high angle of attack technologies and provide an in-depth review of the latest high angle of attack activities. Areas that were covered include high angle of attack aerodynamics, propulsion and inlet dynamics, thrust vectoring, control laws and handling qualities, and tactical utility.

  2. Dephosphorylation of alpha(s)- and beta-caseins and its effect on chaperone activity: a structural and functional investigation.

    PubMed

    Koudelka, Tomas; Hoffmann, Peter; Carver, John A

    2009-07-08

    Milk casein proteins can act as molecular chaperones: under conditions of stress, such as elevated temperature, molecular chaperones stabilize proteins from unfolding, aggregating, and precipitating. In this study, alpha(s)- and beta-caseins were dephosphorylated using alkaline phosphatase. A structural and functional investigation was undertaken to determine the effect of dephosphorylation on the chaperone activity of alpha(s)- and beta-caseins against two types of protein misfolding, i.e., amorphous aggregation and amyloid fibril assembly. The dephosphorylation of alpha(s)- and beta-caseins resulted in a decrease in the chaperone efficiency against both heat- and reduction-induced amorphously aggregating target proteins. In contrast, dephosphorylation had no effect on the chaperone activity of alpha(s)- and beta-caseins against the amyloid-forming target protein kappa-casein. Circular dichroism and fluorescence spectroscopic data indicated that the loss of negative charge associated with dephosphorylation led to an increase in ordered structure of alpha(s)- and beta-caseins. It is concluded that the flexible, dynamic, and relatively unstructured and amphiphatic nature of alpha(s)- and beta-caseins is important in their chaperone action.

  3. Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal cells of ischemic myocardium.

    PubMed

    Jürgensen, Jan Steffen; Rosenberger, Christian; Wiesener, Michael S; Warnecke, Christina; Hörstrup, Jan H; Gräfe, Michael; Philipp, Sebastian; Griethe, Wanja; Maxwell, Patrick H; Frei, Ulrich; Bachmann, Sebastian; Willenbrock, Roland; Eckardt, Kai-Uwe

    2004-09-01

    Hypoxia-inducible factor (HIF)-1alpha and -2alpha are key regulators of the transcriptional response to hypoxia and pivotal in mediating the consequences of many disease states. In the present work, we define their temporo-spatial accumulation after myocardial infarction and systemic hypoxia. Rats were exposed to hypoxia or underwent coronary artery ligation. Immunohistochemistry was used for detection of HIF-1alpha and -2alpha proteins and target genes, and mRNA levels were determined by RNase protection. Marked nuclear accumulation of HIF-1alpha and -2alpha occurred after both systemic hypoxia and coronary ligation in cardiomyocytes as well as interstitial and endothelial cells (EC) without pronounced changes in HIF mRNA levels. While systemic hypoxia led to widespread induction of HIF, expression after coronary occlusion occurred primarily at the border of infarcted tissue. This expression persisted for 4 wk, included infiltrating macrophages, and colocalized with target gene expression. Subsets of cells simultaneously expressed both HIF-alpha subunits, but EC more frequently induced HIF-2alpha. A progressive increase of HIF-2alpha but not HIF-1alpha occurred in areas remote from the infarct, including the interventricular septum. Cardiomyocytes and cardiac stromal cells exhibit a marked potential for a prolonged transcriptional response to ischemia mediated by HIF. The induction of HIF-1alpha and -2alpha appears to be complementary rather than solely redundant.

  4. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

    PubMed

    Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

    2015-01-01

    The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants.

  5. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

    PubMed

    Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

    2007-09-01

    Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

  6. Lunar Surface Outgassing and Alpha Particle Measurements

    NASA Astrophysics Data System (ADS)

    Lawson, S. L.; Feldman, W. C.; Lawrence, D. J.; Moore, K. R.; Elphic, R. C.; Maurice, S.; Belian, R. D.; Binder, A. B.

    2002-01-01

    The Lunar Prospector Alpha Particle Spectrometer (LP APS) searched for lunar surface gas release events and mapped their distribution by detecting alpha particles produced by the decay of gaseous radon-222 (5.5 MeV, 3.8 day half-life), solid polonium-218 (6.0 MeV, 3 minute half-life), and solid polonium-210 (5.3 MeV, 138 day half-life, but held up in production by the 21 year half-life of lead-210). These three nuclides are radioactive daughters from the decay of uranium-238. Radon reaches the lunar surface either at areas of high soil porosity or where fissures release the trapped gases in which radon is entrained. Once released, the radon spreads out by "bouncing" across the surface on ballistic trajectories in a randomwalk process. The half-life of radon-222 allows the gas to spread out by several 100 km before it decays (depositing approximately half of the polonium-218 recoil nuclides on the lunar surface) and allows the APS to detect gas release events up to several days after they occur. The long residence time of the lead-210 precursor to polonium-210 allows the mapping of gas vents which have been active over the last approximately 60 years. Because radon and polonium are daughter products of the decay of uranium, the background level of alpha particle activity is a function of the lunar crustal uranium distribution.

  7. Alpha Background Rejection in Bolometer Detectors

    NASA Astrophysics Data System (ADS)

    Deporzio, Nicholas; Cuore Collaboration

    This study presents the modification of bolometer detectors used in particle searches to veto or otherwise reject alpha radiation background and the statistical advantages of doing so. Several techniques are presented in detail - plastic film scintillator vetoes, metallic film ionization vetoes, and Cherenkov radiation vetoes. Plastic scintillator films are cooled to bolometer temperatures and bombarded with 1.4MeV to 6.0MeV alpha particles representative of documented detector background. Quantum dot based liquid scintillator is similarly bombarded to produce a background induced scintillation light. Photomultipliers detect this scintillation light and produce a veto signal. Layered metallic films of a primary metal, dielectric, and secondary metal, such as gold-polyethylene-gold films, are cooled to milli-kelvin temperatures and biased to produce a current signal veto when incident 1.4MeV to 6.0MeV alpha particles ionize conduction paths through the film. Calibration of veto signal to background energy is presented. These findings are extrapolated to quantify the statistical impact of such modifications to bolometer searches. Effects of these techniques on experiment duration and signal-background ratio are discussed.

  8. The Alpha Dynamo Effects in Laboratory Plasmas

    SciTech Connect

    Hantao Ji; Stewart C. Prager

    2001-10-16

    A concise review of observations of the alpha dynamo effect in laboratory plasmas is given. Unlike many astrophysical systems, the laboratory pinch plasmas are driven magnetically. When the system is overdriven, the resultant instabilities cause magnetic and flow fields to fluctuate, and their correlation induces electromotive forces along the mean magnetic field. This alpha-effect drives mean parallel electric current, which, in turn, modifies the initial background mean magnetic structure towards the stable regime. This drive-and-relax cycle, or the so-called self-organization process, happens in magnetized plasmas in a timescale much shorter than resistive diffusion time, thus it is a fast and unquenched dynamo process. The observed alpha-effect redistributes magnetic helicity (a measure of twistedness and knottedness of magnetic field lines) but conserves its total value. It can be shown that fast and unquenched dynamos are natural consequences of a driven system where fluctuations are statistically either not stationary in time or not homogeneous in space, or both. Implications to astrophysical phenomena will be discussed.

  9. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    PubMed

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  10. Detection of alpha radiation in a beta radiation field

    DOEpatents

    Mohagheghi, Amir H.; Reese, Robert P.

    2001-01-01

    An apparatus and method for detecting alpha particles in the presence of high activities of beta particles utilizing an alpha spectrometer. The apparatus of the present invention utilizes a magnetic field applied around the sample in an alpha spectrometer to deflect the beta particles from the sample prior to reaching the detector, thus permitting detection of low concentrations of alpha particles. In the method of the invention, the strength of magnetic field required to adequately deflect the beta particles and permit alpha particle detection is given by an algorithm that controls the field strength as a function of sample beta energy and the distance of the sample to the detector.

  11. Phenylpiperazinylalkylamino substituted pyridazinones as potent alpha(1) adrenoceptor antagonists.

    PubMed

    Barlocco, D; Cignarella, G; Piaz, V D; Giovannoni, M P; De Benedetti, P G; Fanelli, F; Montesano, F; Poggesi, E; Leonardi, A

    2001-07-19

    QSAR models have been used for designing a series of compounds characterized by a N-phenylpiperazinylalkylamino moiety linked to substituted pyridazinones, which have been synthesized. Measurements of the binding affinities of the new compounds toward the alpha(1a)-, alpha(1b)-, and alpha(1d)-AR cloned subtypes as well as the 5-HT(1A) receptor have been done validating, at least in part, the estimations of the theoretical models. This study provides insight into the structure activity relationships of the alpha(1)-ARs ligands and their alpha(1)-AR/5-HT(1A) selectivity.

  12. Alpha-synuclein propagation: New insights from animal models.

    PubMed

    Dehay, Benjamin; Vila, Miquel; Bezard, Erwan; Brundin, Patrik; Kordower, Jeffrey H

    2016-02-01

    Aggregation of alpha-synuclein is implicated in several neurodegenerative diseases collectively termed synucleinopathies. Emerging evidence strongly implicates cell-to-cell transmission of misfolded alpha-synuclein as a common pathogenetic mechanism in synucleinopathies. The impact of alpha-synuclein pathology on neuronal dysfunction and behavioral impairments is being explored in animal models. This review provides an update on how research in animal models supports the concept that misfolded alpha-synuclein spreads from cell to cell and describes how findings in animal models might relate to the disease process in humans. Finally, we discuss the current underlying molecular and cellular mechanisms and future therapeutic strategies targeting alpha-synuclein propagation.

  13. Secretion of laminin alpha 2 chain in cerebrospinal fluid.

    PubMed

    Yamada, H; Hori, H; Tanaka, T; Fujita, S; Fukuta-Ohi, H; Hojo, S; Tamura, A; Shimizu, T; Matsumura, K

    1995-11-27

    The absence of laminin alpha 2 chain causes muscle cell degeneration and peripheral dysmyelination in congenital muscular dystrophy patients and dy mice, suggesting its role in the maintenance of sarcolemmal architecture and peripheral myelinogenesis. Here we demonstrate the secretion of laminin alpha 2 chain in cerebrospinal fluid (CSF). Laminin alpha 2 chain was detected as a minor component of the total CSF proteins or glycoproteins. Laminin alpha 2 chain was localized in the cytoplasm of epithelial cells of choroid plexus, suggesting active secretion. Our results suggest that immunochemical analysis of CSF laminin alpha 2 chain could be useful as an aid for the diagnosis of congenital muscular dystrophy.

  14. High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

    PubMed Central

    Rivera, M T; Marques de Araujo, S; Lucas, R; Deman, J; Truyens, C; Defresne, M P; de Baetselier, P; Carlier, Y

    1995-01-01

    Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto-maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically infected mice displayed significantly higher levels of circulating TNF-alpha than animals either only infected or only pregnant. TNF-alpha was undetectable in sera of uninfected and nonpregnant mice as well as in breast milk obtained from infected and uninfected animals. Fetuses from infected mice exhibited significantly more cells containing TNF-alpha mRNA in their thymus than fetuses from uninfected mothers. When infected 2 months after birth, offspring born to infected and uninfected mothers displayed similar amounts of circulating TNF-alpha during chronic infection, whereas this cytokine was only weakly detectable during the acute phase of the disease. An intravenous injection of lipopolysaccharide during acute infection strongly increased the production of TNF-alpha in offspring born to infected mothers to levels higher than those in progeny from uninfected mice. These results suggest that TNF-alpha is an important cytokine in the feto-maternal relationship during T. cruzi infection and that fetuses and offspring of infected mothers are primed to produce elevated levels of TNF-alpha. PMID:7822027

  15. Bioisosteric phentolamine analogs as potent alpha-adrenergic antagonists.

    PubMed

    Hong, Seoung-Soo; Bavadekar, Supriya A; Lee, Sang-Il; Patil, Popat N; Lalchandani, S G; Feller, Dennis R; Miller, Duane D

    2005-11-01

    The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described. Replacement of the carbon next to the imidazoline ring of phentolamine with a nitrogen atom provides compounds (2, 3) that are about 1.6 times and 4.1 times more potent functionally than phentolamine on rat alpha1-adrenergic receptors, respectively. In receptor binding assays, the affinities of phentolamine and its bioisosteric analogs were determined on the human embryonic kidney (HEK) and Chinese Hamster ovary (CHO) cell lines expressing the human alpha1- and alpha2-AR subtypes, respectively. Analogs 2 and 3, both, displayed higher binding affinities at the alpha2- versus the alpha1-ARs, affinities being the least at the alpha1B-AR. Binding affinities of the methoxy ether analog 2 were greater than those of the phenolic analog 3 at all six alpha-AR subtypes. One of the nitrogen atoms in the imidazoline ring of phentolamine was replaced with an oxygen atom to give compounds 4 and 5, resulting in a 2-substituted oxazoline ring. The low functional antagonist activity on rat aorta, and binding potencies of these two compounds on human alpha1A- and alpha2A-AR subtypes indicate that a basic functional group is important for optimum binding to the alpha1- and alpha2A-adrenergic receptors.

  16. Isolation and characterization of the human Gs alpha gene.

    PubMed Central

    Kozasa, T; Itoh, H; Tsukamoto, T; Kaziro, Y

    1988-01-01

    The gene for Gs alpha (the alpha subunit of the guanine nucleotide-binding protein Gs) was isolated from human genomic libraries using rat Gs alpha cDNA as a probe. Comparison of the nucleotide sequence of the human gene with that of the rat cDNA revealed that the human Gs alpha gene spans approximately equal to 20 kilobases and is composed of 13 exons and 12 introns. Genomic Southern blot analysis suggests that the human haploid genome contains a single Gs alpha gene. Previous reports indicated the presence of multiple species of Gs alpha cDNA. The structure of the human Gs alpha gene suggests that four types of Gs alpha mRNAs may be generated from a single Gs alpha gene by alternate use of exon 3 and/or of two 3' splice sites of intron 3, where an unusual splice junction sequence (TG) instead of the consensus (AG) is used. S1 nuclease mapping analysis of human Gs alpha mRNA identified multiple transcriptional initiation sites. The promoter region of the human Gs alpha gene has extremely high G + C content (85%). It contains 4 "GC" boxes, but no typical "TATA" or "CAAT" box sequence. In the 5' flanking region, there are several blocks of sequences that are similar to the sequences of the 5' flanking region of the human c-Ki-ras2 gene. Images PMID:3127824

  17. Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes.

    PubMed

    Auffray, C; Lillie, J W; Arnot, D; Grossberger, D; Kappes, D; Strominger, J L

    DNA sequences of four human class II histocompatibility antigen alpha chain DNA sequences (derived from cDNA and genomic clones representing DC1 alpha, DC4 alpha, DX alpha and SB alpha) are presented and compared to DR alpha and to mouse I-A alpha and I-E alpha sequences. These data suggest possible mechanisms for the generation of polymorphism and the evolution of the DR, DC and SB families.

  18. Ozone inactivation of human alpha 1-proteinase inhibitor

    SciTech Connect

    Johnson, D.A.

    1980-06-01

    Ozone decreased the trypsin, chymotrypsin, and elastase inhibitory activities of human alpha 1-proteinase inhibitor both in plasma and in solutions of the pure inhibitor. The total loss of porcine elastase inhibitory activity required 18 mol of ozone/mol of pure alpha 1-PI and approximately 850 mol of ozone/mol of alpha 1-PI in plasma. A corresponding loss of the ability to inhibit human leukocyte elastase was observed. Inactivated alpha 1-PI contains four residues of methionine sulfoxide, in addition to oxidized tryosine and tryptophan. Electrophoretic analysis demonstrated that the ozone-inactivated alpha 1-PI did not form normal complexes with serine proteinases. These findings suggest that the inhalation of ozone could inactivate alpha 1-PI on the airspace side of the lung to create a localized alpha 1-PI deficiency, which might contribute to the development of emphysema.

  19. Modulating alpha-actinin-4 dynamics in podocytes.

    PubMed

    Michaud, Jean-Louis R; Hosseini-Abardeh, Mona; Farah, Kevin; Kennedy, Chris R J

    2009-03-01

    Podocytes are epithelial cells that line the outer aspect of renal blood vessels and provide a platform for the kidney's filtering apparatus, the slit diaphragm. Mutations in alpha-actinin-4, an actin bundling protein highly expressed in podocytes, result in increased affinity for actin and cause a familial form of focal segmental glomerulosclerosis. We hypothesized that such gain-of-affinity mutations would override alpha-actinin-4's sensitivity to regulatory factors such as calcium (acting via two EF-hand motifs), and phosphoinositides. We generated calcium- (mutEF) and phosphoinositide- (mutPI) insensitive variants of alpha-actinin-4, comparing their properties to a disease-associated mutant (K256E) and to the wildtype (wt) protein. alpha-Actinin-4(mutPI) displayed increased affinity for actin, while the affinity of alpha-actinin-4(mutEF) was unchanged. Addition of calcium to actin sedimentation assays caused a decrease in the association of alpha-actinin-4(wt) with filamentous actin, while phosphoinositides generally increased this association. Similar to alpha-actinin-4(K256E), alpha-actinin-4(mutPI) was mislocalized in cultured podocytes, being preferentially associated with filamentous actin and focal adhesions. Fluorescence recovery after photobleaching experiments revealed a rapid turnover of alpha-actinin-4(wt) and alpha-actinin-4(mutEF) along stress fibers and focal adhesions, while the turnover of alpha-actinin-4(K256E) and alpha-actinin-4(mutPI) was dramatically reduced at these subcellular locales. Equibiaxial mechanical stimulation of podocytes, a mimic of intraglomerular forces, reduced podocyte surface area by 50%; this decrease was more severe (70%) in the presence of high-affinity mutants of alpha-actinin-4. These data suggest that dynamic regulation of alpha-actinin-4/actin interactions may be necessary for maintaining podocyte structure in response to glomerular hydrostatic forces.

  20. Three new alpha-globin variants: Hb Itapira [alpha30(B11)Glu-->Val (alpha1)], Hb Bom Jesus Da Lapa [alpha30(B11)Glu-->Ala (alpha1)] and Hb Boa Esperança [alpha16(A14)Lys-->Thr (alpha2)].

    PubMed

    Jorge, Susan E Costa; Kimura, Elza M; Oliveira, Denise M; Ogo, Satie; Albuquerque, Dulcinéia M; Costa, Fernando F; Sonati, Maria de Fátima

    2007-01-01

    Three novel alpha-globin variants were found during a screening program for hemoglobinopathies in blood donors at the UNICAMP Hematology and Hemotherapy Center, Campinas, State of São Paulo, Southeastern Brazil. They were named for the town of origin of the carrier as Hb Itapira [alpha30(B11)Glu-->Val], Hb Bom Jesus da Lapa [alpha30(B11)Glu-->Ala] and Hb Boa Esperança [alpha16(A14)Lys-->Thr]. Hb Itapira, like Hb Bom Jesus da Lapa, shows an electrophoretic mobility similar to that of Hb S [beta6(A3)GluVal, GAG-->GTG] at alkaline pH; it is associated with a triplicate alpha-globin allele (alphaalphaalpha(anti 3.7)) and corresponds to only 5.5% of the total hemoglobin (Hb). Hb Boa Esperança, found in two different individuals, moves faster than Hb A and exhibits an abnormal functional performance.

  1. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells.

    PubMed

    Lempereur, Maëlle; Majewska, Claire; Brunquers, Amandine; Wongpramud, Sumalee; Valet, Bénédicte; Janssens, Philippe; Dillemans, Monique; Van Nedervelde, Laurence; Gallo, Dominique

    2016-01-01

    Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif.

  2. Producing a compound Nucleus via Inelastic Scattering: The 90Zr(alpha,alpha')90Zr* Case

    SciTech Connect

    Escher, J E; Dietrich, F S

    2008-05-23

    In a Surrogate reaction a compound nucleus is produced via a direct reaction (pickup, stripping, or inelastic scattering). For a proper application of the Surrogate approach it is necessary to predict the resulting angular momentum and parity distribution in the compound nucleus. A model for determining these distributions is developed for the case of inelastic alpha scattering off a spherical nucleus. The focus is on obtaining a first, simple description of the direct-reaction process that produces the compound nucleus and on providing the basis for a more complete treatment of the problem. The approximations employed in the present description are discussed and the extensions required for a more rigorous treatment of the problem are outlined. To illustrate the formalism, an application to {sup 90}Zr({alpha},{alpha}{prime}){sup 90}Zr* is presented.

  3. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

    PubMed Central

    Lempereur, Maëlle; Majewska, Claire; Brunquers, Amandine; Wongpramud, Sumalee; Valet, Bénédicte; Janssens, Philippe; Dillemans, Monique; Van Nedervelde, Laurence; Gallo, Dominique

    2016-01-01

    Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif. PMID:27190515

  4. Molecular cloning and expression analysis of sea bass (Dicentrarchus labrax L.) tumor necrosis factor-alpha (TNF-alpha).

    PubMed

    Nascimento, Diana S; Pereira, Pedro J B; Reis, Marta I R; do Vale, Ana; Zou, Jun; Silva, Manuel T; Secombes, Christopher J; dos Santos, Nuno M S

    2007-09-01

    In the search for pro-inflammatory genes in sea bass a TNF-alpha gene was cloned and sequenced. The sea bass TNF-alpha (sbTNF-alpha) putative protein conserves the TNF-alpha family signature, as well as the two cysteines usually involved in the formation of a disulfide bond. The mouse TNF-alpha Thr-Leu cleavage sequence and a potential transmembrane domain were also found, suggesting that sbTNF-alpha exists as two forms: a approximately 28 kDa membrane-bound form and a approximately 18.4 kDa soluble protein. The single copy sbTNF-alpha gene contains a four exon-three intron structure similar to other known TNF-alpha genes. Homology modeling of sbTNF-alpha is compatible with the trimeric quaternary architecture of its mammalian counterparts. SbTNF-alpha is constitutively expressed in several unstimulated tissues, and was not up-regulated in the spleen and head-kidney, in response to UV-killed Photobacterium damselae subsp. piscicida. However, an increase of sbTNF-alpha expression was detected in the head-kidney during an experimental infection using the same pathogen.

  5. p38 MAPK mediates renal tubular cell TNF-alpha production and TNF-alpha-dependent apoptosis during simulated ischemia.

    PubMed

    Meldrum, K K; Meldrum, D R; Hile, K L; Yerkes, E B; Ayala, A; Cain, M P; Rink, R C; Casale, A J; Kaefer, M A

    2001-08-01

    Ischemia causes renal tubular cell loss through apoptosis; however, the mechanisms of this process remain unclear. Using the renal tubular epithelial cell line LLC-PK(1), we developed a model of simulated ischemia (SI) to investigate the role of p38 MAPK (mitogen-activated protein kinase) in renal cell tumor necrosis factor-alpha (TNF-alpha) mRNA production, protein bioactivity, and apoptosis. Results demonstrate that 60 min of SI induced maximal TNF-alpha mRNA production and bioactivity. Furthermore, 60 min of ischemia induced renal tubular cell apoptosis at all substrate replacement time points examined, with peak apoptotic cell death occurring after either 24 or 48 h. p38 MAPK inhibition abolished TNF-alpha mRNA production and TNF-alpha bioactivity, and both p38 MAPK inhibition and TNF-alpha neutralization (anti-porcine TNF-alpha antibody) prevented apoptosis after 60 min of SI. These results constitute the initial demonstration that 1) renal tubular cells produce TNF-alpha mRNA and biologically active TNF-alpha and undergo apoptosis in response to SI, and 2) p38 MAPK mediates renal tubular cell TNF-alpha production and TNF-alpha-dependent apoptosis after SI.

  6. Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin Mmineral springs allele.

    PubMed Central

    Curiel, D T; Vogelmeier, C; Hubbard, R C; Stier, L E; Crystal, R G

    1990-01-01

    The Mmineral springs alpha 1-antitrypsin (alpha 1AT) allele, causing alpha 1AT deficiency and emphysema, is unique among the alpha 1AT-deficiency alleles in that it was observed in a black family, whereas most mutations causing alpha 1AT deficiency are confined to Caucasian populations of European descent. Immobilized pH gradient analysis of serum demonstrated that alpha 1AT Mmineral springs migrated cathodal to the normal M2 allele. Evaluation of Mmineral springs alpha 1AT as an inhibitor of neutrophil elastase, its natural substrate, demonstrated markedly lower than normal function. Characterization of the alpha 1AT Mmineral springs gene demonstrated that it differed from the common normal M1(Ala213) allele by a single-base substitution causing the amino acid substitution Gly-67 (GGG)----Glu-67 (GAG). Capitalizing on the fact that this mutation creates a polymorphism for the restriction endonuclease AvaII, family analysis demonstrated that the Mmineral springs alpha 1AT allele was transmitted in an autosomal-codominant fashion. Evaluation of genomic DNA showed that the index case was homozygous for the alpha 1AT Mmineral springs allele. Cytoplasmic blot analysis of blood monocytes of the Mmineral springs homozygote demonstrated levels of alpha 1AT mRNA transcripts comparable to those in cells of a normal M1 (Val213) homozygote control. Evaluation of in vitro translation of Mmineral springs alpha 1AT mRNA transcripts demonstrated a normal capacity to direct the translation of alpha 1AT. Evaluation of secretion of alpha 1AT by the blood monocytes by pulse-chase labeling with [35S]methionine, however, demonstrated less secretion by the Mmineral springs cells than normal cells. To characterize the posttranslational events causing the alpha 1AT-secretory defect associated with the alpha 1AT Mmineral springs gene, retroviral gene transfer was used to establish polyclonal populations of murine fibroblasts containing either a normal human M1 alpha 1AT cDNA or an Mmineral

  7. Autocatalytic tyrosine-phosphorylation of protein kinase CK2 alpha and alpha' subunits: implication of Tyr182.

    PubMed Central

    Donella-Deana, A; Cesaro, L; Sarno, S; Brunati, A M; Ruzzene, M; Pinna, L A

    2001-01-01

    CK2 is a pleiotropic and constitutively active serine/threonine protein kinase composed of two catalytic (alpha and/or alpha') and two regulatory beta-subunits, whose mechanism of modulation is still obscure. Here we show that CK2 alpha/alpha' subunits undergo intermolecular (trans) tyrosine-autophosphorylation, which is dependent on intrinsic catalytic activity and is suppressed by the individual mutation of Tyr182, a crucial residue of the activation loop, to phenylalanine. At variance with serine-autophosphorylation, tyrosine-autophosphorylation of CK2alpha is reversed by ADP and GDP and is counteracted by the beta-subunit and by a peptide reproducing the activation loop of CK2alpha/alpha' (amino acids 175-201). These results disclose new perspectives about the mode of regulation of CK2 catalytic subunits. PMID:11439109

  8. Far-Infrared and Millimeter Continuum Studies of K-Giants: Alpha Boo and Alpha Tau

    NASA Technical Reports Server (NTRS)

    Cohen, Martin; Carbon, Duane F.; Welch, William J.; Lim, Tanya; Forster, James R.; Goorvitch, David; Thigpen, William (Technical Monitor)

    2002-01-01

    We have imaged two normal, non-coronal, infrared-bright K-giants, alpha Boo and alpha Tau, in the 1.4-millimeter and 2.8-millimeter continuum using BIMA. These stars have been used as important absolute calibrators for several infrared satellites. Our goals are: (1) to probe the structure of their upper photospheres; (2) to establish whether these stars radiate as simple photospheres or possess long-wavelength chromospheres; and (3) to make a connection between millimeter-wave and far-infrared absolute flux calibrations. To accomplish these goals we also present ISO Long Wavelength Spectrometer (LWS) measurements of both these K-giants. The far-infrared and millimeter continuum radiation is produced in the vicinity of the temperature minimum in a Boo and a Tau, offering a direct test of the model photospheres and chromospheres for these two cool giants. We find that current photospheric models predict fluxes in reasonable agreement with those observed for those wavelengths which sample the upper photosphere, namely less than or equal to 170 micrometers in alpha Tau and less than or equal to 125 micrometers in alpha Boo. It is possible that alpha Tau is still radiative as far as 0.9 - 1.4 millimeters. We detect chromospheric radiation from both stars by 2.8 millimeters (by 1.4 millimeters in alpha Boo), and are able to establish useful bounds on the location of the temperature minimum. An attempt to interpret the chromospheric fluxes using the two-component "bifurcation model" proposed by Wiedemann et al. (1994) appears to lead to a significant contradiction.

  9. Li production in alpha-alpha reactions. [relation to gamma ray observation

    NASA Technical Reports Server (NTRS)

    Kozlovsky, B.; Ramaty, R.

    1974-01-01

    The cross section for Li-7 production in alpha-alpha reactions is shown to be increased by about a factor of 2 due to the excitation levels of Li-7 and Be-7 at 478 keV and 431 keV, respectively. The cross section for Li-6 production, however, remains the same as calculated on the basis of the detailed balance principle. The lines at 478 keV and 431 keV may link Li-7 production to feasible gamma-ray observations.

  10. {alpha}-cluster and {alpha}-binucleon states of 1p-shell nuclei

    SciTech Connect

    Wolsky, R.; Gnilozub, I. A.; Kurgalin, S. D.; Tchuvil'sky, Yu. M.

    2010-08-15

    States that exhibit the properties of an {alpha}-cluster or an {alpha}-binucleon condensate are studied in 1p-shell nuclei. The generalized Hamiltonian of the Elliott SU(3) model is used to classify these states and to calculate their spectra. The results of the calculations are found to be in good agreement with experimental data. States not observed so far in the cluster spectra of the {sup 12}C, {sup 16}O, {sup 10}Be, and {sup 12}Be nuclei are predicted.

  11. [Alpha 1-antitrypsin, alpha 2-macroglobulin and reactive protein C in gastric cancer].

    PubMed

    Dumitraşcu, D; Radu, D; Stanciu, L; Ioniţă, A; Petcovici, M

    1989-01-01

    Proteins of acute phase: alpha 1-antitrypsin (AAT), alpha 2-macroglobulin (AMG), reactive C protein (RCP) were determined in the serum of 50 patients with gastric cancer. The Mancini, simple radial immunodiffusion method was used (SRID). The concentration of these proteins increased at 32/50 (64%) for AAT; 30/50 (60%) for AMG and 33/50 (66%) for RCP. By cumulative evaluation, the positivity of serum markers increased to 88%. The importance of differential diagnosis with regard to the benign gastric lesions (adenoma, ulcer, segmentary fibrosis, before receiving the bioptic result, is emphasized.

  12. Synthesis and transformations of a pyrazole containing alpha, beta-didehydro-alpha-amino acid derivatives.

    PubMed

    Vranicar, L; Pozgan, F; Polanc, S; Kocevar, M

    2003-04-01

    2H-Pyran-2-ones 1 were transformed with various hydrazines into (E)- or (Z)-alpha, beta-didehydro-alpha-amino acid (DDAA) derivatives 4 (and 7) containing a highly substituted pyrazolyl moiety attached at the beta-position. With heterocyclic hydrazines, the products 4 were accompanied also by decarboxylated enamines E-6. In order to separate (E/Z)-mixtures of acids, they were transformed to the corresponding methyl esters 9 and 10 by the application of diazomethane. Catalytic hydrogenation under high pressures with Pd/C as a catalyst resulted in the formation of racemic alanine derivatives 11.

  13. Pharmacological profiles of a novel alpha 1-adrenoceptor agonist, PNO-49B, at alpha 1-adrenoceptor subtypes.

    PubMed

    Muramatsu, I; Ohmura, T; Kigoshi, S

    1995-01-01

    The effects of a newly synthesized compound, PNO-49B, (R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, on alpha 1-adrenoceptor subtypes were examined in various tissues in which the following distribution of alpha 1-adrenoceptor subtypes has been suggested: dog carotid artery (alpha 1B), dog mesenteric artery (alpha 1N), rabbit thoracic aorta (alpha 1B + alpha 1L), rat liver (alpha 1B), rat vas deferens (alpha 1A + alpha 1L), rat cerebral cortex (alpha 1A + alpha 1B) and rat thoracic aorta (controversial subtype). PNO-49B (0.1-100 microM) produced concentration-dependent contractions in dog mesenteric artery, rabbit thoracic aorta, rat thoracic aorta and rat vas deferens; and the maximal amplitudes of contraction were almost the same as or slightly less than those of noradrenaline. By contrast, the maximal response to PNO-49B in dog carotid artery was markedly smaller than the response to noradrenaline. In rabbit thoracic aorta, the contractile response to PNO-49B was not affected by inactivation of the alpha 1B subtype with chloroethylclonidine (CEC), although the response to noradrenaline was attenuated by that treatment. The dissociation constants (KA) of PNO-49B were not different among the rat thoracic aorta, dog carotid and mesenteric arteries and rabbit thoracic aorta (CEC-pretreated). The contractile responses to PNO-49B were inhibited competitively by prazosin, HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)-ethyl)- amino(propyl)benzeneacetonitrile fumarate) and by WB4101 (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4- benzodioxane).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. All histological types of primary human rhabdomyosarcoma express alpha-cardiac and not alpha-skeletal actin messenger RNA.

    PubMed Central

    Schürch, W.; Bochaton-Piallat, M. L.; Geinoz, A.; d'Amore, E.; Laurini, R. N.; Cintorino, M.; Bégin, L. R.; Boivin, Y.; Gabbiani, G.

    1994-01-01

    Eleven human primary rhabdomyosarcomas (RMSs), including all histological variants, were analyzed morphologically, immunohistochemically for intermediate filament proteins and actin isoforms, and by means of Northern blots with probes specific for total actin, alpha-skeletal (SK), alpha-cardiac (CARD), and alpha-smooth muscle actin messenger (m)RNAs. All tumors disclosed ultrastructural evidence of skeletal muscle features with terminal differentiation in three cases. The RMSs contained immunohistochemically the intermediate filament proteins vimentin and desmin and reacted positively with the alpha-sarcomeric actin antibody, which recognizes alpha-SK and alpha-CARD actin isoforms. All RMSs reacted with the total actin probe, recognizing at 2.1 kb cytoplasmic actin mRNAs and at 1.7 kb alpha-actin mRNAs. With the specific probes, all RMSs expressed alpha-CARD actin mRNA, four neoplasms expressed also alpha-smooth muscle actin mRNA, whereas the probe for alpha-SK actin mRNA never produced a signal except in one case, in which the tumor masses were intermingled with non-neoplastic preexistent striated muscle fibers. Because alpha-CARD and alpha-smooth muscle actins are transiently expressed during normal skeletal muscle development, RMSs seem to follow normal skeletal myogenesis without completing the final step, consisting of alpha-SK actin mRNA expression. The use of Northern blots for alpha-CARD actin as an adjunct to conventional techniques may be helpful for the precise identification of primary RMSs compared to other soft tissue neoplasms. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8160781

  15. Influence of residual milk-clotting enzyme on alpha(s1) casein hydrolysis during ripening of Reggianito Argentino cheese.

    PubMed

    Hynes, E R; Aparo, L; Candioti, M C

    2004-03-01

    Milk-clotting enzyme is considered largely denatured after the cooking step in hard cheeses. Nevertheless, typical hydrolysis products derived from rennet action on alpha(s1)-casein have been detected during the ripening of hard cheeses. The aim of the present work was to investigate the influence of residual milk-clotting enzyme on alpha(s1)-casein hydrolysis in Reggianito cheeses. For that purpose, we studied the influence of cooking temperature (45, 52, and 60 degrees C) on milk-clotting enzyme residual activity and alpha(s1)-casein hydrolysis during ripening. Milk-clotting enzyme residual activity in cheeses was assessed using a chromatographic method, and the hydrolysis of alpha(s1)-casein was determined by electrophoresis and high performance liquid chromatography. Milk-clotting enzyme activity was very low or undetectable in 60 degrees C- and 52 degrees C-cooked cheeses at the beginning of the ripening, but it increased afterwards, particularly in 52 degrees C-cooked cheeses. Cheese curds that were cooked at 45 degrees C had higher initial milk clotting activity, but also in this case, there was a later increase. Hydrolysis of alpha(s1)-casein was detected early in cheeses made at 45 degrees C, and later in those made at higher temperatures. The peptide alpha(s1)-I was not detected in 60 degrees C-cooked cheeses. The results suggest that residual milk-clotting enzyme can contribute to proteolysis during ripening of hard cheeses, because it probably renatures partially after the cooking step. Consequently, the production of peptides derived from alpha(s1)-casein in hard cheeses may be at least, partially due to this proteolytic agent.

  16. The behavior of alpha2-plasmin inhibitor in fibrinolytic states.

    PubMed Central

    Aoki, N; Moroi, M; Matsuda, M; Tachiya, K

    1977-01-01

    Human plasma alpha2-plasmin inhibitor in fibrinolytic states was studied using immunochemical methods and radioiodinated plasminogen. The concentration and activity of plasma alpha2-plasmin inhibitor decreased when urokinase was added to plasma in vitro or infused intravenously in man. The decrease was associated with the appearance of plasmin-alpha2-plasmin inhibitor complex which subsequently disappeared from the circulation in a short time. A decrease of other major inhibitors, such as alpha2-macroglobulin and alpha1-antitrypsin, was not observed when the amount of urokinase added or infused was relatively small, and conversion of plasminogen to plasmin was not extensive. The formation of plasmin-alpha2-macroglobulin complex was observed only when plasma plasminogen was activated with a larger amount of urokinase, and after most of the alpha2-plasmin inhibitor was consumed by forming complexes with plasmin. The formation of plasmin-alpha1-antitrypsin complex was not observed even in the highly activated plasma unless exogenous plasmin was added to the plasma. alpha2-Plasmin inhibitor was the only inhibitor of which the concentration in plasma was significantly decreased in patients with disseminated intravascular coagulation and fibrinolysis among the major plasmin inhibitors in plasma. The most reactive inhibitor for regulating plasma fibrinolysis very likely is alpha2-plasmin inhibitor. Images PMID:68962

  17. cap alpha. -2 adrenergic receptor: a radiohistochemical study

    SciTech Connect

    Unnerstall, J.R.

    1984-01-01

    ..cap alpha..-2 adrenergic agents have been shown to influence blood pressure, heart rate and other physiological and behavioral functions through interactions with adrenergic pathways within the central nervous system. Pharmacologically relevant ..cap alpha..-1 adrenergic receptors were biochemically characterized and radiohistochemically analyzed in intact tissue sections of the rat and human central nervous system. The anatomical distribution of the ..cap alpha..-2 receptors, labeled with the agonist (/sup 3/H)para-aminoclonidine, verified the concept that ..cap alpha..-2 receptors are closely associated with adrenergic nerve terminals and that ..cap alpha..-2 agents can influence autonomic and endocrine function through an action in the central nervous system. Since ..cap alpha..-2 agonists can influence sympathetic outflow, ..cap alpha..-2 binding sites were closely analyzed in the intermediolateral cell column of the thoracic spinal cord. The transport of putative presynaptic ..cap alpha..-2 binding sites in the rat sciatic nerve was analyzed by light microscopic radiohistochemical techniques. Finally, in intact tissue section of the rat central nervous system, the biochemical characteristics of (/sup 3/H)rauwolscine binding were analyzed. Data were also shown which indicates that the synthetic ..cap alpha..-2 antagonist (/sup 3/H)RX781094 also binds to ..cap alpha..-2 receptors with high-affinity. Further, the distribution of (/sup 3/H)RX781094 binding sites in the rat central nervous system was identical to the distribution seen when using (/sup 3/H)para-aminoclonidine.

  18. Studies on New Activities of Enantiomers of 2-(2-Hydroxypropanamido) Benzoic Acid: Antiplatelet Aggregation and Antithrombosis

    PubMed Central

    Zhang, Qili; Wang, Danlin; Zhang, Meiyan; Zhao, Yunli; Yu, Zhiguo

    2017-01-01

    R-/S-2-(2-Hydroxypropanamido) benzoic acid (R-/S-HPABA), a marine-derived anti-inflammatory drug, however, the antiplatelet and antithrombotic effects have not been investigated. In this paper, the in vitro antiplatelet activities and in vivo antithrombotic effects of R-/S-HPABA were investigated, for the first time. The effects of R-/S-HPABA on platelet aggregation induced by adenosine diphosphate (ADP), collagen (COLL) and arachidonic acid (AA) were evaluated. In addition, the in vivo bleeding time, clotting time, collagen-epinephrine induced pulmonary thrombosis and common carotid artery thrombosis were also investigated in rats. R-/S-HPABA significantly inhibited ADP, COLL and AA induced platelet aggregation in rabbit platelet rich plasma in vitro compared with control group, to a degree similar to that of aspirin. Besides, R-/S-HPABA prolonged bleeding time and clotting time as well as increased the recovery rate obviously in pulmonary thrombosis. Moreover, the level of thromboxane B2 (TXB2) was decreased while the production of 6-keto-prostaglandin F1α (6-keto-PGF1α) was increased markedly by R-/S-HPABA. Furthermore, R-/S-HPABA reduced carotid artery thrombosis weight. These results illustrated that R-/S-HPABA could be a potent antiplatelet aggregation and antithrombotic agent. PMID:28107496

  19. Targeted alpha particle immunotherapy for myeloid leukemia.

    PubMed

    Jurcic, Joseph G; Larson, Steven M; Sgouros, George; McDevitt, Michael R; Finn, Ronald D; Divgi, Chaitanya R; Ballangrud, Ase M; Hamacher, Klaus A; Ma, Dangshe; Humm, John L; Brechbiel, Martin W; Molinet, Roger; Scheinberg, David A

    2002-08-15

    Unlike beta particle-emitting isotopes, alpha emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the beta-emitters (131)I and (90)Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of beta-emitting constructs, the alpha-emitting isotope (213)Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg (213)Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the (213)Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with beta-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of (213)Bi-HuM195, and it is the first proof-of-concept for systemic targeted alpha particle immunotherapy in humans.

  20. On the mechanism of alpha-amylase.

    PubMed

    Oudjeriouat, Naïma; Moreau, Yann; Santimone, Marius; Svensson, Birte; Marchis-Mouren, Guy; Desseaux, Véronique

    2003-10-01

    Two inhibitors, acarbose and cyclodextrins (CD), were used to investigate the active site structure and function of barley alpha-amylase isozymes, AMY1 and AMY2. The hydrolysis of DP 4900-amylose, reduced (r) DP18-maltodextrin and maltoheptaose (catalysed by AMY1 and AMY2) was followed in the absence and in the presence of inhibitor. Without inhibitor, the highest activity was obtained with amylose, kcat/Km decreased 103-fold using rDP18-maltodextrin and 10(5) to 10(6)-fold using maltoheptaose as substrate. Acarbose is an uncompetitive inhibitor with inhibition constant (L1i) for amylose and maltodextrin in the micromolar range. Acarbose did not bind to the active site of the enzyme, but to a secondary site to give an abortive ESI complex. Only AMY2 has a second secondary binding site corresponding to an ESI2 complex. In contrast, acarbose is a mixed noncompetitive inhibitor of maltoheptaose hydrolysis. Consequently, in the presence of this oligosaccharide substrate, acarbose bound both to the active site and to a secondary binding site. alpha-CD inhibited the AMY1 and AMY2 catalysed hydrolysis of amylose, but was a very weak inhibitor compared to acarbose.beta- and gamma-CD are not inhibitors. These results are different from those obtained previously with PPA. However in AMY1, as already shown for amylases of animal and bacterial origin, in addition to the active site, one secondary carbohydrate binding site (s1) was necessary for activity whereas two secondary sites (s1 and s2) were required for the AMY2 activity. The first secondary site in both AMY1 and AMY2 was only functional when substrate was bound in the active site. This appears to be a general feature of the alpha-amylase family.

  1. Lexical access and evoked traveling alpha waves

    PubMed Central

    Zauner, Andrea; Gruber, Walter; Himmelstoß, Nicole Alexandra; Lechinger, Julia; Klimesch, Wolfgang

    2014-01-01

    Retrieval from semantic memory is usually considered within a time window around 300–600 ms. Here we suggest that lexical access already occurs at around 100 ms. This interpretation is based on the finding that semantically rich and frequent words exhibit a significantly shorter topographical latency difference between the site with the shortest P1 latency (leading site) and that with the longest P1 latency (trailing site). This latency difference can be described in terms of an evoked traveling alpha wave as was already shown in earlier studies. PMID:24486978

  2. [Alpha-1-antitrypsin deficiency - an update].

    PubMed

    Bernhard, Nikolas; Bals, Robert; Fähndrich, Sebastian

    2016-09-01

    Alpha-1-antitrypsin deficiency is a genetic risk factor for the development of chronic obstructive airway disease (COPD) and liver cirrhosis. The disease is widely underdiagnosed. The hallmarks of therapy are smoking cessation, prevention from environmental dust exposure and augmentation therapy. Findings from the recently published prospective, placebo-controlled and randomized RAPID trial proved effectiveness of AAT augmentation therapy for slowing progression of emphysema, measured by CT lung density. CT lung density may be more sensitive than forced exspiratory volume in one second (FEV1) or monoxid diffusion capacity (DLCO). The data suggest that higher therapeutic serum AAT levels lead to lower decline in lung density.

  3. Alpha resonant scattering for astrophysical reaction studies

    SciTech Connect

    Yamaguchi, H.; Kahl, D.; Nakao, T.; Wakabayashi, Y.; Kubano, S.; Hashimoto, T.; Hayakawa, S.; Kawabata, T.; Iwasa, N.; Teranishi, T.; Kwon, Y. K.; Binh, D. N.; Khiem, L. H.; Duy, N. G.

    2014-05-02

    Several alpha-induced astrophysical reactions have been studied at CRIB (CNS Radioactive Ion Beam separator), which is a low-energy RI beam separator at Center for Nuclear Study (CNS) of the University of Tokyo. One of the methods to study them is the α resonant scattering using the thick-target method in inverse kinematics. Among the recent studies at CRIB, the measurement of {sup 7}Be+α resonant scattering is discussed. Based on the result of the experiment, we evaluated the contributions of high-lying resonances for the {sup 7}Be(α,γ) reaction, and proposed a new cluster band in {sup 11}C.

  4. Excitons and Optical Properties of {alpha} -Quartz

    SciTech Connect

    Chang, Eric K.; Rohlfing, Michael; Louie, Steven G. [Department of Physics, University of California at Berkeley, Berkeley, California 94720

    2000-09-18

    We present an ab initio study of the optical properties of {alpha} -quartz. The absorption spectrum is calculated by solving the Bethe-Salpeter equation for the interacting electron-hole system and found to be in excellent agreement with the measured spectrum up to 10 eV above the absorption threshold. We find that excitonic effects are crucial in understanding the sharp features in the absorption spectrum in this energy range. They are also crucial in the ab initio computation of the static dielectric constant, significantly enhancing its value. (c) 2000 The American Physical Society.

  5. MFTF-. cap alpha. + T shield design

    SciTech Connect

    Gohar, Y.

    1985-01-01

    MFTF-..cap alpha..+T is a DT upgrade option of the Tandem Mirror Fusion Test Facility (MFTF-B) to study better plasma performance, and test tritium breeding blankets in an actual fusion reactor environment. The central cell insert, designated DT axicell, has a 2-MW/m/sup 2/ neutron wall loading at the first wall for blanket testing. This upgrade is completely shielded to protect the reactor components, the workers, and the general public from the radiation environment during operation and after shutdown. The shield design for this upgrade is the subject of this paper including the design criteria and the tradeoff studies to reduce the shield cost.

  6. Alpha Channeling in a Rotating Plasma

    SciTech Connect

    Abraham J. Fetterman and Nathaniel J. Fisch

    2008-09-23

    The wave-particle α-channeling effect is generalized to include rotating plasma. Specifically, radio frequency waves can resonate with α particles in a mirror machine with E × B rotation to diffuse the α particles along constrained paths in phase space. Of major interest is that the α-particle energy, in addition to amplifying the RF waves, can directly enhance the rotation energy which in turn provides additional plasma confinement in centrifugal fusion reactors. An ancillary benefit is the rapid removal of alpha particles, which increases the fusion reactivity.

  7. Alpha particle collective Thomson scattering in TFTR

    SciTech Connect

    Machuzak, J.S.; Woskov, P.P.; Rhee, D.Y.; Gilmore, J.; Bretz, N.L.; Park, H.K.; Aamodt, R.E.; Cheung, P.Y.; Russell, D.A.; Bindslev, H.

    1993-11-01

    A collective Thomson scattering diagnostic is being implemented on TFTR to measure alpha particle, energetic and thermal ion densities and velocity distributions. A 60 GHz, 0.1-1 kW gyrotron will be used as the transmitter source, and the scattering geometry will be perpendicular to the magnetic field in the extraordinary mode polarization. An enhanced scattered signal is anticipated from fluctuations in the lower hybrid frequency range with this scattering geometry. Millimeter wave collective Thomson scattering diagnostics have the advantage of larger scattering angles to decrease the amount of stray light, and long, high power, modulated pulses to obtain improved signal to noise through synchronous detection techniques.

  8. Syntheses of Synthetic Hydrocarbons Via Alpha Olefins.

    DTIC Science & Technology

    1981-10-01

    Chem. Educ., 42, 502 (1965). 4. A. Priola, C. Corna , and S. Cesca, Macromolecules, 13, 1110 (1980). 5. R. F . Brown, Organic Chemistry, Wadsworth...AD-A110 380 GULF RESEARCH AND DEVELOPENT Co PITTSBURGH PA F /G T/A 1 SYNTHESES OF SYNTHETIC HYDROCARBONS VIA ALPHA OLEFINS.(U) OCT 81 B L CUPPLES, A...FOR THE COMMANDER F . D. CHERRY, Chief Nonmetallic Materials Division "If your address has changed, if you wish to be removed from our mailing list

  9. Synthesis of alpha-amino acids

    DOEpatents

    Davis, Jr., Jefferson W.

    1983-01-01

    A method for synthesizing alpha amino acids proceding through novel intermediates of the formulas: R.sub.1 R.sub.2 C(OSOCl)CN, R.sub.1 R.sub.2 C(Cl)CN and [R.sub.1 R.sub.2 C(CN)O].sub.2 SO wherein R.sub.1 and R.sub.2 are each selected from hydrogen monovalent substituted and unsubstituted hydrocarbon radicals of 1 to 12 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the synthesis methods of the prior art.

  10. Synthesis of alpha-amino acids

    DOEpatents

    Davis, Jr., Jefferson W.

    1983-01-01

    A method for synthesizing alpha amino acids proceding through novel intermediates of the formulas: R.sub.1 R.sub.2 C(OSOCl)CN, R.sub.1 R.sub.2 C(Cl)CN and [R.sub.1 R.sub.2 C(CN)O].sub.2 SO wherein R.sub.1 and R.sub.2 are each selected from hydrogen monovalent substituted and unsubstituted hydrocarbon radicals of 1 to 10 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the snythesis methods of the prior art.

  11. Synthesis of alpha-amino acids

    DOEpatents

    Davis, Jr., Jefferson W.

    1983-01-01

    A method for synthesizing alpha amino acids proceeding through novel intermediates of the formulas: R.sub.1 R.sub.2 C(OSOCl)CN, R.sub.1 R.sub.2 C(Cl)CN and [R.sub.1 R.sub.2 C(CN)O].sub.2 SO wherein R.sub.1 and R.sub.2 are each selected from hydrogen monovalent substituted and unsubstituted hydrocarbon radicals of 1 to 12 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the synthesis methods of the prior art.

  12. Alpha 1-antitrypsin Null(isola di procida): an alpha 1-antitrypsin deficiency allele caused by deletion of all alpha 1-antitrypsin coding exons.

    PubMed Central

    Takahashi, H; Crystal, R G

    1990-01-01

    alpha 1-Antitrypsin (alpha 1AT) deficiency, a common hereditary disorder responsible for emphysema in Caucasians of northern European descent, is caused by single base substitutions, deletions, or additions in the seven exons (IA-IC and II-V), of the 12.2-kb alpha 1AT gene located on chromosome 14 at q31-32.3. Of the five known representatives of the "null" group of alpha 1AT-deficiency alleles (alpha 1AT genes incapable of producing alpha 1AT protein detectable in serum) evaluated at the gene level, all result from mutations causing the formation of stop codons in coding exons of the alpha 1AT gene. The present study identifies an alpha 1AT allele (referred to as "Null(isola di procida")) caused by complete deletion of the alpha 1AT coding exons. The Null(isola di procida) allele was identified in an individual with heterozygous inheritance of M(procida) (an allele associated with alpha 1AT deficiency) and a null allele. Although results of karyotypic analysis were normal, quantification of the copies of alpha 1AT genes in this individual revealed that the index case had only half the normal copies of alpha 1AT genes. Cloning and mapping of the Null(isola di procida) gene demonstrated a deletion of a 17-kb fragment that included exons II-V of the alpha 1AT structural gene. As a consequence of the deletion, the normal noncoding exons (IA-IC) were followed by exons II-V of the downstream alpha 1AT-like gene. Sequence analysis of the deletion demonstrated a 7-bp repeat sequence (GAGGACA) both 5' to the deletion and at the 3' end of the deletion, a 4-bp palindromic sequence (ACAG vs. CTGT) bracketing the deletion, and a novel inserted 4-bp sequence (CCTG) at the breakpoint, suggesting that the mechanism of the deletion may have been "slipped mispairing." Images Figure 4 Figure 5 Figure 6 Figure 7 PMID:1975477

  13. The Alpha-1A Adrenergic Receptor in the Rabbit Heart

    PubMed Central

    Myagmar, Bat-Erdene; Swigart, Philip M.; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse. PMID:27258143

  14. The region of CQQQKPQRRP of PGC-1{alpha} interacts with the DNA-binding complex of FXR/RXR{alpha}

    SciTech Connect

    Kanaya, Eiko; Jingami, Hisato . E-mail: jingami@mfour.med.kyoto-u.ac.jp

    2006-04-14

    PGC-1{alpha} co-activates transcription by several nuclear receptors. To study the interaction among PGC-1{alpha}, RXR{alpha}/FXR, and DNA, we performed electrophoresis mobility shift assays. The RXR{alpha}/FXR proteins specifically bound to DNA containing the IR-1 sequence in the absence of ligand. When the fusion protein of GST-PGC-1{alpha} was added to the mixture of RXR{alpha}/FXR/DNA, the ligand-influenced retardation of the mobility was observed. The ligand for RXR{alpha} (9-cis-retinoic acid) was necessary for this retardation, whereas, the ligand for FXR, chenodeoxycholic acid, barely had an effect. The results obtained using truncated PGC-1{alpha} proteins suggested that two regions are necessary for PGC-1{alpha} to interact with the DNA-binding complex of RXR{alpha}/FXR. One is the region of the second leucine-rich motif, and the other is that of the amino acid sequence CQQQKPQRRP, present between the second and third leucine-rich motifs. The results obtained with the SPQSS mutation for KPQRR suggested that the basic amino acids are important for the interaction.

  15. Effects of wortmannin on alpha-1/alpha-2 adrenergic receptor-mediated contractile responses in rabbit vascular tissues.

    PubMed

    Waen-Safranchik, V I; Deth, R C

    1994-06-01

    The inhibitory effect of wortmannin (WO), a fungus-derived protein kinase inhibitor, was assessed on contractile responses elicited by phenylephrine-induced alpha 1-(alpha 1 R) and UK 14304-induced alpha 2-adrenergic receptor (alpha 2R) stimulation in the rabbit aorta and saphenous vein, respectively. In agonist dose-response studies, WO caused a noncompetitive inhibition of both alpha 1R and alpha 2R responses, but was more potent against alpha 2R. Maximally effective single-dose responses at both receptors were less sensitive to WO. The initial alpha 1R contractile response, associated with intracellular Ca2+ release and myosin light chain kinase activation, was relatively insensitive to WO, while the Ca2+ influx-dependent tonic contraction was more sensitive. Contractions induced by high K+ buffer were relatively insensitive to WO in both the aorta and saphenous vein. These results indicate that WO inhibits receptor-initiated Ca2+ influx-dependent contractile responses such as those caused by alpha 2R stimulation and the sustained phase of alpha 1R stimulation more readily than Ca2+ release-dependent responses.

  16. The neuronal nicotinic acetylcholine receptors alpha 4* and alpha 6* differentially modulate dopamine release in mouse striatal slices.

    PubMed

    Meyer, Erin L; Yoshikami, Doju; McIntosh, J Michael

    2008-06-01

    Striatal dopamine (DA) plays a major role in the regulation of motor coordination and in the processing of salient information. We used voltammetry to monitor DA-release evoked by electrical stimulation in striatal slices, where interneurons continuously release acetylcholine. Use of the alpha6-selective antagonist alpha-conotoxin MII[E11A] and alpha4 knockout mice enabled identification of two populations of DA-ergic fibers. The first population had a low action potential threshold, and action potential-evoked DA-release from these fibers was modulated by alpha6. The second population had a higher action potential threshold, and only alpha4(non-alpha6) modulated action potential-evoked DA-release. Striatal DA-ergic neurons fire in both tonic and phasic patterns. When stimuli were applied in a train to mimic phasic firing, more DA-release was observed in alpha4 knockout versus wild-type mice. Furthermore, block of alpha4(non-alpha6), but not of alpha6, increased DA release evoked by a train. These results indicate that there are different classes of striatal DA-ergic fibers that express different subtypes of nicotinic receptors.

  17. Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

    PubMed

    Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

    2004-01-16

    Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

  18. An alpha particle instrument with alpha, proton, and X-ray modes for planetary chemical analyses

    NASA Technical Reports Server (NTRS)

    Economou, T. E.; Turkevich, A. L.

    1976-01-01

    The interaction of alpha particles with matter is employed in a compact instrument that could provide rather complete in-situ chemical analyses of surfaces and thin atmospheres of extraterrestrial bodies. The instrument is a miniaturized and improved version of the Surveyor lunar instrument. The backscattering of alpha particles and (alpha, p) reactions provide analytical data on the light elements (carbon-iron). An X-ray mode that detects the photons produced by the alpha sources provides sensitivity and resolution for the chemical elements heavier than about silicon. The X-rays are detected by semiconductor detectors having a resolution between 150 and 250 eV at 5.9 keV. Such an instrument can identify and determine with good accuracy 99 percent of the atoms (except hydrogen) in rocks. For many trace elements, the detecting sensitivity is a few ppm. Auxiliary sources could be used to enhance the sensitivities for elements of special interest. The instrument could probably withstand the acceleration involved in semi-hard landings.

  19. T-cell receptor V alpha and C alpha alleles associated with multiple and myasthenia gravis.

    PubMed Central

    Oksenberg, J R; Sherritt, M; Begovich, A B; Erlich, H A; Bernard, C C; Cavalli-Sforza, L L; Steinman, L

    1989-01-01

    Polymorphic markers in genes encoding that alpha chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, we amplified selected sequences derived from the full-length TcR alpha cDNA probe. These PCR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of the polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, we have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic V alpha and C alpha markers were identified between patients and healthy individuals. Images PMID:2915992

  20. Aqueous chemical growth of alpha-Fe2O3-alpha-Cr203 nanocompositethin films

    SciTech Connect

    Vayssieres, Lionel; Guo, Jinghua; Nordgren, Joseph

    2001-06-30

    We are reporting here on the inexpensive fabrication and optical properties of an iron(III) oxide chromium(III) oxide nanocomposite thin film of corundum crystal structure. Its novel and unique-designed architecture consists of uniformed, well-defined and oriented nanorods of Hematite (alpha-Fe2O3) of 50 nm in diameter and 500nm in length and homogeneously distributed nonaggregated monodisperse spherical nanoparticles of Eskolaite (alpha-Cr2O3) of 250 nm in diameter. This alpha-Fe2O3 alpha-Cr2O3 nanocomposite thin film is obtained by growing, directly onto transparent polycrystalline conducting substrate, an oriented layer of hematite nanorods and growing subsequently, the eskolaite layer. The synthesis is carried out by a template-free, low-temperature, multilayer thin film coating process using aqueous solution of metal salts as precursors. Almost 100 percent of the light is absorbed by the composite film between 300 and 525 nm and 40 percent at 800 nm which yields great expectations as photoanode materials for photovoltaic cells and photocatalytic devices.

  1. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

    NASA Astrophysics Data System (ADS)

    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

    2016-09-01

    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

  2. A gamma-2 herpesvirus nucleocytoplasmic shuttle protein interacts with importin alpha 1 and alpha 5.

    PubMed

    Goodwin, D J; Whitehouse, A

    2001-06-08

    Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus. This is an increasing important subfamily of herpesviruses due to the identification of the first human gamma-2 herpesvirus, Kaposi's sarcoma-associated herpesvirus. The HVS open reading frame (ORF) 57 protein is a multifunctional trans-regulatory protein homologous to genes identified in all classes of herpesviruses. Recent analysis has demonstrated that ORF 57 has the ability to bind viral RNA and to shuttle between the nucleus and cytoplasm, and is required for efficient nuclear export of viral transcripts. Here we have investigated the nucleocytoplasmic shuttling mechanism utilized by the ORF 57 protein. The yeast two-hybrid system was employed to identify interacting cellular proteins using ORF 57 as bait. We demonstrate that ORF 57 interacts with importin alpha isoforms 1 and 5. In addition, the binding of ORF 57 to importin alpha was mediated by the importin alpha hydrophobic internal armadillo repeats. An ORF 57 amino-terminal arginine-rich sequence, which functions as a nuclear localization sequence, was also required for this interaction. Furthermore, the ORF 57 protein is responsible for the redistribution of importin alpha into the nucleoli. These results identify novel cellular interactions essential for the functioning of this important herpesvirus regulatory protein.

  3. Neuroprotection by Alpha 2-Adrenergic Agonists in Cerebral Ischemia

    PubMed Central

    Zhang, Yonghua; Kimelberg, Harold K.

    2005-01-01

    Ischemic brain injury is implicated in the pathophysiology of stroke and brain trauma, which are among the top killers worldwide, and intensive studies have been performed to reduce neural cell death after cerebral ischemia. Alpha 2-adrenergic agonists have been shown to improve the histomorphological and neurological outcome after cerebral ischemic injury when administered during ischemia, and recent studies have provided considerable evidence that alpha 2-adrenergic agonists can protect the brain from ischemia/reperfusion injury. Thus, alpha 2-adrenergic agonists are promising potential drugs in preventing cerebral ischemic injury, but the mechanisms by which alpha 2-adrenergic agonists exert their neuroprotective effect are unclear. Activation of both the alpha 2-adrenergic receptor and imidazoline receptor may be involved. This mini review examines the recent progress in alpha 2-adrenergic agonists - induced neuroprotection and its proposed mechanisms in cerebral ischemic injury. PMID:18369397

  4. Turbulent transport of alpha particles in reactor plasmas

    SciTech Connect

    Estrada-Mila, C.; Candy, J.; Waltz, R. E.

    2006-11-15

    A systematic study of the behavior of energetic ions in reactor plasmas is presented. Using self-consistent gyrokinetic simulations, in concert with an analytic asymptotic theory, it is found that alpha particles can interact significantly with core ion-temperature-gradient turbulence. Specifically, the per-particle flux of energetic alphas is comparable to the per-particle flux of thermal species (deuterium or helium ash). This finding opposes the conventional wisdom that energetic ions, because of their large gyroradii, do not interact with the turbulence. For the parameters studied, a turbulent modification of the alpha-particle density profile appears to be stronger than turbulent modification of the alpha-particle pressure profile. Crude estimates indicate that the alpha density modification, which is directly proportional to the core turbulence intensity, could be in the range of 15% at midradius in a reactor. The corresponding modification of the alpha-particle pressure profile is predicted to be smaller (in the 1% range)

  5. The role of alpha oscillations for illusory perception.

    PubMed

    Lange, Joachim; Keil, Julian; Schnitzler, Alfons; van Dijk, Hanneke; Weisz, Nathan

    2014-09-01

    Alpha oscillations are a prominent electrophysiological signal measured across a wide range of species and cortical and subcortical sites. Alpha oscillations have been viewed for a long time as an "idling" rhythm, purely reflecting inactive sites. Despite earlier evidence from neurophysiology, awareness that alpha oscillations can substantially influence perception and behavior has grown only recently in cognitive neuroscience. Evidence for an active role of alpha for perception comes mainly from several visual, near-threshold experiments. In the current review, we extend this view by summarizing studies showing how alpha-defined brain states relate to illusory perception, i.e. cases of perceptual reports that are not "objectively" verifiable by distinct stimuli or stimulus features. These studies demonstrate that ongoing or prestimulus alpha oscillations substantially influence the perception of auditory, visual or multisensory illusions.

  6. Severe periodontal destruction in alpha-mannosidosis: a case series.

    PubMed

    Kalsi, Jagdip S; Auplish, Gita; Johnson, Adele R; Darbar, Ulpee R

    2012-01-01

    Alpha-mannosidosis is a rare genetic lysosomal storage disorder that is inherited in an autosomal recessive pattern. Severe periodontal breakdown in alpha-mannosidosis patients has not previously been reported in the literature. The purposes of this paper are to: present the cases of 2 siblings diagnosed with alpha-mannosidosis, each of whom had varying severity of periodontal destruction; and provide an overview of alpha-mannosidosis, the possible reasons for the periodontal destruction, and the periodontal management in the 2 affected siblings. Both had preventive and nonsurgical periodontal therapy followed by a 5-year period of supportive therapy. Their pattern of bone loss was consistent with those with periodontitis as a manifestation of systemic diseases, with the extent of periodontal destruction being related to the severity of the alpha-mannosidosis. Alpha-mannosidosis patients present with social disfigurements and, to prevent tooth loss that can add to this, early periodontal diagnosis is important to optimize management and intervention.

  7. Technical Equivalency Documentation for a New Alpha Spectroscopy System

    SciTech Connect

    Hickman, D P; Fisher, S K; Zeman, R A; Hann, P R

    2005-04-05

    The response of a new Canberra{trademark} Alpha Analyst (Chamber No.'s 101-124) used by the Hazards Control, Radiation Safety Section, WBC/Spectroscopy Team has been studied with respect to an existing Canberra system. The existing Canberra system consists of thirty six Model 7401 alpha spectrometry chambers (Chamber No.'s 1-36) and has been DOELAP qualified for the routine Alpha Spectroscopy program used in LLNL's in vitro bioassay program. The new Alpha Analyst system is an automated system that is controlled by the same software and computer system as that used for the existing Canberra system. This document compares results from the existing Alpha System with the newer Alpha Analyst system.

  8. Alpha Backgrounds in the SNO ^3He Proportional Counter Array

    NASA Astrophysics Data System (ADS)

    Stonehill, Laura

    2006-04-01

    The Sudbury Neutrino Observatory (SNO) has recently deployed an array of proportional counters known as Neutral Current Detectors (NCDs) to detect thermalized neutrons via the ^3He(n,p)^3H reaction. The primary physics background to the neutron-capture signal is alpha particle emission from uranium- and thorium-chain decays in the NCD walls. The expected capture rate of neutrons from the neutral-current neutrino reaction on deuterium is three per day and the intrinsic alpha background rate is approximately 250 alphas per day. Fewer than 10% of these alphas fall into the energy range where neutron-capture signals occur, and a substantial number of these can be eliminated by pulse-shape analysis. This talk will focus on measurements of the alpha backgrounds in the NCDs and the extent to which these alphas contaminate the neutron-capture signal region.

  9. Measurement of surface alpha contamination using electret ion chambers.

    PubMed

    Dua, S K; Biswas, S K; Szerszen, P; Boudreaux, J; Ebadian, M A

    1999-06-01

    Electret ion chambers are inexpensive, light-weight, commercially available, passive charge-integrating devices for accurate measurement of different radiations. Performance of electret ion chambers for surface alpha contamination measurement was evaluated. Ion chambers of two types and electrets of three thicknesses were used for the study. Calibration of the electret ion chambers was performed using reference alpha standards of different energies and radioactivities. Effects of various parameters such as chamber dimensions, electret thickness, alpha particle energy, position of alpha source from the chamber centerline, source localized or uniformly distributed, level of alpha contamination, Mylar window covering the chamber, and ambient radon and gamma radiation on the response of the electret ion chambers were determined. Suitable combinations of chambers and electrets to measure surface alpha contamination were determined.

  10. L-alpha intensity in coronal streamers

    NASA Technical Reports Server (NTRS)

    Noci, G.; Poletto, G.; Suess, S. T.; Wang, A.-H.; Wu, S. T.

    1993-01-01

    White-light images are presently the primary source of information on physical conditions in the solar corona at distances greater than a few tenths of a solar radius above the limb. As a consequence, we still only have an incomplete description of structures extending beyond the solar limb. In particular, streamers, although observed for decades, represent a poorly known phenomenon. SOHO, to be launched in 1995, will be able to make long-term observations of these features up to heights of a few solar radii, both in white light and UV. In this paper we present simulations of L-alpha intensity in coronal streamers, based on the two-dimensional (2D) model developed by Wang et at. (1992, 1993) via a time-dependent numerical relaxation approach. Because the model is 2D, we make an a priori hypothesis about the extension of streamers in the third dimension. L-alpha data, obtained from a rocket (Kohl et al., 1983), allowed us to identify a shape which fits the observations.

  11. Nonlinear feedback control for high alpha flight

    NASA Technical Reports Server (NTRS)

    Stalford, Harold

    1990-01-01

    Analytical aerodynamic models are derived from a high alpha 6 DOF wind tunnel model. One detail model requires some interpolation between nonlinear functions of alpha. One analytical model requires no interpolation and as such is a completely continuous model. Flight path optimization is conducted on the basic maneuvers: half-loop, 90 degree pitch-up, and level turn. The optimal control analysis uses the derived analytical model in the equations of motion and is based on both moment and force equations. The maximum principle solution for the half-loop is poststall trajectory performing the half-loop in 13.6 seconds. The agility induced by thrust vectoring capability provided a minimum effect on reducing the maneuver time. By means of thrust vectoring control the 90 degrees pitch-up maneuver can be executed in a small place over a short time interval. The agility capability of thrust vectoring is quite beneficial for pitch-up maneuvers. The level turn results are based currently on only outer layer solutions of singular perturbation. Poststall solutions provide high turn rates but generate higher losses of energy than that of classical sustained solutions.

  12. Alpha frequency, cognitive load and memory performance.

    PubMed

    Klimesch, W; Schimke, H; Pfurtscheller, G

    1993-01-01

    EEG-signals were recorded from subjects as they performed a modified version of Schneider's and Shiffrin's memory search paradigm. The hypothesis was tested whether individual (centre of gravity) alpha frequency, termed IAF, is related to memory performance and/or attentional demands. The results show that memory performance exerts the strongest effect on IAF. As compared to a resting period, the difference in IAF between age-matched good and bad memory performers reached a maximum when subjects were actually retrieving information from their memory. During retrieval, the IAF of good performers is 1.25 Hz higher than for bad performers. Attentional and task demands also tend to reduce IAF, but as compared to memory performance-to a much lesser degree. The results of amplitude analyses demonstrate further that during retrieval, alpha desynchronization is more pronounced for bad performers than for good performers. Taken together, the results indicate that a decrease in IAF is always related to a drop in performance.

  13. MFTF-. cap alpha. + T progress report

    SciTech Connect

    Nelson, W.D.

    1985-04-01

    Early in FY 1983, several upgrades of the Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) were proposed to the fusion community. The one most favorably received was designated MFTF-..cap alpha..+T. The engineering design of this device, guided by LLNL, has been a principal activity of the Fusion Engineering Design Center during FY 1983. This interim progress report represents a snapshot of the device design, which was begun in FY 1983 and will continue for several years. The report is organized as a complete design description. Because it is an interim report, some parts are incomplete; they will be supplied as the design study proceeds. As described in this report, MFTF-..cap alpha..+T uses existing facilities, many MFTF-B components, and a number of innovations to improve on the physics parameters of MFTF-B. It burns deuterium-tritium and has a central-cell Q of 2, a wall loading GAMMA/sub n/ of 2 MW/m/sup 2/ (with a central-cell insert module), and an availability of 10%. The machine is fully shielded, allows hands-on maintenance of components outside the vacuum vessel 24 h after shutdown, and has provisions for repair of all operating components.

  14. {alpha} decay of {sup 194}At

    SciTech Connect

    Andreyev, A. N.; Antalic, S.; Streicher, B.; Saro, S.; Venhart, M.; Ackermann, D.; Heinz, S.; Hessberger, F. P.; Kojouharov, I.; Kindler, B.; Lommel, B.; Mann, R.; Sulignano, B.; Bianco, L.; Page, R. D.; Sapple, P.; Thomson, J.; Franchoo, S.; Hofmann, S.; Huyse, M.

    2009-06-15

    Detailed {alpha}-decay studies of the neutron-deficient isotope {sup 194}At have been performed in the complete fusion reaction {sup 56}Fe+{sup 141}Pr{yields}{sup 194}At+3n at the velocity filter SHIP. Two {alpha}-decaying isomeric states with half-lives of T{sub 1/2}({sup 194}At{sup m1})=310(8) ms and T{sub 1/2}({sup 194}At{sup m2})=253(10) ms were identified in this nucleus. Their complex decays to the states in the daughter nucleus {sup 190}Bi are discussed in the article. We propose that similar to the case of the neighboring {sup 191,192,193,195}At isotopes, the oblate-deformed configurations based on the proton 1/2{sup +}[440] and/or 7/2{sup -}[514] Nilsson orbitals become important in {sup 194}At. A new isomeric state with the half-life of 175(8) ns was observed in {sup 190}Bi.

  15. Characterizing Lyman Alpha Scattering in Nearby Galaxies

    NASA Astrophysics Data System (ADS)

    Bridge, Joanna; Hayes, Matthew; Melinder, Jens; Östlin, Göran; Gronwall, Caryl

    2017-01-01

    The hydrogen emission line of Lyman alpha (Lyα) has long been recognized as key to studying high redshift star-forming galaxies. However, due to the resonance of the emission line, the path that a Lyα photon takes from emission to eventual escape from the galaxy is essentially a mystery. This scattering poses a problem for using Lyα as a key emission feature of galaxies because it results in Lyα not being observed in all star-forming galaxies, and, in galaxies where it is observed, the place where the photon is originally emitted and where it is observed are two very different things. We discuss here how the Lyman-Alpha Reference Sample (LARS) provides a unique sample of 14 nearby (0.02 < z < 0.2) galaxies in which we investigate the role of scattering, both on the global scale of the galaxies and down to scales of ~ 50 parsecs using Hubble Space Telescope imaging. We compare the Lyα/Hα ratios with those expected from pure dust attenuation models, finding that in some cases significant positive departures are found on small scales, consistent with geometrical effects being important on sizes comparable to the HII regions. We then develop a simple scattering model in which we are able to estimate the average path length a Lyα photon travels with respect to non-resonant radiation, and quantifiy the excess dust optical depth to which Lyα radiation may be susceptible.

  16. Oral phentolamine: an alpha-1, alpha-2 adrenergic antagonist for the treatment of erectile dysfunction.

    PubMed

    Goldstein, I

    2000-03-01

    Phentolamine mesylate is an alpha-1 and alpha-2 selective adrenergic receptor antagonist which has undergone clinical trials for erectile dysfunction treatment. Biochemical and physiological studies in human erectile tissue have revealed a high affinity of phentolamine for alpha-1 and alpha-2 adrenergic receptors. Based on pharmacokinetic studies, it is suggested that 30-40 min following oral ingestion of 40 or 80 mg of phentolamine (Vasomax), the mean plasma phentolamine concentrations are sufficient to occupy the alpha-1 and -2 adrenergic receptors in erectile tissue and thereby result in inhibition of adrenergic-mediated physiologic activity. In large multi-center, placebo-controlled pivotal phase III clinical trials, the mean change in the erectile function domain of the International Index of Erectile Function scores (Questions 1-5 and 15) from screening to the end of treatment was significantly higher following use of active drug (40 mg and 80 mg) compared to placebo. Three to four times as many patients receiving phentolamine reported being satisfied or very satisfied compared with those receiving placebo. At doses of 40 mg and 80 mg respectively, 55% and 59% of men were able to achieve vaginal penetration with 51% and 53% achieving penetration on 75% of attempts. The correction of erectile dysfunction or improvement to a less severe category of dysfunction was experienced by 53% of men with the 80 mg dose and 40% with the 40 mg dose of phentolamine. All trends of response were the same regardless of any concomitant medication. There were no severe adverse events. At 40 mg, 7.7% experienced rhinitis and fewer than 3.1% experienced any other side effect of treatment. Phentolamine is safe, well tolerated and efficacious for the treatment of erectile dysfunction.

  17. Mapping of the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor.

    PubMed Central

    Neumann, D; Barchan, D; Safran, A; Gershoni, J M; Fuchs, S

    1986-01-01

    Synthetic peptides and their respective antibodies have been used in order to map the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor. By using antibodies to a synthetic peptide corresponding to residues 169-181 of the alpha subunit, we demonstrate that this sequence is included within the 18-kDa toxin binding fragment previously reported. Furthermore, the 18-kDa fragment was also found to bind a monoclonal antibody (5.5) directed against the cholinergic binding site. Sequential proteolysis of the acetylcholine receptor with trypsin, prior to Staphylococcus aureus V8 protease digestion, resulted in a 15-kDa toxin binding fragment that is included within the 18-kDa fragment but is shorter than it only at its carboxyl terminus. This 15-kDa fragment therefore initiates beyond Asp-152 and terminates in the region of Arg-313/Lys-314. In addition, experiments are reported that indicate that in the intact acetylcholine receptor, Cys-128 and/or Cys-142 are not crosslinked by disulfide bridges with any of the cysteines (at positions 192, 193, and 222) that reside in the 15-kDa toxin binding fragment. Finally, the synthetic dodecapeptide Lys-His-Trp-Val-Tyr-Tyr-Thr-Cys-Cys-Pro-Asp-Thr, which is present in the 15-kDa fragment (corresponding to residues 185-196 of the alpha subunit) was shown to bind alpha-bungarotoxin directly. This binding was completely inhibited by competition with d-tubocurarine. Images PMID:3458258

  18. Mapping of the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor.

    PubMed

    Neumann, D; Barchan, D; Safran, A; Gershoni, J M; Fuchs, S

    1986-05-01

    Synthetic peptides and their respective antibodies have been used in order to map the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor. By using antibodies to a synthetic peptide corresponding to residues 169-181 of the alpha subunit, we demonstrate that this sequence is included within the 18-kDa toxin binding fragment previously reported. Furthermore, the 18-kDa fragment was also found to bind a monoclonal antibody (5.5) directed against the cholinergic binding site. Sequential proteolysis of the acetylcholine receptor with trypsin, prior to Staphylococcus aureus V8 protease digestion, resulted in a 15-kDa toxin binding fragment that is included within the 18-kDa fragment but is shorter than it only at its carboxyl terminus. This 15-kDa fragment therefore initiates beyond Asp-152 and terminates in the region of Arg-313/Lys-314. In addition, experiments are reported that indicate that in the intact acetylcholine receptor, Cys-128 and/or Cys-142 are not crosslinked by disulfide bridges with any of the cysteines (at positions 192, 193, and 222) that reside in the 15-kDa toxin binding fragment. Finally, the synthetic dodecapeptide Lys-His-Trp-Val-Tyr-Tyr-Thr-Cys-Cys-Pro-Asp-Thr, which is present in the 15-kDa fragment (corresponding to residues 185-196 of the alpha subunit) was shown to bind alpha-bungarotoxin directly. This binding was completely inhibited by competition with d-tubocurarine.

  19. Central alpha 1- and alpha 2-adrenoceptors and brain cholinergic stimulation in sinoaortic denervated rats.

    PubMed

    Taira, C A; Enero, M A

    1994-12-12

    The central alpha-adrenoceptor role in cardiovascular responses to intracerebroventricular (i.c.v.) injection of neostigmine, a tertiary anticholinesterase, was studied in conscious sham-operated and sinoaortic-denervated rats. Neostigmine (0.1-1 micrograms i.c.v.) showed dose-dependent pressor and bradycardiac effects in vehicle-pretreated sham-operated rats but only an increased pressor effect in sinoaortic-denervated animals. The pretreatment with the catecholaminergic neurotoxin, 6-hydroxydopamine (250 micrograms i.c.v.), given 72 h previous to the corresponding operation, blunted the cardiovascular effects of neostigmine in both groups of rats. Prazosin (10 and 30 micrograms i.c.v.), an alpha 1-adrenoceptor antagonist, prevented the pressor response to neostigmine (0.3 micrograms i.c.v.) in sham-operated and sinoaortic-denervated rats. Yohimbine, a alpha 2-adrenoceptor antagonist (10 and 30 micrograms i.c.v.), only prevented the bradycardia induced by neostigmine (0.3 micrograms i.c.v.) in the sham-operated rats. 6-Hydroxydopamine pretreatment lowered the norepinephrine content in hypothalamus, midbrain, medulla oblongata and spinal cord, but did not modify it in the pons, in sham-operated rats and sinoaortic-denervated animals. The present results suggested that brain alpha 1-adrenoceptors would mediate the pressor response to neostigmine (i.c.v.) in sham-operated and sinoaortic-denervated rats and central alpha 2-adrenoceptors mediate the bradycardia in sham-operated rats. This work lends support to the view that cardiovascular responses to brain cholinergic stimulation in sham-operated and sinoaortic-denervated rats could be mediated by a central catecholaminergic activation.

  20. Quantitative determination of cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides in rat skin.

    PubMed

    Yamazaki, S; Ozawa, N; Hiratsuka, A; Watanabe, T

    1999-07-01

    An assay method for determination of cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides (ChOOHs) in rat skin using high-performance liquid chromatography (HPLC) with a chemiluminescence detector has been developed. In the assay method, free form and free plus ester forms of ChOOHs could be separately determined by HPLC in combination with the treatment of a tissue extract by cholesterol esterase. Lower limits of quantitation for cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides were 0.2, 0.1, and 0.5 nmol/g skin, respectively. This assay method showed that (i) good absolute recoveries of ChOOHs from rat skin (80-90% of radiolabeled ChOOHs added to rat skin); (ii) negligible autoxidation of cholesterol caused by the assay procedure (<9.4x10(-5)% of radiolabeled cholesterol added to rat skin); and (iii) good correlation between ChOOHs added to rat skin and ChOOHs determined, indicating this assay method is applicable to quantify ChOOHs in rat skin. By using this assay method, we observed that (i) cholesterol 5alpha-hydroperoxide was detected in skin of rats pretreated with oral doses of pheophorbide a and subsequent visible irradiation; (ii) concentrations of cholesterol 7-hydroperoxides in skin of rats in an ambient light room were not significantly different from those in a dark room for 12 weeks; and (iii) ultraviolet light B irradiation markedly enhanced the concentrations of cholesterol 7-hydroperoxides in the skin of rats.

  1. Evolution of the alpha particle driven toroidicity induced Alfven mode

    SciTech Connect

    Wu, Y.; White, R.B.; Cheng, C.Z.

    1994-04-01

    The interaction of alpha particles with a toroidicity induced Alfven eigenmode is investigated self-consistently by using a kinetic dispersion relation. All important poloidal harmonics and their radial mode profiles are included. A Hamiltonian guiding center code is used to simulate the alpha particle motion. The simulations include particle orbit width, nonlinear particle dynamics and the effects of the modes on the particles. Modification of the particle distribution leading to mode saturation is observed. There is no significant alpha particle loss.

  2. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    SciTech Connect

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  3. Sex differences in alpha-adrenergic support of blood pressure.

    PubMed

    Schmitt, Judith A M; Joyner, Michael J; Charkoudian, Nisha; Wallin, B Gunnar; Hart, Emma C

    2010-08-01

    We tested whether the inter-individual variability in alpha-adrenergic support of blood pressure plays a critical role in the sex differences in tonic support of blood pressure by the autonomic nervous system. Blockade of the alpha-adrenergic receptors was achieved via phentolamine and showed a smaller (P < 0.05) decrease in blood pressure in women compared to men, implying that alpha-adrenergic support of blood pressure is less in women than in men.

  4. Evidence for Alpha Receptors in the Human Ureter

    NASA Astrophysics Data System (ADS)

    Madeb, Ralph; Knopf, Joy; Golijanin, Dragan; Bourne, Patricia; Erturk, Erdal

    2007-04-01

    An immunohistochemical and western blot expression analysis of human ureters was performed in order to characterize the alpha-1-adrenergic receptor distribution along the length of the human ureteral wall. Mapping the distribution will assist in understanding the potential role alpha -1-adrenergic receptors and their subtype density might have in the pathophysiology of ureteral colic and stone passage. Patients diagnosed with renal cancer or bladder cancer undergoing nephrectomy, nephroureterectomy, or cystectomy had ureteral specimens taken from the proximal, mid, distal and tunneled ureter. Tissues were processed for fresh frozen examination and fixed in formalin. None of the ureteral specimens were involved with cancer. Serial histologic sections and immunohistochemical studies were performed using antibodies specific for alpha-1-adrenergic receptor subtypes (alpha 1a, alpha 1b, alpha 1d). The sections were examined under a light microscope and scored as positive or negative. In order to validate and quantify the alpha receptor subtypes along the human ureter. Western blotting techniques were applied. Human ureter stained positively for alpha -1-adrenergic receptors. Immunostaining appeared red, with intense reaction in the smooth muscle of the ureter and endothelium of the neighboring blood vessels. There was differential expression between all the receptors with the highest staining for alpha-1D subtype. The highest protein expression for all three subtypes was in the renal pelvis and decreased with advancement along the ureter to the distal ureter. At the distal ureter, there was marked increase in expression as one progressed towards the ureteral orifice. The same pattern of protein expression was exhibited for all three alpha -1-adrenergic receptor subtypes. We provide preliminary evidence for the ability to detect and quantify the alpha-1-receptor subtypes along the human ureter which to the best of our knowledge has never been done with

  5. Alpha inelastic scattering and cluster structures in {sup 24}Mg

    SciTech Connect

    Kawabata, T.; Ishiguro, Y.; Nozawa, Y.; Tomida, N.; Yokota, N.; Adachi, T.; Fujiwara, M.; Hatanaka, K.; Tamii, A.; Yasuda, Y.; Zenihiro, J.; Itoh, M.; Takahashi, T.; Yoshida, H. P.; Maeda, Y.; Miyasako, H.; Saito, T.; Matsubara, H.; Sasamoto, Y.; Tokieda, H.

    2011-05-06

    The alpha inelastic scattering from {sup 24}Mg was measured to obtain the isoscalar natural-parity excitation strengths and to search for the {alpha}-condensed states. The multipole decomposition analysis for the measured cross sections was performed. The strength distributions for the {Delta}L = 0-3 were successfully obtained and the possible candidates for the {alpha}-condensed states around the {sup 16}O core were found.

  6. Studies of alpha-induced astrophysical reactions at CRIB

    SciTech Connect

    Yamaguchi, H.; Hashimoto, T.; Hayakawa, S.; Binh, D. N.; Kahl, D.; Kubono, S.

    2010-08-12

    CRIB (CNS Radioactive Ion Beam separator) is a low-energy RI beam separator at the Center for Nuclear Study (CNS) of the University of Tokyo. Using the RI beams at CRIB, many measurements on proton alpha resonance scatterings, ({alpha},p) reactions, and others were performed in recent years mainly for studying astrophysical reactions and exotic nuclear structure. Among them, the results on the {sup 7}Li+{alpha} resonance scatterings are presented.

  7. Alpha particle destabilization of the toroidicity-induced Alfven eigenmodes

    SciTech Connect

    Cheng, C.Z.

    1990-10-01

    The high frequency, low mode number toroidicity-induced Alfven eigenmodes (TAE) are shown to be driven unstable by the circulating and/or trapped {alpha}-particles through the wave-particle resonances. Satisfying the resonance condition requires that the {alpha}-particle birth speed v{sub {alpha}} {ge} v{sub A}/2{vert bar}m-nq{vert bar}, where v{sub A} is the Alfven speed, m is the poloidal model number, and n is the toroidal mode number. To destabilize the TAE modes, the inverse Landau damping associated with the {alpha}-particle pressure gradient free energy must overcome the velocity space Landau damping due to both the {alpha}-particles and the core electrons and ions. The growth rate was studied analytically with a perturbative formula derived from the quadratic dispersion relation, and numerically with the aid of the NOVA-K code. Stability criteria in terms of the {alpha}-particle beta {beta}{sub {alpha}}, {alpha}-particle pressure gradient parameter ({omega}{sub {asterisk}}/{omega}{sub A}) ({omega}{sub {asterisk}} is the {alpha}-particle diamagnetic drift frequency), and (v{sub {alpha}}/v{sub A}) parameters will be presented for TFTR, CIT, and ITER tokamaks. The volume averaged {alpha}-particle beta threshold for TAE instability also depends sensitively on the core electron and ion temperature. Typically the volume averaged {alpha}-particle beta threshold is in the order of 10{sup {minus}4}. Typical growth rates of the n=1 TAE mode can be in the order of 10{sup {minus}2}{omega}{sub A}, where {omega}{sub A}=v{sub A}/qR. Other types of global Alfven waves are stable in D-T tokamaks due to toroidal coupling effects.

  8. alpha-synuclein and LRRK2: partners in crime.

    PubMed

    Tong, Youren; Shen, Jie

    2009-12-24

    In this issue of Neuron, Lin et al. report that LRRK2 modulates age-related neurodegeneration caused by overexpression of alpha-synuclein in the forebrain of transgenic mice. Overexpression of LRRK2 accelerates the progression of alpha-synuclein-mediated neuropathological changes, whereas deletion of LRRK2 alleviates these alterations. The results reveal an interesting interaction between alpha-synuclein and LRRK2, two gene products linked to dominantly inherited Parkinson's disease.

  9. Waves for Alpha-Channeling in Mirror Machines

    SciTech Connect

    A. I. Zhmoginov and N. J. Fisch

    2009-07-08

    Alpha-channeling can, in principle, be implemented in mirror machines via exciting weaklydamped modes in the ion cyclotron frequency range with perpendicular wavelengths smaller than the alpha particle gyroradius. Assuming quasi-longitudinal or quasi-transverse wave propagation, we search systematically for suitable modes in mirror plasmas. Considering two device designs, a proof-of-principle facility and a fusion rector prototype, we in fact identify candidate modes suitable for alpha-channeling.

  10. Alpha particle effects on the internal kink and fishbone modes

    SciTech Connect

    Wu, Y.; Cheng, C.Z.; White, R.B. )

    1994-10-01

    The effects of alpha particles on the internal kink and fishbone modes are studied analytically. The nonadiabatic contribution from untrapped alpha particles is negligible. Finite inverse aspect ratio, plasma [beta], and plasma shaping effects can significantly enhance the trapped particle drift reversal domain in the pitch angle space and reduce the bounce-averaged magnetic drift frequency. The decrease of the drift magnitude and drift reversal effects on the ideal kink mode is small, but the [beta][sub [alpha

  11. Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin.

    PubMed

    Kawataki, Tomoyuki; Yamane, Tetsu; Naganuma, Hirofumi; Rousselle, Patricia; Andurén, Ingegerd; Tryggvason, Karl; Patarroyo, Manuel

    2007-11-01

    Glioma cell infiltration of brain tissue often occurs along the basement membrane (BM) of blood vessels. In the present study we have investigated the role of laminins, major structural components of BMs and strong promoters of cell migration. Immunohistochemical studies of glioma tumor tissue demonstrated expression of alpha2-, alpha3-, alpha4- and alpha5-, but not alpha1-, laminins by the tumor vasculature. In functional assays, alpha3 (Lm-332/laminin-5)- and alpha5 (Lm-511/laminin-10)-laminins strongly promoted migration of all glioma cell lines tested. alpha1-Laminin (Lm-111/laminin-1) displayed lower activity, whereas alpha2 (Lm-211/laminin-2)- and alpha4 (Lm-411/laminin-8)-laminins were practically inactive. Global integrin phenotyping identified alpha3beta1 as the most abundant integrin in all the glioma cell lines, and this laminin-binding integrin exclusively or largely mediate the cell migration. Moreover, pretreatment of U251 glioma cells with blocking antibodies to alpha3beta1 integrin followed by intracerebral injection into nude mice inhibited invasion of the tumor cells into the brain tissue. The cell lines secreted Lm-211, Lm-411 and Lm-511, at different ratios. The results indicate that glioma cells secrete alpha2-, alpha4- and alpha5-laminins and that alpha3- and alpha5-laminins, found in brain vasculature, selectively promote glioma cell migration. They identify alpha3beta1 as the predominant integrin and laminin receptor in glioma cells, and as a brain invasion-mediating integrin.

  12. Studies of alpha-granule proteins in cultured human megakaryocytes.

    PubMed

    Veljkovic, Dragoslava Kika; Cramer, Elisabeth M; Alimardani, Gulie; Fichelson, Serge; Massé, Jean-Marc; Hayward, Catherine P M

    2003-11-01

    alpha-Granule protein storage is important for producing platelets with normal haemostatic function. The low to undetectable levels of several megakaryocyte-synthesized alpha-granule proteins in normal plasma suggest megakaryocytes are important to sequester these proteins in vivo. alpha-Granule protein storage in vitro has been studied using other cell types, with differences observed in how some proteins are processed compared to platelets. Human megakaryocytes, cultured from cord blood CD34(+) cells and grown in serum-free media containing thrombopoietin, were investigated to determine if they could be used as a model for studying normal alpha-granule protein processing and storage. ELISA indicated that cultured megakaryocytes contained the alpha-granule proteins multimerin, von Willebrand factor, thrombospondin-1, beta-thromboglobulin and platelet factor 4, but no detectable fibrinogen and factor V. A significant proportion of the alpha-granule protein in megakaryocyte cultures was contained within the cells (averages: 41-71 %), consistent with storage. Detailed analyses of multimerin and von Willebrand factor confirmed that alpha-granule proteins were processed to mature forms and were predominantly located in the alpha-granules of cultured megakaryocytes.Thrombopoietin-stimulated cultured megakaryocytes provide a useful model for studying alpha-granule protein processing and storage.

  13. Anisotropic. cap alpha. -emission of on-line separated isotopes

    SciTech Connect

    Wouters, J.; Vandeplassche, D.; van Walle, E.; Severijns, N.; Van Haverbeke, J.; Vanneste, L.

    1987-12-10

    The technical realization of particle detection at very low temperatures (4K) has made it possible to study for the first time the anisotropic ..cap alpha..-decay of oriented nuclei which have been produced, separated and implanted on line. The measured ..cap alpha..-angular distributions reveal surprising new results on nuclear aspects as well as in solid state physics. The nuclear structure information from these data questions the older ..cap alpha..-decay theoretical interpretation and urges for a reaxamination of the earliest work on anisotropic ..cap alpha..-decay.

  14. Purification of alpha-1-antitrypsin monomer by preparative electrophoresis.

    PubMed Central

    Spada, F; Candiano, G; Sergi, C; Ghiggeri, G M; Callea, F; Gusmano, R

    1994-01-01

    Alfa-1-antitrypsin (alpha 1AT) was purified by pseudoligand chromatography and preparative electrophoresis from the serum of a patient with alpha 1AT deficiency. The combination of the two techniques yielded a high grade batch of alpha 1AT monomer and this was successfully used to purify the protein from the serum of PiMIM1, PiMIM2, and PiZZ phenotype subjects. This procedure should facilitate structural studies of alpha 1AT variants susceptible to intracellular accumulation. Images PMID:8089226

  15. On the relationship between coefficient alpha and composite reliability.

    PubMed

    Peterson, Robert A; Kim, Yeolib

    2013-01-01

    Cronbach's coefficient alpha is the most widely used estimator of the reliability of tests and scales. However, it has been criticized as being a lower bound and hence underestimating true reliability. A popular alternative to coefficient alpha is composite reliability, which is usually calculated in conjunction with structural equation modeling. A quantitative analysis of 2,524 pairs of coefficient alpha and composite reliability values derived from empirical investigations revealed that although the average composite reliability value (.86) exceeded the average corresponding coefficient alpha value (.84), the difference was relatively inconsequential for practical applications such as meta-analysis.

  16. A catalog of stellar Lyman-alpha fluxes

    NASA Technical Reports Server (NTRS)

    Landsman, Wayne; Simon, Theodore

    1993-01-01

    We present a catalog of stellar Ly-alpha emission fluxes, based on new and archival images obtained with the IUE spacecraft. The catalog includes 227 stars with detectable Ly-alpha emission fluxes, and upper limits on the Ly-alpha emission flux for another 48 stars. Multiple flux measurements are given for 52 stars. We present a model for correcting the observed Ly-alpha flux for attenuation by the local interstellar medium, and we apply this model to derive intrinsic Ly-alpha fluxes for 149 catalog stars which are located in low H I column density directions of the local interstellar medium. In our catalog, there are 14 late-A and early-F stars at B-V = 0.29 or less that show detectable emission at Ly-alpha. We find a linear correlation between the intrinsic Ly-alpha flux and C II 1335 A flux for stars with B-V greater than 0.60, but the A and F stars deviate from this relation in the sense that their Ly-alpha flux is too low. We also find a good correlation between Ly-alpha strength and coronal X-ray emission. This correlation holds over most of the H-R diagram, even for the F stars, where an X-ray deficit has previously been found relative to the transition region lines of C II and C IV.

  17. Technical Equivalency Documentation for a Newly Acquired Alpha Spectroscopy System

    SciTech Connect

    Hickman, D P; Fisher, S K; Zeman, R A; Hann, P R

    2005-09-28

    The response of a newly acquired Canberra{trademark} Alpha Analyst (Chamber No.'s 137-172) used by the Hazards Control, Radiation Safety Section WBC/Spectroscopy Team has been studied with respect to an existing Canberra system. The existing Canberra system consists of thirty-six Model 7401 alpha spectrometry chambers (Chamber No.'s 1-36) and has previously been DOELAP qualified for the routine Alpha Spectroscopy program used in LLNL's in vitro bioassay program. The newly acquired Alpha Analyst system operates on a network with software that controls and performs analysis of a one-year-old twenty-four chamber Alpha Analyst system (Chamber No.'s 101-124) that has also been previously evaluated and recently DOELAP accredited. The Alpha Analyst system is an automated system that is controlled by the same software and computer system as that used for the existing Canberra alpha analysis systems. This document compares results from the existing Alpha System with the newer Alpha Analyst system.

  18. New potential uroselective NO-donor alpha1-antagonists.

    PubMed

    Boschi, Donatella; Tron, Gian Cesare; Di Stilo, Antonella; Fruttero, Roberta; Gasco, Alberto; Poggesi, Elena; Motta, Gianni; Leonardi, Amedeo

    2003-08-14

    A recent uroselective alpha(1)-adrenoceptor antagonist, REC15/2739, has been joined with nitrooxy and furoxan NO-donor moieties to give new NO-donor alpha(1)-antagonists. All the compounds studied proved to be potent and selective ligands of human cloned alpha(1a)-receptor subtype. Derivatives 6 and 7 were able to relax the prostatic portion of rat vas deferens contracted by (-)-noradrenaline because of both their alpha(1A)-antagonist and their NO-donor properties.

  19. Unique copper-induced oligomers mediate alpha-synuclein toxicity.

    PubMed

    Wright, Josephine A; Wang, Xiaoyan; Brown, David R

    2009-08-01

    Parkinson's disease and a number of other neurodegenerative diseases have been linked to either genetic mutations in the alpha-synuclein gene or show evidence of aggregates of the alpha-synuclein protein, sometimes in the form of Lewy bodies. There currently is no clear evidence of a distinct neurotoxic species of alpha-synuclein to explain the death of neurons in these diseases. We undertook to assess the toxicity of alpha-synuclein via exogenous application in cell culture. Initially, we showed that only aggregated alpha-synuclein is neurotoxic and requires the presence copper but not iron. Other members of the synuclein family showed no toxicity in any form and inherited point mutations did not alter the effective toxic concentration of alpha-synuclein. Through protein fractionation techniques, we were able to isolate an oligomeric species responsible for the toxicity of alpha-synuclein. This oligomeric species has a unique stellate appearance under EM and again, requires association with copper to induce cell death. The results allow us to suggest that the toxic species of alpha-synuclein in vivo could possibly be these stellate oligomers and not fibrils. Our data provide a link between the recently noted association of copper and alpha-synuclein and a potential role for the combination in causing neurodegeneration.

  20. Effects of excitation laser wavelength on Ly-{alpha} and He-{alpha} line emission from nitrogen plasmas

    SciTech Connect

    Harilal, S. S.; Miloshevsky, G. V.; Sizyuk, T.; Hassanein, A.

    2013-01-15

    Laser-produced nitrogen plasmas emitting radiation at 2.48 nm (Ly-{alpha}) and 2.88 nm (He-{alpha}) are considered potential efficient sources for water-window (WW) microscopy. The atomic and optical properties of nitrogen plasma and influence of the laser wavelength on the line emission in the WW range are investigated. It is found that the optimal temperatures for maximum emission from Ly-{alpha} and He-{alpha} spectral lines are 40-60 eV and 80-100 eV, respectively. The WW line emission and the conversion efficiency (CE) are estimated for three distinct Nd:YAG laser wavelengths (1064 nm, 532 nm, and 266 nm). The calculated CEs are compared with experimentally observed CE values. It is found that 1064 nm wavelength provides the highest CE from laser to Ly-{alpha} and He-{alpha} radiation.

  1. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  2. Hereditary persistence of alpha-fetoprotein: a rare cause for unexplained alpha-fetoprotein elevations in pregnancy.

    PubMed

    Rood, Kara; Stiller, Robert

    2013-01-01

    Markedly elevated maternal serum alpha-fetoprotein (MSAFP) levels were found in a 26 year old healthy, nulliparous Polish woman during pregnancy. No fetal abnormalities were identified on targeted ultrasound and amniocentesis revealed normal amniotic fluid alpha-fetoprotein (AFP) values. Maternal ultrasound screening for liver and ovarian germ cell malignancies were also negative. The mother delivered a live, healthy female at term and a repeat maternal serum AFP postpartum remained markedly elevated, suggestive of hereditary persistence of alpha-fetoprotein.

  3. Alpha-conotoxin-ImI: a competitive antagonist at alpha-bungarotoxin-sensitive neuronal nicotinic receptors in hippocampal neurons.

    PubMed

    Pereira, E F; Alkondon, M; McIntosh, J M; Albuquerque, E X

    1996-09-01

    In the present study, the patch-clamp technique was applied to rat hippocampal neurons or myoballs in culture to study the actions of alpha-conotoxin-ImI on the native alpha-bungarotoxin-sensitive, presumably alpha 7-bearing, neuronal nicotinic receptor and on other ligand-gated channels. Preexposure of the neurons for 5 min to alpha-conotoxin-ImI decreased the peak amplitude of alpha-BGT-sensitive currents (referred to as type IA currents) in a concentration-dependent fashion. Several lines of evidence revealed that the inhibitory effect of alpha-conotoxin-ImI was competitive with respect to the agonist (IC50 approximately 85 nM) and reversible by washing. At 300 nM, alpha-conotoxin-ImI decreased by only 15% the peak amplitude of ACh-evoked currents in rat myoballs, did not affect the activation of currents gated by gamma-aminobutyric acid, glycine, N-methyl-D-aspartate, kainate, or quisqualate in hippocampal neurons, but reduced to approximately 60% the peak amplitude and shortened the decay phase of curare-sensitive, serotonin-gated currents in these neurons. The competitive and reversible nature of the alpha-conotoxin-ImI-induced inhibition of native alpha 7-bearing neuronal nicotinic receptors makes this peptide a valuable new tool for the functional and structural characterization of these receptors in the central nervous system.

  4. alpha-latrotoxin action probed with recombinant toxin: receptors recruit alpha-latrotoxin but do not transduce an exocytotic signal.

    PubMed Central

    Ichtchenko, K; Khvotchev, M; Kiyatkin, N; Simpson, L; Sugita, S; Südhof, T C

    1998-01-01

    alpha-Latrotoxin stimulates neurotransmitter release probably by binding to two receptors, CIRL/latrophilin 1 (CL1) and neurexin Ialpha. We have now produced recombinant alpha-latrotoxin (LtxWT) that is as active as native alpha-latrotoxin in triggering synaptic release of glutamate, GABA and norepinephrine. We have also generated three alpha-latrotoxin mutants with substitutions in conserved cysteine residues, and a fourth mutant with a four-residue insertion. All four alpha-latrotoxin mutants were found to be unable to trigger release. Interestingly, the insertion mutant LtxN4C exhibited receptor-binding affinities identical to wild-type LtxWT, bound to CL1 and neurexin Ialpha as well as LtxWT, and similarly stimulated synaptic hydrolysis of phosphatidylinositolphosphates. Therefore, receptor binding by alpha-latrotoxin and stimulation of phospholipase C are insufficient to trigger exocytosis. This conclusion was confirmed in experiments with La3+ and Cd2+. La3+ blocked release triggered by LtxWT, whereas Cd2+ enhanced it. Both cations, however, had no effect on the stimulation by LtxWT of phosphatidylinositolphosphate hydrolysis. Our data show that receptor binding by alpha-latrotoxin and activation of phospholipase C do not by themselves trigger exocytosis. Thus receptors recruit alpha-latrotoxin to its point of action without activating exocytosis. Exocytosis probably requires an additional receptor-independent activity of alpha-latrotoxin that is selectively inhibited by the LtxN4C mutation and by La3+. PMID:9799228

  5. The chromosomal arrangement of human alpha-like globin genes: sequence homology and alpha-globin gene deletions.

    PubMed

    Lauer, J; Shen, C K; Maniatis, T

    1980-05-01

    We report the isolation of a cluster of four alpha-like globin genes from a bacteriophage lambda library of human DNA (Lawn et al., 1978). Analysis of the cloned DNA confirms the linkage arrangement of the two adult alpha-globin genes (alpha 1 and alpha 2) previously derived from genomic blotting experiments (Orkin, 1978) and identifies two additional closely linked alpha-like genes. The nucleotide sequence of a portion of each of these alpha-like genes was determined. One of these sequences is tentatively identified as an embryonic zeta-globin gene (zeta 1) by comparison with structural data derived from purified zeta-globin protein (J. Clegg, personal communication), while the other sequence cannot be matched with any known alpha-like polypeptide sequence (we designate this sequence phi alpha 1). Localization of the four alpha-like sequences on a restriction map of the gene cluster indicates that the genes have the same transcriptional orientation and are arranged in the order 5'-zeta 1-phi alpha 1-alpha 2-alpha 1-3'. Genomic blotting experiments identified a second, nonallelic zeta-like globin gene (phi 2) located 10-12 kb 5' to the cloned zeta-globin gene. Comparison of the locations of restriction sites within alpha 1 and alpha 2 and heteroduplex studies reveal extensive sequence homology within and flanking the two genes. The homologous sequences, which are interrupted by two blocks of nonhomology, span a region of approximately 4 kb. This extensive sequence homology between two genes which are thought to be the products of an ancient duplication event suggests the existence of a mechanism for sequence matching during evolution. One consequence of this arrangement of homologous sequences is the occurrence of two types of deletions in recombinant phage DNA during propagation in E. coli. The locations and sizes of the two types of deletions are indistinguishable from those of the two types of deletions associated with alpha-thalassemia 2 (Embury et al., 1979

  6. The crystal structure of a TL/CD8{alpha}{alpha} complex at 2.1 {angstrom} resolution : implications for modulation of T cell activation and memory.

    SciTech Connect

    Liu, Y.; Xiong, Y.; Naidenko, O. V.; Liu, J.-H.; Zhang, R.; Joachimiak, A.; Kronenberg, M.; Cheroutre, H.; Reinherz, E. L.; Wang, J.-H.; Biosciences Division; Dana-Farber Cancer Inst.; Harvard Medical School; La Jolla Inst. of Allergy and Immunology

    2003-02-01

    TL is a nonclassical MHC class I molecule that modulates T cell activation through relatively high-affinity interaction with CD8{alpha}{alpha}. To investigate how the TL/CD8{alpha}{alpha} interaction influences TCR signaling, we characterized the structure of the TL/CD8{alpha}{alpha} complex using X-ray crystallography. Unlike antigen-presenting molecules, the TL antigen-binding groove is occluded by specific conformational changes. This feature eliminates antigen presentation, severely hampers direct TCR recognition, and prevents TL from participating in the TCR activation complex. At the same time, the TL/CD8{alpha}{alpha} interaction is strengthened through subtle structure changes in the TL {alpha}3 domain. Thus, TL functions to sequester and redirect CD8{alpha}{alpha} away from the TCR, modifying lck-dependent signaling.

  7. Summary of alpha-neutron sources in GADRAS.

    SciTech Connect

    Mitchell, Dean James; Thoreson, Gregory G.; Harding, Lee T.

    2012-05-01

    A common source of neutrons for calibration and testing is alpha-neutron material, named for the alpha-neutron nuclear reaction that occurs within. This material contains a long-lived alpha-emitter and a lighter target element. When the alpha particle from the emitter is absorbed by the target, neutrons and gamma rays are released. Gamma Detector Response and Analysis Software (GADRAS) includes built-in alpha-neutron source definitions for AcC, AmB, AmBe, AmF, AmLi, CmC, and PuC. In addition, GADRAS users may create their own alpha-neutron sources by placing valid alpha-emitters and target elements in materials within their one-dimensional models (1DModel). GADRAS has the ability to use pre-built alpha-neutron sources for plotting or as trace-sources in 1D models. In addition, if any material (existing or user-defined) specified in a 1D model contains both an alpha emitter in conjunction with a target nuclide, or there is an interface between such materials, then the appropriate neutron-emission rate from the alpha-neutron reaction will be computed. The gamma-emissions from these sources are also computed, but are limited to a subset of nine target nuclides. If a user has experimental data to contribute to the alpha-neutron gamma emission database, it may be added directly or submitted to the GADRAS developers for inclusion. The gadras.exe.config file will be replaced when GADRAS updates are installed, so sending the information to the GADRAS developers is the preferred method for updating the database. This is also preferable because it enables other users to benefit from your efforts.

  8. Smooth muscle alpha-actinin interaction with smitin.

    PubMed

    Chi, Richard J; Olenych, Scott G; Kim, Kyoungtae; Keller, Thomas C S

    2005-07-01

    Actin-myosin II filament-based contractile structures in striated muscle, smooth muscle, and nonmuscle cells also contain the actin filament-crosslinking protein alpha-actinin. In striated muscle sarcomeres, interactions between the myosin-binding protein titin and alpha-actinin in the Z-line provide an important structural linkage. We previously discovered a titin-like protein, smitin, associated with the contractile apparatus of smooth muscle cells. Purified native smooth muscle alpha-actinin binds with nanomolar affinity to smitin in smitin-myosin coassemblies in vitro. Smooth muscle alpha-actinin also interacts with striated muscle titin. In contrast to striated muscle alpha-actinin interaction with titin and smitin, which is significantly enhanced by PIP2, smooth muscle alpha-actinin interacts with smitin and titin equally well in the presence and absence of PIP2. Using expressed regions of smooth muscle alpha-actinin, we have demonstrated smitin-binding sites in the smooth muscle alpha-actinin R2-R3 spectrin-like repeat rod domain and a C-terminal domain formed by cryptic EF-hand structures. These smitin-binding sites are highly homologous to the titin-binding sites of striated muscle alpha-actinin. Our results suggest that direct interaction between alpha-actinin and titin or titin-like proteins is a common feature of actin-myosin II contractile structures in striated muscle and smooth muscle cells and that the molecular bases for alpha-actinin interaction with these proteins are similar, although regulation of these interactions may differ according to tissue.

  9. Modeling of polypeptide chains as C alpha chains, C alpha chains with C beta, and C alpha chains with ellipsoidal lateral chains.

    PubMed Central

    Fogolari, F; Esposito, G; Viglino, P; Cattarinussi, S

    1996-01-01

    In an effort to reduce the number of degrees of freedom necessary to describe a polypeptide chain we analyze the statistical behavior of polypeptide chains when represented as C alpha chains, C alpha chains with C beta atoms attached, and C alpha chains with rotational ellipsoids as models of side chains. A statistical analysis on a restricted data set of 75 unrelated protein structures is performed. The comparison of the database distributions with those obtained by model calculation on very short polypeptide stretches allows the dissection of local versus nonlocal features of the distributions. The database distribution of the bend angles of polypeptide chains of pseudo bonded C alpha atoms spans a restricted range of values and shows a bimodal structure. On the other hand, the torsion angles of the C alpha chain may assume almost all possible values. The distribution is bimodal, but with a much broader probability distribution than for bend angles. The C alpha - C beta vectors may be taken as representative of the orientation of the lateral chain, as the direction of the bond is close to the direction of the vector joining C alpha to the ad hoc defined center of the "steric mass" of the side chain. Interestingly, both the bend angle defined by C alpha i-C alpha i+1-C beta i+1 and the torsional angle offset of the pseudo-dihedral C alpha i-C alpha i+1-C alpha i+2-C beta i+2 with respect to C alpha i-C alpha i+1-C alpha i+2-C alpha i+3 span a limited range of values. The latter results show that it is possible to give a more realistic representation of polypeptide chains without introducing additional degrees of freedom, i.e., by just adding to the C alpha chain a C beta with given side-chain properties. However, a more realistic description of side chains may be attained by modeling side chains as rotational ellipsoids that have roughly the same orientation and steric hindrance. To this end, we define the steric mass of an atom as proportional to its van der

  10. Alpha-Ketoglutarate: Physiological Functions and Applications

    PubMed Central

    Wu, Nan; Yang, Mingyao; Gaur, Uma; Xu, Huailiang; Yao, Yongfang; Li, Diyan

    2016-01-01

    Alpha-ketoglutarate (AKG) is a key molecule in the Krebs cycle determining the overall rate of the citric acid cycle of the organism. It is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. AKG as a precursor of glutamate and glutamine is a central metabolic fuel for cells of the gastrointestinal tract as well. AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in the skeletal muscles and can be used in clinical applications. In addition to these health benefits, a recent study has shown that AKG can extend the lifespan of adult Caenorhabditis elegans by inhibiting ATP synthase and TOR. AKG not only extends lifespan, but also delays age-related disease. In this review, we will summarize the advances in AKG research field, in the content of its physiological functions and applications. PMID:26759695

  11. Pressure-confined Lyman-alpha clouds

    SciTech Connect

    Baron, E.; Carswell, R.F.; Hogan, C.J.; Weymann, R.J.

    1989-02-01

    Results are presented of numerical models of pressure-confined spherical gas clouds which produce absorption resembling the low to intermediate atomic column density lines found in high-redshift QSO spectra. One-dimensional hydrodynamical models including electron conduction are described, and the rate equations are solved to find ionization and excitation states. Results are presented for both static and adiabatically expanding confining media covering a range of initial pressures. It is found that Ly-alpha lines are very similar over a wide range of conditions and that the most promising diagnostic of pressure is to compare the column density in H I to that in He I and He II. No single-pressure model can explain the wide range of observed H I column densities. 18 references.

  12. Alpha Radiation Effects on Silicon Oxynitride Waveguides

    SciTech Connect

    Morichetti, Francesco; Grillanda, Stefano; Manandhar, Sandeep; Shutthanandan, Vaithiyalingam; Kimerling, Lionel; Melloni, Andrea; Agarwal, Anuradha M.

    2016-09-21

    Photonic technologies are today of great interest for use in harsh environments, such as outer space, where they can potentially replace current communication systems based on radiofrequency components. However, very much alike to electronic devices, the behavior of optical materials and circuits can be strongly altered by high-energy and high-dose ionizing radiations. Here, we investigate the effects of alpha () radiation with MeV-range energy on silicon oxynitride (SiON) optical waveguides. Irradiation with a dose of 5×1015 cm-2 increases the refractive index of the SiON core by nearly 10-2, twice as much that of the surrounding silica cladding, leading to a significant increase of the refractive index contrast of the waveguide. The higher mode confinement induced by -radiation reduces the loss of tightly bent waveguides. We show that this increases the quality factor of microring resonators by 20%, with values larger than 105 after irradiation.

  13. Miniature Neutron-Alpha Activation Spectrometer

    NASA Astrophysics Data System (ADS)

    Rhodes, Edgar; Holloway, James Paul; He, Zhong; Goldsten, John

    2002-10-01

    We are developing a miniature neutron-alpha activation spectrometer for in-situ analysis of chem-bio samples, including rocks, fines, ices, and drill cores, suitable for a lander or Rover platform for Mars or outer-planet missions. In the neutron-activation mode, penetrating analysis will be performed of the whole sample using a γ spectrometer and in the α-activation mode, the sample surface will be analyzed using Rutherford-backscatter and x-ray spectrometers. Novel in our approach is the development of a switchable radioactive neutron source and a small high-resolution γ detector. The detectors and electronics will benefit from remote unattended operation capabilities resulting from our NEAR XGRS heritage and recent development of a Ge γ detector for MESSENGER. Much of the technology used in this instrument can be adapted to portable or unattended terrestrial applications for detection of explosives, chemical toxins, nuclear weapons, and contraband.

  14. Severe alpha1-antitrypsin deficiency and pregnancy.

    PubMed

    Dempsey, O J; Godden, D J; Martin, P D; Danielian, P J

    1999-06-01

    This case study describes a successful pregnancy in a 27-yr-old patient with severe emphysema, secondary to alpha1-antitrypsin deficiency, genotype PiZZ. Despite significant respiratory compromise, more severe than previously reported, no complications ensued. Maternal pulmonary function did not deteriorate significantly until the 32nd week of pregnancy, with an elective Caesarean section being performed during the 37th week. This experience suggests that even severe maternal airflow obstruction is, in itself, not an absolute contra-indication to pregnancy. Pre-pregnancy multidisciplinary counselling is likely to be helpful in these patients, including frank discussion on the risks of pregnancy, the prospects of successful completion and the mother's future prognosis in relation to caring for the child.

  15. Targeting folate receptor alpha for cancer treatment

    PubMed Central

    Josephs, Debra H.; Ilieva, Kristina M.; Pellizzari, Giulia; Opzoomer, James; Bloomfield, Jacinta; Fittall, Matthew; Grigoriadis, Anita; Figini, Mariangela; Canevari, Silvana; Spicer, James F.; Tutt, Andrew N.; Karagiannis, Sophia N.

    2016-01-01

    Promising targeted treatments and immunotherapy strategies in oncology and advancements in our understanding of molecular pathways that underpin cancer development have reignited interest in the tumor-associated antigen Folate Receptor alpha (FRα). FRα is a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Its overexpression in tumors such as ovarian, breast and lung cancers, low and restricted distribution in normal tissues, alongside emerging insights into tumor-promoting functions and association of expression with patient prognosis, together render FRα an attractive therapeutic target. In this review, we summarize the role of FRα in cancer development, we consider FRα as a potential diagnostic and prognostic tool, and we discuss different targeted treatment approaches with a specific focus on monoclonal antibodies. Renewed attention to FRα may point to novel individualized treatment approaches to improve the clinical management of patient groups that do not adequately benefit from current conventional therapies. PMID:27248175

  16. [Alpha fetoprotein in umbilical cord blood].

    PubMed

    Guibaud, S; Bonnet, M; Thoulon, J M; Dorche, J; Dumont, M

    1975-02-08

    Quantitative measurement of alpha-foetoprotein was made on the cord blood of 158 new-born of gestational age ranging between 15 and 43 weeks. The technique used was that of simple radial immunodiffusion of Mancini which made possible the exact measurement of A.F.P. in all the specimens apart from 3. The correlation coefficient between the A.F.P. level in cord blood and gestational age is significant (r equals 0,85 for a risk p equals 0,001). However, the degree of difference at a given point in pregnancy and the difference in levels found in certain cases of twin pregnancies, suggest that factors other than gestational age (certain complications of pregnancy, for example) may influence foetal A,F.P.

  17. Alpha-synuclein structure, functions, and interactions

    PubMed Central

    Emamzadeh, Fatemeh Nouri

    2016-01-01

    At present, when a clinical diagnosis of Parkinson's disease (PD) is made, serious damage has already been done to nerve cells of the substantia nigra pars compacta. The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of this disease that possibly prevents accumulation of toxic aggregates. As a molecular biomarker for the detection of PD in its earlier stages, alpha-synuclein (α-syn), which is a key component of Lewy bodies, in which it is found in an aggregated and fibrillar form, has attracted considerable attention. Here, α-syn is reviewed in details. PMID:27904575

  18. Laboratory diagnosis of alpha1-antitrypsin deficiency.

    PubMed

    Ferrarotti, Ilaria; Scabini, Roberta; Campo, Ilaria; Ottaviani, Stefania; Zorzetto, Michele; Gorrini, Marina; Luisetti, Maurizio

    2007-11-01

    The laboratory diagnosis of alpha(1)-antitrypsin (AAT) deficiency (AATD) has evolved over the last 40 years since the first cases of the disorder were reported. It is currently performed in specialized centers, and it requires a combination of different biochemical methods: nephelometric AAT concentration, isoelectric focusing, genotyping, and sequencing. The availability of matrices such as the dried blood spot have facilitated the implementation of laboratory analyses for AATD, but they have also challenged laboratories to develop more reliable and reproducible techniques starting from dried blood. In this article, we describe the protocols we have optimized for AATD diagnosis from dried blood spot, in an attempt to hopefully provide useful information for physicians and scientists involved in this diagnostic line. We also describe the diagnostic flowchart for AATD detection that we have developed accordingly.

  19. [Estrogen receptor alpha in obesity and diabetes].

    PubMed

    Cahua-Pablo, José Ángel; Flores-Alfaro, Eugenia; Cruz, Miguel

    2016-01-01

    Estradiol (E2) is an important hormone in reproductive physiology, cardiovascular, skeletal and in the central nervous system (CNS). In human and rodents, E2 and its receptors are involved in the control of energy and glucose metabolism in health and metabolic diseases. The estrogen receptor (ER) belongs to the superfamily of nuclear receptors (NR), which are transcription factors that regulate gene expression. Three ER, ER-alpha, ER-beta and the G protein-coupled ER (GPER; also called GPR30) in tissues are involved in glucose and lipid homeostasis. Also, it may have important implications for risk factors associated with metabolic syndrome (MS), insulin resistance (IR), obesity and type 2 diabetes (T2D).

  20. Transamination of aminoalkylphosphonic acids with alpha ketoglutarate.

    PubMed

    Roberts, E; Simonsen, D G; Horiguchi, M; Kittredge, J S

    1968-02-23

    Dialyzed homogenates prepared from Escherichia coli, Tetrahymena pyriformis, sea anemone (Anthopleura elegantissima), and mouse liver were tested for ability to transaminate 17 aminoalkylphosphonic acids with alpha-ketoglutarate. 2-Aminoethylphosphonic acid (2-AEP), which occurs naturally in Tetrahymena and anemone, was transaminated by these latter organisms more than any of the substances tested, but not by preparations from liver or E. coli. 3-Aminopropylphosphonic acid was transaminated by all preparations, but much less by Tetrahymena or anemone than was 2-AEP. 2-Amino-3-phosphonopropionic acid was transaminated by all preparations. 2-Amino-4-phosphonobutyric acid was transaminated by three of the preparations, but not by liver. Of the other 13 substances tested, the following gave positive results: DL-1,2-diaminoethylphosphonic acid with E. coli, DL-1,2-diaminoethylphosphonic and aminomethylphosphonic acids with Tetrahymena, DL-1-aminopropylphosphonic acid with anemone, and DL-1-aminoethylphosphonic and DL-1-aminobutylphosphonic acids with liver. The significance of these transaminations is discussed.