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Sample records for analogue iloprost protects

  1. Early protective effects of Iloprost after experimental spinal cord injury.

    Science.gov (United States)

    Attar, A; Tuna, H; Sargon, M F; Yüceer, N; Türker, R K; Egemen, N

    1998-06-01

    This investigation was undertaken to study the early protective effects of Iloprost, a stable analogue of prostacyclin, after spinal cord injury in rabbit. Sixteen adult male rabbits (New Zealand Albino) were injured by application of epidural aneurysm clip. Eight rabbits received an intravenous (i.v.) infusion of 30 micrograms kg-1 Iloprost, and eight rabbits received an infusion of saline (SF). Treatment with Iloprost started immediately after spinal cord injury and continued for one hour. Evoked potentials were recorded for each rabbit at one, 15, and 60 minutes after the spinal cord injury. Twenty-four hours later, all the rabbits were deeply anesthetized and spinal cords were removed for histopathological examinations. There was no meaningful statistical difference between cortical somatosensorial evoked potentials (CSEP) of the saline and Iloprost group. However, light and electron microscopic studies showed that the Iloprost treated group had moderate protection of myelin and axons; and limited edema. These results suggest that intravenous Iloprost treatment after spinal cord injury has a highly protective effect without any side effects.

  2. Early protective effects of iloprost after experimental spinal cord ischemia in rabbits.

    Science.gov (United States)

    Coskun, K; Attar, A; Tuna, H; Sargon, M F; Yüceer, N; Türker, R K; Egemen, N

    2000-01-01

    The potential role of Iloprost, a stable analogue of prostocyclin, in treating spinal cord ischemia was investigated in rabbits subjected to aortic occlusion for 15 minutes. Ten adult rabbits weighing 2-2.5 kg received an intravenous infusion of saline (SF) as a control group and 14 rabbits received an intravenous infusion of Iloprost, 25 microg/kg/h. Iloprost infusion was started immediately after clamping of the aorta and continued 60 minutes thereafter. Cortical somatosensorial evoked potentials (CSEP) were recorded during the pre-ischemic period as a baseline and post-ischemic readings were taken at 15, 30 and 60 minutes. There was no statistically significant difference between CSEP of the saline and Iloprost treated groups (p < 0.05). All animals were examined neurologically by using a modification of Tarlov scale and all subjects were then deeply anesthetized and their spinal cords were removed for light and electron microscopic examinations at 24 h after spinal cord ischemia. In order to obtain an accurate comparison of ultrastructural changes between saline treated and Iloprost treated groups, a grading scale was performed. The light microscopic and ultrastructural analysis of the Iloprost treated group revealed that there was moderate protection of the myelin and axons and edema was attenuated. Findings of this study suggest that Iloprost exerts a protective effect on spinal cord ischemia. However, further studies are needed to reveal possible mechanisms of protection provided by Iloprost.

  3. The stable prostacyclin-analogue, iloprost, unlike prostanoids and leukotrienes, potently stimulates cyclic adenosine monophosphate synthesis of primary astroglial cell cultures.

    Science.gov (United States)

    Seregi, A; Schobert, A; Hertting, G

    1988-06-01

    The effect of different eicosanoids on adenosine-3', 5'-cyclic-monophosphate (cAMP) accumulation in primary astroglial cell cultures prepared from newborn rat brain was studied. The stable prostacyclin-analogue, iloprost, effectively stimulated cAMP synthesis in a concentration-dependent, saturable manner, the EC50 being about 3 x 10(-8) M. Prostaglandin (PG) E2 was less potent, without reaching plateau even at 10(-5) M. Prostaglandins D2 and F2 alpha, and the stable thromboxane A2-analogue, U 46619, as well as leukotrienes (LT) B4, C4, D4 and E4 were not effective and did not attenuate basal or isoprenaline (10(-8) M)-stimulated astroglial cAMP formation. This is the first indication for the existence of a prostacyclin receptor coupled positively to the adenylate cyclase in astrocytes. Other eicosanoids are unlikely to be involved in receptor-mediated regulation of astroglial cAMP levels.

  4. Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

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    Weissmann Norbert

    2005-07-01

    Full Text Available Abstract Inhaled prostanoids and phosphodiesterase (PDE inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor, motapizone (PDE3 inhibitor or 8-Methoxymethyl-IBMX (PDE1 inhibitor synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of PPA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor.

  5. Iloprost-induced desensitization of the prostacyclin receptor in isolated rabbit lungs

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    Schrör Karsten

    2007-01-01

    Full Text Available Abstract Background The rapid desensitization of the human prostacyclin (IP in response to agonist binding has been shown in cell culture. Phosphorylation of the IP receptor by protein kinase C (PKC has been suggested to be involved in this process. Methods and results In this study we investigated the vasodilatory effects of iloprost, a stable prostacyclin analogue, in perfused rabbit lungs. Continuous infusion of the thromboxane mimetic U46619 was employed to establish stable pulmonary hypertension. A complete loss of the vasodilatory response to iloprost was observed in experiments with continuous iloprost perfusion, maintaining the intravascular concentration of this prostanoid over a 180 min period. When lungs under chronic iloprost infusion were acutely challenged with inhaled iloprost, a corresponding complete loss of vasoreactivity was observed. This desensitization was not dependent on upregulation of cAMP-specific phosphodiesterases or changes in adenylate cyclase activity, as suggested by unaltered dose-response curves to agents directly affecting these enzymes. Application of a prostaglandin E1 receptor antagonist 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH 6809 or the PKC inhibitor bisindolylmaleimide I (BIM enhanced the vasodilatory response to infused iloprost and partially prevented tachyphylaxis. Conclusion A three-hour infusion of iloprost in pulmonary hypertensive rabbit lungs results in complete loss of the lung vasodilatory response to this prostanoid. This rapid desensitization is apparently not linked to changes in adenylate cyclase and phosphodiesterase activation, but may involve PKC function and co-stimulation of the EP1 receptor in addition to the IP receptor by this prostacyclin analogue.

  6. Inhaled iloprost for the treatment of pulmonary hypertension

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    H. Olschewski

    2009-03-01

    Full Text Available Prostacyclin and its analogues (prostanoids are potent vasodilators, and exhibit antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary arterial hypertension (PAH is characterised by vasoconstriction, thrombosis and proliferation, and is associated with reduced synthesis of endogenous prostacyclin. This provides a strong rationale for the use of prostanoids to treat PAH, a concept that is now supported by more than two decades of clinical research and experience. Intravenous and subcutaneous prostanoids have clearly demonstrated efficacy in severe PAH, but adverse events related to the drug delivery system, systemic side-effects and tachyphylaxis have driven research into alternative prostanoid treatments. Iloprost is administered by inhalation, and thus avoids most of the systemic side-effects associated with i.v. or subcutaneous prostanoid infusion. Two randomised controlled 12-week trials in patients with PAH have demonstrated efficacy and a favourable safety profile for iloprost as monotherapy (the AIR trial and in combination with oral bosentan (STEP. Open-label uncontrolled long-term studies of inhaled iloprost therapy indicate that this treatment may improve long-term outcomes in PAH.

  7. Long-term clinical results after iloprost treatment for bone marrow edema and avascular necrosis

    OpenAIRE

    Tim Claßen; Antonia Becker; Stefan Landgraeber; Marcel Haversath; Xinning Li; Christoph Zilkens; Rüdiger Krauspe; Marcus Jäger

    2016-01-01

    The treatments of avascular osteonecrosis (AVN) include both conservative and surgical methods which are dependent on the stage and progression of the disease. The vasoactive- prostaglandin-analogue iloprost (PGI2) has been utilized in several areas of medicine and recently has been used for the treatment of AVN. A total of 108 patients with 136 osteonecrosis of different joints, etiology and severity were treated with iloprost. The mean follow-up was 49.71 months: range 15-96 months, and out...

  8. Iloprost infusion by a new device as a portable syringe pump: safety, tolerability and agreement

    Directory of Open Access Journals (Sweden)

    Paola Faggioli

    2012-12-01

    Full Text Available Background Iloprost, prostacyclin (PGI2 analogue, effective in treatment of peripheral arterial disease, secondary Raynaud's phenomenon (RP to connective tissue disease (CTD, vasculitis, pulmonary hypertension, is usually infused through peristaltic pump, or recently through a flow regulator.Materials and methods We tested a new portable syringe pump (Pompa Infonde®, Italfarmaco S.p.A., Cinisello Balsamo, Milano on 120 patients affected by RP to CTD and cryoglobulinaemia, in iloprost therapy with a flow regulator.Results Iloprost infused through portable syringe pump is better tolerated, better appreciated by the patients and nurses and no difference was observed on therapeutic effects, with a lower incidence of side effects statistically significant. Only 3 patients were unable to tolerate the device (2 for changes in pressure and 1 for fear and shifted to traditional method of iloprost infusion.Conclusions Iloprost infusion through the portable syringe Pompa Infonde® appears to be safe, better tolerated, more acceptable and equally effective compared to infusion through a flow regulator.

  9. Long-term clinical results after iloprost treatment for bone marrow edema and avascular necrosis

    Directory of Open Access Journals (Sweden)

    Tim Claßen

    2016-03-01

    Full Text Available The treatments of avascular osteonecrosis (AVN include both conservative and surgical methods which are dependent on the stage and progression of the disease. The vasoactive- prostaglandin-analogue iloprost (PGI2 has been utilized in several areas of medicine and recently has been used for the treatment of AVN. A total of 108 patients with 136 osteonecrosis of different joints, etiology and severity were treated with iloprost. The mean follow-up was 49.71 months: range 15-96 months, and outcome measurements recorded regarding subjective complaints, visual analog scale (pain, function and survival. The outcome scores used include the Harris Hip Score, Knee Society score, Foot and Ankle Survey, visual analogue scale (VAS and a separate questionnaire. The location and etiology of AVN in our study demonstrated the typical pattern. All of the observed side effects of the therapy were minor and completely reversible. Most of patients (74.8% showed a significant improvement of subjective complaints and decrease in VAS pain scores after the treatment with iloprost. However, 20% of the treated joints with the stadium Association for Research on Osseous Circulation (ARCO grade 2, 71% with ARCO 3 and 100% with ARCO 4 underwent subsequent total joint replacement. The medical treatment of bone marrow edema or avascular osteonecrosis by Iloprost provides an safe and effective alternative strategy in the management of AVN presenting in the early stages (ARCO 1 or 2. For more advanced stages (ARCO 3 or 4, surgical intervention should be prioritized.

  10. Long-term Clinical Results after Iloprost Treatment for Bone Marrow Edema and Avascular Necrosis

    Science.gov (United States)

    Claßen, Tim; Becker, Antonia; Landgraeber, Stefan; Haversath, Marcel; Li, Xinning; Zilkens, Christoph; Krauspe, Rüdiger; Jäger, Marcus

    2016-01-01

    The treatments of avascular osteonecrosis (AVN) include both conservative and surgical methods which are dependent on the stage and progression of the disease. The vasoactive-prostaglandin-analogue iloprost (PGI2) has been utilized in several areas of medicine and recently has been used for the treatment of AVN. A total of 108 patients with 136 osteonecrosis of different joints, etiology and severity were treated with iloprost. The mean follow-up was 49.71 months: range 15-96 months, and outcome measurements recorded regarding subjective complaints, visual analog scale (pain), function and survival. The outcome scores used include the Harris Hip Score, Knee Society score, Foot and Ankle Survey, visual analogue scale (VAS) and a separate questionnaire. The location and etiology of AVN in our study demonstrated the typical pattern. All of the observed side effects of the therapy were minor and completely reversible. Most of patients (74.8%) showed a significant improvement of subjective complaints and decrease in VAS pain scores after the treatment with iloprost. However, 20% of the treated joints with the stadium Association for Research on Osseous Circulation (ARCO) grade 2, 71% with ARCO 3 and 100% with ARCO 4 underwent subsequent total joint replacement. The medical treatment of bone marrow edema or avascular osteonecrosis by Iloprost provides an safe and effective alternative strategy in the management of AVN presenting in the early stages (ARCO 1 or 2). For more advanced stages (ARCO 3 or 4), surgical intervention should be prioritized. PMID:27114807

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

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

    2010-05-15

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

  12. Transcutaneous oxygen and carbon dioxide levels with iloprost administration in diabetic critical limb ischemia.

    Science.gov (United States)

    Melillo, Elio; Ferrari, Mauro; Balbarini, Alberto; Pedrinelli, Roberto

    2006-01-01

    Iloprost, a prostacyclin analogue, is a treatment option for surgically unsuitable diabetic chronic critical limb ischemia (CLI), although its outcome is difficult to be anticipated clinically. Whether transcutaneous (tc) oxygen tension (PO2) predicts the response to iloprost in diabetic CLI is unclear at this point and, in that same context, the prognostic role of tc carbon dioxide tension (PCO2), another ischemia-sensitive parameter, is unknown. Supine and dependent tcPO2 and tcPCO2 were measured at baseline and after 4 weeks of iloprost treatment in 31 limbs of 26 type-2 diabetic angiopathies with CLI not amenable to surgery. Success was defined as pain relief and significant reduction of analgesics. Clinical outcome was stratified by baseline tcPO2 and tcPCO2 tertiles, and likelihood ratios (LR) quantified the increase from pretest chances given a certain result. Iloprost succeeded in 16 (52%) and failed in 15 limbs (48%) and post-treatment tcPO2 followed a parallel course. Failures increased by ascending baseline tcPCO2 and descending tcPO2 tertiles; successes behaved specularly. Predictions of failure based on elevated tcPCO2 (>53 mm Hg) were more efficient than relying on depressed tcPO2 (LR 10.7 vs 3.6); success was almost certain when tcPO2 was >23 mm Hg (LR = 17.8). Dependent determinations were less useful than supine measurements for prognostic use. Elevated tcPCO2 predicted failure efficiently and high tcPO2 was a useful prognostic tool for success of iloprost, suggesting that their combined use may allow better prognostic stratification and improve the therapeutic approach to diabetic CLI.

  13. Effect of cyclic intravenous Iloprost therapy in patients with Idiopathic Pulmonary Artery Hypertension

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    Majid MalekMohammad

    2017-02-01

    Full Text Available Background: Prostacyclin have positive effects in improving the cardiopulmonary variables, signs and the hemodynamics of cases with a idiopathic pulmonary artery hypertension (IPAH.The objective of this study was to determine the benefits of intermittent intravenous Iloprost infusion on IPAH cases. Material and Methods: This longitudinal study was conducted on IPAH cases (no=20 at Massih Daneshvari Hospital (2011-2013, treated with cyclic intravenous Iloprost. The treatment consisted of a 6 hours/day Iloprost infusion for three consecutive days. Every 6 weeks the infusion was repeated again with a velocity of 0.5-2.0 ng/kg/min. Before, during and after the completion of functional class, six-minute walk test (6MWD, pulmonary artery pressure (PAP, right ventricular pressure (RVP, and plasma NT-ProBNP level were measured. Result: At follow-up, NYHA score, PAP, RVP, NT-ProBNP and PASP were significantly decreased (P<0.001, while the distance walked in 6MWD was significantly increased. Conclusion: Our results suggest that cyclic intravenous Iloprost might improve the NYHA score, PAP, RVP and can provide a protection against the development or worsening of PAH in patients with IPAH.

  14. Effects of iloprost on bleomycin-induced pulmonary fibrosis in rats compared with methyl-prednisolone

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    Z.A. Aytemur

    2012-11-01

    Full Text Available Objective: Prostacyclin (PGI2 has been shown to inhibit the expression of pro-inflammatory and pro-fibrotic mediators in pulmonary fibrosis. In this study, we aimed to test the preventive effects of intraperitoneally administered iloprost, a stable PGI2 analog, on bleomycin-induced pulmonary fibrosis in rats and to compare the effects of iloprost with the effects of methyl-prednisolone, a traditional therapy. Methods: Rats were randomly allocated into four groups: 1. Saline alone (n = 6; 2. Bleomycin + placebo (n = 7; 3. Bleomycin + methyl-prednisolone (n = 7; 4. Bleomycin + iloprost (n = 7. Fibrotic changes in the lungs were demonstrated by analyzing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content. Results: Fibrosis was made in the lungs of rats by bleomycin experimentally. Fibrosis scores in the methyl-prednisolone and the iloprost groups were significantly lower than in the placebo group (p < 0.05. Furthermore, the score of the iloprost group was significantly lower than the score of the methyl-prednisolone group. The hydroxyproline content was significantly less in the methyl-prednisolone and the iloprost groups (p < 0.05. In the placebo group, the neutrophil percentage in bronchoalveolar lavage was significantly higher than in the other groups, whereas the macrophage percentage in placebo group was significantly lower (p < 0.05. Conclusion: Iloprost has protective effect on the pulmonary fibrosis induced by bleomycin and it may be more effective in decreasing fibrotic changes than methyl-prednisolone. Resumo: Objetivo: A prostaciclina (PGI2 é conhecida por inibir a expressão de mediadores pró-inflamatórios e pró-fibróticos na fibrose pulmonar. Neste estudo, procurou-se testar os efeitos preventivos do iloprost administrado por via intraperitoneal, um análogo estável do PGI2, na fibrose

  15. Inhaled iloprost for sarcoidosis associated pulmonary hypertension.

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    Baughman, R P; Judson, M A; Lower, E E; Highland, K; Kwon, S; Craft, N; Engel, P J

    2009-07-01

    Patients with sarcoidosis associated pulmonary hypertension (SAPH) have responded to systemic prostacyclin therapy. To determine the rate of response to inhaled prostacyclin, iloprost, in SAPH. Sarcoidosis patients with pulmonary hypertension and no evidence for left ventricular dysfunction were enrolled in an open label, prospective study. Patients underwent right heart catheterization and six minute walk (6MW) test. Quality of life was evaluated using several instruments, including the Saint George Respiratory Questionnaire (SGRQ). Patients received 5 mcg of inhaled iloprost every 2-3 hours while awake. After four months of therapy, patients underwent repeat cardiac catheterization, 6 MW test, and completed quality of life questionnaires. Of the 22 patients enrolled, 15 completed all 16 weeks of therapy. The most common reasons for study discontinuation included drug associated cough (3 patients) and compliance with the prescribed number of treatments per day (2 patients). Six patients experienced a 20% or greater decrease in pulmonary vascular resistance (PVR) from baseline with five of these six patients also showing > or = 5 mm Hg reduction in PA mean. Although three patients improved the 6MW distance by at least 30 meters, only one had a decrease in PVR. At 16 weeks a significant decrease was reported in the SGRQ activity score (p = 0.0273), with seven patients having a 4 point or greater decrease. Inhaled iloprost as monotherapy was associated with an improvement in pulmonary hemodynamics and quality of life as assessed by the SGRQ activity score in some sarcoidosis patients with SAPH.

  16. Iloprost Instillation in Two Neonates with Pulmonary Hypertension

    International Nuclear Information System (INIS)

    Aktas, S.; Aksu, M.; Hirfanoglu, I. M.; Atalay, Y.; Turkyilmaz, C.; Unal, S.

    2017-01-01

    Pulmonary hypertension may coexist with certain diseases in neonates. Iloprost inhalation is one of the treatments which cause selective pulmonary vasodilatation. Inhalation is not an easy way of drug administration in mechanically ventilated infants; as some exhibit desaturations during inhalation. Moreover, inhalation of drug requires cessation of mechanical ventilation, if patient is on high frequency oscillatory ventilation. We presented two patients with pulmonary hypertension; term baby with congenital diaphragmatic hernia and preterm baby with respiratory distress syndrome; who had iloprost instillation during mechanical ventilation treatment. Iloprost instillation was well tolerated with no side effects in the term patient with diaphragmatic hernia; whereas severe blood pressure fluctuations were observed in the preterm infant. This report may courage administration of iloprost in term neonates with resistant pulmonary hypertension. (author)

  17. Role of iloprost and bosentan in pulmonary arterial hypertension ...

    African Journals Online (AJOL)

    Results: Several studies were able to outline the haemodynamic advantages of iloprost and bosentan in pulmonary arterial hypertension, as evident by improvement in six-minute walk test of patients treated with these agents. Conclusion: This review was able to outline the pharmacotherapeutic benefits and role played by ...

  18. Functional Analogues of Salicylic Acid and Their Use in Crop Protection

    OpenAIRE

    Lydia Faize; Mohamed Faize

    2018-01-01

    Functional analogues of salicylic acid are able to activate plant defense responses and provide attractive alternatives to conventional biocidal agrochemicals. However, there are many problems that growers must consider during their use in crop protection, including incomplete disease reduction and the fitness cost for plants. High-throughput screening methods of chemical libraries allowed the identification of new compounds that do not affect plant growth, and whose mechanisms of action are ...

  19. Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A(4)-Mediated Effect.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia\\/reperfusion (I\\/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A(4) in experimental I\\/R-mediated lung injury. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I\\/R group); (3) I\\/R and SC236, a selective COX-2 inhibitor; (4) I\\/R and aspirin; and (5) I\\/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed by wet\\/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed. RESULTS: I\\/R significantly increased tissue MPO, the wet\\/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I\\/R increased COX-2 immunostaining and both PGE(2) and 6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I\\/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.

  20. [Aerosolized iloprost therapy for pulmonary hypertensive crisis in 4 patients with idiopathic pulmonary arterial hypertension].

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    Deng, Ke-wu; Zhou, Yu-jie; Xu, Xi-qi; Wu, Ming-ying; Wang, Guo-hong; Bian, Hong; Chen, Bo; Wang, Chun-bo

    2012-10-01

    To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

  1. User preference for a portable syringe pump for iloprost infusion.

    Science.gov (United States)

    Laria, Antonella; Lurati, Alfredo Maria; Re, Katia Angela; Marrazza, Maria Grazia; Mazzocchi, Daniela; Farina, Alberto; Scarpellini, Magda

    2015-01-01

    Administration of intravenous iloprost - a first-line European League Against Rheumatism (EULAR)-recommended choice for the treatment of scleroderma (SSc)-related digital vasculopathy - requires repeated treatment cycles of 6 hours per day in a hospital setting. During the infusion, patient mobility is considerably restricted due to the size and fixity of traditional syringe pumps. The aim of this study was to evaluate the satisfaction level of patients and nurses, after the introduction of a new portable syringe pump (Infonde(®), Italfarmaco S.p.A., Milan, Italy) at the Department of Rheumatology, Magenta Hospital, Milan, Italy. Thirty-four consecutive SSc patients receiving stable therapy with iloprost, previously administered with a fixed pump, were treated using the portable Infonde(®) pump. Patients (n=34) and nurses (n=4) were asked to answer a nine- and six-item questionnaire, respectively, to assess the satisfaction of the administration comparing the new device versus the previous one. The health care staff of the ward developed the questionnaire, and the response scores ranged from 0 (fixed device better) to 10 (portable device better); thus a score >5 indicates a preference for Infonde(®). Patients' answers indicated a preference towards the new portable syringe pump, versus the previous fixed pump. Questionnaires administered to patients generated a total of 306 responses, with over 95% of the responses in the range 8-10, of which 89% had a score equal to 10. The responses of nurses showed a score equal to 10 in 100% cases. No significant adverse events were recorded, indicating no change in the tolerability profile of the drug. Iloprost administration with Infonde(®) pump was preferred by both patients and health care professionals, and was well tolerated. The possibility to perform daily activities and the freedom of movement suggest a positive impact of Infonde(®) on the treatment, with a potential favorable effect on the quality of life of

  2. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

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    Camats, N. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, F. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, J.J. [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, J. [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin-Mateo, M. [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, M. Garcia, E-mail: Montserrat.Garcia.Caldes@uab.es [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)

    2009-10-02

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F{sub 0}) with reproductive parameters, and in the somatic cells of the resulting foetuses (F{sub 1}) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  3. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    International Nuclear Information System (INIS)

    Camats, N.; Garcia, F.; Parrilla, J.J.; Calaf, J.; Martin-Mateo, M.; Caldes, M. Garcia

    2009-01-01

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F 0 ) with reproductive parameters, and in the somatic cells of the resulting foetuses (F 1 ) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  4. Oral sildenafil and inhaled iloprost in the treatment of pulmonary hypertension of the newborn.

    Science.gov (United States)

    Kahveci, Hasan; Yilmaz, Osman; Avsar, Ummu Zeynep; Ciftel, Murat; Kilic, Omer; Laloglu, Fuat; Ozturk, Kezban

    2014-12-01

    This study was performed to examine the effectiveness and safety of oral sildenafil and inhaled iloprost in term newborns with persistent pulmonary hypertension of the newborn (PPHN). Oral sildenafil and inhaled iloprost were administered to 27 and 20 neonates, respectively, for treatment of persistent pulmonary hypertension. All patients were term infants at 37 gestational weeks or older. In the sildenafil group, 14 patients had meconium aspiration syndrome, 8 had asphyxia (hypoxic ischemic encephalopathy stages II and III), 3 had congenital pneumonia, 1 had transient tachypnea, and 1 had idiopathic PPHN. In the iloprost group, 9 patients had meconium aspiration syndrome, 7 had asphyxia (hypoxic ischemic encephalopathy stages II and III), 3 had congenital pneumonia, and 1 had transient tachypnea. Sildenafil citrate was administered via an oral feeding tube. Iloprost was administered endotracheally to patients on mechanical ventilation using a jet nebulizer. Iloprost appeared to be more effective than sildenafil in the treatment of PPHN with regard to time to adequate clinical response, ventilatory parameters, duration of drug administration, duration of mechanical ventilation, duration of return to normal values of respiratory failure indices, use of MgSO4 as a second vasodilator and requirement for support with inotropic agents. We observed no side effects on blood pressure or homeostasis in any of the patients in the iloprost group. Systemic hypotension was significantly elevated in the sildenafil group. Four and three infants died of PPHN in the sildenafil and iloprost groups, respectively. Pulmonary systolic arterial pressure decreased to normal levels in the remaining 40 patients, and they were discharged from hospital. We suggested that inhaled iloprost may be a safe and effective treatment choice in newborn infants with persistent pulmonary hypertension. In cases where treatment with inhaled iloprost, ECMO or INO is not possible, oral sildenafil can be an

  5. The application of high voltage digital and analogue unit protections to utility telecommunications systems

    Energy Technology Data Exchange (ETDEWEB)

    Farthing, H. [SNC Group, Montreal, PQ (Canada); Verzosa, Q.R.; Care, J.M. [SNC Group, Montreal, PQ (Canada)

    1996-08-01

    The use of fibre optic and digital microwave systems, both within and without utility communications networks was discussed. Their availability has led to the development of phase comparison and differential current relaying systems which provide enhanced protective features for transmission circuits. The application of fibre optic cable or microwave radio data links overcomes problems caused by ground potential rise and transferred potential damage in metallic pilot wire schemes. Some problems were encountered when installing digital differential current and analogue phase comparison relaying systems to a 220 kV power transmission system where a mix of analog microwave, digital microwave radio and multiplexed fibre optic channels were available. However, the relays were successfully installed with the application of digital pilot differential relays to the power system which enabled fast fault clearance to be achieved. 7 refs., 1 tab., 1 fig.

  6. User preference for a portable syringe pump for iloprost infusion

    Directory of Open Access Journals (Sweden)

    Laria A

    2015-05-01

    Full Text Available Antonella Laria,1 Alfredo Maria Lurati,1 Katia Angela Re,1 Maria Grazia Marrazza,1 Daniela Mazzocchi,1 Alberto Farina,2 Magda Scarpellini,1 1Department of Rheumatology, Fornaroli Hospital, Magenta, Milan, Italy; 2Medical Affairs Department, Italfarmaco S.p.A., Cinisello Balsamo, Milan, Italy Purpose: Administration of intravenous iloprost – a first-line European League Against Rheumatism (EULAR-recommended choice for the treatment of scleroderma (SSc-related digital vasculopathy – requires repeated treatment cycles of 6 hours per day in a hospital setting. During the infusion, patient mobility is considerably restricted due to the size and fixity of traditional syringe pumps. The aim of this study was to evaluate the satisfaction level of patients and nurses, after the introduction of a new portable syringe pump (Infonde®, Italfarmaco S.p.A., Milan, Italy at the Department of Rheumatology, Magenta Hospital, Milan, Italy. Patients and methods: Thirty-four consecutive SSc patients receiving stable therapy with iloprost, previously administered with a fixed pump, were treated using the portable Infonde® pump. Patients (n=34 and nurses (n=4 were asked to answer a nine- and six-item questionnaire, respectively, to assess the satisfaction of the administration comparing the new device versus the previous one. The health care staff of the ward developed the questionnaire, and the response scores ranged from 0 (fixed device better to 10 (portable device better; thus a score >5 indicates a preference for Infonde®. Results: Patients' answers indicated a preference towards the new portable syringe pump, versus the previous fixed pump. Questionnaires administered to patients generated a total of 306 responses, with over 95% of the responses in the range 8–10, of which 89% had a score equal to 10. The responses of nurses showed a score equal to 10 in 100% cases. No significant adverse events were recorded, indicating no change in the tolerability

  7. Binding of 3H-iloprost to rat gastric mucosa: a pitfall in performing radioligand binding assays

    International Nuclear Information System (INIS)

    Beinborn, M.; Kromer, W.; Staar, U.; Sewing, K.F.

    1985-01-01

    Binding of 3 H-iloprost was studied in a 20,000 x g sediment of the rat gastric mucosa. When pH in both test tubes for total and non-specific binding was kept identical, no displaceable binding of iloprost could be detected. When no care was taken to keep the pH identical in corresponding test tubes of the binding assay, changes in pH simulated specific and displaceable binding of iloprost. Therefore it is concluded that - in contrast to earlier reports - it is not possible to demonstrate specific iloprost binding using the given method

  8. The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749

    Directory of Open Access Journals (Sweden)

    Bärthel Erik

    2013-01-01

    Full Text Available Abstract Background Liver graft dysfunction can deteriorate to complete organ failure and increases perioperative morbidity and mortality after liver transplantation. Therapeutic strategies reducing the rate of graft dysfunction are of current clinical relevance. One approach is the systemic application of prostaglandins, which were demonstrated to be beneficial in reducing ischemia-reperfusion injury. Preliminary data indicate a positive effect of prostacyclin analogue iloprost on allograft viability after liver transplantation. The objective of the study is to evaluate the impact of iloprost in a multi-center trial. Methods/Design A prospective, double-blinded, randomized, placebo-controlled multicenter study in a total of 365 liver transplant recipients was designed to assess the effect of intravenous iloprost after liver transplantation. Primary endpoint will be the primary graft dysfunction characterized as presentation of one or more of the following criteria: ALAT or ASAT level > 2000 IU/ml within the first 7 postoperative days, bilirubine ≥ 10 mg/dl on postoperative day 7; INR ≥ 1.6 on postoperative day 7 or initial non-function. Secondary endpoints are parameters of post-transplant morbidity, like rates of infections, biliary complications, need of clotting factors or renal replacement therapy and the graft and patient survival. Discussion A well-established treatment concept to avoid graft dysfunction after liver transplantation does not exist at the moment. If the data of this research project confirm prior findings, iloprost would improve the general outcome after liver transplantation. Trial Registration German Clinical Trials Register: DRKS00003514. Current Controlled Trials Register: ISRCTN12622749.

  9. Antioxidant, Liver Protective and Angiotensin I-converting Enzyme Inhibitory Activities of Old Laying Hen Hydrolysate in Crab Meat Analogue

    Directory of Open Access Journals (Sweden)

    Sang Keun Jin

    2016-12-01

    Full Text Available The purpose of this study was to evaluate the antioxidative activities of Crab meat analogue prepared with protein hydrolysates obtained from mechanically deboned chicken meat (MDCM from spent laying hens. 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH radical-scavenging activity was increased by adding MDCM hydrolysates during storage, and activity correlated with the concentration of DPPH added up to 6 weeks of storage. Hydroxyl radical-scavenging activity was increased in all analogues containing MDCM hydrolysates. At 0 days of storage, angiotensin I-converting enzyme (ACE-inhibitory activity was increased by the addition of MDCM hydrolysates. Activity did not correlate after 6 weeks of storage, in which ACE-inhibitory activity was increased with low concentrations of MDCM hydrolysates, but no ACE-inhibitory activity was observed at higher concentrations. The liver-protecting activity of crab meat analogue was shown to be around 60% of the positive control; however, it was not significantly different among the samples during storage. These results support the use of MDCM as a source of health-promoting constituents in crab meat analogue.

  10. Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis : A multicentre, placebo-controlled, dose-comparison study

    NARCIS (Netherlands)

    Black, CM; Halkier-Sorensen, L; Belch, JJF; Ullman, S; Madhok, R; Smit, AJ; Banga, JD; Watson, HR

    Objective. To identify the optimal dose of oral iloprost bn the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis. Design. Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo. Setting. European

  11. Compartment syndrome as a rare complication of iloprost infusion for peripheral vascular disease.

    Science.gov (United States)

    Thomas, Gregory P; Kadam, Sameer; Mohammed, Mohammed; Andrews, Brian T E

    2011-05-01

    We report a case of acute compartment syndrome associated with the use of iloprost in the treatment of Buerger's disease. After a four-compartmental fasciotomy of the affected lower limb, the patient made a complete recovery. Copyright © 2011. Published by Elsevier Inc.

  12. Effects of iloprost and piracetam in spinal cord ischemia-reperfusion injury in the rabbit.

    Science.gov (United States)

    Kalkan, E; Keskin, F; Kaya, B; Esen, H; Tosun, M; Kalkan, S S; Erdi, F; Unlü, A; Avunduk, M C; Cicek, O

    2011-01-01

    Experimental Study. The aim of this study was to investigate the neuroprotective effects of iloprost and piracetam on spinal cord ischemia/reperfusion (I/R) injury in the rabbit. The Experimental Research Center of Selcuk University, Konya, Turkey. A total of 24 rabbits were divided into four groups of six rabbits each, as follows: group 1 (n = 6) sham, laparotomy only; group 2 (n = 6) I/R; group 3 (n = 6) I/R+iloprost; and group 4 (n = 6) I/R+piracetam. I/R was established in groups 2, 3 and 4. Subsequently, they were followed up neurologically for 24 h until the rabbits were killed; biochemical and histopathological examinations of samples from the spinal cord were carried out. Neurological examination results were significantly better in the iloprost and piracetam groups compared with the I/R group (P piracetam by suppressing malondialdehyde (P piracetam groups were statistically different from the I/R group in terms of the number of apoptotic neurons in gray matter and white matter, as well as in terms of degenerated neurons and glial cells (P 0.05). This study has shown that iloprost and piracetam have neuroprotective effects in I/R injury both neurologically and histopathologically because of inhibition of lipid peroxidation.

  13. A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy and Heart Failure

    DEFF Research Database (Denmark)

    Aubdool, Aisah A; Thakore, Pratish; Argunhan, Fulye

    2017-01-01

    was investigated over 14 days. Blood pressure was measured by radio-telemetry. The ability of the αAnalogue to modulate heart failure was studied in an abdominal aortic constriction (AAC) model of murine cardiac hypertrophy and heart failure over 5 weeks. Extensive ex vivo analysis was performed via RNA analysis......, Western blot and histology. Results -The AngII-induced hypertension was attenuated by co-treatment with the αAnalogue (50nmol/kg/day, s.c., at a dose selected for lack of long term hypotensive effects at baseline). The αAnalogue protected against vascular, renal and cardiac dysfunction, characterised...

  14. Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

    Science.gov (United States)

    Dykes, John C; Torres, Marilyn; Alexander, Plato J

    2016-03-01

    This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.

  15. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

  16. Paradoxical reaction of raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis.

    Science.gov (United States)

    Barreira, Rebeca Iglesias; García, Belén Bardán; López, Mónica Granero; Legazpi, Iria Rodríguez; Díaz, Hortensia Álvarez; Penín, Isaura Rodríguez

    2012-10-01

    To report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5-1 ng/kg/min (6 hours per day, for 5 days every 6-8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.

  17. Iloprost, Prostaglandin E1, and Papaverine Relax Human Mesenteric Arteries With Similar Potency.

    Science.gov (United States)

    Mahlke, Christoph; Kühn, Jens-Peter; Mensel, Birger; Schreiber, André; Juretzko, Annett; Steinbach, Antje; Grisk, Olaf

    2017-09-01

    Nonocclusive mesenteric ischemia (NOMI) is accompanied by mesenteric artery spasms that are at least in part due to endothelin system activation. Acute treatment includes intra-arterial infusion of vasodilators such as iloprost, prostaglandin E1 (PGE1), and papaverine. Their effectiveness is not well characterized in human mesenteric arteries. We directly compared their potency to relax isolated human mesenteric arteries. To explore the potential of Rock inhibition to treat mesenteric artery spasms, we tested if endothelin-1 (ET-1)-induced mesenteric artery constrictions depend on rho kinase (Rock). Mesenteric artery segments were obtained from patients who underwent elective abdominal surgery. Vasodilator concentration-response curves were recorded from ET-1-preconstricted vessels by small vessel myography. Rock expression was investigated by Western blot and the potency of Rock inhibition to blunt ET-1-induced mesenteric artery constriction was tested. Iloprost, PGE1, and papaverine similarly reduced vascular tone to 20% to 30% of ET-1-induced wall tension. In human mesenteric arteries, logEC50 was significantly less for iloprost than for PGE1 or papaverine. Respective logEC50 values were -7.72 ± 0.08 mol/L, -6.58 ± 0.17 mol/L, and -6.73 ± 0.19 mol/L in 150 μm to 300 μm lumen diameter arteries. These vessels were also more sensitive to iloprost than 500 μm to 1,000 μm lumen diameter arteries (logEC50 -7.29 ± 0.07 mol/L). Rock1 and Rock2 were expressed in human mesenteric arteries but Rock inhibition did not significantly affect ET-1-induced vasoconstrictions. Iloprost, PGE1, and papaverine have a similar potency to relax mesenteric arteries. Our data suggest that iloprost but not Rock inhibition may be particularly useful to treat ET-1-induced spasms of distal mesenteric arteries.

  18. Chlorogenic acid analogues from Gynura nepalensis protect H9c2 cardiomyoblasts against H2O2-induced apoptosis.

    Science.gov (United States)

    Yu, Bang-Wei; Li, Jin-Long; Guo, Bin-Bin; Fan, Hui-Min; Zhao, Wei-Min; Wang, He-Yao

    2016-11-01

    Chlorogenic acid has shown protective effect on cardiomyocytes against oxidative stress-induced damage. Herein, we evaluated nine caffeoylquinic acid analogues (1-9) isolated from the leaves of Gynura nepalensis for their protective effect against H 2 O 2 -induced H9c2 cardiomyoblast damage and explored the underlying mechanisms. H9c2 cardiomyoblasts were exposed to H 2 O 2 (0.3 mmol/L) for 3 h, and cell viability was detected with MTT assay. Hoechst 33342 staining was performed to evaluate cell apoptosis. MMPs (mitochondrial membrane potentials) were measured using a JC-1 assay kit, and ROS (reactive oxygen species) generation was measured using CM-H 2 DCFDA. The expression levels of relevant proteins were detected using Western blot analysis. Exposure to H 2 O 2 markedly decreased the viability of H9c2 cells and catalase activity, and increased LDH release and intracellular ROS production; accompanied by a loss of MMP and increased apoptotic rate. Among the 9 chlorogenic acid analogues as well as the positive control drug epigallocatechin gallate (EGCG) tested, compound 6 (3,5-dicaffeoylquinic acid ethyl ester) was the most effective in protecting H9c2 cells from H 2 O 2 -induced cell death. Pretreatment with compound 6 (1.56-100 μmol/L) dose-dependently alleviated all the H 2 O 2 -induced detrimental effects. Moreover, exposure to H 2 O 2 significantly increased the levels of Bax, p53, cleaved caspase-8, and cleaved caspase-9, and decreased the level of Bcl-2, resulting in cell apoptosis. Exposure to H 2 O 2 also significantly increased the phosphorylation of p38, JNK and ERK in the H9c2 cells. Pretreatment with compound 6 (12.5 and 25 μmol/L) dose-dependently inhibited the H 2 O 2 -induced increase in the level of cleaved caspase-9 but not of cleaved caspase-8. It also dose-dependently suppressed the H 2 O 2 -induced phosphorylation of JNK and ERK but not that of p38. Compound 6 isolated from the leaves of Gynura nepalensis potently protects H9c2

  19. Efficacy of inhaled iloprost in cor pulmonale and severe pulmonary hypertension associated with tuberculous destroyed lung.

    Science.gov (United States)

    Park, Yae Min; Chung, Wook-Jin; Lee, Sang Pyo; Choi, Deok Young; Baek, Han Joo; Jung, Sung Hwan; Choi, In Suck; Shin, Eak Kyun

    2014-06-01

    Chronic obstructive pulmonary disease (COPD) is one of the causes of cor pulmonale. Cor pulmonale patients with pulmonary hypertension have a significant lower survival rate than patients without. However, there is no conclusive treatment options in cor pulmonale and pulmonary hypertension associated with COPD until now. We report a patient with cor pulmonale and pulmonary hypertension associated with severe form of COPD and tuberculous destroyed lung who achieved marked clinical, functional and echocardiographic hemodynamic improvements with inhaled iloprost for six months.

  20. Intravenous iloprost in the combination therapy of vascular disorders in patients with systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Aleksandr Vitalyevich Volkov

    2013-01-01

    Full Text Available Systemic connective tissue diseases, systemic scleroderma in particular, constitute a group of diseases in which vascular disorders underlying diverse clinical manifestations are one of the pathogenetic components. Raynaud 's syndrome and ulceration are the most common symptoms of these diseases, which influence quality of life in patients and require constant drug therapy. The paper discusses the authors' clinical experience with intravenous iloprost used in the combination therapy of the vascular manifestations of systemic scleroderma and systemic lupus erythematosus.

  1. Central venous catheter infections in outpatients with pulmonary hypertension treated with continuous iloprost.

    Science.gov (United States)

    Keusch, Stephan; Speich, Rudolf; Treder, Ulla; Ulrich Somaini, Silvia

    2013-01-01

    Intravenous prostanoid therapy is one cornerstone of therapy for patients with pre-capillary pulmonary hypertension (PH). Long-term central venous catheters expose patients to infectious complications. We report the incidence of catheter-related infection (CRI) and the spectrum of bacteria for ambulatory PH patients treated with iloprost via non-tunnelled central venous catheters from our Swiss referral centre in Zurich. Data from 15 PH patients treated with intravenous iloprost between May 2000 and June 2012 were reviewed. We found 11 CRI in 4 cases by two different organisms. Pathogens found were Brevibacterium (55%), Micrococcus luteus (18%), coagulase-negative Staphylococcus (9%) and Staphylococcus aureus (9%), as well as unusual organisms such as Agrobacterium tumefaciens or Delftia tsuruhatensis. The overall CRI rate was 1.28 per 1,000 catheter days, or 0.47 per year. The incidence of CRI using long-term, non-tunnelled central venous catheters in PH patients treated with iloprost is low. Uncommon, rare pathogens causing CRI were found in a substantial number of patients. Copyright © 2013 S. Karger AG, Basel.

  2. Astrobiological Field Campaign to a Volcanosedimentary Mars Analogue Methane Producing Subsurface Protected Ecosystem: Imuruk Lake (Alaska

    Directory of Open Access Journals (Sweden)

    F. Gómez

    2011-01-01

    Full Text Available Viking missions reported adverse conditions for life in Mars surface. High hydrogen signal obtained by Mars orbiters has increased the interest in subsurface prospection as putative protected Mars environment with life potential. Permafrost has attracted considerable interest from an astrobiological point of view due to the recently reported results from the Mars exploration rovers. Considerable studies have been developed on extreme ecosystems and permafrost in particular, to evaluate the possibility of life on Mars and to test specific automated life detection instruments for space missions. The biodiversity of permafrost located on the Bering Land Bridge National Preserve has been studied as an example of subsurface protected niche of astrobiological interest. Different conventional (enrichment and isolation and molecular ecology techniques (cloning, fluorescence “in situ” probe hybridization, FISH have been used for isolation and bacterial identification.

  3. Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment

    Directory of Open Access Journals (Sweden)

    Larrick James W

    2009-07-01

    Full Text Available Abstract Background While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1. The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated. Methods In alloxan-treated mice (a model of type 1 diabetes, drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-κB activation induced by IL-1β and IFN-γ was investigated. Results In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4 membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-κB activation. Conclusion We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-κB inhibitory activity. AL-1 is a potential new anti-diabetic agent.

  4. Proposal of early retreatment with iloprost in partially responsive patients with bone marrow edema syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Simone Meini

    2012-12-01

    Full Text Available Background Avascular Necrosis (AVN is defined as the cellular death of bone components due to an alteration of the blood supply, resulting in Edema of the Bone Marrow (BME, structural collapse and bone destruction. In advanced stages, AVN requires surgery. One emerging medical treatment for supporting osseous perfusion is the administration of iloprost.Materials and methods A 38-year-old woman presented with severe BME of the left hip (primary, persisting for 6 weeks. She was treated with iloprost iv at 2 ng/kg/min for 6 hours/day for 5 days, and after 4 weeks, the treatment was repeated at 1.5 ng/kg/min for 6 hours for 5 days because she exhibited only a partial response to the first treatment. Complete remission was obtained, documented clinically and on Magnetic Resonance Imaging (MRI. Her Harris Hip Score (HHS increased from 29.90 to 97. No significant adverse events related to iloprost were registered. No surgical procedures were necessary.Conclusions In most cases, iloprost is administered in a single cycle of treatment over 5 days at 1-2 ng/kg/min for 6 hours/day, but no research has investigated the effectiveness of early retreatment after the first cycle results in only a partially response. Only a few studies examining small numbers of patients have evaluated iloprost in AVN/BME, preferring, in most cases, the dose of 1 ng/kg/min and obtaining clinical improvement both in BME and in AVN in times comparable to surgical core decompression. This case report demonstrates the safety and effectiveness of early repetition of the maximal dose of iloprost before BME evolves into AVN, as well as in cases initially appearing serious and requiring surgical procedures.

  5. Reducing error in feline platelet enumeration by addition of Iloprost to blood specimens: comparison to prostaglandin E1 and EDTA.

    Science.gov (United States)

    Tvedten, Harold W; Bäcklund, Kerstin; Lilliehöök, Inger E

    2015-06-01

    Prostaglandin E1 (PGE1) and Iloprost inhibit platelet aggregation and should prevent or minimize preanalytic error with feline platelet enumeration. The objective was to compare the relative effectiveness in reducing errors in platelet enumeration by adding Iloprost to feline EDTA blood specimens in comparison to adding PGE1 or EDTA alone. In addition, a grading system for platelet aggregation in blood smears was evaluated for effectiveness in predicting prominent errors and compared to ADVIA's PLT-CLM flag. Finally, the use of plateletcrit in feline blood with platelet aggregation was evaluated. Blood specimens from 35 cats were included. Blood was collected into EDTA tubes with or without Iloprost or PGE1, and was rapidly mixed. Platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet flags were determined with an ADVIA 2120. Manual PLT was performed with a Leucoplate stain. PLT was determined by an IDEXX VetAutoread hematology analyzer (QBC). Neither addition of Iloprost nor PGE1 to EDTA blood specimens completely prevented platelet aggregation. Iloprost-treated specimens had the least severe aggregation. PGE1 was better than EDTA alone. Significant errors in PLT results were consistently identified by the grading system. ADVIA's PLT-CL flag usually predicted significant errors in PLT. QBC PLT results showed high imprecision. Manual PLT error was smaller than ADVIA PLT in EDTA specimens with aggregation. Adding Iloprost to feline blood specimens improved platelet enumeration accuracy. A grading system for severity of platelet aggregation and usually the ADVIA's PLT-CL alarm predicted specimens with significant errors in platelet enumeration. © 2015 American Society for Veterinary Clinical Pathology.

  6. Effect of treatment with iloprost with or without bosentan on nailfold videocapillaroscopic alterations in patients with systemic sclerosis.

    Science.gov (United States)

    Cestelli, Valentina; Manfredi, Andreina; Sebastiani, Marco; Praino, Emanuela; Cannarile, Francesca; Giuggioli, Dilia; Ferri, Clodoveo

    2017-01-01

    Vascular involvement plays a decisive role in systemic sclerosis (SSc) pathogenesis; it is responsible for some important clinical manifestations of the disease such as Raynaud's phenomenon and digital ulcers (DU). Bosentan, a dual receptor endothelin antagonist, and iloprost, often in combination therapy, seems to be able to interfere with the scleroderma microangiopathy. Aim of the study was to evaluate the effect of bosentan and iloprost on scleroderma microangiopathy, analyzed by means of capillaroscopic skin ulcer risk index (CSURI), in SSc patients treated for the prevention of DU. Nailfold videocapillaroscopy (NVC) was performed in 95 SSc patients, treated with iloprost alone (group 1) or combination therapy with iloprost and bosentan (group 2), at baseline and after one year. In all patients CSURI was calculated according to the formula "diameter × number of megacapillaries/(total number of capillaries) 2 ": in addition, total number of capillaries, giant capillaries, micro-hemorrhages, disorganization of the vascular array, and ramified capillaries were evaluated by means of a semiquantitative score. After 12 months, we observed a reduction of the number of giant capillaries in both groups, while an increase of ramified capillaries was recorded only in group 2. CSURI improved slightly in group 2 without statistical significance; on the contrary, in group 1 a significant worsening was recorded (p ≤ 0.001). Our study confirms the effectiveness of bosentan, in combination with iloprost, in SSc microangiopathy observed to NVC. Moreover, the observed findings further support the role of CSURI in the evaluation and monitoring of SSc microangiopathy.

  7. Radiation protection of the murine intestine by Misoprostol, a prostaglandin E/sub 1/ analogue, given alone or with WR-2721, is stereospecific

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.R.; Houseman, K.A.; Nelson, A.K.; Collins, P.W.

    1988-06-01

    Misoprostol, a prostaglandin (PG) E/sub 1/ analogue, is one of the most effective radiation protectors of the PGs investigated to date. Misoprostol-induced protection is also additive to protection by the widely studied thio compound, WR-2721. The mechanism of PG-induced radiation protection and its interaction with WR-2721 is unknown. One important step in the investigation of the mechanism is to determine if PG-induced protection and its interaction with WR-2721 is mediated through PG receptor sites. A direct determination of receptor sites on murine intestinal clonogenic cells could not be made; however an indirect approach was possible. Misoprostol is composed of four stereoisomers of about equal proportions of which only one is gastric antisecretory and cytoprotective. Studies reported here compared radiation protection by this active isomer with that of one of the three inactive isomers. Furthermore, the additional protection of the two isomers when administered with WR-2721 was investigated. Results showed that only the active isomer was protective from radiation injury and this isomer was the only one which afforded additional protection with WR-2721. These data show that PG-induced radiation protection is receptor site dependent and stereospecific.

  8. Radiation protection of the murine intestine by Misoprostol, a prostaglandin E1 analogue, given alone or with WR-2721, is stereospecific

    International Nuclear Information System (INIS)

    Hanson, W.R.; Houseman, K.A.; Nelson, A.K.

    1988-01-01

    Misoprostol, a prostaglandin (PG) E 1 analogue, is one of the most effective radiation protectors of the PGs investigated to date. Misoprostol-induced protection is also additive to protection by the widely studied thio compound, WR-2721. The mechanism of PG-induced radiation protection and its interaction with WR-2721 is unknown. One important step in the investigation of the mechanism is to determine if PG-induced protection and its interaction with WR-2721 is mediated through PG receptor sites. A direct determination of receptor sites on murine intestinal clonogenic cells could not be made; however an indirect approach was possible. Misoprostol is composed of four stereoisomers of about equal proportions of which only one is gastric antisecretory and cytoprotective. Studies reported here compared radiation protection by this active isomer with that of one of the three inactive isomers. Furthermore, the additional protection of the two isomers when administered with WR-2721 was investigated. Results showed that only the active isomer was protective from radiation injury and this isomer was the only one which afforded additional protection with WR-2721. These data show that PG-induced radiation protection is receptor site dependent and stereospecific. (author)

  9. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Barceló Carlos

    2005-12-01

    Full Text Available Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  10. Study on reactivity and protection of the alpha-hydroxyphosphonate moiety in 5'-nucleotide analogues: formation of the 3'-O-P-C(OH)-C4' internucleotide linkage.

    Science.gov (United States)

    Králíková, Sárka; Masojídková, Milena; Budĕsínský, Milos; Rosenberg, Ivan

    2003-03-01

    The recently described epimeric nucleosidyl-5'-C-phosphonates (alpha-hydroxyphosphonates) represent novel nucleotide analogues that can be incorporated into chimeric oligonucleotides by the phosphotriester condensation method. In order to prepare suitable protected monomer(s) we have studied condensation reaction between protected 2'-deoxythymidine and 2'-deoxythymidinyl-5'-C-phosphonate, both as model compounds, in dependence on the nature of the 5'-hydroxyl protecting group. We have found that the O-acetyl group is unstable in the presence of TPSCl or MSNT used as condensing agents for activation of the phosphorus moiety. This instability negatively influences the scope of the condensation process. On the other hand, introduction of the O-methoxycarbonyl group gave excellent results. The O-methoxycarbonyl group does not participate in the condensation process, and its quantitative introduction into the nucleotide analo gues is accomplished using a novel acylating agent, methoxycarbonyl tetrazole.

  11. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Carlos Barceló

    2011-05-01

    Full Text Available Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  12. The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice.

    Science.gov (United States)

    Lue, YanHe; Swerdloff, Ronald; Wan, Junxiang; Xiao, Jialin; French, Samuel; Atienza, Vince; Canela, Victor; Bruhn, Kevin W; Stone, Brian; Jia, Yue; Cohen, Pinchas; Wang, Christina

    2015-12-01

    Humanin is a peptide that is cytoprotective against stresses in many cell types. We investigated whether a potent humanin analogue S14G-humanin (HNG) would protect against chemotherapy-induced damage to normal cells without interfering with the chemotherapy-induced suppression of cancer cells. Young adult male mice were inoculated iv with murine melanoma cells. After 1 week, cancer-bearing mice were randomized to receive either: no treatment, daily ip injection of HNG, a single ip injection of cyclophosphamide (CP), or CP+HNG and killed at the end of 3 weeks. HNG rescued the CP-induced suppression of leucocytes and protected germ cell from CP-induced apoptosis. Lung metastases were suppressed by HNG or CP alone, and further suppressed by CP+HNG treatment. Plasma IGF-1 levels were suppressed by HNG with or without CP treatment. To investigate whether HNG maintains its protective effects on spermatogonial stem cells, sperm output, and peripheral leucocytes after repeated doses of CP, normal adult male mice received: no treatment, daily sc injection of HNG, 6 ip injections of CP at 5-day intervals, and the same regimens of CP+HNG and killed at the end of 4 weeks of treatment. Cauda epididymal sperm counts were elevated by HNG and suppressed by CP. HNG rescued the CP-induced suppression of spermatogonial stem cells, sperm count and peripheral leucocytes. We conclude that HNG 1) protects CP-induced loss of male germ cells and leucocytes, 2) enhances CP-induced suppression of cancer metastases, and 3) acts as a caloric-restriction mimetic by suppressing IGF-1 levels. Our findings suggest that humanin analogues may be promising adjuvants to chemotherapy.

  13. Long-term clinical stabilization of scleroderma patients treated with a chronic and intensive IV iloprost regimen.

    Science.gov (United States)

    Foti, Rosario; Visalli, Elisa; Amato, Giorgio; Benenati, Alessia; Converso, Giovanni; Farina, Alberto; Bellofiore, Salvatore; Mulè, Massimiliano; Di Gangi, Marcella

    2017-02-01

    Intravenous iloprost is a first-line option for the treatment of scleroderma-related digital vasculopathy, and some studies have suggested its favourable role on disease progression. The aim of our study is to evaluate the disease progression, specifically in terms of cardiopulmonary function, in a group of consecutive patients chronically treated with intravenous iloprost. Our retrospective study enrolled 68 scleroderma patients (68 F, 54.4 ± 12.3 years) treated with iloprost for 7.1 ± 2.9 years, with a schedule of 5-6 consecutive daily infusions per month (6 h/day, 0.5-2.0 ng/kg/min). In all patients, modified Rodnan skin score (4.7 ± 5.3 vs. 3.7 ± 5.3, p disease in SSc patients, as suggested by stabilization or significant improvement of cardiopulmonary parameters and vasculopathy.

  14. Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart

    DEFF Research Database (Denmark)

    Sonne, David P; Engstrøm, Thomas; Treiman, Marek

    2007-01-01

    to exert cardiovascular effects in a number of experimental models. Here we tested exendin-4 (Exe-4), a peptide agonist at GLP-1 receptors, and GLP-1(9-36) amide, the primary endogenous metabolite of GLP-1 (both in the concentration range 0.03-3.0 nM), for their protective effects against ischemia......Glucagon-Like Peptide-1 (GLP-1) is an incretin peptide secreted from intestinal L-cells, whose potent plasma glucose-lowering action has prompted intense efforts to develop GLP-1 receptor-targeting drugs for treatment of diabetic hyperglycemia. More recently, GLP-1 and its analogues have been shown.......2% of the ischemic area, pGLP-1 receptor antagonist. In contrast, both Exe-4 and GLP-1(9-36) amide were able to augment left ventricular performance (left ventricular developed pressure and rate-pressure product) during...

  15. A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87–99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Mary Emmanouil

    2018-01-01

    Full Text Available In this report, amide-linked cyclic peptide analogues of the 87–99 myelin basic protein (MBP epitope, a candidate autoantigen in multiple sclerosis (MS, are tested for therapeutic efficacy in experimental autoimmune encephalomyelitis (EAE. Cyclic altered peptide analogues of MBP87–99 with substitutions at positions 91 and/or 96 were tested for protective effects when administered using prophylactic or early therapeutic protocols in MBP72–85-induced EAE in Lewis rats. The Lys91 and Pro96 of MBP87–99 are crucial T-cell receptor (TCR anchors and participate in the formation of trimolecular complex between the TCR-antigen (peptide-MHC (major histocompability complex for the stimulation of encephalitogenic T cells that are necessary for EAE induction and are implicated in MS. The cyclic peptides were synthesized using Solid Phase Peptide Synthesis (SPPS applied on the 9-fluorenylmethyloxycarboxyl/tert-butyl Fmoc/tBu methodology and combined with the 2-chlorotrityl chloride resin (CLTR-Cl. Cyclo(91–99[Ala96]MBP87–99, cyclo(87–99[Ala91,96]MBP87–99 and cyclo(87–99[Arg91, Ala96]MBP87–99, but not wild-type linear MBP87–99, strongly inhibited MBP72–85-induced EAE in Lewis rats when administered using prophylactic and early therapeutic vaccination protocols. In particular, cyclo(87–99[Arg91, Ala96]MBP87–99 was highly effective in preventing the onset and development of clinical symptoms and spinal cord pathology and providing lasting protection against EAE induction.

  16. BALANOL ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid...

  17. Protective activity of a novel resveratrol analogue, HS-1793, against DNA damage in 137Cs-irradiated CHO-K1 cells

    International Nuclear Information System (INIS)

    Jeong, Min Ho; Jo, Young Rae; Yang, Kwang Mo; Jeong, Dong Hyeok; Lee, Chang Geun; Oh, Su Jung; Jeong, Soo Kyung; Jo, Wol Soon; Lee, Ki Won

    2014-01-01

    Resveratrol has received considerable attention as a polyphenol with anti-oxidant, anti-carcinogenic, and anti-inflammatory effects. Radiation is an important component of therapy for a wide range of malignant conditions. However, it causes damage to normal cells and, hence, can result in adverse side effects. This study was conducted to examine whether HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, induces a protective effect against radiation-induced DNA damage. HS-1793 effectively scavenged free radicals and inhibited radiation-induced plasmid DNA strand breaks in an in vitro assay. HS-1793 significantly decreased reactive oxygen species and cellular DNA damage in 2 Gy-irradiated Chinese hamster ovary (CHO)-K1 cells. In addition, HS-1793 dose-dependently reduced the levels of phosphorylated H2AX in irradiated CHO-K1 cells. These results indicate that HS-1793 has chemical radioprotective activity. Glutathione levels and superoxide dismutase activity in irradiated CHO-K1 cells increased significantly following HS-1793 treatment. The enhanced biological anti-oxidant activity and chemical radioprotective activity of HS-1793 maintained survival of irradiated CHO-K1 cells in a clonogenic assay. Therefore, HS-1793 may be of value as a radioprotector to protect healthy tissue surrounding tumor cells during radiotherapy to obtain better tumor control with a higher dose. (author)

  18. Antioxidant Properties and PC12 Cell Protective Effects of a Novel Curcumin Analogue (2E,6E-2,6-Bis(3,5- dimethoxybenzylidenecyclohexanone (MCH

    Directory of Open Access Journals (Sweden)

    Gui-Zhen Ao

    2014-03-01

    Full Text Available The antioxidative properties of a novel curcumin analogue (2E,6E-2,6-bis(3,5-dimethoxybenzylidenecyclohexanone (MCH were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•− quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH loss, an increase in malondialdehyde (MDA level, and leakage of lactate dehydrogenase (LDH, cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63–5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2 at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS, the loss of mitochondrial membrane potential (MMP, and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

  19. Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients.

    Science.gov (United States)

    Melillo, E; Lucaccini, E; Berchiolli, R; Adami, D; Nuti, M; Dell'Omo, G; Farina, A; Panigada, G; Roberts, A T; Meini, S

    2016-12-01

    Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ. A retrospective study enrolling 102 consecutive patients between 2004-2008, with clinical and instrumental (ultrasound, angiography, transcutaneous tensiometry of oxygen TcpO2 and carbon dioxide TcpCO2 in the affected and contralateral limbs) diagnosis of critical ischemia. All patients received the best medical therapy. Iloprost was administered (0.5-2 ng/kg/min 6 hours/day for 2-4 weeks) in all patients initially considered unsuitable for revascularization, repeating it regularly in time every six-twelve months in the case of positive response. The minimum expected follow-up was 4 years. 71.5% of patients were treated with iloprost and the responder rate was 71.2%. Most of the patients were regularly retreated with repeated cycles. Initial median supine TcpCO2 in symptomatic limb was higher in untreated patients than those treated (58 vs. 49 mmHg; p TcpCO2 directly and significantly correlated with the highest risk of mortality and seems to represent a new accurate prognostic criterion of unfavourable short and long-term response to prostanoid. In iloprost group, major amputations were significantly reduced. Revascularization was significantly higher in non-responders (57.1% vs. 11.5%; p < 0.05). There was a significantly higher prevalence of subsequent myocardial infarction in the non-iloprost group (27.6% vs. 9.6%; p < 0.05). The survival rate of non-responders was higher than untreated up until the second year (76.2% vs. 62%; p < 0.05). At 4 years we found higher survival in patients treated with iloprost (64.3% vs. 41% in untreated; p < 0.05) and in responders (75% vs. 38.1% in non-responders; p < 0.05). Our results confirm the favourable role of iloprost on the long-term outcome

  20. [Conservative treatment of chronic obstructive arterial disease with iloprost and physical training: assessment of results in 5 years of a study with 360 patients].

    Science.gov (United States)

    Apperti, M; Masella, A; Sabia, D; Verde, I

    2003-01-01

    The treatment of patients with Peripheral Arterial Occlusive Disease (P.A.O.D.) is, until now, a therapeutics challenge. The purpose of this study was to confirm the safety of Iloprost infusion, to estimate the results after an Home Exercise Program joined to the therapy and to identify groups of patients with P.A.O.D. that can benefit from Iloprost therapy. 360 patients with and without diabetic with P.A.O.D. (Peripheral Arterial Occlusive Disease) at the stage of II, III, & IV, with Buerger Syndrome, were treated with Iloprost at the maximum dosage: 2 ng/kg/min for 6 hours a day, for a minimum of 1 week and a maximum of 3 weeks with cycles of therapy every 3, 6 or 12 months. At the end of each cycle of therapy there was assigned an Home Exercise Program. Patients with symptoms of pain are observed in the study and monitored for how long the pain lasted or diminished. The clinical benefit was evaluated on the reduction of the pain and analgesics, on the improvement of the trophics lesions and on the increase of gait's distance. After 5 years of follow up, it was reported 12.2% of major amputations and 3.6% of deads. Over 60% of the patients, that were at risk for amputation at the beginning of the study, were alive. The tolerability of therapy was been very acceptable. This study, at the end of 5 years, showed that the therapeutic infusion of Iloprost associated with an intensive Home Exercise Program, can, before 12 months, show patient improvement of the gait's distance from 50-200%.

  1. Therapeutische Effekte von Iloprost und dem PDE 3/4-Inhibitor Tolafentrin im Modell der Monocrotalin-induzierten chronischen pulmonalen Hypertonie der Ratte

    OpenAIRE

    Kreißelmeier, Klaus-Peter

    2010-01-01

    Die schwere pulmonale Hypertonie ist eine erheblich die Lebensqualität einschränkende Erkrankung mit einer hohen Mortalität. Wir untersuchten die therapeutischen Effekte von Iloprost, einem langwirksamen Prostazyklinanalogon, und dem dual-selektiven Phosphodiesterase 3/4-Inhibitor Tolafentrin während akuter Gabe sowie bei Dauertherapie in einem Tiermodell der Monocrotalin-induzierten pulmonalen Hypertonie der Ratte. Achtundzwanzig Tage nach Gabe des Alkaloids war der rechtsventrikuläre syste...

  2. Analogue computing methods

    CERN Document Server

    Welbourne, D

    1965-01-01

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

  3. [Protective effect of GnRH analogues on the reproductive capacity of women with neoplasia or autoimmune disease who require chemotherapy. Final results of a phase ii clinical trial].

    Science.gov (United States)

    Gris-Martínez, José M; Trillo-Urrutia, Lourdes; Gómez-Cabeza, Juan José; Encabo-Duró, Gloria

    2016-02-05

    In order to avoid the toxic effect of chemotherapy, it has been proposed to use GnRH agonist analogues (GnRHa) to inhibit the depletion of ovarian follicles. Nevertheless, there is controversy about its effectiveness. This clinical trial has been conducted with the aim to assess the protective effect of GnRH analogues on the reproductive capacity of women with malignancies or autoimmune diseases, which require chemotherapy. Open phase ii single-center clinical trial. During chemotherapy, a total of 5 doses of GnRH antagonist analogue at a dose interval of 3 days and/or a monthly dose of GnRHa were administered. Hormonal determinations prior to the start of the CT treatment were conducted during treatment and at the end of it. The inclusion of patients was prematurely concluded when incorporating the determination of anti-Müllerian hormone (AMH) as a parameter for assessing the ovarian reserve. Out of 38 patients, 23 (60.5%, 95%CI 43.4-76.0) had AMH values below normal following completion of treatment. An intermediate analysis was carried out observing that while most patients were recovering the menstrual cycle (86.6% 95%CI 71.9-95.6), they had reduced levels of AMH. Although most patients recovered their menstrual cycles, the ovarian reserve, assessed by the concentration of AMH, decreased in many patients. Therefore, we can conclude that the concomitant treatment of chemotherapy and GnRH analogues does not preserve the loss of follicular ovarian reserve. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  4. Analogue MIMO Detection

    Directory of Open Access Journals (Sweden)

    McNamara Darren

    2006-01-01

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

  5. Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.

    Directory of Open Access Journals (Sweden)

    Guang-Rong Yan

    Full Text Available Oxidative stress is considered to be a major factor contributing to pathogenesis and progression of many diseases. A novel andrographolide-lipoic acid conjugate (AL-1 could protect pancreatic β-cells from reactive oxygen species (ROS-induced oxidative injury. However, its protective mechanism is still unclear. In this work, we used proteomics to identify AL-1-regulated proteins in β-cells and found that 13 of the 71 proteins regulated by AL-1 were closely associated with antioxidation. These differential proteins were mainly involved in the ERK1/2 and AKT1 signaling pathways. Functional investigation demonstrated that AL-1 exerted its protective effects on H2O2-induced cell death of β-cells by generating NADPH oxidase-dependent ROS to activate ERK1/2 and AKT1 signaling pathways. As a consequence, the expressions of antioxidant proteins including Trx1, Prx1 and Prx5, and anti-apoptotic proteins including PDCD6IP, prohibitin, galectin-1 and HSP were upregulated. AL-1 probably worked as a "vaccinum" to activate the cellular antioxidant system by inducing the generation of low concentration ROS which then reciprocally protected β-cells from oxidative damage caused by high-level ROS from H2O2. To the best of our knowledge, this is the first comprehensive proteomic analysis illustrating a novel molecular mechanism for the protective effects of antioxidants on β-cells from H2O2-induced cell death.

  6. Study on reactivity and protection of the ŕ-hydroxyphosphonate Moiety in 5'-nucleotide analogues: formation of the 3'-O-P-C(OH)-C4' internucleotide linkage

    Czech Academy of Sciences Publication Activity Database

    Králíková, Šárka; Masojídková, Milena; Buděšínský, Miloš; Rosenberg, Ivan

    2003-01-01

    Roč. 22, - (2003), s. 329-347 ISSN 1525-7770 R&D Projects: GA ČR GA203/01/1166; GA AV ČR IAA4055101 Institutional research plan: CEZ:AV0Z4055905 Keywords : protection * ŕ- hydroxyphosphonate s * oligonucleotides Subject RIV: CC - Organic Chemistry Impact factor: 0.813, year: 2003

  7. Rapid photolytic release of adenosine 5'-triphosphate from a protected analogue: utilization by the Na:K pump of human red blood cell ghosts

    International Nuclear Information System (INIS)

    Kaplan, J.H.; Forbush, B. III; Hoffman, J.F.

    1978-01-01

    2-Nitrobenzyl phosphate and 1-(2-nitro)phenylethyl phosphate have been synthesized and demonstrated to be suitable as photolabile sources of inorganic phosphate. The same protecting groups were attached to the terminal phosphate of adenosine 5'-triphosphate. These caged ATP compounds released adenosine 5'-triphosphate on illumination at 340 nm in aqueous solution and P 3 -1-(2-nitro)phenylethyl-ATP gave about a 70 percent yield in under 30 s. The unphotolyzed caged ATP was neither a substrate nor inhibitor of purified renal Na,K-ATPase (EC 3.61.3). Following photolysis in the presence of the enzyme, the liberated ATP was hydrolyzed but at an inhibited rate. The photo-dependent inhibition could be eliminated by prior addition of glutathione or bisulfite to the irradiated solution. Caged ATP was incorporated into resealed human erythrocyte ghosts prepared from red blood cells depleted of internal energy stores. While the NA : K pump was unable to use incorporated caged ATP as a substrate, the ATP liberated by photolysis activated the pump as evidenced by measurements of K-dependent, ouabain-sensitive Na efflux. Thus the caged ATP can be used as a stable source of ATP unmetabolizable by intracellular ATPases until the ATP is released following photolytic irradiation

  8. Natural Analogue Synthesis Report

    Energy Technology Data Exchange (ETDEWEB)

    A. M. Simmons

    2002-05-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport

  9. NATURAL ANALOGUE SYNTHESIS REPORT

    International Nuclear Information System (INIS)

    Simmons, A.M.

    2004-01-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature along with results of quantitative studies conducted specifically for the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement-drift degradation, waste-form degradation, waste-package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated-zone (SZ) transport, impact of radionuclide release on the biosphere

  10. CEC natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1986-01-01

    The second meeting of the CEC Natural Analogue Working Group took place on June 17-19, 1986, hosted by the Swiss NAGRA in Interlaken (CH). A review of recent progress in natural analogue programmes was carried out, and complemented by detailed discussions about geomicrobiology, archaeological analogues, natural colloids, and use of analogues to increase confidence in safety assessments for radioactive waste disposal. A statement drafted by the Group, and the presentations made, are put together in this report

  11. CEC Natural Analogue Working Group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1989-01-01

    The central theme for the third meeting of the CEC analogue working group was ''How can analogue data be used for performance assessments, both in support of the results and for presentation to the public''. This report puts together the most recent achievements in this field, together with a review of on-going natural analogue programmes

  12. Natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.

    1986-01-01

    A Natural Analogue Working Group was established by the Commission of the European Communities in 1985. The purpose of this group is to bring together modellers with earth scientists and others, so that maximum benefit can be obtained from natural analogue studies with a view to safe geological disposal of radioactive waste. The first meeting of this group was held in Brussels from November 5 to 7, 1985. The discussions mainly concerned the identification of the modellers' needs and of the earth scientists' capacity to provide for them. Following the debates, a written statement was produced by the Group; this document forms the core of the present Report. Notes and outlines of many of the presentations made are grouped in four appendixes. The valuable contribution of all those involved in the meeting is gratefully acknowledged

  13. Quantum analogue computing.

    Science.gov (United States)

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

    2010-08-13

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

  14. The Palmottu analogue project

    International Nuclear Information System (INIS)

    Ahonen, L.; Blomqvist, R.; Suksi, J.

    1993-01-01

    The report gives a summary of the results of investigations carried out in 1992 at the Palmottu natural analogue study site, which is a small U-Th mineralization in Nummi-Pusula, southwestern Finland. Additionally, the report includes several separate articles dealing with various aspects of the Palmottu Analogue Project: (1) deep groundwater flow, (2) interpretation of hydraulic connections, (3) characterization of groundwater colloids, (4) uranium mineral-groundwater equilibrium, (5) water-rock interaction and (6) modelling of in situ matrix diffusion. The Palmottu Analogue Project aims at a more profound understanding of radionuclide transport processes in fractured crystalline bedrock. The essential factors controlling transport are groundwater flow and interaction between water and rock. Accordingly, the study includes (1) structural interpretations partly based on geophysical measurements, (2) hydrological studies including hydraulic drill-hole measurements, (3) flow modelling, (4) hydrogeochemical characterization of groundwater, uranium chemistry and colloid chemistry, (5) mineralogical studies, (6) geochemical interpretation and modelling, (7) studies of radionuclide mobilization and retardation including matrix diffusion, and (8) modelling of uranium series data. Palaeohydrogeological aspects, due to the anticipated future glaciation of the Fennoscandian Shield, are of special interest. Quaternary sediments are studied to gain information on post-glacial migration in the overburden. (orig.)

  15. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    acids, $g(b)-amino acids and/or longer chain $g(v)-amino acids, and a difunctional group which preferably is a cyclic entity, in particular, an aromatic or heteroaromatic entity acting as an intercalator group. Specific compounds and a library of such compounds may be prepared using conventional solid......The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g(a)-amino...

  16. Transaxial analogue tomography

    International Nuclear Information System (INIS)

    Duinker, S.; Geluk, R.J.; Mulder, H.

    1978-01-01

    After an introduction on computerized tomography (CT) scanners summarizing the various generations, the general outline of the concept of a transaxial tomography system is given, which is entirely based on analogue instead of digital techniques (AT system). In particular, the use of X-ray image-intensifier systems as a means of detecting the transmission profiles of the object in a so-called half-field detection method are discussed as well as various possibilities of detector scanning. It is further discussed how in a purely electronic way with the aid of a scan-converter, density profiles representative of parallel beams can be derived from the family of profiles as obtained from the fan-shaped beams in the actual experiment. A practical opto-electronic solution of the analogue spatial filtering problem is described as to how to process, on a real-time basis, parallel density profiles so that after back-projection tomographic images which are free from point-spreading effects will be obtained. Finally, after a brief indication of certain technical details for which corrective measures have to be worked out in the course of practical realization, the main relative advantages of AT scanners in comparison to CT scanners are enumerated. (Auth.)

  17. Alligator Rivers analogue project

    International Nuclear Information System (INIS)

    Duerden, P.

    1990-01-01

    Australian Nuclear Science and Technology Organization has extensively evaluated uranium ore bodies in the Alligator Rivers Uranium Province in Australia as analogues of radioactive waste repositories. The work was extended for a three-year program as an international project based on the Koongarra uranium deposit and sponsored by the OECD Nuclear Energy Agency. The technical program comprises six major sub-projects involving modelling and experimental work: modelling of radionuclide migration; hydrogeology of the Koongarra uranium deposit; uranium/thorium series disequilibria studies; groundwater and colloid studies; fission product studies; transuranic nuclide studies; an outline of the technical programs and a summary of progress in the technical sub-projects is given. This is followed by a series of technical reports which briefly describe current research tasks, and which have been separately indexed

  18. A Short Term Analogue Memory

    DEFF Research Database (Denmark)

    Shah, Peter Jivan

    1992-01-01

    A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...

  19. Effects of Longterm Treatment with Bosentan and Iloprost on Nailfold Absolute Capillary Number, Fingertip Blood Perfusion, and Clinical Status in Systemic Sclerosis.

    Science.gov (United States)

    Trombetta, Amelia Chiara; Pizzorni, Carmen; Ruaro, Barbara; Paolino, Sabrina; Sulli, Alberto; Smith, Vanessa; Cutolo, Maurizio

    2016-11-01

    To quantify in patients with systemic sclerosis (SSc) the absolute nailfold capillary number/mm (the absolute number of capillaries, observable in the first row, in 1 mm per field) and fingertip blood perfusion (FBP) during longterm therapy with the endothelin receptor antagonist bosentan (BOSE) and the synthetic analog of prostacyclin PGI 2 iloprost (ILO) by multiple diagnostic tools. Observed values were correlated with clinical outcomes. Thirty patients with SSc already receiving intravenous ILO (80 μg/day) for 5 continuous days (every 3 mos) were recruited in the clinic. Fifteen patients continued such treatment (ILO group), while in 15 patients BOSE (125 mg twice/day) was added (ILO + BOSE group) because of the onset of pulmonary arterial hypertension or digital ulcers (DU). The followup period was 4 years (T0-T4). Every year the following were evaluated: absolute nailfold capillary number/mm by nailfold videocapillaroscopy, FBP by laser Doppler flowmetry, DU incidence, DLCO, systolic pulmonary arterial pressure (sPAP), renal arterial resistive index, and other biomarkers. From T2 to T4, laser speckled contrast analysis was added. Nonparametric tests were used for statistical analysis. Limited to the ILO + BOSE group, absolute capillary number/mm and FBP showed a progressive increase independently from other variables. In addition, during followup there was a significant reduction (80%) in the incidence of new DU, whereas DLCO and sPAP did not worsen. The study shows in patients with SSc with up to 4 years of combined therapy a progressive significant recovery in structure and function of microvasculature linked to improved clinical outcomes, independent of disease severity.

  20. Protective

    Directory of Open Access Journals (Sweden)

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  1. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  2. Chemoenzymatic preparation of germacrene analogues.

    Science.gov (United States)

    Cascón, Oscar; Touchet, Sabrina; Miller, David J; Gonzalez, Veronica; Faraldos, Juan A; Allemann, Rudolf K

    2012-10-09

    A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies.

  3. Chemoenzymatic preparation of germacrene analogues

    OpenAIRE

    Cascón, Oscar; Touchet, Sabrina; Miller, David James; Gonzalez, Veronica; Faraldos, Juan A.; Allemann, Rudolf Konrad

    2012-01-01

    A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies.

  4. Synthesis of phosphono analogues of dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

    Science.gov (United States)

    Page, P; Blonski, C; Périé, J

    1999-07-01

    The present paper describes the synthetic routes of six phosphono analogues of dihydroxyacetone phosphate and five phosphono analogues of glyceraldehyde 3-phosphate through alpha-, beta- and gamma-hydroxyphosphonate esters precursors containing a protected carbonyl group. In some situations, depending on the sequence used for the deprotection of the phosphonate and carbonyl groups, the aldol/ketol rearrangement allowed the synthesis of either dihydroxyacetone phosphate or glyceraldehyde 3-phosphate analogues from the same precursors. All these analogues are of interest both as active-site probes and as potential substrates for glycolytic enzymes such as fructose 1,6-diphosphate aldolases (EC 4.1.2.13).

  5. Research on uranium deposits as analogues of radioactive waste repositories

    International Nuclear Information System (INIS)

    Hardy, C.J.

    1987-01-01

    The disposal of highly radioactive waste deep underground in suitable geological formations is proposed by many countries to protect public health and safety. The study of natural analogues of nuclear waste repositories is one method of validating mathematical models and assuring that a proposed repository site and design will be safe. (author)

  6. Terapêutica prolongada da Hipertensão Pulmonar Primária com um análogo da prostaciclina, o iloprost, em aerossol

    Directory of Open Access Journals (Sweden)

    M.M. Hoeper

    2001-07-01

    Full Text Available RESUMO: No presente estudo, os autores avaliaram a eficácia da terapêutica inalatória com iloprost (análogo estável da prostaciclina efectuada durante o período de um ano em doentes com Hipertensão Pulmonar (HTP severa, monitorizando, para tal, o grau de tolerância ao esforço físico e diversos parâmetros hemodinâmicos.Foram estudados 24 doentes com o diagnóstico de Hipertensão Pulmonar Primária refractária à terapêutica médica convencional, incluindo os blo- queadores dos canais de cálcio, que apresentavam uma grave limitação da sua capacidade de exercício físico – classes funcionais III/IV da New York Heart Association (NYHA. O grau de tolerância ao esforço foi determinado pela prova de marcha de 6 minutos e as variáveis hemodinâmicas por cateterismo cardíaco direito. Doentes com HTP secundária, bem como indivíduos com Insuficiência Cardíaca Direita grave sob terapêutica com catecolaminas foram excluídos.Após a diluição de 50 μg de iloprost em 5 ml de solução salina isotónica, este foi administrado utilizando um nebulizador ultrassónico, durante cerca de 10 a 15 minutos, do que resultou uma dose cumulativa de iloprost entre 14 a 17 μg. Imediatamente após a inalação e a cada 15 minutos no espaço de uma hora, foram avaliadas as variáveis hemodinâmicas, no sentido de determinar o efeito máximo atingido num curto intervalo de tempo após a inalação e registar temporalmente a resposta hemodinâmica. Todos os doentes iniciaram o tra-tamento com 100 μg/dia de iloprost distribuídos por 6 a 8 nebulizações com o intervalo de 2 a 3 horas (interrupção nocturna de acordo com a informação obtida pelo cateterismo cardíaco direito efectuado anteriormente. Se a resistência vascular pulmonar diminuía mais de 20% em relação ao valor basal, mas

  7. Introduction to electronic analogue computers

    CERN Document Server

    Wass, C A A

    1965-01-01

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

  8. Prostacyclin Suppresses Twist Expression in the Presence of Indomethacin in Bone Marrow-Derived Mesenchymal Stromal Cells

    OpenAIRE

    Kemper, Oliver; Herten, Monika; Fischer, Johannes; Haversath, Marcel; Beck, Sascha; Classen, Tim; Warwas, Sebastian; Tassemeier, Tjark; Landgraeber, Stefan; Lensing-Höhn, Sabine; Krauspe, Rüdiger; Jäger, Marcus

    2014-01-01

    Background Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of t...

  9. Superconductive analogue of spin glasses

    International Nuclear Information System (INIS)

    Feigel'man, M.; Ioffe, L.; Vinokur, V.; Larkin, A.

    1987-07-01

    The properties of granular superconductors in magnetic fields, namely the existence of a new superconductive state analogue of the low-temperature superconductive state in spin glasses are discussed in the frame of the infinite-range model and the finite-range models. Experiments for elucidation of spin-glass superconductive state in real systems are suggested. 30 refs

  10. PTH analogues and osteoporotic fractures

    NARCIS (Netherlands)

    Verhaar, H.J.; Lems, W.F.

    2010-01-01

    Importance of the field: At present there are two parathyroid hormone (PTH) analogues (PTH 1 34 and PTH 1 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 34 and PTH 1 84) and in men (PTH 1 34 only) who are at increased risk of having a fracture. Areas

  11. Chemopreventive properties of curcumin analogues ...

    African Journals Online (AJOL)

    Chemopreventive properties of curcumin analogues, hexagamavunone-0 and gamavutone-0, in rat colorectal cancer model. ... Histopathological analysis was performed using H & E staining and immunohistochemistry with antibodies against adenomatous polyposis coli (APC) and cyclooxygenase 2 (COX-2). Results: All ...

  12. Natural analogues, paradigm for manmade repositories for radioactive wastes

    International Nuclear Information System (INIS)

    Pavelescu, M.; Pavelescu, A.

    2004-01-01

    Natural analogues are given by nature. They show the results of natural processes which have lasted thousands or millions of years. They provide an excellent example of what could happen in an underground site, offering in the same time the opportunity to test by observation and measurement, many of the geochemical processes that are expected to influence in a realistic and appropriate way, the predicted reliability of the radioactive waste repository over long periods of geological time. The natural analogue studies attempt to understand the multiprocessing complexity of the natural system, which contrasts with the limitations of the laboratory experiments and bring arguments to overcome the difficult time scale issue. By this the natural analogues are a useful paradigm for manmade repository for radioactive wastes. The paper discusses the implicit link in the public mind between natural analogues and manmade waste repository with an accent of the positive impact on public acceptance. It is also discussed the decisive qualities of the natural analogues concerning providing valid long term data and increasing the confidence of the public for manmade repositories. The debate is conducting in terms of sustainable development, having at base high-level principles in order to protect humans and their environment, both now and in the future, from potential hazards arising from such wastes. Safe radwaste management involves the application of technology and resources in a regulated manner so that the public, workers and the environment are protected in accordance with the accepted national and international standards. There are at least seven high-level principles which are mentioned in the paper. It is presented the general concept of the deep geological repository, very important for an acceptable solution for the management of nuclear waste, what is a prerequisite for a renewal of nuclear power. Further are introduced natural and archaeological (manufactured) analogue

  13. Novel acetylcholine and carbamoylcholine analogues

    DEFF Research Database (Denmark)

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

    2008-01-01

    A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity...... for this subtype over alpha 3beta 4, alpha 4beta 4, and alpha 7 nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced alpha 4beta 2 selectivities exhibited...... by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial alpha 4beta 2 nAChR agonist with negligible activities at the alpha 3beta 4 and alpha 7 subtypes, thus being one of the few truly functionally selective alpha 4beta 2 nACh...

  14. Substrate analogues for isoprenoid enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Stremler, K.E.

    1987-01-01

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

  15. The Valles natural analogue project

    International Nuclear Information System (INIS)

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    1994-12-01

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

  16. Condensed matter analogues of cosmology

    Science.gov (United States)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

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

  17. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    Malik Chalal

    2014-06-01

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

  18. Enzymatic ligation for synthesis of single-chain analogue of monellin by transglutaminase.

    Science.gov (United States)

    Ota, M; Sawa, A; Nio, N; Ariyoshi, Y

    1999-08-01

    Monellin, a sweet protein, consists of two noncovalently associated polypeptide chains: an A chain of 44 amino acid residues and a B chain of 50 residues. Microbial transglutaminase (MTGase) was used for ligation of the monellin subunits without any protecting groups, and without activation of the C alpha-carboxyl group at the C-terminus. Since a peptide fragment LLQG is a good substrate for MTGase to form an amide bond between the gamma-amide group of the Gln residue and the epsilon-amino group of Lys, a monellin B chain analogue in which LLQG was elongated at the C-terminus (B-LLQG) was synthesized by solid-phase synthesis. The monellin A chain analogue in which KGK was elongated at the N-terminus (KGK-A) was synthesized by the same method as that of the B chain analogue. The KGK-A chain and the B-LLQG chain were coupled by MTGase to give single-chain analogue of monellin. The single-chain analogue of monellin was characterized by analytical reverse phase high performance liquid chromatography, electrospray ionization, and amino acid analyses. All analyses gave satisfactory results. The single-chain analogue of monellin was more heat stable than natural monellin.

  19. An arsenical analogue of adenosine diphosphate.

    Science.gov (United States)

    Webster, D; Sparkes, M J; Dixon, H B

    1978-01-01

    An analogue of ADP was made in which the terminal phosphono-oxy group, -O-PO(OH)2, has been replaced by the arsonomethyl group, -CH2-AsO(OH)2. This compound cannot form a stable analogue of ATP because anhydrides of arsonic acids are rapidly hydrolysed, so that any enzyme that phosphorylates ADP and accepts this analogue as a substrate should release orthophosphate in its presence. The analogue proves to be a poor substrate for 3-phosphoglycerate kinase (V/Km is diminished by a factor of 10(2)-10(3)) and a very poor substrate for pyruvate kinase (V/Km is diminished by a factor of 10(5)-10(6)). No substrate action was detected with adenyl kinase and creatine kinase. PMID:204292

  20. International video project on natural analogues

    International Nuclear Information System (INIS)

    Guentensperger, Marcel

    1993-01-01

    A natural analogue can be defined as a natural process which has occurred in the past and is studied in order to test predictions about the future evolution of similar processes. In recent years, natural analogues have been used increasingly to test the mathematical models required for repository performance assessment. Analogues are, however, also of considerable use in public relations as they allow many of the principles involved in demonstrating repository safety to be illustrated in a clear manner using natural systems with which man is familiar. The international Natural Analogue Working Group (NAWG), organised under the auspices of the CEC, has recognised that such PR applications are of considerable importance and should be supported from a technical level. At the NAWG meeting in Pitlochry, Scotland (June 1990), it was recommended that the possibilities for making a video film on this topic be investigated and Nagra was requested to take the lead role in setting up such a project

  1. Natural analogues and radionuclide transport model validation

    International Nuclear Information System (INIS)

    Lever, D.A.

    1987-08-01

    In this paper, some possible roles for natural analogues are discussed from the point of view of those involved with the development of mathematical models for radionuclide transport and with the use of these models in repository safety assessments. The characteristic features of a safety assessment are outlined in order to address the questions of where natural analogues can be used to improve our understanding of the processes involved and where they can assist in validating the models that are used. Natural analogues have the potential to provide useful information about some critical processes, especially long-term chemical processes and migration rates. There is likely to be considerable uncertainty and ambiguity associated with the interpretation of natural analogues, and thus it is their general features which should be emphasized, and models with appropriate levels of sophistication should be used. Experience gained in modelling the Koongarra uranium deposit in northern Australia is drawn upon. (author)

  2. Experiential acceptance and trait-mindfulness as predictors of analogue post-traumatic stress.

    Science.gov (United States)

    Boelen, Paul A; Lenferink, Lonneke I M

    2018-03-01

    Experiential acceptance and trait-mindfulness are associated with post-traumatic stress disorder (PTSD) after traumatic events. This study was a preliminary attempt to examine (1) associations of experiential acceptance and trait-mindfulness with post-traumatic stress (PTS) associated with negative, but not necessarily traumatizing, life events ('analogue' PTS), (2) the role of these variables in the context of neuroticism as well as worry and rumination - two other regulatory strategies associated with PTS, and (3) the impact of pre-trauma tendencies towards experiential acceptance and mindfulness on analogue PTS. Data were obtained from two distinct student samples. A first sample provided cross-sectional data. In a second sample, indices of acceptance, mindfulness, neuroticism, worry, and rumination were tapped at inclusion into the study, and analogue PTS and confrontation with stressful life events were subsequently assessed 1 year later. In the cross-sectional sample, higher acceptance and mindfulness were associated with lower analogue PTS, even when controlling for neuroticism, worry, and rumination. In the prospective sample, pre-trauma mindfulness (but not experiential acceptance, neuroticism, worry, and rumination) assessed at baseline predicted levels of analogue PTS 1 year later. Findings suggest that experiential acceptance and trait-mindfulness are incrementally related to PTS beyond neuroticism, worry, and rumination and that pre-trauma trait-mindfulness may be a resilience factor protecting against severe PTS. We examined associations of experiential acceptance and trait-mindfulness with post-traumatic stress (PTS) associated with negative life events ('analogue' PTS). Experiential acceptance and trait-mindfulness were associated with concurrent analogue PTS, over and above neuroticism, worry, and rumination. Pre-trauma trait-mindfulness (but not pre-trauma experiential acceptance) significantly predicted analogue PTS in prospective analyses

  3. A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Jaroszewski, Jerzy W; Hansen, Steen Honoré

    2003-01-01

    A general, improved procedure for rapid synthesis of philanthotoxin analogues, a pharmacologically important class of polyamine conjugates, is described. The solution-phase procedure is illustrated by gram-scale synthesis of philanthotoxins PhTX-343 and PhTX-12. Selectively protected polyamines...

  4. Radioprotective efficacy of serotonin and its analogues in the experiments with sea urchin eggs (Strongylocentrotus nudus)

    International Nuclear Information System (INIS)

    Parkhomenko, I.M.; Graevskaya, E.Eh.; Tarasenko, A.G.; Kudryashov, Yu.B.

    1975-01-01

    Serotonin and mexamine, added to cells before or after irradiation, were found to increase the survival rate of S. nudus eggs. Their analogues (6-oxytryptamine, 5-sulphamidotryptamine-2-carboxylic acid), which do not have a protective effect on mammals, increased the survival rate of irradiated eggs when used before and after irradiation. Histamine also had a protective action. The possible mechanism underlying the action of the amines used is discussed. (V.A.P.)

  5. Between Analogue and Digital Diagrams

    Directory of Open Access Journals (Sweden)

    Zoltan Bun

    2012-10-01

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

  6. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

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

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

    CERN Document Server

    Small, James S

    2013-01-01

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

  8. Prostacyclin Suppresses Twist Expression in the Presence of Indomethacin in Bone Marrow-Derived Mesenchymal Stromal Cells

    Science.gov (United States)

    Kemper, Oliver; Herten, Monika; Fischer, Johannes; Haversath, Marcel; Beck, Sascha; Classen, Tim; Warwas, Sebastian; Tassemeier, Tjark; Landgraeber, Stefan; Lensing-Höhn, Sabine; Krauspe, Rüdiger; Jäger, Marcus

    2014-01-01

    Background Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of the iliac crest followed by density gradient centrifugation and flow cytometry with defined antigens (CD105+/73+/45−/14−). The cells were seeded and incubated as follows: without additives (Group 0; donor A/B/C), with 10−7 M iloprost only (Group 0+ilo; A/B), with indomethacin only in concentrations of 10−6 M (Group 1, A), 10−5 M (Group 2, B), 10−4 M (Group 3, A/B), and together with 10−7 M iloprost (Groups 4–6, A/B/C). On Day 10 and 28, UV/Vis spectrometric and immunocytochemical assays (4 samples per group and donor) were performed to investigate cell proliferation (cell count measurement) and differentiation towards the osteoblastic lineage (CD34−, CD45−, CD105+, type 1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Runx2, Twist, specific ALP-activity). Results Indomethacin alone suppressed BMSC differentiation towards the osteoblastic lineage by downregulation of Runx2, Col1, and ALP. In combination with indomethacin, iloprost increased cell proliferation and differentiation and it completely suppressed Twist expression at Day 10 and 28. Iloprost alone did not promote cell proliferation, but moderately enhanced Runx2 and Twist expression. However, the proliferative effects and the specific ALP-activity varied donor-dependently. Conclusions Iloprost partially antagonized the suppressing effects of indomethacin on BMSC differentiation towards the osteoblast lineage. It enhanced the expression of Runx2 and, only in the presence of indomethacin

  9. Total synthesis of sannanine and analogues thereof

    Indian Academy of Sciences (India)

    BADHER NAVEEN

    2018-03-02

    Mar 2, 2018 ... concise manner. The key strategies involve Friedländer quinoline synthesis, demethylation, in situ oxidation and amination process. ..... (b) Hargreaves R, David C L, Whitesell L and Skibo E. B 2003 Design of Quinolinedione-Based Geldanamycin. Analogues Bioorg. Med. Chem. Lett. 13 3075; (c) Arg-.

  10. Ultrasound exfoliation of inorganic analogues of graphene

    Czech Academy of Sciences Publication Activity Database

    Štengl, Václav; Henych, Jiří; Slušná, Michaela; Ecorchard, Petra

    2014-01-01

    Roč. 9, APR (2014), s. 1-14 ISSN 1556-276X R&D Projects: GA ČR(CZ) GA14-05146S Institutional support: RVO:61388980 Keywords : Ultrasound * Exfoliation * Graphene inorganic analogues Subject RIV: CA - Inorganic Chemistry Impact factor: 2.779, year: 2014

  11. The World Is either Digital or Analogue

    NARCIS (Netherlands)

    Berto, F.; Tagliabue, J.

    2014-01-01

    We address an argument by Floridi (Synthese 168(1):151-178, 2009; 2011a), to the effect that digital and analogue are not features of reality, only of modes of presentation of reality. One can therefore have an informational ontology, like Floridi’s Informational Structural Realism, without

  12. Somatostatin analogue scintigraphy and tuberculosis: case report

    International Nuclear Information System (INIS)

    Biancheri, I.; Rudenko, B.; Vautrin, P.; Raddoul, J.; Lamfichek, N.; Kantelip, B.; Mantion, G.

    2005-01-01

    Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

  13. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

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

    2012-01-01

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

  14. The Palmottu analogue project: overview for 1993

    International Nuclear Information System (INIS)

    Ruskeeniemi, T.; Blomqvist, R.; Suksi, J.; Niini, H.

    1994-01-01

    This article gives a summary of the activities carried out within the Palmottu analogue project in 1993. It consists of (1) an introductory part, followed by (2) a geological description of the site, and (3)an up-to-date summary of the results of the project. (orig.) (33 refs., 6 figs.)

  15. Natural product analogues: towards a blueprint for analogue-focused synthesis.

    Science.gov (United States)

    Bebbington, Magnus W P

    2017-08-14

    For the first time a general overview of approaches to the synthesis of natural product analogues is presented. This reflects a process of evolution of natural product synthesis which has accelerated in the years since the implementation of diversity-oriented synthesis, which has emerged in parallel with collective synthesis, diverted total synthesis and the preparation of truncated natural products optimised for biological activity. A method involving computational assessment for the validation of core-modified natural product analogues is discussed.

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

    Science.gov (United States)

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

    1982-06-01

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

  17. Novel short-chain analogues of somatostatin as ligands for Cu(II) ions. Role of the metal ion binding on the spatial structure of the ligand.

    Science.gov (United States)

    Marciniak, Aleksandra; Cebrat, Marek; Czyżnikowska, Żaneta; Brasuń, Justyna

    2012-12-01

    In this paper we present the studies on coordination abilities of two short-chain analogues of somatostatin with free N-terminal and protected amino group towards copper (II) ions. The octreotide is the most popular analogue of the somatostatin (peptide hormone) used in medicine. Somatostatin analogues are used in diagnosis and treatment of the neuroendocrine tumors. Both analyzed analogues are characterized by the presence of two His instead of Cys residues in characteristic fragment of native peptide. We characterize coordination abilities of the ligands using potentiometric and spectroscopic methods. His-analogues of somatostatin are effective ligands for copper (II) ions. Both peptides are able to form the complexes with the cyclic structure. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Radioprotection of intestinal stem cells and whole body radiation lethality from photons and neutrons by prostaglandins along or in combination with WR-2721. Technical report 24 Feb 86-30 Sep 89

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.R.

    1990-12-01

    Prostaglandins (PGs) have been shown to protect the gastrointestinal and hematopoietic cell renewal systems from some degree of radiation damage. The mechanism(s) to account for these observations are unknown. Based on preliminary evidence that PGs varied in the degree to which they afforded protection of intestinal stem cells, we studied protection by several PGs and their analogues. The most protective PGs found to date were 16,16 dm PGE2, misoprostol, a PGE1 analogues, and iloprost, a PGI2 analogue. The relative degrees of protection were 400%, 700% and 800% above control values at a dose of 13.5 137 Cs gamma radiation. These three PGs were used for subsequent studies. Iloprost is a stable PG at room temperature and was found to be protective given orally. In addition to radioprotection of the intestinal stem cells, these Pgs increased the LD50/6, LD50/30 and animal longevity through both the gastrointestinal and hematopoietic syndromes. Misoprostol protected the gut from JANUS neutrons and increased animal longevity following neutron irradiation. Although the mechanism for PG-induced radioprotection is unknown, it appears to be different compared to the widely studied amino thiol, WR-2721. Evidence to support this contention came from data showing that all these analogues were additive to the protective effect of Wr-2721.

  19. Somatostatin analogues for acute bleeding oesophageal varices

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C.; Hrobjartsson, A.

    2008-01-01

    BACKGROUND: Somatostatin and its derivatives are sometimes used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver. OBJECTIVES: To study whether somatostatin or its analogues improve survival or reduce the need for blood transfusions in patients...... with bleeding oesophageal varices. SEARCH STRATEGY: PubMed and The Cochrane Library were searched (November 2007). Reference lists of publications, contacts with authors. SELECTION CRITERIA: All randomised trials comparing somatostatin or analogues with placebo or no treatment in patients suspected of acute...... or recent bleeding from oesophageal varices. DATA COLLECTION AND ANALYSIS: The outcome measures extracted were: mortality, blood transfusions, use of balloon tamponade, initial haemostasis and rebleeding. Intention-to-treat analyses including all randomised patients were conducted if possible; a random...

  20. Studies of natural analogues and geological systems

    International Nuclear Information System (INIS)

    Brandberg, F.; Grundfelt, B.; Hoeglund, L.; Skagius K.; Karlsson, F.; Smellie, J.

    1993-04-01

    This review has involved studies of natural analogues and natural geological systems leading to the identification and quantification of processes and features of importance to the performance and safety of repositories for radioactive waste. The features and processes selected for the study comprise general geochemical issues related to the performance of the near- and far-field, the performance and durability of construction materials and the effects of glaciation. For each of these areas a number of potentially important processes for repository performance have been described, and evidence for their existence, as well as quantification of parameters of models describing the processes have been sought from major natural analogue studies and site investigations. The review has aimed at covering a relatively broad range of issues at the expense of in-depth analysis. The quantitative data presented are in most cases compilations of data from the literature; in a few cases results of evaluations made within the current project are included

  1. Boron hydride analogues of the fullerenes

    International Nuclear Information System (INIS)

    Quong, A.A.; Pederson, M.R.; Broughton, J.Q.

    1994-01-01

    The BH moiety is isoelectronic with C. We have studied the stability of the (BH) 60 analogue of the C 60 fullerene as well as the dual-structure (BH) 32 icosahedron, both of them being putative structures, by performing local-density-functional electronic calculations. To aid in our analysis, we have also studied other homologues of these systems. We find that the latter, i.e., the dual structure, is the more stable although the former is as stable as one of the latter's lower homologues. Boron hydrides, it seems, naturally form the dual structures used in algorithmic optimization of complex fullerene systems. Fully relaxed geometries are reported as well as electron affinities and effective Hubbard U parameters. These systems form very stable anions and we conclude that a search for BH analogues of the C 60 alkali-metal supeconductors might prove very fruitful

  2. The synthesis and pharmacology of ephedrine analogues

    OpenAIRE

    Mullen, Aidan J

    1991-01-01

    In this report we set out to extend recent studies on substituted PAC analogues produced by the fermentation of aromatic aldehydes with Saccharomyces cerevisiae. The medium selected contained glucose as a carbon source for the biotransformation, and sodium pyruvate as an inhibitor for alcohol dehydrogenase, the enzyme responsible for the conversion of the carbinol to a benzyl alcohol derivatives. An investigation of sodium cyanoborohydride for a selective reductive ami...

  3. Electromagnetic wave analogue of electronic diode

    OpenAIRE

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

    2010-01-01

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

  4. Geometric Analogue of Holographic Reduced Representation

    OpenAIRE

    Aerts, Diederik; Czachor, Marek; De Moor, Bart

    2007-01-01

    Holographic reduced representations (HRR) are based on superpositions of convolution-bound $n$-tuples, but the $n$-tuples cannot be regarded as vectors since the formalism is basis dependent. This is why HRR cannot be associated with geometric structures. Replacing convolutions by geometric products one arrives at reduced representations analogous to HRR but interpretable in terms of geometry. Variable bindings occurring in both HRR and its geometric analogue mathematically correspond to two ...

  5. Analogue forecasting of New Zealand climate anomalies

    Science.gov (United States)

    Mullan, A. Brett; Thompson, Craig S.

    2006-03-01

    An analogue forecast scheme is described for multifield prediction of monthly and seasonal New Zealand climate anomalies on the basis of the methodology of Livezey and Barnston ([1988]) for US seasonal temperatures. The method is applied to predicting terciles of temperature and precipitation for six regions of New Zealand. Empirical orthogonal function analysis is used to reduce sea surface temperature and sea-level pressure predictors down to a set of five independent indices, which incorporate variations due to El Niño-Southern Oscillation, Indian Ocean sea temperatures and a wave 3 pattern in the Southern Hemisphere westerlies. A full bootstrap cross-validation procedure is carried out, along with Monte Carlo tests, to assess the skill of the method on independent data and to determine the significance of the results. Significant skill is found for seasonal temperature forecasts for the summer and winter seasons; there is less success in predicting monthly temperatures or rainfall at either timescale. Considerable care is required to constrain the climate state vector, from which analogues are defined, and to constrain the search procedure itself, in order to produce results that are stable with respect to small parameter changes in the model. For the New Zealand region, 5 to 7 is found to be the optimum number of closest analogues, and the inclusion of anti-analogues improves the predictions, at least in the seasonal case. Skill in predicting regional temperature and rainfall is shown to be related to a combination of skill in predicting sea-level pressure patterns and to how strongly these patterns project onto temperature and rainfall anomalies.

  6. The Brookhaven electron analogue, 1953--1957

    International Nuclear Information System (INIS)

    Plotkin, M.

    1991-01-01

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

  7. The Brookhaven electron analogue, 1953--1957

    Energy Technology Data Exchange (ETDEWEB)

    Plotkin, M.

    1991-12-18

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

  8. Synthesis of D-nor steroid analogues

    Czech Academy of Sciences Publication Activity Database

    Slavíková, Barbora; Kudová, Eva

    2014-01-01

    Roč. 108, S2 (2014), s142 ISSN 0009-2770. [Conference on Isoprenoids /22./. 07.09.2014-10.09.2014, Praha] R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GAP303/12/1464 Institutional support: RVO:61388963 Keywords : D-nor steroid analogues * patch clamp technique Subject RIV: CC - Organic Chemistry

  9. New alloferon analogues: synthesis and antiviral properties.

    Science.gov (United States)

    Kuczer, Mariola; Majewska, Anna; Zahorska, Renata

    2013-02-01

    We have extended our study on structure/activity relationship studies of insect peptide alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) by evaluating the antiviral effects of new alloferon analogues. We synthesized 18 alloferon analogues: 12 peptides with sequences shortened from N- or C-terminus and 6 N-terminally modified analogues H-X(1)-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH, where X(1) = Phe (13), Tyr (14), Trp (15), Phg (16), Phe(p-Cl) (17), and Phe(p-OMe) (18). We found that most of the evaluated peptides inhibit the replication of Human Herpesviruses or Coxsackievirus B2 in Vero, HEp-2 and LLC-MK(2) cells. Our results indicate that the compound [3-13]-alloferon (1) exhibits the strongest antiviral activity (IC(50) = 38 μM) among the analyzed compound. Moreover, no cytotoxic activity against the investigated cell lines was observed for all studied peptides at concentration 165 μM or higher. © 2012 John Wiley & Sons A/S.

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

    CERN Document Server

    Pickering, J.

    2015-06-15

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

  11. The Greenland analogue project. Yearly report 2010

    International Nuclear Information System (INIS)

    Harper, J.; Brinkerhoff, D.; Johnson, J.; Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I.

    2012-04-01

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

  12. The Greenland analogue project. Yearly report 2010

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

  13. Natural Analogues of CO2 Geological Storage

    International Nuclear Information System (INIS)

    Perez del Villar, L.; Pelayo, M.; Recreo, F.

    2007-01-01

    Geological storage of carbon dioxide is nowadays, internationally considered as the most effective method for greenhouse gas emission mitigation, in order to minimize the global climate change universally accepted. Nevertheless, the possible risks derived of this long-term storage have a direct influence on its public acceptance. Among the favourable geological formations to store CO2, depleted oil and gas fields, deep saline reservoirs, and unamiable coal seams are highlighted. One of the most important objectives of the R and D projects related to the CO2 geological storage is the evaluation of the CO2 leakage rate through the above mentioned geological formations. Therefore, it is absolutely necessary to increase our knowledge on the interaction among CO2, storage and sealing formations, as well as on the flow paths and the physical resistance of the sealing formation. The quantification of the CO2 leakage rate is essential to evaluate the effects on the human and animal health, as well as for the ecosystem and water quality. To achieve these objectives, the study of the natural analogues is very useful in order to know the natural leakage rate to the atmosphere, its flow paths, the physical, chemical and mineralogical modifications due to the long term interaction processes among the CO2 and the storage and sealing formations, as well as the effects on the groundwaters and ecosystems. In this report, we have tried to summarise the main characteristics of the natural reservoirs and surficial sources of CO2, which are both natural analogues of the geological storage and CO2 leakage, studied in EEUU, Europe and Australia. The main objective of this summary is to find the possible applications for long-term risk prediction and for the performance assessment by means of conceptual and numerical modelling, which will allow to validate the predictive models of the CO2 storage behaviour, to design and develop suitable monitoring techniques to control the CO2 behaviour

  14. Nuclear waste geochemistry: natural and anthropic analogues

    International Nuclear Information System (INIS)

    Petit, J.C.

    1997-01-01

    The geochemical evolution of nuclear waste storage is difficult to describe, due to the long time scales involved, the radioactivity confinement complexity and the un-natural radionuclides which evolution is not known. In order to carry out a long term prediction, a special approach is used, based on a combination of experiments conducted in laboratories and in situ, modelizations and comparisons with process and material analogues (natural or man-made, such as basaltic and rhyolitic volcanic glasses, plutonium, historical and archaeological artefacts)

  15. Somatostatin analogue scintigraphy in granulomatous diseases

    Energy Technology Data Exchange (ETDEWEB)

    Vanhagen, P.M. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands) Dept. of Immunology, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Krenning, E.P. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands) Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Reubi, J.C. (Inst. of Pathology, Bern Univ. (Switzerland)); Kwekkeboom, D.J. (Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Bakker, W.H. (Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Mulder, A.H. (Dept. of Pathology, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Laissue, I. (Inst. of Pathology, Bern Univ. (Switzerland)); Hoogstede, H.C. (Dept. of Chest Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Lamberts, S.W.J. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands))

    1994-06-01

    In the present study 20 consecutive patients were investigated, 12 with sarcoidosis, one with both sarcoidosis and aspergillosis, four with tuberculosis and three with Wegener's granulomatosis. For in vivo SS-R imaging, total-body scintigraphy was performed 24 and 48 h after the administration of [sup 111]In-octreotide. Granuloma localizations could be visualized in all patients studied; additional sites were found in nine patients with sarcoidosis and in two patients with tuberculosis. In vitro autoradiography of fresh tissue biopsies, using the SS analogue [[sup 125]I-Tyr[sup 3

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

    International Nuclear Information System (INIS)

    Kovach, L.A.; Ott, W.R.

    1995-01-01

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

  17. Ways to Optimize Analogue Switched Circuits

    Directory of Open Access Journals (Sweden)

    J. Hospodka

    2008-12-01

    Full Text Available This paper describes how analogue switched circuits (switched-capacitor and switched-current circuits can be optimized by means of a personal computer. The optimization of this kind of circuits is not so common and their analysis is more difficult in comparison with continuously working circuits. Firstly, the nonidealities occurring in these circuits whose effect on their characteristics should be optimized are discussed. Then a few ways to analyze analogue switched circuits are shown. From all optimization algorithms applicable for this kind of optimization, two ones that seem to be the most promising are proposed. The differential evolution (one of evolutionary algorithms combined with the simplex method was found to be most appropriate from these two ones. Two types of programs are required for the optimization of these circuits: a program for implementing calculations of the used optimization algorithm and a program for the analysis of the optimized circuit. Several suitable computer programs from both of the groups together with their proper settings according to authors’ experience are proposed. At the end of the paper, an example of a switched-current circuit optimization documenting the previous description is presented.

  18. Andrographolide and analogues in cancer prevention.

    Science.gov (United States)

    Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

    2015-01-01

    Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

  19. Radio-modifying effects of amifostine analogues in whole body gamma irradiated mice

    International Nuclear Information System (INIS)

    Soni, Ravi; Arora, Aastha; Singh, Saurabh; Bhuria, Vikas; Sharma, Anjali; Bhatt, A.N.; Dwarakanath, B.S.; Pathak, Uma; Mathur, Shweta; Sandhir, Rajat

    2014-01-01

    Damage to hematopoietic and gastro-intestinal systems contribute mainly to acute effects (mortality) following exposures to moderate doses of ionizing radiation. The aminothiol, amifostine (WR2721, a FDA approved pro-drug) has been well established protector of normal tissues against radiation damage and chemo-therapeutic drugs induced toxicity. A number of amifostine analogues (DRDE-07, DRDE-30 and DRDE-35) have been recently synthesized that afford protection against Sulfur Mustard (SM) when administered orally. Since, the mechanisms underlying toxicity by SM share a great deal with ionizing radiation and certain anti-cancer drugs, we investigated the potential of DRDE analogues in reducing the acute effects of radiation in whole body irradiated mice. Animal survival, body weight, changes in haematological parameters and CFU-S as well as morphology of GI was studied. DRDE analogues significantly enhanced the animal survival and reduced the radiation sickness (loss of weight) in a dose dependent manner when administered 30 min. before irradiation; optimal doses were 125 mg/kg body weight for DRDE-07; 220 mg/kg for DRDE-30 and 200 mg/kg for DRDE-35. All three analogues were orally effective unlike amifostine, albeit to different extents. The order of radio-protective efficacy in C57BL/6 mice when administered orally was DRDE-35 (60%) > DRDE-07 (50%) > DRDE-30 (40%), while it was DRDE-07 (58%) > DRDE-30 (44%) > DRDE-35 (40%) following intra-peritoneal administration. These analogues enhanced the recovery from radiation-induced hematopoietic damage (peripheral blood counts and improvement in endogenous spleen colony forming units) and gastrointestinal injury (improved structural integrity of GI, increase in villi height, regenerating crypts and mitotic figures) that correlated with the increase in survival. There were no survivors in the radiation group after 35 days of exposure and the values for the analyzed parameters were comparable to the control group. These

  20. Prostaglandin E₂ protects murine lungs from bleomycin-induced pulmonary fibrosis and lung dysfunction.

    Science.gov (United States)

    Dackor, Ryan T; Cheng, Jennifer; Voltz, James W; Card, Jeffrey W; Ferguson, Catherine D; Garrett, Ryan C; Bradbury, J Alyce; DeGraff, Laura M; Lih, Fred B; Tomer, Kenneth B; Flake, Gordon P; Travlos, Gregory S; Ramsey, Randle W; Edin, Matthew L; Morgan, Daniel L; Zeldin, Darryl C

    2011-11-01

    Prostaglandin E(2) (PGE(2)) is a lipid mediator that is produced via the metabolism of arachidonic acid by cyclooxygenase enzymes. In the lung, PGE(2) acts as an anti-inflammatory factor and plays an important role in tissue repair processes. Although several studies have examined the role of PGE(2) in the pathogenesis of pulmonary fibrosis in rodents, results have generally been conflicting, and few studies have examined the therapeutic effects of PGE(2) on the accompanying lung dysfunction. In this study, an established model of pulmonary fibrosis was used in which 10-12-wk-old male C57BL/6 mice were administered a single dose (1.0 mg/kg) of bleomycin via oropharyngeal aspiration. To test the role of prostaglandins in this model, mice were dosed, via surgically implanted minipumps, with either vehicle, PGE(2) (1.32 μg/h), or the prostacyclin analog iloprost (0.33 μg/h) beginning 7 days before or 14 days after bleomycin administration. Endpoints assessed at 7 days after bleomycin administration included proinflammatory cytokine levels and measurement of cellular infiltration into the lung. Endpoints assessed at 21 days after bleomycin administration included lung function assessment via invasive (FlexiVent) analysis, cellular infiltration, lung collagen content, and semiquantitative histological analysis of the degree of lung fibrosis (Ashcroft method). Seven days after bleomycin administration, lymphocyte numbers and chemokine C-C motif ligand 2 expression were significantly lower in PGE(2)- and iloprost-treated animals compared with vehicle-treated controls (P bleomycin challenge, PGE(2) also protected against the decline in lung static compliance, lung fibrosis, and collagen production that is associated with 3 wk of bleomycin exposure. However, PGE(2) had no therapeutic effect on these parameters when administered 14 days after bleomycin challenge. In summary, PGE(2) prevented the decline in lung static compliance and protected against lung fibrosis when it

  1. Prostaglandin E2 protects murine lungs from bleomycin-induced pulmonary fibrosis and lung dysfunction

    Science.gov (United States)

    Dackor, Ryan T.; Cheng, Jennifer; Voltz, James W.; Card, Jeffrey W.; Ferguson, Catherine D.; Garrett, Ryan C.; Bradbury, J. Alyce; DeGraff, Laura M.; Lih, Fred B.; Tomer, Kenneth B.; Flake, Gordon P.; Travlos, Gregory S.; Ramsey, Randle W.; Edin, Matthew L.; Morgan, Daniel L.

    2011-01-01

    Prostaglandin E2 (PGE2) is a lipid mediator that is produced via the metabolism of arachidonic acid by cyclooxygenase enzymes. In the lung, PGE2 acts as an anti-inflammatory factor and plays an important role in tissue repair processes. Although several studies have examined the role of PGE2 in the pathogenesis of pulmonary fibrosis in rodents, results have generally been conflicting, and few studies have examined the therapeutic effects of PGE2 on the accompanying lung dysfunction. In this study, an established model of pulmonary fibrosis was used in which 10–12-wk-old male C57BL/6 mice were administered a single dose (1.0 mg/kg) of bleomycin via oropharyngeal aspiration. To test the role of prostaglandins in this model, mice were dosed, via surgically implanted minipumps, with either vehicle, PGE2 (1.32 μg/h), or the prostacyclin analog iloprost (0.33 μg/h) beginning 7 days before or 14 days after bleomycin administration. Endpoints assessed at 7 days after bleomycin administration included proinflammatory cytokine levels and measurement of cellular infiltration into the lung. Endpoints assessed at 21 days after bleomycin administration included lung function assessment via invasive (FlexiVent) analysis, cellular infiltration, lung collagen content, and semiquantitative histological analysis of the degree of lung fibrosis (Ashcroft method). Seven days after bleomycin administration, lymphocyte numbers and chemokine C-C motif ligand 2 expression were significantly lower in PGE2- and iloprost-treated animals compared with vehicle-treated controls (P bleomycin challenge, PGE2 also protected against the decline in lung static compliance, lung fibrosis, and collagen production that is associated with 3 wk of bleomycin exposure. However, PGE2 had no therapeutic effect on these parameters when administered 14 days after bleomycin challenge. In summary, PGE2 prevented the decline in lung static compliance and protected against lung fibrosis when it was administered

  2. Space Analogue Environments: Are the Populations Comparable?

    Science.gov (United States)

    Sandal, G. M.

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

  3. Jupiter analogues and planets of active stars

    Directory of Open Access Journals (Sweden)

    Henning T.

    2013-04-01

    Full Text Available Combined results are now available from a 15 year long search for Jupiter analogues around solar-type stars using the ESO CAT + CES, ESO 3.6 m + CES, and ESO 3.6 m + HARPS instruments. They comprise planet (co-discoveries (ι Hor and HR 506 and confirmations (three planets in HR 3259 as well as non-confirmations of planets (HR 4523 and ɛ Eri announced elsewhere. A long-term trend in ɛ Ind found by our survey is probably attributable to a Jovian planet with a period >30 yr, but we cannot fully exclude stellar activity effects as the cause. A 3.8 year periodic variation in HR 8323 can be attributed to stellar activity.

  4. The gravitational analogue of the Witten effect

    International Nuclear Information System (INIS)

    Foda, O.

    1984-06-01

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

  5. Gravitational analogue of the Witten effect

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-07-22

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

  6. The gravitational analogue of the Witten effect

    International Nuclear Information System (INIS)

    Foda, O.

    1985-01-01

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

  7. Reflective analogue optical link operating issues

    CERN Document Server

    Batten, Jeremy

    1996-01-01

    The proposed readout of analogue data from CMS tracker will use an optical fibre link. The choice of transmitter/receiver technology, however, has been the subject of intense research and development by the RD23 collaboration. One solution uses passive devices, multi-quantum well modulators, at the detector front end, and continuous wave driving lasers at the readout back end. This system has been tested at Imperial College. We report on the following: problems of noise associated with multimoded behaviour of a degraded laser; measurements of laser wavelength dependence on both drive current and temperature; and modulator reflectance dependence on laser wavelength. We extrapolate the findings to system issues, highlighting the degree of temperature control required of the driving laser.

  8. The glaciogenic reservoir analogue studies project (GRASP)

    DEFF Research Database (Denmark)

    Moscariello, A.; Moreau, Julien; Vegt, P. van der

    increasing the risk associated with developing effectively these reservoirs. Therefore a analogue-based predictive stratigraphical and sedimentological model can help to steer drilling strategy and reduce uncertainties and associated risks. For this purpose the GRASP joint industry programme was established......Tunnel galleys are common features in Palaeozoic glacigenic succession in North Afrcica and Middle East and they are amongst the most challenging target for hydrocarbon exploration and developing drilling in these regions. Similarly, these buried valleys form important groundwater reservoirs...... in Quaternary glaciated areas and their nature and sediment composition is critical to drive a sustainable production strategy and assess their vulnerability. Seismic resolution however, often limits the understanding of channel valleys morphology, 3D geometry and internal reservoir distribution, thus...

  9. Synthesis of an Orthogonal Topological Analogue of Helicene

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  10. Caged ceramide 1-phosphate analogues: synthesis and properties.

    Science.gov (United States)

    Lankalapalli, Ravi S; Ouro, Alberto; Arana, Lide; Gómez-Muñoz, Antonio; Bittman, Robert

    2009-11-20

    Sphingolipid phosphate analogues bearing 7-(diethylamino)coumarin (DECM) and 4-bromo-5-hydroxy-2-nitrobenzhydryl (BHNB) groups in a photolabile ester bond were synthesized. The ability of the "caged" ceramide 1-phosphate analogues to release the bioactive parent molecule upon irradiation at 400-500 nm was demonstrated by stimulation of macrophage cell proliferation.

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

    DEFF Research Database (Denmark)

    Bloch, Rene

    The research and development carried out in this Ph.D. study focusses on two key areas of the design flow for analogue and mixed-signal integrated circuit design, the mixed-signal floorplanning and the analogue layout generation.A novel approach to floorplanning is presented which provides true i...

  12. Uncertainties and credibility building of safety analyses. Natural analogues

    International Nuclear Information System (INIS)

    Laciok, A.

    2001-07-01

    The substance of natural analogues and their studies is defined as a complementary method to laboratory and in-situ experiments and modelling. The role of natural analogues in the processes of development of repositories is defined, mainly in performance assessment of repository system and communication with public. The criteria for identification of natural analogues which should be evaluated in the phase of initiation of new studies are specified. Review part of this report is divided to study of natural analogues and study of anthropogenic and industrial analogues. The main natural analogue studies performed in various countries, in different geological setting, with various aims are characterized. New results acquired in recently finished studies are included: Palmottu (2nd phase of project financed by European Commission), Oklo (results of research financed also by European Commission), Maqarin (3rd phase) and other information obtained from last meetings and workshops of NAWG. In view of the fact that programmes of development of deep repositories in Czech and Slovak Republics are interconnected, the natural analogues studies carried out in the Czech republic are incorporated in separate chapter - study of uranium accumulation in Tertiary clays at Ruprechtov site and study of degradation of natural glasses. In final part the areas of natural analogue studies as an integral part of development of deep geological repository are proposed along with characterization of broader context and aspects of realization of these studies (international cooperation, preparation and evaluation of procedures, communication with public). (author)

  13. Insulin analogues and severe hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  14. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-01

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

  15. Natural analogues of nuclear waste glass corrosion

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  16. Natural analogues of nuclear waste glass corrosion.

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-01-06

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

  17. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-01

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

  18. Magnetic properties of Proxima Centauri b analogues

    Science.gov (United States)

    Zuluaga, Jorge I.; Bustamante, Sebastian

    2018-03-01

    The discovery of a planet around the closest star to our Sun, Proxima Centauri, represents a quantum leap in the testability of exoplanetary models. Unlike any other discovered exoplanet, models of Proxima b could be contrasted against near future telescopic observations and far future in-situ measurements. In this paper we aim at predicting the planetary radius and the magnetic properties (dynamo lifetime and magnetic dipole moment) of Proxima b analogues (solid planets with masses of ∼ 1 - 3M⊕ , rotation periods of several days and habitable conditions). For this purpose we build a grid of planetary models with a wide range of compositions and masses. For each point in the grid we run the planetary evolution model developed in Zuluaga et al. (2013). Our model assumes small orbital eccentricity, negligible tidal heating and earth-like radiogenic mantle elements abundances. We devise a statistical methodology to estimate the posterior distribution of the desired planetary properties assuming simple lprior distributions for the orbital inclination and bulk composition. Our model predicts that Proxima b would have a mass 1.3 ≤Mp ≤ 2.3M⊕ and a radius Rp =1.4-0.2+0.3R⊕ . In our simulations, most Proxima b analogues develop intrinsic dynamos that last for ≥4 Gyr (the estimated age of the host star). If alive, the dynamo of Proxima b have a dipole moment ℳdip >0.32÷2.9×2.3ℳdip , ⊕ . These results are not restricted to Proxima b but they also apply to earth-like planets having similar observed properties.

  19. MAQARIN natural analogue study: phase III

    International Nuclear Information System (INIS)

    Alexander, W.R.; Mazurek, M.; Waber, H.N.; Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K.; Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J.; Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J.; Clark, I.D.; Karlsson, F.; Khoury, H.N.; Salameh, E.; Lagerblad, B.; Longworth, G.; Savage, D.; Smellie, J.A.T.

    1998-12-01

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

  20. ENDOCRINE EVALUATION OF ATHLETE FOR TESTOSTERONE OR ITS ANALOGUES ABUSE

    Directory of Open Access Journals (Sweden)

    Joško Osredkar

    2003-12-01

    Full Text Available Background. Doping involves the use of substances and methods prohibited by international and national sports institutions. The use of certain substances and methods is harmful to the human organism, so all sports organisations are trying to protect athletes from the harmful side effects of such substances and methods.Methods. The article deals with special protocol, which is used in the case, when the testosterone/epitestosterone ratio in urine is higher than 6 and less then 10. When establishing the use of testosterone or analogues, ketoconazol is used. If after the application the presence of a testosterone (T to epitestosterone (E ratio is greater than six (6 to one (1, there is an evidence of doping offence.Conclusions. In the case of T/E greater than 6, it is mandatory that the relevant medical authority conducts an investigation before the sample is declared positive. A full report should be written and should include a review of previous tests, subsequent tests and any results of endocrine investigations.

  1. Superconducting Analogue of the Parafermion Fractional Quantum Hall States

    Directory of Open Access Journals (Sweden)

    Abolhassan Vaezi

    2014-07-01

    Full Text Available Read-Rezayi Z_{k} parafermion wave functions describe ν=2+(k/kM+2 fractional quantum Hall (FQH states. These states support non-Abelian excitations from which protected quantum gates can be designed. However, there is no experimental evidence for these non-Abelian anyons to date. In this paper, we study the ν=2/k FQH-superconductor heterostructure and find the superconducting analogue of the Z_{k} parafermion FQH state. Our main tool is the mapping of the FQH into coupled one-dimensional chains, each with a pair of counterpropagating modes. We show that by inducing intrachain pairing and charge preserving backscattering with identical couplings, the one-dimensional chains flow into gapless Z_{k} parafermions when k<4. By studying the effect of interchain coupling, we show that every parafermion mode becomes massive except for the two outermost ones. Thus, we achieve a fractional topological superconductor whose chiral edge state is described by a Z_{k} parafermion conformal field theory. For instance, we find that a ν=2/3 FQH in proximity to a superconductor produces a Z_{3} parafermion superconducting state. This state is topologically indistinguishable from the non-Abelian part of the ν=12/5 Read-Rezayi state. Both of these systems can host Fibonacci anyons capable of performing universal quantum computation through braiding operations.

  2. JACoW Lightweight acquisition system for analogue signals

    CERN Document Server

    Bielawski, Bartosz

    2018-01-01

    In a complex machine such as a particle accelerator there are thousands of analogue signals that need monitoring and even more signals that could be used for debugging or as a tool for detecting symptoms of potentially avoidable problems. Usually it is not feasible to acquire and monitor all of these signals not only because of the cost but also because of cabling and space required. The Radio Frequency system in the Large Hadron Collider (LHC) is protected by multiple hardware interlocks that ensure safe operation of klystrons, superconducting cavities and all the other equipment. In parallel, a diagnostic system has been deployed to monitor the health of the klystrons. Due to the limited amount of space and the moderate number of signals to be monitored, a standard approach with a full VME or Compact PCI crate has not been selected. Instead, small embedded industrial computers with Universal Serial Bus (USB) oscilloscopes chosen for the specific application have been installed. This cost effective, rapidly ...

  3. Analogue Hawking radiation from astrophysical black-hole accretion

    International Nuclear Information System (INIS)

    Das, Tapas K

    2004-01-01

    We show that spherical accretion onto astrophysical black holes can be considered as a natural example of an analogue system. We provide, for the first time, an exact analytical scheme for calculating the analogue Hawking temperature and surface gravity for general relativistic accretion onto astrophysical black holes. Our calculation may bridge the gap between the theory of transonic astrophysical accretion and the theory of analogue Hawking radiation. We show that the domination of the analogue Hawking temperature over the actual Hawking temperature may be a real astrophysical phenomenon, though observational tests of this fact will at best be difficult and at worst might prove to be impossible. We also discuss the possibilities of the emergence of analogue white holes around astrophysical black holes. Our calculation is general enough to accommodate accreting black holes with any mass

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

    CERN Multimedia

    CERN. Geneva

    2002-01-01

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

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

    Science.gov (United States)

    Segal, Meirav; Fischer, Bilha

    2012-02-28

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

  6. The Greenland Analogue Project. Yearly Report 2009

    International Nuclear Information System (INIS)

    2010-12-01

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

  7. The Greenland Analogue Project. Yearly Report 2009

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

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

  8. UK Natural Analogue Coordinating Group: fourth annual report

    International Nuclear Information System (INIS)

    Read, D.; Hooker, P.J.

    1992-01-01

    HMIP has a research programme investigating some naturally radioactive sites as geochemical analogues of radionuclide migration. All of the analogue sites under investigation, both in the U.K. and overseas, are located where elevated uranium concentrations occur naturally. Coordination of the programme is achieved through the UK Natural Analogue Co-ordinating Group (NACG) which has met three times in this reporting period. The NACG is steered by the British Geological Survey. Its purpose is to ensure that the different research projects have an integrated function aimed at increasing our understanding of natural geochemical processes. Effort is also being expended in testing research models which may be used in such assessments. (author)

  9. A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

    Directory of Open Access Journals (Sweden)

    Arno Verlee

    2017-02-01

    Full Text Available For the synthesis of m-sulfamoylbenzamide analogues, small molecules which are known for their bioactivity, a chemoselective procedure has been developed starting from m-(chlorosulfonylbenzoyl chloride. Although a chemoselective process in batch was already reported, a continuous-flow process reveals an increased selectivity at higher temperatures and without catalysts. In total, 15 analogues were synthesized, using similar conditions, with yields ranging between 65 and 99%. This is the first automated and chemoselective synthesis of m-sulfamoylbenzamide analogues.

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

    CERN Document Server

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

    2009-01-01

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

  11. Long-term predictions using natural analogues

    International Nuclear Information System (INIS)

    Ewing, R.C.

    1995-01-01

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

  12. Analogues of both Leu- and Met-enkephalin containing a constrained dipeptide isostere prepared from a Baylis-Hillman adduct.

    Science.gov (United States)

    Galeazzi, Roberta; Martelli, Gianluca; Marcucci, Eleonora; Orena, Mario; Rinaldi, Samuele; Lattanzi, Roberta; Negri, Lucia

    2010-04-01

    An efficient route was developed for the synthesis of the Fmoc-protected dipeptide 4, isostere of Gly-Gly containing an alpha-methylene beta-amino acid; the conformationally restricted analogues of Leu-enkephalin, 3a, and Met-enkephalin, 3b, respectively, were prepared by changing 4 for Gly(2)-Gly(3) in the native compounds 3a and 3b whose biological activities were significantly lower than the parent compounds.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  14. Heterocyclic Analogues of Modafinil as Novel, Atypical Dopamine Transporter Inhibitors.

    Science.gov (United States)

    Kalaba, Predrag; Aher, Nilima Y; Ilić, Marija; Dragačević, Vladimir; Wieder, Marcus; Miklosi, Andras G; Zehl, Martin; Wackerlig, Judith; Roller, Alexander; Beryozkina, Tetyana; Radoman, Bojana; Saroja, Sivaprakasam R; Lindner, Wolfgang; Gonzalez, Eduardo Perez; Bakulev, Vasiliy; Leban, Johann Jakob; Sitte, Harald H; Urban, Ernst; Langer, Thierry; Lubec, Gert

    2017-11-22

    Modafinil is a wake promoting compound with high potential for cognitive enhancement. It is targeting the dopamine transporter (DAT) with moderate selectivity, thereby leading to reuptake inhibition and increased dopamine levels in the synaptic cleft. A series of modafinil analogues have been reported so far, but more target-specific analogues remain to be discovered. It was the aim of this study to synthesize and characterize such analogues and, indeed, a series of compounds were showing higher activities on the DAT and a higher selectivity toward DAT versus serotonin and norepinephrine transporters than modafinil. This was achieved by substituting the amide moiety by five- and six-membered aromatic heterocycles. In vitro studies indicated binding to the cocaine pocket on DAT, although molecular dynamics revealed binding different from that of cocaine. Moreover, no release of dopamine was observed, ruling out amphetamine-like effects. The absence of neurotoxicity of a representative analogue may encourage further preclinical studies of the above-mentioned compounds.

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

    Science.gov (United States)

    Rothmeier, Rosemarie C.; Dixon, David N.

    1980-01-01

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

  16. Synthesis and antifungal activity of two novel spermidine analogues.

    Science.gov (United States)

    Mackintosh, C A; Slater, L A; McClintock, C A; Walters, D R; Havis, N D; Robins, D J

    1997-03-01

    Two spermidine analogues were synthesised and examined for antifungal activity. Both compounds used as 1 mM post-inoculation sprays reduced infection of barley seedlings by the powdery mildew fungus, Erysiphe graminis f.sp. hordei, infection of broad bean seedlings by the rust fungus, Uromyces viciae-fabae, and infection of apple seedlings by the powdery mildew fungus, Podosphaera leucotricha. Since these fungal pathogens cannot be cultured axenically, the effects of the two spermidine analogues on mycelial growth in vitro, as well as preliminary investigations on polyamine biosynthesis, were undertaken using the oat stripe pathogen, Pyrenophora avenae. Although neither compound affected radial growth of the fungus on plates, both analogues reduced fungal biomass in liquid culture substantially. The two spermidine analogues, used at a concentration of 1 mM, had no significant effect on the conversion of labelled ornithine into polyamines in P. avenae.

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

    Directory of Open Access Journals (Sweden)

    Youxi Zhang

    2014-04-01

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

  18. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

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

    2016-01-01

    women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we...... included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate...... was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference...

  19. Analogue Signal Processing: Collected Papers 1996-97

    DEFF Research Database (Denmark)

    1997-01-01

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

  20. 3-alkyl fentanyl analogues: Structure-activity-relationship study

    OpenAIRE

    Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

    2012-01-01

    Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

  1. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

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

  2. The Greenland Analogue Project, Yearly Report 2009

    International Nuclear Information System (INIS)

    2011-08-01

    To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a realistic understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. The project includes three sub-projects (A-C) with specific individual objectives, which collectively aim at contributing knowledge and input to the overall project aim. Three field campaigns were carried out in SPA during 2009. These campaigns focused on: (1) deployment and maintenance of AWS and GPS stations and to test the deep-look radar equipment; (2) investigating the hydrological processes and feedbacks and testing of passive seismic equipment; (3) downloading of weather station data and GPS data and winterizing the equipment. An extensive archive of real-time satellite remote sensing datasets has been obtained to be able to better constraint the surface elevation and dynamics of basal hydrological mechanisms. From this archive it has been possible to obtain Russell Glacier Cachment (RGC)-wide constraints on annual, seasonal and specific temporal snapshots of surface speed, initial lake and moulin distribution, drainage and network connections along with the temporal

  3. Antioxidant activity and protective role on protein glycation of synthetic aminocoumarins

    Directory of Open Access Journals (Sweden)

    Akram Aminjafari

    2016-11-01

    Conclusions: By the analogues, in vitro ascertained AO and AG properties of 4-ACD may be recognized as rationale for their protective role against oxidative changes of proteins, thereby precluding diabetic complications in humans.

  4. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    Science.gov (United States)

    Foing, Bernard

    2014-05-01

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

  5. Application of natural analogues in the Yucca Mountain project - overview

    International Nuclear Information System (INIS)

    Simmons, Ardyth M.

    2003-01-01

    The Natural Analogue Synthesis Report (NASR) [1] provides a compilation of information from analogues that test, corroborate, and add confidence to process models and model predictions pertinent to total system performance assessment (TSPA). The report updated previous work [2] with new literature examples and results of quantitative studies conducted by the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate greater understanding of processes expected to occur during postclosure of a proposed Yucca Mountain repository. Natural analogues, as used here, refer to either natural or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have occurred over long time periods (decades to millenia) and large spatial scales (up to tens of kilometers). In the past, the YMP has used analogues for testing and building confidence in conceptual and numerical process models in a number of ways. Yucca Mountain mineral alteration phases provided a self-analogue for postclosure alteration [3]. Thermodynamic parameters for silica minerals of the Wairakai, New Zealand geothermal field were added to databases used in geochemical modeling [4]. Scoping calculations of radionuclide transport using the Yucca Mountain TSPA numerical model were conducted for the Peqa Blanca site [5]. Eruption parameters from the Cerro Negro volcano, Nicaragua, were used to verify codes that model ash plume dispersion [6]. Analogues have also been used in supplemental science and performance analyses to provide multiple lines of evidence in support of both analyses and model reports (AMRs) [7]; in screening arguments for inclusion or exclusion of features, events, and processes (FEP)s in TSPAs; in the quantification of uncertainties [7]; in expert elicitations of volcanic and seismic hazards [8, 9] and in peer reviews [10]. Natural analogues may be applied

  6. Characterisation of insulin analogues therapeutically available to patients

    KAUST Repository

    Adams, Gary G.

    2018-03-29

    The structure and function of clinical dosage insulin and its analogues were assessed. This included \\'native insulins\\' (human recombinant, bovine, porcine), \\'fast-acting analogues\\' (aspart, glulisine, lispro) and \\'slow-acting analogues\\' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

  7. Mechanism of inhibition of Shiga-toxigenicEscherichia coliSubAB cytotoxicity by steroids and diacylglycerol analogues.

    Science.gov (United States)

    Yahiro, Kinnosuke; Nagasawa, Sayaka; Ichimura, Kimitoshi; Takeuchi, Hiroki; Ogura, Kohei; Tsutsuki, Hiroyasu; Shimizu, Takeshi; Iyoda, Sunao; Ohnishi, Makoto; Iwase, Hirotaro; Moss, Joel; Noda, Masatoshi

    2018-12-01

    Shiga toxigenic Escherichia coli (STEC) are responsible for a worldwide foodborne disease, which is characterized by severe bloody diarrhea and hemolytic uremic syndrome (HUS). Subtilase cytotoxin (SubAB) is a novel AB 5 toxin, which is produced by Locus for Enterocyte Effacement (LEE)-negative STEC. Cleavage of the BiP protein by SubAB induces endoplasmic reticulum (ER) stress, followed by induction of cytotoxicity in vitro or lethal severe hemorrhagic inflammation in mice. Here we found that steroids and diacylglycerol (DAG) analogues (e.g., bryostatin 1, Ingenol-3-angelate) inhibited SubAB cytotoxicity. In addition, steroid-induced Bcl-xL expression was a key step in the inhibition of SubAB cytotoxicity. Bcl-xL knockdown increased SubAB-induced apoptosis in steroid-treated HeLa cells, whereas SubAB-induced cytotoxicity was suppressed in Bcl-xL overexpressing cells. In contrast, DAG analogues suppressed SubAB activity independent of Bcl-xL expression at early time points. Addition of Shiga toxin 2 (Stx2) with SubAB to cells enhanced cytotoxicity even in the presence of steroids. In contrast, DAG analogues suppressed cytotoxicity seen in the presence of both toxins. Here, we show the mechanism by which steroids and DAG analogues protect cells against SubAB toxin produced by LEE-negative STEC.

  8. A Modular Synthetic Approach to Isosteric Sulfonic Acid Analogues of the Anticoagulant Pentasaccharide Idraparinux

    Directory of Open Access Journals (Sweden)

    Erika Mező

    2016-11-01

    Full Text Available Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we elaborated a modular pathway to obtain a series of idraparinux-analogue pentasaccharides bearing one or two primary sulfonic acid moieties. Five protected pentasaccharides with different C-sulfonation patterns were prepared by two subsequent glycosylation reactions, respectively, using two monosaccharide and four disaccharide building blocks. Transformation of the protected derivatives into the fully O-sulfated, O-methylated sulfonic acid end-products was also studied.

  9. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Science.gov (United States)

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

    2016-05-01

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

  10. Insulin analogues and cancer: a note of caution

    Directory of Open Access Journals (Sweden)

    Joseph A.M.J.L. eJanssen

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    SERGIY KOZERENKO

    2016-04-01

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

  12. Theoretical study on absorption and emission spectra of adenine analogues.

    Science.gov (United States)

    Liu, Hongxia; Song, Qixia; Yang, Yan; Li, Yan; Wang, Haijun

    2014-04-01

    Fluorescent nucleoside analogues have attracted much attention in studying the structure and dynamics of nucleic acids in recent years. In the present work, we use theoretical calculations to investigate the structural and optical properties of four adenine analogues (termed as A1, A2, A3, and A4), and also consider the effects of aqueous solution and base pairing. The results show that the fluorescent adenine analogues can pair with thymine to form stable H-bonded WC base pairs. The excited geometries of both adenine analogues and WC base pairs are similar to the ground geometries. The absorption and emission maxima of adenine analogues are greatly red shifted compared with nature adenine, the oscillator strengths of A1 and A2 are stronger than A3 and A4 in both absorption and emission spectra. The calculated low-energy peaks in the absorption spectra are in good agreement with the experimental data. In general, the aqueous solution and base pairing can slightly red-shift both the absorption and emission maxima, and can increase the oscillator strengths of absorption spectra, but significantly decrease the oscillator strengths of A3 in emission spectra.

  13. A preliminary feasibility study on natural analogue in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chun Soo; Bae, Dae Seok; Kim, Kyung Su; Koh, Yong Kwon; Park, Byung Yun

    2000-03-01

    Preliminary study on the assessment of natural analogue study in Korea for the deep geological disposal of high-level radioactive waste was carried out. The project on natural analogue study in other countries are introduced. The uranium-bearing deposit in Okcheon belt are summarized, which reported to be uranium-bearing minerals in order to assess to feasibility for natural analogue study in Korea. Among the uranium-bearing deposits, the Deokpyeong area, reported to be the highest reservoir and grade, are selected as the study site, and the elementary investigation, including survey of radioactivity and geochemistry are carried out. According to the investigation of surface environment, the radioactivity and uranium content in the surface water and shallow groundwater does not show any anormal values. However, the radioactivity is expected to be increased in depth and the groundwater reacted with uranium-bearing graphite formation shows high unanium content, indicating the potential possibility for natural analogue study in Korea. In future, if more detail study are performed, the assessment of natural analogue study in Korea are expected.

  14. Radiation protection

    International Nuclear Information System (INIS)

    Koelzer, W.

    1975-01-01

    Physical and radiological terms, quantities, and units. Basic principles of radiation protection (ICRP, IAEA, EURATOM, FRG). Biological effects of ionizing radiation. Objectives of practical radiation protection. (HP) [de

  15. Semisynthetic macrolide antibacterials derived from tylosin. Synthesis and structure-activity relationships of novel desmycosin analogues.

    Science.gov (United States)

    Mutak, Stjepan; Marsić, Natasa; Kramarić, Miroslava Dominis; Pavlović, Drazen

    2004-01-15

    A series of 20-O-substituted and 3,20-di-O-substituted derivatives of desmycosin were synthesized and their biological properties were evaluated. In particular, we have synthesized numerous side chain modified analogues of desmycosin as well as some analogues possessing a combination of modified side chain and alternative C-3 substituents. Thus, alpha,beta-unsaturated analogues of desmycosin (2), tylosin (1), 10,11,12,13-tetrahydrotylosin (11), and 2,3-didehydrodesmycosin (13) were prepared from the corresponding aldehydes by a Wittig reaction with the stabilized ylides (a-d), generating a trans-double bond, followed by modified Pfitzner-Moffat oxidation of the C-3 hydroxyl group. To evaluate the importance of the C-3 position of desmycosin for biological activity, the C-3 substituted derivatives were synthesized by a standard sequence of protective group chemistry followed by Wittig reaction and esterification as the key steps. For the attachment of the C-3 ester functionality, a mixed anhydride protocol was adopted. Reaction proceeded smoothly to give corresponding esters in yields ranging from 70 to 80%. Base- and acid-catalyzed rearrangement products including desmycosin 8,20-aldols (24a and 24b) and desmycosin 3,19-aldol (25) are also described. Parallel array synthesis and purification techniques allowed for the rapid exploration of structure-activity relationships within this class and for the improvement in potency. In vitro evaluation of these derivatives demonstrated good antimicrobial activity against Gram-positive bacteria for most of the compounds. The present derivatives of 16-membered macrolides were active against MLS(B)-resistant strains that were inducibly resistant, but not those constitutively resistant to erythromycin.

  16. α-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice.

    Directory of Open Access Journals (Sweden)

    Petteri Rinne

    Full Text Available Melanocyte-stimulating hormones, α-, β- and γ-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that α-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of α-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable α-MSH analogue [Nle(4, D-Phe(7]-α-MSH (NDP-α-MSH and investigated whether it has protective effects in deoxycorticosterone acetate (DOCA-salt hypertensive mice. Adult male C57Bl/6N mice were subjected to DOCA-salt treatment and randomized to receive intraperitoneal injections of either saline as vehicle or NDP-α-MSH (0.3 mg/kg/day for 14 days starting 7 days after the DOCA-salt treatment. Systemic hemodynamics, serum and urine electrolytes, and oxidative stress markers were assessed in control sham-operated and DOCA-salt mice. NDP-α-MSH elicited marked diuretic and natriuretic responses that were reversible with the MC3/4 receptor antagonist SHU9119. Chronic NDP-α-MSH treatment attenuated blood pressure elevation in DOCA-salt mice without affecting the blood pressure of normotensive control animals. Owing to the enhanced sodium excretion, NDP-α-MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt treatment mildly increased oxidative stress at the tissue level, but NDP-α-MSH had no significant effects on the oxidative stress markers. In conclusion, treatment with NDP-α-MSH increases urinary sodium excretion and protects against DOCA-salt-induced hypertension. These findings point to the potential future use of α-MSH analogues in the treatment of hypertension.

  17. Concise synthesis of new bridged-nicotine analogues

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  18. Desert spring mounds: a potential analogue to Martian arid environments?

    Science.gov (United States)

    Franchi, F.; Frisia, S.

    2017-09-01

    Spring carbonates have been often considered as putative analogues of Martian arid environments. On Earth these are believed to form by the interaction of highly saline water and microbial communities, which favor the formation of authigenic micrite. Here we present new data from spring mounds in the western Makgadikgadi Pan (Botswana) and the Great Artesian Basin (South Australia). In both areas, upwelling of ground water give rise to mounds and layered deposits which are close morphological analogues of landforms documented on Mars. The authigenic carbonates and evaporites associated with the spring mounds retain evidence of microbial microfabric founded elsewhere, pointing to the potential existence of similar microbial in the extreme Martian conditions.

  19. Medical applications of analogue and digital telephone data links.

    Science.gov (United States)

    Hill, D W; Mable, S E; Payne, J P

    1976-07-20

    The increasing use of digital computer techniques for the analysis of signals such as the EEG, ECG, plethysmograms and cardiac output curves has led to the use of multichannel analogue frequency modulation telephone data links in the forward direction from the patient to the computer and digital links in the return direction. Single-channel analogue links are also being used for the surveillance of cardiac pacemaker patients and the television Viewphone offers the possibility of a visual contact between two centers. Examples will be given of the use of these various forms of telephone link.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-01-01

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

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

    CERN Document Server

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

    2009-01-01

    A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The implementation of the signal generator is presented as well as an application where it was successfully utilized.

  3. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    OpenAIRE

    Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

    2016-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

  4. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril

    Science.gov (United States)

    Akif, Mohd; Masuyer, Geoffrey; Schwager, Sylva L U; Bhuyan, Bhaskar J; Mugesh, Govindasamy; Isaac, R Elwyn; Sturrock, Edward D; Acharya, K Ravi

    2011-01-01

    Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin–angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356–1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 Å resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein–selenolate interaction. These new structures of tACE–SeCap and AnCE–SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity. Database Structural data for the two SeCap complexes with ACE and AnCE have been deposited with the RCSB Protein Data Bank under the codes 2YDM and 3ZQZ, respectively. PMID:21810173

  5. Detection of macromolecules in desert cyanobacteria mixed with a lunar mineral analogue after space simulations.

    Science.gov (United States)

    Baqué, Mickael; Verseux, Cyprien; Rabbow, Elke; de Vera, Jean-Pierre Paul; Billi, Daniela

    2014-09-01

    In the context of future exposure missions in Low Earth Orbit and possibly on the Moon, two desert strains of the cyanobacterium Chroococcidiopsis, strains CCMEE 029 and 057, mixed or not with a lunar mineral analogue, were exposed to fractionated fluencies of UVC and polychromatic UV (200-400 nm) and to space vacuum. These experiments were carried out within the framework of the BIOMEX (BIOlogy and Mars EXperiment) project, which aims at broadening our knowledge of mineral-microorganism interaction and the stability/degradation of their macromolecules when exposed to space and simulated Martian conditions. The presence of mineral analogues provided a protective effect, preserving survivability and integrity of DNA and photosynthetic pigments, as revealed by testing colony-forming abilities, performing PCR-based assays and using confocal laser scanning microscopy. In particular, DNA and pigments were still detectable after 500 kJ/m(2) of polychromatic UV and space vacuum (10(-4) Pa), corresponding to conditions expected during one-year exposure in Low Earth Orbit on board the EXPOSE-R2 platform in the presence of 0.1 % Neutral Density (ND) filter. After exposure to high UV fluencies (800 MJ/m(2)) in the presence of minerals, however, altered fluorescence emission spectrum of the photosynthetic pigments were detected, whereas DNA was still amplified by PCR. The present paper considers the implications of such findings for the detection of biosignatures in extraterrestrial conditions and for putative future lunar missions.

  6. Physical protection

    International Nuclear Information System (INIS)

    Myers, D.A.

    1989-01-01

    Physical protection is defined and its function in relation to other functions of a State System of Accounting for and Control of Nuclear Materials is described. The need for a uniform minimum international standard for physical protection as well as the need for international cooperation in physical protection is emphasized. The IAEA's INFCIRC/225/Rev. 1 (Annex 1) is reviewed. The Convention on the Physical Protection of Nuclear Material (Annex 2) is discussed. Photographs show examples of typical physical protection technology (Annex 3)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

  8. Are structural analogues to bisphenol A a safe alternative?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Gitte Alsing

    2013-01-01

    of which are found in foods and have been measured in humans. Due to the structural analogy there is an inherent risk that these compounds may lead to similar effects as BPA. The aim of this study was to characterize the toxicological profile of BPA and the five analogues using in vitro assays assessing...

  9. A new analogue of fatty alcohol from Tamarix hampeana L.

    Science.gov (United States)

    Aykac, Ahmet; Akgül, Yurdanur

    2010-01-01

    New analogues of a long-chain secondary alcohol (1) and laserine (2) were isolated from the flowers of Tamarix hampeana L. The isolated compounds were identified using 1D and 2D NMR, LCMS/APCI, and chemical methods. Laserine was isolated for the first time from T. hampeana L.

  10. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

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

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

  11. Influence of Bakuchiol, a JH analogue from Bemchi ( Psoralea ...

    African Journals Online (AJOL)

    The influence of a juvenile hormone analogue (JHA), bakuchiol on the silk yield of silkworm, Bombyx mori L. was studied involving two popular commercial hybrids, KA x NB4D2 (bivoltine x bivoltine) and PM x NB4D2 (multivoltine x bivoltine). The compound was administered topically to 5th instars at 24, 48, 72 and 96 h as ...

  12. Difference in brain activations during appreciating paintings and photographic analogues

    Directory of Open Access Journals (Sweden)

    Yoshinori eMizokami

    2014-07-01

    Full Text Available Several studies have investigated neural correlates of aesthetic appreciation for paintings but to date the findings have been heterogeneous. This heterogeneity may be attributed to previous studies’ measurement of aesthetic appreciation of not only the beauty of paintings but also the beauty of motifs of the paintings. In order to better elucidate the beauty of paintings, it seems necessary to compare aesthetic appreciation of paintings and photographic analogues which included corresponding real images. We prepared for famous painters’ pictures and their photographic analogues which were set up to resemble each painting in order to investigate the hypothesis that there exist specific neural correlates associated with the aesthetic appreciation for paintings. Forty-four subjects participated in functional magnetic resonance study which required comparisons of aesthetic appreciation of paintings of still life and landscape versus photographic analogues including corresponding real images of still life and landscape. Bilateral cuneus and the left lingual gyrus were activated in the comparison of aesthetic appreciation of paintings versus photographic analogues. In conclusion, the present findings suggest a possibility of the existence of specific neural correlates associated with the aesthetic appreciation for paintings and that bilateral cuneus and the left lingual gyrus may be involved.

  13. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    Directory of Open Access Journals (Sweden)

    Maarten Walmagh

    2015-06-01

    Full Text Available Trehalose (α-d-glucopyranosyl α-d-glucopyranoside is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals, medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside, offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis.

  14. An Analysis of an Autoclitic Analogue in Pigeons

    Science.gov (United States)

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

    2014-01-01

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

  15. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    Science.gov (United States)

    Walmagh, Maarten; Zhao, Renfei; Desmet, Tom

    2015-01-01

    Trehalose (α-d-glucopyranosyl α-d-glucopyranoside) is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals), medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside) or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside), offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis. PMID:26084050

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

    DEFF Research Database (Denmark)

    Villadsen, Jesper; Kitir, Betül; Wich, Kathrine

    2014-01-01

    + - coordinating moiety. Herein, we describe the synthesis of an azumamide analogue lacking its native Zn 2+ -binding group and evaluation of its inhibitory activity against recombinant human HDAC1 – 11. Furthermore, kinetic investigation of the inhibitory mechanism of both parent natural product and synthetic...

  17. Evaluation of the antibacterial spectrum of drosocin analogues

    NARCIS (Netherlands)

    Bikker, F.J.; Kaman-van Zanten, W.E.; Vries-van de Ruit, A.M.B.C. de; Voskamp-Visser, I.; Hooft, P.A.V. van; Mars-Groenendijk, R.H.; Visser, P.C. de; Noort, D.

    2006-01-01

    Drosocin is a 19-mer, cationic antimicrobial peptide from Drosophila melanogaster. The aim of the study was to examine the antibacterial spectrum of unglycosylated drosocin analogues. Furthermore, the amino acid sequence of DnaK, drosocin's intracellular target, from susceptible species was aligned

  18. Scattering matrices and expansion coefficients of martian analogue palagonite particles

    NARCIS (Netherlands)

    Laan, E.C.; Volten, H.; Stam, D.M.; Muñoz, O.; Hovenier, J.W.; Roush, T.L.

    2009-01-01

    We present measurements of ratios of elements of the scattering matrix of martian analogue palagonite particles for scattering angles ranging from 3° to 174° and a wavelength of 632.8 nm. To facilitate the use of these measurements in radiative transfer calculations we have devised a method that

  19. Reasoning by analogy: rational foundation of natural analogue studies

    International Nuclear Information System (INIS)

    Petit, J.-C.

    1992-01-01

    Long-term extrapolations concerning the safety of a nuclear waste repository cannot be satisfactorily made on the sole basis of short-term laboratory investigations. Most nuclear countries have hence developed an approach relying on the following research directions: 1. laboratory experiments; 2. in situ testing; 3. modeling; and 4. natural analogues, which are the only means by which very slow mechanisms can be identified and by which long-term predictions of models can be tested for pertinence (if not truly validated). Although the field of natural analogues has grown very rapidly in recent years, receiving support from varied specialists and institutions involved in radioactive waste disposal, there is not yet a full consensus on their actual usefulness. More problematic is the criticism sometimes made that analogical reasoning is not ''true science'' and that information retrieved from the study of natural analogues will always remain questionable. The present paper gives some clues about the exact status of reasoning by analogy, compared to more ''scientific'' ways of deriving information from investigated systems. It is not a thorough discussion of this very complex, and by far too philosophical issue but we hope, at least, to present to readers of papers devoted to natural analogue studies arguments showing that this approach has some sound foundation. (author)

  20. Using natural analogue studies in the secondary science curriculum

    International Nuclear Information System (INIS)

    Ebert, E.K.

    1995-01-01

    This paper discusses an atomic theory unit of a high school chemistry course taught in Nevada. The unit is based on the application of natural analogues to nuclear waste issues. The paper focuses on the students' reactions to the subject material

  1. A Short Review on Cardiotonic Steroids and Their Aminoguanidine Analogues

    Directory of Open Access Journals (Sweden)

    Arturo San Feliciano

    2000-01-01

    Full Text Available A short review on cardiotonic steroids and their analogues is presented. The natural, semisynthetic and synthetic derivatives, as well as their mechanism of action and structure-activity relationships are shown, with a special reference to aminoguanidine derivatives.

  2. Design and synthesis of epicocconone analogues with improved fluorescence properties.

    Science.gov (United States)

    Peixoto, Philippe A; Boulangé, Agathe; Ball, Malcolm; Naudin, Bertrand; Alle, Thibault; Cosette, Pascal; Karuso, Peter; Franck, Xavier

    2014-10-29

    Epicocconone is a natural latent fluorophore that is widely used in biotechnology because of its large Stokes shift and lack of fluorescence in its unconjugated state. However, the low photostability and quantum yields of epicocconone have limited its wider use, and in the absence of a total synthesis, this limitation has been a long-standing problem. Here we report a general strategy for the synthesis of epicocconone analogues that relies on a 2-iodoxybenzoic acid-mediated dearomatization and on the replacement of the triene tail of the natural product by an aromatic ring. This design element is general and the synthesis is straightforward, providing ready access to libraries of polyfunctional fluorophores with long Stokes shifts based on the epicocconone core. Our structural modifications resulted in analogues with increased photostability and quantum yields compared with the natural product. Staining proteomic gels with these new analogues showed significant lowering of the detection limit and a 30% increase in the number of low-abundance proteins detected. These epiccoconone analogues will substantially improve the discovery rate of biomarker needles in the proteomic haystack.

  3. Evaluative comparison of palm wine analogue and oil palm wine ...

    African Journals Online (AJOL)

    0.05 and P=0.01) in colour, odour, effervescence and general acceptability between palm wine analogue and oil palm wine. While there also was no significant difference in the tastes and balance of sweetness at P=0.01, a slight difference ...

  4. Vitamin E analogues and immune response in cancer treatment

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Neužil, Jiří

    2007-01-01

    Roč. 76, - (2007), s. 463-491 ISSN 0083-6729 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : vitamin E analogues * inducers of apoptosis * immune surveillance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.889, year: 2007

  5. Analogue Building Blocks Based on Digital CMOS Gates

    DEFF Research Database (Denmark)

    Mucha, Igor

    1996-01-01

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

  6. Brassinosteroids: Synthesis and activity of some fluoro analogues

    Czech Academy of Sciences Publication Activity Database

    Slavíková, Barbora; Kohout, Ladislav; Buděšínský, Miloš; Swaczynová, Jana; Kasal, Alexander

    2008-01-01

    Roč. 51, č. 13 (2008), s. 3979-3984 ISSN 0022-2623 R&D Projects: GA AV ČR IAA400550609 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50380511 Keywords : brassinosteroids * fluor o analogues Subject RIV: CC - Organic Chemistry Impact factor: 4.898, year: 2008

  7. Bosonic Analogue of Dirac Composite Fermi Liquid

    Science.gov (United States)

    Mross, David; Alicea, Jason; Motrunich, Olexei

    The status of particle-hole symmetry has long posed a challenge to the theory of the quantum Hall effect. It is expected to be present in the half-filled Landau level, but is absent in the conventional field theory, i.e., the composite Fermi liquid. Recently, Son proposed an alternative, explicitly particle-hole symmetric theory which features composite fermions that exhibit a Dirac dispersion. In my talk, I will introduce an analogous particle-hole-symmetric metallic state of bosons at odd-integer filling. This state hosts composite fermions whose energy dispersion features a quadratic band touching and corresponding 2 Ï Berry flux, protected by particle-hole and discrete rotation symmetries. As in the Dirac composite Fermi liquid introduced by Son, breaking particle-hole symmetry recovers the familiar Chern-Simons theory. I will discuss realizations of this phase both in 2D and on bosonic topological insulator surfaces, as well as its signatures in experiments and simulations.

  8. Comparison of overlay metrology with analogue and digital cameras

    Science.gov (United States)

    Rigden, Timothy C.; Soroka, Andrew J.; Binns, Lewis A.

    2005-05-01

    Overlay metrology is a very demanding image processing application; current applications are achieving dynamic precision of one hundredth of a pixel or better. As such it requires an accurate image acquisition system, with minimal distortions. Distortions can be physical (e.g. pixel size / shape) or electronic (e.g. clock skew) in nature. They can also affect the image shape, or the gray level intensity of individual pixels, the former causing severe problems to pattern recognition and measurement algorithms, the latter having an adverse effect primarily on the measurement itself. This paper considers the artifacts that are present in a particular analogue camera, with a discussion on how these artifacts translate into a reduction of overlay metrology performance, in particular their effect on precision and tool induced shift (TIS). The observed effects include, but are not limited to, banding and interlacing. This camera is then compared to two digital cameras. The first of these operates at the same frame rate as the analogue camera, and is found to have fewer distortions than the analogue camera. The second camera operates with a frame rate twice that of the other two. It is observed that this camera does not exhibit the distortions of the analogue camera, but instead has some very specific problems, particularly with regards to noise. The quantitative data on the effect on precision and TIS under a wide variety of conditions, is presented. These show that while it is possible to achieve metrology-capable images using an analogue camera, it is preferable to use a digital camera, both from the perspective of overall system performance, and overall system complexity.

  9. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    Science.gov (United States)

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

  10. Analogue model studies of induction effects at auroral latitudes

    Directory of Open Access Journals (Sweden)

    A. Viljanen

    1995-11-01

    Full Text Available In addition to field observations and numerical models, geomagnetic induction effects can be studied by scaled analogue model experiments. We present here results of analogue model studies of the auroral electrojet with an Earth model simulating the Arctic Ocean and inland conductivity structures in northern Fennoscandia. The main elements of the analogue model used were salt water simulating the host rock, an aluminium plate corresponding to the ocean and graphite pieces producing the inland highly conducting anomalies. The electrojet was a time-harmonic line current flowing at a (simulated height of 100 km above northern Fennoscandia. The period simulated was 9 min. The analogue model results confirmed the well-known rapid increase of the vertical field when the coast is approached from the continent. The increase of the horizontal field due to induced ocean currents was demonstrated above the ocean, as well as the essentially negligible effect of these currents on the horizontal field on the continent. The behaviour of the magnetic field is explained with a simple two-dimensional thin-sheet model. The range, or the adjustment distance, of the ocean effect inland was found to be some hundreds of kilometers, which also agrees with earlier results of the Siebert-Kertz separation of IMAGE magnetometer data. The modelled inland anomalies evidently had too large conductivities, but on the other hand, their influence decayed on scales of only some tens of kilometers. Analogue model results, thin-sheet calculations, and field observations show that the induction effect on the horizontal magnetic field Bx near the electrojet is negligible. On the other hand, the vertical component Bz is clearly affected by induced currents in the ocean. Evidence of this is the shift of the zero point of Bz 0-1° southwards from the maximum of Bx. The importance of these results are discussed, emphasizing the determination of ionospheric currents.

  11. Insecticidal action of synthetic girgensohnine analogues and essential oils on Rhodnius prolixus (Hemiptera: Reduviidae

    Directory of Open Access Journals (Sweden)

    Juliana Cuadros

    2017-03-01

    Conclusion: Synthetic girgensohnine analogues, and C. flexuosus and C. sinensis essential oils showed insecticidal activity in R. prolixus. Analogue 3 showed the greatest insecticidal activity among all molecules and oils evaluated under our laboratory conditions.

  12. The impact of watching educational video clips on analogue patients' physiological arousal and information recall

    NARCIS (Netherlands)

    Bruinessen, I.R. van; Ende, I.T. van den; Visser, L.N.; Dulmen, S. van

    2016-01-01

    OBJECTIVE: Investigating the influence of watching three educational patient-provider interactions on analogue patients' emotional arousal and information recall. METHODS: In 75 analogue patients the emotional arousal was measured with physiological responses (electrodermal activity and heart rate)

  13. The impact of watching educational video clips on analogue patients' physiological arousal and information recall

    NARCIS (Netherlands)

    van Bruinessen, I. R.; van den Ende, I. T. A.; Visser, L. N. C.; van Dulmen, S.

    2016-01-01

    Investigating the influence of watching three educational patient-provider interactions on analogue patients' emotional arousal and information recall. In 75 analogue patients the emotional arousal was measured with physiological responses (electrodermal activity and heart rate) and self-reported

  14. Altering the communication networks of multispecies microbial systems using a diverse toolbox of AI-2 analogues.

    Science.gov (United States)

    Gamby, Sonja; Roy, Varnika; Guo, Min; Smith, Jacqueline A I; Wang, Jingxin; Stewart, Jessica E; Wang, Xiao; Bentley, William E; Sintim, Herman O

    2012-06-15

    There have been intensive efforts to find small molecule antagonists for bacterial quorum sensing (QS) mediated by the "universal" QS autoinducer, AI-2. Previous work has shown that linear and branched acyl analogues of AI-2 can selectively modulate AI-2 signaling in bacteria. Additionally, LsrK-dependent phosphorylated analogues have been implicated as the active inhibitory form against AI-2 signaling. We used these observations to synthesize an expanded and diverse array of AI-2 analogues, which included aromatic as well as cyclic C-1-alkyl analogues. Species-specific analogues that disrupted AI-2 signaling in Escherichia coli and Salmonella typhimurium were identified. Similarly, analogues that disrupted QS behaviors in Pseudomonas aeruginosa were found. Moreover, we observed a strong correlation between LsrK-dependent phosphorylation of these acyl analogues and their ability to suppress QS. Significantly, we demonstrate that these analogues can selectively antagonize QS in single bacterial strains in a physiologically relevant polymicrobial culture.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  16. The impact of watching educational video clips on analogue patients' physiological arousal and information recall.

    NARCIS (Netherlands)

    Bruinessen, I.R. van; Ende, I.T.A. van den; Visser, I.N.C.; Dulmen, S. van

    2016-01-01

    Objective: Investigating the influence of watching three educational patient–provider interactions on analogue patients’ emotional arousal and information recall. Methods: In 75 analogue patients the emotional arousal was measured with physiological responses (electrodermal activity and heart rate)

  17. Advancing Translational Space Research Through Biospecimen Sharing: Amplified Impact of Studies Utilizing Analogue Space Platforms

    Science.gov (United States)

    Staten, B.; Moyer, E.; Vizir, V.; Gompf, H.; Hoban-Higgins, T.; Lewis, L.; Ronca, A.; Fuller, C. A.

    2016-01-01

    Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hindlimb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth.

  18. The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs.

    Science.gov (United States)

    Jia, Yue; Ohanyan, Aikoui; Lue, Yan-He; Swerdloff, Ronald S; Liu, Peter Y; Cohen, Pinchas; Wang, Christina

    2015-04-01

    Human (HN) prevents stress-induced apoptosis in many cells/tissues. In this study we showed that HN ameliorated chemotherapy [cyclophosphamide (CP) and Doxorubicin (DOX)]-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or insulin-like growth factor binding protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L12A (a HN antagonist) on CP-induced male germ cell apoptosis in mice. CP-induced germ cell apoptosis was inhibited by HN, HNG, HNG-F6A, HN-S7A, and HN-C8P (less effective); but not by HN-L12A. HN-L12A, but not HN-S7A or HN-C8P, blocked the protective effect of HN against CP-induced male germ cell apoptosis. HN, HN-S7A, and HN-C8P restored CP-suppressed STAT3 phosphorylation. These results suggest that HN: (1) decreases DOX (ex vivo) and CP (in vivo) induced male germ cell apoptosis; (2) action is mediated by the membrane receptor/STAT3 with minor contribution by BAX-binding pathway; (3) self-dimerization or binding to IGFBP-3 may not be involved in HN's effect in testis. HN is an important molecule in the regulation of germ cell homeostasis after injury and agonistic analogues may be developed for treating male infertility or protection against chemotherapy side effects.

  19. Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue

    NARCIS (Netherlands)

    Fiebrich, H. -B.; van den Berg, G.; Kema, I. P.; Links, T. P.; Kleibeuker, J. H.; van Beek, A. P.; Walenkamp, A. M. E.; Sluiter, W. J.; de Vries, E. G. E.

    2010-01-01

    P>Background Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels

  20. On Using Current Steering Logic in Mixed Analogue-digital Circuits

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    The authors investigate power supply noise in mixed analogue-digital circuits, arising from communication between the analogue and digital parts of the circuit. Current steering techniques and proper buffering are used to show which noise currents can be reduced and which cannot. In addition......, a high-swing current steering buffer for driving analogue switches or external digital signals is proposed....

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

    International Nuclear Information System (INIS)

    Skagius, K.; Wingefors, S.

    1992-01-01

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

  2. Negotiating Protection

    DEFF Research Database (Denmark)

    Bille, Mikkel

    strategies are entangled in cultural, religious, and national identities. Using ethnographic methods, I investigate protection against selected risks: harm from evil eyes, violation of domestic sanctity, and cultural heritage dilapidation. Protection against these risks is examined through studies...

  3. [Protective eyeglasses].

    Science.gov (United States)

    Hermans, G

    1997-01-01

    Reminder of the materials used for the manufacture of corrective lenses. Belgian statistics concerning eye accidents at work and European legislation concerning the prevention of eye accidents, personal protective equipment, P.P.E. Eye protection for sports.

  4. Environmental protection

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    In this chapter environmental protection in the Slovak Republic in 1997 are reviewed. The economics of environmental protection, state budget, Slovak state environmental fund, economic instruments, environmental laws, environmental impact assessment, environmental management systems, and environmental education are presented

  5. Melatonin analogue new indole hydrazide/hydrazone derivatives with antioxidant behavior: synthesis and structure-activity relationships.

    Science.gov (United States)

    Gürkök, Gökce; Coban, Tulay; Suzen, Sibel

    2009-04-01

    Melatonin (MLT) is a hormone produced in the brain by the pineal gland, from the amino acid tryptophan. It is also an antioxidant hormone with a particular role in the protection of nuclear and mitochondrial DNA. In recent years, many physiological properties of MLT have been described resulting in much attention in the development of synthetic compounds possessing the indole ring. Sixteen MLT analogue indole hydrazide/hydrazone derivatives were synthesized and in vitro antioxidant activity was investigated. Most of the compounds showed significantly higher activity than MLT at 10(-3) M and 10(-4) M concentrations.

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

    NARCIS (Netherlands)

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

    1994-01-01

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

  7. Protecting knowledge

    DEFF Research Database (Denmark)

    Sofka, Wolfgang; de Faria, Pedro; Shehu, Edlira

    2018-01-01

    Most firms use secrecy to protect their knowledge from potential imitators. However, the theoretical foundations for secrecy have not been well explored. We extend knowledge protection literature and propose theoretical mechanisms explaining how information visibility influences the importance...... of secrecy as a knowledge protection instrument. Building on mechanisms from information economics and signaling theory, we postulate that secrecy is more important for protecting knowledge for firms that have legal requirements to reveal information to shareholders. Furthermore, we argue that this effect...... and a firm's investment in fixed assets. Our findings inform both academics and managers on how firms balance information disclosure requirements with the use of secrecy as a knowledge protection instrument....

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

    Science.gov (United States)

    Horton, Pascal; Obled, Charles; Jaboyedoff, Michel

    2017-07-01

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

  9. Optoelectronic analogue signal transfer for LHC detectors, 1991

    CERN Document Server

    Dowell, John D; Homer, R J; Jovanovic, P; Kenyon, I; Staley, R; Webster, K; Da Via, C; Feyt, J; Nappey, P; Stefanini, G; Dwir, B; Reinhart, F K; Davies, J; Green, N; Stewart, W; Young, T; Hall, G; Akesson, T; Jarlskog, G; Kröll, S; Nickerson, R; Jaroslawski, S; CERN. Geneva. Detector Research and Development Committee

    1991-01-01

    We propose to study and develop opto-electronic analogue front-ends based on electro-optic intensity modulators. These devices translate the detector electrical analogue signals into optical signals which are then transferred via optical fibres to photodetector receivers at the remote readout. In comparison with conventional solutions based on copper cables, this technique offers the advantages of high speed, very low power dissipation and transmission losses, compactness and immunity to electromagnetic interference. The linearity and dynamic range that can be obtained are more than adequate for central tracking detectors, and the proposed devices have considerable radiation- hardness capabilities. The large bandwidth and short transit times offer possibilities for improved triggering schemes. The proposed R&D programme is aimed at producing multi-channel "demonstrator" units for evaluation both in laboratory and beam tests. This will allow the choice of the most effective technology. A detailed study wil...

  10. Ribosome-catalyzed formation of an abnormal peptide analogue

    International Nuclear Information System (INIS)

    Roesser, J.R.; Chorghade, M.S.; Hecht, S.M.

    1986-01-01

    The peptidyl-tRNA analogue N-(chloracetyl) phenylalanyl-tRNA/sup Phe/ was prepared by chemical aminoacylation and prebound to the P site of Escherichia coli ribosomes in response to poly(uridylic acid). Admixture of phenylalanyl-tRNA/sup Phe/ to the A site resulted in the formation of two dipeptides, one of which was found by displacement of chloride ion from the peptidyl-tRNA. This constitutes the first example of ribosome-mediated formation of a peptide of altered connectivity and suggests a need for revision of the current model of peptide bond formation. Also suggested by the present finding is the feasibility of utilizing tRNAs to prepare polypeptides of altered connectivity in an in vitro protein biosynthesizing system. [ 32 P]-oligo(rA), [ 3 H]- and [ 14 C] phenylalanines were used in the assay of the peptidye-tRNA analogue

  11. Concentration and second-gas effects in the water analogue.

    Science.gov (United States)

    Mapleson, W W; Korman, B

    1998-12-01

    The water analogue provides a visual model of the process of anaesthetic exchange. In the standard version, a single pipe connects the mouth container to the lung container and the conductance of this mouth-lung pipe is proportional to alveolar ventilation. This implies that inspired and expired ventilations are equal. In fact, with high inspired concentrations of nitrous oxide, early rapid uptake of gas by solution leads to a substantial difference between inspired and expired ventilation which in turn leads to concentration and second-gas effects. It is shown that by representing inspired and expired ventilations separately, and keeping one of them constant while varying the other to compensate for rapid uptake, concentration and second-gas effects are reproduced in the water analogue. Other means of reproducing the effects are reported but we believe that the first method is the most realistic and the most appropriate for teaching.

  12. A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

    Science.gov (United States)

    Jameson, Bradford A.; McDonnell, James M.; Marini, Joseph C.; Korngold, Robert

    1994-04-01

    EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS)1,2. The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset3-5. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents6-9, and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4+ subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

  13. From the Canadian High Arctic to Mars by Analogue

    Science.gov (United States)

    Soare, R. J.; Pollard, W. H.

    2002-12-01

    Planetary scientists are limited in their understanding of physical bodies in the solar system by the lack of primary data or knowledge. Analogue science is science practised in absentia, precisely in those instances when a non-terrestrial physical environment lies beyond one's direct, empirical grasp. Recognising that some environments on Earth may mirror present or past conditions on Mars, planetary scientists have invoked terrestrial analogues with increasing regularity over the last thirty years as fonts of putative understanding. Notwithstanding its ubiquity in planetary science, analogical reasoning has stood, by and large, unconstrained by rules or guidelines of usage. In order to redress this imbalance we propose to take two steps: 1. introduce primary data on newly discovered pingos at Axel Heiberg Island in the Canadian High Arctic, and 2. coalesce these and related data on Martian glacial, peri-glacial and fluvio-glacial landforms as a model with which to evaluate the meaningfulness of analogical reasoning in planetary science.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-15

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

  15. Somatostatin analogues labelled with 99mTc

    International Nuclear Information System (INIS)

    Obenaus, Esteban R.; Crudo, Jose L.; Edreira, Martin M.; Castiglia, Silvia G.

    1999-01-01

    Biological and radiochemical studies have been carried out on two labelled somatostatin analogues, the peptide RC-150 and the Tyr 3 -Octreotide. Both analogues have been labelled with 99m Tc using the direct and the indirect method and MAG-3 and HYNIC as chelating agents. By the direct method RC-150 was labelled using sodium ascorbate and dithionite as reducing agents. The radiochemical purity was 70%. By the indirect method, in the case of RC-160 with MAG-3 a radiochemical purity higher than 70% was attained while a purity of 100% was reached in the case of Tyr 3 -Octreotide with HYNIC. The biological distribution of HYNIC-Tyr 3 -Octreotide has been studied in rats. (author)

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

    KAUST Repository

    Sagar, Sunil

    2010-09-01

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

  17. Solid-phase synthesis of polyamine toxin analogues

    DEFF Research Database (Denmark)

    Kromann, Hasse; Krikstolaityte, Sonata; Andersen, Anne J

    2002-01-01

    The wasp toxin philanthotoxin-433 (PhTX-433) is a nonselective and noncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are extensively used for the characterization of subtypes of ionotropic glutamate...... receptors, in particular Ca(2+)-permeable AMPA and kainate receptors. We have previously shown that an analogue of PhTX-433 with one of the amino groups replaced by a methylene group, philanthotoxin-83 (PhTX-83) is a selective and potent antagonist of AMPA receptors. We now describe the solid...... of analogues, the acyl moiety of PhTX-83 was replaced by acids of different size and lipophilicity. Using electrophysiological techniques, PhTX-56 was shown to be a highly potent (K(i) = 3.3 +/- 0.78 nM) and voltage-dependent antagonist of homomeric GluR1 receptors and was more than 1000-fold less potent when...

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

    Science.gov (United States)

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

    2016-01-01

    A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps. PMID:27966660

  19. Haplopappus gracilis cell strains resistant to pyrimidine analogues.

    Science.gov (United States)

    Jones, G E; Hann, J

    1979-03-01

    Strains of Haplopappus gracilis (Nutt.) Gray cells resistant to 6-azauracil have been isolated from cultures of diploid cells. These strains are also resistant to 8-azaguanine, as is their parent. The variants are 100- to 125-fold more resistant to 6-azauracil than their parent, and they exhibit different spectra of cross resistance to other pyrimidine analogues. The phenotype of each variant is stable in the absence of selection. The majority of cells in cultures of the variants are diploid; all others examined were tetraploid. Initial rates of uptake of uracil are not reduced in the variants. Fluorouracil, to which two variants are resistant, is taken up by one of them as well as by the parent. Responses of the other two to fluorouracil are not correlated with decreased ability to accumulate this analogue.

  20. Higher-dimensional analogues of Donaldson-Witten theory

    International Nuclear Information System (INIS)

    Acharya, B.S.; Spence, B.

    1997-01-01

    We present a Donaldson-Witten-type field theory in eight dimensions on manifolds with Spin(7) holonomy. We prove that the stress tensor is BRST exact for metric variations preserving the holonomy and we give the invariants for this class of variations. In six and seven dimensions we propose similar theories on Calabi-Yau threefolds and manifolds of G 2 holonomy, respectively. We point out that these theories arise by considering supersymmetric Yang-Mills theory defined on such manifolds. The theories are invariant under metric variations preserving the holonomy structure without the need for twisting. This statement is a higher-dimensional analogue of the fact that Donaldson-Witten field theory on hyper-Kaehler 4-manifolds is topological without twisting. Higher-dimensional analogues of Floer cohomology are briefly outlined. All of these theories arise naturally within the context of string theory. (orig.)

  1. Models and Analogues for the Evaluation of Human Biodynamic Response, Performance and Protection

    Science.gov (United States)

    1979-06-01

    relationship between the tolerable step loads which form the exposure polygon and the driving point mobility , where the real part of mobility relates to the...ligaments and two facet joints, Figure 2. 7, FCERVICAL VERTEBRAE it THORACIC- VERTEBRAE LUMBAR - Z X VIESR. -- SACRUM -- • (S5p~.cn | - COCCYX -.. 14...subject to the table. Resonances in the abdominal wall displacements were found to occur typically between 3 and 4 Mr. Restricting the mobility of the

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-10-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    In the light of the principle of aggregation-induced emission enhancement (AIEE), the rubrene analogue with orange light-emitting properties is designed and synthesized by substituting the phenyl side groups of rubrene with thienyl groups. To the best of our knowledge, this is the first report on...... on the synthesis of rubrene with AIEE behaviour, thus paving the way for the development of light-emitting rubrene derivatives. This journal is...

  4. Synthetic analogues of natural semiochemicals as promising insect control agents

    International Nuclear Information System (INIS)

    Ujvary, Istvan; Toth, Miklos; Guerin, Patrick

    2000-01-01

    After decades of research and development, insect pheromones and other semiochemicals became indispensable tools of ecologically based agricultural pest and disease vector management programmes with main uses as: 1) detection and population monitoring of emerging and migrating insects, 2) mass trapping of insects, 3) combined formulation of semiochemicals and insecticides ('lure-and-kill'), and 4) mating disruption with specially formulated pheromone components. In spite of their demonstrated safety and biodegradability, the direct application of these semiochemicals for pest control has not fulfilled initial expectations. Nonetheless considerable field experience has been accumulated (Carde and Minks 1995). Evidently, two important factors limit the practical potential of these substances: 1) inherent in their particular mode of action, semiochemicals, especially pheromones, are effectively cleared by specific enzymes in the insect antennae, and 2) some of these compounds contain labile functional moieties that are prone to degradation (oxidation, isomerisation and polymerisation) under field conditions. Appropriate chemical modifications of these natural compounds, however, can circumvent these problems by providing synthetic analogues (sometimes also called parapheromones or antipheromones; for early studies, see Roelofs and Comeau 1971, Payne et al. 1973) which in ideal cases are not only more potent and environmentally acceptable but more economical as well. It should also be mentioned that many effective attractants have been discovered through the empirical screening of synthetic chemicals, some of which have actually turned out to be structural relatives of natural semiochemicals of the particular insect. In this paper, selected case studies of analogues of sex pheromones and kairomones will be presented. The examples from our work include nitrile bioisosteres of labile aldehyde pheromone components of the cranberry girdler moth, Chrysoteuchia topiaria

  5. Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

    Science.gov (United States)

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

    2015-01-01

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

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

    Science.gov (United States)

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

    2015-01-02

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. The Two-Dimensional Analogue of General Relativity

    OpenAIRE

    Lemos, José P. S.; Sá, Paulo M.

    1993-01-01

    General Relativity in three or more dimensions can be obtained by taking the limit $\\omega\\rightarrow\\infty$ in the Brans-Dicke theory. In two dimensions General Relativity is an unacceptable theory. We show that the two-dimensional closest analogue of General Relativity is a theory that also arises in the limit $\\omega\\rightarrow\\infty$ of the two-dimensional Brans-Dicke theory.

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

    International Nuclear Information System (INIS)

    Rasilainen, K.

    1997-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-11-01

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

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

    Science.gov (United States)

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

    2009-05-01

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

  11. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

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

  12. Alkaloids of family Amaryllidaceae and their analogues as potential drugs

    OpenAIRE

    Kavková, Zuzana

    2016-01-01

    Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Zuzana Kavková Supervisor: doc. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Alkaloids of family Amaryllidaceae and their analogues as potential drugs The object of this diploma thesis was to prepare derivatives of alkaloids of Amaryllidaceae family and to deal with their biological activity. These alkaloids are famous for their antibacterial, antiinfectives, a...

  13. Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer

    Science.gov (United States)

    2006-06-01

    product analogs. J Am Chem Soc 1978; 100: 2551–2553. 39 Burri C, Brun R. Eflornithine for the treatment of human African trypanosomiasis . Parasitol Res...ototoxicity) at high therapeutic doses [29]. Currently, DFMO is the front-line agent in the treatment of African trypanosomiasis and is undergoing...Polyamine Analogues in Human Breast Cancer. PRINCIPAL INVESTIGATOR: Yi Huang, M.D., Ph.D. CONTRACTING ORGANIZATION: Johns

  14. Bisphenol A and Its Analogues Activate Human Pregnane X Receptor

    OpenAIRE

    Sui, Yipeng; Ai, Ni; Park, Se-Hyung; Rios-Pilier, Jennifer; Perkins, Jordan T.; Welsh, William J.; Zhou, Changcheng

    2012-01-01

    Background: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA and its analogues are present in environmental and human samples. Many endocrine-disrupting chemicals, including BPA, have been shown to activate the pregnane X receptor (PXR), a nuclear receptor that functions as a master regulator of xenobiotic metabolism. However, the detailed mechanism by which these chemicals activate PXR remains unknown. Objective: We investigated the mechanism by which BPA ...

  15. Manipulating lightcone fluctuations in an analogue cosmic string

    Directory of Open Access Journals (Sweden)

    Jiawei Hu

    2018-02-01

    Full Text Available We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

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

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

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

  17. Degludec: the new ultra-long insulin analogue.

    Science.gov (United States)

    Tambascia, Marcos Antonio; Eliaschewitz, Freddy Goldberg

    2015-01-01

    The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, "De") and the attachment, via a glutamic acid linker ("glu"), of a 16-carbon fatty diacid (hexadecanoic diacid, "dec") to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26-52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia.

  18. Natural analogue studies as supplements to biomineralization research

    International Nuclear Information System (INIS)

    McNeil, M.B.

    1995-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly regarded films to generate a set of highly ranked action/adventure, dramatic, horror and war films. We then scored the presence of a variety of nonlinear analogues in these film soundtracks. Dramatic films suppressed noise of all types, contained more abrupt frequency transitions and musical sidebands, and fewer noisy screams than expected. Horror films suppressed abrupt frequency transitions and musical sidebands, but had more non-musical sidebands, and noisy screams than expected. Adventure films had more male screams than expected. Together, our results suggest that film-makers manipulate sounds to create nonlinear analogues in order to manipulate our emotional responses. PMID:20504815

  20. Design and synthesis of biotin analogues reversibly binding with streptavidin.

    Science.gov (United States)

    Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

    2015-04-01

    Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G. Saulnier and W. Statham

    2006-04-16

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

  2. Manipulating lightcone fluctuations in an analogue cosmic string

    Science.gov (United States)

    Hu, Jiawei; Yu, Hongwei

    2018-02-01

    We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

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

    Science.gov (United States)

    Branis, Natalia M; Wittlin, Steven D

    2015-01-01

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

  4. On the Use of the Analogue Transformation Acoustics in Aeroacoustics

    Directory of Open Access Journals (Sweden)

    Umberto Iemma

    2017-01-01

    Full Text Available The objective of the paper is the assessment of the Analogue Transformation Acoustics (ATA in the design of acoustic metamaterial for aeronautical applications. The work focuses on the consistency of the background flow resulting from the application of the ATA with the equations governing the potential aerodynamics. Indeed, in case of acoustic perturbations propagating within moving media, the convective terms in the governing equations are responsible for the failure of formal invariance under the action of conformal mappings. The ATA approach overcomes this limitation, introducing the possibility of handling the convective form of the wave equation in a straightforward and elegant way. It is based on the concept of analogue space-time and fully relies on the analytical tools of Lorentzian differential geometry. The present paper analyses the relationship between the analogue velocity field with a realistic potential flow. The method is validated through numerical simulations using two widely assessed acoustic cloaking problems. The preliminary results obtained show that the use of numerical, quasi-conformal mappings can lead to transformed streamlines negligibly deviating from those of the potential velocity field satisfying the fluid-dynamic conservation laws, but with incompatible intensity of the local velocity.

  5. Insider protection

    Energy Technology Data Exchange (ETDEWEB)

    Waddoups, I.G.

    1993-07-01

    The government community is broadly addressing the insider threat. The first section of this paper defines protection approaches and the latter sections present various applicable technology developments. The bulk of the paper discusses technology developments applied to (1) personnel and material tracking and inventory, (2) classified document protection, and (3) protecting security systems. The personnel and material tracking system uses a PC based-host to (1) collect information from proximity tags and material movement sensors, (2) apply rules to this input to assure that the ongoing activity meets the site selectable rules and, (3) forward the results to either an automated inventory system or an alarm system. The document protection system uses a PC network to efficiently and securely control classified material which is stored on write-once-read-mostly optical media. The protection of sensor to multiplexer communications in a security system is emphasized in the discussion of protecting security systems.

  6. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    International Nuclear Information System (INIS)

    G.J. Saulnier Jr; W. Statham

    2006-01-01

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO 2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 ± 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory analysis

  7. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

  8. High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines

    International Nuclear Information System (INIS)

    Kumar, K.S.; Srinivasan, V.; Toles, R.E.; Miner, V.L.; Jackson, W.E.; Seed, T.M.

    2002-01-01

    There is an urgent need to develop non-toxic radioprotectors. We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion. Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of 60 Co radiation. Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin). Peripheral blood cell profile and 60-day survival were used as indices of protection. At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days. Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation. Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion. The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines. These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines. Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls. (author)

  9. High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, K.S.; Srinivasan, V.; Toles, R.E.; Miner, V.L.; Jackson, W.E.; Seed, T.M. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)

    2002-12-01

    There is an urgent need to develop non-toxic radioprotectors. We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion. Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of {sup 60}Co radiation. Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin). Peripheral blood cell profile and 60-day survival were used as indices of protection. At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days. Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation. Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion. The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines. These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines. Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls. (author)

  10. Novel Methods for the Chemical Synthesis of Insulin Superfamily Peptides and of Analogues Containing Disulfide Isosteres.

    Science.gov (United States)

    Hossain, Mohammed Akhter; Wade, John D

    2017-09-19

    The insulin superfamily of peptides is ubiquitous within vertebrates and invertebrates and is characterized by the presence of a set of three disulfide bonds in a unique disposition. With the exception of insulin-like growth factors I and II, which are single chain peptides, the remaining 8 members of the human insulin superfamily are two-chain peptides containing one intramolecular and two intermolecular disulfide bridges. These structural features have long made the chemical synthesis of the peptides a considerable challenge, in particular, including their correct disulfide bond pairing and formation. However, they have also afforded the opportunity to develop modern solid phase synthesis methods for the preparation of such peptides that incorporate novel or improved chemical methods for the controlled introduction of both disulfide bonds and their surrogates, both during and after peptide chain assembly. In turn, this has enabled a detailed probing of the structure and function relationship of this small but complex superfamily of peptides. After initially using and subsequently identifying significant limitations of the approach of simultaneous random chain combination and oxidative folding, our laboratory undertook to develop robust chemical synthesis strategies in concert with orthogonal cysteine S-protecting groups and corresponding regioselective disulfide bond formation. These have included the separate synthesis of each of the two chains or of the two chains linked by an artificial C-peptide that is removed following postoxidative folding. These, in turn, have enabled an increased ease of acquisition in a good yield of not only members of human insulin superfamily but other insulin-like peptides. Importantly, these successful methods have enabled, for the first time, a detailed analysis of the role that the disulfide bonds play in the structure and function of such peptides. This was achieved by selective removal of the disulfide bonds or by the judicious

  11. Novel Vitamin K analogues suppress seizures in zebrafish and mouse models of epilepsy

    Science.gov (United States)

    Rahn, Jennifer J.; Bestman, Jennifer E.; Josey, Benjamin J.; Inks, Elizabeth S.; Stackley, Krista D.; Rogers, Carolyn E.; Chou, C. James; Chan, Sherine S. L.

    2014-01-01

    Epilepsy is a debilitating disease affecting 1-2% of the world’s population. Despite this high prevalence, 30% of patients suffering from epilepsy are not successfully managed by current medication suggesting a critical need for new anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the management of epilepsy, we began our study by screening drugs that, like some currently used AEDs, inhibit HDACs using a well-established larval zebrafish model. In this model, 7-day post fertilization (dpf) larvae are treated with the widely used seizure-inducing compound pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior previously determined to be a measurable manifestation of seizures. In our first screen, we tested a number of different HDAC inhibitors and found that one, NQN1, significantly decreased swim activity to levels equal to that of VPA. We continued to screen structurally related compounds including Vitamin K3 (VK3) and a number of novel Vitamin K (VK) analogues. We found that VK3 was a robust inhibitor of the PTZ-induced swim activity, as were several of our novel compounds. Three of these compounds were subsequently tested on mouse seizure models at the National Institute of Neurological Disorders and Stroke (NINDS) Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well in the minimal clonic seizure (6 Hz) and corneal kindled mouse models of epilepsy, with no observable toxicity. As VK3 affects mitochondrial function, we tested the effects of our compounds on mitochondrial respiration and ATP production in a mouse hippocampal cell line. We demonstrate that these compounds affect ATP metabolism and increase total cellular ATP. Our data indicate the potential utility of these and other VK analogues for prevention of seizures and suggest the potential mechanism for this protection may lie in the ability of these compounds to affect energy production. PMID:24291671

  12. Eye Protection

    Science.gov (United States)

    ... is very important to read the product safety materials before using any new chemicals. The appropriate personal protective equipment for eye protection will be listed. This is particularly important for applying and handling pesticides, working with caustics such as lime fertilizer, ...

  13. Quantum Analogues: From Phase Transitions to Black Holes and Cosmology

    International Nuclear Information System (INIS)

    Liberati, Stefano

    2008-01-01

    'And I cherish more than anything else the analogies, my most trustworthy masters. They know all the secrets of nature, and they ought to be least neglected in geometry.' These words of the great astronomer Johannes Kepler embody the philosophy behind the research recounted in this interesting book-a book composed of nine selected lectures (and a nice introduction by Bill Unruh) from the international workshop on 'Quantum Simulations via Analogues', which was held in the Max Planck Institute for the Physics of Complex Systems in Dresden during the summer of 2005. Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. However the last decade has seen a remarkable and steady development of analogue gravity models based on condensed matter systems, leading to some hundreds of published articles, numerous workshops, and several books. While the main driver for this booming field has definitely been the puzzling physics associated with quantum effects in black holes, more recently much attention has also been devoted to other interesting issues-such as cosmological particle production or the cosmological constant problem. Moreover, together with these new themes there has been a persistent interest in the possibility of simulating cosmic topological defects in the laboratory (although it should be said that momentum for this line of research has been somewhat weakened by the progressive decrease of interest in cosmological topological defects as an alternative to inflationary scenarios). All these aspects are faithfully accounted for in this book, which does a good job at presenting a vivid snapshot of many (if not quite all) of the most interesting lines of research in the field. All the articles have a self-consistent structure-which allows one to read them in arbitrary order and appreciate the full richness of each topic. However, when considered together I would say that they also provide a

  14. Quantitative comparisons of analogue models of brittle wedge dynamics

    Science.gov (United States)

    Schreurs, Guido

    2010-05-01

    Analogue model experiments are widely used to gain insights into the evolution of geological structures. In this study, we present a direct comparison of experimental results of 14 analogue modelling laboratories using prescribed set-ups. A quantitative analysis of the results will document the variability among models and will allow an appraisal of reproducibility and limits of interpretation. This has direct implications for comparisons between structures in analogue models and natural field examples. All laboratories used the same frictional analogue materials (quartz and corundum sand) and prescribed model-building techniques (sieving and levelling). Although each laboratory used its own experimental apparatus, the same type of self-adhesive foil was used to cover the base and all the walls of the experimental apparatus in order to guarantee identical boundary conditions (i.e. identical shear stresses at the base and walls). Three experimental set-ups using only brittle frictional materials were examined. In each of the three set-ups the model was shortened by a vertical wall, which moved with respect to the fixed base and the three remaining sidewalls. The minimum width of the model (dimension parallel to mobile wall) was also prescribed. In the first experimental set-up, a quartz sand wedge with a surface slope of ˜20° was pushed by a mobile wall. All models conformed to the critical taper theory, maintained a stable surface slope and did not show internal deformation. In the next two experimental set-ups, a horizontal sand pack consisting of alternating quartz sand and corundum sand layers was shortened from one side by the mobile wall. In one of the set-ups a thin rigid sheet covered part of the model base and was attached to the mobile wall (i.e. a basal velocity discontinuity distant from the mobile wall). In the other set-up a basal rigid sheet was absent and the basal velocity discontinuity was located at the mobile wall. In both types of experiments

  15. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  16. Alligator Rivers Analogue Project. Final Report - Volume 1

    International Nuclear Information System (INIS)

    Duerden, P.; Lever, D.A.; Sverjensky, D.A.; Townley, L.R.

    1992-01-01

    This summary report, which highlights the work and findings of the Alligator Rivers Analogue Project (ARAP) is one of a series of 16 volumes, listed below. Detailed descriptions and results are provided in Volumes 2 to 16. Full acknowledgment to individual contributions is provided in the individual reports, and in Appendix I of this report. The findings from the technical studies are discussed in the context of assessments of the long-term performance of geological repositories for radioactive wastes, which are being undertaken in many countries. They are also considered in an integrated 'Scenario Development' approach, aimed to understand the formation of the ore deposit. Despite their inherent uncertainties, the findings provide a basis for assessing the way in which radionuclides will migrate in environments with a variety of geologic settings and over a range of different geologic timescales. Thus, section 2 of this report discusses the concept of using uranium deposits as natural analogues and refers to a number of such studies, including those at the Koongarra deposit in the Alligator Rivers Region of the Northern Territory of Australia. Section 3 reviews early scientific work in the Alligator Rivers Region and summarises the results of the analogue studies undertaken between 1981 and 1987 that were funded by the US Nuclear Regulatory Commission (USNRC) and the UK Department of the Environment (UKDoE). Section 4 describes the objectives of ARAP and the manner in which the study was conducted and provides a general outline of the project and a summary of the findings. A general description of the Koongarra ore deposit, the focus of ARAP, is provided in Section 5, with Sections 6-13 providing summaries of the work carried out to characterise the site in detail and provide data for modelling. Sections 14-18 discuss how this data was used in modelling and how the results may be applied for performance assessment studies. Finally, Section 19 considers the

  17. Pena Blanca Natural Analogue Project: Summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-02-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  18. Application of FPGA's in Flexible Analogue Electronic Image Generator Design

    Directory of Open Access Journals (Sweden)

    Peter Kulla

    2006-01-01

    Full Text Available This paper focuses on usage of the FPGAs (Field Programmable Gate Arrays Xilinx as a part of our more complex workdedicated to design of flexible analogue electronic images generator for application in TV measurement technique or/and TV servicetechnique or/and education process. The FPGAs performs here the role of component colour R, G, B, synchronization and blanking signals source. These signals are next processed and amplified in other parts of the generator as NTSC/PAL source encoder and RF modulator. The main aim of this paper is to show the possibilities how with suitable development software use a FPGAs in analog TV technology.

  19. Captopril analogues as metallo-β-lactamase inhibitors.

    Science.gov (United States)

    Yusof, Yusralina; Tan, Daniel T C; Arjomandi, Omid Khalili; Schenk, Gerhard; McGeary, Ross P

    2016-03-15

    A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure-activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Synthesis, Preliminary Bioevaluation and Computational Analysis of Caffeic Acid Analogues

    Directory of Open Access Journals (Sweden)

    Zhiqian Liu

    2014-05-01

    Full Text Available A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.

  1. Optical analogues of nanostructures with Rashba–Dresselhaus interactions

    International Nuclear Information System (INIS)

    Dragoman, Daniela

    2014-01-01

    We demonstrate that light propagation through uniaxial crystals with suitably oriented optical axes is quantitatively analogous to electron propagation in a two-dimensional electron gas in the presence of Rashba and/or Dresselhaus effects. It is shown that, through an appropriate shaping of light beams and a rigorous control of their incidence angle on properly oriented uniaxial crystals, it is possible to investigate independently the effects of angular divergence and energy broadening on electron wavefunction evolution. Such optical analogues could be useful in designing spintronic devices, in particular those relying on the equality of Rashba and Dresselhaus coefficients. (paper)

  2. A high speed digital-to-analogue converter

    International Nuclear Information System (INIS)

    Hallgren, B.I.

    1974-02-01

    An 8-bit Digital-to-Analogue converter of the current-weighting type has been constructed using 8 monolithic integrated circuit transistor arrays -one for each bit. The D/A-converter has a voltage output within the range 0 to -2V. The settling time to within half of the least significant bit is about 50 nsec. The temperature dependence and transient response of the converter has been analysed using computer aided design techniques. A comparison is made between the experimental and simulated transient performance. (Auth.)

  3. Pena blanca natural analogue project: summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

    2010-12-08

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  4. Isosteric phosphonate pyrrolidine-based dinucleoside monophosphate analogues

    Czech Academy of Sciences Publication Activity Database

    Vaněk, Václav; Buděšínský, Miloš; Kavenová, Ivana; Rinnová, Markéta; Rosenberg, Ivan

    2003-01-01

    Roč. 22, 5/8 (2003), s. 1065-1067 ISSN 1525-7770. [International Roundtable Nucleosides, Nucleotides and Nucleic Acids /15./. Leuven, 10.09.2002-14.09.2002] R&D Projects: GA ČR GA203/01/1166; GA AV ČR IAA4055101 Institutional research plan: CEZ:AV0Z4055905 Keywords : pyrrolidine-based phosphonate nucleotides * ApA analogues * triplex Subject RIV: CC - Organic Chemistry Impact factor: 0.813, year: 2003

  5. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    Directory of Open Access Journals (Sweden)

    B S Jackson

    2017-04-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA. To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  6. Are Structural Analogues to Bisphenol A Safe Alternatives?

    DEFF Research Database (Denmark)

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

    2014-01-01

    Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives......, there is a risk of effects similar to BPA.Objectives: The aim was to elucidate and compare the hazards of bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), bisphenol S (BPS) and 4-cumylphenol (HPP) to BPA.Methods: In vitro studies on steroidogenesis, receptor activity, and biomarkers of effect, as well...

  7. Synthesis of Analogues of Thyroid Hormones: Nuclear Receptor Modulators

    Directory of Open Access Journals (Sweden)

    Guilherme Vieira de Castro

    2015-09-01

    Full Text Available Thyroid hormones are essential for the development and differentiation of all cells of the human body. This work reports the synthesis of some synthetic structural analogues of thyroid hormones, which may be modulators of the thyroid hormone receptor. The known compounds GC-1 (Sobetirome and CG-24 were successfully prepared and two novel analogous molecules were also synthesized by a new and efficient synthetic methodology. DOI: http://dx.doi.org/10.17807/orbital.v7i3.739  

  8. Tidal regimes and salt marshes - the River Hamble analogue

    International Nuclear Information System (INIS)

    Gray, A.J.; Moy, I.L.; Warman, E.A.; Dawson, F.H.; Henville, P.

    1993-01-01

    Construction of estuarine tidal-energy barrages has a potentially major effect on the tidal regime of the estuary, particularly upstream of a barrage. Because tidal regime largely controls the distribution and species composition of intertidal plant and animal communities, it is important to understand how barrages may affect such communities. The main objectives of the research described in this report were to relate recent changes in tidal regime within an embanked area of salt marsh and mudflat to changes in the distribution of plant species. This was to test predictions about tidal control of species' range and to assess the site's suitability as an analogue of post-barrage conditions. (author)

  9. Radiation protection

    International Nuclear Information System (INIS)

    1989-01-01

    A NRPB leaflet in the 'At-a-Glance' series explains in a simple but scientifically accurate way what radiation is, the biological effects and the relative sensitivity of different parts of the human body. The leaflet then discusses radiation protection principles, radiation protection in the UK and finally the effectiveness of this radiation protection as judged by a breakdown of the total dose received by an average person in the UK, a heavy consumer of Cumbrian seafood, an average nuclear industry worker and an average person in Cornwall. (UK)

  10. The arsonomethyl analogue of adenosine 5'-phosphate. An uncoupler of adenylate kinase.

    Science.gov (United States)

    Adams, S R; Sparkes, M J; Dixon, H B

    1984-01-01

    Adenosine was converted into the arsonomethyl analogue of AMP. The reactions used provide a general route for converting an alcohol, R-CH2-OH, into the arsonomethyl analogue, R-CH2-CH2-AsO3H2, of its phosphate, R-CH2-O-PO3H2. The analogue of AMP proves to be a substrate for rabbit adenylate kinase, which shows a limiting velocity with it of 1/17 that with AMP, a Michaelis constant raised 70-fold to about 10 mM, and hence a specificity constant lowered about 1200-fold. The product of transfer of a phospho group from ATP to the analogue is, like all anhydrides of arsonic acids, unstable to hydrolysis, and so breaks down to yield orthophosphate and regenerate the analogue. Hence adenylate kinase is converted into an ATPase by the presence of the analogue. PMID:6089748

  11. Pollinator Protection

    Science.gov (United States)

    What the EPA is doing to protect bees and other pollinators from pesticides; including addressing the issue of Colony Collapse Disorder (CCD), risk assessment, decline in pollinator health in general, and why pollinators are important.

  12. Protective clothing

    International Nuclear Information System (INIS)

    Malet, J.C.; Regnier, J.

    1979-01-01

    The present operational and intervention suits are described. Research work is currently in progress to improve the performance of the existing suits and to develop more resistant protective clothing. (author)

  13. Memory protection

    Science.gov (United States)

    Denning, Peter J.

    1988-01-01

    Accidental overwriting of files or of memory regions belonging to other programs, browsing of personal files by superusers, Trojan horses, and viruses are examples of breakdowns in workstations and personal computers that would be significantly reduced by memory protection. Memory protection is the capability of an operating system and supporting hardware to delimit segments of memory, to control whether segments can be read from or written into, and to confine accesses of a program to its segments alone. The absence of memory protection in many operating systems today is the result of a bias toward a narrow definition of performance as maximum instruction-execution rate. A broader definition, including the time to get the job done, makes clear that cost of recovery from memory interference errors reduces expected performance. The mechanisms of memory protection are well understood, powerful, efficient, and elegant. They add to performance in the broad sense without reducing instruction execution rate.

  14. Radiation protection

    International Nuclear Information System (INIS)

    Ures Pantazi, M.

    1994-01-01

    This work define procedures and controls about ionizing radiations. Between some definitions it found the following topics: radiation dose, risk, biological effects, international radioprotection bodies, workers exposure, accidental exposure, emergencies and radiation protection

  15. Protective Eyewear

    Science.gov (United States)

    ... Whether you’re on the basketball court, in chemistry class, or sitting by the pool, wearing protective ... remember to wear safety goggles. Using chemicals in chemistry class? Look like a real scientist by wearing ...

  16. Negotiating Protection

    DEFF Research Database (Denmark)

    Bille, Mikkel

    of architecture, the social use of luminosity, prophylactic items, saint veneration, Qur'anic items, and heritage production. The thesis challenges the preoccupation with "meaning" in material culture studies, by focusing on conceptualizations of "presence" and "absence" as equally important to protective...... strategies are confirming their efficacy, and act as material anchors for negotiating Bedouin identities in response to a rapid transformation from nomadic pastoralists to sedentary wageworkers. The tensions surrounding the materiality of protection, along with the role of the past in the present is further...... investigated through the contested public representations of Ammarin culture, along with a detailed study of the process leading to the protection of Bedouin culture by UNESCO Intangible Cultural Heritage. The overall conclusion of this research is that negotiating efficacious protection against perceived...

  17. Corrosion protection

    Science.gov (United States)

    Brown, Donald W.; Wagh, Arun S.

    2003-05-27

    There has been invented a chemically bonded phosphate corrosion protection material and process for application of the corrosion protection material for corrosion prevention. A slurry of iron oxide and phosphoric acid is used to contact a warm surface of iron, steel or other metal to be treated. In the presence of ferrous ions from the iron, steel or other metal, the slurry reacts to form iron phosphates which form grains chemically bonded onto the surface of the steel.

  18. Radiation protection

    International Nuclear Information System (INIS)

    Koelzer, W.

    1976-01-01

    The lecture is divided into five sections. The introduction deals with the physical and radiological terms, quantities and units. Then the basic principles of radiological protection are discussed. In the third section attention is paid to the biological effects of ionizing radiation. The fourth section deals with the objectives of practical radiological protection. Finally the emergency measures are discussed to be taken in radiation accidents. (HP) [de

  19. Environmental protection

    International Nuclear Information System (INIS)

    Martinez, A.S.

    1987-01-01

    The question of environment protection related to the use of nuclear energy aiming to power generation, based on the harmonic concept of economic and industrial development, preserving the environment, is discussed. A brief study of environmental impacts for some energy sources, including nuclear energy, to present the systems of a nuclear power plant which aim at environmental protection, is done. (M.C.K.) [pt

  20. Radiation Protection

    International Nuclear Information System (INIS)

    Loos, M.

    2001-01-01

    Major achievements of SCK-CEN's Radiation Protection Department in 2000 are described. The main areas for R and D of the department remain neutron dosimetry and neutron activation analysis, safeguards information handling and non-destructive assay techniques. Further activities include low-level radioactivity measurements in environmental and biological samples and radiation protection research. Finally, achievements in decision strategy research and social sciences in nuclear research are reported

  1. Applications of natural analogue studies to Yucca Mountain as a potential high level radioactive waste repository

    International Nuclear Information System (INIS)

    1995-02-01

    The 5-member group convened in Las Vegas, Nov. 11-13, 1991, to clarify the extent to which studies of natural analogues can assist the Yucca Mountain site characterization (SC) project. This document is to provide guidance and recommendations to DOE for the implementation of natural analogue studies in the SC program. Performance assessment, integrity of engineered barriers, and communication to the public and the scientific community are stressed. The reference design being developed by Babcock ampersand Wilcox Fuel Company are reviewed. Guidelines for selecting natural analogues are given. Quality assurance is discussed. Recommendations are given for developing an effective natural analogue program within the SC program

  2. Isolation and structural identification of a novel minoxidil analogue in an illegal dietary supplement: triaminodil.

    Science.gov (United States)

    Lee, Ji Hyun; Park, Han Na; Park, Hyoung Joon; Kim, Nam Sook; Park, Sung-Kwan; Lee, Jongkook; Baek, Sun Young

    2018-01-01

    A new minoxidil analogue was detected in an illegal dietary supplement advertised as a hair-growth treatment. The analogue was identified using ultra-performance liquid chromatography (UPLC), high-resolution mass spectrometry (LC-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound was structurally elucidated as a minoxidil analogue in which the piperidinyl group of minoxidil was replaced with a pyrrolidinyl group corresponding to a molecular formula of C 8 H 13 N 5 O. The new analogue has been named triaminodil. As this is the first report of the compound, there are no chemical, toxicology or pharmacological data available.

  3. Martian analogue test site - pilbara craton, western Australia

    Science.gov (United States)

    Brown, A.; Allwood, A.; Walter, M. R.; van Kranendonk, M.

    All exploration for life elsewhere depends on extrapolation from our knowledge of Earth. If the target is former microbial life, for example on Mars, there is no better analogue on Earth than the 3.5 billion year old rocks of the Pilbara region, Western Australia. This area is home to signs of the earliest life on Earth in the form of microbe, many famous stromatolitic horizons and carbon isotope biosignatures. These occur in a volcanic terrain, with weathering and hydrothermal alteration, which also has some similarity to Mars. The geology of this region is known in detail after decades of mapping and other studies. Current work includes studies to resolve disputes about the biogenicity of the microfossils and stromatolites. On balance, biological origins are most likely. In any event, problems of demonstrating biogenicity on other planets will be far more severe, and the work on the Pilbara materials will illuminate those problems. Also underway is mineral mapping of the volcanic, hydrothermal and fossiliferous units using both airborne and hand-held short-wave infrared spectrometers, We are able to map the fossiliferous units using this technique and contend that it would be a powerful exploration technique on Mars and elsewhere. Using the Pilbara as an analogue for other bodies in the Solar System can extend to using it as a place to test instrument packages under realistic conditions. The region has good air and road access, and good supporting infrastructure.

  4. Integrating TEMPO and Its Analogues with Visible-Light Photocatalysis.

    Science.gov (United States)

    Lang, Xianjun; Zhao, Jincai

    2018-01-16

    Visible light has risen to become a very important facilitator for selective radical reactions enabled by well-cognized photocatalysts. The renaissance of visible-light photocatalysis on this matter partly relies on integrating it with other fields of catalysis. In parallel, 2,2,6,6-tetramethylpiperidin N-oxide (TEMPO), a quintessential persistent radical, has a wide range of uses owing to its exceptional redox behavior, which gives rise to its latest prominence in catalysis. Therefore, integrating the catalysis of TEMPO with photocatalysis to perform visible-light-induced selective reactions becomes a very convenient marriage of merits. In this context, the integration of different types of photocatalysts, including metal complexes, metal-free organic dyes, and semiconductors, with TEMPO for outstanding organic transformations will be summarized. To expand further the catalytic repertoire, the integration of TEMPOH analogues such as NHPI (N-hydroxyphthalimide) and NHS (N-hydroxysuccinimide) with photocatalysis will also be discussed. Hopefully, these advances will pave the way for more breakthroughs by integrating TEMPO and its analogues with photocatalysis to lead to a valuable blueprint for visible-light-induced selective organic transformations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. A Bosonic Analogue of a Topological Dirac Semi-Metal

    Science.gov (United States)

    Lapa, Matthew; Cho, Gil Young; Hughes, Taylor

    We construct a bosonic analogue of a two-dimensional topological Dirac Semi-Metal (DSM). The low-energy description of the most basic 2D DSM model consists of two Dirac cones at positions +/-k0 in momentum space. The local stability of the Dirac cones is guaranteed by a composite symmetry Z2, where  is time-reversal and  is inversion. This model also exhibits interesting time-reversal and inversion symmetry breaking electromagnetic responses. In this work we construct a bosonic analogue of a DSM by replacing each Dirac cone with a copy of the O (4) Nonlinear Sigma Model (NLSM) with topological theta term and theta angle θ = +/- π . One copy of this NLSM also describes the gapless surface termination of the 3D Bosonic Topological Insulator (BTI). We compute the time-reversal and inversion symmetry breaking electromagnetic responses for our model and show that they are twice the value one gets in the DSM case. We also investigate the local stability of the individual O (4) NLSM's in the BSM model. Along the way we clarify many aspects of the surface theory of the BTI including the electromagnetic response, the charges of vortex excitations, and the stability to symmetry-allowed perturbations. Nsf CAREER DMR-1351895.

  6. Classical analogue of an interstellar travel through a hydrodynamic wormhole

    Science.gov (United States)

    Euvé, L.-P.; Rousseaux, G.

    2017-09-01

    The classical theory of space-time, namely general relativity, suggests but does not demonstrate the existence of so-called wormholes allowing for interstellar journeys. Alternative proposals such as quantum gravity theories are developed nowadays to allow for wormhole travels by assuming hypothetical trans-Planckian effects at tiny scales. Here we show experimentally that analogue traversable and bidirectional wormholes exist in hydrodynamics following a suggestion by Wheeler. Using a water channel, we sent free surface waves on a countercurrent in an analogue gravity setup aiming at showing that hydrodynamic wormhole travels are controlled by a cascade of dispersive scales including surface tension effects: the capillary wavelength plays the role of a Planckian scale below which long gravity waves are transformed into short capillary waves that are able to move at speeds higher than the "flow" of space-time. Whereas our results do not apply to putative astrophysical wormholes per se, we anticipate that they will trigger new ideas to explore quantum gravity physics.

  7. Limonene hydroperoxide analogues show specific patch test reactions.

    Science.gov (United States)

    Christensson, Johanna Bråred; Hellsén, Staffan; Börje, Anna; Karlberg, Ann-Therese

    2014-05-01

    The fragrance terpene R-limonene is a very weak sensitizer, but forms allergenic oxidation products upon contact with air. The primary oxidation products of oxidized limonene, the hydroperoxides, have an important impact on the sensitizing potency of the oxidation mixture. One analogue, limonene-1-hydroperoxide, was experimentally shown to be a significantly more potent sensitizer than limonene-2-hydroperoxide in the local lymph node assay with non-pooled lymph nodes. To investigate the pattern of reactivity among consecutive dermatitis patients to two structurally closely related limonene hydroperoxides, limonene-1-hydroperoxide and limonene-2-hydroperoxide. Limonene-1-hydroperoxide, limonene-2-hydroperoxide, at 0.5% in petrolatum, and oxidized limonene 3.0% pet. were tested in 763 consecutive dermatitis patients. Of the tested materials, limonene-1-hydroperoxide gave most reactions, with 2.4% of the patients showing positive patch test reactions. Limonene-2-hydroperoxide and oxidized R-limonene gave 1.7% and 1.2% positive patch test reactions, respectively. Concomitant positive patch test reactions to other fragrance markers in the baseline series were frequently noted. The results are in accordance with the experimental studies, as limonene-1-hydroperoxide gave more positive patch test reactions in the tested patients than limonene-2-hydroperoxide. Furthermore, the results support the specificity of the allergenic activity of the limonene hydroperoxide analogues and the importance of oxidized limonene as a cause of contact allergy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Metabolites of saxitoxin analogues in bivalves contaminated by Gymnodinium catenatum.

    Science.gov (United States)

    Vale, Paulo

    2010-01-01

    Bivalve metabolites of saxitoxin analogues, not present in microalgae, were recently described as an important toxin fraction in mussels contaminated by Alexandrium tamarense. These possess very low fluorescence, and require mass spectrometry detection. HILIC-MS was implemented to look for these metabolites in bivalves contaminated during Gymnodinium catenatum blooms at the Portuguese coast. The presence of M1 was tentatively identified in several bivalves, ranging from estuarine (Mytilus galloprovinciallis, Cerastoderma edule and Ruditapes decussatus) to oceanic habitat (Donax trunculus and Ensis spp.). It was hypothesized that M1 could contribute to an important fraction of the profile of STX analogues. M1 was more abundant in estuarine bivalves that retain longer PSP toxins, in the following order: mussels>cockles>clams. These data highlight that the study by fluorimetry alone of the carbamoyl, N-sulfocarbamoyl, and decarbamoyl families is manifestly insufficient to fully understand toxin dynamics in bivalves feeding on G. catenatum without a proper study of hydroxybenzoate and hydroxylated M-toxins.

  9. Parabolic flights as Earth analogue for surface processes on Mars

    Science.gov (United States)

    Kuhn, Nikolaus J.

    2017-04-01

    The interpretation of landforms and environmental archives on Mars with regards to habitability and preservation of traces of life requires a quantitative understanding of the processes that shaped them. Commonly, qualitative similarities in sedimentary rocks between Earth and Mars are used as an analogue to reconstruct the environments in which they formed on Mars. However, flow hydraulics and sedimentation differ between Earth and Mars, requiring a recalibration of models describing runoff, erosion, transport and deposition. Simulation of these processes on Earth is limited because gravity cannot be changed and the trade-off between adjusting e.g. fluid or particle density generates other mismatches, such as fluid viscosity. Computational Fluid Dynamics offer an alternative, but would also require a certain degree of calibration or testing. Parabolic flights offer a possibility to amend the shortcomings of these approaches. Parabolas with reduced gravity last up to 30 seconds, which allows the simulation of sedimentation processes and the measurement of flow hydraulics. This study summarizes the experience gathered during four campaigns of parabolic flights, aimed at identifying potential and limitations of their use as an Earth analogue for surface processes on Mars.

  10. The role of natural analogues in safety assessment and acceptability

    International Nuclear Information System (INIS)

    Papp, Toenis

    1987-01-01

    The safety assessment must evaluate the level of safety for a repository, the confidence that can be placed on the assessment and how well the repository can meet the acceptance criteria of the society. Many of the processes and phenomena that govern the long term performance of a deep geologic repository for radioactive waste also take place in nature. To investigate these natural analogues and try to validate the models on which the safety assessment are based is a main task in the effort to build of confidence in the safety assessments. The assessment of the safety of a repository can, however, not only be based on good models. The possible role of natural analogues or natural evidence in other parts of the safety assessment is discussed. Specially with regard to - the need to demonstrate that all relevant processes have been taken into account, and that the important ones have been validated to an acceptable level for relevant parameters spans, -the definition and analysis of external scenarios for the safety assessment and for the claim that all reasonable scenarios have been addressed, - the public confidence in the long-term relevance of the acceptance criteria. (author)

  11. Historical space psychology: Early terrestrial explorations as Mars analogues

    Science.gov (United States)

    Suedfeld, Peter

    2010-03-01

    The simulation and analogue environments used by psychologists to circumvent the difficulties of conducting research in space lack many of the unique characteristics of future explorations, especially the mission to Mars. This paper suggests that appropriate additional analogues would be the multi-year maritime and terrestrial explorations that mapped the surface of the Earth in previous centuries. These, like Mars, often involved a hazardous trek through unknown territory, flanked by extended, dangerous voyages to and from the exploration sites. Characteristic issues included interpersonal relationships under prolonged stress, stretches of boredom interspersed with intense work demands, the impossibility of rescue, resupply, or other help from home, chronic danger, physical discomfort and lack of privacy, and the crucial role of the leader. Illustrative examples of one important factor, leadership style, are discussed. The examination of such expeditions can help to identify the psychological stressors that are likely to be experienced by Mars explorers, and can also indicate countermeasures to reduce the damaging impact of those stressors.

  12. A low-dimensional analogue of holographic baryons

    Science.gov (United States)

    Bolognesi, Stefano; Sutcliffe, Paul

    2014-04-01

    Baryons in holographic QCD correspond to topological solitons in the bulk. The most prominent example is the Sakai-Sugimoto model, where the bulk soliton in the five-dimensional spacetime of AdS-type can be approximated by the flat space self-dual Yang-Mills instanton with a small size. Recently, the validity of this approximation has been verified by comparison with the numerical field theory solution. However, multi-solitons and solitons with finite density are currently beyond numerical field theory computations. Various approximations have been applied to investigate these important issues and have led to proposals for finite density configurations that include dyonic salt and baryonic popcorn. Here we introduce and investigate a low-dimensional analogue of the Sakai-Sugimoto model, in which the bulk soliton can be approximated by a flat space sigma model instanton. The bulk theory is a baby Skyrme model in a three-dimensional spacetime with negative curvature. The advantage of the lower-dimensional theory is that numerical simulations of multi-solitons and finite density solutions can be performed and compared with flat space instanton approximations. In particular, analogues of dyonic salt and baryonic popcorn configurations are found and analysed.

  13. The costal landslide from analogue experiments: perspectives and limitation

    Science.gov (United States)

    Del Ventisette, C.; Nolesini, T.; Moretti, S.; Fanti, R.

    2010-12-01

    Understanding the triggering mechanism of coastal landslides (triggered and/or developed at air-water interface) and their evolution is fundamental to evaluate their hazard and, predicting the energy, the associated tsunami risk. The aim of this work is to verify the suitability of analogue modelling to understand the triggering mechanism and the evolution of landslide along the costal line. As a starting case study the Sciara del Fuoco (SdF), northwest flank of the volcanic island of Stromboli (Italy), was chosen. The analogue modelling technique has been proven to represent an useful tool to understand many geological processes, as it allows studying the progressive deformation, providing also useful indications about the role of distinct factors controlling the final deformation pattern. The models simulated at a first approximation the geological geometries observed at Stromboli, a composite volcano forming the northernmost island of the Aeolian Archipelago (Tyrrhenian Sea). The activity of Stromboli volcano is characterized by a persistent mild explosive activity at the summit craters sporadically interrupted by episodes of lava effusion and violent paroxysmal explosions as in 2002-2003 and in 2007. During the 2002 effusion a large landslide occurred on the SdF. The landslide caused a tsunami, which produced severe damages along the island shores. A series of analogue models was performed to investigate the influence of two different types of triggering mechanism and the behaviour of landslides both in air and air-water interface: 1) surface bulging due to the intrusion of a dike; 2) accumulation of material due to an uppermost landslide or due to opening of a new vent. The models, constructed in a Plexiglas tank, were scaled to the natural prototype following the geometrical, rheological, kinematical and dynamical similarities (e.g. Hubbert, 1937; Ramberg, 1981). The modelling material (Fontainbleau sand and rice) was sieved on a slope, inclination of which

  14. Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C, on Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Anahí Magdaleno

    Full Text Available It is well established that L-proline has several roles in the biology of trypanosomatids. In Trypanosoma cruzi, the etiological agent of Chagas' disease, this amino acid is involved in energy metabolism, differentiation processes and resistance to osmotic stress. In this study, we analyzed the effects of interfering with L-proline metabolism on the viability and on other aspects of the T. cruzi life cycle using the proline analogue L- thiazolidine-4-carboxylic acid (T4C. The growth of epimastigotes was evaluated using different concentrations of T4C in standard culture conditions and at high temperature or acidic pH. We also evaluated possible interactions of this analogue with stress conditions such as those produced by nutrient starvation and oxidative stress. T4C showed a dose-response effect on epimastigote growth (IC(50 = 0.89+/-0.02 mM at 28 degrees C, and the inhibitory effect of this analogue was synergistic (p<0.05 with temperature (0.54+/-0.01 mM at 37 degrees C. T4C significantly diminished parasite survival (p<0.05 in combination with nutrient starvation and oxidative stress conditions. Pre-incubation of the parasites with L-proline resulted in a protective effect against oxidative stress, but this was not seen in the presence of the drug. Finally, the trypomastigote bursting from infected mammalian cells was evaluated and found to be inhibited by up to 56% when cells were treated with non-toxic concentrations of T4C (between 1 and 10 mM. All these data together suggest that T4C could be an interesting therapeutic drug if combined with others that affect, for example, oxidative stress. The data also support the participation of proline metabolism in the resistance to oxidative stress.

  15. Machine Protection

    CERN Document Server

    Schmidt, R

    2014-01-01

    The protection of accelerator equipment is as old as accelerator technology and was for many years related to high-power equipment. Examples are the protection of powering equipment from overheating (magnets, power converters, high-current cables), of superconducting magnets from damage after a quench and of klystrons. The protection of equipment from beam accidents is more recent. It is related to the increasing beam power of high-power proton accelerators such as ISIS, SNS, ESS and the PSI cyclotron, to the emission of synchrotron light by electron–positron accelerators and FELs, and to the increase of energy stored in the beam (in particular for hadron colliders such as LHC). Designing a machine protection system requires an excellent understanding of accelerator physics and operation to anticipate possible failures that could lead to damage. Machine protection includes beam and equipment monitoring, a system to safely stop beam operation (e.g. dumping the beam or stopping the beam at low energy) and an ...

  16. Climate Analogues for agricultural impact projection and adaptation – a reliability test

    Directory of Open Access Journals (Sweden)

    Swen P.M. Bos

    2015-10-01

    Full Text Available The climate analogue approach is often considered a valuable tool for climate change impact projection and adaptation planning, especially for complex systems that cannot be modelled reliably. Important examples are smallholder farming systems using agroforestry or other mixed-cropping approaches. For the projected climate at a particular site of interest, the analogue approach identifies locations where the current climate is similar to these projected conditions. By comparing baseline-analogue site pairs, information on climate impacts and opportunities for adaptation can be obtained. However, the climate analogue approach is only meaningful, if climate is a dominant driver of differences between baseline and analogue site pairs. For a smallholder farming setting on Mt. Elgon in Kenya, we tested this requirement by comparing yield potentials of maize and coffee (obtained from the IIASA Global Agro-ecological Zones dataset among 50 close analogue sites for different future climate scenarios and models, and by comparing local ecological knowledge and farm characteristics for one baseline-analogue pair.Yield potentials among the 50 closest analogue locations varied strongly within all climate scenarios, hinting at factors other than climate as major drivers of what the analogue approach might interpret as climate effects. However, on average future climatic conditions seemed more favourable to maize and coffee cultivation than current conditions. The detailed site comparison revealed substantial differences between farms in important characteristics, such as farm size and presence of cash crops, casting doubt on the usefulness of the comparison for climate change analysis. Climatic constraints were similar between sites, so that no apparent lessons for adaptation could be derived. Pests and diseases were also similar, indicating that climate change may not lead to strong changes in biotic constraints at the baseline site in the near future. From

  17. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)

    2010-07-15

    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

  18. Lightning Protection

    Science.gov (United States)

    1994-01-01

    Kit-built airplanes are more affordable because they are assembled by the owner and do not require Federal Aviation Administration (FAA) certification. The Glasair III, is an advanced technology homebuilt, constructed of a fiberglass and graphite fiber composite material, and equipped with digital instruments. Both technologies make the airplane more susceptible to lightning effects. When Glasair manufacturer, Stoddard-Hamilton, decided that lightning protection would enable more extensive instrument flight and make the plane more marketable, they proposed a joint development program to NASA Langley Research Center (LAR). Under a Small Business Innovation Research (SBIR) contract, Langley contractors designed and tested a lightning protection system, and the Glasair III-LP became the first kit-built composite aircraft to be lightning tested and protection-verified under FAA guidelines for general aviation aircraft.

  19. Machine Protection

    CERN Document Server

    Zerlauth, Markus; Wenninger, Jörg

    2012-01-01

    The present architecture of the machine protection system is being recalled and the performance of the associated systems during the 2011 run will be briefly summarized. An analysis of the causes of beam dumps as well as an assessment of the dependability of the machine protection systems (MPS) itself is being presented. Emphasis will be given to events that risked exposing parts of the machine to damage. Further improvements and mitigations of potential holes in the protection systems will be evaluated along with their impact on the 2012 run. The role of rMPP during the various operational phases (commissioning, intensity ramp up, MDs...) will be discussed along with a proposal for the intensity ramp up for the start of beam operation in 2012.

  20. Cyprus natural analogue project (CNAP). Phase II Final Report

    International Nuclear Information System (INIS)

    Alexander, W.R.; Milodowski, A.E.

    2011-02-01

    Due to the extremely slow kinetics of bentonite reaction in low alkali cement leachates, natural analogues would appear to be the only viable method of studying bentonite reaction. As a result of a review of the available literature, several sites in Cyprus were selected as particularly promising for this purpose. This report presents the results of two short field campaigns in Cyprus in November/December, 2008 and February, 2009. The main aim of these campaigns was to establish if appropriate sites existed for a natural analogue study of bentonite-low alkali cement leachate reaction. Focus is on mineralogical changes and not changes in physical properties (such as porosity and permeability) of bentonite as the industrially-processed bentonite used in a repository will be completely different in terms of its engineering and hydrogeological properties to the unprocessed natural bentonite or analogue smectite-rich materials. The first campaign was in the form of a reconnaissance study to identify sites of likely interest and the second, follow-up, campaign focussed on obtaining preliminary groundwater and solid phase (bentonites/clay-rich sediments/altered igneous rocks/soils) samples which would allow a more detailed assessment of several of the potential sites. A large amount of information was collected during these short field campaigns and subsequent laboratory analysis of the collected samples so, to keep the main report down to a digestible size, much of the supporting information has been collated in seven appendices. These include full details of all 30 sites visited during both campaigns along with sample details, information on the analytical techniques, the analytical raw data and numerous photographs of the sites. The intention is that this report will provide full supporting information for a potential Phase III and a detailed database for our colleagues at the Geological Survey Department (GSD) in Cyprus. Consequently, all the information acquired

  1. Noise Protection

    Science.gov (United States)

    1980-01-01

    Environmental Health Systems puts forth an increasing effort in the U.S. to develop ways of controlling noise, particularly in industrial environments due to Federal and State laws, labor union insistence and new findings relative to noise pollution impact on human health. NASA's Apollo guidance control system aided in the development of a noise protection product, SMART. The basis of all SMART products is SMART compound a liquid plastic mixture with exceptional energy/sound absorbing qualities. The basic compound was later refined for noise protection use.

  2. Synthesis and antimicrobial activity of cholic acid hydrazone analogues.

    Science.gov (United States)

    Rasras, Anas J M; Al-Tel, Taleb H; Al-Aboudi, Amal F; Al-Qawasmeh, Raed A

    2010-06-01

    Synthesis and antimicrobial activity of cholic acid analogues 4a-t are reported. The synthesis of 4a-t was accomplished from ethylcholate 2. The hydrazone moiety was introduced via coupling of the cholic acid hydrazide (3) with appropriately functionalized aldehyde utilizing acetic acid as a catalyst. Quiet of interest in relation to the synthesized hydrazones is the formation of two rotamers s-cis.E and s-trans.E. Most compounds showed stronger antimicrobial activity against Gram-positive bacteria than Cefaclor and Cefixime. Compounds 4d, 4i and 4j indicated 15-fold stronger antimicrobial activities against Enterobacter faecalis compared to Cefaclor and Cefixime. Some of the synthesized compounds (e.g. 4a, 4c, 4d, 4i, and 4l) reflected two-folds less activity against Escherichia coli relative to Cefixime. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  3. Quasi-particle creation by analogue black holes

    Science.gov (United States)

    Barceló, Carlos; Liberati, Stefano; Sonego, Sebastiano; Visser, Matt

    2006-09-01

    We discuss the issue of quasi-particle production by 'analogue black holes' with particular attention to the possibility of reproducing Hawking radiation in a laboratory. By constructing simple geometric acoustic models, we obtain a somewhat unexpected result: we show that in order to obtain a stationary and Planckian emission of quasi-particles, it is not necessary to create an ergoregion in the acoustic spacetime (corresponding to a supersonic regime in the flow). It is sufficient to set up a suitable dynamically changing flow. For instance, either a flow that eventually generates an arbitrarily small sonic region v = c, but without any ergoregion, or even a flow that just asymptotically, in laboratory time, approaches a sonic regime with sufficient rapidity.

  4. Quasi-particle creation by analogue black holes

    Energy Technology Data Exchange (ETDEWEB)

    Barcelo, Carlos [Instituto de AstrofIsica de AndalucIa, CSIC, Camino Bajo de Huetor 50, 18008 Granada (Spain); Liberati, Stefano [International School for Advanced Studies, Via Beirut 2-4, 34014 Trieste (Italy); Sonego, Sebastiano [Universita di Udine, Via delle Scienze 208, 33100 Udine (Italy); Visser, Matt [School of Mathematics, Statistics, and Computer Science, Victoria University of Wellington, Wellington (New Zealand)

    2006-09-07

    We discuss the issue of quasi-particle production by 'analogue black holes' with particular attention to the possibility of reproducing Hawking radiation in a laboratory. By constructing simple geometric acoustic models, we obtain a somewhat unexpected result: we show that in order to obtain a stationary and Planckian emission of quasi-particles, it is not necessary to create an ergoregion in the acoustic spacetime (corresponding to a supersonic regime in the flow). It is sufficient to set up a suitable dynamically changing flow. For instance, either a flow that eventually generates an arbitrarily small sonic region v = c, but without any ergoregion, or even a flow that just asymptotically, in laboratory time, approaches a sonic regime with sufficient rapidity.

  5. The Mojave vadose zone: a subsurface biosphere analogue for Mars.

    Science.gov (United States)

    Abbey, William; Salas, Everett; Bhartia, Rohit; Beegle, Luther W

    2013-07-01

    If life ever evolved on the surface of Mars, it is unlikely that it would still survive there today, but as Mars evolved from a wet planet to an arid one, the subsurface environment may have presented a refuge from increasingly hostile surface conditions. Since the last glacial maximum, the Mojave Desert has experienced a similar shift from a wet to a dry environment, giving us the opportunity to study here on Earth how subsurface ecosystems in an arid environment adapt to increasingly barren surface conditions. In this paper, we advocate studying the vadose zone ecosystem of the Mojave Desert as an analogue for possible subsurface biospheres on Mars. We also describe several examples of Mars-like terrain found in the Mojave region and discuss ecological insights that might be gained by a thorough examination of the vadose zone in these specific terrains. Examples described include distributary fans (deltas, alluvial fans, etc.), paleosols overlain by basaltic lava flows, and evaporite deposits.

  6. An IMS-IMS Analogue of MS-MS

    Energy Technology Data Exchange (ETDEWEB)

    Koeniger, Stormy L.; Merenbloom, Samuel I.; Valentine, Stephen J.; Jarrold, Martin F.; Udseth, Harold R.; Smith, Richard D.; Clemmer, David E.

    2006-06-15

    The development of a new ion mobility/mass spectrometry instrument that incorporates a multifield drift tube/ion funnel design is described. In this instrument, individual components from a mixture of ions can be resolved and selected on the basis of mobility differences prior to collisional activation inside the drift tube. The fragment ions that are produced can be dispersed again in a second ion mobility spectrometry (IMS) region prior to additional collisional activation and MS analysis. The result is an IMS-IMS analogue of MS-MS. Here, we describe the preliminary instrumental design and experimental approach. We illustrate the approach by examining the highly characterized bradykinin and ubiquitin systems. Mobility-resolved fragment ions of bradykinin show that b-type ions are readily discernible fragments, because they exist as two easily resolvable structural types. Current limitations and future directions are briefly discussed.

  7. Thermal environment and sleep in winter shelter-analogue settings

    Science.gov (United States)

    Mochizuki, Yosuke; Maeda, Kazuki; Nabeshima, Yuki; Tsuzuki, Kazuyo

    2017-10-01

    We aimed to examine sleep in shelter-analogue settings in winter to determine the sleep and environmental conditions in evacuation shelters. Twelve young healthy students took part in the sleep study of two nights for seven hours from 0 AM to 7 AM in a gymnasium. One night the subject used a pair of futons and on the other the subject used emergency supplies consisting of four blankets and a set of portable partitions. Air temperature, humidity were measured around the sleeping subjects through the night. Sleep parameters, skin temperature, microclimate temperature, rectal temperature, and heart rate of the subjects were continuously measured and recorded during the sleeping period. The subjects completed questionnaires relating to thermal comfort and subjective sleep before and after sleep. The sleep efficiency indices were lower when the subjects slept using the blankets. As the microclimate temperature between the human body and blanket was lower, mean skin temperature was significantly lower in the case of blankets.

  8. Pheophytin analogues from the medicinal lichen Usnea diffracta.

    Science.gov (United States)

    Xu, Hong-Bo; Yang, Tong-Hua; Xie, Pei; Liu, Shi-Jun; Liang, Yan-Ni; Zhang, Yu; Song, Zhong-Xing; Tang, Zhi-Shu

    2018-05-01

    A new pheophytin, (13 2 S, 17S, 18S)-13 2 -hydroxy-20-chloro-ethylpheophorbide a (3), along with two known analogues (1-2) were isolated from the lichen Usnea diffracta Vainio (Parmeliaceae). Among them, compound 3 was a rare C-20-chloro type pheophytin obtained from lichens. Their structures were elucidated by extensive spectroscopic analysis, and all the compounds were obtained for the first time from U. diffracta. Compounds (1-3) were evaluated for their xanthine oxidase (XO) inhibitory activities in vitro, and the results showed that 1-3 possessed significant enzyme inhibitory actions with IC 50 values of 46.9 ± 3.8, 75.9 ± 7.4 and 42.1 ± 1.7 μg/mL, respectively.

  9. Synthesis and antifungal evaluation of PCA amide analogues.

    Science.gov (United States)

    Qin, Chuan; Yu, Di-Ya; Zhou, Xu-Dong; Zhang, Min; Wu, Qing-Lai; Li, Jun-Kai

    2018-04-18

    To improve the physical and chemical properties of phenazine-1-carboxylic acid (PCA) and find higher antifungal compounds, a series of PCA amide analogues were designed and synthesized and their structures were confirmed by 1 H NMR, HRMS, and X-ray. Most compounds showed some antifungal activities in vitro. Particularly, compound 3d exhibited inhibition effect against Pyriculariaoryzac Cavgra with EC 50 value of 28.7 μM and compound 3q exhibited effect against Rhizoctonia solani with EC 50 value of 24.5 μM, more potently active than that of the positive control PCA with its EC 50 values of 37.3 μM (Pyriculariaoryzac Cavgra) and 33.2 μM (Rhizoctonia solani), respectively.

  10. Determination of micro amounts of praseodymium by analogue derivative spectrophotometry

    International Nuclear Information System (INIS)

    Ishii, Hajime; Satoh, Katsuhiko.

    1986-01-01

    Derivative spectrophotometry using the analogue differentiation circuit was applied to the determination of praseodymium at the ppm level. By the proposed method, in which the second or fourth derivative spectrum of the characteristic absorption band of praseodymium(III) at 444 nm is measured, as little as 3 ppm of praseodymium can be determined directly and easily even in the presence of large amounts of other rare earths without any prior separation. Interferences from neodymium, samarium, dysprosium, holmium and erbium ions which have characteristic absorption bands around 444 nm can easily be removed by utilizing the isosbestic point in the derivative spectra of praseodymium(III) and the interfering rare earth(III). (author)

  11. A green multicomponent synthesis of tocopherol analogues with antiproliferative activities.

    Science.gov (United States)

    Ingold, Mariana; Dapueto, Rosina; Victoria, Sabina; Galliusi, Germán; Batthyàny, Carlos; Bollati-Fogolín, Mariela; Tejedor, David; García-Tellado, Fernando; Padrón, José M; Porcal, Williams; López, Gloria V

    2018-01-01

    A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI 50 values between 1 and 5 μM. A structure-activity relationship is also discussed. One of the studied compounds comes up as a future candidate for the development of potent tocopherol-mimetic therapeutic agents for cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Pocos de Caldas, Minas Gerais, Brazil: a natural analogue study

    International Nuclear Information System (INIS)

    Smellie, J.

    1989-01-01

    The Pocos de Caldas natural analogue project is an internationally funded project hosted by Brazil; the contributary organizations are SKB (Sweden), NAGRA (Switzerland), DOE (United Kingdom) and the DOE (United States). The Project is a multidisciplinary study of two mineralized areas within an alkaline igneous caldera complex located near the town of Pocos de Caldas in the state of Minas Gerais. One area, the Osamu Utsumi mine, is characterized by redox deposits of secondary remobilized pitchblende, and the other area, Morro do Ferro, comprises a highly weathered deposit of thorium and REE with subordinate uranium. The project, scheduled for three years (1986-1989), is now entering its third and final year. The pilot and feasibility studies, which characterized the first year, helped to establish the major drilling programme and the sampling protocols for both rock and groundwater studies which constituted the major part of the second year. The latest status of the investigations are briefly reported

  13. Quasinormal modes and classical wave propagation in analogue black holes

    International Nuclear Information System (INIS)

    Berti, Emanuele; Cardoso, Vitor; Lemos, Jose P.S.

    2004-01-01

    Many properties of black holes can be studied using acoustic analogues in the laboratory through the propagation of sound waves. We investigate in detail sound wave propagation in a rotating acoustic (2+1)-dimensional black hole, which corresponds to the 'draining bathtub' fluid flow. We compute the quasinormal mode frequencies of this system and discuss late-time power-law tails. Because of the presence of an ergoregion, waves in a rotating acoustic black hole can be superradiantly amplified. We also compute superradiant reflection coefficients and instability time scales for the acoustic black hole bomb, the equivalent of the Press-Teukolsky black hole bomb. Finally we discuss quasinormal modes and late-time tails in a nonrotating canonical acoustic black hole, corresponding to an incompressible, spherically symmetric (3+1)-dimensional fluid flow

  14. Synthesis and Biological Evaluation of 7-Deoxy-Epothilone Analogues

    Directory of Open Access Journals (Sweden)

    Laura M. Woods

    2017-03-01

    Full Text Available The synthesis of two deoxygenated analogues of potent epothilones is reported in an effort to analyze the relative importance of molecular conformation and ligand–target interactions to biological activity. 7-deoxy-epothilone D and 7-deoxy-(S-14-methoxy-epothilone D were prepared through total synthesis and shown to maintain the conformational preferences of their biologically active parent congeners through computer modeling and nuclear magnetic resonance (NMR studies. The significant decrease in observed potency for each compound suggests that a hydrogen bond between the C7-hydroxyl group and the tubulin binding site plays a critical role in the energetics of binding in the epothilone class of polyketides.

  15. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

    Directory of Open Access Journals (Sweden)

    Bryan L Roth

    Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

  16. Radiation protection

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    This will be a simple explanation of the reasons why CERN has to be careful about radiation protections issues, a practical guide on how to recognize radiation dangers, the monitoring systems that make sure radiation levels are well tolerable norms, and a quick summary of what radiation levels mean in terms of personal risk.

  17. Protective Clothing

    Science.gov (United States)

    1981-01-01

    Beta Glass material, originating from the Apollo program is supplied to Fyrepel by Owens-Corning and incorporated into Fyrepel's Fyretex and Beta-Mex aluminized fabrics. Fabrics are used in fire entry suits, several other types of protective suits for wear in hot industrial environments and such accessory items as heat-reflecting curtains for industrial applications.

  18. Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes

    DEFF Research Database (Denmark)

    Frølund, Sidsel; Bella, Angelo; Kristensen, Anders Skov

    2010-01-01

    -electrode voltage-clamp electrophysiology employing Xenopus laevis oocytes expressing GluA1(i) AMPA or GluN1/2A NMDA receptors. Several of the analogues showed significantly increased inhibition of the GluN1/2A NMDA receptor. Thus, an analogue containing N-(1-naphtyl)acetyl group showed an IC(50) value of 47 n...

  19. How Analogue Research Can Advance Descriptive Evaluation Theory: Understanding (and Improving) Stakeholder Dialogue

    Science.gov (United States)

    Campbell, Bernadette; Mark, Melvin M.

    2015-01-01

    Evaluation theories can be tested in various ways. One approach, the experimental analogue study, is described and illustrated in this article. The approach is presented as a method worthy to use in the pursuit of what Alkin and others have called descriptive evaluation theory. Drawing on analogue studies conducted by the first author, we…

  20. New analogues of ACPD with selective activity for group II metabotropic glutamate receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Madsen, U; Mikiciuk-Olasik, E

    1997-01-01

    In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-hom...

  1. Insulin analogues in pregnancy and specific congenital anomalies; a literature review

    NARCIS (Netherlands)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-01-01

    BACKGROUND: Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. METHODS: We performed a literature search for

  2. Rational design of a-conotoxin analogues targeting a7 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Armishaw, Christopher; Jensen, Anders Asbjørn; Balle, Thomas

    2009-01-01

    ], by introducing a range of substituents on the Pro6 residue in these toxins to probe the importance of this residue for their binding to the nAChRs. Pharmacological characterization of the toxin analogues at the alpha(7) nAChR show that while polar and charged groups on Pro6 result in analogues with significantly...

  3. Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors

    NARCIS (Netherlands)

    Mooney, Caitlin A.; Johnson, Stuart A.; 'T Hart, Peter; Quarles Van Ufford, Linda; De Haan, Cornelis A M; Moret, Ed E.; Martin, Nathaniel I.

    2014-01-01

    A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza the two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display

  4. Synthesis of new 4,6-disubstituted-1,3-oxazinan-2-one analogues

    Indian Academy of Sciences (India)

    Abstract. 1,3-Oxazinan-2-one analogues are important heterocyclic compounds having significant biologi- cal activities. This study reports the synthesis of eight new 4,6-disubstituted -1,3-oxazinan-2-one analogues from corresponding homoallylic carbamates. Homoallylic carbamates were synthesized via a three- ...

  5. Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile.

    Science.gov (United States)

    Coney, Leigh D; Maier, Larissa J; Ferris, Jason A; Winstock, Adam R; Barratt, Monica J

    2017-05-01

    This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them. An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues. Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD. LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Upgrading of analogue gamma cameras with PC based computer system

    International Nuclear Information System (INIS)

    Fidler, V.; Prepadnik, M.

    2002-01-01

    Full text: Dedicated nuclear medicine computers for acquisition and processing of images from analogue gamma cameras in developing countries are in many cases faulty and technologically obsolete. The aim of the upgrading project of International Atomic Energy Agency (IAEA) was to support the development of the PC based computer system which would cost 5.000 $ in total. Several research institutions from different countries (China, Cuba, India and Slovenia) were financially supported in this development. The basic demands for the system were: one acquisition card an ISA bus, image resolution up to 256x256, SVGA graphics, low count loss at high count rates, standard acquisition and clinical protocols incorporated in PIP (Portable Image Processing), on-line energy and uniformity correction, graphic printing and networking. The most functionally stable acquisition system tested on several international workshops and university clinics was the Slovenian one with a complete set of acquisition and clinical protocols, transfer of scintigraphic data from acquisition card to PC through PORT, count loss less than 1 % at count rate of 120 kc/s, improvement of integral uniformity index by a factor of 3-5 times, reporting, networking and archiving solutions for simple MS network or server oriented network systems (NT server, etc). More than 300 gamma cameras in 52 countries were digitized and put in the routine work. The project of upgrading the analogue gamma cameras yielded a high promotion of nuclear medicine in the developing countries by replacing the old computer systems, improving the technological knowledge of end users on workshops and training courses and lowering the maintenance cost of the departments. (author)

  7. State selective reactions of cosmic dust analogues at cryogenic temperatures

    International Nuclear Information System (INIS)

    Perry, James Samuel Anthony

    2001-01-01

    Molecular hydrogen (H 2 ) is the most abundant molecule in interstellar space. It is crucial for initiating all of the chemistry in the Interstellar Medium (ISM) and consequently plays an important role in star formation. However, the amount of H 2 believed to exist in the ISM cannot be accounted for by formation through gas-phase reactions alone. The current, widely accepted theory, is that H 2 forms on the surface of cosmic dust grains. These grains are thought to be composed of amorphous forms of carbon or silicates with temperatures of around 10 K. This thesis describes a new experiment that has been constructed to study H 2 formation on the surface of cosmic dust analogues and presents the initial experimental results. The experiment simulates, through ultra-high vacuum and the use of cryogenics, the conditions of the ISM where cosmic dust grains and H 2 molecules exist. During the experiment, a beam of atomic hydrogen is aimed at a cosmic dust analogue target. H 2 formed on the target's surface is ionised using a laser spectroscopy technique known as Resonance Enhanced Multiphoton lonisation (REMPI) and detected using time-of-flight mass spectrometry. The sensitivity of REMPI is such that H 2 molecules can be ionised in selective internal energy states. This allows the rovibrational populations of the H 2 molecules desorbing from the cosmic dust targets to be determined, providing information on the energy budget of the H 2 formation process in the ISM. Preliminary results from the experiment show that H 2 molecules formed on a diamond-like-carbon surface have a significant non-thermal population of excited vibrational and rotational energy states. (author)

  8. Natural analogues of bitumen and bituminized radioactive waste

    International Nuclear Information System (INIS)

    Hellmuth, K.-H.

    1989-07-01

    Occurrences of natural bitumen provide possibilities to identify and assess materials, processes, phenomena and conditions in nature which can serve as model cases valid also with respect to a final repository. Natural bitumens meet the basic requirements for use as natural analogues. In natural sites, processes of bitumen formation and degradation often work simultaneously. The major processes are thermal alteration, evaporation, reaction with water, biodegradation, oxidation, weathering and radiation degradation. Progress in analytical organic geochemistry made during recent years has enabled a deeper understanding of the structural and compositional effects of these processes on bitumen. This is necessary in natural analogue applications. The time scales involved in degradation processes, as observed in natural occurrences, exceed the time scales dictated by the half-lives of most important fission products in low and medium level waste by orders of magnitude. Only exposure to the weather at the surface leads to a more rapid destruction of bitumen. Trace metals in bitumen arenot released until the matrix is completely destroyed. Products of radiation degradation and weathering of bitumen are able, to a certain degree, to delay migration of the metal ions released. Impregnation with bitumen may effectively reduce the microbial decomposition of easily destructable organic waste components, as can be deduced on the basis of the excellent preservation of fossils observed in bitumen. The complexity of all the natural sites described requires extensive understanding of the origin and kind of organic material in bitumen, its maturation, migration, alteration and degradation and of the geological and tectonic evolution of the site. The latter is used for establishing the time scale

  9. A novel nucleic acid analogue shows strong angiogenic activity

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Ikuko, E-mail: tukamoto@med.kagawa-u.ac.jp [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Sakakibara, Norikazu; Maruyama, Tokumi [Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193 (Japan); Igarashi, Junsuke; Kosaka, Hiroaki [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Kubota, Yasuo [Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Tokuda, Masaaki [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Ashino, Hiromi [The Tokyo Metropolitan Institute of Medical Science, 1-6 Kamikitazawa2-chome, Setagaya-ku, Tokyo 156-8506 (Japan); Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro [Teikoku Seiyaku Co., Ltd., Sanbonmatsu, Higashikagawa, Kagawa 769-2695 (Japan); Konishi, Ryoji [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan)

    2010-09-03

    Research highlights: {yields} A novel nucleic acid analogue (2Cl-C.OXT-A, m.w. 284) showed angiogenic potency. {yields} It stimulated the tube formation, proliferation and migration of HUVEC in vitro. {yields} 2Cl-C.OXT-A induced the activation of ERK1/2 and MEK in HUVEC. {yields} Angiogenic potency in vivo was confirmed in CAM assay and rabbit cornea assay. {yields} A synthesized small angiogenic agent would have great clinical therapeutic value. -- Abstract: A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 {mu}M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.

  10. Functional and structural characteristics of anticancer peptide Pep27 analogues

    Directory of Open Access Journals (Sweden)

    Seo Youn-Kyung

    2005-07-01

    Full Text Available Abstract Background A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. Results Pep27anal2 characterized substituting (2R→W, (4E→W, (11S→W and (13Q→W in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC50 values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601. Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. Conclusion The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents.

  11. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century.

    Science.gov (United States)

    Montag, Christian; Kannen, Christopher; Lachmann, Bernd; Sariyska, Rayna; Duke, Éilish; Reuter, Martin; Markowetz, Alexander

    2015-12-01

    Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution - particularly since the advent of the smartphone - mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based applications). Of N = 3084 participants, 45% reported wearing a wristwatch and 67% used an analogue alarm clock. We observed that participants who reported using analogue zeitgebers used their mobile-/smartphone significantly less. Use of analogue zeitgebers may prove a practical tool for therapeutic and preventative interventions for problematic Internet use in an increasingly digital age.

  12. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century

    Directory of Open Access Journals (Sweden)

    Christian Montag

    2015-12-01

    Full Text Available Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution – particularly since the advent of the smartphone – mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based applications. Of N = 3084 participants, 45% reported wearing a wristwatch and 67% used an analogue alarm clock. We observed that participants who reported using analogue zeitgebers used their mobile-/smartphone significantly less. Use of analogue zeitgebers may prove a practical tool for therapeutic and preventative interventions for problematic Internet use in an increasingly digital age.

  13. Shielding biomolecules from effects of radiation by Mars analogue minerals and soils

    Science.gov (United States)

    Ertem, G.; Ertem, M. C.; McKay, C. P.; Hazen, R. M.

    2017-07-01

    Organic compounds have been delivered over time to Mars via meteorites, comets and interplanetary dust particles. The fate of organic material on the surface of Mars must be affected by the Martian environment, in particular by ultraviolet (UV) and other ionizing radiation. Penetration depth of UV radiation into soils is in the sub-millimetre to millimetre range and depends on the properties of the soil. The aim of this research is to study the possible protective role of Martian analogue minerals and soils for survivability of biomolecules against UV radiation and to compare their decomposition rates within a 1 mm-thick portion of the surface. Results demonstrated that minerals offer significant protection to biomolecules purine, pyrimidine and uracil against UV photolysis. In the absence of these minerals, organic compounds are completely degraded when subjected directly to UV photolysis equivalent to only 5 Martian day's exposure. However, similar UV exposure of organics dried from solution onto powdered calcium carbonate (calcite; CaCO3), calcium sulphate (anhydrite; CaSO4), clay-bearing Atacama dessert soil and 7 Å clay mineral kaolinite [Al2Si2O5(OH)4] results in only 1-2% loss of organics. Mixtures of purine and uracil with calcium carbonate exposed to gamma radiation of 3 Gy (3 Gray), which corresponds to approximately 15 000 days on Mars, results in up to 10% loss of organics. By contrast, these organic compounds completely decomposed upon mixing with iron oxide (Fe2O3) before UV irradiation. As the search for extinct or extant life on Mars has been identified as a goal of top priority in NASA's Mars Exploration Program and continues with several missions planned to the red planet by both NASA and the European Space Agency (ESA) in the next few decades, our findings may play a useful role in identifying optimal target sites on the Martian surface for future missions.

  14. Protection Myopia

    DEFF Research Database (Denmark)

    Laursen, Keld; Salter, Ammon; Li, Cher

    from having an orientation towards legal appropriability, we conjecture that protection myopia may lead some firms to allocate too much attention to legal appropriability, in particular when the behavioral and structural contingencies are unfavorable. Examining a panel of three successive waves......The strategies firms use to protect their intellectual property and knowledge can strongly influence their ability to capture the benefits of their innovative efforts. Using the attention-based theory, we explore positive and negative sides of legal appropriability. While asserting the benefits...... of a large-scale survey data of UK manufacturing firms, we find that an orientation towards legal appropriability is curvilinearly (taking an inverted U-shape) related to innovative performance. However, this effect is only present when the firms? product innovations are radical or when they are involved...

  15. Protective articles

    International Nuclear Information System (INIS)

    Wardley, R.B.

    1983-01-01

    This patent specification describes an article affording protection against radiation, and especially against X-rays comprising at least one flexible layer of lead filled material in an envelope of, or sandwiched between two layers of a knitted, woven or non-woven fabric preferably of synthetic fibrous material, carrying on its outer surface a coating of flexible polyurethane. The outer fabric provides a resilient, extremely tough and cut resistant covering for the relatively soft lead filled material. (author)

  16. Ribonuclease protection.

    Science.gov (United States)

    Thorvaldsen, J L; Bartolomei, M S

    2001-01-01

    The ribonuclease protection assay (RPA) is a sensitive technique for the analysis of total cellular RNA. It involves generating a specific antisense riboprobe, hybridizing the probe to total RNA, removing unprotected RNA by RNases, and finally isolating and analyzing the protected RNA on a denaturing gel. Although the RPA is somewhat more labor-intensive than Northern analysis, it has the advantage of being more sensitive (as little as 0.1 pg of target RNA can be detected with ideal hybridization conditions). RPAs are also more tolerant of partially degraded RNA (provided the area that is protected is intact). Although RPAs are not as sensitive as polymerase chain reaction (PCR)-based RNA analyses, the target RNA is analyzed directly; a reverse transcription step is not required. Finally, the RPA is quantitative as long as the probe is in excess. More important for the study of imprinted genes, the RPA can be designed to detect allele-specific expression of the target gene of interest.

  17. Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2

    Energy Technology Data Exchange (ETDEWEB)

    Calamini, Barbara; Santarsiero, Bernard D.; Boutin, Jean A.; Mesecar, Andrew D. (IdRS); (UIC)

    2008-09-12

    Melatonin exerts its biological effects through at least two transmembrane G-protein-coupled receptors, MT1 and MT2, and a lower-affinity cytosolic binding site, designated MT3. MT3 has recently been identified as QR2 (quinone reductase 2) (EC 1.10.99.2) which is of significance since it links the antioxidant effects of melatonin to a mechanism of action. Initially, QR2 was believed to function analogously to QR1 in protecting cells from highly reactive quinones. However, recent studies indicate that QR2 may actually transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage. Therefore it is hypothesized that inhibition of QR2 in certain cases may lead to protection of cells against these highly reactive species. Since melatonin is known to inhibit QR2 activity, but its binding site and mode of inhibition are not known, we determined the mechanism of inhibition of QR2 by melatonin and a series of melatonin and 5-hydroxytryptamine (serotonin) analogues, and we determined the X-ray structures of melatonin and 2-iodomelatonin in complex with QR2 to between 1.5 and 1.8 {angstrom} (1 {angstrom} = 0.1 nm) resolution. Finally, the thermodynamic binding constants for melatonin and 2-iodomelatonin were determined by ITC (isothermal titration calorimetry). The kinetic results indicate that melatonin is a competitive inhibitor against N-methyldihydronicotinamide (K{sub i} = 7.2 {mu}M) and uncompetitive against menadione (K{sub i} = 92 {mu}M), and the X-ray structures shows that melatonin binds in multiple orientations within the active sites of the QR2 dimer as opposed to an allosteric site. These results provide new insights into the binding mechanisms of melatonin and analogues to QR2.

  18. Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2.

    Science.gov (United States)

    Calamini, Barbara; Santarsiero, Bernard D; Boutin, Jean A; Mesecar, Andrew D

    2008-07-01

    Melatonin exerts its biological effects through at least two transmembrane G-protein-coupled receptors, MT1 and MT2, and a lower-affinity cytosolic binding site, designated MT3. MT3 has recently been identified as QR2 (quinone reductase 2) (EC 1.10.99.2) which is of significance since it links the antioxidant effects of melatonin to a mechanism of action. Initially, QR2 was believed to function analogously to QR1 in protecting cells from highly reactive quinones. However, recent studies indicate that QR2 may actually transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage. Therefore it is hypothesized that inhibition of QR2 in certain cases may lead to protection of cells against these highly reactive species. Since melatonin is known to inhibit QR2 activity, but its binding site and mode of inhibition are not known, we determined the mechanism of inhibition of QR2 by melatonin and a series of melatonin and 5-hydroxytryptamine (serotonin) analogues, and we determined the X-ray structures of melatonin and 2-iodomelatonin in complex with QR2 to between 1.5 and 1.8 A (1 A=0.1 nm) resolution. Finally, the thermodynamic binding constants for melatonin and 2-iodomelatonin were determined by ITC (isothermal titration calorimetry). The kinetic results indicate that melatonin is a competitive inhibitor against N-methyldihydronicotinamide (K(i)=7.2 microM) and uncompetitive against menadione (K(i)=92 microM), and the X-ray structures shows that melatonin binds in multiple orientations within the active sites of the QR2 dimer as opposed to an allosteric site. These results provide new insights into the binding mechanisms of melatonin and analogues to QR2.

  19. Purine nucleoside analogues inhibit the repair of radiation-induced potentially lethal damage in mammalian cells in culture

    International Nuclear Information System (INIS)

    Nakatsugawa, S.; Kumar, A.

    1982-01-01

    Three purine nucleoside analogues were found to be much more effective than pyrimidine nucleoside analogues in the screening of PLD repair inhibitors using X-irradiated Chinese hamster HA-1 cells. Among the three purine nucleoside analogues, 3'-dG was the most effective at a non-toxic concentration. (author)

  20. Biphasic Insulin Analogues in Type 2 Diabetes: Expert Panel Recommendations

    Directory of Open Access Journals (Sweden)

    Sema Akalın

    2011-09-01

    Full Text Available Recently, the prevalence of type 2 diabetes has reached pandemic levels all over the world, and the problem is still growing. Type 2 diabetes is a progressive disease, in which insulin resistance and decrease in beta cell function accompany obesity. Early disorder, which ensues in clinical progression of the disease, is the defect of early phase insulin secretion. Patients have already lost approximately half of their beta cell reserve at the time of diagnosis. Aims of type 2 diabetes treatment are to eliminate hyperglycemia caused by insufficient insulin secretion and/or insulin resistance, to slow down beta cell destruction/depletion, to improve concomitant metabolic problems and to prevent complications. In treatment algorithms, insulin is evaluated as a replacement therapy at the following stage after life style changes (medical nutrition therapy, exercise and oral anti-diabetic drugs (OADs options. Since beta cell depletion is present at initial stages of the disease, it transforms insulin therapy into an earlier approach in treatment stages. Premixed insulin forms are one of the proposed treatment options in patients with hyperglycemia that is not controlled by OADs. These types of insulins are developed to meet both basal and postprandial insulin requirements of patients. Currently, premixed human insulin forms are replaced by analogue insulin forms, which can mimic the physiological secretion in more acceptable manner. Biphasic analogue insulin is one of the readily available pre-mixed analogue insulin forms, an example of this, Biphasic Insulin aspart 30 which is the one of the premixed analoge insulin forms, contains 30% insulin aspart and 70% protaminated insulin aspart. Consensus recommending the individualized approach in insulin therapy implies that physicians should have more detailed information about the use of different insulin forms. Although a global consensus report about initiation, titration and intensification and the use

  1. Rough Precipitation Forecasts based on Analogue Method: an Operational System

    Science.gov (United States)

    Raffa, Mario; Mercogliano, Paola; Lacressonnière, Gwendoline; Guillaume, Bruno; Deandreis, Céline; Castanier, Pierre

    2017-04-01

    In the framework of the Climate KIC partnership, has been funded the project Wat-Ener-Cast (WEC), coordinated by ARIA Technologies, having the goal to adapt, through tailored weather-related forecast, the water and energy operations to the increased weather fluctuation and to climate change. The WEC products allow providing high quality forecast suited in risk and opportunities assessment dashboard for water and energy operational decisions and addressing the needs of sewage/water distribution operators, energy transport & distribution system operators, energy manager and wind energy producers. A common "energy water" web platform, able to interface with newest smart water-energy IT network have been developed. The main benefit by sharing resources through the "WEC platform" is the possibility to optimize the cost and the procedures of safety and maintenance team, in case of alerts and, finally to reduce overflows. Among the different services implemented on the WEC platform, ARIA have developed a product having the goal to support sewage/water distribution operators, based on a gradual forecast information system ( at 48hrs/24hrs/12hrs horizons) of heavy precipitation. For each fixed deadline different type of operation are implemented: 1) 48hour horizon, organisation of "on call team", 2) 24 hour horizon, update and confirm the "on call team", 3) 12 hour horizon, secure human resources and equipment (emptying storage basins, pipes manipulations …). More specifically CMCC have provided a statistical downscaling method in order to provide a "rough" daily local precipitation at 24 hours, especially when high precipitation values are expected. This statistical technique consists of an adaptation of analogue method based on ECMWF data (analysis and forecast at 24 hours). One of the most advantages of this technique concerns a lower computational burden and budget compared to running a Numerical Weather Prediction (NWP) model, also if, of course it provides only this

  2. Rheological and physical characteristics of crustal-scaled materials for centrifuge analogue modelling

    Science.gov (United States)

    Waffle, Lindsay; Godin, Laurent; Harris, Lyal B.; Kontopoulou, M.

    2016-05-01

    We characterize a set of analogue materials used for centrifuge analogue modelling simulating deformation at different levels in the crust simultaneously. Specifically, we improve the rheological characterization in the linear viscoelastic region of materials for the lower and middle crust, and cohesive synthetic sands without petroleum-binding agents for the upper crust. Viscoelastic materials used in centrifuge analogue modelling demonstrate complex dynamic behaviour, so viscosity alone is insufficient to determine if a material will be an effective analogue. Two series of experiments were conducted using an oscillating bi-conical plate rheometer to measure the storage and loss moduli and complex viscosities of several modelling clays and silicone putties. Tested materials exhibited viscoelastic and shear-thinning behaviour. The silicone putties and some modelling clays demonstrated viscous-dominant behaviour and reached Newtonian plateaus at strain rates centrifuge test models. These synthetic sands are recommended as analogues for the brittle upper crust. These new results increase the accuracy of scaling analogue models to prototype. Additionally, with the characterization of three new materials, we propose a complete lithospheric profile of analogue materials for centrifuge modelling, allowing future studies to replicate a broader range of crustal deformation behaviours.

  3. Labelling and evaluation of new stabilised neurotensin (8-13) analogues for SPET

    International Nuclear Information System (INIS)

    Chavatte, K.; Terriere, D.; Jeannin, L.

    1998-01-01

    Neurotensin (8-13) analogues were biologically stabilised by replacement of the peptide bond between amino acids 8 and 9 by the reduced ψ(CH 2 -NH) isostere. DTPA analogues for In-111 labelling and 2-bromo-phenyl-acetyl analogues for radioiodination, showed receptor affinities in the low nanomolar range in combination with a biological half live in human plasma up to 275 minutes. Biodistribution studies in male Wistar rats of metabolically stabilised and non-stabilised 111 In-DTPA-NT(8-13) analogues showed a major clearance from the blood through the kidneys. 125 I-labelled Neurotensin (8-13) analogues showed accumulation up to 2.2% of the injected dose per g tissue in the liver which might be an important disadvantage when diagnosis of tumours in the gut is aimed. It is strongly suggested that stabilised neurotensin (8-13) analogues whether labelled with In-111, I-123 and the near future with Tc-99m, may act as new potential peptidergic radiopharmaceuticals for SPET diagnosis of different NT-receptor positive tumours like non-endocrine pancreas carcinoma, small cell lung carcinoma or colon adeno carcinoma. It is enticing to speculate that metabolically stabilised Neurotensin (8-13) analogues labelled with an appropriate isotope might be useful in therapy of different human cancers. (author)

  4. Large seismic source imaging from old analogue seismograms

    Science.gov (United States)

    Caldeira, Bento; Buforn, Elisa; Borges, José; Bezzeghoud, Mourad

    2017-04-01

    In this work we present a procedure to recover the ground motions by a proper digital structure, from old seismograms in analogue physical support (paper or microfilm) to study the source rupture process, by application of modern finite source inversion tools. Despite the quality that the analog data and the digitizing technologies available may have, recover the ground motions with the accurate metrics from old seismograms, is often an intricate procedure. Frequently the general parameters of the analogue instruments response that allow recover the shape of the ground motions (free periods and damping) are known, but the magnification that allow recover the metric of these motions is dubious. It is in these situations that the procedure applies. The procedure is based on assign of the moment magnitude value to the integral of the apparent Source Time Function (STF), estimated by deconvolution of a synthetic elementary seismogram from the related observed seismogram, corrected with an instrument response affected by improper magnification. Two delicate issues in the process are 1) the calculus of the synthetic elementary seismograms that must consider later phases if applied to large earthquakes (the portions of signal should be 3 or 4 times larger than the rupture time) and 2) the deconvolution to calculate the apparent STF. In present version of the procedure was used the Direct Solution Method to compute the elementary seismograms and the deconvolution was processed in time domain by an iterative algorithm that allow constrains the STF to stay positive and time limited. The method was examined using synthetic data to test the accuracy and robustness. Finally, a set of 17 real old analog seismograms from the Santa Maria (Azores) 1939 earthquake (Mw=7.1) was used in order to recover the waveforms in the required digital structure, from which by inversion allows compute the finite source rupture model (slip distribution). Acknowledgements: This work is co

  5. Meglitinide analogues in the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Landgraf, R

    2000-11-01

    Type 2 diabetes mellitus is a complex heterogenous metabolic disorder in which peripheral insulin resistance and impaired insulin release are the main pathogenetic factors. The rapid response of the pancreatic beta-cells to glucose is already markedly disturbed in the early stages of type 2 diabetes mellitus. The consequence is often postprandial hyperglycaemia, which seems to be extremely important in the development of secondary complications, especially macrovascular disease. Therefore one of the main aims of treatment is to minimise blood glucose oscillations and attain near-normal glycosylated haemoglobin levels. Meglitinide analogues belong to a new family of insulin secretagogues which stimulate insulin release by inhibiting ATP-sensitive potassium channels of the beta-cell membrane via binding to a receptor distinct from that of sulphonylureas (SUR1/KIR 6.2). The pharmacokinetic and pharmacodynamic properties of repaglinide, the first drug of these new antihyperglycaemic agents on the market, and of nateglinide, which will be available soon, differ markedly from the currently used sulphonylureas [mainly glibenclamide (glyburide) and glimepiride]. Repaglinide and nateglinide are absorbed rapidly, stimulate insulin release within a few minutes, are rapidly metabolised in the liver and are mainly excreted in the bile. Therefore, following preprandial administration of these drugs, insulin is more readily available during and just after the meal. This leads to a significant reduction in postprandial hyperglycaemia without the danger of hypoglycaemia between meals. The short action of these compounds and biliary elimination makes repaglinide and nateglinide especially suitable for patients with type 2 diabetes mellitus who would like to have a more flexible lifestyle, need more flexibility because of unplanned eating behaviour (e.g. geriatric patients) or in whom one of the other first-line antidiabetic drugs, i.e. metformin, is strictly contraindicated (e

  6. The Greenland Analogue Project (GAP). Literature review of hydrogeology/ hydrogeochemistry

    International Nuclear Information System (INIS)

    Wallroth, Thomas; Lokrantz, Hanna; Rimsa, Andrius

    2010-09-01

    This report is produced as part of the Greenland Analogue Project (GAP), carried out as a collaboration project with the Canadian Nuclear Waste Management Organization (NWMO), Posiva Oy and the Swedish Nuclear Fuel and Waste Management Co (SKB). The overall aim of the project is to improve the current understanding of hydrogeological and hydrogeochemical processes associated with continental-scale glacial periods including with the presence of permafrost and the advance/retreat of ice sheets. The project will focus on studying how an ice sheet affects groundwater flow and water chemistry around a deep geological repository in crystalline bedrock. The Greenland Analogue Project consists of three active sub-projects (A-C) with individual objectives. Field studies are conducted in the Kangerlussuaq region, in central Western Greenland. Sub-projects A and B collectively aim at improving the understanding of ice sheet hydrology by combining investigations on surface water processes with ice sheet drilling and instrumentation. In sub-project C, the penetration of glacial melt water into the bedrock, groundwater flow and the chemical composition of water will be studied. Main planned activities in sub-project C include drilling of a deep borehole in front of the ice sheet, in which different downhole surveys, sampling and monitoring will be carried out. The primary aim of this report is to review available information about hydrogeology and hydrogeochemistry in central Western Greenland, with special emphasis on the area around Kangerlussuaq. The relevant information about this area is however very limited, and it was decided to extend the review to briefly include studies made in other regions with similar conditions in terms of geology, climate and glaciology. The number of published studies made in other areas with glaciers, ice sheets or permafrost is very large, and the review and list of references in this report is far from complete. It is also obvious that both

  7. The Greenland Analogue Project (GAP). Literature review of hydrogeology/ hydrogeochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Wallroth, Thomas; Lokrantz, Hanna; Rimsa, Andrius (Bergab Consulting Geologists, Goeteborg (Sweden))

    2010-09-15

    This report is produced as part of the Greenland Analogue Project (GAP), carried out as a collaboration project with the Canadian Nuclear Waste Management Organization (NWMO), Posiva Oy and the Swedish Nuclear Fuel and Waste Management Co (SKB). The overall aim of the project is to improve the current understanding of hydrogeological and hydrogeochemical processes associated with continental-scale glacial periods including with the presence of permafrost and the advance/retreat of ice sheets. The project will focus on studying how an ice sheet affects groundwater flow and water chemistry around a deep geological repository in crystalline bedrock. The Greenland Analogue Project consists of three active sub-projects (A-C) with individual objectives. Field studies are conducted in the Kangerlussuaq region, in central Western Greenland. Sub-projects A and B collectively aim at improving the understanding of ice sheet hydrology by combining investigations on surface water processes with ice sheet drilling and instrumentation. In sub-project C, the penetration of glacial melt water into the bedrock, groundwater flow and the chemical composition of water will be studied. Main planned activities in sub-project C include drilling of a deep borehole in front of the ice sheet, in which different downhole surveys, sampling and monitoring will be carried out. The primary aim of this report is to review available information about hydrogeology and hydrogeochemistry in central Western Greenland, with special emphasis on the area around Kangerlussuaq. The relevant information about this area is however very limited, and it was decided to extend the review to briefly include studies made in other regions with similar conditions in terms of geology, climate and glaciology. The number of published studies made in other areas with glaciers, ice sheets or permafrost is very large, and the review and list of references in this report is far from complete. It is also obvious that both

  8. Efficacy of Antimicrobials on Bacteria Cultured in a Spaceflight Analogue

    Science.gov (United States)

    Nickerson, CA; Wotring, Virginia; Barrila, Jennifer; Crabbe, Aurelie; Castro, Sarah; Davis, Richard; Rideout, April; McCarthy, Breanne; Ott, C. Mark

    2014-01-01

    As humans travel in space, they will interact with microbial flora from themselves, other crewmembers, their food, and the environment. While evaluations of microbial ecology aboard the Mir and ISS suggest a predominance of common environmental flora, the presence of (and potential for) infectious agents has been well documented. Likewise, pathogens have been detected during preflight monitoring of spaceflight food, resulting in the disqualification of that production lot from flight. These environmental and food organisms range from the obligate pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium), which has been responsible for disqualification and removal of food destined for ISS and has previously been reported from Shuttle crew refuse, to the opportunistic pathogen Staphylococcus aureus, isolated numerous times from ISS habitable compartments and the crew. Infectious disease events have affected spaceflight missions, including an upper respiratory infection that delayed the launch of STS-36 and an incapacitating Pseudomonas aeruginosa urinary tract infection of a crewmember during Apollo 13. These observations indicate that the crew has the potential to be exposed to obligate and opportunistic pathogens. This risk of exposure is expected to increase with longer mission durations and increased use of regenerative life support systems. As antibiotics are the primary countermeasure after infection, determining if their efficacy during spaceflight missions is comparable to terrestrial application is of critical importance. The NASA Rotating Wall Vessel (RWV) culture system has been successfully used as a spaceflight culture analogue to identify potential alterations in several key microbial characteristics, such as virulence and gene regulation, in response to spaceflight culture. We hypothesized that bacteria cultured in the low fluid shear RWV environment would demonstrate changes in efficacy of antibiotics compared to higher fluid shear controls

  9. Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond.

    Science.gov (United States)

    Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei

    2016-06-08

    Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.

  10. Decoy receptor 3 analogous supplement protects steatotic rat liver from ischemia–reperfusion injury

    Directory of Open Access Journals (Sweden)

    Tzu-Hao Li

    2017-07-01

    Conclusion: Using multimodal in vivo and in vitro approaches, we found that DcR3a analogue was a potential agent to protect steatotic liver against IR injury by simultaneous blockade of the multiple IR injury-related pathogenic changes.

  11. Biocatalysis of a Paclitaxel Analogue: Conversion of Baccatin III to N-Debenzoyl-N-(2-furoyl)paclitaxel and Characterization of an Amino Phenylpropanoyl CoA Transferase.

    Science.gov (United States)

    Thornburg, Chelsea K; Walter, Tyler; Walker, Kevin D

    2017-11-07

    In this study, we demonstrate an enzyme cascade reaction using a benzoate CoA ligase (BadA), a modified nonribosomal peptide synthase (PheAT), a phenylpropanoyltransferase (BAPT), and a benzoyltransferase (NDTNBT) to produce an anticancer paclitaxel analogue and its precursor from the commercially available biosynthetic intermediate baccatin III. BAPT and NDTNBT are acyltransferases on the biosynthetic pathway to the antineoplastic drug paclitaxel in Taxus plants. For this study, we addressed the recalcitrant expression of BAPT by expressing it as a soluble maltose binding protein fusion (MBP-BAPT). Further, the preparative-scale in vitro biocatalysis of phenylisoserinyl CoA using PheAT enabled thorough kinetic analysis of MBP-BAPT, for the first time, with the cosubstrate baccatin III. The turnover rate of MBP-BAPT was calculated for the product N-debenzoylpaclitaxel, a key intermediate to various bioactive paclitaxel analogues. MBP-BAPT also converted, albeit more slowly, 10-deacetylbaccatin III to N-deacyldocetaxel, a precursor of the pharmaceutical docetaxel. With PheAT available to make phenylisoserinyl CoA and kinetic characterization of MBP-BAPT, we used Michaelis-Menten parameters of the four enzymes to adjust catalyst and substrate loads in a 200-μL one-pot reaction. This multienzyme network produced a paclitaxel analogue N-debenzoyl-N-(2-furoyl)paclitaxel (230 ng) that is more cytotoxic than paclitaxel against certain macrophage cell types. Also in this pilot reaction, the versatile N-debenzoylpaclitaxel intermediate was made at an amount 20-fold greater than the N-(2-furoyl) product. This reaction network has great potential for optimization to scale-up production and is attractive in its regioselective O- and N-acylation steps that remove protecting group manipulations used in paclitaxel analogue synthesis.

  12. Concepts of radiation protection

    International Nuclear Information System (INIS)

    2013-01-01

    This seventh chapter presents the concepts and principles of safety and radiation protection, emergency situations; NORM and TENORM; radiation protection care; radiation protection plan; activities of the radiation protection service; practical rules of radiation protection and the radiation symbol

  13. Environmental protection

    International Nuclear Information System (INIS)

    Hull, A.P.

    1979-01-01

    Environmental Studies and Internal Dosimetry projects include: Environmental Protection; 1977 Environmental Monitoring Report; Sewage Sludge Disposal on the Sanitary Landfill; Radiological Analyses of Marshall Islands Environmental Samples, 1974 to 1976; External Radiation Survey and Dose Predictions for Rongelap, Utirik, Rongerik, Ailuk, and Wotje Atolls; Marshall Islands - Diet and Life Style Study; Dose Reassessment for Populations on Rongelap and Utirik Following Exposure to Fallout from BRAVO Incident (March 1, 1954); Whole Body Counting Results from 1974 to 1979 for Bikini Island Residents; Dietary Radioactivity Intake from Bioassay Data, a Model Applied to 137 Cs Intake by Bikini Island Residents; and External Exposure Measurements at Bikini Atoll

  14. Protecting Antarctica

    Science.gov (United States)

    Carlowicz, Michael

    House Science Committee Chairman Robert Walker (R-Pa.) has introduced a bill into Congress to give the United States the legislative authority to implement the 1991 Environmental Protocol to the Antarctic Treaty. That protocol established rules and principles to shield the Antarctic environment from human spoilage—placing limits on the discharge of pollutants, protecting plant and animal life, and requiring environmental impact assessments before new activities and programs are launched. The protocol also forbids prospecting or developing of mineral resources except for scientific research.

  15. How stakeholders view the use of analogues in safety cases: PAMINA

    International Nuclear Information System (INIS)

    Atherton, Elizabeth; Bailey, Lucy

    2008-01-01

    The aim of this presentation is to provide an overview of some research that has been undertaken in the UK to investigate stakeholders' views of analogues. There are various reasons for using analogues including: to try and explain difficult concepts; to compare disposal facility features with familiar and/or natural systems; to provide an alternative, non-numerical line of reasoning to support the Safety Case conclusions; to provide evidence of behaviour over very long timescales, that cannot be achieved in the laboratory. There are some dangers when using analogues that people should be aware of: the analogue conditions may not be the same as those found in a disposal facility, so the analogue may have limited application. Some analogues may have negative implications, for example artefacts that have corroded. Analogues can be taken too far and used in inappropriate ways to try and support an assumption. So it is important to find out how stakeholders view the use of analogues in a safety case. NDA is involved in an EC funded project called Pamina (Performance Assessment Methodologies in Application). The project involves 26 partners from 11 European countries, plus other associated members and runs for 3 years from October 2006 to October 2009. The NDA is involved in several parts of the project: Exploring issues of modelling uncertainty; Evaluating effectiveness of approaches for communicating safety cases with stakeholders. NDA ran a workshop in October 2007 in Manchester. The aims of the workshop were to explore how different methods of communicating aspects of a safety case were received by stakeholders. The workshop presented stakeholders with: Examples of different repository concepts; Descriptions of barrier performance; Different ways of presenting numerical results; Use of natural analogues

  16. Identification and quantitation of cobalamin and cobalamin analogues in human feces

    Science.gov (United States)

    Allen, Robert H.; Stabler, Sally P.

    2010-01-01

    Background Cobalamin (vitamin-B12) and cobalamin analogues are present in human feces, but a complete identification has not been established, and the amounts present have not been determined. Objective We aimed to develop a liquid chromatography-mass spectrometry method for cobalamin and cobalamin analogues and to identify and quantitiate the amounts present in human feces. Design Fecal samples were obtained from 20 human subjects in good general health. The samples were analyzed for the presence and amounts of cobalamin and 12 cobalamin analogues that were synthesized with and without the incorporation of stable isotopes. Results Cobalamin and 7 cobalamin analogues were identified and quantitated in human feces. The mean for the total amount present in 18 subjects whose daily intake was ≤ 25 ug cobalamin from vitamin supplements was 1309 ng cobalamin equivalents/g wet wt of feces. Cobalamin (1.4%) and cobinamide (1.8%) (an incomplete corrinoid) represented a small portion of the total amount. Six cobalamin analogues that contain a base other than the 5,6-dimethylbenzimidizidole in cobalamin were present. The bases and their mean amounts (in %) are 2-methyladenine (60.6%), p-cresol (16.3%), adenine (12.5%), 2-(methylthio)adenine (15.5%), 5-hydroxybenzimidazole (1.8%), and phenol (0.1%). One subject ingested 1 mg cobalamin/d and another ingested 2 mg cobalamin/d, and they appeared to convert most of the cobalamin to cobinamide and the 4 analogues that contain the bases – 2-methyladenine, p-cresol, adenine and 2-(methylthio)adenine. Conclusion Cobalamin analogues are present in human feces and account for > 98% of the total of cobalamin plus cobalamin analogues. A major portion of large amounts of ingested cobalamin appears to be converted to cobalamin analogues. PMID:18469256

  17. Serotonin receptor binding affinities of several hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues.

    Science.gov (United States)

    Glennon, R A; Liebowitz, S M; Mack, E C

    1978-08-01

    Hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues are known to affect serotonergic systems both in vivo and in vitro. Using a rat stomach fundus model, the 5-HT receptor binding affinities of several of these analogues were determined and compared. The most behaviorally potent analogues examined, DOB, DOM, and 5-methoxy-N,N-dimethyltryptamine, were found to possess rather high affirmities (pA2 = 7.35, 7.12, and 7.08, respectively) for the 5-HT receptors of the model system.

  18. New analogues of Cucurbita maxima trypsin inhibitor III (CMTI III) with simplified structure.

    Science.gov (United States)

    Rolka, K; Kupryszewski, G; Rózycki, J; Ragnarsson, U; Zbyryt, T; Otlewski, J

    1992-10-01

    Seven new analogues of trypsin inhibitor CMTI III were obtained by solid-phase peptide synthesis. Three analogues contained only two, instead of three, disulfide bridges, whereas the molecules of the next four analogues were shortened at the N- and/or C-terminus. The elimination of one disulfide bridge in CMTI III induces a decrease in the association equilibrium constants by 6-7 orders of magnitude, whereas the removal of one, two or three amino-acid residues at the N- and/or C-terminus does not significantly affect the activity.

  19. Canangalias C-H, juvenile hormone III analogues from the roots of Cananga latifolia.

    Science.gov (United States)

    Phatchana, Ratchanee; Thongsri, Yordhathai; Yenjai, Chavi

    2016-10-01

    Chemical investigation of the roots of Cananga latifolia led to the isolation and purification of thirteen juvenile hormone III analogues. Six new analogues, canangalias C-H (1-6) and a new natural product, (2E,6E,10R)-10-acetoxy-11-hydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid methyl ester (7), were isolated. In addition, six known juvenile hormone III analogues were isolated. Their structures were established by spectroscopic methods including 1D and 2D NMR, IR and mass spectrometry. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

    DEFF Research Database (Denmark)

    Rabe, Patrick; Klapschinski, Tim A.; Brock, Nelson L.

    2014-01-01

    aureus and Vibrio anguillarum for a structure-activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues......Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus...... is presented and the bioactivity of the synthetic compounds is discussed....

  1. Detecting Pyrolysis Products from Bacteria in a Mars Soil Analogue

    Science.gov (United States)

    Glavin, D. P.; Cleaves, H. J.; Schubert, M.; Aubrey, A.; Buch, A.; Mahaffy, P. R.; Bada, J. L.

    2004-01-01

    One of the primary objectives of the 1976 Viking missions was to determine whether organic compounds, possibly of biological origin, were present in the Martian surface soils. The Viking gas chromatography mass spectrometry (GCMS) instruments found no evidence for any organic compounds of Martian origin above a few parts per billion in the upper 10 cm of surface soil, suggesting the absence of a widely distributed Martian biota. However, it is now known that key organic compounds important to biology, such as amino acids, carboxylic acids and nucleobases, would likely have been missed by the Viking GCMS instruments. In this study, a Mars soil analogue that was inoculated with approx. 10 billion Escherichia coli cells was heated at 500 C under Martian ambient pressure to release volatile organic compounds from the sample. The pyrolysis products were then analyzed for amino acids and nucleobases using high performance liquid chromatography (HPLC) and GCMS. Our experimental results indicate that at the part per billion level, the degradation products generated from several million bacterial cells per gram of Martian soil would not have been detected by the Viking GCMS instruments. Upcoming strategies for Mars exploration will require in-situ analyses by instruments that can assess whether any organic compounds, especially those that might be associated with life, are present in Martian surface samples.

  2. Cetalox and analogues: synthesis via acid-mediated polyene cyclizations.

    Science.gov (United States)

    Snowden, Roger L

    2008-06-01

    Using a novel, acid-mediated cyclization methodology, a direct access to Cetalox ((+/-)-1; a commercially important ambergris-type odorant) and various structurally related didehydro (i.e., 19, 26, and 30) and tetradehydro (i.e., 28 and 37/38) analogues is described. Treatment of either (E,E)-14 or (E)-15 with an excess of FSO(3)H in 2-nitropropane at -90 degrees stereospecifically afforded (+/-)-1 in 40 and 42% yield, respectively. Under similar conditions, cyclization of (E)-18 or 20 furnished 19 in 60 and 64% yield, respectively. Analogously, using an excess of ClSO(3)H in CH(2)Cl(2) at -80 degrees, 26 is formed with high stereoselectivity by cyclization of either (E)-24 or (Z)-25 (52 and 31% yield, resp.); in the same manner, 28 was prepared from 27 (22% yield). The same principle was applied to the synthesis of racemic Superambrox (30), via cyclization of 35, but only with poor selectivity (22%) and low yield (7%). Another approach via cyclization of (E)-40 under solvolysis conditions (excess TFA in CH(2)Cl(2) at -10 degrees) gave a higher yield (15%) with improved selectivity (43%). Finally, cyclization of 34 (1:1 diastereoisomer mixture) afforded 37/38 (10:1) in 27% yield. The qualitative organoleptic properties of 19, 26, 28, 30, and 37/38 (10:1) are briefly discussed.

  3. Effects of cognitive and pharmacologic strategies on analogued labor pain.

    Science.gov (United States)

    Geden, E A; Beck, N C; Anderson, J S; Kennish, M E; Mueller-Heinze, M

    1986-01-01

    Using an analogued labor pain procedure, the efficacy of combinations of five cognitive and one pharmacologic approach to pain management was examined. Nulliparous undergraduates (N = 120) were randomly assigned to 1 of 12 groups. Cognitive groups included: systematic desensitization (SYS DENS); sensory description (SEN DESC); sensory transformation (ST); modeling (M); and relaxation (R); combined groups: SYS DENS, SEN DESC, and ST; SEN DESC, ST, and R; SEN DESC, R, ST, and Demerol. Pharmacologic groups included expected Demerol, did not expect Demerol, placebo, and no treatment control. Subjects assigned to a cognitive group received two 1-hour training sessions 1 week apart. Remaining subjects were given the assigned pharmacologic treatment one-half hour prior to the exposure to the painful stimulus. Assessment of the cognitive and pharmacologic approaches were made in a 1-hour session involving twenty 80-second exposures to a laboratory pain stimulus patterned to resemble labor contractions. Dependent variables included self-reported pain, blood pressure, frontalis electromyograph, heart rate, and respiratory rate. Significant treatment by trials and treatment effects were found for self-reported pain. No other effects achieved statistical significance.

  4. Nontoxic piperamides and their synthetic analogues as novel antifouling reagents

    KAUST Repository

    Huang, Xiang-Zhong

    2014-03-25

    Bioassay-guided isolation of an acetone extract from a terrestrial plant Piper betle produced four known piperamides with potent antifouling (AF) activities, as evidenced by inhibition of settlement of barnacle cypris larvae. The AF activities of the four piperamides and 15 synthesized analogues were compared and their structure-activity relationships were probed. Among the compounds, piperoleine B and 1-[1-oxo-7-(3′,4′-methylenedioxyphenyl)-6E-heptenyl]-piperidine (MPHP) showed strong activity against settlement of cyprids of the barnacle Balanus amphitrite, having EC50 values of 1.1 ± 0.3 and 0.5 ± 0.2 μg ml-1, respectively. No toxicity against zebra fish was observed following incubation with these two compounds. Besides being non-toxic, 91% of piperoleine B-treated cyprids and 84% of MPHP-treated cyprids at a concentration of 100 μM completed normal metamorphosis in recovery bioassays, indicating that the anti-settlement effect of these two compounds was reversible. Hydrolysis and photolysis experiments indicated that MPHP could be decomposed in the marine environment. It is concluded that piperamides are promising compounds for use in marine AF coatings. © 2014 © 2014 Taylor & Francis.

  5. Phospholipid analogue distributions of Iranian isolates of candida

    International Nuclear Information System (INIS)

    Zarei Mahmoudabadi, A.; Brucker, D.B.

    2004-01-01

    The aim of this study was to analyse polar lipids of candida species isolated from Ahwas (Iran) by fast Atom bombardment mass spectrometry . Nine isolates of Candida Sp. were identified by growth at 45 d ig c , production of chlamydoconidia on cornmeal agar, colonial colour on CHROMagar Candida, germ tube production and ID 32 C kits. Then polar lipids were extracted from freeze-dried cultures and analysed using Fast Atom Bombardment Mass Spectrometry. The most intense carboxylate and phospholipid molecular species anions were of m/z 281 (C 1 8 : 1 ) and m/z 515 (PA 23:2). However, the most intense carboxylate and phospholipid analogues in Candida Parapsilosis were 292 (Un) and 555 (PA 26:3), which differed from other yeasts. Isolates were grouped by single linkage clustering based on correlation coefficient for strain pairs calculated with carboxylate and phospholipid molecular species distributions. Fast Atom Bombardment Mass Spectrometry can differentiate the C. albicans based on analysis of polar lipid distributions.These findings support that differentiation between C. albicans and other species is possible based on polar lipids

  6. Native copper as a natural analogue for copper canisters

    International Nuclear Information System (INIS)

    Marcos, N.

    1989-12-01

    This paper discusses the occurrence of native copper as found in geological formations as a stability analogue of copper canisters that are planned to be used for the disposal of spent nuclear fuel in the Finnish bedrock. A summary of several publications on native copper occurrences is presented. The present geochemical and geohydrological conditions in which copper is met with in its metallic state show that metallic copper is stable in a wide range of temperatures. At low temperatures native copper is found to be stable where groundwater has moderate pH (about 7), low Eh (< +100 mV), and low total dissolved solids, especially chloride. Microscopical and microanalytical studies were carried out on a dozen of rock samples containing native copper. The results reveal that the metal shows no significant alteration. Only the surface of copper grains is locally coated. In the oldest samples there exist small corrosion cracks; the age of the oldest samples is over 1,000 million years. A review of several Finnish groundwater studies suggests that there are places in Finland where the geohydrological conditions are favourable for native copper stability. (orig.)

  7. Implementation of Power Efficient Flash Analogue-to-Digital Converter

    Directory of Open Access Journals (Sweden)

    Taninki Sai Lakshmi

    2014-01-01

    Full Text Available An efficient low power high speed 5-bit 5-GS/s flash analogue-to-digital converter (ADC is proposed in this paper. The designing of a thermometer code to binary code is one of the exacting issues of low power flash ADC. The embodiment consists of two main blocks, a comparator and a digital encoder. To reduce the metastability and the effect of bubble errors, the thermometer code is converted into the gray code and there after translated to binary code through encoder. The proposed encoder is thus implemented by using differential cascade voltage switch logic (DCVSL to maintain high speed and low power dissipation. The proposed 5-bit flash ADC is designed using Cadence 180 nm CMOS technology with a supply rail voltage typically ±0.85 V. The simulation results include a total power dissipation of 46.69 mW, integral nonlinearity (INL value of −0.30 LSB and differential nonlinearity (DNL value of −0.24 LSB, of the flash ADC.

  8. Potential of carbon nanotube field effect transistors for analogue circuits

    Directory of Open Access Journals (Sweden)

    Khizar Hayat

    2013-11-01

    Full Text Available This Letter presents a detailed comparison of carbon nanotube field effect transistors (CNFETs and metal oxide semiconductor field effect transistors (MOSFETs with special focus on carbon nanotube FET's potential for implementing analogue circuits in the mm-wave and sub-terahertz range. The latest CNFET lithographic dimensions place it at-par with complementary metal oxide semiconductor in terms of current handling capability, whereas the forecasted improvement in the lithography enables the CNFETs to handle more than twice the current of MOSFETs. The comparison of RF parameters shows superior performance of CNFETs with a g(m, f(T and f(max of 2.7, 2.6 and 4.5 times higher, respectively. MOSFET- and CNFET-based inverter, three-stage ring oscillator and LC oscillator have been designed and compared as well. The CNFET-based inverters are found to be ten times faster, the ring oscillator demonstrates three times higher oscillation frequency and CNFET-based LC oscillator also shows improved performance than its MOSFET counterpart.

  9. Antifolate resistance and its circumvention by new analogues.

    Science.gov (United States)

    Takemura, Y; Kobayashi, H; Miyachi, H

    2001-09-01

    We have established human leukemia cell lines made resistant to various antifolate drugs and analyzed resistance mechanisms developed in these cells at the cellular and molecular levels. The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Each resistance mechanism was not necessarily induced at random, but appeared to relate to the biochemical and pharmacological properties of the drug exposed, biological dispositions of the cells, drug-exposure manners to, or culture conditions of the cells. Since it has been shown that a minor modification at the specified position of the folate structure resulted in a drastic change in its pharmacological properties, many new compounds have been rationally designed on the basis of the knowledge of relationships between structure modifications and pharmacological properties. The step-by-step approach to the development of new analogues led to the discoveries of several promising antifolate drugs such as trimetrexate and raltitrexed, which can overcome the acquired and natural resistance to methotrexate, a classical antifolate, and clinical trials of these newer classes of antifolate compounds are currently underway.

  10. Pyrazine analogues from wolf urine induced unlearned fear in rats.

    Science.gov (United States)

    Kashiwayanagi, Makoto; Miyazono, Sadaharu; Osada, Kazumi

    2017-08-01

    Urine excreted from the common grey wolf ( Canis lupus ) contains a kairomone, inducing fear-related behaviors in various mammals. Numerous fear-inducing substances activate neurons at the main and/or accessory olfactory bulb (AOB), medial and central amygdala, and hypothalamus. Our previous study showed that the mixture of pyrazine analogues (P-mix) contained in wolf urine induced avoidance and fear-related behaviors in laboratory mice and Hokkaido deer ( Cervus nippon yesoensis ), a species native to Japan. Exposure to wolf urine or P-mix induced expression of Fos, a marker of neuronal excitation, in the AOB of mice. In the present study, we explored the effects of P-mix on fear-related behaviors and Fos-expression in rats. Exposure to P-mix induced avoidance and immobilization in rats, while that to a mixture of i -amyl acetate, linalool and R(+)-limonene (O-mix), which generate floral and fruity odors, induced avoidance but not immobilization. P-mix but not O-mix increased Fos-immunoreactivity of the AOB, medial and central amygdala, and hypothalamus of rats. The present results suggest that P-mix odor induces unlearned fear-related behaviors in rats.

  11. Pyrazine analogues from wolf urine induced unlearned fear in rats

    Directory of Open Access Journals (Sweden)

    Makoto Kashiwayanagi

    2017-08-01

    Full Text Available Urine excreted from the common grey wolf (Canis lupus contains a kairomone, inducing fear-related behaviors in various mammals. Numerous fear-inducing substances activate neurons at the main and/or accessory olfactory bulb (AOB, medial and central amygdala, and hypothalamus. Our previous study showed that the mixture of pyrazine analogues (P-mix contained in wolf urine induced avoidance and fear-related behaviors in laboratory mice and Hokkaido deer (Cervus nippon yesoensis, a species native to Japan. Exposure to wolf urine or P-mix induced expression of Fos, a marker of neuronal excitation, in the AOB of mice. In the present study, we explored the effects of P-mix on fear-related behaviors and Fos-expression in rats. Exposure to P-mix induced avoidance and immobilization in rats, while that to a mixture of i-amyl acetate, linalool and R(+-limonene (O-mix, which generate floral and fruity odors, induced avoidance but not immobilization. P-mix but not O-mix increased Fos-immunoreactivity of the AOB, medial and central amygdala, and hypothalamus of rats. The present results suggest that P-mix odor induces unlearned fear-related behaviors in rats.

  12. Synthesis and metabolism of pheromones and pheromone analogues

    International Nuclear Information System (INIS)

    Ding, Y.S.

    1987-01-01

    [9, 10- 3 H 2 ]Z9-14:Ac was synthesized at high specific activity ( 3 H, 58 Ci/mmole) by partial tritiation of the corresponding alkyne and was converted to the labeled Z9-14:OH and Z9-14:Al to study tissue specificity of acetate esterase (E), alcohol oxidase (OX), and aldehyde dehydrogenase (ALDH) in male and female Heliothis virescens. Soluble and membrane-associated enzyme activities were determined by radio-TLC assays. Compounds of the tritium-labeled Z11-16 series were synthesized and their in vitro fates examined as well. In order to achieve an alternative approach in which (1) pheromone receptor proteins would be stoichiometrically and irreversibly modified, or (2) pheromone-catabolizing enzymes are inactivated by tight-binding or irreversible inhibitors, we have designed analogues of pheromones of lepidopterous insect pests and assayed their biological activity in vitro and in vivo. Various fluorinated molecules such as acyl fluorides, fluoroolefins, 2-fluoro aldehydes, 2,2-difluoro aldehydes and trifluoromethyl ketones were synthesized. The synthesis of some other functional groups such as cyclopropanones, cyclopropanols, cyclopropyl carbinols, cyclopropyl aldehydes and Michael acceptors will also be discussed

  13. Neurotoxicity Caused by the Treatment with Platinum Analogues

    Directory of Open Access Journals (Sweden)

    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  14. Potential of carbon nanotube field effect transistors for analogue circuits

    KAUST Repository

    Hayat, Khizar

    2013-05-11

    This Letter presents a detailed comparison of carbon nanotube field effect transistors (CNFETs) and metal oxide semiconductor field effect transistors (MOSFETs) with special focus on carbon nanotube FET\\'s potential for implementing analogue circuits in the mm-wave and sub-terahertz range. The latest CNFET lithographic dimensions place it at-par with complementary metal oxide semiconductor in terms of current handling capability, whereas the forecasted improvement in the lithography enables the CNFETs to handle more than twice the current of MOSFETs. The comparison of RF parameters shows superior performance of CNFETs with a g m , f T and f max of 2.7, 2.6 and 4.5 times higher, respectively. MOSFET- and CNFET-based inverter, three-stage ring oscillator and LC oscillator have been designed and compared as well. The CNFET-based inverters are found to be ten times faster, the ring oscillator demonstrates three times higher oscillation frequency and CNFET-based LC oscillator also shows improved performance than its MOSFET counterpart.

  15. Bioactivity of permselective PVA hydrogels with mixed ECM analogues.

    Science.gov (United States)

    Nafea, Eman H; Poole-Warren, Laura A; Martens, Penny J

    2015-12-01

    The presentation of multiple biological cues, which simulate the natural in vivo cell environment within artificial implants, has recently been identified as crucial for achieving complex cellular functions. The incorporation of two or more biological cues within a largely synthetic network can provide a simplified model of multifunctional ECM presentation to encapsulated cells. Therefore, the aim of this study was to examine the effects of simultaneously and covalently incorporating two dissimilar biological molecules, heparin and gelatin, within a PVA hydrogel. PVA was functionalized with 7 and 20 methacrylate functional groups per chain (FG/c) to tailor the permselectivity of UV photopolymerized hydrogels. Both heparin and gelatin were covalently incorporated into PVA at an equal ratio resulting in a final PVA:heparin:gelatin composition of 19:0.5:0.5. The combination of both heparin and gelatin within a PVA network has proven to be stable over time without compromising the PVA base characteristics including its permselectivity to different proteins. Most importantly, this combination of ECM analogues supplemented PVA with the dual functionalities of promoting cellular adhesion and sequestering growth factors essential for cellular proliferation. Multi-functional PVA hydrogels with synthetically controlled network characteristics and permselectivity show potential in various biomedical applications including artificial cell implants. © 2015 Wiley Periodicals, Inc.

  16. Robenidine Analogues as Gram-Positive Antibacterial Agents.

    Science.gov (United States)

    Abraham, Rebecca J; Stevens, Andrew J; Young, Kelly A; Russell, Cecilia; Qvist, Anastasia; Khazandi, Manouchehr; Wong, Hui San; Abraham, Sam; Ogunniyi, Abiodun D; Page, Stephen W; O'Handley, Ryan; McCluskey, Adam; Trott, Darren J

    2016-03-10

    Robenidine, 1 (2,2'-bis[(4-chlorophenyl)methylene]carbonimidic dihydrazide), was active against MRSA and VRE with MIC's of 8.1 and 4.7 μM, respectively. SAR revealed tolerance for 4-Cl isosteres with 4-F (8), 3-F (9), 3-CH3 (22), and 4-C(CH3)3 (27) (23.7-71 μM) and with 3-Cl (3), 4-CH3 (21), and 4-CH(CH3)2 (26) (8.1-13.0 μM). Imine carbon alkylation identified a methyl/ethyl binding pocket that also accommodated a CH2OH moiety (75; 2,2'-bis[1-(4-chlorophenyl)-2-hydroxyethylidene]carbonimidic dihydrazide). Analogues 1, 27 (2,2'-bis{[4-(1,1-dimethylethyl)phenyl]methylene}carbonimidic dihydrazide), and 69 (2,2'-bis[1-(4-chlorophenyl)ethylidene]carbonimidic dihydrazide hydrochloride) were active against 24 clinical MRSA and MSSA isolates. No dose-limiting cytotoxicity at ≥2× MIC or hemolysis at ≥8× MIC was observed. Polymyxin B addition engendered Escherichia coli and Pseudomonas aeruginosa Gram-negative activity MIC's of 4.2-21.6 μM. 1 and 75 displayed excellent microsomal stability, intrinsic clearance, and hepatic extraction ratios with T1/2 > 247 min, CLint < 7 μL/min/mg protein, and EH < 0.22 in both human and mouse liposomes for 1 and in human liposomes for 75.

  17. Synthesis and Properties of Group IV Graphane Analogues

    Science.gov (United States)

    Goldberger, Joshua

    Similar to how carbon networks can be sculpted into low-dimensional allotropes such as fullerenes, nanotubes, and graphene with fundamentally different properties, it is possible to create similar ligand terminated sp3-hybridized honeycomb graphane derivatives containing Ge or Sn that feature unique and tunable properties. Here, we will describe our recent success in the creation of hydrogen and organic-terminated group IV graphane analogues, from the topochemical deintercalation of precursor Zintl phases, such as CaGe2. We will discuss how the optical, electronic, and thermal properties of these materials can be systematically controlled by substituting either the surface ligand or via alloying with other Group IV elements. Additionally, we have also developed an epitopotaxial approach for integrating precise thicknesses of germanane layers onto Ge wafers that combines the epitaxial deposition of CaGe2 precursor phases with the topotactic interconversion into the 2D material. Finally, we will describe our recent efforts on the synthesis and crystal structures of Sn-containing graphane alloys in order to access novel topological phenomena predicted to occur in these graphanes.

  18. Human sperm swimming in a high viscosity mucus analogue.

    Science.gov (United States)

    Ishimoto, Kenta; Gadêlha, Hermes; Gaffney, Eamonn A; Smith, David J; Kirkman-Brown, Jackson

    2018-02-17

    Remarkably, mammalian sperm maintain a substantive proportion of their progressive swimming speed within highly viscous fluids, including those of the female reproductive tract. Here, we analyse the digital microscopy of a human sperm swimming in a highly viscous, weakly elastic mucus analogue. We exploit principal component analysis to simplify its flagellar beat pattern, from which boundary element calculations are used to determine the time-dependent flow field around the sperm cell. The sperm flow field is further approximated in terms of regularized point forces, and estimates of the mechanical power consumption are determined, for comparison with analogous low viscosity media studies. This highlights extensive differences in the structure of the flows surrounding human sperm in different media, indicating how the cell-cell and cell-boundary hydrodynamic interactions significantly differ with the physical microenvironment. The regularized point force decomposition also provides cell-level information that may ultimately be incorporated into sperm population models. We further observe indications that the core feature in explaining the effectiveness of sperm swimming in high viscosity media is the loss of cell yawing, which is related with a greater density of regularized point force singularities along the axis of symmetry of the flagellar beat to represent the flow field. In turn this implicates a reduction of the wavelength of the distal beat pattern - and hence dynamical wavelength selection of the flagellar beat - as the dominant feature governing the effectiveness of sperm swimming in highly viscous media. Copyright © 2018. Published by Elsevier Ltd.

  19. Bead-Based Microfluidic Sediment Analogues: Fabrication and Colloid Transport.

    Science.gov (United States)

    Guo, Yang; Huang, Jingwei; Xiao, Feng; Yin, Xiaolong; Chun, Jaehun; Um, Wooyong; Neeves, Keith B; Wu, Ning

    2016-09-13

    Mobile colloids can act as carriers for low-solubility contaminants in the environment. However, the dominant mechanism for this colloid-facilitated transport of chemicals is unclear. Therefore, we developed a bead-based microfluidic platform of sediment analogues and measured both single and population transport of model colloids. The porous medium is assembled through a bead-by-bead injection method. This approach has the versatility to build both electrostatically homogeneous and heterogeneous media at the pore scale. A T-junction at the exit also allowed for encapsulation and enumeration of colloids effluent at single particle resolution to give population dynamics. Tortuosity calculated from pore-scale trajectory analysis and its comparison with lattice Boltzmann simulations revealed that transport of colloids was influenced by the size exclusion effect. The porous media packed by positively and negatively charged beads into two layers showed distinctive colloidal particle retention and significant remobilization and re-adsorption of particles during water flushing. We demonstrated the potential of our method to fabricate porous media with surface heterogeneities at the pore scale. With both single and population dynamics measurement, our platform has the potential to connect pore-scale and macroscale colloid transport on a lab scale and to quantify the impact of grain surface heterogeneities that are natural in the subsurface environment.

  20. Hydrogen adsorption in thin films of Prussian blue analogue

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dali [Los Alamos National Laboratory; Ding, Vivian [Los Alamos National Laboratory; Luo, Junhua [Los Alamos National Laboratory; Currier, Robert P [Los Alamos National Laboratory; Obrey, Steve [Los Alamos National Laboratory; Zhao, Yusheng [Los Alamos National Laboratory

    2008-01-01

    Quartz crystal microbalance with dissipation (QCM-D) measurement was used to investigate the kinetics of the molecular hydrogen adsorption into thin films of prussian blue analogues - Cu{sub 3}[Co(CN){sub 6}]{sub 2} at ambient conditions. Although the equilibrium adsorption seems to be independent of the thickness, the adsorption rate substantially decreases with the thickness of the films. In addition, the reversibility of H{sub 2} adsorption into the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films was investigated. The results indicate that the Cu{sub 3}[Co(CN){sub 6}]{sub 2} maily interacts with H{sub 2} molecules physically. The highest H{sub 2} uptake by the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films is obtained when the gas phase is stagnant inside the testing cell. However, the unusual high H{sub 2} uptake obtained from the QCM-D measurement makes us question how reliable this analytic methodology is.

  1. Synthesis and metabolism of pheromones and pheromone analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.

    1987-01-01

    (9, 10-/sup 3/H/sub 2/)Z9-14:Ac was synthesized at high specific activity (/sup 3/H, 58 Ci/mmole) by partial tritiation of the corresponding alkyne and was converted to the labeled Z9-14:OH and Z9-14:Al to study tissue specificity of acetate esterase (E), alcohol oxidase (OX), and aldehyde dehydrogenase (ALDH) in male and female Heliothis virescens. Soluble and membrane-associated enzyme activities were determined by radio-TLC assays. Compounds of the tritium-labeled Z11-16 series were synthesized and their in vitro fates examined as well. In order to achieve an alternative approach in which (1) pheromone receptor proteins would be stoichiometrically and irreversibly modified, or (2) pheromone-catabolizing enzymes are inactivated by tight-binding or irreversible inhibitors, we have designed analogues of pheromones of lepidopterous insect pests and assayed their biological activity in vitro and in vivo. Various fluorinated molecules such as acyl fluorides, fluoroolefins, 2-fluoro aldehydes, 2,2-difluoro aldehydes and trifluoromethyl ketones were synthesized. The synthesis of some other functional groups such as cyclopropanones, cyclopropanols, cyclopropyl carbinols, cyclopropyl aldehydes and Michael acceptors will also be discussed.

  2. Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Science.gov (United States)

    Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

    2017-09-01

    Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  3. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues

    Directory of Open Access Journals (Sweden)

    Monika Stompor

    2016-05-01

    Full Text Available The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus. The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus and Gram-negative (Escherichia coli bacteria, fungi (Alternaria sp., and yeasts (Rhodotorula rubra, Candida albicans revealed that compounds with at least one hydroxyl group—all of them have it at the C-4 position—demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones. The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4’-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4’-methoxychalcones or its replacement by a halogen atom (−Cl, −Br, nitro group (−NO2, ethoxy group (−OCH2CH3, or aliphatic substituent (−CH3, −CH2CH3 resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4-hydroxy-4′-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra.

  4. Of mongooses and mitigation: ecological analogues to geoengineering

    International Nuclear Information System (INIS)

    Matthews, H Damon; Turner, Sarah E

    2009-01-01

    Anthropogenic global warming is a growing environmental problem resulting from unintentional human intervention in the global climate system. If employed as a response strategy, geoengineering would represent an additional intentional human intervention in the climate system, with the intent of decreasing net climate impacts. There is a rich and fascinating history of human intervention in environmental systems, with many specific examples from ecology of deliberate human intervention aimed at correcting or decreasing the impact of previous unintentionally created problems. Additional interventions do not always bring the intended results, and in many cases there is evidence that net impacts have increased with the degree of human intervention. In this letter, we report some of the examples in the scientific literature that have documented such human interventions in environmental systems, which may serve as analogues to geoengineering. We argue that a high degree of system understanding is required for increased intervention to lead to decreased impacts. Given our current level of understanding of the climate system, it is likely that the result of at least some geoengineering efforts would follow previous ecological examples where increased human intervention has led to an overall increase in negative environmental consequences.

  5. Protective Coatings

    Science.gov (United States)

    1980-01-01

    General Magnaplate Corporation's pharmaceutical machine is used in the industry for high speed pressing of pills and capsules. Machine is automatic system for molding glycerine suppositories. These machines are typical of many types of drug production and packaging equipment whose metal parts are treated with space spinoff coatings that promote general machine efficiency and contribute to compliance with stringent federal sanitation codes for pharmaceutical manufacture. Collectively known as "synergistic" coatings, these dry lubricants are bonded to a variety of metals to form an extremely hard slippery surface with long lasting self lubrication. The coatings offer multiple advantages; they cannot chip, peel or be rubbed off. They protect machine parts from corrosion and wear longer, lowering maintenance cost and reduce undesired heat caused by power-robbing friction.

  6. Fire protection

    International Nuclear Information System (INIS)

    Janetzky, E.

    1980-01-01

    Safety and fire prevention measurements have to be treated like the activities developing, planning, construction and erection. Therefore it is necessary that these measurements have to be integrated into the activities mentioned above at an early stage in order to guarantee their effectiveness. With regard to fire accidents the statistics of the insurance companies concerned show that the damage caused increased in the last years mainly due to high concentration of material. Organization of fire prevention and fire fighting, reasons of fire break out, characteristics and behaviour of fire, smoke and fire detection, smoke and heat venting, fire extinguishers (portable and stationary), construction material in presence of fire, respiratory protection etc. will be discussed. (orig./RW)

  7. Protective clothing

    International Nuclear Information System (INIS)

    Winnett, G.F.

    1979-01-01

    A protective suit used for isolating its wearer from radioactively contaminated areas is described in three parts. The first part includes the covering for the wearer's head, arms and upper body and at the waist is releasably fitted around an opening into the contaminated area. The second part includes the legs of the suit and is releasably connectible to the first part of the suit to enclose the wearer who is then supplied with air through an umbilical pipe. A further part surrounds the second part and is releasably connectible to it, enclosing a space between the parts. This further part is also releasably connectible to the opening at the waist to prevent egress from the contaminated area. The releasable connections between the parts may be bayonet type fittings or may be rotating T-shaped projections which engage in T-shaped grooves. (author)

  8. Offspring Protection

    Directory of Open Access Journals (Sweden)

    Eric T. Steiner

    2016-08-01

    Full Text Available Parental aggression, that is, offspring protection aggression, can be viewed as a type of parental investment. Most mammalian males do not exhibit parental investment and therefore exhibit little, if any, parental aggression. Men demonstrate parental investment, and are typically more physically aggressive than women, but parental physical aggression in humans has been largely unexplored. The current study examined potential sex differences in estimates of parental physical aggression involving hypothetical situations, while controlling for general physical aggression. A self-report measure was administered to 217 students from a western U.S. university (55 male nonparents, 50 female nonparents, 54 fathers, and 58 mothers. Male nonparents reported higher parental physical aggression than female nonparents, but there was no difference between mothers and fathers. The results are interpreted in light of ancestral effects of sexual selection and proximal effects of sex differences in testosterone, risk taking, and fear aversion.

  9. Multidisciplinary integrated field campaign to an acidic Martian Earth analogue with astrobiological interest: Rio Tinto

    Czech Academy of Sciences Publication Activity Database

    Gómez, F.; Walter, N.; Amils, R.; Rull, F.; Klingelhöfer, G.; Kvíderová, Jana; Sarrazin, P.; Foing, B.; Behar, A.; Fleischer, I.; Parro, V.; Garcia-Villadangos, M.; Blake, D.; Martin-Ramos, J. D.; Direito, S.; Mahapatra, P.; Stam, C.; Venkateswaran, K.; Voytek, M.

    2011-01-01

    Roč. 10, č. 3 (2011), 291-305 ISSN 1473-5504 Institutional research plan: CEZ:AV0Z60050516 Keywords : astrobiology * extreme environments * Earth analogue Subject RIV: EF - Botanics Impact factor: 1.723, year: 2011

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

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

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

  11. Promising Strategy To Improve Charge Separation in Organic Photovoltaics : Installing Permanent Dipoles in PCBM Analogues

    NARCIS (Netherlands)

    de Gier, Hilde D.; Jahani, Fatemeh; Broer, Ria; Hummelen, Jan C.; Havenith, Remco W. A.

    2016-01-01

    A multidisciplinary approach involving organic synthesis and theoretical chemistry was applied to investigate a promising strategy to improve charge separation in organic photovoltaics: installing permanent dipoles in fullerene derivatives. First, a PCBM analogue with a permanent dipole in the side

  12. Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

    DEFF Research Database (Denmark)

    Petersen, Asger Bjørn; Andersen, Nikolaj Sten; Konotop, Gleb

    2017-01-01

    potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve...... the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation...... studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral...

  13. Physical Characterization of Synthetic Phosphatidylinositol Dimannosides and Analogues in Binary Systems with Phosphatidylcholine

    DEFF Research Database (Denmark)

    Hubert, Madlen; Larsen, David S; Hayman, Colin M

    2014-01-01

    Native phosphatidylinositol mannosides (PIMs) from the cell wall of Mycobacterium bovis (M. bovis) and synthetic analogues have been identified to exert immunostimulatory activities. These activities have been investigated using particulate delivery systems containing native mannosylated lipids o...

  14. Transient High-Temperature Processing of Silicates in Fulgurites as Analogues for Meteorite and Impact Melts

    Science.gov (United States)

    Parnell, J.; Thackrey, S.; Muirhead, D. K.; Wright, A. J.

    2008-03-01

    A fulgurite from the Sahara yielded petrographic data valuable as an analogue for highly reduced meteorite and impact melts, including iron silicide formation, devolatilization features, zircon melting and extreme melt heterogeneity.

  15. Testing safety assessment models using natural analogues in high natural-series groundwaters

    International Nuclear Information System (INIS)

    Smellie, J.; Chapman, N.; McKinley, I.; Franca, E.P.; Shea, M.

    1989-01-01

    Progress in the second year of the project is outlined in terms of four analogue objectives. Results of modelling of the preliminary data sets on groundwater chemical speciation of radionuclides, colloids, redox processes, and hydrothermal fluid transport are presented

  16. Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars; Jensen, Simon Skøde

    2009-01-01

    Two lipophilic methotrexate analogues have been synthesized and evaluated for cytotoxicity against KATO III and HT-29 human colon cancer cells. Both analogues contained a C-16-alkyl chain attached to the gamma-carboxylic acid and one of the analogues had an additional benzyl group attached...... cytotoxicity was incorporated into liposomes that were designed to be particularly Susceptible to a liposome degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high concentrations in tumors of several different cancer types. Liposome incorporation was investigated by differential...... of the MTX-liposomes against KATO III and HT-29 cancer cells was found to be independent of sPLA(2) hydrolysis, indicating that the alkylated MTX-analogue was available for cancer cell uptake even in the absence of liposome hydrolysis. Using a DSC based method for assessing the anchoring stability...

  17. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century

    OpenAIRE

    Christian Montag; Christopher Kannen; Bernd Lachmann; Rayna Sariyska; Éilish Duke; Martin Reuter; Alexander Markowetz

    2015-01-01

    Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution – particularly since the advent of the smartphone – mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based app...

  18. Long-acting lipidated analogue of human pancreatic polypeptide is slowly released into circulation

    DEFF Research Database (Denmark)

    Bellmann-Sickert, Kathrin; Elling, Christian E; Madsen, Andreas N

    2011-01-01

    The main disadvantages of peptide pharmaceuticals are their rapid degradation and excretion, their low hydrophilicity, and low shelf lifes. These bottlenecks can be circumvented by acylation with fatty acids (lipidation) or polyethylene glycol (PEGylation). Here, we describe the modification....... Lipidation resulted in prolonged action of the hPP analogue in respect of reducing food intake in mice after subcutaneous administration. Therefore, the lipidated hPP analogue could constitute a potential new therapeutic agent against obesity....

  19. Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes

    OpenAIRE

    Li Wang; Ping-Ping Shou; Si-Ping Wei; Chun Zhang; Shuang-Xun Li; Ping-Xian Liu; Xi Du; Qin Wang

    2016-01-01

    An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

  20. Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-01-01

    Full Text Available An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

  1. Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes.

    Science.gov (United States)

    Wang, Li; Shou, Ping-Ping; Wei, Si-Ping; Zhang, Chun; Li, Shuang-Xun; Liu, Ping-Xian; Du, Xi; Wang, Qin

    2016-01-19

    An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

  2. Synthesis of pyrimidine containing nucleoside β-(R/S)-hydroxyphosphonate analogues

    OpenAIRE

    Meurillon, Maïa; Chaloin, Laurent; Peyrottes, Suzanne; Périgaud, Christian

    2011-01-01

    A concise route to nucleoside β-hydroxyphosphonate analogues is described. The use of a nucleoside β-ketophosphonate as the key intermediate allowed both the (R) and (S) isomers of β-hydroxyphosphonate analogues in the pyrimidine series to be accessed. Such derivatives may be considered as stable mimics of 5′-monophosphate nucleosides and, therefore, could be the starting point for the development of potential therapeutic agents.

  3. Exploring the Patient Experience of Changes in Appetite and Diet with Incretin Analogue Therapy

    OpenAIRE

    Paisey, Rosamund May

    2014-01-01

    Incretin analogue therapies are a valuable recent treatment option for type 2 diabetes (T2D) as they can improve blood glucose control and aid weight loss. The way in which an individual recognises and responds to changes in satiety signals induced by these treatments may explain why individual response is variable. Purposive sampling of individuals with successful outcome of incretin analogue therapy (GLP-1) for T2D gathered a participant cohort 15 people with 37 years (448 months) combined ...

  4. The value of pseudo 3D techniques for the interpretation of analogue archaeological research

    OpenAIRE

    Overmars, G.; Panhuysen, R.; Börner, W.; Uhlirz, S.

    2014-01-01

    The use of virtual 3D techniques as a research tool in the interpretation of analogue archaeological data has gained little attention. The current paper will explore whether the use of 3D techniques can help to understand data from old archaeological excavations. A method is presented which facilitates the translation of analogue data into a pseudo 3D environment. One trench from the famous excavations of the early medieval trading town of Dorestad serves as a case study. This trench was exca...

  5. Inhibition of lipid peroxidation by IRFI 042, a vitamin E analogue, decreases monensin cardiotoxicity in chicks

    International Nuclear Information System (INIS)

    Calo, Margherita; Altavilla, Domenica; Seminara, Paolo; Marini, Herbert; Minutoli, Letteria; Bitto, Alessandra; Naccari, Francesco; Squadrito, Francesco

    2005-01-01

    Monensin, a well-known ionophore antibiotic, may cause severe damage in myocardial cells. We investigated whether IRFI 042, a new analogue of vitamin E, may block lipid peroxidation in myocardial cells and in turn protect against monensin toxicity. Monensin toxicity was induced by repeated daily administration of the ionophore antibiotic (150 mg/kg/day for 7 days). Sham animals received by oral gavages only a saline solution and were used as controls. All animals were randomized to receive concomitantly by oral gavages IRFI 042 (20 mg/kg) or its vehicle. The experiment lasted 8 days. Survival rate, heart lipid peroxidation, studied by means of thiobarbituric acid-reactive substances (TBARs) levels, cardiac expression of endothelial nitric oxide (e-NOS) and histological analysis of the heart were performed. Monensin administration caused a decrease in survival rate. Mortality appeared following the second monensin injection and at day 7 caused a survival rate of 20%. Thereafter, no further mortality was observed. IRFI 042 administration improved survival rate. Injection of the ionophore antibiotic resulted in a marked cardiac lipid peroxidation and in a significant reduction in cardiac e-NOS message and protein expression. IRFI 042 decreased heart TBARs levels (Monensin + vehicle = 6.5 ± 0.8 nmol/mg; Monensin + IRFI 042 = 3.2 ± 1.1 nmol/mg; P < 0.001) and increased e-NOS message and protein expression. Histological analysis showed that IRFI 042 improved myocardial cells damage and enhanced the depressed e-NOS expression in chick heart samples following monensin administration. Our data suggest that IRFI 042 is a promising drug to reduce monensin cardio-toxicity in chicks

  6. 3D Strain Modelling of Tear Fault Analogues

    Science.gov (United States)

    Hindle, D.; Vietor, T.

    2005-12-01

    Tear faults can be described as vertical discontinuities, with near fault parallel displacements terminating on some sort of shallow detachment. As such, they are difficult to study in "cross section" i.e. 2 dimensions as is often the case for fold-thrust systems. Hence, little attempt has been made to model the evolution of strain around tear faults and the processes of strain localisation in such structures due to the necessity of describing these systems in 3 dimensions and the problems this poses for both numerical and analogue modelling. Field studies suggest that strain in such regions can be distributed across broad zones on minor tear systems, which are often not easily mappable. Such strain is probably assumed to be due to distributed strain and to displacement gradients which are themselves necessary for the initiation of the tear itself. We present a numerical study of the effects of a sharp, basal discontinutiy parallel to the transport direction in a shortening wedge of material. The discontinuity is represented by two adjacent basal surfaces with strongly contrasting (0.5 and 0.05) friction coefficient. The material is modelled using PFC3D distinct element software for simulating granular material, whose properties are chosen to simulate upper crustal, sedimentary rock. The model geometry is a rectangular bounding box, 2km x 1km, and 0.35-0.5km deep, with a single, driving wall of constant velocity. We show the evolution of strain in the model in horizontal and vertical sections, and interpret strain localization as showing the spontaneous development of tear fault like features. The strain field in the model is asymmetrical, rotated towards the strong side of the model. Strain increments seem to oscillate in time, suggesting achievement of a steady state. We also note that our model cannot be treated as a critical wedge, since the 3rd dimension and the lateral variations of strength rule out this type of 2D approximation.

  7. Hypocalcemic action of the several types of salicylic acid analogues.

    Science.gov (United States)

    Kato, Y; Nishishita, K; Sakai, H; Tatsumi, M; Yamamoto, K

    1989-02-01

    The present study was performed to see the structure-activity relationships on the aspirin-induced hypocalcemia. Several kinds of salicylic acid (SA) analogues administered orally with a stomach tube. In general, the drugs were suspended in the 2% CMC solution. At the scheduled times after the treatment, 60 microliters of the blood was collected to determine the level of calcium. Aspirin, sodium salt of o-hydroxybenzoic acid (Na-salicylate), sodium salt of m- and p-hydroxybenzoic acid (HBA), 2,5-dihydroxybenzoic acid (DHBA), PAS sodium dihydrate (PAS-Na), salicylamide (SAM) and 2% CMC control were used. Hypocalcemia was induced by aspirin and Na-salicylate but not by m- and p-HBA-Na. In addition, DHBA and PAS caused hypocalcemia when they were administered intravenously but not orally. These results suggest that the carboxyl group must be adjacent to the hydroxyl group on the benzene ring to induce this type of hypocalcemia and that the SA structure would be able to induce hypocalcemia, even in the presence of the additional third substituent on the same ring. On the comparison between aspirin-DL lysine (water soluble aspirin) and SA-DL lysine, SA-DL lysine, which is not an inhibitor of PG synthetase, was more effective on the hypocalcemic action than ASP-DL lysine. The phenomenon was observed at the stage especially immediately after intravenous injection, when the acetyl group may be more responsible to acetylate the PG synthetase in the aspirin-DL lysine group. The present results seems to be consistent with the previous hypothesis that PGs are not involved in the process of aspirin-induced hypocalcemia in the rat.

  8. Design of potent substrate-analogue inhibitors of canine renin

    Science.gov (United States)

    Hui, K. Y.; Siragy, H. M.; Haber, E.

    1992-01-01

    Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.

  9. Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Armaković, Stevan, E-mail: stevan.armakovic@df.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Physics, Trg Dositeja Obradovića 4, 21000, Novi Sad (Serbia); Armaković, Sanja J. [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000, Novi Sad (Serbia); Holodkov, Vladimir [Educons University, Faculty of Sport and Tourism - TIMS, Radnička 30a, 21000, Novi Sad (Serbia); Pelemiš, Svetlana [University of East Sarajevo, Faculty of Technology, Karakaj bb, 75400, Zvornik, Republic of Srpska, Bosnia and Herzegovina (Bosnia and Herzegovina)

    2016-02-15

    We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S{sub 1}−T{sub 1}). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S{sub 1}−T{sub 1}) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S{sub 1}−T{sub 1}), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

  10. Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability.

    Science.gov (United States)

    Petersen, Asger B; Andersen, Nikolaj S; Konotop, Gleb; Hanafiah, Nur Hafzan Md; Raab, Marc S; Krämer, Alwin; Clausen, Mads H

    2017-04-21

    Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral and intravenous administration. Finally, 2'-benzylamine analogue 10 was confirmed to induce G2/M cell cycle arrest in vitro. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues with Improved Water Solubility

    Directory of Open Access Journals (Sweden)

    Ahmed K. Hamdy

    2017-01-01

    Full Text Available Griseofulvin 1 is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Study of SAR of some griseofulvin analogues has led to the identification of 2′-benzyloxy griseofulvin 3, a more potent analogue which retards tumor growth through inhibition of centrosomal clustering. However, similar to griseofulvin 1, compound 3 exhibited poor aqueous solubility. In order to improve the poor water solubility, six new griseofulvin analogues 5–10 were synthesized and tested for their antiproliferative activity and water solubility. The semicarbazone 9 and aminoguanidine 10 analogues were the most potent against HCT116 and MCF-7 cell lines. In combination studies, compound 9 was found to exert synergistic effects with tamoxifen and 5-fluorouracil against MCF-7 and HCT116 cells proliferation, respectively. The flow cytometric analysis of effect of 9 on cell cycle progression revealed G2/M arrest in HCT116. In addition, compound 9 induced apoptosis in MCF-7 cells. Finally, all synthesized analogues revealed higher water solubility than griseofulvin 1 and benzyloxy analogue 3 in pH 1.2 and 6.8 buffer solutions.

  12. From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents

    International Nuclear Information System (INIS)

    Spielvogel, B.F.; Sood, Anup; Duke Univ., Durham, NC; Shaw, B.R.; Hall, I.H.

    1991-01-01

    Isoelectronic and isostructural boron analogues of the α-amino acids ranging from simple glycine analogues such as H 3 NBH 2 COOH and Me 2 NHBH 2 COOH to alanine analogues have been synthesised. A diverse variety of analogues, including precursors and derivatives (such as peptides) have potent pharmacological activity, including anticancer, antiinflammatory, analgesic, and hypolipidemic activity in animal model studies and in vitro cell cultures. Boronated nucleosides and (oligo)nucleotides, synthetic oligonucleotide analogues of ''antisense'' agents interact with a complementary nucleic acid sequence blocking the biological effect of the target sequence. Nucleosides boronated on the pyrimidine and purine bases have been prepared. It has been established that an entirely new class of nucleic acid derivatives is feasible in which one of the non-bridging oxygens in the internucleotide phosphodiester linkage can be replaced by an isoelectronic analogue, the borane group, (BH 3 ). The boronated oligonucleotides can be viewed as hybrids of the normal oxygen oligonucleotides and the methylphosphonate oligonucleotides. (author)

  13. Creatine and creatine analogues in hypertension and cardiovascular disease

    NARCIS (Netherlands)

    Horjus, Deborah L.; Oudman, Inge; van Montfrans, Gert A.; Brewster, Lizzy M.

    2011-01-01

    The creatine kinase system, the central regulatory system of cellular energy metabolism, provides ATP in situ at ATP-ases involved in ion transport and muscle contraction. Furthermore, the enzyme system provides relative protection from tissue ischaemia and acidosis. The system could therefore be a

  14. Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Yong Son

    2013-01-01

    Full Text Available Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress, oxidative stress, and endoplasmic reticulum (ER stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1 plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

  15. Li depletion in solar analogues with exoplanets. Extending the sample

    Science.gov (United States)

    Delgado Mena, E.; Israelian, G.; González Hernández, J. I.; Sousa, S. G.; Mortier, A.; Santos, N. C.; Adibekyan, V. Zh.; Fernandes, J.; Rebolo, R.; Udry, S.; Mayor, M.

    2014-02-01

    Aims: We want to study the effects of the formation of planets and planetary systems on the atmospheric Li abundance of planet host stars. Methods: In this work we present new determinations of lithium abundances for 326 main sequence stars with and without planets in the Teff range 5600-5900 K. The 277 stars come from the HARPS sample, the remaining targets were observed with a variety of high-resolution spectrographs. Results: We confirm significant differences in the Li distribution of solar twins (Teff = T⊙ ± 80 K, log g = log g⊙ ± 0.2 and [Fe/H] = [Fe/H]⊙ ± 0.2): the full sample of planet host stars (22) shows Li average values lower than "single" stars with no detected planets (60). If we focus on subsamples with narrower ranges in metallicity and age, we observe indications of a similar result though it is not so clear for some of the subsamples. Furthermore, we compare the observed spectra of several couples of stars with very similar parameters that show differences in Li abundances up to 1.6 dex. Therefore we show that neither age, mass, nor metallicity of a parent star is the only cause for enhanced Li depletion in solar analogues. Conclusions: We conclude that another variable must account for that difference and suggest that this could be the presence of planets that causes additional rotationally induced mixing in the external layers of planet host stars. Moreover, we find indications that the amount of depletion of Li in planet-host solar-type stars is higher when the planets are more massive than Jupiter. Based on observations collected at the La Silla Observatory, ESO (Chile), with the HARPS spectrograph at the 3.6 m ESO telescope, with CORALIE spectrograph at the 1.2 m Euler Swiss telescope and with the FEROS spectrograph at the 1.52 m ESO telescope; at the Paranal Observatory, ESO (Chile), using the UVES spectrograph at the VLT/UT2 Kueyen telescope, and with the FIES, SARG, and UES spectrographs at the 2.5 m NOT, the 3.6 m TNG and the 4

  16. Alligator Rivers Analogue project. Hydrogeological modelling. Final Report - Volume 6

    Energy Technology Data Exchange (ETDEWEB)

    Townley, L.R.; Trefry, M.G.; Barr, A.D. [CSIRO Div of Water Resources, PO Wembley, WA (Australia); Braumiller, S. [Univ of Arizona, Tucson, AZ (United States). Dept of Hydrology and Water Resources; Kawanishi, M. [Central Research Institute of Electric Power Industry, Abiko-Shi, Chiba-Ken (Japan)] [and others

    1992-12-31

    This volume describes hydrogeological modelling carried out as part of the Alligator Rivers Analogue Project. Hydrogeology has played a key integrating role in the Project, largely because water movement is believed to have controlled the evolution of the Koongarra uranium Orebody and therefore affects field observations of all types at all scales. Aquifer testing described uses the concept of transmissivity in its interpretation of aquifer response to pumping. The concept of an aquifer, a layer transmitting significant quantities of water in a mainly horizontal direction, seems hard to accept in an environment as heterogeneous as that at Koongarra. But modelling of aquifers both in one dimension and two dimensionally in plan has contributed significantly to our understanding of the site. A one-dimensional model with three layers (often described as a quasi two dimensional model) was applied to flow between the Fault and Koongarra Creek. Being a transient model, this model was able to show that reverse flows can indeed occur back towards the Fault, but only if there is distributed recharge over the orebody as well as a mechanism for the Fault, or a region near the Fault, to remove water from the simulated cross-section. The model also showed clearly that the response of the three-layered system, consisting of a highly weathered zone, a fractured transmissive zone and a less conductive lower schist zone, is governed mainly by the transmissivity and storage coefficient of the middle layer. The storage coefficient of the higher layer has little effect. A two-dimensional model in plan used a description of anisotropy to show that reverse flows can also occur even without a conducting Fault. Modelling of a three-dimensional region using discrete fractures showed that it is certainly possible to simulate systems like that observed at Koongarra, but that large amounts of data are probably needed to obtain realistic descriptions of the fracture networks. Inverse modelling

  17. Alligator Rivers Analogue project. Hydrogeological modelling. Final Report - Volume 6

    International Nuclear Information System (INIS)

    Townley, L.R.; Trefry, M.G.; Barr, A.D.; Braumiller, S.

    1992-01-01

    This volume describes hydrogeological modelling carried out as part of the Alligator Rivers Analogue Project. Hydrogeology has played a key integrating role in the Project, largely because water movement is believed to have controlled the evolution of the Koongarra uranium Orebody and therefore affects field observations of all types at all scales. Aquifer testing described uses the concept of transmissivity in its interpretation of aquifer response to pumping. The concept of an aquifer, a layer transmitting significant quantities of water in a mainly horizontal direction, seems hard to accept in an environment as heterogeneous as that at Koongarra. But modelling of aquifers both in one dimension and two dimensionally in plan has contributed significantly to our understanding of the site. A one-dimensional model with three layers (often described as a quasi two dimensional model) was applied to flow between the Fault and Koongarra Creek. Being a transient model, this model was able to show that reverse flows can indeed occur back towards the Fault, but only if there is distributed recharge over the orebody as well as a mechanism for the Fault, or a region near the Fault, to remove water from the simulated cross-section. The model also showed clearly that the response of the three-layered system, consisting of a highly weathered zone, a fractured transmissive zone and a less conductive lower schist zone, is governed mainly by the transmissivity and storage coefficient of the middle layer. The storage coefficient of the higher layer has little effect. A two-dimensional model in plan used a description of anisotropy to show that reverse flows can also occur even without a conducting Fault. Modelling of a three-dimensional region using discrete fractures showed that it is certainly possible to simulate systems like that observed at Koongarra, but that large amounts of data are probably needed to obtain realistic descriptions of the fracture networks. Inverse modelling

  18. Response of Staphylococcus Aureus to a Spaceflight Analogue

    Science.gov (United States)

    Castro, S. L.; Ott, C. M.

    2010-01-01

    The decreased gravity of the spaceflight environment creates quiescent, low fluid shear conditions. This environment can impart considerable effects on the physiology of microorganisms as well as their interactions with potential hosts. Using the rotating wall vessel (RWV), as a spaceflight analogue, the consequence of low fluid shear culture on microbial pathogenesis has provided a better understanding of the risks to the astronaut crew from infectious microorganisms. While the outcome of low fluid shear culture has been investigated for several bacterial pathogens, little has been done to understand how this environmental factor affects Staphylococcus aureus. S. aureus is an opportunistic human pathogen which presents a high level of infection risk to the crew, as it has been isolated from both the space shuttle and International Space Station. Given that approximately forty percent of the population are carriers of the bacteria, eradication of this organism from in flight environments is impractical. These reasons have lead to us to assess the response of S. aureus to a reduced fluid shear environment. Culture in the RWV demonstrated that S. aureus grown under the low-shear condition had lower cell concentrations after 10 hours when compared to the control culture. Furthermore, the low-shear cultured bacteria displayed a reduction in carotenoid production, pigments responsible for their yellow/gold coloration. When exposed to various environmental stressors, post low-shear culture, a decrease in the ability to survive oxidative assault was observed compared to control cultures. The low fluid shear environment also resulted in a decrease in hemolysin secretion, a staphylococcal toxin responsible for red blood cell lysis. When challenged by the immune components present in human whole blood, low-shear cultured S. aureus demonstrated significantly reduced survival rates as compared to the control culture. Assays to determine the duration of these alterations

  19. Interaction between subducting plates: results from numerical and analogue modeling

    Science.gov (United States)

    Kiraly, Agnes; Capitanio, Fabio A.; Funiciello, Francesca; Faccenna, Claudio

    2016-04-01

    The tectonic setting of the Alpine-Mediterranean area is achieved during the late Cenozoic subduction, collision and suturing of several oceanic fragments and continental blocks. In this stage, processes such as interactions among subducting slabs, slab migrations and related mantle flow played a relevant role on the resulting tectonics. Here, we use numerical models to first address the mantle flow characteristic in 3D. During the subduction of a single plate the strength of the return flow strongly depends on the slab pull force, that is on the plate's buoyancy, however the physical properties of the slab, such as density, viscosity or width, do not affect largely the morphology of the toroidal cell. Instead, dramatic effects on the geometry and the dynamics of the toroidal cell result in models where the thickness of the mantle is varied. The vertical component of the vorticity vector is used to define the characteristic size of the toroidal cell, which is ~1.2-1.3 times the mantle depth. This latter defines the range of viscous stress propagation through the mantle and consequent interactions with other slabs. We thus further investigate on this setup where two separate lithospheric plates subduct in opposite sense, developing opposite polarities and convergent slab retreat, and model different initial sideways distance between the plates. The stress profiles in time illustrate that the plates interacts when slabs are at the characteristic distance and the two slabs toroidal cells merge. Increased stress and delayed slab migrations are the results. Analogue models of double-sided subduction show similar maximum distance and allow testing the additional role of stress propagated through the plates. We use a silicon plate subducting on its two opposite margins, which is either homogeneous or comprises oceanic and continental lithospheres, differing in buoyancy. The modeling results show that the double-sided subduction is strongly affected by changes in plate

  20. Prevention of postpartum haemorrhage with the oxytocin analogue carbetocin.

    Science.gov (United States)

    Rath, Werner

    2009-11-01

    Postpartum haemorrhage is the leading cause of maternal mortality worldwide: 67-80% of cases are caused by uterine atony. Preventive measures include prophylactic drug use to aid uterine contraction after delivery, thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin is a synthetic analogue of oxytocin with a half-life approximately 4-10 times longer than that reported for oxytocin. It combines the safety and tolerability profile of oxytocin with the sustained uterotonic activity of injectable ergot alkaloids. Furthermore, carbetocin can be administered as a single dose injection either intravenously or intramuscularly rather than as an infusion over several hours as is the case with oxytocin. Carbetocin is currently indicated for prevention of uterine atony after delivery by caesarean section in spinal or epidural anaesthesia. Data from three randomised controlled trials in caesarean delivery and a meta-analysis indicate that carbetocin significantly reduces the need for additional uterotonic agents or uterine massage to prevent excessive bleeding compared with placebo or oxytocin. The risk of headache, tremor, hypotension, flushing, nausea, abdominal pain, pruritus and feeling of warmth was similar in women who received carbetocin or oxytocin. The findings from two more recent double-blind randomised trials and one retrospective study suggest that carbetocin may also represent a good alternative to conventional uterotonic agents for prevention of postpartum haemorrhage after vaginal deliveries. A reduced need for additional uterotonics was observed with carbetocin vs. oxytocin in high-risk women and carbetocin was at least as effective as syntometrine in low-risk women. In these studies of vaginal deliveries, carbetocin was associated with a low incidence of adverse effects and demonstrated a better tolerability profile than syntometrine. Carbetocin had a long duration of action compared with intravenous oxytocin alone and a

  1. Deoxyfluoro-d-trehalose (FDTre) analogues as potential PET probes for imaging mycobacterial infection.

    Science.gov (United States)

    Rundell, Sarah R; Wagar, Zachary L; Meints, Lisa M; Olson, Claire D; O'Neill, Mara K; Piligian, Brent F; Poston, Anne W; Hood, Robin J; Woodruff, Peter J; Swarts, Benjamin M

    2016-09-28

    Mycobacterium tuberculosis, the etiological agent of human tuberculosis, requires the non-mammalian disaccharide trehalose for growth and virulence. Recently, detectable trehalose analogues have gained attention as probes for studying trehalose metabolism and as potential diagnostic imaging agents for mycobacterial infections. Of particular interest are deoxy-[(18)F]fluoro-d-trehalose ((18)F-FDTre) analogues, which have been suggested as possible positron emission tomography (PET) probes for in vivo imaging of M. tuberculosis infection. Here, we report progress toward this objective, including the synthesis and conformational analysis of four non-radioactive deoxy-[(19)F]fluoro-d-trehalose ((19)F-FDTre) analogues, as well as evaluation of their uptake by M. smegmatis. The rapid synthesis and purification of several (19)F-FDTre analogues was accomplished in high yield using a one-step chemoenzymatic method. Conformational analysis of the (19)F-FDTre analogues using NMR and molecular modeling methods showed that fluorine substitution had a negligible effect on the conformation of the native disaccharide, suggesting that fluorinated analogues may be successfully recognized and processed by trehalose metabolic machinery in mycobacteria. To test this hypothesis and to evaluate a possible route for delivery of FDTre probes specifically to mycobacteria, we showed that (19)F-FDTre analogues are actively imported into M. smegmatis via the trehalose-specific transporter SugABC-LpqY. Finally, to demonstrate the applicability of these results to the efficient preparation and use of short-lived (18)F-FDTre PET radiotracers, we carried out (19)F-FDTre synthesis, purification, and administration to M. smegmatis in 1 hour.

  2. Assessment of core protection and monitoring systems for an advanced reactor SMART

    International Nuclear Information System (INIS)

    In, Wang Kee; Hwang, Dae Hyun; Yoo, Yeon Jong; Zee, Sung Qunn

    2002-01-01

    Analogue and digital core protection/monitoring systems were assessed for the implementation in an advanced reactor. The core thermal margins to nuclear fuel design limits (departure from nucleate boiling and fuel centerline melting) were estimated using the design data for a commercial pressurized water reactor and an advanced reactor. The digital protection system resulted in a greater power margin to the fuel centerline melting by at least 30% of rated power for both commercial and advanced reactors. The DNB margin with the digital system is also higher than that for the analogue system by 8 and 12.1% of rated power for commercial and advanced reactors, respectively. The margin gain with the digital system is largely due to the on-line calculations of DNB ratio and peak local power density from the live sensor signals. The digital core protection and monitoring systems are, therefore, believed to be more appropriate for the advanced reactor

  3. The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position

    International Nuclear Information System (INIS)

    Byun, Youngjoo; Yan Junhua; Al-Madhoun, A.S.; Johnsamuel, Jayaseharan; Yang Weilian; Barth, R.F.; Eriksson, Staffan; Tjarks, Werner

    2004-01-01

    Several thymidine analogues substituted with closo- and nido-carborane at the N-3 position were synthesized. The nido-carboranyl thymidine analogues were designed to be effective substrates for human thymidine kinase 1 in combination with an increased water solubility sufficient for clinical application in boron neutron capture therapy. This was done because N-3 substituted closo-carboranyl thymidine analogues previously synthesized in our laboratories were good TK1 substrates but were poorly water-soluble. Newly synthesized zwitterionic amino nido- and the corresponding neutral closo-m-carboranyl thymidine analogues exhibited excellent TK1 phosphorylation rates up to 75% relative to thymidine, indicating that these compounds were good substrates for thymidine kinase 1. Thin layer chromatographic studies were indicative of increased hydrophilicity of the synthesized nido-carboranyl thymidine analogues compared with their closo-carboranyl counterparts and previously reported closo-carboranyl thymidine analogues

  4. Sharp phase variations from the plasmon mode causing the Rabi-analogue splitting

    Directory of Open Access Journals (Sweden)

    Wang Yujia

    2017-06-01

    Full Text Available The Rabi-analogue splitting in nanostructures resulting from the strong coupling of different resonant modes is of importance for lasing, sensing, switching, modulating, and quantum information processes. To give a clearer physical picture, the phase analysis instead of the strong coupling is provided to explain the Rabi-analogue splitting in the Fabry-Pérot (FP cavity, of which one end mirror is a metallic nanohole array and the other is a thin metal film. The phase analysis is based on an analytic model of the FP cavity, in which the reflectance and the reflection phase of the end mirrors are dependent on the wavelength. It is found that the Rabi-analogue splitting originates from the sharp phase variation brought by the plasmon mode in the FP cavity. In the experiment, the Rabi-analogue splitting is realized in the plasmonic-photonic coupling system, and this splitting can be continually tuned by changing the length of the FP cavity. These experimental results agree well with the analytic and simulation data, strongly verifying the phase analysis based on the analytic model. The phase analysis presents a clear picture to understand the working mechanism of the Rabi-analogue splitting; thus, it may facilitate the design of the plasmonic-photonic and plasmonic-plasmonic coupling systems.

  5. Accumulation of radium in relation to some chemical analogues in Dicranopteris linearis

    Energy Technology Data Exchange (ETDEWEB)

    Chao, J.H., E-mail: jhchao@mx.nthu.edu.t [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chuang, C.Y. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan (China)

    2011-01-15

    This study elucidates the uptake and accumulation of radium in the field-growing fern Dicranopteris linearis by relating the radium concentration to some potential chemical analogues, including alkaline earth metals, rare earth elements, and some important heavy metals. Time-dependent accumulation of radium and these chemical analogues for D. linearis were described by the {sup 228}Th/{sup 228}Ra activity ratio, an index for inferring plant age. The correlation between radium and these elements was assessed by statistical analysis and used as a reference to elucidate the uptake and accumulation of radium in relation to the chemical analogues. Analytical and statistical results showed that the concentrations of alkaline earth metals (except for Mg) rare earth elements and some heavy metals in D. linearis increased linearly with plant age. These elements, exhibiting a similar accumulation pattern to radium and significant correlation coefficients with radium, were considered as the chemical analogues to radium. Additionally, the plant/soil concentration ratios (CRs) for radium and most of these analogues in D. linearis exceeded 1, consistent with the definition of hyper-accumulator plants.

  6. Current insulin analogues in the treatment of diabetes: emphasis on type 2 diabetes.

    Science.gov (United States)

    Esposito, Katherine; Giugliano, Dario

    2012-02-01

    Although traditionally used as a final treatment option, early use of insulin is a therapeutic option after metformin failure in type 2 diabetes. Injection of native insulin lacks the rapid onset of action after food ingestion and the chronic maintenance of a steady-state low-level basal insulin in fasting periods. These limitations have fuelled the development of insulin analogues, which mainly fall into two different categories: short-acting and long-acting analogues. We review the recent literature investigating the efficacy and safety of insulin analogues in human diabetes, with emphasis on type 2 diabetes, as about 30% of these patients are being treated with insulin. We also examine novel developments in this area, including the new long-acting basal analogues whose longer duration of action might reduce dosing frequency to three times a week. Insulin analogues show some advantage compared with native insulin. However, improvements in reducing their pharmacological variability would be expected to lower the risk of hypoglycemia and hyperglycemia, as well as to simplify and perhaps also encourage optimal insulin titration in real-life clinical practice. Extending the duration of insulin effect would also allow for greater flexibility and potentially reduce the frequency of blood glucose monitoring.

  7. Differential Top10 promoter regulation by six tetracycline analogues in plant cells

    Science.gov (United States)

    Love, John; Allen, George C.; Gatz, Christiane; Thompson, William F.; Brown, C. S. (Principal Investigator)

    2002-01-01

    The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

  8. Induction of apoptosis in cholangiocarcinoma by an andrographolide analogue is mediated through topoisomerase II alpha inhibition.

    Science.gov (United States)

    Nateewattana, Jintapat; Dutta, Suman; Reabroi, Somrudee; Saeeng, Rungnapha; Kasemsook, Sakkasem; Chairoungdua, Arthit; Weerachayaphorn, Jittima; Wongkham, Sopit; Piyachaturawat, Pawinee

    2014-01-15

    Cholangiocarcinoma (CCA), the common primary malignant tumor of bile duct epithelial cells, is unresponsive to most chemotherapeutic drugs. Diagnosis with CCA has a poor prognosis, and therefore urgently requires effective therapeutic agents. In the present study we investigated anti-cancer effects of andrographolide analogue 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) and its mechanism in human CCA cell line KKU-M213 derived from a Thai CCA patient. By 24h after exposure, the analogue 3A.1 exhibited a potent cytotoxic effect on KKU-M213 cells with an inhibition concentration 50 (IC50) of approximately 8.0µM. Analogue 3A.1 suppressed DNA topoisomerase II α (Topo II α) protein expression, arrested the cell cycle at sub G0/G1 phase, induced cleavage of DNA repair protein poly (ADP-ribose) polymerases-1 (PARP-1), and enhanced expression of tumor suppressor protein p53 and pro-apoptotic protein Bax. In addition, analogue 3A.1 induced caspase 3 activity and inhibited cyclin D1, CDK6, and COX-2 protein expression. These results suggest that andrographolide analogue 3A.1, a novel topo II inhibitor, has significant potential to be developed as a new anticancer agent for the treatment of CCA. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Abhasnee Sobhonslidsuk

    2017-01-01

    Full Text Available Aims. Proximal renal tubular dysfunction (PRTD is an infrequent complication after nucleotide analogue therapy. We evaluated the outcomes of PRTD and nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB. Methods. A longitudinal follow-up study was performed in patients with PRTD after nucleotide analogue discontinuation. Serum and urine were collected at baseline and every 3 months for one year. The fractional excretion of phosphate (PO4, uric acid (UA, and potassium and tubular maximal reabsorption rate of PO4 to glomerular filtration rate (TmPO4/GFR were calculated. Renal losses were defined based on the criteria of substance losses. Subclinical PRTD and overt PRTD were diagnosed when 2 and ≥3 criteria were identified. Results. Eight subclinical and eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal, there were overall improvements in GFR, serum PO4, and UA. Renal loss of PO4, UA, protein, and β2-microglobulin reduced over time. At one year, complete reversal of PRTD was seen in 13 patients (81.2%. Improvements in PRTD were seen in all but one patient. Conclusion. One year after nucleotide analogue withdrawal, PRTD was resolved in most patients. Changes in TmPO4/GFR, urinary protein, and β2-microglobulin indicate that urinary biomarkers may represent an early sign of PRTD recovery.

  10. Diuretic activity of C-terminal group analogues of the insect kinins in Acheta domesticus.

    Science.gov (United States)

    Nachman, R J; Coast, G M; Holman, G M; Beier, R C

    1995-01-01

    A series of insect kinin analogues, AFFPWG-X, modified at the C-terminal group, were evaluated in a cricket Malpighian tubule secretion bioassay. The results were compared with activity profiles observed in a cockroach hindgut myotropic bioassay for these analogues. Although the replacement of the C-terminal amide group with a negatively charged acid leads to a precipitious drop in diuretic activity, it can be partially restored with the introduction of ester groups such as methyl or benzyl. The presence of branched chain character in the C-terminal group or a C-terminal alpha-carbon-amide distance spanning five methylene group spacers is incompatible with the receptor interaction required for biological activity. Significant diuretic activity is retained with four or fewer methylene groups in this region. C-terminal group analogues containing -SCH3, -NHCH2CH2OCH3, or -OCH2(C6H5) offered the greatest retention of diuretic activity while providing increased hydrophobicity and/or steric bulk. The data are of potential value in the development of mimetic analogues of this insect neuropeptide family. Mimetic analogues are potentially valuable tools to insect neuroendocrinologists studying diuresis and/or engaged in the development of future pest management strategies.

  11. Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jignesh Lunagariya

    2017-01-01

    Full Text Available Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP, and reactive oxygen species (ROS generation using flow cytometry in human breast cancer MCF-7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF-7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB-MDA-231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF-7 cells. This galaxamide analogue significantly induced apoptosis in a dose-dependent manner in MCF-7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.

  12. Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent.

    Directory of Open Access Journals (Sweden)

    Panpan Wu

    Full Text Available Ursolic acid (UA is a naturally bioactive compound that possesses potential anti-diabetic activity. The relatively safe and effective molecule intrigued us to further explore and to improve its anti-diabetic activity. In the present study, a series of novel UA analogues was synthesized and their structures were characterized. Their bioactivities against the α-glucosidase from baker's yeast were determined in vitro. The results suggested that most of the analogues exhibited significant inhibitory activity, especially analogues 8b and 9b with the IC50 values of 1.27 ± 0.27 μM (8b and 1.28 ± 0.27 μM (9b, which were lower than the other analogues and the positive control. The molecular docking and 2D-QSAR studies were carried out to prove that the C-3 hydroxyl could interact with the hydrophobic region of the active pocket and form hydrogen bonds to increase the binding affinity of ligand and the homology modelling protein. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from UA analogues.

  13. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ Formation and Increase Aβ-Degradation

    Directory of Open Access Journals (Sweden)

    Marcus O. W. Grimm

    2017-12-01

    Full Text Available Alzheimer’s disease (AD is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ, as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol on AD-relevant mechanisms. D2 and D3 analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.

  14. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation.

    Science.gov (United States)

    Grimm, Marcus O W; Thiel, Andrea; Lauer, Anna A; Winkler, Jakob; Lehmann, Johannes; Regner, Liesa; Nelke, Christopher; Janitschke, Daniel; Benoist, Céline; Streidenberger, Olga; Stötzel, Hannah; Endres, Kristina; Herr, Christian; Beisswenger, Christoph; Grimm, Heike S; Bals, Robert; Lammert, Frank; Hartmann, Tobias

    2017-12-19

    Alzheimer's disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D₂ and D₃ analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.

  15. Protective effects of veskamide, enferamide, becatamide, and oretamide on H2O2-induced apoptosis of PC-12 cells

    Science.gov (United States)

    Veskamide, enferamide, becatamide, and oretamide are phenolic amides whose analogues are found in plants. In this study, the four amides were prepared by chemical synthesis and their protective effects on H(2)O(2)-induced apoptosis in PC-12 cells were investigated. The syntheses were relatively si...

  16. Behavioral and electroencephalographic effects of delta sleep inducing peptide and its analogue on metaphit-induced audiogenic seizures in rats

    Directory of Open Access Journals (Sweden)

    Stanojlović Olivera P.

    2004-01-01

    later. Both DSIP and DSIP1-4 significantly increased the power spectra of d waves and decreased the incidence of seizures, mean seizure grade and tonic component of metaphit-induced convulsions. DISCUSSION Metaphit has been shown to induce audiogenic seizures after systemic and intracerebroventricular administration and to be truly epileptic in small rodents [8-11], although about 8 h after metaphit administration, the power spectra increased and was more intense in the period of sound onset and seizure events. Taken together, DSIP makes an optimal ratio between inhibitory and excitatory amino acid neurotransmitters and may represent one of the endogenous control systems of the brain, thus exerting the protective effect against the seizures [14,15,19]. The results obtained throughout the present study corroborate and broaden the data on prolonged antiepileptic DSIP effect. CONCLUSION The results of the present study strongly suggest that treatment of adult rats with DSIP and its analogue DSIPM should be considered as potential natural antiepileptics.

  17. Six years' experience with prostaglandin I2 infusion in elective open repair of abdominal aortic aneurysm: a parallel group observational study in a tertiary referral vascular center.

    LENUS (Irish Health Repository)

    Beirne, Chris

    2008-11-01

    The prostaglandin I(2) (PGI(2)) analogue iloprost, a potent vasodilator and inhibitor of platelet activation, has traditionally been utilized in pulmonary hypertension and off-label use for revascularization of chronic critical lower limb ischemia. This study was designed to assess the effect of 72 hr iloprost infusion on systemic ischemia post-open elective abdominal aortic aneurysm (EAAA) surgery. Between January 2000 and 2007, 104 patients undergoing open EAAA were identified: 36 had juxtarenal, 15 had suprarenal, and 53 had infrarenal aneurysms, with a mean maximal diameter of 6.9 cm. The male-to-female ratio was 2.5:1, with a mean age of 71.9 years. No statistically significant difference was seen between the study groups with regard to age, sex, risk factors, American Society of Anesthesiologists (ASA) grade, or diameter of aneurysm repaired. All emergency, urgent, and endovascular procedures for aneurysms were excluded. Fifty-seven patients received iloprost infusion for 72 hr in the immediate postoperative period compared with 47 patients who did not. Patients were monitored for signs of pulmonary, renal, cardiac, systemic ischemia, and postoperative intensive care unit (ICU) morbidity. Statistically significantly increased ventilation rates (p=0.0048), pulmonary complication rates (p=0.0019), and myocardial ischemia (p=0.0446) were noted in those patients not receiving iloprost. These patients also had significantly higher renal indices including estimate glomerular filtration rate changes (p=0.041) and postoperative urea level rises (p=0.0286). Peripheral limb trashing was noted in five patients (11.6%) in the non-iloprost group compared with no patients who received iloprost. Increased rates of transfusion requirements and bowel complications were noted in those who did not receive iloprost, with their ICU stay greater than twice that of iloprost patients. All-cause morbidity affected 67% of patients not receiving iloprost compared to 40% who did

  18. Synthesis, biological activity and solution structure of new analogues of the antimicrobial Gramicidin S.

    Science.gov (United States)

    Kamysz, Elżbieta; Mickiewicz, Beata; Kamysz, Wojciech; Bielińska, Sylwia; Rodziewicz-Motowidło, Sylwia; Ciarkowski, Jerzy

    2011-03-01

    Gramicidin S (GS) is a cyclo-decapeptide antibiotic isolated from Bacillus brevis. The structural studies have shown that GS forms a two-stranded antiparallel β-sheet imposed by two II' β-turns. Despite its wide Gram+ and Gram- antimicrobial spectrum, GS is useless in therapy because of its high hemotoxicity in humans. It was found, however, that the analogues of GS-14 (GS with 14 amino acid residues) attained a better antimicrobial selectivity when their amphipatic moments were perturbed. In this study, we report effects of similar perturbations imposed on GS cyclo-decapeptide analogues. Having solved their structures by NMR/molecular dynamics and having tested their activities/selectivities, we have concluded that the idea of perturbation of the amphipatic moment does not work for GS-10_0 analogues. An innovative approach to the synthesis of head-to-tail cyclopeptides was used. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

  19. Vacuum ultraviolet photoabsorption of prime ice analogues of Pluto and Charon

    Science.gov (United States)

    Pavithraa, S.; Lo, J.-I.; Rahul, K.; Raja Sekhar, B. N.; Cheng, B.-M.; Mason, N. J.; Sivaraman, B.

    2018-02-01

    Here we present the first Vacuum UltraViolet (VUV) photoabsorption spectra of ice analogues of Pluto and Charon ice mixtures. For Pluto the ice analogue is an icy mixture containing nitrogen (N2), carbon monoxide (CO), methane (CH4) and water (H2O) prepared with a 100:1:1:3 ratio, respectively. Photoabsorption of icy mixtures with and without H2O were recorded and no significant changes in the spectra due to presence of H2O were observed. For Charon a VUV photoabsorption spectra of an ice analogue containing ammonia (NH3) and H2O prepared with a 1:1 ratio was recorded, a spectrum of ammonium hydroxide (NH4OH) was also recorded. These spectra may help to interpret the P-Alice data from New Horizons.

  20. Immediate, non-submerged, root-analogue zirconia implant in single tooth replacement.

    Science.gov (United States)

    Pirker, W; Kocher, A

    2008-03-01

    This report demonstrates the successful clinical use of a modified root-analogue zirconia implant for immediate single tooth replacement. A right maxillary premolar was removed and a custom-made, root-analogue, roughened zirconia implant with macro-retentions in the interdental space was fabricated and placed into the extraction socket 4 days later. Four months after root implantation a composite crown was cemented. No complications occurred during the healing period. An excellent esthetic and functional result was achieved with the composite crown. No clinically noticeable bone resorption or soft-tissue recession was observed at 26 months follow up. Significant modifications such as macro-retentions seem to indicate that primary stability and excellent osseointegration of immediate root-analogue zirconia implants can be achieved, while preventing unesthetic bone resorption. The macro-retentions must be limited to the interdental space to avoid fracture of the thin buccal cortex. This successful case warrants further clinical research in well controlled trials.

  1. Design, Synthesis and Cytotoxic Evaluation of o-Carboxamido Stilbene Analogues

    Directory of Open Access Journals (Sweden)

    Mohamad Nurul Azmi

    2013-11-01

    Full Text Available Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50 = 16.68 µM, colon cancer HT-29 (IC50 = 7.51 µM and breast cancer MCF-7 (IC50 = 21.24 µM, respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.

  2. VizieR Online Data Catalog: Fe-rich silicate analogues mass absorption coeff. (Demyk+, 2017)

    Science.gov (United States)

    Demyk, K.; Meny, C.; Leroux, H.; Depecker, C.; Brubach, J.-B.; Roy, P.; Nayral, C.; Ojo, W.-S.; Delpech, F.

    2017-10-01

    The data available here are part of the Database STOPCODA where they can be retrieved too (SpecTroscopy and Optical Properties of Cosmic Dust Analogues, https://sshade.eu). See also https://blog.sshade.eu/. They contain the mass absorption coefficient of cosmic dust analogues in the spectral domain 5-1000microns and in the temperature range 300-10K. The cosmic dust analogues are amorphous silicates of composition Mg1-xFexSiO3 with x=0.1, 0.2, 0.3, 0.4. The first column is the wavenumber in cm-1, the second column is the mass absorption coefficient in cm2/g. (40 data files).

  3. Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues.

    Science.gov (United States)

    Richers, Johannes; Pöthig, Alexander; Herdtweck, Eberhardt; Sippel, Claudia; Hausch, Felix; Tiefenbacher, Konrad

    2017-03-02

    Neurotrophic natural products hold potential as privileged structures for the development of therapeutic agents against neurodegeneration. However, only a few studies have been conducted to investigate a common pharmacophoric motif and structure-activity relationships (SARs). Here, an investigation of structurally more simple analogues of neurotrophic sesquiterpenes of the illicium family is presented. A concise synthetic route enables preparation of the carbon framework of (±)-Merrilactone A and (±)-Anislactone A/B on a gram scale. This has allowed access to a series of structural analogues by modification of the core structure, including variation of oxidation levels and alteration of functional groups. In total, 15 derivatives of the natural products have been synthesized and tested for their neurite outgrowth activities. Our studies indicate that the promising biological activity can be retained by structurally simpler natural product analogues, which are accessible by a straightforward synthetic route. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Synthesis of analogues of Congo red and evaluation of their anti-prion activity.

    Science.gov (United States)

    Sellarajah, Shane; Lekishvili, Tamuna; Bowring, Claire; Thompsett, Andrew R; Rudyk, Helene; Birkett, Christopher R; Brown, David R; Gilbert, Ian H

    2004-10-21

    No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

  5. The effect of synthetic ceramide analogues on gastritis and esophagitis in rats.

    Science.gov (United States)

    Kim, Sung Hyo; Um, Seung In; Nam, Yoonjin; Park, Sun Young; Dong, Je Hyun; Ko, Sung Kwon; Sohn, Uy Dong; Lee, Sang Joon

    2016-09-01

    The effects of ceremide analogues on esophagitis and gastritis in rats were examined. Gastritis induced by indomethacin was significantly reduced after CY3325 and CY3723 treatment, whereas other analogues had no effect. The amount of malondialdehyde in gastritis was significantly reduced by CY3325 or CY 3723. CY3325 or CY 3723 decreased the glutathione levels in gastritis. The myeloperoxidase level in gastritis is increased, and its increment was decreased by CY3325 and CY3723. In reflux esophagitis, the ulceration was decreased by CY3325, CY3723. The gastric volume and acid output are reduced, whereas the pH value is increased by CY3325 or CY3723 after esophagitis. These results suggest that ceramide analogues, CY3325 and CY3723, can prevent the development of gastritis and reflux esophagitis in rats.

  6. Premenstrual Exacerbation of Life-Threatening Asthma: Effect of Gonadotrophin Releasing Hormone Analogue Therapy

    Directory of Open Access Journals (Sweden)

    Alun L Edwards

    1996-01-01

    Full Text Available Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

  7. Synthesis and biological evaluation of andrographolide analogues as anti-cancer agents.

    Science.gov (United States)

    Preet, Ranjan; Chakraborty, Biswajit; Siddharth, Sumit; Mohapatra, Purusottam; Das, Dipon; Satapathy, Shakti Ranjan; Das, Supriya; Maiti, Nakul C; Maulik, Prakas R; Kundu, Chanakya Nath; Chowdhury, Chinmay

    2014-10-06

    A new family of andrographolide analogues were synthesized and screened in vitro against kidney (HEK-293) and breast (MCF-7) cancer cells. The anti-cancer effects of the active analogues (2b, 2c and 4c) were determined by multiple cell based assays such as MTT, immunostaining, FACS, western blotting and transcriptional inhibition of NF-κB activity. Importantly, these compounds were found to possess higher anti-cancer potency than andrographolide and low toxicity to normal (VERO and MCF-10A) cells. Increased level of Bax/Bcl-xL ratio, caspase 3, and sub G1 population, higher expression level of tumor suppressor protein p53 and lower expression level of NF-κB suggested potent apoptotic property of the active analogues. Data revealed that the andrographolide derivative-mediated cell death in cancer cells was p53 dependent. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Receptor-isoform-selective insulin analogues give tissue-preferential effects

    DEFF Research Database (Denmark)

    Vienberg, Sara Gry; Bouman, Stephan D; Sørensen, Heidi

    2011-01-01

    The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can...... be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI...... (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI...

  9. Design, synthesis and exploring the quantitative structure-activity relationship of some antioxidant flavonoid analogues.

    Science.gov (United States)

    Das, Sreeparna; Mitra, Indrani; Batuta, Shaikh; Niharul Alam, Md; Roy, Kunal; Begum, Naznin Ara

    2014-11-01

    A series of flavonoid analogues were synthesized and screened for the in vitro antioxidant activity through their ability to quench 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. The activity of these compounds, measured in comparison to the well-known standard antioxidants (29-32), their precursors (38-42) and other bioactive moieties (38-42) resembling partially the flavone skeleton was analyzed further to develop Quantitative Structure-Activity Relationship (QSAR) models using the Genetic Function Approximation (GFA) technique. Based on the essential structural requirements predicted by the QSAR models, some analogues were designed, synthesized and tested for activity. The predicted and experimental activities of these compounds were well correlated. Flavone analogue 20 was found to be the most potent antioxidant. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Assessment of efficiency of application of various analogues of insulin in treatment of diabetes type 2

    Directory of Open Access Journals (Sweden)

    Rodionova T.l.

    2014-09-01

    Full Text Available Purpose: to estimate efficiency of treatment of analogues of insulin Glargin and insulin Detemir in patients with diabetes type 2. Material and methods. 147 patients with diabetes type 2 which have been initially receiving combined therapy by oral antihyperglycemic agent and NPH-insulin have been under the study. Level of glycated hemoglobin has been defined in 3 and 6 months for the general assessment of control of aglycemia. Results. According to the study the use of insulin analogues (Detemir, Glargin versus NPH insulin for 6 months allowed to reach individual target values of glycemia in 70% of patients with diabetes type 2 with a low risk of hypoglycemia. Conclusion. The use in clinical practice of modern insulin analogues and simple algorithm for dose titration, allows simulating as closely as possible the physiological insulin secretion, helping to achieve compensation of carbohydrate metabolism in larger numbers of patients in comparison with NPH insulin.

  11. MICROSCOPIC ANALOGUE OF THE LANDAU FREE ENERGY FOR THREE-DIMENSIONAL ISING-LIKE SYSTEM

    Directory of Open Access Journals (Sweden)

    I.V.Pylyuk

    2003-01-01

    Full Text Available A microscopic analogue of the Landau free energy for a three-dimensional one-component spin system is found below the critical temperature as a result of direct calculations. The obtained explicit expressions make it possible to analyse the dependence of coefficients of the analogue on temperature and microscopic parameters of the system. In contrast to the case for the Landau theory, the temperature dependence of these coefficients is nonanalytic. The quantities determining the coefficients in the expression for a microscopic analogue of the Landau free energy as well as the temperature-dependence curves for the order parameter of the system are given for different values of the effective radius of the exponentially decreasing interaction potential.

  12. Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide-Oligonucleotide Conjugates.

    Science.gov (United States)

    Taskova, Maria; Mantsiou, Anna; Astakhova, Kira

    2017-09-05

    The main objective of this work is to provide an update on synthetic nucleic acid analogues and nanoassemblies as tools in gene therapy. In particular, the synthesis and properties of peptide-oligonucleotide conjugates (POCs), which have high potential in research and as therapeutics, are described in detail. The exploration of POCs has already led to fruitful results in the treatment of neurological diseases, lung disorders, cancer, leukemia, viral, and bacterial infections. However, delivery and in vivo stability are the major barriers to the clinical application of POCs and other analogues that still have to be overcome. This review summarizes recent achievements in the delivery and in vivo administration of synthetic nucleic acid analogues, focusing on POCs, and compares their efficiency. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Experimental models, protocols, and reference values for evaluation of iodinated analogues of glucose

    International Nuclear Information System (INIS)

    Henry, C.; Koumanov, F.; Ghezzi, C.; Mathieu, J.P.; Hamant, S.; Leiris, J. de; Comet, M.

    1995-01-01

    For an iodinated analogue of glucose to be useful for evaluating glucose uptake using single-photon emission computed tomography (SPECT), it must enter the cell via the same transporter as glucose and accumulate within the cell without being degraded. The biological behavior of the iodinated tracer must therefore be similar to that of 2-deoxy-d-[1- 14 C]-glucose(2-DG). In the present study, four experimental models (biodistribution in mouse, isolated rat heart, human erythrocytes in suspension and cultured neonatal rat cardiomyocytes) have been chosen and protocols have been set up which allow for the examination of small quantities of iodinated analogues of glucose. The uptakes of 2-DG and l-[1- 14 C]-glucose have been measured in these models to establish reference values which will be compared with uptake values for iodinated analogues of glucose

  14. Synthesis and Biological Evaluation of New (−)‐Englerin Analogues

    Science.gov (United States)

    López‐Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T.

    2016-01-01

    Abstract We report the synthesis and biological evaluation of a series of (−)‐englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier‐to‐synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth‐inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC). PMID:27005578

  15. Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Grube; Frølund, Bente Flensborg; Kehler, Jan

    2011-01-01

    A 5-HT(3) receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5-HT(3) A receptor...... yielded substantial information concerning the analogues as 5-HT(3) receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5-HT(3) receptor agonist, as it does not possess...... a positively charged functionality, which is essential for the binding of all orthosteric ligands to the receptor. Preliminary investigations suggest that the compounds may exert their effects on 5-HT(3) receptors by binding to an allosteric site in the receptor complex....

  16. Field Exploration and Life Detection Sampling for Planetary Analogue Research (FELDSPAR): Variability and Correlation in Biomarker and Mineralogy Measurements from Icelandic Mars Analogues

    Science.gov (United States)

    Gentry, D.; Amador, E.; Cable, M. L.; Cantrell, T.; Chaudry, N.; Cullen, T.; Duca, Z.; Jacobsen, M.; Kirby, J.; McCaig, H.; hide

    2018-01-01

    In situ exploration of planetary environments allows biochemical analysis of sub-centimeter-scale samples; however, landing sites are selected a priori based on measurable meter- to kilometer-scale geological features. Optimizing life detection mission science return requires both understanding the expected biomarker distributions across sample sites at different scales and efficiently using first-stage in situ geochemical instruments to justify later-stage biological or chemical analysis. Icelandic volcanic regions have an extensive history as Mars analogue sites due to desiccation, low nutrient availability, and temperature extremes, in addition to the advantages of geological youth and isolation from anthropogenic contamination. Many Icelandic analogue sites are also rugged and remote enough to create the same type of instrumentation and sampling constraints typically faced by robotic exploration.

  17. The quality of processed cheeses and cheese analogues the same brand domestic and foreign production

    Directory of Open Access Journals (Sweden)

    Jana Bezeková

    2015-08-01

    Full Text Available Processed cheeses belong to Slovakia favorite dairy products. Processed cheeses are made from natural cheeses. In recent years the trend is to replace natural cheeses with other raw materials of non-dairy nature. The composition of the processed cheese analogues is not in many countries defined by legislation. The objective of this study was to determine and compare chemical properties (fat, dry matter, fat in dry matter, NaCl two samples of processed cheeses (C, D - Veselá krava and two samples cheese analogues (A, B - Kiri the same brand domestic and foreign production. The evaluated was taste of processed cheeses and cheese analogues, too. Chemical analysis and sensory analysis were repeated four times. The results of chemical analysis shows that all rated samples processed cheeses made on Slovakia fulfilled demands declared (dry matter and fat in dry matter as producers provided on the label. The most commonly fluctuate content of NaCl from 1 to 1.24 g.100g-1. The higher coefficient of variation in the determination of NaCl (3.88% was found in processed cheeses made in France. Processed cheese and cheese analogues made in France had not specified parameters for dry matter and fat in dry matter on the label. For production cheese analogues Kiri made in Slovakia was used different raw material than Kiri made in France. The taste of products was determined by descriptors - salty, slightly sweet, milky, buttery-creamy, fatty, sour, bitter, and unknown. The interesting that Kiri made in Slovakia had stronger milky and buttery-creamy taste than cheese analogue Kiri made in France. Significant differences were found in the slighty sweet taste of processed cheeses, the most points won processed cheese Veselá krava made in Slovakia.

  18. On the q-Analogues of Srivastava’s Triple Hypergeometric Functions

    Directory of Open Access Journals (Sweden)

    Thomas Ernst

    2013-04-01

    Full Text Available We find Euler integral formulas, summation and reduction formulas for q-analogues of Srivastava’s three triple hypergeometric functions. The proofs use q-analogues of Picard’s integral formula for the first Appell function, a summation formula for the first Appell function based on the Bayley–Daum formula, and a general triple series reduction formula of Karlsson. Many of the formulas are purely formal, since it is difficult to find convergence regions for these functions of several complex variables. We use the Ward q-addition to describe the known convergence regions of q-Appell and q-Lauricella functions.

  19. Dipolar Quinoidal Acene Analogues as Stable Isoelectronic Structures of Pentacene and Nonacene

    KAUST Repository

    Shi, Xueliang

    2015-10-08

    Quinoidal thia-acene analogues, as the respective isoelectronic structures of pentacene and nonacene, were synthesized and an unusual 1,2-sulfur migration was observed during the Friedel-Crafts alkylation reaction. The analogues display a closed-shell quinoidal structure in the ground state with a distinctive dipolar character. In contrast to their acene isoelectronic structures, both compounds are stable because of the existence of more aromatic sextet rings, a dipolar character, and kinetic blocking. They exhibit unique packing in single crystals resulting from balanced dipole-dipole and [C-H⋯π]/[C-H⋯S] interactions.

  20. Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

    DEFF Research Database (Denmark)

    Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral

    2012-01-01

    The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.......The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF....