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Sample records for analogue ap214 protects

  1. Radio-protective effect of some new curcumin analogues.

    PubMed

    El-Gazzar, Marwa G; Zaher, Nashwa H; El-Hossary, Ebaa M; Ismail, Amel F M

    2016-09-01

    In the present study, novel symmetrical curcumin analogues (2-7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2-7) were elucidated by elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2-7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2-7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition. PMID:27505300

  2. Protection against developmental deficiencies by a lipophilic VIP analogue.

    PubMed

    Gozes, I; Bachar, M; Bardea, A; Davidson, A; Rubinraut, S; Fridkin, M

    1998-05-01

    Stearyl-Nle-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP) exhibiting a 100-fold greater potency than the parent molecule and specificity for a receptor associated with neuronal survival. Here, the developmental and protective effects of SNV were investigated in vivo using two models of developmental retardation, hypoxia and cholinergic blockade. In both cases chronic administration of SNV during development provided protective effects. Water maze experiments on the weaned animals have demonstrated a prophylactic action for SNV and enhancement of spatial memory in animals exposed to a cholinotoxin. SNV may act by providing neuroprotection, thereby improving cognitive functions. This work is dedicated to Prof. R.J. Wurtman whose inspiration and leadership in the field of neuroscience and cognition is beyond comparison. PMID:9566607

  3. Expanding Diversity without Protecting Groups: (+)-Sclareolide to Indolosesquiterpene Alkaloid Mycoleptodiscin A and Analogues.

    PubMed

    Nagaraju, Karre; Chegondi, Rambabu; Chandrasekhar, Srivari

    2016-06-01

    Short and scalable synthesis of the complex pentacyclic indolosesquiterpene natural product mycoleptodiscin A has been achieved from commercially available diterpenoid (+)-sclareolide in 19% overall yield. This approach allows one to prepare various analogues of mycoleptodiscin using McMurry cyclization as a key reaction with just three chromatographic purifications. PMID:27181938

  4. Comparison of the structural stability and dynamic properties of recombinant anthrax protective antigen and its 2-fluorohistidine-labeled analogue.

    PubMed

    Hu, Lei; Joshi, Sangeeta B; Andra, Kiran K; Thakkar, Santosh V; Volkin, David B; Bann, James G; Middaugh, C Russell

    2012-11-01

    Protective antigen (PA) is the primary protein antigenic component of both the currently used anthrax vaccine and related recombinant vaccines under development. An analogue of recombinant PA (2-FHis rPA) has been recently shown to block the key steps of pore formation in the process of inducing cytotoxicity in cells, and thus can potentially be used as an antitoxin or a vaccine. This rPA analogue was produced by fermentation to incorporate the unnatural amino acid 2-fluorohistidine (2-FHis). In this study, the effects of 2-FHis labeling on rPA antigen's conformational stability and dynamic properties were investigated by various biophysical techniques. Temperature/pH stability profiles of rPA and 2-FHis rPA were analyzed by the empirical phase diagram (EPD) approach, and physical stability differences between them were identified. Results showed that rPA and 2-FHis rPA had similar stability at pH 7-8. With decreasing solution pH, however, 2-FHis rPA was found to be more stable. Dynamic sensitive measurements of the two proteins at pH 5 found that 2-FHis rPA was more dynamic and/or differentially hydrated under acidic pH conditions. The biophysical characterization and stability data provide information useful for the potential development of 2-FHis rPA as a more stable rPA vaccine candidate. PMID:22911632

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

    SciTech Connect

    Li, Weixin; Wu, Mingchai; Tang, Longguang; Pan, Yong; Liu, Zhiguo; Zeng, Chunlai; Wang, Jingying; Wei, Tiemin; Liang, Guang

    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

  6. Selenocysteine containing analogues of Atx1-based peptides protect cells from copper ion toxicity.

    PubMed

    Shoshan, Michal S; Lehman, Yonat; Goch, Wojciech; Bal, Wojciech; Tshuva, Edit Y; Metanis, Norman

    2016-08-01

    Seleno-substituted model peptides of copper metallochaperone proteins were analyzed for the metal affinity and in vitro anti-oxidative reactivity. An acyclic MTCXXC (X is any amino acid) reference peptide previously analyzed as a potent inhibitor of ROS production underwent substitution of the cysteine residues with selenocysteine to give two singly substituted derivatives C3U and C6U and the doubly substituted analogue C3U/C6U. Presumably due to the softer nature of Se vs. S, all selenocysteine containing peptides demonstrated high affinity to Cu(i), higher than that of the reference peptide, and in the same order of magnitude as that measured for the native protein, Atox1. A stronger impact of residue 3 confirmed previous findings on its more dominant role in metal coordination. In vitro studies on the HT-29 human colon cancer cell line, MEF mice embryonic fibroblasts, and MEF with the knocked-out Atox1 gene (Atox1-/-) consistently identified C3U/C6U as the most potent inhibitor of ROS cellular production based on the 2',7'-dichlorodihydrofluorescin diacetate (H2DCF-DA) assay, also in comparison with known drugs employed in the clinic for Wilson's disease. The selenocysteine containing peptides are thus promising drug candidates for chelation therapy of Wilson's disease and related conditions relevant to excessive copper levels. PMID:27349676

  7. Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation

    PubMed Central

    Al-Riyami, Lamyaa; Rodgers, David T.; Rzepecka, Justyna; Pineda, Miguel A.; Suckling, Colin J.; Harnett, Margaret M.; Harnett, William

    2015-01-01

    ES-62 is the major secreted protein of the rodent filarial nematode Acanthocheilonema viteae. The molecule contains covalently attached phosphorylcholine (PC) residues, which confer anti-inflammatory properties on ES-62, underpinning the idea that drugs based on this active moiety may have therapeutic potential in human diseases associated with aberrant inflammation. Here we demonstrate that two synthetic small molecule analogues (SMAs) of ES-62 termed SMA 11a and SMA 12b are protective in the oxazolone-induced acute allergic contact dermatitis mouse model of skin inflammation, as measured by a significant reduction in ear inflammation following their administration before oxazolone sensitisation and before oxazolone challenge. Furthermore, it was found that when tested, 12b was effective at reducing ear swelling even when first administered before challenge. Histological analysis of the ears showed elevated cellular infiltration and collagen deposition in oxazolone-treated mice both of which were reduced by treatment with the two SMAs. Likewise, the oxazolone-induced increase in IFNγ mRNA in the ears was reduced but no effect on other cytokines investigated was observed. Finally, no influence on the mast cell populations in the ear was observed. PMID:25836375

  8. Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological Changes in Cuprizone Model of Demyelination.

    PubMed

    Vakilzadeh, Gelareh; Khodagholi, Fariba; Ghadiri, Tahereh; Darvishi, Marzieh; Ghaemi, Amir; Noorbakhsh, Farshid; Gorji, Ali; Sharifzadeh, Mohammad

    2015-08-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease that leads to neuronal cell loss. Cyclic AMP and its analogs are well known to decrease inflammation and apoptosis. In the present study, we examined the effects of bucladesine, a cell-permeable analogue of cyclic adenosine monophosphate (cAMP), on myelin proteins (PLP, PMP-22), inflammation, and apoptotic, as well as anti-apoptotic factors in cuprizone model of demyelination. C57BL/6J mice were fed with chow containing 0.2% copper chelator cuprizone or vehicle by daily oral gavage for 5 weeks to induce reversible demyelination predominantly of the corpus callosum. Bucladesine was administered intraperitoneally at different doses (0.24, 0.48, or 0.7 μg/kg body weight) during the last 7 days of 5-week cuprizone treatment. Bucladesine exhibited a protective effect on myelination. Furthermore, bucladesine significantly decreased the production of interleukin-6 pro-inflammatory mediator as well as nuclear factor-κB activation and reduced the mean number of apoptotic cells compared to cuprizone-treated mice. Bucladesine also decreased production of caspase-3 as well as Bax and increased Bcl-2 levels. Our data revealed that enhancement of intracellular cAMP prevents demyelination and plays anti-inflammatory and anti-apoptotic properties in mice cuprizone model of demyelination. This suggests the modulation of intracellular cAMP as a potential target for treatment of MS. PMID:25128030

  9. Absence of testicular protection by a gonadotropin-releasing hormone analogue against cyclophosphamide-induced testicular cytotoxicity in the mouse.

    PubMed

    da Cunha, M F; Meistrich, M L; Nader, S

    1987-02-15

    Protection of testicular integrity against damage from cyclophosphamide (CY) by simultaneous treatment with a gonadotropin-releasing hormone (GnRH) analogue was reported in BALB/c mice (L.M. Glode et al., Lancet, 1: 1132-1134, 1981). This approach has been used as the basis for clinical trials in various treatment centers (D. H. Johnson et al., Blood, 65:832-836, 1985) in an attempt to prevent iatrogenic sterility in males. This study aims at duplicating the original findings and obtaining quantitative data on spermatogonial killing by CY, and possible protection by GnRH, of differentiating and stem cell spermatogonia. Mice were treated with 23 daily injections of 0.4 micrograms D-leucine-6 GnRH, and with 200 mg/kg CY on Days 8, 15, and 22. Three additional groups of mice received phosphate-buffered saline and bovine serum albumin only, GnRH only, and CY only. Animals were killed at 29 days after the last injection to determine the number of late spermatids in testicular homogenates, and at 56 days for histological measurement of the ratio of elongated spermatids to Sertoli cells in the tubules. The twenty-ninth day assay was a measure of damage to differentiating spermatogonia, whose killing results in temporary sterility. The fifty-sixth day point assay assessed damage to stem spermatogonia, whose killing results in long-term or permanent sterility. Sperm counts at 29 days were identical in saline-treated control mice and GnRH-treated mice; no sperm were present in the CY-treated mice, both with and without GnRH. Thus, killing of differentiating spermatogonia by CY is not prevented by GnRH treatment. Similarly, counts of spermatids at 56 days showed no difference between saline- and GnRH-treated groups; a reduction to approximately 40% of control counts was observed equally with CY and CY plus GnRH treatments. Since GnRH treatment did not alter spermatogonial kinetics in BALB/c mice, it is not surprising that it did not protect against CY-induced damage. Thus

  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.

    PubMed

    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. PMID:12816391

  11. Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage

    PubMed Central

    Hanusch, Alex Lucas; de Oliveira, Guilherme Roberto; de Sabóia-Morais, Simone Maria Teixeira; Machado, Rafael Cosme; dos Anjos, Murilo Machado; Chen Chen, Lee

    2015-01-01

    Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities. PMID:26554835

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

    PubMed

    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. PMID:26384090

  13. Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase.

    PubMed

    Deng, Chang-Bo; Li, Juan; Li, Lu-Yi; Sun, Feng-Jie

    2016-07-01

    In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50=19.4±2.5μM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury. PMID:27216999

  14. The application of the AMB protective group in the solid-phase synthesis of methylphosphonate DNA analogues.

    PubMed Central

    Kuijpers, W H; Kuyl-Yeheskiely, E; van Boom, J H; van Boeckel, C A

    1993-01-01

    Partially methylphosphonate-modified oligodeoxynucleotides were synthesized on solid-phase by employing the easily removable 2-(acetoxymethyl)benzoyl (AMB) group as base-protecting group. Although a rapid AMB deprotection can be accomplished in methanolic potassium carbonate, the lability of the methylphosphonate linkage towards potassium carbonate/methanol excludes the use of this deprotection reagent. Thus, saturated ammonia solution in methanol was investigated as an alternative reagent for AMB removal. It is demonstrated that the combination of the AMB protective group and ammonia/methanol as deprotection reagent significantly improves the synthesis of methylphosphonate-modified DNA fragments. A mild overnight treatment at room temperature is sufficient for complete removal of the AMB group, whereas deprotection of conventionally protected oligonucleotides requires much longer exposure to basic conditions at elevated temperatures. PMID:8346028

  15. Antioxidant Properties and PC12 Cell Protective Effects of a Novel Curcumin Analogue (2E,6E)-2,6-Bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH)

    PubMed Central

    Ao, Gui-Zhen; Chu, Xiao-Jing; Ji, Yuan-Yuan; Wang, Jian-Wen

    2014-01-01

    The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (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. PMID:24603537

  16. Novel nitrogen-enriched oridonin analogues with thiazole-fused A-ring: protecting group-free synthesis, enhanced anticancer profile, and improved aqueous solubility.

    PubMed

    Ding, Chunyong; Zhang, Yusong; Chen, Haijun; Yang, Zhengduo; Wild, Christopher; Chu, Lili; Liu, Huiling; Shen, Qiang; Zhou, Jia

    2013-06-27

    Oridonin (1), a complex ent-kaurane diterpenoid isolated from the traditional Chinese herb Isodon rubescens , has demonstrated great potential in the treatment of various human cancers due to its unique and safe anticancer pharmacological profile. Nevertheless, the clinical development of oridonin for cancer therapy has been hampered by its relatively moderate potency, limited aqueous solubility, and poor bioavailability. Herein, we report the concise synthesis of a series of novel nitrogen-enriched oridonin derivatives with thiazole-fused A-ring through an efficient protecting group-free synthetic strategy. Most of them, including compounds 7-11, 13, and 14, exhibited potent antiproliferative effects against breast, pancreatic, and prostate cancer cells with low micromolar to submicromolar IC50 values as well as markedly enhanced aqueous solubility. These new analogues obtained by rationally modifying the natural product have been demonstrated not only to significantly induce the apoptosis and suppress growth of triple-negative MDA-MB-231 breast cancer both in vitro and in vivo but also effective against drug-resistant ER-positive MCF-7 clones. PMID:23746196

  17. Teduglutide, a glucagon-like peptide 2 analogue: a novel protective agent with anti-apoptotic and anti-oxidant properties in mice with lung injury.

    PubMed

    Arda-Pirincci, Pelin; Oztay, Fusun; Bayrak, Bertan Boran; Yanardag, Refiye; Bolkent, Sehnaz

    2012-12-01

    Teduglutide is a long-acting synthetic analogue of human glucagon-like peptide-2 (GLP-2). GLP-2 regulates cell proliferation and apoptosis as well as normal physiology in the gastrointestinal tract. In the present study, possible cytoprotective and reparative effects of teduglutide were analyzed on a mouse model with lung injury induced by tumor necrosis factor-alpha (TNF-α) and actinomycin D (Act D). BALB/c mice were divided into six groups: control mice (I), mice injected intraperitoneally with 15 μg/kg TNF-α (II), 800 μg/kg Act D (III), Act D 2 min prior to TNF-α administration with the same doses (IV), mice injected subcutaneously with 200 μg/kg teduglutide every 12h for 10 consecutive days (V), and mice given Act D 2 min prior to TNF-α administration on day 11 after receiving teduglutide for 10 days (VI). The TNF-α/Act D administration made the lung a sensitive organ to damage. Mice lung subjected to TNF-α/Act D were characterized by the disruption of alveolar wall, induced pulmonary endothelial/epithelial cell apoptosis and expression of active caspase-3. These mice exhibited an increase in lipid peroxidation, glutathione levels, and activities of myeloperoxidase, superoxide dismutase, catalase, glutathione peroxidase and xanthine oxidase, as well as reduced tissue factor and sodium-potassium/ATPase activities. Teduglutide pretreatment regressed the structural damage, cell apoptosis and oxidative stress by reducing lipid peroxidation in mice received TNF-α/Act D. GLP-2 receptors were present on the cell membrane of type II pneumocytes and interstitial cells. Thus, teduglutide can be suggested as a novel protective agent, which possesses anti-apoptotic and anti-oxidant properties, against lung injury. PMID:23059393

  18. Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues.

    PubMed

    Rapti, Irene; Hadziyannis, Stephanos

    2015-05-18

    Hepatocellular carcinoma (HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus (HBV) infection (CHB) is the most important etiologic factor of this tumor, accounting for the development of more than 50% of the cases in the world. Primary prevention of HCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204 (update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and

  19. Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: Preliminary structure-activity relationship and pharmacophore modeling

    PubMed Central

    Eterović, Vesna A.; Valle-Rodriguez, Angelie Del; Pérez, Dinely; Carrasco, Marimée; Khanfar, Mohammad A.; El Sayed, Khalid A.; Ferchmin, Pedro A.

    2013-01-01

    Diisopropylfluorophosphate (DFP) is an organophosphorous insecticide used as a surrogate for the more toxic chemical warfare nerve agent sarin. DFP produces neurotoxicity in vivo and irreversibly decreases the area of population spikes recorded from the CA1 region of acute hippocampal slices. (1S,2E,4R,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) is a neuroprotective natural cembranoid that reverses DFP-induced damage both in vivo and in the hippocampal slice. Cembranoid 1 acts by noncompetitive inhibition of the α7 nicotinic acetylcholine receptor. This study aims at establishing a preliminary structure-activity relationship to define the neuroprotective cembranoid pharmacophores using the hippocampal slice assay and pharmacophore modeling. Fourteen natural, semisyntheti or biocatalytic cembranoid analogues 2-15 related to 1 were tested for their capacity to protect the population spikes from DFP-induced damage and intrinsic toxicity. Twelve cembranoids caused significant reversal of DFP toxicity; only 3 active analogues displayed minor intrinsic toxicity at 10 μM. The C-4 epimer of 1 (2) and the 4-O-methyl ether analogue of 1 (3), were totally devoid of neuroprotective activity. The results suggested a model for cembranoid binding where the hydrophobic ring surface binds to a hydrophobic (Hbic) patch on the receptor molecule and an electronegative atom (oxygen or sulfur) in proper spatial relationship to the ring surface interacts with an electropositive group in the receptor binding site. A pharmacophore model consisting of 1 hydrogen bond acceptor (HBA), 2 Hbic, and 10 exclusion spheres was established using HipHop-REFINE and supported the above mentioned pharmacophoric hypothesis. PMID:23769165

  20. Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: preliminary structure-activity relationship and pharmacophore modeling.

    PubMed

    Eterović, Vesna A; Del Valle-Rodriguez, Angelie; Pérez, Dinely; Carrasco, Marimée; Khanfar, Mohammad A; El Sayed, Khalid A; Ferchmin, Pedro A

    2013-08-01

    Diisopropylfluorophosphate (DFP) is an organophosphorous insecticide used as a surrogate for the more toxic chemical warfare nerve agent sarin. DFP produces neurotoxicity in vivo and irreversibly decreases the area of population spikes recorded from the CA1 region of acute hippocampal slices. (1S,2E,4R,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) is a neuroprotective natural cembranoid that reverses DFP-induced damage both in vivo and in the hippocampal slice. Cembranoid 1 acts by noncompetitive inhibition of the α7 nicotinic acetylcholine receptor. This study aims at establishing a preliminary structure-activity relationship to define the neuroprotective cembranoid pharmacophores using the hippocampal slice assay and pharmacophore modeling. Fourteen natural, semisynthetic, or biocatalytic cembranoid analogues 2-15 related to 1 were tested for their capacity to protect the population spikes from DFP-induced damage and intrinsic toxicity. Twelve cembranoids caused significant reversal of DFP toxicity; only 3 active analogues displayed minor intrinsic toxicity at 10 μM. The C-4 epimer of 1 (2) and the 4-O-methyl ether analogue of 1 (3), were totally devoid of neuroprotective activity. The results suggested a model for cembranoid binding where the hydrophobic ring surface binds to a hydrophobic (Hbic) patch on the receptor molecule and an electronegative atom (oxygen or sulfur) in proper spatial relationship to the ring surface interacts with an electropositive group in the receptor binding site. A pharmacophore model consisting of 1 hydrogen bond acceptor (HBA), 2 Hbic, and 10 exclusion spheres was established using HipHop-REFINE and supported the above mentioned pharmacophoric hypothesis. PMID:23769165

  1. Copper inhibits activated protein C: protective effect of human albumin and an analogue of its high-affinity copper-binding site, d-DAHK.

    PubMed

    Bar-Or, David; Rael, Leonard T; Winkler, James V; Yukl, Richard L; Thomas, Gregory W; Shimonkevitz, Richard P

    2002-02-01

    Activated protein C (APC) is useful in the treatment of sepsis. Ischemia and acidosis, which often accompany sepsis, cause the release of copper from loosely bound sites. We investigated (i) whether physiological concentrations of copper inhibit APC anticoagulant activity and (ii) if any copper-induced APC inhibition is reversible by human serum albumin (HSA) or a high-affinity copper-binding analogue of the human albumin N-terminus, d-Asp-d-Ala-d-His-d-Lys (d-DAHK). APC activity after 30 min of incubation with CuCl2 (10 microM) was decreased 26% below baseline. HSA, both alone and when combined with various ratios of CuCl2, increased APC activity significantly above baseline. d-DAHK alone and 2:1 and 4:1 ratios of d-DAHK:CuCl2 also increased APC activity. APC contained 1.4 microM copper, which helps explain the increased APC activity with HSA and d-DAHK alone. These in vitro results indicate that copper inhibits APC activity and that albumin and d-DAHK reverse the copper-induced APC deactivation. PMID:11820775

  2. Convergent syntheses of LeX analogues

    PubMed Central

    Wang, An; Hendel, Jenifer

    2010-01-01

    Summary The synthesis of three Lex derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N-acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40 °C under excess of BF3·OEt2 activation and proceeded best if the acceptor carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Lex trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6-acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70–95%). In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led respectively to the n-hexyl and 6-aminohexyl trisaccharide targets. Unexpectedly, the 6-acetylthiohexyl analogue underwent desulfurization and gave the n-hexyl glycoside product, whereas the 6-benzylthiohexyl analogue gave the desired disulfide trisaccharide dimer. This study constitutes a particularly efficient and convergent preparation of these three Lex analogues. PMID:20485599

  3. An analogue study of intrusions.

    PubMed

    Laposa, Judith M; Alden, Lynn E

    2006-07-01

    According to cognitive theorists, intrusive trauma memories have their origin in how information during the event is processed. Two studies investigated functional cognitive strategies during medical crises that might protect against intrusions. In Study 1, interviews with health-care professionals were used to identify cognitive strategies judged to be effective in controlling emotions and dealing with medical crises. Study 2 systematically manipulated the use of those strategies in a trauma analogue film paradigm. Experimental participants reported fewer intrusions, and less fear and avoidance of film-related stimuli during the subsequent week than controls. The manipulation did not affect anxiety during the film or memory disorganization. Implications for cognitive theories of intrusion development are discussed. PMID:16125135

  4. Aspartame and Its Analogues

    NASA Astrophysics Data System (ADS)

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

    1981-04-01

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

  5. Phonon analogue of topological nodal semimetals

    NASA Astrophysics Data System (ADS)

    Po, Hoi Chun; Bahri, Yasaman; Vishwanath, Ashvin

    2015-03-01

    Recently, Kane and Lubensky proposed a mapping between bosonic phonon problems on isostatic lattices to chiral fermion systems based on factorization of the dynamical matrix [Nat. Phys. 10, 39 (2014)]. The existence of topologically protected zero modes in such mechanical problems is related to their presence in the fermionic system and is dictated by a local index theorem. Here we adopt the proposed mapping to construct a two-dimensional mechanical analogue of a fermionic topological nodal semimetal that hosts a robust bulk node in its linearized phonon spectrum. Such topologically protected soft modes with tunable wavevector may be useful in designing mechanical structures with fault-tolerant properties.

  6. Structural Analogues of Selfotel.

    PubMed

    Dziuganowska, Zofia A; Ślepokura, Katarzyna; Volle, Jean-Noël; Virieux, David; Pirat, Jean-Luc; Kafarski, Paweł

    2016-06-17

    A small library of phosphonopiperidylcarboxylic acids, analogues of NMDA antagonist selfotel (CGS 19755), was synthesized. First, the series of aromatic esters was obtained via a palladium-catalyzed cross-coupling reaction (Hirao coupling) of dialkyl phosphites with bromopyridinecarboxylates, followed by their hydrolysis. Then, hydrogenation of the resulting phosphonopyridylcarboxylic acids over PtO2 yielded the desired phosphonopiperidylcarboxylic acids. NMR studies indicated that the hydrogenation reaction proceeds predominantly by cis addition. Several compounds were obtained as monocrystal structures. Preliminary biological studies performed on cultures of neurons suggest that the obtained compounds possess promising activity toward NMDA receptors. PMID:27187758

  7. Practical enantiospecific syntheses of lysobisphosphatidic acid and its analogues.

    PubMed

    Jiang, Guowei; Xu, Yong; Prestwich, Glenn D

    2006-02-01

    We describe a versatile, efficient, and practical method for the preparation of enantiomerically pure lysobisphosphatidic acid (LBPA), bisether analogues, and phosphorothioate analogues of LBPA from solketal. Phosphorylation of a protected sn-2-O-oleoyl glycerol with 2-cyanoethyl bis(N,N-diisopropylamino)phosphite, followed by oxidation and deprotection, generated the enantiomers of 2,2'-LBPA. The corresponding phosphorothioate analogues were obtained by oxidation with sulfur. The (R,R) and (S,S) enantiomers of both LBPA and phosphorothioate LBPA were synthesized from (S)- and (R)-solketal, respectively. The ether analogue of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer were synthesized from the same enantiomer (S)-solketal by simply changing the sequence of deprotection steps. PMID:16438504

  8. Synthesis and proteinase inhibitory properties of diphenyl phosphonate analogues of aspartic and glutamic acids.

    PubMed

    Hamilton, R; Walker, B; Walker, B J

    1998-07-01

    The synthesis of diphenyl phosphonate analogues of aspartic and glutamic acid, and their inhibitory activity against S. aureus V8 protease and granzyme B, is described. The study has revealed difficulties with protecting group compatibility in the synthesis of these analogues. Two analogues, Acetyl. AspP (OPh)2 and Acetyl.GluP (OPh)2 were found to function as irreversible inactivators of V8 proteinase, yet exhibit no activity against granzyme B. PMID:9873408

  9. Analogue-to-Digital and Digital-to-Analogue Conversion.

    ERIC Educational Resources Information Center

    Gregory, Martin

    1997-01-01

    Discusses circuits for three-bit and four-bit analogue digital converters and digital analogue converters. These circuits feature slow operating speeds that enable the circuitry to be used to demonstrate the mode of operation using oscilloscopes and signal generators. (DDR)

  10. Phosphonate analogues of aminoacyl adenylates.

    PubMed Central

    Southgate, C C; Dixon, H B

    1978-01-01

    Phosphonomethyl analogues of glycyl phosphate and valyl phosphate, i.e. NH2-CHR-CO-CH2-PO(OH)2, were synthesized and esterified with adenosine to give analogues of aminoacyl adenylates. The interaction of these adenylate analogues with valyl-tRNA synthetase from Escherichia coli was studied by fluorescence titration. The analogue of valyl phosphate has an affinity for the enzyme comparable with that of valine, but that of valyl adenylate is bound much less tightly than either valyl adenylate or corresponding derivative of valinol. The affinity of the analogue of glycyl adenylate was too low to be measured. We conclude that this enzyme interacts specifically with both the side chain and the anhydride linkage of the adenylate intermediate. PMID:743207

  11. NASA/ESMD Analogue Mission Plans

    NASA Technical Reports Server (NTRS)

    Hoffman, Stephen J.

    2007-01-01

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

  12. Concise synthesis of ether analogues of lysobisphosphatidic acid.

    PubMed

    Jiang, Guowei; Xu, Yong; Falguières, Thomas; Gruenberg, Jean; Prestwich, Glenn D

    2005-09-01

    We describe a versatile, efficient method for the preparation of ether analogues of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer from (S)-solketal. Phosphorylation of a protected sn-2-O-octadecenyl glyceryl ether with 2-cyanoethyl bis-N,N-diisopropylamino phosphine and subsequent deprotection generated the bisether LBPA analogues. By simply changing the sequence of deprotection steps, we obtained the (R,R)- and (S,S)-enantiomers of 2,2'-bisether LBPA. An ELISA assay with anti-LBPA monoclonal antibodies showed that the bisether LBPAs were recognized with the same affinity as the natural 2,2'-bisoleolyl LBPA. [reaction: see text] PMID:16119911

  13. Synthesis of Conformationally Locked Versions of Puromycin Analogues

    PubMed Central

    Saneyoshi, Hisao; Michel, Benoît Y.; Choi, Yongseok; Strazewski, Peter; Marquez, Victor E.

    2009-01-01

    Conformationally locked North and South versions of puromycin analogues built on a bicyclo[3.1.0]hexane pseudosugar template were synthesized. The final assembly of the products was accomplished by the Staudinger-Vilarrasa coupling of the corresponding North (2 and 3) and South (6 and 7) 3′-azidopurine carbanucleosides with the Fmoc-protected 1-hydroxybenzotriazole ester of 4-methoxy-L-tyrosine. North azides 2 and 3 were reported earlier. The 3′-azido intermediates 6 and 7 that are necessary for the synthesis of the South puromycin analogues are described herein for the first time. PMID:18991379

  14. Synthesis of 4” manipulated Lewis X trisaccharide analogues

    PubMed Central

    Moore, Christopher J

    2012-01-01

    Summary Three analogues of the Lex trisaccharide antigen (β-D-Galp(1→4)[α-L-Fucp(1→3)]-D-GlcNAcp) in which the galactosyl residue is modified at O-4 as a methyloxy, deoxychloro or deoxyfluoro, were synthesized. We first report the preparation of the modified 4-OMe, 4-Cl and 4-F trichloroacetimidate galactosyl donors and then report their use in the glycosylation of an N-acetylglucosamine glycosyl acceptor. Thus, we observed that the reactivity of these donors towards the BF3·OEt2-promoted glycosylation at O-4 of the N-acetylglucosamine glycosyl acceptors followed the ranking 4-F > 4-OAc ≈ 4-OMe > 4-Cl. The resulting disaccharides were deprotected at O-3 of the glucosamine residue and fucosylated, giving access to the desired protected Lex analogues. One-step global deprotection (Na/NH3) of the protected 4”-methoxy analogue, and two-step deprotections (removal of a p-methoxybenzyl with DDQ, then Zemplén deacylation) of the 4”-deoxychloro and 4”-deoxyfluoro protected Lex analogues gave the desired compounds in good yields. PMID:23019441

  15. Phosphonomethyl analogues of hexose phosphates.

    PubMed

    Webster, D; Jondorf, W R; Dixon, H B

    1976-05-01

    The analogue of fructose 1,6-bisphosphate in which the phosphate group, -O-PO3H2, on C-6 is replaced by the phosphonomethyl group, -CH2-PO3H2, was made enzymically from the corresponding analogue of 3-phosphoglycerate. It was a substrate for aldolase, which was used to form it, but not for fructose 1,6-bisphosphatase. It was hydrolysed chemically to yield the corresponding analogue of fructose 6-phosphate [i.e. 6-deoxy-6-(phosphonomethyl)-D-fructose, or, more strictly, 6,7-dideoxy-7-phosphono-D-arabino-2-heptulose]. This proved to be a substrate for the sequential actions of glucose 6-phosphate isomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Thus seven out of the nine enzymes of the glycolytic and pentose phosphate pathways so far tested catalyse the reactions of the phosphonomethyl isosteres of their substrates. PMID:7247

  16. Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin-Releasing Hormone (TRH) Analogues

    PubMed Central

    Monga, Vikramdeep; Meena, Chhuttan L.; Rajput, Satyendra; Pawar, Chandrashekhar; Sharma, Shyam S.; Lu, Xinping; Gershengorn, Marvin C.

    2012-01-01

    As part of our search for selective and CNS-active thyrotropin-releasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRH-R1 and TRH-R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRH-R1 and TRH-R2 with good to moderate affinities, and are full agonists at both receptor subtypes. Specifically, analogue 21 a (R = CH3) exhibited binding affinities (Ki values) of 0.17 μM for TRH-R1 and 0.016 μM for TRH-R2; it is 10-fold less potent than TRH in binding to TRH-R1 and equipotent with TRH in binding to TRH-R2. Compound 21 a, the most selective agonist, activated TRH-R2 with a potency (EC50 value) of 0.0021 μM, but activated TRH-R1 at EC50 = 0.05 μM, and exhibited 24-fold selectivity for TRH-R2 over TRH-R1. The newly synthesized TRH analogues were also evaluated in vivo to assess their potencies in antagonism of barbiturate-induced sleeping time, and several analogues displayed potent analeptic activity. Specifically, analogues 21 a,b and 22 a,b decreased sleeping time by nearly 50 % more than TRH. These analogues also displayed potent anticonvulsant activity and provided significant protection against PTZ-induced seizures, but failed to provide any protection in MES-induced seizures at 10 μmol kg−1. The results of this study provide evidence that TRH analogues that show selectivity for TRH-R2 over TRH-R1 possess potent CNS activity. PMID:21302359

  17. Synthesis of thioglycoside-based UDP-sugar analogues.

    PubMed

    Zhu, Xiangming; Stolz, Florian; Schmidt, Richard R

    2004-10-15

    Arbuzov reaction of O-acetyl-protected glycosylthiomethyl chlorides with triethyl phosphite and then phosphonate ethyl ester cleavage with trimethylsilyl bromide afforded glycosylthiomethyl phosphonates 13, 18, 22, and 26. These intermediates could be readily transformed into the O-deprotected phosphonates 7-10 and into title compounds 1-4. Similarly, sulfonomethyl phosphonate moieties containing UDP-sugar analogues 5 and 6 were obtained. PMID:15471496

  18. Synthesis of monophytanyl ether analogues of lysophosphatidic and lysophosphatidyl glycerol.

    PubMed

    Kates, M; Hancock, A J

    1976-10-01

    The chemical synthesis of 3-O-phytanyl-sn-glycero-1-phosphoric acid (monophytanyl ether analogue of lysophosphatidic acid) was effected by condensation of 1-iodo-2-O-benzyl-3-O-phytanyl-sn-glycerol with silver di-p-nitrobenzyl phosphate in anhydrous toluene followed by catalytic hydrogenolysis of the resulting phosphotriester to remove the benzyl and p-nitrobenzyl groups. Synthesis of 3-O-phytanyl-sn-glycero-1-phosphoryl-1'-sn-glycerol (monophytanyl ether analogue of lysophosphatidyl glycerol) was carried out by conversion of the above phosphotriester to the monosilver salt of the suitably blocked lysophosphatidic acid which was condensed with 1-iodo-2-O-t-butyl-3-O-benzyl-sn-glycerol. Removal of the protecting aromatic and t-butyl groups from the resulting blocked triester intermediate gave the desired phytanyl ether analogue of lysophosphatidyl glycerol. Both lyso analogues were isolated as analytically and chromatographically pure potassium salts. Their physical properties and behavior towards acid hydrolysis are described. PMID:991376

  19. Muscarinic interactions of bisindolylmaleimide analogues.

    PubMed

    Lazareno, S; Popham, A; Birdsall, N J

    1998-11-01

    We have used radioligand binding studies to determine the affinities of seven bisindolylmaleimide analogues, six of which are selective inhibitors of protein kinase C, at human muscarinic M1-M4 receptors. The compounds were most potent at M1 receptors, and Ro-31-8220 was the most potent analogue, with a Kd of 0.6 microM at M1 receptors. The weakest compounds, bisindolylmaleimide IV and bisindolylmaleimide V, had Kd values of 100 microM. If it is necessary to use protein kinase C inhibitors at concentrations of 10 microM or more in studies involving muscarinic receptors then bisindolylmaleimide IV may be the most appropriate inhibitor to use. PMID:9851596

  20. Substrate analogues for isoprenoid enzymes

    SciTech Connect

    Stremler, K.E.

    1987-01-01

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

  1. Policy issues in space analogues

    NASA Astrophysics Data System (ADS)

    Auger, Robin N.; Facktor, Debra D.

    Space mission planning is increasingly focusing on destinations beyond Earth orbit. Advancements in technology will inevitably be required to enable long-duration human spaceflight missions, and breakthroughs in the policy arena will also be needed to achieve success in such missions. By exploring how policy issues have been addressed in analogous extreme environments, policymakers can develop a framework for addressing these issues as they apply to long-term human spaceflight. Policy issues that need to be addressed include: crew selection, training, organization, and activities, medical testing, illness, injury, and death; communication; legal accountability and liability; mission safety and risk management; and environmental contamination. This paper outlines the approach of a study underway by The George Washington University and ANSER to examine how these policy issues have been addressed in several analogues and how the experiences of these analogues can help formulate policies for long-duration human spaceflight missions. Analogues being studied include Antarctic bases, submarine voyages, undersea stations, Biosphere 2, and the U.S. Skylab and Russian Mir space stations.

  2. Phosphonate analogue substrates for enolase.

    PubMed

    Anderson, V E; Cleland, W W

    1990-11-20

    Phosphonate analogues in which the bridge between C-2 and phosphorus is a CH2 group are slow substrates for yeast enolase. The pH variation of the kinetic parameters for the methylene analogue of 2-phosphoglycerate suggests that the substrate binds as a dianion and that Mg2+ can bind subsequently only if a metal ligand and the catalytic base are unprotonated. Primary deuterium isotope effects of 4-8 on V/KMg, but ones of only 1.15-1.32 on V for dehydration, show that proton removal to give the carbanion intermediate largely limits V/KMg and that a slow step follows which largely limits V (presumably carbanion breakdown). Since there is a D2O solvent isotope effect on V for the reverse reaction of 5, but not an appreciable one on the forward reaction, it appears that the slow rates with phosphonate analogues result from the fact that the carbanion intermediate is more stable than that formed from the normal substrates, and its reaction in both directions limits V. Increased stability as a result of replacement of oxygen by carbon at C-2 of the carbanion is the expected chemical behavior. PMID:2271661

  3. FUNCTION GENERATOR FOR ANALOGUE COMPUTERS

    DOEpatents

    Skramstad, H.K.; Wright, J.H.; Taback, L.

    1961-12-12

    An improved analogue computer is designed which can be used to determine the final ground position of radioactive fallout particles in an atomic cloud. The computer determines the fallout pattern on the basis of known wind velocity and direction at various altitudes, and intensity of radioactivity in the mushroom cloud as a function of particle size and initial height in the cloud. The output is then displayed on a cathode-ray tube so that the average or total luminance of the tube screen at any point represents the intensity of radioactive fallout at the geographical location represented by that point. (AEC)

  4. Ecstasy analogues found in cacti.

    PubMed

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

    2008-06-01

    Human interest in psychoactive phenethylamines is known from the use of mescaline-containing cacti and designer drugs such as Ecstasy. From the alkaloid composition of cacti we hypothesized that substances resembling Ecstasy might occur naturally. In this article we show that lophophine, homopiperonylamine and lobivine are new minor constituents of two cactus species, Lophophora williamsii (peyote) and Trichocereus pachanoi (San Pedro). This is the first report of putatively psychoactive phenethylamines besides mescaline in these cacti. A search for further biosynthetic analogues may provide new insights into the structure-activity relationships of mescaline. An intriguing question is whether the new natural compounds can be called "designer drugs." PMID:18720674

  5. The Valles natural analogue project

    SciTech Connect

    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 {sup 39}Ar/{sup 4O} isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

  6. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-11-08

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

  7. Fully analogue photonic reservoir computer.

    PubMed

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-01-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers. PMID:26935166

  8. Fully analogue photonic reservoir computer

    PubMed Central

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-01-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers. PMID:26935166

  9. Acyclic nucleoside/nucleotide analogues with an imidazole ring skeleton.

    PubMed

    Chen, H M; Hosmane, R S

    2001-08-01

    Syntheses of a few acyclic nucleoside and acyclic nucleoside phosphonate analogues containing an imidazole ring have been reported. These analogues include methyl 1-(2-hydroxyethoxymethyl)imidazole-4, 5-dicarbo-xylate (1), 4,5-dicarbamoyl-1-(2-hydroxyethoxymethyl)imidazole (2), 4,5-dicyano-1-(2-hydroxyethoxymethyl)imidazole (4), Methyl 1-(2-bromoethoxymethyl)imidazole-4,5-dicarboxylate (7), 4,5-dicyano-(2-bromoethoxymethyl)imidazole (8), and Methyl 1-(2-phosphonomethoxyethyl)imidazole (10). Also reported are a few potential prodrugs of the above compounds, including the acetyl derivatives 5 and 6 (of 1 and 4, respectively), and the diethyl phosphonate ester 9 (of 10). In addition, the corresponding benzyl-protected precursors 11 and 12 (of 1 and 4, respectively), along with their common hydrolysis product, 1-(2-benzyloxy-ethoxymethyl)-4,5-imidazoledicarboxylic acid (3), are reported. Another potential prodrug included in the list is 1-(2-acetoxyethyl)-4,5-dicyanoimidazole (15). The compounds were screened for in vitro antiviral activity against a wide variety of herpes and respiratory viruses. The most active compound was the phosphonate analogue 9 which exhibited an anti-measles virus activity with an EC50 of <2.5 microg/mL and an SI value of > 176. PMID:11554548

  10. Laboratory study of cometary analogues

    NASA Astrophysics Data System (ADS)

    Colangeli, L.; Brucato, J.; Mennella, V.; Palumbo, P.

    In situ exploration (e.g., GIOTTO mission) and astronomical observations (e.g., ISO) of comets have provided fundamental information about the structure, chemistry and physical properties of materials present in such primordial bodies of the Solar System. Moreover, it is known that cosmic materials evolve, depending on the efficiency of active processes (e.g., thermal annealing, UV irradiation, ion bombardment, gassolid interactions) in different space environments. Thus, the properties of cometary constituents must be considered in a wider perspective, including cosmic dust formation around cold stars and evolution in the interstellar medium until the formation of proto-planetary nebulae. In this scenario, laboratory experiments provide important hints to clarify the status of cometary compounds. The laboratory work is aimed at both reproducing material properties and at simulating their evolution based on the most effective mechanisms active in space. Several techniques are used to synthesise "analogues" of cometary compounds with controlled chemical and physical characteristics. The study of optical properties, complemented by other analytical techniques, is applied to investigate the products of synthesis in the experiments. The monitoring of the effects produced by processing methods, similar to those active in space, provides information both on the reactivity of materials and on the efficiency of treatments. Such an approach is able to provide quantitative information on chemical and structural modifications produced on organic and refractory materials. The comparison of laboratory results with data coming from space observations and in situ measurements provides a powerful tool to understand the real nature of comets and to place constraints on formation and evolution pathways. The laboratory experiments on analogues gain even more relevance as a sort of training in the future perspective of analysing cometary samples returned to Earth by space missions (e

  11. Component-based syntheses of trioxacarcin A, DC-45-A1 and structural analogues

    NASA Astrophysics Data System (ADS)

    Magauer, Thomas; Smaltz, Daniel J.; Myers, Andrew G.

    2013-10-01

    The trioxacarcins are polyoxygenated, structurally complex natural products that potently inhibit the growth of cultured human cancer cells. Here we describe syntheses of trioxacarcin A, DC-45-A1 and structural analogues by late-stage stereoselective glycosylation reactions of fully functionalized, differentially protected aglycon substrates. Key issues addressed in this work include the identification of an appropriate means to activate and protect each of the two 2-deoxysugar components, trioxacarcinose A and trioxacarcinose B, as well as a viable sequencing of the glycosidic couplings. The convergent, component-based sequence we present allows for rapid construction of structurally diverse, synthetic analogues that would be inaccessible by any other means, in amounts required to support biological evaluation. Analogues that arise from the modification of four of five modular components are assembled in 11 steps or fewer. The majority of these are found to be active in antiproliferative assays using cultured human cancer cells.

  12. Novel synthesis of cyclic amide-linked analogues of angiotensins II and III.

    PubMed

    Matsoukas, J M; Hondrelis, J; Agelis, G; Barlos, K; Gatos, D; Ganter, R; Moore, D; Moore, G J

    1994-09-01

    Cyclic amide-linked angiotension II (ANGII) analogues have been synthesized by novel strategies, in an attempt to test the ring clustering and the charge relay bioactive conformation recently suggested. These analogues were synthesized by connecting side chain amino and carboxyl groups at positions 1 and 8, 2 and 8, 3 and 8, and 3 and 5, N-terminal amino and C-terminal carboxyl groups at positions 1 and 8, 2 and 8, and 4 and 8, and side chain amino to C-terminal carboxyl group at positions 1 and 8. All these analogues were biologically inactive, except for cyclic [Sar1, Asp3, Lys5]ANGII (analogue 10) which had high contractile activity in the rat uterus assay (30% of ANGII) and [Lys1, Tyr(Me)4, Glu8]ANGII (analogue 7) which had weak antagonist activity (PA2 approximately 6). Precyclic linear peptides synthesized using 2-chlorotrityl chloride resin and N alpha-Fmoc-amino acids with suitable side chain protection were obtained in high yield and purity and were readily cyclized with benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate as coupling reagent. Molecular modeling suggests that the ring structure of the potent analogue can be accommodated in the charge relay conformation proposed for ANGII. PMID:8071943

  13. Plant volatile analogues strengthen attractiveness to insect.

    PubMed

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of β-ionone and benzaldehyde. The stabilities of β-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than β-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than β-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  14. Plant Volatile Analogues Strengthen Attractiveness to Insect

    PubMed Central

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A.; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of β-ionone and benzaldehyde. The stabilities of β-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than β-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than β-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  15. Space analogue studies in Antarctica

    NASA Astrophysics Data System (ADS)

    Lugg, D.; Shepanek, M.

    1999-09-01

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

  16. Condensed matter analogues of cosmology

    NASA Astrophysics Data System (ADS)

    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.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    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. PMID:24918540

  18. Space analogue studies in Antarctica

    NASA Technical Reports Server (NTRS)

    Lugg, D.; Shepanek, M.

    1999-01-01

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

  19. Heterocyclic chalcone analogues as potential anticancer agents.

    PubMed

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  20. Synthesis of 5′-Functionalized Nucleosides: S-Adenosylhomocysteine Analogues with the Carbon-5′ and Sulfur Atoms Replaced by a Vinyl or Halovinyl Unit

    PubMed Central

    Wnuk, Stanislaw F.; Sacasa, Pablo R.; Lewandowska, Elzbieta; Andrei, Daniela; Cai, Sumin; Borchardt, Ronald T.

    2008-01-01

    Adenosine and uridine analogues functionalized with alkenyl or fluoroalkenyl chain at C5′ were prepared employing cross-metathesis, Negishi couplings and Wittig reactions. Metathesis of the protected 5′-deoxy-5′-methyleneadenosine or uridine analogues with six-carbon amino acids (homoallylglycines) in the presence of Grubbs catalysts gave nucleoside analogues with the C5′-C6′ double bond. Alternatively, the Pd-catalyzed cross-coupling between the protected 5′-deoxy-5′-(iodomethylene) nucleosides and suitable alkylzinc bromides also provided analogues with alkenyl unit. Stereoselective Pd-catalyzed monoalkylation of 5′-(bromofluoromethylene)-5′-deoxyadenosine with alkylzinc bromides afforded adenosylhomocysteine analogues with a 6′-(fluoro)vinyl motif. The vinylic adenine nucleosides produced time-dependent inactivation of the S-adenosyl-L-homocysteine hydrolases. PMID:18457953

  1. Synthesis and SAR of vinca alkaloid analogues.

    PubMed

    Voss, Matthew E; Ralph, Jeffery M; Xie, Dejian; Manning, David D; Chen, Xinchao; Frank, Anthony J; Leyhane, Andrew J; Liu, Lei; Stevens, Jason M; Budde, Cheryl; Surman, Matthew D; Friedrich, Thomas; Peace, Denise; Scott, Ian L; Wolf, Mark; Johnson, Randall

    2009-02-15

    Versatile intermediates 12'-iodovinblastine, 12'-iodovincristine and 11'-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues 27 and 36 show promising anticancer activity in the P388 murine leukemia model. PMID:19147348

  2. Attenuation of Ischemic Liver Injury by Prostaglandin E1 Analogue, Misoprostol, and Prostaglandin I2 Analogue, OP-41483

    PubMed Central

    Totsuka, Eishi; Todo, Satoru; Zhu, Yue; Ishizaki, Naoki; Kawashima, Yoshiyuki; Jin, Maeng Bong; Urakami, Atsushi; Shimamura, Tsuyoshi; Starzl, Thomas E

    2010-01-01

    Background Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drug-related side effects. This study investigated whether misoprostol, prostaglandin E1 analogue, and OP-41483, prostaglandin I2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage. Study Design Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 μg/kg/min) and for 3 hours after reperfusion (0.5 μg/kg/min). Animals were divided into five groups: untreated control group (n = 10); high-dose misoprostol (total 100 μg/kg) group (MP-H, n = 5); middle-dose misoprostol (50 μg/kg) group (MP-M, n = 5); low-dose misoprostol (25 μg/kg) group (MP-L, n = 5); and OP-41483 group (OP, n = 5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed. Results Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBF, and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP-M, MP-L, and OP animals experienced only transient hypotension. Conclusions These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects. PMID:9740185

  3. Planetary habitability: lessons learned from terrestrial analogues

    NASA Astrophysics Data System (ADS)

    Preston, Louisa J.; Dartnell, Lewis R.

    2014-01-01

    Terrestrial analogue studies underpin almost all planetary missions and their use is essential in the exploration of our Solar system and in assessing the habitability of other worlds. Their value relies on the similarity of the analogue to its target, either in terms of their mineralogical or geochemical context, or current physical or chemical environmental conditions. Such analogue sites offer critical ground-truthing for astrobiological studies on the habitability of different environmental parameter sets, the biological mechanisms for survival in extreme environments and the preservation potential and detectability of biosignatures. The 33 analogue sites discussed in this review have been selected on the basis of their congruence to particular extraterrestrial locations. Terrestrial field sites that have been used most often in the literature, as well as some lesser known ones which require greater study, are incorporated to inform on the astrobiological potential of Venus, Mars, Europa, Enceladus and Titan. For example, the possibility of an aerial habitable zone on Venus has been hypothesized based on studies of life at high-altitudes in the terrestrial atmosphere. We also demonstrate why many different terrestrial analogue sites are required to satisfactorily assess the habitability of the changing environmental conditions throughout Martian history, and recommend particular sites for different epochs or potential niches. Finally, habitable zones within the aqueous environments of the icy moons of Europa and Enceladus and potentially in the hydrocarbon lakes of Titan are discussed and suitable analogue sites proposed. It is clear from this review that a number of terrestrial analogue sites can be applied to multiple planetary bodies, thereby increasing their value for astrobiological exploration. For each analogue site considered here, we summarize the pertinent physiochemical environmental features they offer and critically assess the fidelity with which

  4. A new approach to the synthesis of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotide analogues.

    PubMed Central

    Szabó, T; Kers, A; Stawinski, J

    1995-01-01

    A new synthetic method for the preparation of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotides (5'-methylenephosphonate analogues) was developed. The method is based on the use of a phosphonate protecting group, 4-methoxy-1-oxido-2-picolyl, enabling intramolecular nucleophilic catalysis which together with the condensing agent, 2,4,6-triisopropylbenzenesulfonyl chloride, secures fast and efficient formation of the 5'-methylenephosphonate internucleosidic bonds. The produced protected oligomers were treated with thiophenol and triethylamine to remove the phosphonate protecting groups, cleaved from the solid support using concentrated aqueous ammonia, and purified by HPLC. Several thymidine oligonucleotide analogues with the chain length of up to 20 nucleotidic units, in which all internal 5'-oxygen atoms have been replaced by methylene groups directly bound to phosphorus, were synthesised using this methodology. PMID:7731801

  5. Glucagonlike Peptide 2 Analogue Teduglutide

    PubMed Central

    Chaturvedi, Lakshmi S.; Basson, Marc D.

    2015-01-01

    IMPORTANCE Short bowel syndrome occurs when a shortened intestine cannot absorb sufficient nutrients or fluids. Teduglutide is a recombinant analogue of human glucagonlike peptide 2 that reduces dependence on parenteral nutrition in patients with short bowel syndrome by promoting enterocytic proliferation, increasing the absorptive surface area. However, enterocyte function depends not only on the number of cells that are present but also on differentiated features that facilitate nutrient absorption and digestion. OBJECTIVE To test the hypothesis that teduglutide impairs human intestinal epithelial differentiation. DESIGN AND SETTING We investigated the effects of teduglutide in the modulation of proliferation and differentiation in human Caco-2 intestinal epithelial cells at a basic science laboratory. This was an in vitro study using Caco-2 cells, a human-derived intestinal epithelial cell line commonly used to model enterocytic biology. EXPOSURE Cells were exposed to teduglutide or vehicle control. MAINOUTCOMESAND MEASURES We analyzed the cell cycle by bromodeoxyuridine incorporation or propidium iodide staining and flow cytometry and measured cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. We used quantitative reverse transcription–polymerase chain reaction to assay the expression of the enterocytic differentiation markers villin, sucrase-isomaltase, glucose transporter 2 (GLUT2), and dipeptidyl peptidase 4 (DPP-4), as well as that of the putative differentiation signals schlafen 12 (SLFN12) and caudal-related homeobox intestine-specific transcription factor (Cdx2). Villin promoter activity was measured by a luciferase-based assay. RESULTS The MTS assay demonstrated that teduglutide increased cell numbers by a mean (SD) of 10% (2%) over untreated controls at a maximal 500nM (n = 6, P < .05). Teduglutide increased bromodeoxyuridine-positive cells vs untreated controls by a mean (SD

  6. Chemical Synthesis and Molecular Recognition of Phosphatase-Resistant Analogues of Phosphatidylinositol-3-phosphate

    PubMed Central

    Xu, Yong; Lee, Stephanie A.; Kutateladze, Tatiana G.; Sbrissa, Diego; Shisheva, Assia; Prestwich, Glenn D.

    2008-01-01

    The remodeling of phosphatidylinositol polyphosphates in cellular membranes by phosphatases and kinases orchestrates the signaling by these lipids in space and time. In order to provide chemical tools to study of the changes in cell physiology mediated by these lipids, three new metabolically-stabilized (ms) analogues of phosphatidylinositol-3-phosphate (PtdIns(3)P were synthesized. We describe herein the total asymmetric synthesis of 3-methylphosphonate, 3-monofluoromethylphosphonate and 3-phosphorothioate analogues of PtdIns(3)P. From differentially protected D-myo-inositol key intermediates, a versatile phosphoramidite reagent was employed in the synthesis of PtdIns(3)P analogues with diacylglyceryl moieties containing dioleoyl, dipalmitoyl and dibutyryl chains. In addition, we introduce a new phosphorlyation reagent, monofluoromethylphosphonyl chloride, which has general applications for the preparation of “pKa-matched” monofluorophosphonates. These ms-PtdIns(3)P analogues exhibited reduced binding activities with 15N-labelled FYVE and PX domains, as significant 1H and 15N chemical shift changes in the FYVE domain were induced by titrating ms-PtdIns(3)Ps into membrane-mimetic dodecylphosphocholine (DPC) micelles. In addition, the PtdIns(3)P analogues with dioleyl and dipalmitoyl chains were substrates for the 5-kinase enzyme PIKfyve; the corresponding phosphorylated ms-PI(3,5)P2 products were detected by radio-TLC analysis. PMID:16417379

  7. Neuroprotective actions of a histidine analogue in models of ischemic stroke.

    PubMed

    Tang, Sung-Chun; Arumugam, Thiruma V; Cutler, Roy G; Jo, Dong-Gyu; Magnus, Tim; Chan, Sic L; Mughal, Mohamed R; Telljohann, Richard S; Nassar, Matthew; Ouyang, Xin; Calderan, Andrea; Ruzza, Paolo; Guiotto, Andrea; Mattson, Mark P

    2007-05-01

    Histidine is a naturally occurring amino acid with antioxidant properties, which is present in low amounts in tissues throughout the body. We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE). We now report that the histidine analogue histidyl hydrazide is effective in reducing brain damage and improving functional outcome in a mouse model of focal ischemic stroke when administered intravenously at a dose of 20 mg/kg, either 30 min before or 60 min and 3 h after the onset of middle cerebral artery occlusion. The histidine analogue also protected cultured rat primary neurons against death induced by HNE, chemical hypoxia, glucose deprivation, and combined oxygen and glucose deprivation. The histidine analogue prevented neuronal apoptosis as indicated by decreased production of cleaved caspase-3 protein. These findings suggest a therapeutic potential for HNE-scavenging histidine analogues in the treatment of stroke and related neurodegenerative conditions. PMID:17254011

  8. Dolastatin 11 conformations, analogues and pharmacophore.

    PubMed

    Ali, Md Ahad; Bates, Robert B; Crane, Zackary D; Dicus, Christopher W; Gramme, Michelle R; Hamel, Ernest; Marcischak, Jacob; Martinez, David S; McClure, Kelly J; Nakkiew, Pichaya; Pettit, George R; Stessman, Chad C; Sufi, Bilal A; Yarick, Gayle V

    2005-07-01

    Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energy conformations. The amide bonds are all trans except for the one between the Tyr and Val units, which is cis. Since an analogue restricted to negative 2-3-4-5 angles stimulated actin polymerization but was inactive in cells, the binding conformation (most likely the lowest-energy conformation in water) has a negative 2-3-4-5 angle, whereas a conformation with a positive 2-3-4-5 angle (most likely the lowest energy conformation in chloroform) goes through cell walls. The highly active R alcohol from borohydride reduction of dolastatin 11 is a candidate for conversion to prodrugs. PMID:15878670

  9. Classical Simulated Annealing Using Quantum Analogues

    NASA Astrophysics Data System (ADS)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-08-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  10. Classical Simulated Annealing Using Quantum Analogues

    NASA Astrophysics Data System (ADS)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-06-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  11. D-luciferin analogues: a multicolor toolbox for bioluminescence imaging.

    PubMed

    Sun, Yuan-Qiang; Liu, Jing; Wang, Pi; Zhang, Jingyu; Guo, Wei

    2012-08-20

    Colorful mixture: Three types of luciferin analogues, that is, alkylaminoluciferins, aminoselenoluciferin, and luciferins with a benzimidazole scaffold, have been reported. These analogues show excellent bioluminescent properties and great potential in bioluminescence imaging. PMID:22807027

  12. Synthesis and Cytoxicity of Sempervirine and Analogues.

    PubMed

    Pan, Xiaohong; Yang, Chunying; Cleveland, John L; Bannister, Thomas D

    2016-03-01

    Sempervirine and analogues were synthesized using a route featuring Sonogashira and Larock Pd-catalyzed reactions. Structure-activity relationships were investigated using three human cancer cell lines. 10-Fluorosempervirine is the most potently cytotoxic member of the family yet described. PMID:26828413

  13. Solanapyrone analogues from a Hawaiian fungicolous fungus

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. New cytotoxic analogues of annonaceous acetogenins.

    PubMed

    Rodier, S; Le Huerou, Y; Renoux, B; Doyon, J; Renard, P; Pierré, A; Gesson, J P; Grée, R

    2001-01-01

    A series of new acetogenin analogues incorporating a central catechol moiety instead of the tetrahydrofuran ring(s) have been prepared and tested against L1210 leukemia cells. Although less potent than bullatacinone, which has the same terminal lactone, these compounds display interesting cell cycle effects. PMID:11962508

  15. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-03-01

    Project overview provides background on carbonic anhydrase transport mechanism for CO2 in the human body and proposed approach for ARPA-E project to create a synthetic enzyme analogue and utilize it in a membrane for CO2 capture from flue gas.

  16. Synthesis of lipid II phosphonate analogues.

    PubMed

    Borbás, Anikó; Herczegh, Pál

    2011-09-01

    Simple analogues of lipid II were synthesized from 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-β-D-glucopyranose using conjugate addition onto ethylidene bisphosphonate and subsequent Wadsworth-Horner-Emmons reaction with long chain aliphatic aldehydes. PMID:21600568

  17. The arsonomethyl analogue of 3-phosphoglycerate.

    PubMed Central

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

    1983-01-01

    4-Arsono-2-hydroxybutanoic acid, the analogue of 3-phosphoglycerate in which -CH2-AsO3H2 replaces -O-PO3H2, was synthesized. It proved to be a substrate for phosphoglycerate kinase. Its Michaelis constant was only slightly higher than that of the natural substrate, but its catalytic constant was about 1300 times smaller. PMID:6615422

  18. Synthesis and antimicrobial activity of squalamine analogue.

    PubMed

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

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

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

    PubMed

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

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. PMID:27301366

  20. Recent advances in topoisomerase I-targeting agents, camptothecin analogues.

    PubMed

    Kim, Dae-Kee; Lee, Namkyu

    2002-12-01

    The present review concentrates on camptothecin (CPT) analogues, the most extensively studied topoisomerase I (topo I) inhibitors, and provides concise information on the structural features of human topo I enzyme, mechanisms of interaction of CPT with topo I, structure-activity relationship study of CPT analogues including the influence of lactone stability on antitumor activity, and recent updates of valuable CPT analogues. PMID:12370044

  1. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    PubMed

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  2. Design and synthesis of new fluconazole analogues.

    PubMed

    Pore, Vandana S; Agalave, Sandip G; Singh, Pratiksha; Shukla, Praveen K; Kumar, Vikash; Siddiqi, Mohammad I

    2015-06-21

    We have synthesized new fluconazole analogues containing two different 1,2,3-triazole units in the side chain. The synthesis of new amide analogues using a variety of acids is also described. All the compounds showed very good antifungal activity. A hemolysis study of the most active compounds 6e and 13j showed that both compounds did not cause any hemolysis at the dilutions tested. These compounds did not exhibit any toxicity to L929 cells at MIC and lower concentrations. In the docking study, the overall binding mode of 6e and 13j appeared to be reasonable and provided a good insight into the structural basis of inhibition of Candida albicans Cyp51 by these compounds. PMID:25975803

  3. Efficient synthesis of esermethole and its analogues.

    PubMed

    Zhou, Yongyun; Zhao, Yuanhong; Dai, Xiaoyong; Liu, Jianping; Li, Liang; Zhang, Hongbin

    2011-06-01

    In this work, a general and flexible synthetic route towards the synthesis of pyrroloindoline alkaloids was developed. This new strategy features with a palladium mediated sequential arylation-allylation of o-bromoanilides and leads to the construction of oxindoles bearing a full carbon quaternary center. The cheap triphenylphosphine was proved to be a highly effective ligand for this one pot transformation. On the basis of this new method, esermethole and its analogues were synthesized. PMID:21472186

  4. Synthesis of constrained analogues of tryptophan

    PubMed Central

    Negrato, Marco; Abbiati, Giorgio; Dell’Acqua, Monica

    2015-01-01

    Summary A Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues. PMID:26664620

  5. Synthesis and cytotoxic activity of acetogenin analogues.

    PubMed

    Rodier, S; Le Huérou, Y; Renoux, B; Doyon, J; Renard, P; Pierré, A; Gesson, J P; Grée, R

    2000-06-19

    A set of 16 new simplified analogues of acetogenins has been designed based on: (i) the replacement of the bis THF moiety of these natural products by an ethylene glycol bis ether unit; (ii) the introduction of different lipophilic side chains (alkyl, aryl, dialkylamino, O-cholesteryl); (iii) the presence of the same terminal isolactone. In vitro cytotoxic activity against L1210 leukemia is reported. PMID:10890167

  6. The Brookhaven electron analogue, 1953--1957

    SciTech Connect

    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.

  7. Blood Loss Estimation Using Gauze Visual Analogue

    PubMed Central

    Ali Algadiem, Emran; Aleisa, Abdulmohsen Ali; Alsubaie, Huda Ibrahim; Buhlaiqah, Noora Radhi; Algadeeb, Jihad Bagir; Alsneini, Hussain Ali

    2016-01-01

    Background Estimating intraoperative blood loss can be a difficult task, especially when blood is mostly absorbed by gauze. In this study, we have provided an improved method for estimating blood absorbed by gauze. Objectives To develop a guide to estimate blood absorbed by surgical gauze. Materials and Methods A clinical experiment was conducted using aspirated blood and common surgical gauze to create a realistic amount of absorbed blood in the gauze. Different percentages of staining were photographed to create an analogue for the amount of blood absorbed by the gauze. Results A visual analogue scale was created to aid the estimation of blood absorbed by the gauze. The absorptive capacity of different gauze sizes was determined when the gauze was dripping with blood. The amount of reduction in absorption was also determined when the gauze was wetted with normal saline before use. Conclusions The use of a visual analogue may increase the accuracy of blood loss estimation and decrease the consequences related to over or underestimation of blood loss. PMID:27626017

  8. S-Ribosylhomocysteine analogues with the carbon-5 and sulfur atoms replaced by a vinyl or (fluoro)vinyl unit

    PubMed Central

    Wnuk, Stanislaw F.; Lalama, Jennifer; Garmendia, Craig A.; Robert, Jenay; Zhu, Jinge; Pei, Dehua

    2008-01-01

    Treatment of the protected ribose or xylose 5-aldehyde with sulfonyl-stabilized fluorophosphonate gave (fluoro)vinyl sulfones. Stannyldesulfonylation followed by iododestannylation afforded 5,6-dideoxy-6-fluoro-6-iodo-d-ribo or xylo-hex-5-enofuranoses. Coupling of the hexenofuranoses with alkylzinc bromides gave ten-carbon ribosyl- and xylosylhomocysteine analogues incorporating a fluoroalkene. The fluoroalkenyl and alkenyl analogues were evaluated for inhibition of Bacillus subtilis S-ribosylhomocysteinase (LuxS). One of the compounds, 3,5,6-trideoxy-6-fluoro-d-erythro-hex-5-enofuranose, acted as a competitive inhibitor of moderate potency (KI = 96 µM). PMID:18375129

  9. Synthesis of fully active biotinylated analogues of parathyroid hormone and parathyroid hormone-related protein as tools for the characterization of parathyroid hormone receptors.

    PubMed

    Roubini, E; Duong, L T; Gibbons, S W; Leu, C T; Caulfield, M P; Chorev, M; Rosenblatt, M

    1992-04-28

    The synthesis, purification, and characterization of biotinylated analogues of parathyroid hormone (PTH) and PTH-related protein (PTHrP) are described. A novel methodology was developed which allowed the selective biotinylation during solid-phase synthesis of either the Lys13 or Lys26 residue in PTH/PTHrP sequences. Incorporation of orthogonally protected N alpha-Boc-Lys(N epsilon-Fmoc) at a selected position in the sequence, followed by selective side-chain deprotection and biotinylation of the epsilon-amino group, permitted modification of the specific lysine only. Biotinylated analogues of [Nle8,18,Tyr34]bPTH(1-34)NH2 (analogue 1a) were prepared by modification of Lys13 with a biotinyl group (analogue 1) or a biotinyl-epsilon-aminohexanoyl group (analogue 2) or at Lys26 with a biotinyl-epsilon-aminohexanoyl group (analogue 3). A biotinylated PTHrP antagonist [Leu11,D-Trp12,Lys13(N epsilon-(biotinyl-beta-Ala))]PTHrP(7-34)NH2 (analogue 5), was also prepared. In a different synthetic approach, selective modification of the thiol group of [Cys35]PTHrP(1-35)NH2, in solution, with N-biotinyl-N'-(6-maleimidohexanoyl)hydrazide, resulted in analogue 4. The high affinities of the biotinylated analogues for PTH receptors present in human osteosarcoma B-10 cells or in porcine renal cortical membranes (PRCM), were comparable to those of the underivatized parent peptides. The analogues were also highly potent in stimulation of cAMP formation (analogues 1-4) or inhibition of PTH-stimulated adenylyl cyclase (analogue 5) in B-10 cells. The most potent analogue (analogue 1) had potencies in B-10 cells (Kb = 1.5 nM, Km = 0.35 nM) and in porcine renal membranes (Kb = 0.70 nM) identical or similar to those of its parent peptide, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1314656

  10. Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases.

    PubMed

    Basith, Shaherin; Cui, Minghua; Hong, Sunhye; Choi, Sun

    2016-01-01

    Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions. PMID:27455231

  11. Three Efficient Methods for Preparation of Coelenterazine Analogues.

    PubMed

    Shakhmin, Anton; Hall, Mary P; Walker, Joel R; Machleidt, Thomas; Binkowski, Brock F; Wood, Keith V; Kirkland, Thomas A

    2016-07-18

    The growing popularity of bioluminescent assays has highlighted the need for coelenterazine analogues possessing properties tuned for specific applications. However, the structural diversity of known coelenterazine analogues has been limited by current syntheses. Known routes for the preparation of coelenterazine analogues employ harsh reaction conditions that limit access to many substituents and functional groups. Novel synthetic routes reported here establish simple and robust methods for synthesis and investigation of structurally diverse marine luciferase substrates. Specifically, these new routes allow synthesis of coelenterazine analogues containing various heterocyclic motifs and substituted aromatic groups with diverse electronic substituents at the R(2) position. Interesting analogues described herein were characterized by their physicochemical properties, bioluminescent half-life, light output, polarity and cytotoxicity. Some of the analogues represent leads that can be utilized in the development of improved bioluminescent systems. PMID:27305599

  12. [GnRH analogues containing SV-40 virus T-antigen nuclear localization sequence].

    PubMed

    Burov, S V; Iablokova, T V; Dorosh, M Iu; Kriviziuk, E V; Efremov, A M; Orlov, S V

    2010-01-01

    To improve the efficiency of anticancer drugs due to their delivery to intracellular targets a set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized. NLS was attached to the parent molecule via ε-amino group of D-Lysine in position 1 or 6 of peptide sequence using orthogonal protection strategy. The biological activity studies revealed that incorporation of NLS moiety significantly increases cytotoxic activity of palmitoyl-containing GnRH analogues in vitro. The influence of tested peptides on tumor cells does not accompanied by the destruction of cell membrane, as confirmed in experiments with normal fibroblasts, used as a control. PMID:21063449

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

    SciTech Connect

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

    1995-09-01

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

  14. CO2 Removal using a Synthetic Analogue of Carbonic Anhydrase

    SciTech Connect

    Cordatos, Harry

    2010-09-14

    Project attempts to develop a synthetic analogue for carbonic anhydrase and incorporate it in a membrane for separation of CO2 from coal power plant flue gas. Conference poster presents result of first 9 months of project progress including concept, basic system architecture and membrane properties target, results of molecular modeling for analogue - CO2 interaction, and next steps of testing analogue resistance to flue gas contaminants.

  15. Conformationally restrained aromatic analogues of fosmidomycin and FR900098.

    PubMed

    Kurz, Thomas; Schlüter, Katrin; Pein, Miriam; Behrendt, Christoph; Bergmann, Bärbel; Walter, Rolf D

    2007-07-01

    The synthesis and in-vitro antimalarial activity of conformationally restrained bis(pivaloyloxymethyl) ester analogues of the natural product fosmidomycin is presented. In contrast to alpha-aryl-substituted analogues, conformationally restrained aromatic analogues exhibit only moderate in-vitro antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The most active derivative displays an IC(50) value of 47 microM. PMID:17611943

  16. Digitoxin Analogues with Improved Anticytomegalovirus Activity

    PubMed Central

    2014-01-01

    Cardiac glycosides are potent inhibitors of cancer cell growth and possess antiviral activities at nanomolar concentrations. In this study we evaluated the anticytomegalovirus (CMV) activity of digitoxin and several of its analogues. We show that sugar type and sugar length attached to the steroid core structure affects its anticytomegalovirus activity. Structure–activity relationship (SAR) studies identified the l-sugar containing cardiac glycosides as having improved anti-CMV activity and may lead to better understanding of how these compounds inhibit CMV replication. PMID:24900847

  17. Analogue factoring algorithm based on polychromatic interference

    NASA Astrophysics Data System (ADS)

    Tamma, Vincenzo; Garuccio, Augusto; Shih, Yanhua

    2010-08-01

    We present a novel factorization algorithm which can be computed using an analogue computer based on a polychromatic source with a given wavelength bandwidth, a multi-path interferometer and a spectrometer. The core of this algorithm stands on the measurement of the periodicity of a "factoring" function given by an exponential sum at continuous argument by recording a sequence of interferograms associated with suitable units of displacement in the inteferometer. A remarking rescaling property of such interferograms allows, in principle, the prime number decomposition of several large integers. The information about factors is encoded in the location of the inteferogram maxima.

  18. Spectroscopic study of solar twins and analogues

    NASA Astrophysics Data System (ADS)

    Datson, Juliet; Flynn, Chris; Portinari, Laura

    2015-02-01

    Context. Many large stellar surveys have been and are still being carried out, providing huge amounts of data, for which stellar physical parameters will be derived. Solar twins and analogues provide a means to test the calibration of these stellar catalogues because the Sun is the best-studied star and provides precise fundamental parameters. Solar twins should be centred on the solar values. Aims: This spectroscopic study of solar analogues selected from the Geneva-Copenhagen Survey (GCS) at a resolution of 48 000 provides effective temperatures and metallicities for these stars. We test whether our spectroscopic parameters, as well as the previous photometric calibrations, are properly centred on the Sun. In addition, we search for more solar twins in our sample. Methods: The methods used in this work are based on literature methods for solar twin searches and on methods we developed in previous work to distinguish the metallicity-temperature degeneracies in the differential comparison of spectra of solar analogues versus a reference solar reflection spectrum. Results: We derive spectroscopic parameters for 148 solar analogues (about 70 are new entries to the literature) and verify with a-posteriori differential tests that our values are well-centred on the solar values. We use our dataset to assess the two alternative calibrations of the GCS parameters; our methods favour the latest revision. We show that the choice of spectral line list or the choice of asteroid or time of observation does not affect the results. We also identify seven solar twins in our sample, three of which are published here for the first time. Conclusions: Our methods provide an independent means to differentially test the calibration of stellar catalogues around the values of a well-known benchmark star, which makes our work interesting for calibration tests of upcoming Galactic surveys. Based on observations made with ESO Telescopes at the La Silla Observatory under programme ID 077.D

  19. Materials analogue of zero-stiffness structures

    NASA Astrophysics Data System (ADS)

    Kumar, Arun; Subramaniam, Anandh

    2011-04-01

    Anglepoise lamps and certain tensegrities are examples of zero-stiffness structures. These structures are in a state of neutral equilibrium with respect to changes in configuration of the system. Using Eshelby's example of an edge dislocation in a thin plate that can bend, we report the discovery of a non-trivial new class of material structures as an analogue to zero-stiffness structures. For extended positions of the edge dislocation in these structures, the dislocation experiences a zero image force. Salient features of these material structures along with the key differences from conventional zero-stiffness structures are pointed out.

  20. Aromatic A-ring analogues of orobanchol, new germination stimulants for seeds of parasitic weeds.

    PubMed

    Malik, Heetika; Kohlen, Wouter; Jamil, Muhammad; Rutjes, Floris P J T; Zwanenburg, Binne

    2011-04-01

    Strigolactones are signaling compounds in plants of increasing importance. In this paper the focus is on their activity as germinating agents for seeds of parasitic weeds. The syntheses of aromatic A-ring analogues of the germination stimulant orobanchol have been described. Starting substrate is the ABC unit of the stimulant GR24. Oxidation at the C-4 position gives a 4-oxo derivative which on subsequent reduction produces two C-4 epimeric alcohols, syn and anti in a ratio of 82 : 3. For practical access of the C-4 anti alcohol, the predominant syn epimer is inverted by a Mitsunobu procedure. The anti C-4 alcohol is then coupled with the D-ring in a one-pot two-step process involving a formylation and a reaction with bromobutenolide to give a mixture of the diastereomeric aromatic A-ring analogues of orobanchol. In contrast, the syn C-4 alcohol cannot be coupled directly with the D-ring. Protection of the C-4 syn OH is a prequisite. The best protecting function is the SEM group as deprotection after coupling with the D-ring can then readily be achieved. The structures of these new analogues have been ascertained by X-ray analyses. Both diastereomers of the C-4 syn as well as the C-4 anti orobanchol analogues have been tested as germination agents of seeds of Striga hermonthica and Orobanche ramosa. In addition, the acetates of both epimeric C-4 alcohols have been prepared and tested. Both diastereomers of the 4-oxo derivative have been prepared and bioassayed as well. The bioassays reveal that the diastereomers having the natural relative configuration are most active. The data also suggest that hydrogen bonding is not an important factor in the binding of the stimulant molecules in the receptor. PMID:21321762

  1. The electrical properties of Mars analogue dust

    NASA Astrophysics Data System (ADS)

    Merrison, J.; Jensen, J.; Kinch, K.; Mugford, R.; Nørnberg, P.

    2004-03-01

    Dust is a major environmental factor on the surface and in the atmosphere of Mars. Knowing the electrical charge state of this dust would be of both scientific interest and important for the safety of instruments on the Martian surface. In this study the first measurements have been performed of dust electrification using suspended Mars analogue material. This has been achieved by attracting suspended dust onto electrodes placed inside a Mars simulation wind tunnel. The Mars analogue used was from Salten Skov in Denmark, this contained a high concentration of ferric oxide precipitate. Once suspended, this dust was found to consist of almost equal quantities of negatively (46±6%) and positively (44±15%) charged grains. These grains were estimated to typically carry a net charge of around 10 5e, this is sufficient to dominate the processes of adhesion and cohesion of this suspended dust. Evidence is presented for electrostatic aggregation of the dust while in suspension. Development of a simple instrument for measuring electrical charging of the suspended dust on Mars will be discussed.

  2. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

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

  3. Self-Powered Analogue Smart Skin.

    PubMed

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

    2016-04-26

    The progress of smart skin technology presents unprecedented opportunities for artificial intelligence. Resolution enhancement and energy conservation are critical to improve the perception and standby time of robots. Here, we present a self-powered analogue smart skin for detecting contact location and velocity of the object, based on a single-electrode contact electrification effect and planar electrostatic induction. Using an analogue localizing method, the resolution of this two-dimensional smart skin can be achieved at 1.9 mm with only four terminals, which notably decreases the terminal number of smart skins. The sensitivity of this smart skin is remarkable, which can even perceive the perturbation of a honey bee. Meanwhile, benefiting from the triboelectric mechanism, extra power supply is unnecessary for this smart skin. Therefore, it solves the problems of batteries and connecting wires for smart skins. With microstructured poly(dimethylsiloxane) films and silver nanowire electrodes, it can be covered on the skin with transparency, flexibility, and high sensitivity. PMID:27010713

  4. Therapeutic use of vitamin D and its analogues in autoimmunity.

    PubMed

    Fletcher, Jean M; Basdeo, Sharee A; Allen, Aideen C; Dunne, Padraic J

    2012-01-01

    In recent years, there has been great interest in the role of vitamin D in a number of diverse human diseases including autoimmunity, allergy, infection, cardiovascular disease, chronic lung disease, transplantation and cancer. Vitamin D is best known for its role in calcium metabolism; however it also has potent immunomodulatory effects. Epidemiological studies suggest that vitamin D deficiency may be a significant risk factor for many diseases. Furthermore, there is accumulating evidence from experimental studies that vitamin D has anti-inflammatory effects. Recent studies have indicated that a surprisingly high proportion of people are vitamin D deficient, suggesting that vitamin D supplementation may be of benefit to human health. This review will focus on the role of vitamin D in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis and diabetes. We will review the epidemiological and experimental evidence for the protective effects of vitamin D in autoimmunity, as well as the preliminary vitamin D intervention studies and the most recent patented vitamin D analogues. PMID:22122009

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

    ERIC Educational Resources Information Center

    Stichter, Janine Peck

    2001-01-01

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

  6. Space Analogue Environments: Are the Populations Comparable?

    NASA Astrophysics Data System (ADS)

    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

  7. Development of new mitomycin C and porfiromycin analogues.

    PubMed

    Iyengar, B S; Lin, H J; Cheng, L; Remers, W A; Bradner, W T

    1981-08-01

    New mitomycin C and porfiromycin analogues were prepared by treating mitomycin A and N-methylmitomycin A with a variety of amines, including aziridines, allylamines, propargylamines, chloroalkylamines, hydroxyalkylamines, glycine derivatives, aralkylamines, and heterocyclic amines. All analogues were evaluated against P-388 murine leukemia and selected ones were examined for their leukopenic properties. Certain analogues were found to be superior to mitomycin C in potency, efficacy, and therapeutic ratio in the P-388 assay. The most active substituents at the mitosane 7 position included aziridine, 2-methylaziridine, propargylamine, furfurylamine, methyl glycinate, and 3-aminopyridine. Mitomycin A and the 7-aziridino, 7-(2-methylaziridino), and 3-aminopyridine analogues were less leukopenic than mitomycin C. Certain other analogues, including propargylamino and methyl glycinate, were highly leukopenic. The three compounds tested against B-16 melanoma in mice were significantly more effective than mitomycin C in this assay. Previously established structure--activity relationships were found inadequate to account for all of the new data. PMID:7328599

  8. Synthesis and biological activity of tetralone abscisic acid analogues.

    PubMed

    Nyangulu, James M; Nelson, Ken M; Rose, Patricia A; Gai, Yuanzhu; Loewen, Mary; Lougheed, Brenda; Quail, J Wilson; Cutler, Adrian J; Abrams, Suzanne R

    2006-04-01

    Bicyclic analogues of the plant hormone abscisic acid (ABA) were designed to incorporate the structural elements and functional groups of the parent molecule that are required for biological activity. The resulting tetralone analogues were predicted to have enhanced biological activity in plants, in part because oxidized products would not cyclize to forms corresponding to the inactive catabolite phaseic acid. The tetralone analogues were synthesized in seven steps from 1-tetralone and a range of analogues were accessible through a second route starting with 2-methyl-1-naphthol. Tetralone ABA 8 was found to have greater activity than ABA in two bioassays. The absolute configuration of (+)-8 was established by X-ray crystallography of a RAMP hydrazone derivative. The hydroxymethyl compounds 10 and 11, analogues for studying the roles of 8- and 9-hydroxy ABA 3 and 6, were also synthesized and found to be active. PMID:16557330

  9. Derivatisable Cyanobactin Analogues: A Semisynthetic Approach

    PubMed Central

    Oueis, Emilia; Adamson, Catherine; Mann, Greg; Ludewig, Hannes; Redpath, Philip; Migaud, Marie

    2015-01-01

    Abstract Many natural cyclic peptides have potent and potentially useful biological activities. Their use as therapeutic starting points is often limited by the quantities available, the lack of known biological targets and the practical limits on diversification to fine‐tune their properties. We report the use of enzymes from the cyanobactin family to heterocyclise and macrocyclise chemically synthesised substrates so as to allow larger‐scale syntheses and better control over derivatisation. We have made cyclic peptides containing orthogonal reactive groups, azide or dehydroalanine, that allow chemical diversification, including the use of fluorescent labels that can help in target identification. We show that the enzymes are compatible and efficient with such unnatural substrates. The combination of chemical synthesis and enzymatic transformation could help renew interest in investigating natural cyclic peptides with biological activity, as well as their unnatural analogues, as therapeutics. PMID:26507241

  10. Solution Processed PEDOT Analogues in Electrochemical Supercapacitors.

    PubMed

    Österholm, Anna M; Ponder, James F; Kerszulis, Justin A; Reynolds, John R

    2016-06-01

    We have designed fully soluble ProDOTx-EDOTy copolymers that are electrochemically equivalent to electropolymerized PEDOT without using any surfactants or dispersants. We show that these copolymers can be incorporated as active layers in solution processed thin film supercapacitors to demonstrate capacitance, stability, and voltage similar to the values of those that use electrodeposited PEDOT as the active material with the added advantage of the possibility for large scale, high-throughput processing. These Type I supercapacitors provide exceptional cell voltages (up to 1.6 V), highly symmetrical charge/discharge behavior, promising long-term stability exceeding 50 000 charge/discharge cycles, as well as energy (4-18 Wh/kg) and power densities (0.8-3.3 kW/kg) that are comparable to those of electrochemically synthesized analogues. PMID:27195798

  11. Liver S9 Fraction-Derived Metabolites of Curcumin Analogue UBS109

    PubMed Central

    2014-01-01

    To address the shortcomings of the natural product curcumin, many groups have created analogues that share similar structural features while displaying superior properties, particularly in anticancer drug discovery. Relatively unexplored have been the mechanisms by which such compounds are metabolized. A comprehensive in vitro study of a curcumin analogue (UBS109) in liver S9 fractions from five different species is presented. Further, we examine the cell-based bioactivity of the major metabolites. In spite of the fact that UBS109 reduces tumor growth in mice, it is quickly metabolized in vitro and 94% protein bound in mouse plasma. The primary monounsaturated metabolite is only modestly bioactive against MDA-MB-231 breast cancer cells. These observations suggest that while the α,β-unsaturated ketone common to curcumin analogues is important for bioactivity, protein binding and tissue distribution may serve to protect UBS109 from full metabolism in vivo while allowing it to exert a pharmacological effect by means of slow drug release. PMID:24900828

  12. Natural analogues of nuclear waste glass corrosion.

    SciTech Connect

    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.

  13. Evolving a polymerase for hydrophobic base analogues.

    PubMed

    Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

    2009-10-21

    Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity. PMID:19778048

  14. Current european regulatory perspectives on insulin analogues.

    PubMed

    Enzmann, Harald G; Weise, Martina

    2011-01-01

    Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions. PMID:21736748

  15. Synthesis of novel spinosyn A analogues by Pd-mediated transformations.

    PubMed

    Tietze, Lutz F; Brasche, Gordon; Grube, Alexander; Böhnke, Niels; Stadler, Christian

    2007-01-01

    The concept of modern crop protection demands for a continuous supply of new or modified established pesticides to avoid the development of serious resistances. Recent reports on the insecticidal spinosyns 1 and 2 show that also this class of pest managing agents is increasingly exposed to the formation of resistances. The synthesis of new derivatives is therefore highly desirable. We describe in this paper a convergent approach towards novel enantiopure spinosyn A analogues of type 3, which is based on investigations of structure-activity relationships and employs a twofold Heck reaction as key step for the preparation of the tricyclic backbone assembly. PMID:17654624

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

    PubMed Central

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

    2012-01-01

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

  17. Testing nucleoside analogues as inhibitors of Bacillus anthracis spore germination in vitro and in macrophage cell culture.

    PubMed

    Alvarez, Zadkiel; Lee, Kyungae; Abel-Santos, Ernesto

    2010-12-01

    Bacillus anthracis, the etiological agent of anthrax, has a dormant stage in its life cycle known as the endospore. When conditions become favorable, spores germinate and transform into vegetative bacteria. In inhalational anthrax, the most fatal manifestation of the disease, spores enter the organism through the respiratory tract and germinate in phagosomes of alveolar macrophages. Germinated cells can then produce toxins and establish infection. Thus, germination is a crucial step for the initiation of pathogenesis. B. anthracis spore germination is activated by a wide variety of amino acids and purine nucleosides. Inosine and l-alanine are the two most potent nutrient germinants in vitro. Recent studies have shown that germination can be hindered by isomers or structural analogues of germinants. 6-Thioguanosine (6-TG), a guanosine analogue, is able to inhibit germination and prevent B. anthracis toxin-mediated necrosis in murine macrophages. In this study, we screened 46 different nucleoside analogues as activators or inhibitors of B. anthracis spore germination in vitro. These compounds were also tested for their ability to protect the macrophage cell line J774a.1 from B. anthracis cytotoxicity. Structure-activity relationship analysis of activators and inhibitors clarified the binding mechanisms of nucleosides to B. anthracis spores. In contrast, no structure-activity relationships were apparent for compounds that protected macrophages from B. anthracis-mediated killing. However, multiple inhibitors additively protected macrophages from B. anthracis. PMID:20921305

  18. The preparation of zaragozic acid A analogues by directed biosynthesis.

    PubMed

    Chen, T S; Petuch, B; MacConnell, J; White, R; Dezeny, G; Arison, B; Bergstrom, J D; Colwell, L; Huang, L; Monaghan, R L

    1994-11-01

    Zaragozic acid A analogues are produced by an unidentified sterile fungus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3-thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, or 4-fluorobenzoic acid. The analogues carry 2-thiophenyl, 3-thiophenyl, 2-furyl, o-fluorophenyl, m-fluorophenyl, or p-fluorophenyl group, respectively, at C-6' of the C-1 alkyl side chain replacing the phenyl group of natural zaragozic acid A. All the new analogues of zaragozic acid A possess picomolar inhibitory activity against squalene synthase in vitro. PMID:8002393

  19. Recent developments in naturally derived antimalarials: cryptolepine analogues.

    PubMed

    Wright, Colin W

    2007-06-01

    Increasing resistance of Plasmodium falciparum to commonly used antimalarial drugs has made the need for new agents increasingly urgent. In this paper, the potential of cryptolepine, an alkaloid from the West African shrub Cryptolepis sanguinolenta, as a lead towards new antimalarial agents is discussed. Several cryptolepine analogues have been synthesized that have promising in-vitro and in-vivo antimalarial activity. Studies on the antimalarial modes of action of these analogues indicate that they may have different or additional modes of action to the parent compound. Elucidation of the mode of action may facilitate the development of more potent antimalarial cryptolepine analogues. PMID:17637183

  20. Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues.

    PubMed

    Roselli, Mariagrazia; Carocci, Alessia; Budriesi, Roberta; Micucci, Matteo; Toma, Maddalena; Di Cesare Mannelli, Lorenzo; Lovece, Angelo; Catalano, Alessia; Cavalluzzi, Maria Maddalena; Bruno, Claudio; De Palma, Annalisa; Contino, Marialessandra; Perrone, Maria Grazia; Colabufo, Nicola Antonio; Chiarini, Alberto; Franchini, Carlo; Ghelardini, Carla; Habtemariam, Solomon; Lentini, Giovanni

    2016-10-01

    Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation. PMID:27267000

  1. Actions of Thyroid Hormone Analogues on Chemokines

    PubMed Central

    Glinsky, Gennadi V.

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  2. Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer.

    PubMed

    Bodei, Lisa; Kwekkeboom, Dik J; Kidd, Mark; Modlin, Irvin M; Krenning, Eric P

    2016-05-01

    Peptide receptor radionuclide therapy (PRRT) has been utilized for more than two decades and has been accepted as an effective therapeutic modality in the treatment of inoperable or metastatic gastroenteropancreatic neuroendocrine neoplasms (NENs) or neuroendocrine tumors (NETs). The two most commonly used radiopeptides for PRRT, (90)Y-octreotide and (177)Lu-octreotate, produce disease-control rates of 68%-94%, with progression-free survival rates that compare favorably with chemotherapy, somatostatin analogues, and newer targeted therapies. In addition, biochemical and symptomatic responses are commonly observed. In general, PRRT is well tolerated with only low to moderate toxicity in most individuals. In line with the need to place PRRT in the therapeutic sequence of gastroenteropancreatic NENs, a recently sponsored phase III randomized trial in small intestine NENs treated with (177)Lu-octreotate vs high-dose octreotide long-acting release demonstrated that (177)Lu-octreotate significantly improved progression-free survival. Other strategies that are presently being developed include combinations with targeted therapies or chemotherapy, intra-arterial PRRT, and salvage treatments. Sophisticated molecular tools need to be incorporated into the management strategy to more effectively define therapeutic efficacy and for an early identification of adverse events. The strategy of randomized controlled trials is a key issue to standardize the treatment and establish the position of PRRT in the therapeutic algorithm of NENs. PMID:27067503

  3. Actions of Thyroid Hormone Analogues on Chemokines.

    PubMed

    Davis, Paul J; Glinsky, Gennadi V; Lin, Hung-Yun; Mousa, Shaker A

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3'-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  4. Cell-Cycle Analyses Using Thymidine Analogues in Fission Yeast

    PubMed Central

    Anda, Silje; Boye, Erik; Grallert, Beata

    2014-01-01

    Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2′-deoxyuridine (EdU) and 5-Chloro-2′-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2′-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry. PMID:24551125

  5. Synthesis of a stable and orally bioavailable englerin analogue.

    PubMed

    Fash, David M; Peer, Cody J; Li, Zhenwu; Talisman, Ian J; Hayavi, Sima; Sulzmaier, Florian J; Ramos, Joe W; Sourbier, Carole; Neckers, Leonard; Figg, W Douglas; Beutler, John A; Chain, William J

    2016-06-01

    Synthesis of analogues of englerin A with a reduced propensity for hydrolysis of the glycolate moiety led to a compound which possessed the renal cancer cell selectivity of the parent and was orally bioavailable in mice. PMID:27107948

  6. Efficient total syntheses and biological activities of two teixobactin analogues.

    PubMed

    Parmar, Anish; Iyer, Abhishek; Vincent, Charlotte S; Van Lysebetten, Dorien; Prior, Stephen H; Madder, Annemieke; Taylor, Edward J; Singh, Ishwar

    2016-04-26

    The discovery of the new antibiotic teixobactin has been timely in the race for unearthing novel antibiotics wherein the emergence of drug resistant bacteria poses a serious threat worldwide. Herein, we present the total syntheses and biological activities of two teixobactin analogues. This approach is simple, efficient and has several advantages: it uses commercially available building blocks (except AllocHN-d-Thr-OH), has a single purification step and a good recovery (22%). By using this approach we have synthesised two teixobactin analogues and established that the d-amino acids are critical for the antimicrobial activity of these analogues. With continuing high expectations from teixobactin, this work can be regarded as a stepping stone towards an in depth study of teixobactin, its analogues and the quest for synthesising similar molecules. PMID:26984316

  7. Defining Analytical Strategies for Mars Sample Return with Analogue Missions

    NASA Astrophysics Data System (ADS)

    Osinski, G. R.; Sapers, H. M.; Francis, R.; Pontefract, A.; Tornabene, L. L.; Haltigin, T.

    2016-05-01

    The characterization of biosignatures in MSR samples will require integrated, cross-platform laboratory analyses carefully correlated and calibrated with Rover-based technologies. Analogue missions provide context for implementation and assessment.

  8. Effects of Prostaglandin Analogues on Aqueous Humor Outflow Pathways

    PubMed Central

    Winkler, Nelson S.

    2014-01-01

    Abstract Elevated intraocular pressure (IOP) is the most prevalent risk factor for glaucoma. All treatments, whether surgical or pharmaceutical, are aimed at lowering IOP. Prostaglandin analogues are a first line therapy for glaucoma due to their ability to reduce IOP, once-daily dosing, efficacy, and minimal side-effect profile. Whereas prostaglandin analogues have been known to alter aqueous humor outflow through the unconventional (uveoscleral) pathway, more recent evidence suggests their action also occurs through the conventional (trabecular) pathway. Understanding how prostaglandin analogues successfully lower IOP is important, as this information may lead to the discovery of new molecular targets for future therapeutic intervention. This review explores the current understanding of prostaglandin analogue biology as it pertains to IOP reduction and improved aqueous humor outflow facility. PMID:24359106

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

    PubMed

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? PMID:27262103

  10. Structural analogues of diosgenyl saponins: synthesis and anticancer activity.

    PubMed

    Kaskiw, Matthew J; Tassotto, Mary Lynn; Mok, Mac; Tokar, Stacey L; Pycko, Roxanne; Th'ng, John; Jiang, Zi-Hua

    2009-11-15

    Saponins display various biological activities including anti-tumor activity. Recently intensive research has been focused on developing saponins for tumor therapies. The diosgenyl saponin dioscin is one of the most common steroidal saponins and exhibits potent anticancer activity in several human cancer cells through apoptosis-inducing pathways. In this paper, we describe the synthesis of several diosgenyl saponin analogues containing either a 2-amino-2-deoxy-beta-d-glucopyranosyl residue or an alpha-l-rhamnopyranosyl-(1-->4)-2-amino-2-deoxy-beta-d-glucopyranosyl residue with different acyl substituents on the amino group. The cytotoxic activity of these compounds was evaluated in MCF-7 breast cancer cells and HeLa cervical cancer cells. Structure-activity relationship studies show that the disaccharide saponin analogues are in general less active than their corresponding monosaccharide analogues. The incorporation of an aromatic nitro functionality into these saponin analogues does not exhibit significant effect on their cytotoxic activity. PMID:19819703

  11. Vitamin E Analogue Improves Rabbit Sperm Quality during the Process of Cryopreservation through Its Antioxidative Action

    PubMed Central

    Zhu, Zhendong; Fan, Xiaoteng; Lv, Yinghua; Zhang, Nan; Fan, Chuning; Zhang, Pengfei; Zeng, Wenxian

    2015-01-01

    The process of cryopreservation results in high concentration of reactive oxygen species which is detrimental to spermatozoa. The aim of this study was to investigate whether addition of vitamin E analogue to freezing extender can facilitate the cryosurvival of spermatozoa in rabbits, and how vitamin E protects spermatozoa against damages during the process of preservation. Freshly ejaculated semen was diluted with Tris-citrate-glucose extender supplemented with different concentrations of Trolox (a vitamin E analogue). The level of radical oxygen species (ROS) in spermatozoa that was exposed to Trolox was significantly lower than that of the control during each step of the process of preservation. The percentage of frozen-thawed spermatozoa with lipid peroxidation in the Trolox treatments was significantly lower than that of the control. The motility, intact acrosome, membrane integrity and mitochondrial potentials of the frozen-thawed spermatozoa in the treatment of 200 μM Trolox were significantly higher than those of the control. These observations suggest that addition of vitamin E to a freezing extender leads to higher integrity of acrosome, plasma membrane and mitochondrial membrane potential as well as higher motility. Vitamin E protects spermatozoa through its capacity to quench ROS accumulation and lipid peroxidation during the process of preservation. Addition of Trolox is recommended to facilitate the improvement of semen preservation for the rabbit breeding industry. PMID:26700473

  12. Carbacaprazamycins: Chemically Stable Analogues of the Caprazamycin Nucleoside Antibiotics.

    PubMed

    Ichikawa, Satoshi; Yamaguchi, Mayumi; Hsuan, Lee Shang; Kato, Yuta; Matsuda, Akira

    2015-04-10

    Carbacaprazamycins, which are chemically stable analogues of caprazamycins, were designed and synthesized. These analogues were active against drug-resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and their activities were comparable to those of the parent caprazamycins. The effect of treatment with carbacaprazamycin on morphological changes in S. aureus indicated that the mode of action was completely different from those of existing peptidoglycan inhibitors. PMID:27622529

  13. Analogue and digital linear modulation techniques for mobile satellite

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  14. Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

    PubMed Central

    Shrestha, Sanjib K.; Fosso, Marina Y.; Green, Keith D.

    2015-01-01

    In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter and 1.95 to 7.8 mg/liter, respectively. However, C4, C6, and C8 TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC50s) for the most potent TOB analogues (C12 and C14) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C12 and C14 appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs. PMID:26033722

  15. Analogue gravitational phenomena in Bose-Einstein condensates

    NASA Astrophysics Data System (ADS)

    Finazzi, Stefano

    2012-08-01

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

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

    PubMed Central

    Satishkumar, Sakilam; Vuram, Prasanna K.; Relangi, Siva Subrahmanyam; Gurram, Venkateshwarlu; Zhou, Hong; Kreitman, Robert J.; Montemayor, Michelle M. Martínez; Yang, Lijia; Kaliyaperumal, Muralidharan; Sharma, Somesh; Pottabathini, Narender; Lakshman, Mahesh K.

    2016-01-01

    Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest on the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL), and chronic lymphocytic leukemia (CLL) cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribo analogue of cladribine possessed activity, but was least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, only cladribine and its ribose analogue were most active. PMID:26556315

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

    PubMed Central

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

    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 interacts with and activates PXR and examined selected BPA analogues to determine whether they bind to and activate PXR. Methods: Cell-based reporter assays, in silico ligand–PXR docking studies, and site-directed mutagenesis were combined to study the interaction between BPA and PXR. We also investigated the influence of BPA and its analogues on the regulation of PXR target genes in human LS180 cells. Results: We found that BPA and several of its analogues are potent agonists for human PXR (hPXR) but do not affect mouse PXR activity. We identified key residues within hPXR’s ligand-binding pocket that constitute points of interaction with BPA. We also deduced the structural requirements of BPA analogues that activate hPXR. BPA and its analogues can also induce PXR target gene expression in human LS180 cells. Conclusions: The present study advances our understanding of the mechanism by which BPA interacts with and activates human PXR. Activation of PXR by BPA may explain some of the adverse effects of BPA in humans. PMID:22214767

  18. Hydrophobic surfactant proteins and their analogues.

    PubMed

    Walther, Frans J; Waring, Alan J; Sherman, Mark A; Zasadzinski, Joseph A; Gordon, Larry M

    2007-01-01

    Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film enriched in surfactant lipids, hence preventing cellular collapse during respiration. Surfactant therapy using bovine or porcine lung surfactant extracts, which contain only polar lipids and native SP-B and SP-C, has dramatically improved the therapeutic outcomes of preterm infants with respiratory distress syndrome (RDS). One important goal of surfactant researchers is to replace animal-derived therapies with fully synthetic preparations based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. Here, we review recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins. Such SP-B and SP-C mimics offer the possibility of studying the mechanisms of action of the respective native proteins, and may allow the design of optimized surfactant formulations for specific pulmonary diseases (e.g., acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)). These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments. PMID:17575474

  19. Vascular disrupting activity of combretastatin analogues.

    PubMed

    Porcù, Elena; Salvador, Alessia; Primac, Irina; Mitola, Stefania; Ronca, Roberto; Ravelli, Cosetta; Bortolozzi, Roberta; Vedaldi, Daniela; Romagnoli, Romeo; Basso, Giuseppe; Viola, Giampietro

    2016-08-01

    Tubulin binding agents (TBAs) are drugs commonly used in cancer therapy as antimitotics. In the last years it has been described that TBAs, like combretastatin A-4 (CA-4), present also vascular disrupting activity and among its derivatives we identified three analogues endowed with potent microtubule depolymerizing activity, higher than that of the lead compound. In this paper we have investigated the anti-vascular activity of these derivatives. We tested the anti-angiogenic effects in human umbilical endothelial cells (HUVEC) and in vivo in chick chorioallantoic membrane assay (CAM), and in a syngeneic tumor mouse model. The three molecules, compound 1: 1-(3,4,5-trimethoxyphenyl)-5-(4-ethoxyphenyl)-1H-1,2,4-triazole; compound 2: (1-(3,4,5-trimethoxyphenyl)-5-(4-ethoxyphenyl)-1H-tetrazole, compound-3 (4-amino-2-p-tolylaminothiazol-5-yl)-(3,4,5-trimethoxyphenyl)-methanone) showed a moderate effect on the growth of HUVEC cells at concentrations below 200nM. At lower concentrations (5-20nM), in particular compound 2, they induced inhibition of capillary tube formation, inhibition of endothelial cell migration and affected endothelial cell morphology as demonstrated by the alteration of the microfilaments network. Moreover, they also increased permeability of HUVEC cells in a time dependent manner. In addition, compounds 1 and 3, as well as the reference compound CA-4, inhibited VEGF-induced phosphorylation of VE-cadherin and in addition compound 3 prevented the VEGF-induced phosphorylation of FAK. In CAM assay, both compounds 2 and 3 efficiently counteracted the strong angiogenic response induced by bFGF, even at the lowest concentration used (1pmol/egg). Moreover in a syngenic mouse model, compounds 1-3 after a single i.p. injection (30mg/kg), showed a stronger reduction of microvascular density. Altogether our results identified these derivatives as potential new vascular disrupting agents candidates. PMID:27235861

  20. Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

    PubMed Central

    Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

    2014-01-01

    Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

  1. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    NASA Astrophysics Data System (ADS)

    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

  2. Testing small molecule analogues of the Acanthocheilonema viteae immunomodulator ES-62 against clinically relevant allergens.

    PubMed

    Janicova, L; Rzepecka, J; Rodgers, D T; Doonan, J; Bell, K S; Lumb, F E; Suckling, C J; Harnett, M M; Harnett, W

    2016-06-01

    ES-62 is a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that protects against ovalbumin (OVA)-induced airway hyper-responsiveness in mice by virtue of covalently attached anti-inflammatory phosphorylcholine (PC) residues. We have recently generated a library of small molecule analogues (SMAs) of ES-62 based around its active PC moiety as a starting point in novel drug development for asthma and identified two compounds - termed 11a and 12b - that mirror ES-62's protective effects. In this study, we have moved away from OVA, a model allergen, to test the SMAs against two clinically relevant allergens - house dust mite (HDM) and cockroach allergen (CR) extract. We show that both SMAs offer some protection against development of lung allergic responses to CR, in particular reducing eosinophil infiltration, whereas only SMA 12b is effective in protecting against eosinophil-dependent HDM-induced allergy. These data therefore suggest that helminth molecule-induced protection against model allergens may not necessarily translate to clinically relevant allergens. Nevertheless, in this study, we have managed to demonstrate that it is possible to produce synthetic drug-like molecules based on a parasitic worm product that show therapeutic potential with respect to asthma resulting from known triggers in humans. PMID:27059010

  3. Incorporation of tryptophan analogues into the lantibiotic nisin.

    PubMed

    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. PMID:26872656

  4. Phosphonate analogues of carboxypeptidase A substrates are potent transition-state analogue inhibitors.

    PubMed

    Hanson, J E; Kaplan, A P; Bartlett, P A

    1989-07-25

    Analogues of tri- and tetrapeptide substrates of carboxypeptidase A in which the scissile peptide linkage is replaced with a phosphonate moiety (-PO2--O-) were synthesized and evaluated as inhibitors of the enzyme. The inhibitors terminated with either L-lactate or L-phenyllactate [designated (O) Ala and (O) Phe, respectively] in the P1' position. Transition-state analogy was shown for a series of 14 tri- and tetrapeptide derivatives containing the structure RCO-AlaP-(O)Ala [RCO-AP(O)A, AP indicates the phosphonic acid analogue of alanine] by the correlation of the Ki values for the inhibitors and the Km/kcat values for the corresponding amide substrates. This correlation supports a transition state for the enzymatic reaction that resembles the tetrahedral intermediate formed upon addition of water to the scissile carbonyl group. The inhibitors containing (O) Phe at the P1' position proved to be the most potent reversible inhibitors of carboxypeptidase A reported to date: the dissociation constants of ZAFP(O)F, ZAAP(O)F, and ZFAP(O)F are 4, 3, and 1 pM, respectively. Because of the high affinity of these inhibitors, their dissociation constants could not be determined by steady-state methods. Instead, the course of the association and dissociation processes was monitored for each inhibitor as its equilibrium with the enzyme was established in both the forward and reverse directions. A phosphonamidate analogue, ZAAPF, in which the peptide linkage is replaced with a -PO2-NH- moiety, was prepared and shown to hydrolyze rapidly at neutral pH (t1/2 = 20 min at pH 7.5). This inhibitor is bound an order of magnitude less tightly than the corresponding phosphonate, ZAAP(O)F, a result that contrasts with the 840-fold higher affinity of phosphonamidates for thermolysin [Bartlett, P. A., & Marlowe, C. K. (1987) Science 235, 569-571], a zinc peptidase with a similar arrangement of active-site catalytic residues. PMID:2790000

  5. Terrestrial research in Mars analogue environments

    NASA Astrophysics Data System (ADS)

    Osipov, G.

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

  6. Spectral analysis of lunar analogue samples

    NASA Astrophysics Data System (ADS)

    Offringa, Marloes; Foing, Bernard

    2016-04-01

    Analyses of samples derived from terrestrial analogue sites are used to study lunar processes in their geological context (Foing, Stoker, Ehrenfreund, 2011). For this study samples from the volcanic region of the Eifel, Germany collected during field campaigns (Foing et al., 2010), are analyzed with a variety of spectrometers. The aim is to obtain a database of analyzed samples that could be used as a reference for future in situ measurements. Equipment used in the laboratory consists of a Fourier Transform Infrared (FTIR) spectrometer, an X-Ray Fluorescence (XRF) spectrometer, a Raman laser spectrometer, as well as UV-VIS and NIR reflectance spectrometers. The Raman, UV-VIS and NIR are also used in combination with the EXoGeoLab mock-up lander during field campaigns (Foing, Stoker, Ehrenfreund, 2011). Calibration of the UV-VIS and NIR reflectance spectrometers is the main focus of this research in order to obtain the clearest spectra. The calibration of the UV-VIS and NIR reflectance spectrometers requires the use of a good light source as well as suitable optical fibers to create a signal that covers the widest range in wavelengths available. To eliminate noise towards the edges of this range, multiple measurements are averaged and data is processed by dividing the signal by reference spectra. Calibration of the devices by creating a new dark and reference spectra has to take place after every sample measurement. In this way we take into account changes that occur in the signal due to the eating of the devices during the measurements. Moreover, the integration time is adjusted to obtain a clear signal without leading to oversaturation in the reflectance spectrum. The typical integration times for the UV-VIS reflectance spectrometer vary between 1 - 18 s, depending on the amount of daylight during experiments. For the NIR reflectance spectrometer the integration time resulting in the best signals is approximately 150 ms in combination with a broad spectrum light

  7. Iron isotopes in an Archean ocean analogue

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  8. Review of insulin and its analogues in diabetes mellitus.

    PubMed

    Mane, Krishnappa; Chaluvaraju, Kc; Niranjan, Ms; Zaranappa, Tr; Manjuthej, Tr

    2012-03-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin's, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  9. Migrastatin analogues target fascin to block tumour metastasis

    SciTech Connect

    Chen, L.; Jakoncic, J.; Yang, S.; Zhang, J.; Huang, X.Y.

    2010-04-15

    Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces, and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.

  10. Membrane-permeable Triphosphate Prodrugs of Nucleoside Analogues.

    PubMed

    Gollnest, Tristan; Dinis de Oliveira, Thiago; Rath, Anna; Hauber, Ilona; Schols, Dominique; Balzarini, Jan; Meier, Chris

    2016-04-18

    The metabolic conversion of nucleoside analogues into their triphosphates often proceeds insufficiently. Rate-limitations can be at the mono-, but also at the di- and triphosphorylation steps. We developed a nucleoside triphosphate (NTP) delivery system (TriPPPro-approach). In this approach, NTPs are masked by two bioreversible units at the γ-phosphate. Using a procedure involving H-phosphonate chemistry, a series of derivatives bearing approved, as well as potentially antivirally active, nucleoside analogues was synthesized. The enzyme-triggered delivery of NTPs was demonstrated by pig liver esterase, in human T-lymphocyte cell extracts and by a polymerase chain reaction using a prodrug of thymidine triphosphate. The TriPPPro-compounds of some HIV-inactive nucleoside analogues showed marked anti-HIV activity. For cellular uptake studies, a fluorescent TriPPPro-compound was prepared that delivered the triphosphorylated metabolite to intact CEM cells. PMID:27008042

  11. The metabolic and mitogenic properties of basal insulin analogues

    PubMed Central

    2013-01-01

    Context Retrospective, observational studies have reported an association between diabetes treatment with insulin and a higher incidence of cancer. Objective Overview the literature for in vitro and in vivo studies of the metabolic and mitogenic properties of basal insulin analogues and assess the implications for clinical use. Methods Relevant studies were identified through PubMed and congress abstract database searches; data on metabolic and mitogenic signalling in relation to insulin treatment of diabetes are included in this review. Results The balance of evidence shows that although some analogues have demonstrated mitogenic potency in some in vitro studies in cancer cell lines, these findings do not translate to the in vivo setting in animals or to the clinical setting in humans. Conclusions The current consensus is that there is no clinical or in vivo evidence to indicate that any commercially available insulin analogue has carcinogenic effects. Large-scale, prospective clinical and observational studies will further establish any potential link. PMID:23373726

  12. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    PubMed

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

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines. PMID:27311894

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

    PubMed

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

    2016-05-01

    We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC). PMID:27005578

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

    PubMed

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

    2015-11-01

    The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies. PMID:26438084

  15. Nicorandil analogues containing NO-donor furoxans and related furazans.

    PubMed

    Boschi, D; Cena, C; Di Stilo, A; Fruttero, R; Gasco, A

    2000-07-01

    The synthesis and in vitro vasodilating properties of hybrid compounds in which furoxan (1,2,5-oxadiazole 2-oxide) moieties, endowed with different NO-donor properties, were substituted for the nitroxy function of Nicorandil are reported. The corresponding cyanoguanidine analogues are also considered. This approach has led to a series of vasorelaxing compounds devoid of affinity for K(ATP) channels, whose activity is prevalently due to their ability to activate sGC, at the concentrations of the experiments. Related furazan (1,2,5-oxadiazole) derivatives, unable to release nitric oxide were also prepared and studied for control. The amide analogues of Nicorandil display feeble vasorelaxing action not involving the activation of K+ channels, while in the guanidine analogues, this mechanism seems to underlie this action. PMID:10976520

  16. Analogue modelling of syntectonic leucosomes in migmatitic schists

    NASA Astrophysics Data System (ADS)

    Druguet, Elena; Carreras, Jordi

    2006-10-01

    Migmatites from the Cap de Creus tectonometamorphic belt display a wide variety of structures, from those formed when the leucosomes were melt-bearing, to those developed during solid-state deformation. The observed field structures have been modelled by means of analogue experiments. The materials used in the models are layered plasticine as a schist analogue, and chocolate as analogue of the crystallizing leucosome. A model for the development of syntectonic migmatites is proposed in which initial melt-bearing patches, preferentially formed within fertile pelitic layers, progressively evolve towards lens-shaped veins. Furthermore, heterogeneous deformation of anisotropic metasediments facilitates formation of extensional sites for further melt accumulation and transport. Melt crystallization implies a rapid increase in effective viscosity of leucosomes producing a reversal in competence contrast with respect to the enclosing schists. During the whole process, deformation localizes around crystallizing veins, giving rise to different and contrasting structures for melt-bearing and for solid-state stages.

  17. Sun protection

    MedlinePlus

    ... age spots are caused by exposure to the sun. The two types of sun rays that can injure the skin are ultraviolet ... changes is to protect your skin from the sun. This includes using sunscreen and other protective measures. ...

  18. Relative benefits of linear analogue and advanced digital hearing aids.

    PubMed

    Wood, Sally A; Lutman, Mark E

    2004-03-01

    Speech recognition performance and self-reported benefit from linear analogue and advanced (digital) hearing aids were compared in 100 first-time hearing aid users with mild-to-moderate sensorineural hearing loss fitted monaurally with a behind-the-ear (BTE) hearing aid in a single-blind randomized crossover trial. Subjects used each aid for 5 weeks in turn, with aid order balanced across subjects. Three alternative models of digital hearing aid were assigned to subjects according to a balanced design. Aid type was disguised to keep subjects blind within practical limitations. Aided speech recognition performance in noise was measured at speech levels of 65 and 75dB at a speech-to-noise ratio (SNR) of +2dB for closed sets of single words. Self-rated benefit was measured using the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Glasgow Hearing Aid Benefit Profile (GHABP). Quality of life, hearing aid use and user preferences were also assessed. Speech recognition scores with the digital aids were significantly better at 75dB than with the analogue aids Self-reported benefit (APHAB, GHABP) and improvement in quality of life were generally not significantly different between analogue and digital aids, although aversiveness measured with the APHAB was significantly lower with digital aids, and satisfaction measured with the GHABP was greater. The digital aids were preferred significantly more often than the analogue aids, with 61 subjects choosing their digital aid, 26 choosing the analogue aid, and nine being equivocal. Overall, this study shows advantages for advanced digital over simple linear analogue aids in terms of both objective and subjective outcomes, although average differences are not large. PMID:15198378

  19. The Object-analogue approach for probabilistic forecasting

    NASA Astrophysics Data System (ADS)

    Frediani, M. E.; Hopson, T. M.; Anagnostou, E. N.; Hacker, J.

    2015-12-01

    The object-analogue is a new method to estimate forecast uncertainty and to derive probabilistic predictions of gridded forecast fields over larger regions rather than point locations. The method has been developed for improving the forecast of 10-meter wind speed over the northeast US, and it can be extended to other forecast variables, vertical levels, and other regions. The object-analogue approach combines the analog post-processing technique (Hopson 2005; Hamill 2006; Delle Monache 2011) with the Method for Object-based Diagnostic Evaluation (MODE) for forecast verification (Davis et al 2006a, b). Originally, MODE is used to verify mainly precipitation forecasts using features of a forecast region represented by an object. The analog technique is used to reduce the NWP systematic and random errors of a gridded forecast field. In this study we use MODE-derived objects to characterize the wind fields forecasts into attributes such as object area, centroid location, and intensity percentiles, and apply the analogue concept to these objects. The object-analogue method uses a database of objects derived from reforecasts and their respective reanalysis. Given a real-time forecast field, it searches the database and selects the top-ranked objects with the most similar set of attributes using the MODE fuzzy logic algorithm for object matching. The attribute probabilities obtained with the set of selected object-analogues are used to derive a multi-layer probabilistic prediction. The attribute probabilities are combined into three uncertainty layers that address the main concerns of most applications: location, area, and magnitude. The multi-layer uncertainty can be weighted and combined or used independently in such that it provides a more accurate prediction, adjusted according to the application interest. In this study we present preliminary results of the object-analogue method. Using a database with one hundred storms we perform a leave-one-out cross-validation to

  20. In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues.

    PubMed

    García-Pupo, Laura; Zaldo-Castro, Armando; Exarchou, Vassiliki; Tacoronte-Morales, Juan Enrique; Pieters, Luc; Vanden Berghe, Wim; Nuñez-Figueredo, Yanier; Delgado-Hernández, René

    2016-01-01

    Two spirosteroid analogues were synthesized and evaluated for their in vitro neuroprotective activities in PC12 cells, against glutamate-induced excitotoxicity and mitochondrial damage in glucose deprivation conditions, as well as their anti-inflammatory potential in LPS/IFNγ-stimulated microglia primary cultures. We also evaluated the in vitro anti-excitotoxic and anti-inflammatory activities of natural and endogenous steroids. Our results show that the plant-derived steroid solasodine decreased PC12 glutamate-induced excitotoxicity, but not the cell death induced by mitochondrial damage and glucose deprivation. Among the two synthetic spirosteroid analogues, only the (25R)-5α-spirostan-3,6-one (S15) protected PC12 against ischemia-related in vitro models and inhibited NO production, as well as the release of IL-1β by stimulated primary microglia. These findings provide further insights into the role of specific modifications of the A and B rings of sapogenins for their neuroprotective potential. PMID:27483221

  1. Detection of Macromolecules in Desert Cyanobacteria Mixed with a Lunar Mineral Analogue After Space Simulations

    NASA Astrophysics Data System (ADS)

    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/m2 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/m2) 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.

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

    SciTech Connect

    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.

  3. Halogenase Engineering for the Generation of New Natural Product Analogues.

    PubMed

    Brown, Stephanie; O'Connor, Sarah E

    2015-10-12

    Halogenases catalyze the incorporation of halogen atoms into organic molecules. Given the importance that halogenation has on the biological activity of small molecules, these enzymes have been subjected to intense engineering efforts to make them more suitable for biotechnology applications. The ability to biohalogenate complex molecules provides, in principle, the opportunity for rapid generation of a series of analogues with new or improved properties. Here we discuss the potential and limitations of using halogenases as biocatalysts, including recent advances in engineering halogenases to generate halogenated natural product analogues. PMID:26256103

  4. Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

    PubMed Central

    Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

    1992-01-01

    In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

  5. 12-Amino-andrographolide analogues: synthesis and cytotoxic activity.

    PubMed

    Kasemsuk, Sakkasem; Sirion, Uthaiwan; Suksen, Kanoknetr; Piyachaturawat, Pawinee; Suksamrarn, Apichart; Saeeng, Rungnapha

    2013-12-01

    Andrographolide, a diterpenoid lactone of the plant Andrographis paniculata, has been shown to be cytotoxic against various cancer cells in vitro. In the present study, a series of β-amino-γ-butyrolactone analogues has been synthesized from naturally occurring andrographolide via one pot tandem aza-conjugate addition-elimination reaction. By using economic procedure without any base or catalyst at room temperature, the products obtained were in fair to excellent yields with high stereoselectivity. The cytotoxicity of all new amino analogues were evaluated against six cancer cell lines and revealed their potential for being developed as promising anti-cancer agents. PMID:23709127

  6. Tumor imaging and therapy using radiolabeled somatostatin analogues.

    PubMed

    de Jong, Marion; Breeman, Wout A P; Kwekkeboom, Dik J; Valkema, Roelf; Krenning, Eric P

    2009-07-21

    Molecular imaging plays an essential role in balancing the clinical benefits and risks of radionuclide-based cancer therapy. To effectively treat individual patients, careful assessment of biodistribution, dosimetry, and toxicity is essential. In this Account, we describe advances that combine features of molecular imaging and radionuclide therapy to provide new avenues toward individualized cancer treatment. Selective receptor-targeting radiopeptides have emerged as an important class of radiopharmaceuticals for molecular imaging and therapy of tumors that overexpress peptide receptors on the cell membrane. After such peptides labeled with gamma-emitting radionuclides bind to their receptors, they allow clinicians to visualize receptor-expressing tumors non-invasively. Peptides labeled with beta-particle emitters could also eradicate receptor-expressing tumors. The somatostatin receptors, which are overexpressed in a majority of neuroendocrine tumors, represent the first and best example of targets for radiopeptide-based imaging and radionuclide therapy. The somatostatin analogue (111)In-octreotide permits the localization and staging of neuroendocrine tumors that express the appropriate somatostatin receptors. Newer modified somatostatin analogues, including Tyr(3)-octreotide and Tyr(3)-octreotate, are successfully being used for tumor imaging and radionuclide therapy. Because there are few effective therapies for patients with inoperable or metastasized neuroendocrine tumors, this therapy is a promising novel treatment option for these patients. Peptide receptor imaging and radionuclide therapy can be combined in a single probe, called a "theranostic". To select patients who are likely to benefit from this type of intervention, we first use a peptide analogue labeled with a diagnostic radionuclide to obtain a scan. Selected patients will be treated using the same or a similar peptide analogue labeled with a therapeutic radionuclide. The development of such

  7. Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues

    PubMed Central

    2013-01-01

    The natural product withaferin A exhibits potent antitumor activity and other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was recently reported to possess cytotoxic activity against head and neck squamous cell carcinomas. Semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure–activity relationships, 20 new semisynthetic analogues of withalongolide A were synthesized and evaluated for cytotoxic activity against four different cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A. PMID:24273633

  8. Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors

    PubMed Central

    Florence, Gordon J.; Fraser, Andrew L.; Gould, Eoin R.; King, Elizabeth F.; Menzies, Stefanie K.; Morris, Joanne C.; Tulloch, Lindsay B.; Smith, Terry K.

    2015-01-01

    A series of novel bis-tetrahydropyran 1,4-triazole analogues based on the acetogenin framework display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness. A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure activity relationship studies. PMID:25145275

  9. Teaching self-protection to young children

    PubMed Central

    Poche, Cheryl; Brouwer, Richard; Swearingen, Michael

    1981-01-01

    Self-protective behaviors were taught to three preschool children in order to prevent the opportunity for abduction. An analogue measure of self-protection was developed in which confederate adults approached and verbally attempted to lure each child from the setting, before, during, and after training. A multiple baseline design across subjects was used. During baseline, all the children displayed susceptibility to the lures. Training procedures included modeling, behavior rehearsal, and social reinforcement. Within 1 week after training began, all children displayed appropriate responses to all of the lures both in the training setting and in the community. PMID:16795643

  10. Pharmacological protection of mitochondrial function mitigates acute limb ischemia/reperfusion injury.

    PubMed

    Bi, Wei; Bi, Yue; Gao, Xiang; Yan, Xin; Zhang, Yanrong; Harris, Jackie; Legalley, Thomas D; Gibson, K Michael; Bi, Lanrong

    2016-08-15

    We describe several novel curcumin analogues that possess both anti-inflammatory antioxidant properties and thrombolytic activities. The therapeutic efficacy of these curcumin analogues was verified in a mouse ear edema model, a rat arterial thrombosis assay, a free radical scavenging assay performed in PC12 cells, and in both in vitro and in vivo ischemia/reperfusion models. Our findings suggest that their protective effects partially reside in maintenance of optimal mitochondrial function. PMID:27390069

  11. Dioxin-like potency of HO- and MeO- analogues of PBDEs' the potential risk through consumption of fish from eastern China.

    PubMed

    Su, Guanyong; Xia, Jie; Liu, Hongling; Lam, Michael H W; Yu, Hongxia; Giesy, John P; Zhang, Xiaowei

    2012-10-01

    Polybrominated diphenyl ethers (PBDEs) and their analogues, such as hydroxylated PBDE (HO-PBDEs) and methoxylated PBDE (MeO-PBDEs) are of interest due to their wide distribution, bioaccumulation and potential toxicity to humans and wildlife. While information on the toxicity/biological potencies of PBDEs was available, information on analogues of PBDEs was limited. Dioxin-like toxicity of 34 PBDEs analogues was evaluated by use of the H4IIE-luc, rat hepatoma transactivation bioassay in 384-well plate format at concentrations ranging from 0 to 10 000 ng/mL. Among the 34 target analogues of PBDEs studied here, 19 activated the aryl hydrocarbon receptor (AhR) and induced significant dioxin-like responses in H4IIE-luc cells. Efficacies of the analogues of PBDEs ranged from 5.0% to 101.8% of the maximum response caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-max) and their respective 2,3,7,8-TCDD potency factors (ReP(H4IIE-luc)) ranged from 7.35 × 10(-12) to 4.00 × 10(-4), some of which were equal to or more potent than some mono-ortho-substituted PCBs (TEF-(WHO) = 3 × 10(-5)). HO-PBDEs exhibited greater dioxin-like activity than did the corresponding MeO-PBDEs. Analogues of PBDEs were detected mostly in marine organisms. Of these 11 detected analogues of PBDEs, 6 were found to have measurable dioxin-like potency. Though some analogues of PBDEs exhibited significant dioxin-like potency as measured by responses of the H4IIE-luc transactivation assay, concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents ((PBDEs analogues)TEQ(H4IIE-luc)), calculated as the sum of the product of concentrations of individual PBDE and their ReP(H4IIE-luc), were less than the tolerance limit proposed by European Union and the oral reference dose (RfD) derived by U.S. Environmental Protection Agency, respectively. (Hazard Quotients (HQ) < 0.005) Additional investigations should be conducted to evaluate the toxic potencies of these chemicals, especially for 2'-Me

  12. A New Alkylation-Elimination Method for Synthesis of Antiviral Fluoromethylenecyclopropane Analogues of Nucleosides

    PubMed Central

    Zhou, Shaoman; Zemlicka, Jiri

    2005-01-01

    A new method for the synthesis of fluoromethylenecyclopropane nucleosides by alkylation-elimination procedure is described. Fluorination of methylenecyclopropane carboxylate 6 gave fluoroester 7. Treatment of 7 with phenylselenenyl bromide afforded the desired ethyl (E)-2-bromomethyl-1-fluoro-2-phenylselenenylcyclopropane-1-carboxylate 11 in 85% yield. DIBALH reduction of 11 gave 13, which after acetylation to 14 was reacted with 2-amino-6-chloropurine to give the 9-alkylated product 15 in 87% yield. Se-oxydation of 15 with hydrogen peroxide afforded 16, which underwent smooth elimination in a mixture of THF-DMF at 60 °C giving rise to a Z,E mixture of protected nucleosides 17. Deacetylation gave Z-1a and E-1a which were separated on a silica gel column. Both Z-1a and E-1a were converted into the respective guanine analogues Z-1b and E-1b. PMID:16801980

  13. New Insights about Cross-Contamination Procedures for Analogue Missions in Space Exploration

    NASA Astrophysics Data System (ADS)

    Sattler, B.; Selch, F.; Klammer, S.; Groemer, G.; Sipiera, P.

    2007-10-01

    Environments such as the surface of other planets like Mars are subject to contamination processes by human exploration. Therefore, this is a crucial issue for planetary protection which needs to be addressed before investigating possible extraterrestrial life forms. Within AustroMars, the module track & trace assessed the dimension of back- and forward contamination which was verifiable in both directions. Sterile filters which were exposed to the environment during repeated EVAs showed persistent contaminations with bacteria. On-site contamination within the habitat was checked by exposed agar plates which were all positive with cultivable strains. The second module LiMa ("Life on Mars") simulates sterile procedures to collect samples with subsequent cultivation efforts under harsh conditions. These modules have been accomplished under high fidelity conditions and are the first analogue experiments conducted within the background of space exploration.

  14. Enzymatic Stability and Immunoregulatory Efficacy of a Synthetic Indolicidin Analogue with Regular Enantiomeric Sequence

    PubMed Central

    2013-01-01

    Cell-mediated immunity plays a major role in protecting the host from viral infections and tumor challenge. Here, we report the enzymatic stability and adjuvanticity of a peptiomimetic stereoisomer of the bovine neutrophil peptide indolicidin. The analogue, dubbed ld-indolicidin, contains the regular enantiomeric sequence of indolicidin and is synthesized by general stepwise solid-phase strategy. ld-Indolicidin possesses high resistance to enzymatic degradation and shows tolerance in mice. As vaccine adjuvant, ld-indolicidin is better able than the native form of indolicidin to enhance cell-mediated immune responses, using inactivated H5N1 virus as a model antigen. Taken together, these results open up a new approach to the development of vaccine adjuvants and immunotherapy technologies. PMID:24900703

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

    PubMed

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

    2015-11-01

    A modular strategy has been developed to access a diversity of cyclic and acyclic oligosaccharide analogues designed as prefunctionalized scaffolds for the synthesis of multivalent ligands. This convergent approach is based on bifunctional sugar building blocks with two temporarily masked functionalities that can be orthogonally activated to perform Cu(I)-catalyzed azide-alkyne cycloaddition reactions (CuAAC). The reducing end is activated as a glycosyl azide and masked as a 1,6-anhydro sugar, while the nonreducing end is activated as a free alkyne and masked as a triethylsilyl-alkyne. Following a cyclooligomerization approach, the first examples of close analogues of cyclodextrins composed of d-glucose residues and triazole units bound together through α-(1,4) linkages were obtained. The cycloglucopyranoside analogue containing four sugar units was used as a template to prepare multivalent systems displaying a protected d-mannose derivative or an iminosugar by way of CuAAC. On the other hand, the modular approach led to acyclic alkyne-functionalized scaffolds of a controlled size that were used to synthesize multivalent iminosugars. PMID:26439895

  16. Facile Synthesis of Natural Alkoxynaphthalene Analogues from Plant Alkoxybenzenes.

    PubMed

    Tsyganov, Dmitry V; Krayushkin, Mikhail M; Konyushkin, Leonid D; Strelenko, Yuri A; Semenova, Marina N; Semenov, Victor V

    2016-04-22

    Analogues of the bioactive natural alkoxynaphthalene pycnanthulignene D were synthesized by an efficient method. The starting plant allylalkoxybenzenes (1) are easily available from the plant essential oils of sassafras, dill, and parsley. The target 1-arylalkoxynaphthalenes (5) exhibited antiproliferative activity in a phenotypic sea urchin embryo assay. PMID:26910798

  17. Thymidine analogues to assess microperfusion in human tumors

    SciTech Connect

    Janssen, Hilde L.; Ljungkvist, Anna S.; Rijken, Paul F.; Sprong, Debbie; Bussink, Jan; Kogel, Albert J. van der; Haustermans, Karin M.; Begg, Adrian C. . E-mail: a.begg@nki.nl

    2005-07-15

    Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation.

  18. Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

    PubMed Central

    Brulikova, Lucie

    2011-01-01

    Summary This review article summarizes the results of a long-term investigation of 5-alkoxymethyluracil analogues and is aimed, in particular, at methods of syntheses. Most of the presented compounds were synthesized in order to evaluate their biological activity, therefore, a brief survey of biological activity, especially antiviral, cytotoxic and antibacterial, is also reported. PMID:21804865

  19. A Macroscopic Analogue of the Nuclear Pairing Potential

    ERIC Educational Resources Information Center

    Dunlap, Richard A.

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

  1. ON A p-ADIC ANALOGUE OF TATE HEIGHT

    NASA Astrophysics Data System (ADS)

    Berzin'sh, A. A.

    1983-04-01

    This paper is devoted to the study of the Tate height of an elliptic curve and its p-adic analogue. The main result is a series of explicit formulas for computing the local archimedean part of the Tate height. These results are used to obtain a new method for constructing the p-adic Tate height. Bibliography: 5 titles.

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

    PubMed Central

    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

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

    PubMed

    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. PMID:20013470

  4. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

    PubMed

    Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W; Shears, Stephen B; Veiga, Nicolás; Fiedler, Dorothea

    2016-08-22

    The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PMID:27460418

  5. New phosphorus analogues of nitrogen classics--no carbon copies.

    PubMed

    Gudat, Dietrich

    2014-05-01

    Getting heavy: The recently prepared phosphorus analogues of two old acquaintances, urea and dinitrogen tetroxide, bear some structural resemblance to their archetypes but are no carbon copies. Their syntheses and chemical properties reveal rather certain peculiarities, which back the doctrine that the electronic properties of the heavier elements in a group differ from those of the lightest congener. PMID:24718995

  6. Synthesis of glycophostones: cyclic phosphonate analogues of biologically relevant sugars

    PubMed

    Hanessian; Rogel

    2000-05-01

    Analogues of L-fucose, N-acetyl-D-glucosamine, N-acetyl-D-mannosamine, and N-acetyl neuraminic acid in which the anomeric carbon atom was replaced by a phosphonyl group (phostones or cyclic phosphonates) were synthesized by stereocontrolled methods relying on the Abramov reaction. PMID:10808439

  7. An Analysis of an Autoclitic Analogue in Pigeons

    ERIC Educational Resources Information Center

    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…

  8. q-bosons and the q-analogue quantized field

    NASA Technical Reports Server (NTRS)

    Nelson, Charles A.

    1995-01-01

    The q-analogue coherent states are used to identify physical signatures for the presence of a 1-analogue quantized radiation field in the q-CS classical limits where the absolute value of z is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/absolute value of z) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H(sub N) = h(omega)(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (Delta N)(exp 2)/ (N) approaches 0 as the absolute value of z approaches infinity. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, phi(sub q), still exhibits normal classical behavior. The standard number-phase uncertainty-relation, Delta(N) Delta phi(sub q) = 1/2, and the approximate commutation relation, (N, phi(sub q)) = i, still hold for the single-mode q-analogue quantized field. So, N and phi(sub q) are almost canonically conjugate operators in the q-CS classical limit. The q-analogue CS's minimize this uncertainty relation for moderate (absolute value of z)(exp 2).

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

    PubMed

    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

  10. Non-robust numerical simulations of analogue extension experiments

    NASA Astrophysics Data System (ADS)

    Naliboff, John; Buiter, Susanne

    2016-04-01

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

  11. New orally active diphenylmethyl-based ester analogues of dihydroartemisinin: Synthesis and antimalarial assessment against multidrug-resistant Plasmodium yoelii nigeriensis in mice.

    PubMed

    Chaudhary, Sandeep; Naikade, Niraj K; Tiwari, Mohit K; Yadav, Lalit; Shyamlal, Bharti Rajesh K; Puri, Sunil K

    2016-03-15

    A new series of ester analogues of artemisinin 8a-f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g-j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis in Swiss mice via oral route. These diphenylmethyl-based ester analogues 8a-f were found to be 2-4 folds more active than the antimalarial drugs β-arteether 4 and artesunic acid 5. Ester 8a, the most active compound of the series, provided complete protection to the infected mice at 24 mg/kg × 4 days as well as 12 mg/kg × 4 days, respectively. In this model β-arteether provided 100% and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively. PMID:26898813

  12. Metric optimisation for analogue forecasting by simulated annealing

    NASA Astrophysics Data System (ADS)

    Bliefernicht, J.; Bárdossy, A.

    2009-04-01

    It is well known that weather patterns tend to recur from time to time. This property of the atmosphere is used by analogue forecasting techniques. They have a long history in weather forecasting and there are many applications predicting hydrological variables at the local scale for different lead times. The basic idea of the technique is to identify past weather situations which are similar (analogue) to the predicted one and to take the local conditions of the analogues as forecast. But the forecast performance of the analogue method depends on user-defined criteria like the choice of the distance function and the size of the predictor domain. In this study we propose a new methodology of optimising both criteria by minimising the forecast error with simulated annealing. The performance of the methodology is demonstrated for the probability forecast of daily areal precipitation. It is compared with a traditional analogue forecasting algorithm, which is used operational as an element of a hydrological forecasting system. The study is performed for several meso-scale catchments located in the Rhine basin in Germany. The methodology is validated by a jack-knife method in a perfect prognosis framework for a period of 48 years (1958-2005). The predictor variables are derived from the NCEP/NCAR reanalysis data set. The Brier skill score and the economic value are determined to evaluate the forecast skill and value of the technique. In this presentation we will present the concept of the optimisation algorithm and the outcome of the comparison. It will be also demonstrated how a decision maker should apply a probability forecast to maximise the economic benefit from it.

  13. Biological evaluation of a novel sorafenib analogue, t-CUPM.

    PubMed

    Wecksler, Aaron T; Hwang, Sung Hee; Liu, Jun-Yan; Wettersten, Hiromi I; Morisseau, Christophe; Wu, Jian; Weiss, Robert H; Hammock, Bruce D

    2015-01-01

    Sorafenib (Nexavar®) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib. PMID:25413440

  14. Convolutamydine A and synthetic analogues have antinociceptive properties in mice.

    PubMed

    Figueiredo, Gabriela S M; Zardo, Renata S; Silva, Bárbara V; Violante, Flávio A; Pinto, Angelo C; Fernandes, Patricia D

    2013-01-01

    Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues. Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues. Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug. In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine's effects. PMID:23046852

  15. Analogue Sites for Mars Missions - A report from two workshops

    NASA Astrophysics Data System (ADS)

    Hipkin, V.; Voytek, M. A.; Glamoclija, M.

    2014-12-01

    Fieldwork, at terrestrial sites that are analogous in some way to Mars, has a key role in defining questions addressed by Mars missions. For MSL, the question is whether its landing site was habitable, and for Mars 2020, the question is how do we search for and what are signs of life in ancient habitable environments. Implementing these investigations by means of a rover mission on a distant planetary surface has challenges due to a limited set of tools and period of operations. Using this context of planetary missions is important in shaping how analog research can be used to advance planetary science. Following a successful 2010 AGU fall meeting session entitled "Analogue Sites for Mars Missions", two community workshops were held at The Woodlands, TX March 2011 and the Carnegie Institute of Washington in July 2013. These activities represent an ongoing dialogue with the analogue and mission communities. The AGU session solicited presentations of current analogue research relevant to MSL, at which time the landing site selection process was still considering four final sites. The 2011 Woodlands workshop solicited details on representative science questions and analogue sites by means of an abstract template. The output from The Woodlands workshop was an initial metric to assess the utility of analogue sites against specific science questions, as well as recommendations for future activities. The 2013 Carnegie workshop, followed up on some of the recommendations from 2011. Both on-line interactive dialogue and in person discussions targeted broad topics, including 'the advantages and problems of using a great terrestrial analog for field testing', and 'knowing what we currently do about Mars, what would be the best place on the planet to collect the first suite of samples to be returned to Earth? What would be appropriate analog sites on Earth?'. The results and recommendations from both workshops are summarized to publicize and stimulate this ongoing discussion.

  16. Insider protection

    SciTech Connect

    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.

  17. Charge deficient analogues of the natural polyamines.

    PubMed

    Weisell, Janne; Hyvönen, Mervi T; Alhonen, Leena; Vepsäläinen, Jouko; Keinänen, Tuomo A; Khomutov, Alex R

    2014-01-01

    Mitochondrial dysfunction, either inherited or acquired, is associated with several diseases in humans. Depending on the cell type and location, cells are prone to multiple types of insults that may compromise their proper function. Generally, these insults are overcome by defensive mechanisms but sometimes they lead to sustained damage, requiring the action of scavenging and repair machineries to retain the viability of the cells. As a final measure, severely damaged cells are targeted to a controlled cell death pathway in order to not to compromise the well-being of the whole tissue. The polyamines, spermine and spermidine are essential cellular constituents, participating in many vital functions such as proliferation and differentiation, immune response and scavenging of reactive oxygen species. Therefore, dysregulation of polyamine metabolism is often associated with different pathological states. Polyamine acetylating enzyme spermidine/spermine-N(1)-acetyltransferase is induced by inflammation, drugs and by several other environmental insults. Resulting accelerated polyamine acetylation with accompanying polyamine biosynthesis induction i.e. activation of polyamine futile cycle generates excessive amount of hydrogen peroxide, hampers cell energy metabolism and induces mitochondrial dysfunction and biogenesis. Therefore, the drugs inhibiting polyamine metabolism are valuable in protecting mitochondria and cell energy metabolism. Here we review the current literature focusing on the applicability of chargedeficient polyamine analogs as drugs to modulate polyamine metabolism. Alteration of pK(a) of amino group(s) in a respective analog is achieved by fluorine substitution of hydrogen atom, hydroxylamine substitution of methylamine or by reducing the numbers of carbon atoms between amine groups to two instead of three or four. PMID:23701551

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

    NASA Astrophysics Data System (ADS)

    Herrnegger, Mathew; Riedl, Michael; Schulz, Karsten

    2016-04-01

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

  19. Inhibition of receptor/G protein coupling by suramin analogues.

    PubMed

    Beindl, W; Mitterauer, T; Hohenegger, M; Ijzerman, A P; Nanoff, C; Freissmuth, M

    1996-08-01

    Suramin analogues act as direct antagonists of heterotrimeric G proteins because they block the rate-limiting step of G protein activation (i.e., the dissociation of GDP prebound to the G protein alpha subunit). We have used the human brain A1 adenosine receptor and the rat striatal D2 dopamine receptor, two prototypical Gi/G(o)-coupled receptors, as a model system to test whether the following analogues suppress the receptor-dependent activation of G proteins: 8-(3-nitrobenzamido)-1,3,5-naphthalenetrisulfonic acid (NF007), 8-(3-(3-nitrobenzamido)-benzamido)-1,3,5-naphthalenetrisulfonic acid (NF018); 8,8'-(carbonylbis(imino-3,1-phenylene))bis-(1,3,5-naphthalenetr isulfonic acid) (NF023); 8,8'-(carbonylbis(imino-3,1-phenylene)carbonylimino-(3,1- phenylene)) bis(1,3,5-naphthalenetrisulfonic acid) (NF037); and suramin. Suramin and its analogues inhibit the formation of the agonist-specific ternary complex (agonist/receptor/G protein). This inhibition is (i) quasicompetitive with respect to agonist binding in that it can be overcome by increasing receptor occupancy but (ii) does not result from an interaction of the analogues with the ligand binding pocket of the receptors because the binding of antagonists or of agonists in the absence of functional receptor/G protein interaction is not affected. In addition to suppressing the spontaneous release of GDP from defined G protein alpha subunits, suramin and its analogues reduce receptor-catalyzed guanine nucleotide exchange. The site, to which suramin analogues bind, overlaps with the docking site for the receptor on the G protein alpha subunit. The structure-activity relationships for inhibition of agonist binding to the A1 adenosine receptor (suramin > NF037 > NF023) and of agonist binding to the inhibition D2 dopamine receptor (suramin = NF037 > NF023 > NF018) differ. Thus, NF037 discriminates between the ternary complexes formed by the agonist-liganded D2 dopamine receptors and those formed by the A1 adenosine

  20. The use of prostaglandins and their analogues for abortion.

    PubMed

    Bygdeman, M

    1984-12-01

    In general, termination of second trimester pregnancy is associated with three to five times higher morbidity and mortality risks than termination during the first trimester. The procedures mainly used are extra- or intra-amniotic administration of solutions such as hypertonic saline, ethacridine lactate, PGF2 alpha and PGE2. In comparison with these procedures, the use of prostaglandin analogues may offer important advantages, the most important one being the possibility of using non-invasive routes of administration. The continuous development of new analogues has now resulted in compounds that are highly effective in stimulating uterine contractility and are associated with a low frequency of side-effects; these compounds are suitable for both vaginal and intramuscular administration and are applicable for termination of pregnancy during both the early and late parts of the second trimester. The most widely used method for termination of first trimester pregnancy is vacuum aspiration. It is a highly effective procedure and the overall complication rate is low. One problem with vacuum aspiration is the mechanical dilatation of the cervical canal which is necessary from at least the 8th week and onwards. Pretreatment with laminaria tents or with prostaglandin analogues eliminates or reduces the need for mechanical dilatation and significantly facilitates the procedure. Pretreatment with prostaglandin analogues also reduces the risk of both operative and postoperative complications. The prostaglandins also offer a possibility as a non-surgical procedure for termination of very early pregnancy. Both vaginal and intramuscular administration of the latest generation of PG analogues have been shown in several studies to be equally as effective as vacuum aspiration if the treatment is restricted to the first three weeks following the first missed menstrual period. Gastrointestinal side-effects are still a problem although of significantly less importance than if natural

  1. C-Terminal Fragment, Aβ32-37, Analogues Protect Against Aβ Aggregation-Induced Toxicity.

    PubMed

    Bansal, Sunil; Maurya, Indresh Kumar; Yadav, Nitin; Thota, Chaitanya Kumar; Kumar, Vinod; Tikoo, Kulbhushan; Chauhan, Virander Singh; Jain, Rahul

    2016-05-18

    Amyloid-β aggregation is a major etiological phenomenon in Alzheimer's disease. Herein, we report peptide-based inhibitors that diminish the amyloid load by obviating Aβ aggregation. Taking the hexapeptide fragment, Aβ32-37, as lead, more than 40 new peptides were synthesized. Upon evaluation of the newly synthesized hexapeptides as inhibitors of Aβ toxicity by the MTT-based cell viability assay, a number of peptides exhibited significant Aβ aggregation inhibitory activity at sub-micromolar concentration range. A hexapeptide (1) showed complete mitigation of Aβ toxicity in the cell culture assay at 2 μM. In the ThT fluorescence assay, upon incubation of Aβ with this peptide, we observed no increase in the ThT fluorescence relative to control. The secondary structure estimation by circular dichroism spectroscopy and morphological examination by transmission electron microscopy further confirmed the results. PMID:26835536

  2. Structure Activity Relationship of (N)-Methanocarba Phosphonate Analogues of 5’-AMP as Cardioprotective Agents Acting Through a Cardiac P2X Receptor

    PubMed Central

    Kumar, T. Santhosh; Zhou, Si-Yuan; Joshi, Bhalchandra V.; Balasubramanian, Ramachandran; Yang, Tiehong; Liang, Bruce T.; Jacobson, Kenneth A.

    2010-01-01

    P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis–Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C-P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart failure) compared to vehicle-infused mice (all inactive at the vasodilatory P2Y1 receptor). Two phosphonates, (1’S,2’R,3’S,4’R,5’S)-4’-(6-amino-2-chloropurin-9-yl)-2’,3’-(dihydroxy)-1’-(phosphonomethylene)-bicyclo[3.1.0]hexane 4 and its homologue 9, both 5’-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5’-extended phosphonates, all 2-H analogues, and a CH3-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure. PMID:20192270

  3. Noncommutative analogue Aharonov-Bohm effect and superresonance

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  4. Analogue Transformations in Physics and their Application to Acoustics

    PubMed Central

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

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an “analogue transformation acoustics” formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft. PMID:23774575

  5. Synthesis and α1-adrenoceptor antagonist activity of tamsulosin analogues.

    PubMed

    Sagratini, Gianni; Angeli, Piero; Buccioni, Michela; Gulini, Ugo; Marucci, Gabriella; Melchiorre, Carlo; Poggesi, Elena; Giardinà, Dario

    2010-12-01

    Tamsulosin (-)-1 is the most utilized α(1)-adrenoceptor antagonist in the benign prostatic hyperplasia therapy owing to its uroselective antagonism and capability in relieving both obstructive and irritative lower urinary tract symptoms. Here we report the synthesis and pharmacological study of the homochiral (-)-1 analogues (-)-2-(-)-5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for α(1)-adrenoceptor subtypes. The benzyl analogue (-)-3, displaying a preferential antagonist profile for α1A-than α1D-and α1B-adrenoceptors, and a 12-fold higher potency at α1A-adrenoceptors with respect to the α1B subtype, may have improved uroselectivity compared to (-)-1. PMID:20934789

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

    SciTech Connect

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

    1983-07-01

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

  7. Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents.

    PubMed

    Yan, Qi; Wang, Yujie; Zhang, Wei; Li, Yingxia

    2016-05-01

    A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC50 values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%-35% inhibition at the end of the experiment. PMID:27136567

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

    SciTech Connect

    Duerden, P.; Airey, P.; Pescatore, C.

    1994-12-31

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

  9. Stereocontrolled Synthesis of Key Advanced Intermediates toward Simplified Acetogenin Analogues.

    PubMed

    Le Huérou, Yvan; Doyon, Julien; Grée, René L.

    1999-09-01

    The stereo- and enantiocontrolled synthesis of substituted beta-hydroxy ethers based on glycol and catechol bearing an alkyne group and a series of substituents is reported. These substrates were designed to mimic the bis-THF array of annonaceous acetogenins and to provide an access to simplified and modified analogues. The key steps of the synthesis involve the condensation of the nonracemic mesylate of solketal with ethylene glycol and catechol, followed by an alkylation with a glycidyl derivative. Under appropriate conditions, the reaction is completely stereoselective and allows the synthesis of all the diastereomers. After the epoxide was opened with triethylsilylacetylene, the second epoxide was unmasked and reacted with a series of alkyl, aryl, amine, and alcohol reagents. A series of 28 analogues was prepared having a glycol or a catechol core, a stereodefined configuration of the flanking hydroxyl groups, and an acetylenic appendage suitable for a coupling to a lactone-bearing fragment. PMID:11674687

  10. Synthesis of Methylenecyclopropane Analogues of Antiviral Nucleoside Phosphonates

    PubMed Central

    Yan, Zhaohua; Zhou, Shaoman; Kern, Earl R.; Zemlicka, Jiri

    2006-01-01

    Synthesis of methylenecyclopropane analogues of nucleoside phosphonates 6a, 6b, 7a and 7b is described. Cyclopropyl phosphonate 8 was transformed in four steps to methylenecyclopropane phosphonate 16. The latter intermediate was converted in seven steps to the key Z- and E-methylenecyclopropane alcohols 23 and 24 separated by chromatography. Selenoxide eliminations (15 → 16 and 22 → 23 + 24) were instrumental in the synthesis. The Z- and E-isomers 23 and 24 were transformed to bromides 25a and 25b which were used for alkylation of adenine and 2-amino-6-chloropurine to give intermediates 26a, 26b, 26c and 26d. Acid hydrolysis provided the adenine and guanine analogues 6a, 6b, 7a and 7b. Phosphonates 6b and 7b are potent inhibitors of replication of Epstein-Barr virus (EBV). PMID:16758001

  11. Millimeter and Submillimeter Studies of Interstellar Ice Analogues

    NASA Astrophysics Data System (ADS)

    Mesko, AJ; Wagner, Ian C.; Smith, Houston Hartwell; Milam, Stefanie N.; Widicus Weaver, Susanna L.

    2015-06-01

    The chemistry of interstellar ice analogues has been a topic of great interest to astrochemists over the last 20 years. Currently, the models of interstellar chemistry feature icy-grain reactions as a primary mechanism for the formation of many astrochemical species as well as potentially astrobiologically-relevant complex organic molecules. This talk presents new spectral results collected by a millimeter and submillimeter spectrometer coupled to a vacuum chamber designed to study the sublimation or sputtered products of icy-grain reactions initiated by thermal-processing or photo-processing of interstellar ice analogues. Initial results from thermal desorption and UV photoprocessing experiments of pure water ice and water + methanol ice mixtures will be presented.

  12. Neurological Effects of Bisphenol A and its Analogues

    PubMed Central

    Inadera, Hidekuni

    2015-01-01

    The endocrine disrupting chemical bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. The use of BPA-containing products in daily life makes exposure ubiquitous, and the potential human health risks of this chemical are a major public health concern. Although numerous in vitro and in vivo studies have been published on the effects of BPA on biological systems, there is controversy as to whether ordinary levels of exposure can have adverse effects in humans. However, the increasing incidence of developmental disorders is of concern, and accumulating evidence indicates that BPA has detrimental effects on neurological development. Other bisphenol analogues, used as substitutes for BPA, are also suspected of having a broad range of biological actions. The objective of this review is to summarize our current understanding of the neurobiological effects of BPA and its analogues, and to discuss preventive strategies from a public health perspective. PMID:26664253

  13. Glaucine analogues as inhibitors of mouse splenocyte activity.

    PubMed

    Philipov, S; Ivanovska, N; Nikolova, P

    1998-10-01

    The inhibitory effect of 15 semi-synthetic analogues of glaucine (1) on the lipopolysaccharide (LPS)-induced and the concanavalin A (Con A)-induced proliferation of mouse splenocytes was compared in vitro. Isoboldine (3), bracteoline (4) and dehydroglaucine (9) showed a significantly higher potency to suppress LPS-induced proliferation than 1, while 7-hydroxy-4-methylglaucine (8), 7-formyldehydroglaucine (11), 7-acetyldehydroglaucine (13), 7-benzoyldehydroglaucine (14), oxoglaucine (15) and glaucine-quinol (16) were less inhibitory. Compounds 3, 4, boldine (5), 15 and 16 surpassed significantly the inhibition expressed by 1 on Con A-induced proliferative response. The effect was equal to the inhibition determined for mitomycin C (Mit C) with both mitogens. In contrast to all others analogues, thaliporphine (2) stimulated splenocyte proliferation in both assays. Antibody response against sheep red blood cells (SRBC) was lowered most strongly by cataline (6), 7-methyldehydroglaucine (10) and 16. PMID:9812336

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

    SciTech Connect

    Tran, Truong X.; Longhi, Stefano; Biancalana, Fabio

    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. Analogue transformations in physics and their application to acoustics.

    PubMed

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

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft. PMID:23774575

  16. A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

    NASA Astrophysics Data System (ADS)

    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.

  17. On-chip learning with analogue VLSI neural networks.

    PubMed

    Tarassenko, L; Tombs, J; Cairns, G

    1993-12-01

    Results from simulations of weight perturbation as an on-chip learning scheme for analogue VLSI neural networks are presented. The limitations of analogue hardware are modelled as realistically as possible. Thus synaptic weight precision is defined according to the smallest change in the weight setting voltage which gives a measurable change at the output of the corresponding neuron. Tests are carried out on a hard classification problem constructed from mobile robot navigation data. The simulations show that the degradation in classification performance on a 500-pattern test set caused by the introduction of realistic hardware constraints is acceptable: with 8-bit weights, updated probabilistically and with a simplified output error criterion, the error rate increases by no more than 7% when compared with weight perturbation implemented with full 32-bit precision. PMID:8049803

  18. Excited state dynamics of brightly fluorescent second generation epicocconone analogues.

    PubMed

    Chatterjee, Soumit; Karuso, Peter; Boulangé, Agathe; Franck, Xavier; Datta, Anindya

    2015-05-21

    The natural product epicocconone, owing to its unique fluorescence properties, has been developed into a range of products used in biotechnology, especially proteomics. However, its weak green fluorescence in its native state, while advantageous for proteomics applications, is a disadvantage in other applications that require two-color readouts. Here we report the photophysical characterization of two brightly fluorescent analogues of epicocconone. These analogues, with naphthyl or pyridyl groups replacing the heptatriene chain, resulted in bright fluorescence in both the native state and the long Stokes shifted enamine. Time-resolved fluorescence studies and DFT calculations were carried out to understand the excited state processes involved in fluorescence. Results showed the p-chloro group on the pyridyl is responsible for the high fluorescence of the native fluorophore. The application of one of these compounds for staining electrophoresis gels is exemplified. PMID:25902354

  19. Synthesis and biological activity of polyalthenol and pentacyclindole analogues.

    PubMed

    Marcos, Isidro S; Moro, Rosalina F; Costales, Isabel; Basabe, Pilar; Díez, David; Gil, Ana; Mollinedo, Faustino; Pérez-de la Rosa, Fátima; Pérez-Roth, Eduardo; Padrón, José M

    2014-02-12

    A series of indole sesquiterpenes analogues of polyalthenol and pentacyclindole have been synthesized starting from ent-halimic acid in order to test their biological activity. These analogues include diverse oxidation levels at the sesquiterpenyl moiety and different functionalization on the indole ring. All synthetic derivatives were tested against a representative panel of Gram positive and Gram negative bacterial strains, and the human solid tumour cell lines A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). Overall, the compounds presented activity against the cancer cell lines. The resulting lead, displaying a polyalthenol scaffold, showed GI50 values in the range 1.2-5.7 μM against all cell lines tested. PMID:24412720

  20. Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents

    PubMed Central

    Yan, Qi; Wang, Yujie; Zhang, Wei; Li, Yingxia

    2016-01-01

    A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC50 values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%–35% inhibition at the end of the experiment. PMID:27136567

  1. Naturally-occurring chemical analogues for repository-derived radionuclides

    SciTech Connect

    Miller, B.

    1996-12-01

    Studies of natural systems are a valuable means of gaining information on the behavior of elements and radionuclides in the geosphere or biosphere that may be used to support performance assessments for radioactive waste repositories. However, these natural system studies face the problem that some of the chemical and isotopic species that occur in radioactive wastes do not occur naturally. Therefore, when attempting to study transport processes for these species other, naturally-occurring species must be examined as {open_quote}chemical analogues{close_quote} for the waste species. Chemical analogues are chosen on the basis of some similarity with the chemical behavior of the waste species in relevant physico-chemical environments. This is a tricky procedure and each system must be considered on a case-by-case basis, although some guidelines can be established and these are given here.

  2. Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF.

    PubMed

    Ertas, Erdal; Demirtas, İlknur; Ozturk, Turan

    2015-01-01

    This review aims to give an overview of the current status of our research on the synthesis of π-electron donor bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF, ET) analogues prepared from 1,8-diketones via a ring forming reaction. The new synthesized π-electron donors have vinyl moieties producing extended π-electron delocalization over the substituent phenyl rings at the peripheries. PMID:25977714

  3. Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF

    PubMed Central

    Demirtas, İlknur; Ozturk, Turan

    2015-01-01

    Summary This review aims to give an overview of the current status of our research on the synthesis of π-electron donor bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF, ET) analogues prepared from 1,8-diketones via a ring forming reaction. The new synthesized π-electron donors have vinyl moieties producing extended π-electron delocalization over the substituent phenyl rings at the peripheries. PMID:25977714

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

    PubMed Central

    Nasomjai, Pitak; Slawin, Alexandra M Z

    2009-01-01

    Summary The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the α- and β-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each α-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya. PMID:19777136

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

    PubMed

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

    2016-03-01

    The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me(2+))-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incompletely understood. Towards this goal, we quantitatively investigated dimerization of MTM and several of its analogues, MTM SDK (for Short side chain, DiKeto), MTM SA-Trp (for Short side chain and Acid), MTM SA-Ala, and a biosynthetic precursor premithramycin B (PreMTM B), and measured the binding affinities of these molecules to DNA oligomers of different sequences and structural forms at physiological salt concentrations. We show that MTM and its analogues form stable dimers even in the absence of DNA. All molecules, except for PreMTM B, can bind DNA with the following rank order of affinities (strong to weak): MTM=MTM SDK>MTM SA-Trp>MTM SA-Ala. An X(G/C)(G/C)X motif, where X is any base, is necessary and sufficient for MTM binding to DNA, without a strong dependence on DNA conformation. These recognition rules will aid in mapping MTM sites across different promoters towards development of MTM analogues as useful anticancer agents. PMID:26760230

  6. Inhibition of telomerase by BIBR 1532 and related analogues.

    PubMed

    Barma, D K; Elayadi, Anissa; Falck, J R; Corey, David R

    2003-04-01

    BIBR 1532 has been reported to be a potent, small molecule inhibitor of human telomerase, suggesting it as a lead for the development of anti-telomerase therapy. We confirm the ability of BIBR 1532 to inhibit telomerase and report the discovery of an equally potent analogue. Importantly, IC(50) values in cell extract are considerably higher than those previously reported using assays for purified enzyme, indicating that substantial improvement may be necessary. PMID:12657276

  7. Lysophosphatidylserine analogues differentially activate three LysoPS receptors.

    PubMed

    Uwamizu, Akiharu; Inoue, Asuka; Suzuki, Kensuke; Okudaira, Michiyo; Shuto, Akira; Shinjo, Yuji; Ishiguro, Jun; Makide, Kumiko; Ikubo, Masaya; Nakamura, Sho; Jung, Sejin; Sayama, Misa; Otani, Yuko; Ohwada, Tomohiko; Aoki, Junken

    2015-03-01

    Lysophosphatidylserine (1-oleoyl-2 R-lysophosphatidylserine, LysoPS) has been shown to have lipid mediator-like actions such as stimulation of mast cell degranulation and suppression of T lymphocyte proliferation, although the mechanisms of LysoPS actions have been elusive. Recently, three G protein-coupled receptors (LPS1/GPR34, LPS2/P2Y10 and LPS3/GPR174) were found to react specifically with LysoPS, raising the possibility that LysoPS serves as a lipid mediator that exerts its role through these receptors. Previously, we chemically synthesized a number of LysoPS analogues and evaluated them as agonists for mast-cell degranulation. Here, we used a transforming growth factor-α (TGFα) shedding assay to see if these LysoPS analogues activated the three LysoPS receptors. Modification of the serine moiety significantly reduced the ability of the analogues to activate the three LysoPS receptors, whereas modification of other parts resulted in loss of activity in receptor-specific manner. We found that introduction of methyl group to serine moiety (1-oleoyl-lysophosphatidylallothreonine) and removal of sn-2 hydroxyl group (1-oleoyl-2-deoxy-LysoPS) resulted in reduction of reactivity with LPS1 and LPS3, respectively. Accordingly, we synthesized a LysoPS analogue with the two modifications (1-oleoyl-2-deoxy-lysophosphatidylallothreonine) and found it to be an LPS2-selective agonist. These pharmacological tools will definitely help to identify the biological roles of these LysoPS receptors. PMID:25320102

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

    PubMed

    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

  9. Using fuzzy sets for data interpretation in natural analogue studies

    SciTech Connect

    De Lemos, F.L.; Sullivan, T.; Hellmuth, K.H.

    2008-07-01

    Natural analogue studies can play a key role in deep geological radioactive disposal systems safety assessment. These studies can help develop a better understanding of complex natural processes and, therefore, provide valuable means of confidence building in the safety assessment. In evaluation of natural analogues, there are, however, several sources of uncertainties that stem from factors such as complexity; lack of data; and ignorance. Often, analysts have to simplify the mathematical models in order to cope with the various sources of complexity and this ads uncertainty to the model results. The uncertainties reflected in model predictions must be addressed to understand their impact on safety assessment and therefore, the utility of natural analogues. Fuzzy sets can be used to represent the information regarding the natural processes and their mutual connections. With this methodology we are able to quantify and propagate the epistemic uncertainties in both processes and, thereby, assign degrees of truth to the similarities between them. An example calculation with literature data is provided. In conclusion: Fuzzy sets are an effective way of quantifying semi-quantitative information such as natural analogues data. Epistemic uncertainty that stems from complexity and lack of knowledge regarding natural processes are represented by the degrees of membership. It also facilitates the propagation of this uncertainty throughout the performance assessment by the extension principle. This principle allows calculation with fuzzy numbers, where fuzzy input results in fuzzy output. This may be one of the main applications of fuzzy sets theory to radioactive waste disposal facility performance assessment. Through the translation of natural data into fuzzy numbers, the effect of parameters in important processes in one site can be quantified and compared to processes in other sites with different conditions. The approach presented in this paper can be extended to

  10. OptZyme: Computational Enzyme Redesign Using Transition State Analogues

    PubMed Central

    Grisewood, Matthew J.; Gifford, Nathanael P.; Pantazes, Robert J.; Li, Ye; Cirino, Patrick C.; Janik, Michael J.; Maranas, Costas D.

    2013-01-01

    OptZyme is a new computational procedure for designing improved enzymatic activity (i.e., kcat or kcat/KM) with a novel substrate. The key concept is to use transition state analogue compounds, which are known for many reactions, as proxies for the typically unknown transition state structures. Mutations that minimize the interaction energy of the enzyme with its transition state analogue, rather than with its substrate, are identified that lower the transition state formation energy barrier. Using Escherichia coli β-glucuronidase as a benchmark system, we confirm that KM correlates (R2 = 0.960) with the computed interaction energy between the enzyme and the para-nitrophenyl- β, D-glucuronide substrate, kcat/KM correlates (R2 = 0.864) with the interaction energy of the transition state analogue, 1,5-glucarolactone, and kcat correlates (R2 = 0.854) with a weighted combination of interaction energies with the substrate and transition state analogue. OptZyme is subsequently used to identify mutants with improved KM, kcat, and kcat/KM for a new substrate, para-nitrophenyl- β, D-galactoside. Differences between the three libraries reveal structural differences that underpin improving KM, kcat, or kcat/KM. Mutants predicted to enhance the activity for para-nitrophenyl- β, D-galactoside directly or indirectly create hydrogen bonds with the altered sugar ring conformation or its substituents, namely H162S, L361G, W549R, and N550S. PMID:24116038

  11. Endiandric Acid Analogues from the Roots of Beilschmiedia erythrophloia.

    PubMed

    Yang, Ping-Shin; Cheng, Ming-Jen; Peng, Chien-Fang; Chen, Jih-Jung; Chen, Ih-Sheng

    2009-01-01

    Investigation of the roots of Beilschmiedia erythrophloia has led to the isolation of seven new endiandric acid analogues, erythrophloins A-F (1-6) and beilcyclone A (7), together with 11 known compounds. The structures of 1-7 were determined using spectroscopic techniques. Two constituents, erythrophloin C (3) and suberosol B (8), exhibited antitubercular activity against Mycobacterium tuberculosis H37Rv, showing MIC values of 50 and 28.9 microg/mL, respectively. PMID:19072217

  12. Contact zones and hydrothermal systems as analogues to repository conditions

    SciTech Connect

    Wollenberg, H.A.; Flexser, S.

    1984-10-01

    Radioactive waste isolation efforts in the US are currently focused on examining basalt, tuff, salt, and crystalline rock as candidate rock types to encompass waste repositories. As analogues to near-field conditions, the distributions of radio- and trace-elements have been examined across contacts between these rocks and dikes and stocks that have intruded them. The intensive study of the Stripa quartz monzonite has also offered the opportunity to observe the distribution of uranium and its daughters in groundwater and its relationship to U associated with fracture-filling and alteration minerals. Investigations of intrusive contact zones to date have included (1) a tertiary stock into Precambrian gneiss, (2) a stock into ash flow tuff, (3) a rhyodacite dike into Columbia River basalt, and (4) a kimberlite dike into salt. With respect to temperature and pressure, these contact zones may be considered "worst-case scenario" analogues. Results indicate that there has been no appreciable migration of radioelements from the more radioactive intrusives into the less radioactive country rocks, either in response to the intrusions or in the fracture-controlled hydrological systems that developed following emplacement. In many cases, the radioelements are locked up in accessory minerals, suggesting that artificial analogues to these would make ideal waste forms. Emphasis should now shift to examination of active hydrothermal systems, studying the distribution of key elements in water, fractures, and alteration minerals under pressure and temperature conditions most similar to those expected in the near-field environment of a repository. 14 refs.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation curve and total stellar mass. We then extract the dark matter density and velocity distribution in the Solar neighbourhood for this set of Milky Way analogues, and use them to analyse the results of current direct detection experiments. For most Milky Way analogues, the event rates in direct detection experiments obtained from the best fit Maxwellian distribution (with peak speed of 223–289 km/s) are similar to those obtained directly from the simulations. As a consequence, the allowed regions and exclusion limits set by direct detection experiments in the dark matter mass and spin-independent cross section plane shift by a few GeV compared to the Standard Halo Model, at low dark matter masses. For each dark matter mass, the halo-to-halo variation of the local dark matter density results in an overall shift of the allowed regions and exclusion limits for the cross section. However, the compatibility of the possible hints for a dark matter signal from DAMA and CDMS-Si and null results from LUX and SuperCDMS is not improved.

  14. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    SciTech Connect

    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.

  15. Noble gas encapsulation: clathrate hydrates and their HF doped analogues.

    PubMed

    Mondal, Sukanta; Chattaraj, Pratim Kumar

    2014-09-01

    The significance of clathrate hydrates lies in their ability to encapsulate a vast range of inert gases. Although the natural abundance of a few noble gases (Kr and Xe) is poor their hydrates are generally abundant. It has already been reported that HF doping enhances the stability of hydrogen hydrates and methane hydrates, which prompted us to perform a model study on helium, neon and argon hydrates with their HF doped analogues. For this purpose 5(12), 5(12)6(8) and their HF doped analogues are taken as the model clathrate hydrates, which are among the building blocks of sI, sII and sH types of clathrate hydrate crystals. We use the dispersion corrected and gradient corrected hybrid density functional theory for the calculation of thermodynamic parameters as well as conceptual density functional theory based reactivity descriptors. The method of the ab initio molecular dynamics (AIMD) simulation is used through atom centered density matrix propagation (ADMP) techniques to envisage the structural behaviour of different noble gas hydrates on a 500 fs timescale. Electron density analysis is carried out to understand the nature of Ng-OH2, Ng-FH and Ng-Ng interactions. The current results noticeably demonstrate that the noble gas (He, Ne, and Ar) encapsulation ability of 5(12), 5(12)6(8) and their HF doped analogues is thermodynamically favourable. PMID:25047071

  16. Natural analogue studies as supplements to biomineralization research

    SciTech Connect

    McNeil, M.B.

    1995-09-01

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

  17. Stereochemical Assignment of Strigolactone Analogues Confirms Their Selective Biological Activity.

    PubMed

    Artuso, Emma; Ghibaudi, Elena; Lace, Beatrice; Marabello, Domenica; Vinciguerra, Daniele; Lombardi, Chiara; Koltai, Hinanit; Kapulnik, Yoram; Novero, Mara; Occhiato, Ernesto G; Scarpi, Dina; Parisotto, Stefano; Deagostino, Annamaria; Venturello, Paolo; Mayzlish-Gati, Einav; Bier, Ariel; Prandi, Cristina

    2015-11-25

    Strigolactones (SLs) are new plant hormones with various developmental functions. They are also soil signaling chemicals that are required for establishing beneficial mycorrhizal plant/fungus symbiosis. In addition, SLs play an essential role in inducing seed germination in root-parasitic weeds, which are one of the seven most serious biological threats to food security. There are around 20 natural SLs that are produced by plants in very low quantities. Therefore, most of the knowledge on SL signal transduction and associated molecular events is based on the application of synthetic analogues. Stereochemistry plays a crucial role in the structure-activity relationship of SLs, as compounds with an unnatural D-ring configuration may induce biological effects that are unrelated to SLs. We have synthesized a series of strigolactone analogues, whose absolute configuration has been elucidated and related with their biological activity, thus confirming the high specificity of the response. Analogues bearing the R-configured butenolide moiety showed enhanced biological activity, which highlights the importance of this stereochemical motif. PMID:26502774

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

    PubMed

    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. PMID:25691069

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

    PubMed

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

    2010-12-23

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

  20. The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression.

    PubMed

    Ferronato, María Julia; Alonso, Eliana Noelia; Gandini, Norberto Ariel; Fermento, María Eugenia; Villegas, María Emilia; Quevedo, Mario Alfredo; Arévalo, Julián; López Romero, Alejandro; Rivadulla, Marcos Lois; Gómez, Generosa; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2016-10-01

    Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease. PMID:27208626

  1. Somatostatin and analogues in the treatment of cancer. A review.

    PubMed Central

    Evers, B M; Parekh, D; Townsend, C M; Thompson, J C

    1991-01-01

    Somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones. The beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized; however its clinical usefulness has been limited in the past by its extremely short plasma half-life. The development of long-acting somatostatin analogues has provided clinically useful agents for treatment of hormone-producing tumors. In addition to well-known inhibiting effects on hormone release and actions, recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms. The exact role of somatostatin analogues in cancer therapy has yet to be established; however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors. In this review, the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized. PMID:1671812

  2. Numerical simulation of an experimental analogue of a planetary magnetosphere

    NASA Astrophysics Data System (ADS)

    Liao, Andy Sha; Li, Shule; Hartigan, Patrick; Graham, Peter; Fiksel, Gennady; Frank, Adam; Foster, John; Kuranz, Carolyn

    2015-12-01

    Recent improvements to the Omega Laser Facility's magneto-inertial fusion electrical discharge system (MIFEDS) have made it possible to generate strong enough magnetic fields in the laboratory to begin to address the physics of magnetized astrophysical flows. Here, we adapt the MHD code AstroBEAR to create 2D numerical models of an experimental analogue of a planetary magnetosphere. We track the secular evolution of the magnetosphere analogue and we show that the magnetospheric components such as the magnetopause, magnetosheath, and bow shock, should all be observable in experimental optical band thermal bremsstrahlung emissivity maps, assuming equilibrium charge state distributions of the plasma. When the magnetosphere analogue nears the steady state, the mid-plane altitude of the magnetopause from the wire surface scales as the one-half power of the ratio of the magnetic pressure at the surface of the free wire to the ram pressure of an unobstructed wind; the mid-plane thickness of the magnetosheath is directly related to the radius of the magnetopause. This behavior conforms to Chapman and Ferraro's theory of planetary magnetospheres. Although the radial dependence of the magnetic field strength differs between the case of a current-carrying wire and a typical planetary object, the major morphological features that develop when a supersonic flow passes either system are identical. Hence, this experimental concept is an attractive one for studying the dynamics of planetary magnetospheres in a controlled environment.

  3. Memory protection

    NASA Technical Reports Server (NTRS)

    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.

  4. Protective Eyewear

    MedlinePlus

    ... 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 ...

  5. Corrosion protection

    DOEpatents

    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.

  6. Benzylidene Acetal Protecting Group as Carboxylic Acid Surrogate: Synthesis of Functionalized Uronic Acids and Sugar Amino Acids.

    PubMed

    Banerjee, Amit; Senthilkumar, Soundararasu; Baskaran, Sundarababu

    2016-01-18

    Direct oxidation of the 4,6-O-benzylidene acetal protecting group to C-6 carboxylic acid has been developed that provides an easy access to a wide range of biologically important and synthetically challenging uronic acid and sugar amino acid derivatives in good yields. The RuCl3 -NaIO4 -mediated oxidative cleavage method eliminates protection and deprotection steps and the reaction takes place under mild conditions. The dual role of the benzylidene acetal, as a protecting group and source of carboxylic acid, was exploited in the efficient synthesis of six-carbon sialic acid analogues and disaccharides bearing uronic acids, including glycosaminoglycan analogues. PMID:26572799

  7. Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues.

    PubMed

    Petruş, Alexandra; Duicu, Oana M; Sturza, Adrian; Noveanu, Lavinia; Kiss, Loránd; Dănilă, Maria; Baczkó, István; Muntean, Danina M; Jost, Norbert

    2015-09-01

    A substantial body of evidence indicates that pharmacological activation of mitochondrial ATP-sensitive potassium channels (mKATP) in the heart is protective in conditions associated with ischemia/reperfusion injury. Several mechanisms have been postulated to be responsible for cardioprotection, including the modulation of mitochondrial respiratory function. The aim of the present study was to characterize the dose-dependent effects of novel synthetic benzopyran analogues, derived from a BMS-191095, a selective mKATP opener, on mitochondrial respiration and reactive oxygen species (ROS) production in isolated rat heart mitochondria. Mitochondrial respiratory function was assessed by high-resolution respirometry, and H2O2 production was measured by the Amplex Red fluorescence assay. Four compounds, namely KL-1487, KL-1492, KL-1495, and KL-1507, applied in increasing concentrations (50, 75, 100, and 150 μmol/L, respectively) were investigated. When added in the last two concentrations, all compounds significantly increased State 2 and 4 respiratory rates, an effect that was not abolished by 5-hydroxydecanoate (5-HD, 100 μmol/L), the classic mKATP inhibitor. The highest concentration also elicited an important decrease of the oxidative phosphorylation in a K(+) independent manner. Both concentrations of 100 and 150 μmol/L for KL-1487, KL-1492, and KL-1495, and the concentration of 150 μmol/L for KL-1507, respectively, mitigated the mitochondrial H2O2 release. In isolated rat heart mitochondria, the novel benzopyran analogues act as protonophoric uncouplers of oxidative phosphorylation and decrease the generation of reactive oxygen species in a dose-dependent manner. PMID:26325241

  8. Enantioselective Inhibition of Squalene Synthase by Aziridine Analogues of Presqualene Diphosphate

    PubMed Central

    Koohang, Ali; Bailey, Jessica L.; Erickson, Hans K.; Owen, David; Poulter, C. Dale

    2013-01-01

    Squalene synthase catalyzes the conversion of two molecules of (E,E)-farnesyl diphosphate to squalene via the cyclopropylcarbinyl intermediate, presqualene diphosphate (PSPP). Since this novel reaction constitutes the first committed step in sterol biosynthesis, there has been considerable interest and research on the stereochemistry and mechanism of the process and in the design of selective inhibitors of the enzyme. This paper reports the synthesis and characterization of five racemic and two enantiopure aziridine analogues of PSPP and the evaluation of their potencies as inhibitors of recombinant yeast squalene synthase. The key aziridine-2-methanol intermediates (6-OH, 7-OH, and 8-OH) were obtained by N-alkylations or by an N-acylation–reduction sequence of (±)-, (2R,3S)-, and (2S,3R)-2,3-aziridinofarnesol (9-OH) protected as tert-butyldi-methylsilyl ethers. SN2 displacements of the corresponding methanesulfonates with pyrophosphate and methanediphosphonate anions afforded aziridine 2-methyl diphosphates and methanediphosphonates bearing N-undecyl, N-bishomogeranyl, and N-(α-methylene)bishomogeranyl substituents as mimics for the 2,6,10-trimethylundeca-2,5,9-trienyl side chain of PSPP. The 2R,3S diphosphate enantiomer bearing the N-bishomogeranyl substituent corresponding in absolute stereochemistry to PSPP proved to be the most potent inhibitor (IC50 1.17 ± 0.08 μM in the presence of inorganic pyrophosphate), a value 4-fold less than that of its 2S,3R stereoisomer. The other aziridine analogues bearing the N-(α-methylene)bishomogeranyl and N-undecyl substituents, and the related methanediphosphonates, exhibited lower affinities for recombinant squalene synthase. PMID:20545375

  9. Epoxyeicosatrienoic acid analogue mitigates kidney injury in a rat model of radiation nephropathy.

    PubMed

    Hye Khan, Md Abdul; Fish, Brian; Wahl, Geneva; Sharma, Amit; Falck, John R; Paudyal, Mahesh P; Moulder, John E; Imig, John D; Cohen, Eric P

    2016-04-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by CYP epoxygenases, and EETs are kidney protective in multiple pathologies. We determined the ability of an EET analogue, EET-A, to mitigate experimental radiation nephropathy. The kidney expression of the EET producing enzyme CYP2C11 was lower in rats that received total body irradiation (TBI rat) compared with non-irradiated control. At 12 weeks after TBI, the rats had higher systolic blood pressure and impaired renal afferent arteriolar function compared with control, and EET-A or captopril mitigated these abnormalities. The TBI rats had 3-fold higher blood urea nitrogen (BUN) compared with control, and EET-A or captopril decreased BUN by 40-60%. The urine albumin/creatinine ratio was increased 94-fold in TBI rats, and EET-A or captopril attenuated that increase by 60-90%. In TBI rats, nephrinuria was elevated 30-fold and EET-A or captopril decreased it by 50-90%. Renal interstitial fibrosis, tubular and glomerular injury were present in the TBI rats, and each was decreased by EET-A or captopril. We further demonstrated elevated renal parenchymal apoptosis in TBI rats, which was mitigated by EET-A or captopril. Additional studies revealed that captopril or EET-A mitigated renal apoptosis by acting on the p53/Fas/FasL (Fas ligand) apoptotic pathway. The present study demonstrates a novel EET analogue-based strategy for mitigation of experimental radiation nephropathy by improving renal afferent arteriolar function and by decreasing renal apoptosis. PMID:26772189

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

    PubMed

    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. PMID:25351683

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

    PubMed Central

    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. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    SciTech Connect

    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

  13. Opioid profiles of Cys2-containing enkephalin analogues.

    PubMed

    Pencheva, Nevena; Milanov, Peter; Vezenkov, Lubomir; Pajpanova, Tamara; Naydenova, Emilia

    2004-09-13

    To elucidate the structural features determining delta-opioid receptor properties of enkephalin analogues containing Cys(O2NH2) in position 2, a series of Cys2-containing derivatives were synthesized and tested for their effectiveness in depressing electrically evoked contractions of the mouse vas deferens (predominantly enkephalin-selective delta-opioid receptors) and the guinea-pig ileum (mu- and kappa-opioid receptors). The peptidase resistance of the compounds was also tested. The ratio IC50 in the guinea-pig ileum/IC50 in the mouse vas deferens, indicating selectivity for delta-opioid receptors, was high for Cys(O2NH2)2-containing analogues and especially for [Cys(O2NH2)2, Leu5]enkephalin, which was about seven times more selective than delta-opioid receptor selective ligand cyclic [D-Pen2, D-Pen5]enkephalin (DPDPE). The dissociation constant (KA) and relative efficacy (e(rel)) of the compounds in the mouse-isolated vas deferens were determined using explicit formulae derived by fitting of the data points with two-parametric hyperbolic function. The obtained values for KA and e(rel) suggest that: (i) incorporation of Cys(O2NH2)2 in the molecule of [Leu5]enkephalin highly increases the efficacy and does not change significantly the affinity of the respective analogues to delta-opioid receptors; [Cys(O2NH2)2, Leu5]enkephalin has higher affinity than DPDPE, but is less resistant to enzyme degradation; the effect of this modification on the efficacy is decreased when methionine is in position 5; (ii) D-configuration of Cys(O2NH2)2-containing analogues increases their peptidase resistance, but reduces efficacy and affinity of the peptides towards delta-opioid receptors; (iii) the substitution of Cys(O2NH2) with Hcy(O2NH2) reduces the efficacy, affinity and potency of the respective analogues and maintains their sensitivity to endogenous peptidases; (iv) the substitution of the sulfonamide group with benzyl group in the molecule of Cys in position 2 decreases their

  14. Past and present of analogue modelling, and its future trend

    NASA Astrophysics Data System (ADS)

    Koyi, Hemin

    2015-04-01

    Since Hull (1815) published his article on modelling, analogue modelling has expanded to simulate both a wider range of tectonic regimes and target more challenging set-ups, and has become an integrated part of the fields of tectonics and structural geology. Establishment of new laboratories testifies for the increased attention the technique receives. The ties between modellers and field geoscientists have become stronger with the focus being on understanding the parameters that govern the evolution of a tectonic regime and the processes that dominate it. Since the first sand castle was built with damp sand on a beach, sand has proven to be an appropriate material analogue. Even though granular materials is the most widely used analogue material, new materials are also (re)introduced as rock analogues. Emphasis has been on more precise measurements of the mechanical properties of the materials and on minimizing the preparation effects, which have a great impact on scaling, interpretations and benchmarking. The analytical technique used to quantify model results has also seen a great deal of improvement. In addition to X-ray tomography used to visualise internal structures of models, new techniques (e.g. PIV, high-resolution laser scanning, and interferometry) have enabled monitoring kinematics with a higher precision. Benchmarking exercises have given modelling an additional checking tool by outlining, in addition to the rheology of the modelling materials, the impact of different preparation approaches, the effect of boundary conditions, and the human factor on model results. However, despite the different approaches and deformation rigs, results of models of different tectonic laboratories have shown a great deal of similarities. Even with the introduction of more sophisticated numerical codes and usage of more powerful computers which enable the simulation of more challenging material properties and combinations of those, and 3D model set-up, analogue modelling

  15. "Why" or "How": The Effect of Concrete Versus Abstract Processing on Intrusive Memories Following Analogue Trauma.

    PubMed

    White, Rachel; Wild, Jennifer

    2016-05-01

    Emergency service workers, military personnel, and journalists working in conflict zones are regularly exposed to trauma as part of their jobs and suffer higher rates of posttraumatic stress compared with the general population. These individuals often know that they will be exposed to trauma and therefore have the opportunity to adopt potentially protective cognitive strategies. One cognitive strategy linked to better mood and recovery from upsetting events is concrete information processing. Conversely, abstract information processing is linked to the development of anxiety and depression. We trained 50 healthy participants to apply an abstract or concrete mode of processing to six traumatic film clips and to apply this mode of processing to a posttraining traumatic film. Intrusive memories of the films were recorded for 1week and the Impact of Events Scale-Revised (IES-R; Weiss & Marmar, 1997) was completed at 1-week follow-up. As predicted, participants in the concrete condition reported significantly fewer intrusive memories in response to the films and had lower IES-R scores compared with those in the abstract condition. They also showed reduced emotional reactivity to the posttraining film. Self-reported proneness to intrusive memories in everyday life was significantly correlated with intrusive memories of the films, whereas trait rumination, trait dissociation, and sleep difficulties were not. Findings suggest that training individuals to adopt a concrete mode of information processing during analogue trauma may protect against the development of intrusive memories. PMID:27157033

  16. Lightning Protection

    NASA Technical Reports Server (NTRS)

    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.

  17. Lightning Protection

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Lightning Technologies, Inc., Pittsfield, MA, - a spinoff company founded by president J. Anderson Plumer, a former NASA contractor employee who developed his expertise with General Electric Company's High Voltage Laboratory - was a key player in Langley Research Center's Storm Hazards Research Program. Lightning Technologies used its NASA acquired experience to develop protective measures for electronic systems and composite structures on aircraft, both of which are particularly susceptible to lightning damage. The company also provides protection design and verification testing services for complete aircraft systems or individual components. Most aircraft component manufacturers are among Lightning Technologies' clients.

  18. Noise Protection

    NASA Technical Reports Server (NTRS)

    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.

  19. Testing technologies and strategies for exploration in Australian Mars analogues: A review

    NASA Astrophysics Data System (ADS)

    West, Michael D.; D. A. Clarke, Jonathan; Laing, Jennifer H.; Willson, David; Waldie, James M. A.; Murphy, Guy M.; Thomas, Matilda; Mann, Graham A.

    2010-03-01

    Australia is an ideal testing ground in preparation for the robotic and human exploration of Mars. Numerous sites with landforms or processes analogous to those on Mars are present and the deserts of central Australia provide a range of locations for free-ranging Mars analogue mission simulations. The latest developments in testing technologies and strategies for exploration in Australian Mars analogues are reviewed. These include trials of analogue space suits based on mechanical counter pressure technology and the development of an analogue, crewed, pressurized rover for long-range exploration. Field science activities and instrumentation testing relevant to robotic and future crewed missions are discussed. Australian-led human factors research undertaken during expeditions to Mars analogue research stations and expeditions to Antarctica are also reviewed. Education and public outreach activities related to Mars analogue research in Australia are also detailed.

  20. Quantitative comparisons of analogue models of brittle wedge dynamics

    NASA Astrophysics Data System (ADS)

    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

  1. Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death.

    PubMed

    Shakeel-u-Rehman; Rah, Bilal; Lone, Shabir H; Rasool, Reyaz Ur; Farooq, Saleem; Nayak, Debasis; Chikan, Naveed Anjum; Chakraborty, Souneek; Behl, Akanksha; Mondhe, Dilip Manikaro; Goswami, Anindya; Bhat, Khursheed Ahmad

    2015-04-23

    Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structure-activity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 μM against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlich's ascitic and solid Sarcoma-180 mouse models. PMID:25825934

  2. Dynamics of water in prussian blue analogues: Neutron scattering study

    NASA Astrophysics Data System (ADS)

    Sharma, V. K.; Mitra, S.; Thakur, N.; Yusuf, S. M.; Juranyi, Fanni; Mukhopadhyay, R.

    2014-07-01

    Dynamics of crystal water in Prussian blue (PB), Fe(III)4[Fe(II)(CN)6]3.14H2O and its analogue Prussian green (PG), ferriferricynaide, Fe(III)4[Fe(III)(CN)6]4.16H2O have been investigated using Quasielastic Neutron Scattering (QENS) technique. PB and its analogue compounds are important materials for their various interesting multifunctional properties. It is known that crystal water plays a crucial role towards the multifunctional properties of Prussian blue analogue compounds. Three structurally distinguishable water molecules: (i) coordinated water molecules at empty nitrogen sites, (ii) non-coordinated water molecules in the spherical cavities, and (iii) at interstitial sites exist in PB. Here spherical cavities are created due to the vacant sites of Fe(CN)6 units. However, PG does not have any such vacant N or Fe(CN)6 units, and only one kind of water molecules, exists only at interstitial sites. QENS experiments have been carried out on both the compounds in the temperature range of 260-360 K to elucidate the dynamical behavior of different kinds of water molecules. Dynamics is found to be much more pronounced in case of PB, compared to PG. A detailed data analysis showed that localized translational diffusion model could describe the observed data for both PB and PG systems. The average diffusion coefficient is found to be much larger in the PB than PG. The obtained domain of dynamics is found to be consistent with the geometry of the structure of the two systems. Combining the data of the two systems, a quantitative estimate of the dynamics, corresponding to the water molecules at different locations is made.

  3. Dynamics of water in prussian blue analogues: Neutron scattering study

    SciTech Connect

    Sharma, V. K.; Mitra, S.; Thakur, N.; Yusuf, S. M.; Mukhopadhyay, R.; Juranyi, Fanni

    2014-07-21

    Dynamics of crystal water in Prussian blue (PB), Fe(III){sub 4}[Fe(II)(CN){sub 6}]{sub 3}.14H{sub 2}O and its analogue Prussian green (PG), ferriferricynaide, Fe(III){sub 4}[Fe(III)(CN){sub 6}]{sub 4}.16H{sub 2}O have been investigated using Quasielastic Neutron Scattering (QENS) technique. PB and its analogue compounds are important materials for their various interesting multifunctional properties. It is known that crystal water plays a crucial role towards the multifunctional properties of Prussian blue analogue compounds. Three structurally distinguishable water molecules: (i) coordinated water molecules at empty nitrogen sites, (ii) non-coordinated water molecules in the spherical cavities, and (iii) at interstitial sites exist in PB. Here spherical cavities are created due to the vacant sites of Fe(CN){sub 6} units. However, PG does not have any such vacant N or Fe(CN){sub 6} units, and only one kind of water molecules, exists only at interstitial sites. QENS experiments have been carried out on both the compounds in the temperature range of 260–360 K to elucidate the dynamical behavior of different kinds of water molecules. Dynamics is found to be much more pronounced in case of PB, compared to PG. A detailed data analysis showed that localized translational diffusion model could describe the observed data for both PB and PG systems. The average diffusion coefficient is found to be much larger in the PB than PG. The obtained domain of dynamics is found to be consistent with the geometry of the structure of the two systems. Combining the data of the two systems, a quantitative estimate of the dynamics, corresponding to the water molecules at different locations is made.

  4. Migrastatin Analogues Inhibit Canine Mammary Cancer Cell Migration and Invasion

    PubMed Central

    Majchrzak, Kinga; Lo Re, Daniele; Gajewska, Małgorzata; Bulkowska, Małgorzata; Homa, Agata; Pawłowski, Karol; Motyl, Tomasz; Murphy, Paul V.; Król, Magdalena

    2013-01-01

    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. However, further in

  5. Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin

    SciTech Connect

    Isab, A.A.; Shaw, C.F. III; Hoeschele, J.D.; Locke, J.

    1988-10-05

    The reactions of bovine serum albumin (BSA) with (trimethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I), Me/sub 3/PAuSAtg, and its chloro analogue, Me/sub 3/PAuCl, were studied to develop insights into the role of the phosphine ligand in the serum chemistry of the related antiarthritic drug auranofin (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I). /sup 31/P NMR spectroscopy, protein modification, and gel-exclusion chromatography methods were employed. Comparison of the reactions of the methyl derivatives to the previously reported reactions of auranofin and Et/sub 3/PAuCl with BSA demonstrated that similar chemical species are formed but revealed three major differences. Despite these differences, the results for the methyl analogues provide important confirmation for previously developed chemical models of auranofin reactions in serum. Me/sub 3/PO was not observed in reaction mixtures lacking tetraacetylthioglucose (AtgSH); this result affirms the role of AtgSH, displaced by the reaction of Me/sub 3/PAuSAtg at Cys-34, in the generation of the phosphine oxide (an important metabolite in vivo). The weak binding sites on albumin react with Me/sub 3/PAuCl, but not Me/sub 3/PAuSAtg, demonstrating the importance of the strength and reactivity of the anionic ligand-gold bond on the reactions of auranofin analogues. The gold binding capacity of albumin is enhanced after Me/sub 3/PO is formed, consistent with reductive cleavage of albumin disulfide bonds by trimethylphosphine. 24 references, 2 figures, 3 tables.

  6. Synthesis of p-aminophenyl aryl H-phosphinic acids and esters via cross-coupling reactions: elaboration to phosphinic acid pseudopeptide analogues of pteroyl glutamic acid and related antifolates.

    PubMed

    Yang, Yonghong; Coward, James K

    2007-07-20

    The synthesis of suitably protected p-aminophenyl H-phosphinic acids and esters from the corresponding para-substituted aryl halides has been accomplished via the Pd-catalyzed cross-coupling reaction of anilinium hypophosphite, either in the absence or presence of a tetraalkyl orthosilicate, to provide the free H-phosphinic acid or the corresponding ester, respectively. Subsequent conjugate addition of either a PIII species or phosphorus anion, generated in situ from either the free H-phosphinic acid or ester, to a 2-methylene glutaric acid ester provided the aryl phosphinic acid analogue of p-aminobenzoyl glutamic acid. Alkylation of these suitably protected p-aminophenyl phosphinic acid esters with a 6-(bromomethyl)pteridine or the corresponding (bromomethyl)pyridopyrmidine, followed by hydrolytic removal of protecting groups, provided the target aryl phosphinic acid analogues of folic acid and related antifolates. Alternatively, for the synthesis of the folate or 5-deazafolate analogues on a slightly larger scale, reductive amination with either N2-acetyl or N2-pivaloyl-6-formylpterin or the corresponding formylpyridopyrmidine and the same suitably protected p-aminophenyl phosphinic acid esters, followed by removal of protecting groups, is preferred. In the course of this research, it was observed that the nucleophilicity of both the aniline nitrogen and various PIII species derived from p-aminophenyl phosphinic acid derivatives is significantly reduced compared to that of the unsubstituted counterpart. PMID:17602593

  7. Protective Clothing

    NASA Technical Reports Server (NTRS)

    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.

  8. Protect thyself

    SciTech Connect

    Sullivan, A.M.

    1982-06-01

    The article considers items of personal protection for miners: Self-rescuers, respirators, hard hats and cap lamps. A table provides a comparison between five types of self-contained self-rescuer. Details are also given of hard hat cap lamp and respirator manufacturers.

  9. Protecting Privacy.

    ERIC Educational Resources Information Center

    Coyle, Karen

    2001-01-01

    Discusses privacy issues related to use of the Internet. Topics include data gathering functions that are built into applications of the World Wide Web; cookies that identify Web site visitors; personal identity information; libraries and privacy, including the need for privacy policies; protecting your privacy; and developing privacy literacy.…

  10. Thiophene-3-carboxamide analogue of annonaceous acetogenins as antitumor drug lead.

    PubMed

    Kojima, Naoto; Fushimi, Tetsuya; Tatsukawa, Takahiro; Tanaka, Tetsuaki; Okamura, Mutsumi; Akatsuka, Akinobu; Yamori, Takao; Dan, Shingo; Iwasaki, Hiroki; Yamashita, Masayuki

    2014-10-30

    Five novel acetogenin analogues with a furan, thiophene, or thiazole ring were synthesized, and their inhibitory activities toward human cancer cell lines were evaluated. The analogues showed more potent activities than natural acetogenin. One of them, the thiophene-3-carboxamide analogue, strongly inhibited the growth of human lung cancer cell line NCI-H23 in the xenograft mouse assay without critical toxicity. PMID:25226228

  11. Estimation of analogue pre-filtering characteristics for CORSA standardisation.

    PubMed

    Sun, X Q; Cheetham, B M; Evans, K G; Earis, J E

    1998-11-01

    This paper is concerned with devising a standard procedure for determining the gain and phase responses of the analogue filters used to pre-process pulmonary signals prior to their digitisation. The customary high-pass filtering, in particular, will strongly affect the time-domain wave-shapes of digitised signals and this must be taken into account when analysing the signals. Several means of determining the effect of the high-pass filtering are investigated and a measurement procedure is proposed which may be easily carried out using simple laboratory equipment. PMID:9924955

  12. Analogue Aharonov-Bohm effect in neo-Newtonian theory

    NASA Astrophysics Data System (ADS)

    Anacleto, M. A.; Salako, I. G.; Brito, F. A.; Passos, E.

    2015-12-01

    We address the issues of the scattering of massless planar scalar waves by an acoustic black hole in neo-Newtonian hydrodynamics. We then compute the differential cross section through the use of the partial wave approach in the neo-Newtonian theory which is a modification of the usual Newtonian theory that correctly incorporates the effects of pressure. We mainly show that the scattering of planar waves leads to a modified analogue Aharonov-Bohm effect due to a nontrivial response of the parameters defining the equation of state.

  13. Galaxies and Saturn's rings: Gravitational analogues of nonneutral plasmas

    SciTech Connect

    Mark, J.W.K.

    1985-04-25

    Orbit and collective dynamics in disk galaxies and in Saturn's rings are gravitational analogues of those occurring in nonneutral plasmas. The interesting problems for such ''gravitational plasmas'' are analogous to single-disk studies of transverse dynamics in particle beams. Of particular interest are various orbit-resonances with spiral density and bending waves in these disks which are analogous to electrostatic waves in nonneutral beam plasmas. The background physics, terminology and results of astrophysical investigations in these fields are surveyed in this paper. 53 refs., 19 figs., 1 tab.

  14. Pena blanca natural analogue project: summary of activities

    SciTech Connect

    Levy, Schon S; Goldstein, Steven J; Abdel - Fattah, Amr I

    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.

  15. Synthesis and study of new paramagnetic resveratrol analogues.

    PubMed

    Kálai, Tamás; Borza, Erzsébet; Antus, Csenge; Radnai, Balázs; Gulyás-Fekete, Gergely; Fehér, Andrea; Sümegi, Balázs; Hideg, Kálmán

    2011-12-15

    New resveratrol analogues containing five- and six-membered nitroxides and isoindoline nitroxides were synthesized. These new compounds were compared to resveratrol based on their ABTS radical scavenging ability as well on their capacity to suppress inflammatory process in macrophages induced by lipopolysaccharides. The ABTS and ROS scavenging activities of new molecules were the same or weaker than that of resveratrol, but some of paramagnetic resveratrol derivatives suppressed nitrite and TNFα production more efficiently than resveratrol. Based on these results the new nitroxide and phenol containing hybrid molecules can be considered as new antioxidant and anti-inflammatory agents. PMID:22088309

  16. Interfacing an analogue infrared spectrometer to a microcomputer.

    PubMed

    Adams, M J; Ewen, G J

    1987-02-01

    An Apple microcomputer has been interfaced to a Perkin-Elmer model 577 infrared spectrometer. The spectral data are digitized with the aid of an in-house designed 12-bit analogue-to-digital interface unit. Control and status signals are obtained from the spectrometer and an optical encoder unit is used to provide an accurate wavenumber marker for the conversion and data recording. The digital data are formatted by the microcomputer and then can be manipulated by programs already developed for handling spectral data recorded from digital spectrometers. PMID:18964290

  17. Novel nicotine analogues with potential anti-mycobacterial activity.

    PubMed

    Gandhi, Paresh T; Athmaram, Thimmasandra Narayanappa; Arunkumar, Gundaiah Ramesh

    2016-04-15

    Tuberculosis (TB) is the second leading lethal infectious disease in the world after acquired immuno deficiency (AIDs). We have developed a series of twenty-five novel nicotine analogues with de-addiction property and tested them for their activity against Mycobacterium tuberculosis (MTB). In an effort to increase the specificity of action and directing nicotine analogues to target MTB, four promising compounds were further optimized via molecular docking studies against the Dihydrofolate reductase of MTB. After lead optimization, one nicotine analogue [3-(5-(3fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one] exhibited minimum inhibitory concentration of 1μg/mL (2.86nM) against M. tuberculosis (H37Rv strain), a human pathogenic strain of clinically significant importance. Pharmacokinetic analysis of [3-(5-(3fluorophenyl)nicotinoyl)-1methylpyrrolidin-2-one] with lowest MIC value via oral route in Wistar rats revealed that at a dosage of 5mg/kg body weight gave a maximum serum drug concentration (Cmax) of 2.86μg/mL, Tmax of one hour and a half-life (T1/2) of more than 24h and Volume of distribution (Vd) of 27.36L. Whereas the parenteral (intra venous) route showed a Cmax of 3.37μg/mL, Tmax of 0.05h, T1/2 of 24h and Vd equivalent to 23.18L. The acute oral toxicity and repeated oral toxicity studies in female Wistar rats had an LD50>2000mg/kg body weight. Our data suggests that nicotine derivatives developed in the present study has good metabolic stability with tunable pharmacokinetics (PK) with therapeutic potential to combat MTB. However, further in vivo studies for anti-tuberculosis activity and elucidation of mode of action could result in more promising novel drug for treating MTB. To the best of our knowledge this is the first report revealing the anti-mycobacterial potential of nicotine analogue at potential therapeutic concentrations. PMID:26951892

  18. Synthesis, preliminary bioevaluation and computational analysis of caffeic acid analogues.

    PubMed

    Liu, Zhiqian; Fu, Jianjun; Shan, Lei; Sun, Qingyan; Zhang, Weidong

    2014-01-01

    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. PMID:24857914

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

    PubMed Central

    Liu, Zhiqian; Fu, Jianjun; Shan, Lei; Sun, Qingyan; Zhang, Weidong

    2014-01-01

    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. PMID:24857914

  20. Dynamic Characteristics Analysis of Analogue Networks Design Process

    NASA Astrophysics Data System (ADS)

    Zemliak, Alexander M.

    The process of designing analogue circuits is formulated as a controlled dynamic system. For analysis of such system's properties it is suggested to use the concept of Lyapunov's function for a dynamic system. Various forms of Lyapunov's function are suggested. Analyzing the behavior of Lyapunov's function and its first derivative allowed us to determine significant correlation between this function's properties and processor time used to design the circuit. Numerical results prove the possibility of forecasting the behavior of various designing strategies and processor time based on the properties of Lyapunov's function for the process of designing the circuit.

  1. B38: an all-boron fullerene analogue

    NASA Astrophysics Data System (ADS)

    Lv, Jian; Wang, Yanchao; Zhu, Li; Ma, Yanming

    2014-09-01

    Fullerene-like structures formed by elements other than carbon have long been sought. Finding all-boron (B) fullerene-like structures is challenging due to the geometrical frustration arising from competitions among various structural motifs. We report here the prediction of a B38 fullerene analogue found through first-principles swarm structure searching calculations. The structure is highly symmetric and consists of 56 triangles and four hexagons, which provide an optimal void in the center of the cage. Energetically, it is more favorable than the planar and tubular structures, and possesses an unusually high chemical stability: a large energy gap (~2.25 eV) and a high double aromaticity, superior to those of most aromatic quasi-planar B12 and double-ring B20 clusters. Our findings represent a key step forward towards to the understanding of structures of medium-sized B clusters and map out the experimental direction of the synthesis of an all-B fullerene analogue.Fullerene-like structures formed by elements other than carbon have long been sought. Finding all-boron (B) fullerene-like structures is challenging due to the geometrical frustration arising from competitions among various structural motifs. We report here the prediction of a B38 fullerene analogue found through first-principles swarm structure searching calculations. The structure is highly symmetric and consists of 56 triangles and four hexagons, which provide an optimal void in the center of the cage. Energetically, it is more favorable than the planar and tubular structures, and possesses an unusually high chemical stability: a large energy gap (~2.25 eV) and a high double aromaticity, superior to those of most aromatic quasi-planar B12 and double-ring B20 clusters. Our findings represent a key step forward towards to the understanding of structures of medium-sized B clusters and map out the experimental direction of the synthesis of an all-B fullerene analogue. Electronic supplementary information

  2. Frequency converter implementing an optical analogue of the cosmological redshift.

    PubMed

    Ginis, Vincent; Tassin, Philippe; Craps, Ben; Veretennicoff, Irina

    2010-03-01

    According to general relativity, the frequency of electromagnetic radiation is altered by the expansion of the universe. This effect-commonly referred to as the cosmological redshift--is of utmost importance for observations in cosmology. Here we show that this redshift can be reproduced on a much smaller scale using an optical analogue inside a dielectric metamaterial with time-dependent material parameters. To this aim, we apply the framework of transformation optics to the Robertson-Walker metric. We demonstrate theoretically how perfect redshifting or blueshifting of an electromagnetic wave can be achieved without the creation of sidebands with a device of finite length. PMID:20389549

  3. Integration of inherent and induced chirality into subphthalocyanine analogue

    NASA Astrophysics Data System (ADS)

    Zhao, Luyang; Qi, Dongdong; Wang, Kang; Wang, Tianyu; Han, Bing; Tang, Zhiyong; Jiang, Jianzhuang

    2016-06-01

    Conventional conjugated systems are characteristic of only either inherent or induced chirality because of synthetic challenge in combination of chiral segment into the main chromophore. In this work, chiral binaphthyl segment is directly fused into the central chromophore of a subphthalocyanine skeleton, resulting in a novel type of chiral subphthalocyanine analogue (R/S)-1 of integrated inherent and induced chirality. Impressively, an obviously enhanced optical activity is discerned for (R/S)-1 molecules, and corresponding enhancement mechanism is elucidated in detail. The synthesis strategy based on rational molecular design will open the door towards fabrication of chiral materials with giant optical activity, which will have great potential in chiroptical devices.

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  5. Towards bottom-up nanopatterning of Prussian blue analogues

    PubMed Central

    Trannoy, Virgile; Faustini, Marco; Grosso, David; Mazerat, Sandra; Brisset, François; Dazzi, Alexandre

    2014-01-01

    Summary Ordered nanoperforated TiO2 monolayers fabricated through sol–gel chemistry were used to grow isolated particles of Prussian blue analogues (PBA). The elaboration of the TiO2/CoFe PBA nanocomposites involves five steps. The samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), infrared spectroscopy and X-ray photoelectron spectroscopy (XPS) all along the synthesis process. Selected physico-chemical parameters have been varied in order to determine the key steps of the synthesis process and to optimize it. This study is an important step towards the full control of the fabrication process. PMID:25383305

  6. Synthesis and biological evaluation of a beauveriolide analogue library.

    PubMed

    Nagai, Kenichiro; Doi, Takayuki; Sekiguchi, Takafumi; Namatame, Ichiji; Sunazuka, Toshiaki; Tomoda, Hiroshi; Omura, Satoshi; Takahashi, Takashi

    2006-01-01

    Synthesis of beauveriolide III (1b), which is an inhibitor of lipid droplet accumulation in macrophages, was achieved by solid-phase assembly of linear depsipeptide using a 2-chlorotrityl linker followed by solution-phase cyclization. On the basis of this strategy, a combinatorial library of beauveriolide analogues was carried out by radio frequency-encoded combinatorial chemistry. After automated purification using preparative reversed-phase HPLC, the library was tested for inhibitory activity of CE synthesis in macrophages to determine structure-activity relationships of beauveriolides. Among them, we found that diphenyl derivative 7{9,1} is 10 times more potent than 1b. PMID:16398560

  7. Astrobiology Field Research in Moon/Mars Analogue Environments: Preface

    NASA Technical Reports Server (NTRS)

    Foing, B. H.; Stoker, C.; Ehrenfreund, P.

    2011-01-01

    Extreme environments on Earth often provide similar terrain conditions to landing/operation sites on Moon and Mars. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) were conducted at the Mars Desert Research Station (MDRS) in Utah. Some of the key astrobiology results are presented in this special issue on Astrobiology field research in Moon/Mars analogue environments relevant to investigate the link between geology, minerals, organics and biota. Preliminary results from a multidisciplinary field campaign at Rio Tinto in Spain are presented.

  8. Pena Blanca Natural Analogue Project: Summary of activities

    SciTech Connect

    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.

  9. Stepwise analogue downscaling for hydrology (SANDHY): validation experiments over France

    NASA Astrophysics Data System (ADS)

    Radanovics, Sabine; Vidal, Jean-Philippe; Sauquet, Eric; Ben Daoud, Aurélien; Bontron, Guillaume

    2014-05-01

    Statistical downscaling aims at finding relationships between local precipitation (predictand) and large-scale predictor fields, in various contexts, from medium-term forecasting to climate change impact studies. One of the challenges of statistical downscaling in a climate change context is that the predictor-predictand relationship should still be valid under climate change conditions. A minimum requirement is therefore to test the performance of the downscaling method on independent data under current climate conditions. The downscaling method considered is the Stepwise ANalog Downscaling method for HYdrology (SANDHY). ERA-40 reanalysis data are used as large scale predictors and daily precipitation from the French near surface reanalysis (Safran) as predictand. Two 20-year periods have been selected from the common archive period of the two data sources: 1958-1978 ('early') and 1982-2002 ('late'). SANDHY has been optimised over the late period in terms of geopotential predictor domains individually for 608 target zones covering France. The validation setup consists of 4 experiments, that all use the parameters as optimised for the late period and that are compared in terms of continous ranked probability skill score (CRPSS) with climatology as reference: Reference simulation. A simulation of the late period is performed using the late period as an archive for searching the analogue dates, thus representing the best possible case. The CRPSS shows a spatial distribution similar to the one of the mean precipitation. Out-of-sample validation. The early period is simulated using the late period as an archive for searching the analogue dates. The idea is to simulate a period whose local data is not 'known' by the model as it would be the case in any application. The average skill loss compared to the reference simulation is reasonable with some more skill loss in the northern part of the country and no loss in the southeastern part. Alternative archive. The late

  10. Anisotropic metamaterial as an analogue of a black hole

    NASA Astrophysics Data System (ADS)

    Fernández-Núñez, Isabel; Bulashenko, Oleg

    2016-01-01

    Propagation of light in a metamaterial medium which mimics curved spacetime and acts like a black hole is studied. We show that for a particular type of spacetimes and wave polarization, the time dilation appears as dielectric permittivity, while the spatial curvature manifests as magnetic permeability. The optical analogue to the relativistic Hamiltonian which determines the ray paths (null geodesics) in the anisotropic metamaterial is obtained. By applying the formalism to the Schwarzschild metric, we compare the ray paths with full-wave simulations in the equivalent optical medium.

  11. Analysis of Vitamins D, Their Metabolites and Analogues

    NASA Astrophysics Data System (ADS)

    Makin, Hugh L. J.; Jones, Glenville; Kaufmann, Martin; Calverley, Martin J.

    The analysis of vitamins D and their metabolites and analogues has been reviewed by us on two occasions (Makin et al., 1995; Jones and Makin, 2000) over the last 10-15 years. In this chapter, we have drawn heavily on the 2000 review, up-dating it to take account of the developments in methodology that have occurred in the intervening years, but including elements of our 1995 review so that the reader can get a picture of the historical context as well as the modern developments.

  12. The Canadian space agency planetary analogue materials suite

    NASA Astrophysics Data System (ADS)

    Cloutis, Edward A.; Mann, Paul; Izawa, Matthew R. M.; Applin, Daniel M.; Samson, Claire; Kruzelecky, Roman; Glotch, Timothy D.; Mertzman, Stanley A.; Mertzman, Karen R.; Haltigin, Timothy W.; Fry, Christopher

    2015-12-01

    The Canadian Space Agency (CSA) recently commissioned the development of a suite of over fifty well-characterized planetary analogue materials. These materials are terrestrial rocks and minerals that are similar to those known or suspected to occur on the lunar or martian surfaces. These include: Mars analogue sedimentary, hydrothermal, igneous and low-temperature alteration rock suites; lunar analogue basaltic and anorthositic rock suites; and a generic impactite rock suite from a variety of terrestrial impact structures. Representative thin sections of the materials have been characterized by optical microscopy and electron probe microanalysis (EPMA). Reflectance spectra have been collected in the ultraviolet, visible, near-infrared and mid-infrared, covering 0.2-25 μm. Thermal infrared emission spectra were collected from 5 to 50 μm. Raman spectra with 532 nm excitation, and laser-induced fluorescence spectra with 405 nm excitation were also measured. Bulk chemical analysis was carried out using X-ray fluorescence, with Fe valence determined by wet chemistry. Chemical and mineralogical data were collected using a field-portable Terra XRD-XRF instrument similar to CheMin on the MSL Curiosity rover. Laser-induced breakdown spectroscopy (LIBS) data similar to those measured by ChemCam on MSL were collected for powdered samples, cut slab surfaces, and as depth profiles into weathered surfaces where present. Three-dimensional laser camera images of rock textures were collected for selected samples. The CSA intends to make available sample powders (<45 μm and 45-1000 μm grain sizes), thin sections, and bulk rock samples, and all analytical data collected in the initial characterisation study to the broader planetary science community. Aiming to complement existing planetary analogue rock and mineral libraries, the CSA suite represents a new resource for planetary scientists and engineers. We envision many potential applications for these materials in the

  13. Detection of cyanobacteria and methanogens embedded in Mars analogue minerals by the use of Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    de Vera, J.-P. P.; Böttger, U.; Fritz, J.; Weber, I.; Malaszkiewicz, J.; Serrano, P.; Meessen, J.; Ott, S.; Wagner, D.; Hübers, H.-W.

    2012-04-01

    RLS (Raman Laser Spectrometer - one of the Pasteur Payload Instruments onboard ExoMars 2018) will perform Raman measurements on Mars to identify organic compounds and mineral products as an indication of biological activity. The measurements will be performed on crushed powdered samples inside the Rover's ALD (Analytical Laboratory Drawer). Raman analytics with the same specifications as those onboard the future ExoMars mission are conducted to test their potential of identifying biological material on martian analogue material. Appropriate measurement parameters for the detection of biological material as well as for the determination of the mineral composition will be derived. In addition, we report on problems using Raman spectroscopy to discriminate cells of microorganisms from the mineral background. Two organisms are chosen as test candidates for potential life on Mars: cyanobacteria and methane producing archaea. Prokaryotes like archaea and bacteria appeared on early Earth at least 3.8 to 3.5 billion years ago (Gya). At this time on Mars the climate was more temperate and wet compared to the present day as inferred from geological evidence for liquid water on the ancient martian surface. Thus life might have developed under similar conditions as on Earth or might have been transferred from Earth (or vice versa). Methane is known to be present on Mars, although the origin (if geothermal or biological activity) is still unknown. Cyanobacteria and prokaryotes using photosystem I belong to the oldest microbes on Earth. These organisms use pigments such as scytonemin and β-carotene as UV protection. Especially β-carotene emits a strong Raman signal. Raman analytics are used for detection of biofilm forming cyanobacteria Nostoc commune strain on the below described Mars analogue mineral mixtures. N. commune is known to be resistant to desiccation, UV B radiation and low temperatures, and thus suitable as a candidate for a potential life form on Mars

  14. Biological space experiments for the simulation of Martian conditions: UV radiation and Martian soil analogues.

    PubMed

    Rettberg, P; Rabbow, E; Panitz, C; Horneck, G

    2004-01-01

    The survivability of resistant terrestrial microbes, bacterial spores of Bacillus subtilis, was investigated in the BIOPAN facility of the European Space Agency onboard of Russian Earth-orbiting FOTON satellites (BIOPAN I -III missions). The spores were exposed to different subsets of the extreme environmental parameters in space (vacuum, extraterrestrial solar UV, shielding by protecting materials like artificial meteorites). The results of the three space experiments confirmed the deleterious effects of extraterrestrial solar UV radiation which, in contrast to the UV radiation reaching the surface of the Earth, also contains the very energy-rich, short wavelength UVB and UVC radiation. Thin layers of clay, rock or meteorite material were shown to be only successful in UV-shielding, if they are in direct contact with the spores. On Mars the UV radiation climate is similar to that of the early Earth before the development of a protective ozone layer in the atmosphere by the appearance of the first aerobic photosynthetic bacteria. The interference of Martian soil components and the intense and nearly unfiltered Martian solar UV radiation with spores of B. subtilis will be tested with a new BIOPAN experiment, MARSTOX. Different types of Mars soil analogues will be used to determine on one hand their potential toxicity alone or in combination with solar UV (phototoxicity) and on the other hand their UV protection capability. Two sets of samples will be placed under different cut-off filters used to simulate the UV radiation climate of Mars and Earth. After exposure in space the survival of and mutation induction in the spores will be analyzed at the DLR, together with parallel samples from the corresponding ground control experiment performed in the laboratory. This experiment will provide new insights into the principal limits of life and its adaptation to environmental extremes on Earth or other planets which and will also have implications for the potential for the

  15. Biological space experiments for the simulation of Martian conditions: UV radiation and Martian soil analogues

    NASA Astrophysics Data System (ADS)

    Rettberg, P.; Rabbow, E.; Panitz, C.; Horneck, G.

    2004-01-01

    The survivability of resistant terrestrial microbes, bacterial spores of Bacillus subtilis, was investigated in the BIOPAN facility of the European Space Agency onboard of Russian Earth-orbiting FOTON satellites (BIOPAN I -III missions). The spores were exposed to different subsets of the extreme environmental parameters in space (vacuum, extraterrestrial solar UV, shielding by protecting materials like artificial meteorites). The results of the three space experiments confirmed the deleterious effects of extraterrestrial solar UV radiation which, in contrast to the UV radiation reaching the surface of the Earth, also contains the very energy-rich, short wavelength UVB and UVC radiation. Thin layers of clay, rock or meteorite material were shown to be only successful in UV-shielding, if they are in direct contact with the spores. On Mars the UV radiation climate is similar to that of the early Earth before the development of a protective ozone layer in the atmosphere by the appearance of the first aerobic photosynthetic bacteria. The interference of Martian soil components and the intense and nearly unfiltered Martian solar UV radiation with spores of B. subtilis will be tested with a new BIOPAN experiment, MARSTOX. Different types of Mars soil analogues will be used to determine on one hand their potential toxicity alone or in combination with solar UV (phototoxicity) and on the other hand their UV protection capability. Two sets of samples will be placed under different cut-off filters used to simulate the UV radiation climate of Mars and Earth. After exposure in space the survival of and mutation induction in the spores will be analyzed at the DLR, together with parallel samples from the corresponding ground control experiment performed in the laboratory. This experiment will provide new insights into the principal limits of life and its adaptation to environmental extremes on Earth or other planets which and will also have implications for the potential for the

  16. The Relationship Between Water Structure and Blood Compatibility in Poly(2-methoxyethyl Acrylate) (PMEA) Analogues.

    PubMed

    Sato, Kazuhiro; Kobayashi, Shingo; Kusakari, Miho; Watahiki, Shogo; Oikawa, Masahiko; Hoshiba, Takashi; Tanaka, Masaru

    2015-09-01

    Six types of poly(2-methoxyethyl acrylate) (PMEA) analogues were synthesized and the water structure in the hydrated polymers was characterized using differential scanning calorimetry (DSC). The hydrated PMEA analogues exhibited the different amounts of intermediate water. Non-thrombogenicity evaluation was performed on PMEA analogues for platelet adhesion and protein adsorption. Platelet adhesion was suppressed on PMEA analogues. In addition, the protein adsorption and deformation were suppressed by increasing the amount of intermediate water. This study demonstrates that the amount of intermediate water might play a key role in expressing the blood compatibility of polymeric materials. PMID:26017931

  17. New metabolically stabilized analogues of lysophosphatidic acid: agonists, antagonists and enzyme inhibitors.

    PubMed

    Prestwich, G D; Xu, Y; Qian, L; Gajewiak, J; Jiang, G

    2005-12-01

    Lysophosphatidic acid (LPA) is a metabolically labile natural phospholipid with a bewildering array of physiological effects. We describe herein a variety of long-lived receptor-specific agonists and antagonists for LPA receptors. Several LPA and PA (phosphatidic acid) analogues also inhibit LPP (lipid phosphate phosphatase). The sn-1 or sn-2 hydroxy groups have been replaced by fluorine, difluoromethyl, difluoroethyl, O-methyl or O-hydroxyethoxy groups to give non-migrating LPA analogues that resist acyltransferases. Alkyl ether replacement of acyl esters produced lipase and acyltransferase-resistant analogues. Replacement of the bridging oxygen in the monophosphate by an alpha-monofluoromethylene-, alpha-bromomethylene- or alpha,alpha-difluoromethylenephosphonate gave phosphatase-resistant analogues. Phosphorothioate analogues with O-acyl and O-alkyl chains are potent, long-lived agonists for LPA1 and LPA3 receptors. Most recently, we have (i) prepared stabilized O-alkyl analogues of lysobisphosphatidic acid, (ii) explored the structure-activity relationship of stabilized cyclic LPA analogues and (iii) synthesized neutral head group trifluoromethylsulphonamide analogues of LPA. Through collaborative studies, we have collected data for these stabilized analogues as selective LPA receptor (ant)agonists, LPP inhibitors, TREK (transmembrane calcium channel) K+ channel agonists, activators of the nuclear transcription factor PPAR-gamma (peroxisome-proliferator-activated receptor-gamma), promoters of cell motility and survival, and radioprotectants for human B-cells. PMID:16246118

  18. The action of structural analogues of ethidium bromide on the mitochondrial genome of yeast.

    PubMed

    Hall, R M; Mattick, J S; Nagley, P; Cobon, G S; Eastwood, F W; Linnane, A W

    1977-12-01

    We have studied the effects on the yeast mitochondrial genome of four analogues of ethidium bromide, in which the phenyl moieyt has been replaced by linear alkyl chains of lengths varying from seven to fifteen carbon atoms. These analogues are more efficient than ethidium bromide in inducing petite mutants in Saccharomyces cervisiae. The drugs also cause a loss of mtDNA from the cells in vivo; however these analogues are in fact less effective inhibitors of mitochondrial DNA replication per se, as shown by direct in vitro studies. It is concluded that these analogues are more efficient than ethidium bromide in causing the fragmentation of mitochondrial DNA in S. cervisiae. PMID:339057

  19. Synthesis and biological evaluation of analogues of the kinase inhibitor nilotinib as Abl and Kit inhibitors

    PubMed Central

    Duveau, Damien Y.; Hu, Xin; Walsh, Martin J.; Shukla, Suneet; Skoumbourdis, Amanda P.; Boxer, Matthew B.; Ambudkar, Suresh V.; Shen, Min; Thomas, Craig J.

    2013-01-01

    The importance of the trifluoromethyl group in the polypharmacological profile of nilotinib was investigated. Molecular editing of nilotinib led to the design, synthesis and biological evaluation of analogues where the trifluoromethyl group was replaced by a proton, fluorine and a methyl group. While these analogues were less active than nilotinib toward Abl, their activity toward Kit was comparable, with the monofluorinated analogue being the most active. Docking of nilotinib and of analogues 2a–c to the binding pocket of Abl and of Kit showed that the lack of shape complementarity in Kit is compensated by the stabilizing effect from its juxtamembrane region. PMID:23273517

  20. Capillary electrokinetic chromatography of insulin and related synthetic analogues.

    PubMed

    Ortner, K; Buchberger, W; Himmelsbach, M

    2009-04-01

    With the implementation of recombinant DNA technology in the pharmaceutical industry, some synthetic insulins have been developed in order to improve the therapy of diabetes. These analogues differ only slightly in the amino acid sequence, therefore displaying a great challenge for analytical chemistry. Within the work presented in this paper, capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC) with sodium dodecylsulphate (SDS) as micelle-forming agent, and microemulsion electrokinetic chromatography (MEEKC) with microemulsions consisting of SDS, n-octane and 1-butanol were investigated for the separation of human insulin and five synthetic analogues. Best results were achieved with a solvent-modified MEKC system consisting of 100mM sodium dodecyl sulphate and 15% acetonitrile in 10mM borate buffer (pH 9.2). A similar system based on perfluorooctanoic acid as micelle-forming agent in ammonium acetate (pH 9.2) was successfully employed for the hyphenation with a quadrupole/time-of-flight mass spectrometer via a sheath-flow interface. In this case, detection limits at 10mg/L could be achieved. PMID:19027906

  1. Human cognitive performance in spaceflight and analogue environments.

    PubMed

    Strangman, Gary E; Sipes, Walter; Beven, Gary

    2014-10-01

    Maintaining intact cognitive performance is a high priority for space exploration. This review seeks to summarize the cumulative results of existing studies of cognitive performance in spaceflight and analogue environments. We focused on long-duration (>21 d) studies for which no review has previously been conducted. There were 11 published studies identified for long-duration spaceflight (N = 42 subjects) as well as 21 shorter spaceflight studies (N = 70 subjects). Overall, spaceflight cognitive studies ranged from 6-438 d in duration. Some 55 spaceflight analogue studies were also identified, ranging from 6 to 520 d. The diverse nature of experimental procedures and protocols precluded formal meta-analysis. In general, the available evidence fails to strongly support or refute the existence of specific cognitive deficits in low Earth orbit during long-duration spaceflight, which may be due in large part to small numbers of subjects. The studies consistently suggest that novel environments (spaceflight or other) induce variable alterations in cognitive performance across individuals, consistent with known astronaut experiences. This highlights the need to better quantify the magnitude and scope of this interindividual variability, and understand its underlying factors, when predicting in-flight cognitive functioning for extended periods. PMID:25245904

  2. Bandwidth based electrical-analogue battery modeling for battery modules

    NASA Astrophysics Data System (ADS)

    Li, Jianwei; Mazzola, Michael S.; Gafford, James; Jia, Bin; Xin, Ming

    2012-11-01

    A technique for building a high fidelity electrical-analogue battery model by identifying the model parameters at the module level, as opposed to the cell level, is proposed in this paper. The battery model, which is represented by electrical circuit components, can be easily integrated into popular simulation environments for system level design and predictive analysis. A novel bandwidth based time-domain procedure is introduced for identifying the model parameters by selective assignment of the limited bandwidth of the battery model approximation according to the natural bandwidth of the system that uses the battery. The aim of this paper is to provide an accurate off-line electrical-analogue battery model for simulation of larger systems containing large-format batteries, as opposed to a detailed electrochemical model suitable for simulation of internal battery processes. The proposed procedure has been experimentally verified on a 6.8 Ah Ultralife UBBL10 Li-ion battery module which is a “microcosm” for a modern large-format battery pack. A maximum 0.25% error was observed during a performance test with arbitrary but bandwidth-limited charging and discharging intervals characteristic of a typical battery application.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Novel nikkomycin analogues generated by mutasynthesis in Streptomyces ansochromogenes

    PubMed Central

    2014-01-01

    Background Nikkomycins are competitive inhibitors of chitin synthase and inhibit the growth of filamentous fungi, insects, acarids and yeasts. The gene cluster responsible for biosynthesis of nikkomycins has been cloned and the biosynthetic pathway was elucidated at the genetic, enzymatic and regulatory levels. Results Streptomyces ansochromogenes ΔsanL was constructed by homologous recombination and the mutant strain was fed with benzoic acid, 4-hydroxybenzoic acid, nicotinic acid and isonicotinic acid. Two novel nikkomycin analogues were produced when cultures were supplemented with nicotinic acid. These two compounds were identified as nikkomycin Px and Pz by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). Bioassays against Candida albicans and Alternaria longipes showed that nikkomycin Px and Pz exhibited comparatively strong inhibitory activity as nikkomycin X and Z produced by Streptomyces ansochromogenes 7100 (wild-type strain). Moreover, nikkomycin Px and Pz were found to be more stable than nikkomycin X and Z at different pH and temperature conditions. Conclusions Two novel nikkomycin analogues (nikkomycin Px and Pz) were generated by mutasynthesis with the sanL inactivated mutant of Streptomyces ansochromogenes 7100. Although antifungal activities of these two compounds are similar to those of nikkomycin X and Z, their stabilities are much better than nikkomycin X and Z under different pHs and temperatures. PMID:24751325

  5. Martian Analogues Emissivity Spectra From the Berlin Emissivity Database (BED)

    NASA Astrophysics Data System (ADS)

    Maturilli, A.; Helbert, J.; Moroz, L.

    2006-12-01

    Remote sensing infrared spectroscopy is the principal field of investigation for planetary surfaces composition. Past, present and future missions to bodies in the solar system include in their payload instruments measuring the emerging radiation in the infrared range. For the interpretation of the measured data an emissivity spectral library of planetary analog materials is needed. The Berlin Emissivity Database (BED) currently contains emissivity spectra of plagioclase and potassium feldspars, low Ca and high Ca pyroxenes, olivine, elemental sulphur, and Martian analogue minerals, measured in the wavelength range from 7 to 22 microns as a function of particle size. For each sample we measured the spectra of four particle size separates ranging from 0 to 250 microns. The device we used is built at DLR (Berlin) and is coupled to a Fourier transform infrared spectrometer (Bruker IFS 88), purged with dry air and equipped with a cooled detector (MCT). All spectra were acquired with a spectral resolution of 4 cm-1. We present here the results of our analysis on well knew and characterized Martian analogue minerals: JSC Mars-1, Salten Skov, and Palagonite from Mauna Kea, Hawaii. We are currently working to upgrade our emissivity facility. A new spectrometer (Bruker VERTEX 80v) and new detectors will allow us to measure the emissivity of samples in the wavelength range from 1 to 50 microns, even in a vacuum environment.

  6. Synthesis of a simplified triazole analogue of pateamine A.

    PubMed

    Hemi Cumming, A; Brown, Sarah L; Tao, Xu; Cuyamendous, Claire; Field, Jessica J; Miller, John H; Harvey, Joanne E; Teesdale-Spittle, Paul H

    2016-06-14

    Pateamine A is a naturally occurring metabolite extracted from the marine sponge Mycale hentscheli. It exhibits potent cytotoxicity towards cancer cell lines and has been shown to target protein translation initiation via inhibition of the function of eukaryotic initiation factor 4A proteins. We have synthesised a simplified analogue of pateamine A, consisting of the skeletal core of the natural product but with the thiazole heterocycle replaced by a triazole. The convergent design of the synthesis features a base-induced opening of a δ-valerolactone to access the Z,E-dienoate moiety, Julia-Kocienski olefination and copper-catalysed azide-alkyne cycloaddition. Bioactivity testing of the simplified pateamine A analogue (3) indicated a significant reduction in cytotoxicity, compared to natural pateamine A. We propose that this reduced activity is due mainly to the substitution of the thiazole for the triazole heterocycle. This supports the hypothesis that the thiazole of pateamine A is important for binding to its biological target. PMID:27180995

  7. The antiviral activity of tetrazole phosphonic acids and their analogues.

    PubMed Central

    Hutchinson, D W; Naylor, M

    1985-01-01

    5-(Phosphonomethyl)-1H-tetrazole and a number of related tetrazoles have been prepared and their effects on the replication of Herpes Simplex Viruses-1 and -2 have been investigated as well as their abilities to inhibit the DNA polymerases induced by these viruses and the RNA transcriptase activity of influenza virus A. Contrary to an earlier report, 5-(phosphonomethyl)-1H-tetrazole was not an efficient inhibitor of the replication of HSV-1 and HSV-2 in tissue culture. Analogues of 5-(phosphonomethyl)-1H-tetrazole were also devoid of significant antiviral activity. Only 5-(phosphonomethyl)-1H-tetrazole and 5-(thiophosphonomethyl)-1H-tetrazole inhibited the influenza virus transcriptase, and both were more effective as inhibitors than phosphonoacetic acid under the same conditions. The DNA polymerases induced by HSV-1 and HSV-2 were inhibited slightly by 5-(phosphonomethyl)-1H-tetrazole and to a lesser extent by its N-ethyl analogue and 3-(phosphonomethyl)-1H-1,2,4-triazole. None of these compounds were as effective as phosphonoacetic acid. 5-(Thiophosphonomethyl)-1H-tetrazole was a better inhibitor of the DNA polymerase induced by HSV-1 than 5-(phosphonomethyl)-1H-tetrazole. PMID:2417198

  8. A Transition State Analogue for an RNA-Editing Reaction

    PubMed Central

    Haudenschild, Brittany L.; Maydanovych, Olena; Véliz, Eduardo A.; Macbeth, Mark R.; Bass, Brenda L.; Beal, Peter A.

    2007-01-01

    Deamination at C6 of adenosine in RNA catalyzed by the ADAR enzymes generates inosine at the corresponding position. Because inosine is decoded as guanosine during translation, this modification can lead to codon changes in messenger RNA. Hydration of 8-azanebularine across the C6–N1 double bond generates an excellent mimic of the transition state proposed for the hydrolytic deamination reaction catalyzed by ADARs. Here, we report the synthesis of a phosphoramidite of 8-azanebularine and its use in the preparation of RNAs mimicking the secondary structure found at a known editing site in the glutamate receptor B subunit pre-mRNA. The binding properties of analogue-containing RNAs indicate that a tight binding ligand for an ADAR can be generated by incorporation of 8-azanebularine. The observed high-affinity binding is dependent on a functional active site, the presence of one, but not the other, of ADAR2’s two double-stranded RNA-binding motifs (dsRBMs), and the correct placement of the nucleoside analogue into the sequence/structural context of a known editing site. These results advance our understanding of substrate recognition during ADAR-catalyzed RNA editing and are important for structural studies of ADAR· RNA complexes. PMID:15355102

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

    NASA Astrophysics Data System (ADS)

    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.

  10. New experimental protocols for tensile testing of abdominal aortic analogues.

    PubMed

    Bailly, L; Deplano, V; Lemercier, A; Boiron, O; Meyer, C

    2014-06-01

    This work proposes an in vitro tensile testing protocol that is able to characterize abdominal aortic (AA) analogues under physiologically inspired mechanical loadings. Kinematic parameters are defined in agreement with in vivo measurements of aortic dynamics. A specific focus is given to the choice of the applied loading rates, deriving from the knowledge of aortic Peterson modulus and blood pressure variations from diastolic to systolic instants. The influence of physiological elongation rates has been tested on both porcine AAs and a thermoplastic polyurethane (TPU) material used to elaborate AA analogues. The diastolic and systolic elongation rates estimates vary between orders of magnitude O(10(-2)) and O(10(-1))s(-1). Negligible differences are obtained when comparing stress-elongation responses between both physiological elongation rates. In contrast, a noticeable stiffening of the TPU mechanical response is observed compared to that obtained under the common low traction rate of O(10(-3))s(-1). This work shows how relevant physiological elongation rates can be evaluated as a function of age, gender and pathological context. PMID:24613685

  11. Carbon storage at defect sites in mantle mineral analogues

    NASA Astrophysics Data System (ADS)

    Wu, Jun; Buseck, Peter R.

    2013-10-01

    A significant fraction of Earth's carbon resides in the mantle, but the mode of carbon storage presents a long-standing problem. The mantle contains fluids rich in carbon dioxide and methane, carbonate-bearing melts, carbonate minerals, graphite, diamond and carbides, as well as dissolved carbon atoms in metals. However, it is uncertain whether these can sufficiently account for the total amount of carbon thought to be stored in the mantle and the volume of carbon degassed from the mantle at volcanoes. Moreover, such carbon hosts should significantly affect the physical and chemical behaviour of the mantle, including its melting temperature, electrical conductivity and oxidation state. Here we use in situ transmission electron microscopy to measure the storage of carbon within common mantle mineral analogues--nickel-doped lanthanum chromate perovskite and titanium dioxide--in laboratory experiments at high pressure and temperature. We detect elevated carbon concentrations at defect sites in the nanocrystals, maintained at high pressures within annealed carbon nanocages. Specifically, our experiments show that small stacking faults within the mantle analogue materials are effective carbon sinks at mantle conditions, potentially providing an efficient mechanism for carbon storage in the mantle. Furthermore, this carbon can be readily released under lower pressure conditions, and may therefore help to explain carbon release in volcanic eruptions.

  12. All-dielectric metasurface analogue of electromagnetically induced transparency.

    PubMed

    Yang, Yuanmu; Kravchenko, Ivan I; Briggs, Dayrl P; Valentine, Jason

    2014-01-01

    Metasurface analogues of electromagnetically induced transparency (EIT) have been a focus of the nanophotonics field in recent years, due to their ability to produce high-quality factor (Q-factor) resonances. Such resonances are expected to be useful for applications such as low-loss slow-light devices and highly sensitive optical sensors. However, ohmic losses limit the achievable Q-factors in conventional plasmonic EIT metasurfaces to values <~10, significantly hampering device performance. Here we experimentally demonstrate a classical analogue of EIT using all-dielectric silicon-based metasurfaces. Due to extremely low absorption loss and coherent interaction of neighbouring meta-atoms, a Q-factor of 483 is observed, leading to a refractive index sensor with a figure-of-merit of 103. Furthermore, we show that the dielectric metasurfaces can be engineered to confine the optical field in either the silicon resonator or the environment, allowing one to tailor light-matter interaction at the nanoscale. PMID:25511508

  13. 1'-Homonucleosides and their structural analogues: A review.

    PubMed

    Wróblewski, Andrzej E; Głowacka, Iwona E; Piotrowska, Dorota G

    2016-08-01

    Nucleoside analogues belong to an important class of antiviral and anticancer drugs. Insertion of a methylene fragment between the anomeric carbon and pyrimidine or purine bases transforms nucleosides into 1'-homonucleosides. When compared with nucleosides this modification lengthens the separation between HO-C5' of pentofuranoside fragments and nitrogen (N1 or N9) atoms of nucleobases, lowers the steric and electronic interactions between nucleobases and sugar rings, introduces greater flexibility around a CH2-Base bond and thus allows for more rotational freedom, and since the anomeric effect no longer operates any sugar or pseudosugar moiety exists in its unique conformation and experiences specific conformational mobility and hydrolysis of the C1'-CH2Base bond by cellular enzymes is no longer feasible. This review covers 1'-homonucleosides with a tetrahydrofuran ring and its nitrogen and sulfur analogues as well as those containing a cyclopentane moiety as a sugar replacer. Achievements in syntheses of sugar or pseudosugar scaffolds are of primary interest since pathways to install nucleobases are well recognized. Whenever possible, the biological activity, mostly antiviral and antitumor but sometimes as inhibitors of specific enzymes, will be presented and discussed to help identify structural features responsible for the particular mode of action and thus possible therapeutic significance. PMID:27128178

  14. Membrane structure and interactions of a short Lycotoxin I analogue.

    PubMed

    Adão, R; Seixas, R; Gomes, P; Pessoa, J Costa; Bastos, M

    2008-04-01

    Lycotoxin I and Lycotoxin II are natural anti-microbial peptides that were identified in the venom of the Wolf Spider Lycosa carolinensis. These peptides were found to be potent growth inhibitors for bacteria (Escherichia coli) and yeast (Candida glabrata) at micromolar concentrations. Recently, shortened analogues of LycoI and LycoII have been reported to have decreased haemolytic effects. A shorter Lyco-I analogue studied, LycoI 1-15 (H-IWLTALKFLGKHAAK-NH2), was active only above 10 microM, but was also the least haemolytic. On the basis of these findings, we became interested in obtaining a deeper insight into the membrane activity of LycoI 1-15, as this peptide may represent the first major step for the future development of selective, i.e. non-haemolytic, Lycotoxin-based antibiotics. The interaction of this peptide with liposomes of different composition was studied by microcalorimetry [differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC)] and CD. The results obtained from the calorimetric and spectroscopic techniques were jointly discussed in an attempt to further understand the interaction of this peptide with model membranes. PMID:18098329

  15. A low-dimensional analogue of holographic baryons

    NASA Astrophysics Data System (ADS)

    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.

  16. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    PubMed

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  17. Process standardization for rennet casein based Mozzarella cheese analogue.

    PubMed

    Shah, Rahul; Jana, Atanu H; Aparnathi, K D; Prajapati, P S

    2010-10-01

    A process for manufacture of Mozzarella cheese analogue (MCA) using rennet casein and plastic cream as protein and fat sources respectively was standardized. The formulation comprised of 25% plastic cream (72% fat), 27% rennet casein along with 3% tri-sodium citrate as emulsifying salt, 2% maltodextrin as binder, 0.55% lactic acid as pH regulator, 1% common salt for seasoning, 1% Mozzarella cheese bud as flavouring and 40.4% water. The process involved (a) dissolving the dry mixture of casein, maltodextrin, flavouring and common salt in hot emulsifying salt solution, (b) incorporation of half the quantity of acid solution in casein-maltodextrin dough, followed by addition and emulsification of plastic cream, and (c) addition of remaining half of the acid solution and heating the mass to 80 °C until a plastic cheese mass was obtained. The analogue was shaped in ball form, cooled and packaged in polyethylene bag. The MCA conformed to the PFA requirements for pizza cheese and had all the requisite baking characteristics expected of pizza cheese topping. PMID:23572688

  18. Transdermal iontophoresis of gonadotropin releasing hormone (LHRH) and two analogues.

    PubMed

    Miller, L L; Kolaskie, C J; Smith, G A; Rivier, J

    1990-06-01

    Gonadotropin releasing hormone (GnRH), as well as an antagonist [Ac-D2Nal,1 D4ClPhe,2 D3Pal,3 NicLys,5 DNicLys,6 ILys,8 DAla10] GnRH.HOAc (1) and a superagonist [DTrp6, Pro9-NHEt]GnRH (2), have been electrochemically driven across excised hairless mouse skin. Determined by HPLC analysis, the delivery rate from aqueous solution into isotonic saline at 0.5 mA cm-2 was as high as 19 nM cm-2 h-1 for 2. Because of its insolubility in water, analogue 1 could only be delivered from an acidic donor solution. Analogue 2 was also delivered in pulsatile fashion using current on/off cycles. For all three peptides, passive transport was negligible and stability is evident when in contact with the stratum corneum. Slow metabolism occurs when GnRH contacts the dermal side of hairless mouse skin. PMID:2203894

  19. Towards an ideal blood analogue for Doppler ultrasound phantoms.

    PubMed

    Oates, C P

    1991-11-01

    If a phantom is to produce Doppler spectral waveforms accurately matching those that would be obtained in vivo, it is necessary to use a fluid that behaves like blood in vivo, both acoustically and rheologically. The use of blood itself is undesirable and an analogue is required. Blood exhibits non-Newtonian behaviour as a result of aggregation of erythrocytes at low shear rates. This behaviour affects flow not only in sub-millimetre diameter vessels, but also in large scale structures. An alternative to blood is described that uses finely powdered nylon suspended in a mixture of glycerol and water. The nylon particles used have dimensions and density close to those of erythrocytes and they aggregate at low shear rates to give non-Newtonian behaviour. Viscosity may be varied over a wide range by the addition of liquid detergent. Consideration is given to the importance of haematocrit in modelling pulsatile and disturbed flows as it affects the haemodynamics of flow and the backscattered power of an ultrasound beam. This adaptable blood analogue is suitable for use in models of both large structures and fine vessels. PMID:1754614

  20. Glucocorticoid analogues: potential therapeutic alternatives for treating inflammatory muscle diseases.

    PubMed

    Reeves, Erica K M; Rayavarapu, Sree; Damsker, Jesse M; Nagaraju, Kanneboyina

    2012-03-01

    Glucocorticoids (GCs) have been prescribed to treat a variety of diseases, including inflammatory myopathies and Duchenne muscular dystrophy for over 50 years. However, their prescription remains controversial due to the significant side effects associated with the chronic treatment. It is a common belief that the clinical efficacy of GCs is due to their transrepression of pro-inflammatory genes through inhibition of inflammatory transcription factors (i.e. NF-κB, AP-1) whereas the adverse side effects are attributed to the glucocorticoid receptor (GR)-mediated transcription of target genes (transactivation). The past decade has seen an increased interest in the development of GR modulators that maintain the effective anti-inflammatory properties but lack the GR-dependent transcriptional response as a safe alternative to traditional GCs. Many of these analogues or "dissociative" compounds show potential promise in in vitro studies but fail to reach human clinical trials. In this review, we discuss molecular effects of currently prescribed GCs on skeletal muscle and also discuss the current state of development of GC analogues as alternative therapeutics for inflammatory muscle diseases. PMID:22214335

  1. Optical Dust Characterization in Manned Mars Analogue Research Stations

    NASA Technical Reports Server (NTRS)

    Bos, B. J.; Krebs, Carolyn (Technical Monitor)

    2003-01-01

    Martian dust has been identified as a potentially serious hazard to any manned Mars landing mission. NASA and other organizations realize this risk and continue to support Martian dust research through the Matador project led by researchers at the University of Arizona. The Mars Society can contribute to this work by beginning a regimen of monitoring and measuring dust properties at its Mars analogue research stations. These research facilities offer the unique opportunity to study the transport and distribution of dust particles within a crewed habitat supporting active geologic exploration. Information regarding the amount, location and size of dust particles that may accumulate in a Mars habitat will be required to design a real Mars habitat and habitat equipment. Beginning such an effort does not require a large outlay of equipment and can be accomplished using crewmembers experienced with station operations. Various optical techniques, such as dark-field illumination, coupled with image processing algorithms enable the collection of dust grain relative size and frequency information. Such approaches can be applied in several different zones within the research stations to evaluate the various dust reduction and isolation procedures implemented during a particular crew rotation. As the stations simulation fidelity increases, the applicability of such data to a functional Mars lander will increase. This presentation describes the optical equipment and procedures for measuring dust properties in Mars analogue research stations that can be implemented during the next field season.

  2. Protective Coating

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Inorganic Coatings, Inc.'s K-Zinc 531 protective coating is water-based non-toxic, non-flammable and has no organic emissions. High ratio silicate formula bonds to steel, and in 30 minutes, creates a very hard ceramic finish with superior adhesion and abrasion resistance. Improved technology allows application over a minimal commercial sandblast, fast drying in high humidity conditions and compatibility with both solvent and water-based topcoats. Coating is easy to apply and provides long term protection with a single application. Zinc rich coating with water-based potassium silicate binder offers cost advantages in materials, labor hours per application, and fewer applications over a given time span.

  3. Analogue Missions on Earth, a New Approach to Prepare Future Missions on the Moon

    NASA Astrophysics Data System (ADS)

    Lebeuf, Martin

    Human exploration of the Moon is a target by 2020 with an initial lunar outpost planned in polar regions. Current architectures maintain a capability for sorties to other latitudes for science activities. In the early stages of design of lunar outpost infrastructure and science activity planning, it has been recognized that analogue missions could play a major role in Moon mission design. Analogue missions, as high fidelity simulations of human and robotic surface operations, can help field scientists and engineers develop and test strategies as well as user requirements, as they provide opportunities to groundtruth measurements, and for the team to share understanding of key science needs and key engineering trades. These types of missions also provide direct training in planning science operations, and in team building and communication. The Canadian Space Agency's Exploration Core Program targets the development of technology infrastructure elements in key areas of science, technology and robotics in preparation for its role in the future exploration of the Moon and Mars. Within this Program, Analogue Missions specifically target the operations requirements and lessons learned that will reduce costs and lower the risk of planetary surface missions. Analogue missions are simulations of planetary surface operations that take place at analogue sites on Earth. A terrestrial analogue site resembles in some key way: eg. geomorphologically or geochemically, a surface environment of another planet. An analogue mission can, therefore, be defined as an integrated set of activities that represent (or simulate) entire mission designs or narrowly focus on specific aspects of planned or potential future planetary exploration missions. Within the CSA's Exploration Core Program, Analogue Missions facilitate the maturation of science instruments and mission concepts by integrating ongoing space instrument and technology development programs with science and analogue elements. As

  4. Synthesis and biological activity of locust AKH-I and its analogues with modifications at the threonine residues.

    PubMed

    Poulos, C; Karagiannis, K; Lee, M; Goldsworthy, G

    1994-12-01

    A convenient method of synthesis, using a combination of solid and liquid phase methodology, for locust Adipokinetic Hormone-I (AKH-I) and its analogues with modifications at the threonine residues are reported. The N-terminal nonapeptide acid of AKH-I is synthesized in the solid phase using the 2-chlorotrityl chloride resin and the Fmoc/t-Bu strategy. Quantitative cleavage of the nonapeptide acid from the resin, with the tert-butyl type side-chain protection intact, is achieved with a mixture of acetic acid/trifluoroethanol/dichloromethane. The nonapeptide acid is then coupled in solution to the threonine derivatives, H-Thr-NH2 or H-Thr(Bzl)-NH2, with the DCC/HOBt method. The efficiency of this approach in the synthesis of AKH-I is demonstrated by the high yields and purity of the synthesized peptides. All the synthesized peptides were tested in two ways: first, in a lipid mobilization assay in locusts in vivo; and second, in a novel assay in vitro concerned with the uptake of radiolabelled acetate into locust tissue. Replacement of the hydroxyl hydrogen in Thr5 of locust AKH-I by the bulky and highly lipophilic tert-butyl group reduced the potency markedly, whereas efficacy is unaffected, but when the hydroxyl hydrogen of Thr10 in AKH-I is replaced by a benzyl group, the activity of the resulting analogue is identical to that of the natural peptide. Structure-activity relationships are discussed. PMID:7705981

  5. Loss of Apelin Exacerbates Myocardial Infarction Adverse Remodeling and Ischemia‐reperfusion Injury: Therapeutic Potential of Synthetic Apelin Analogues

    PubMed Central

    Wang, Wang; McKinnie, Shaun M.K.; Patel, Vaibhav B.; Haddad, George; Wang, Zuocheng; Zhabyeyev, Pavel; Das, Subhash K.; Basu, Ratnadeep; McLean, Brent; Kandalam, Vijay; Penninger, Josef M.; Kassiri, Zamaneh; Vederas, John C.; Murray, Allan G.; Oudit, Gavin Y.

    2013-01-01

    Background Coronary artery disease leading to myocardial ischemia is the most common cause of heart failure. Apelin (APLN), the endogenous peptide ligand of the APJ receptor, has emerged as a novel regulator of the cardiovascular system. Methods and Results Here we show a critical role of APLN in myocardial infarction (MI) and ischemia‐reperfusion (IR) injury in patients and animal models. Myocardial APLN levels were reduced in patients with ischemic heart failure. Loss of APLN increased MI‐related mortality, infarct size, and inflammation with drastic reductions in prosurvival pathways resulting in greater systolic dysfunction and heart failure. APLN deficiency decreased vascular sprouting, impaired sprouting of human endothelial progenitor cells, and compromised in vivo myocardial angiogenesis. Lack of APLN enhanced susceptibility to ischemic injury and compromised functional recovery following ex vivo and in vivo IR injury. We designed and synthesized two novel APLN analogues resistant to angiotensin converting enzyme 2 cleavage and identified one analogue, which mimicked the function of APLN, to be markedly protective against ex vivo and in vivo myocardial IR injury linked to greater activation of survival pathways and promotion of angiogenesis. Conclusions APLN is a critical regulator of the myocardial response to infarction and ischemia and pharmacologically targeting this pathway is feasible and represents a new class of potential therapeutic agents. PMID:23817469

  6. The pivotal role of uridine-cytidine kinases in pyrimidine metabolism and activation of cytotoxic nucleoside analogues in neuroblastoma.

    PubMed

    van Kuilenburg, André B P; Meinsma, Rutger

    2016-09-01

    Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine and cytidine as well as the pharmacological activation of several cytotoxic pyrimidine ribonucleoside analogues. In this study, we investigated the functional role of two isoforms of UCK in neuroblastoma cell lines. Analysis of mRNA coding for UCK1 and UCK2 showed that UCK2 is the most abundantly expressed UCK in a panel of neuroblastoma cell lines. Transient and stable overexpression of UCK2 in neuroblastoma cells increased the metabolism of uridine and cytidine as well as the cytotoxicity of 3-deazauridine. Knockdown of endogenous UCK2 as well as overexpression of UCK1 resulted in decreased metabolism of uridine and cytidine and protected the neuroblastoma cells from 3-deazauridine-induced toxicity. Subcellular localization studies showed that UCK1-GFP and UCK2-GFP were localized in the cell nucleus and cytosol, respectively. However, co-expression of UCK1 with UCK2 resulted in a nuclear localization of UCK2 instead of its normal cytosolic localization, thereby impairing its normal function. The physical association of UCK1 and UCK2 was further demonstrated through pull-down analysis using his-tagged UCK. The discovery that UCK2 is highly expressed in neuroblastoma opens the possibility for selectively targeting neuroblastoma cells using UCK2-dependent pyrimidine analogues, while sparing normal tissues. PMID:27239701

  7. Palladium-Catalyzed Ortho-Arylation of Carbamate-Protected Estrogens.

    PubMed

    Bedford, Robin B; Brenner, Peter B; Durrant, Steven J; Gallagher, Timothy; Méndez-Gálvez, Carolina; Montgomery, Michelle

    2016-05-01

    The palladium-catalyzed ortho-arylation of diethyl carbamate-protected estrone and estriol with aryl iodides gives the 2-arylated analogues. Subsequent removal of the carbamate directing group furnishes 2-arylated estrone, estradiol, or estriol depending on the method used. PMID:27057762

  8. Topologically protected elastic waves in phononic metamaterials

    PubMed Central

    Mousavi, S. Hossein; Khanikaev, Alexander B.; Wang, Zheng

    2015-01-01

    Surface waves in topological states of quantum matter exhibit unique protection from backscattering induced by disorders, making them ideal carriers for both classical and quantum information. Topological matters for electrons and photons are largely limited by the range of bulk properties, and the associated performance trade-offs. In contrast, phononic metamaterials provide access to a much wider range of material properties. Here we demonstrate numerically a phononic topological metamaterial in an elastic-wave analogue of the quantum spin Hall effect. A dual-scale phononic crystal slab is used to support two effective spins for phonons over a broad bandwidth, and strong spin–orbit coupling is realized by breaking spatial mirror symmetry. By preserving the spin polarization with an external load or spatial symmetry, phononic edge states are shown to be robust against scattering from discrete defects as well as disorders in the continuum, demonstrating topological protection for phonons in both static and time-dependent regimes. PMID:26530426

  9. Topologically protected elastic waves in phononic metamaterials.

    PubMed

    Mousavi, S Hossein; Khanikaev, Alexander B; Wang, Zheng

    2015-01-01

    Surface waves in topological states of quantum matter exhibit unique protection from backscattering induced by disorders, making them ideal carriers for both classical and quantum information. Topological matters for electrons and photons are largely limited by the range of bulk properties, and the associated performance trade-offs. In contrast, phononic metamaterials provide access to a much wider range of material properties. Here we demonstrate numerically a phononic topological metamaterial in an elastic-wave analogue of the quantum spin Hall effect. A dual-scale phononic crystal slab is used to support two effective spins for phonons over a broad bandwidth, and strong spin-orbit coupling is realized by breaking spatial mirror symmetry. By preserving the spin polarization with an external load or spatial symmetry, phononic edge states are shown to be robust against scattering from discrete defects as well as disorders in the continuum, demonstrating topological protection for phonons in both static and time-dependent regimes. PMID:26530426

  10. Synthesis of Cross-Linked DNA Containing Oxidized Abasic Site Analogues

    PubMed Central

    2015-01-01

    DNA interstrand cross-links are an important family of DNA damage that block replication and transcription. Recently, it was discovered that oxidized abasic sites react with the opposing strand of DNA to produce interstrand cross-links. Some of the cross-links between 2′-deoxyadenosine and the oxidized abasic sites, 5′-(2-phosphoryl-1,4-dioxobutane) (DOB) and the C4-hydroxylated abasic site (C4-AP), are formed reversibly. Chemical instability hinders biochemical, structural, and physicochemical characterization of these cross-linked duplexes. To overcome these limitations, we developed methods for preparing stabilized analogues of DOB and C4-AP cross-links via solid-phase oligonucleotide synthesis. Oligonucleotides of any sequence are attainable by synthesizing phosphoramidites in which the hydroxyl groups of the cross-linked product were orthogonally protected using photochemically labile and hydrazine labile groups. Selective unmasking of a single hydroxyl group precedes solid-phase synthesis of one arm of the cross-linked DNA. The method is compatible with commercially available phosphoramidites and other oligonucleotide synthesis reagents. Cross-linked duplexes containing as many as 54 nt were synthesized on solid-phase supports. Subsequent enzyme ligation of one cross-link product provided a 60 bp duplex, which is suitable for nucleotide excision repair studies. PMID:24949656

  11. Saturation of DNA mismatch repair and error catastrophe by a base analogue in Escherichia coli.

    PubMed Central

    Negishi, Kazuo; Loakes, David; Schaaper, Roel M

    2002-01-01

    Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G. C --> A. T and A. T --> G. C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL(+) gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains. PMID:12196386

  12. Carbocyclic nucleoside analogues: classification, target enzymes, mechanisms of action and synthesis

    NASA Astrophysics Data System (ADS)

    Matyugina, E. S.; Khandazhinskaya, A. P.; Kochetkov, Sergei N.

    2012-08-01

    Key biological targets (S-adenosyl-L-homocysteine hydrolase, telomerase, human immunodeficiency virus reverse transcriptase, herpes virus DNA polymerase and hepatitis B virus DNA polymerase) and the mechanisms of action of carbocyclic nucleoside analogues are considered. Structural types of analogues are discussed. Methods of synthesis for the most promising compounds and the spectrum of their biological activities are described. The bibliography includes 126 references.

  13. Unusual tubulin-clustering ability of specifically c7-modified colchicine analogues.

    PubMed

    Zefirova, Olga N; Lemcke, Heiko; Lantow, Margareta; Nurieva, Evgeniya V; Wobith, Birgit; Onishchenko, Galina E; Hoenen, Antje; Griffiths, Gareth; Zefirov, Nikolay S; Kuznetsov, Sergei A

    2013-08-19

    Highly cytotoxic C7-modified colchicine analogues, exemplified by tubuloclustin, promote microtubule disassembly followed by the formation of very stable tubulin clusters, both in vitro and in cells. The proposed mechanism of action of tubuloclustin and its analogues, beyond that of colchicine, includes additional specific interactions with the α-tubulin subunit. PMID:23843347

  14. Synthesis and acetylcholinesterase inhibitory activity of several pyrimidone analogues of huperzine A

    SciTech Connect

    Kozlkowski, A.P.; Campiani, G.; Saxena, A.; Doctor, S.P.

    1995-12-31

    Synthesis of four new pyrimidone analogues of the acetyicholinesterase (AChE) inhibitor huperzine A are reported together with the inhibitory potendes of these compounds for foetal bovine calf serum AChE; t3-lactone formation followed by a thermal cycloreversion reaction serves as the key step for introduction of the ethylidene appendage of analogue 12 in the stereochemically correct form.

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

    ERIC Educational Resources Information Center

    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…

  16. Tetrodotoxin and its analogues in extracts from the toad Atelopus oxyrhynchus (family: Bufonidae).

    PubMed

    Yotsu-Yamashita, M; Mebs, D; Yasumoto, T

    1992-11-01

    Tetrodotoxin and its analogues, 4-epitetrodotoxin and 4,9-anhydrotetrodotoxin, were detected in the toad Atelopus oxyrhynchus by HPLC analysis. The toxin and its analogues were still present in a specimen which lived 3.5 years in captivity. PMID:1336632

  17. Making Connections in Math: Activating a Prior Knowledge Analogue Matters for Learning

    ERIC Educational Resources Information Center

    Sidney, Pooja G.; Alibali, Martha W.

    2015-01-01

    This study investigated analogical transfer of conceptual structure from a prior-knowledge domain to support learning in a new domain of mathematics: division by fractions. Before a procedural lesson on division by fractions, fifth and sixth graders practiced with a surface analogue (other operations on fractions) or a structural analogue (whole…

  18. Interleukin 6 is a cause of flu-like symptoms in treatment with a deoxycytidine analogue.

    PubMed Central

    Masuda, N.; Negoro, S.; Takeda, K.; Kurata, N.; Kuwabara, T.; Kobayashi, S.; Fukuoka, M.

    1998-01-01

    The precise mechanism of fever and flu-like syndrome that occurs in treatment with deoxycytidine analogues remains unclear. This study demonstrated a strong correlation between plasma interleukin 6 levels and fever in treatment with oral (E)-2'-deoxy-2'(fluoromethylene)cytidine, another deoxycytidine analogue. PMID:9703288

  19. Farnesyl Diphosphate Analogues with Aryl Moieties are Efficient Alternate Substrates for Protein Farnesyltransferase

    PubMed Central

    Subramanian, Thangaiah; Pais, June E.; Liu, Suxia; Troutman, Jerry M.; Suzuki, Yuta; Subramanian, Karunai Leela; Fierke, Carol; Andres, Douglas A.; Spielmann, H. Peter

    2012-01-01

    Farnesylation is an important post-translational modification essential for proper localization and function of many proteins. Transfer of the farnesyl group from farnesyl diphosphate (FPP) to proteins is catalyzed by protein farnesyltransferase (FTase). We employed a library of FPP analogues with a range of aryl groups substituting for individual isoprene moieties to examine some of the structural and electronic properties of analogue transfer to peptide catalyzed by FTase. Analysis of steady-state kinetics for modification of peptide substrates revealed that the multiple turnover activity depends on the analogue structure. Analogues where the first isoprene is replaced by a benzyl group and an analogue where each isoprene is replaced by an aryl group are good substrates. In sharp contrast with the steady-state reaction, the single turnover rate constant for dansyl-GCVLS alkylation was found to be the same for all analogues, despite the increased chemical reactivity of the benzyl analogues and the increased steric bulk of other analogues. However, the single turnover rate constant for alkylation does depend on the Ca1a2X peptide sequence. These results suggest that the isoprenoid transition state conformation is preferred over the inactive E•FPP• Ca1a2X ternary complex conformation. Furthermore, these data suggest that the farnesyl binding site in the exit groove may be significantly more selective for the farnesyl diphosphate substrate than the active site binding pocket and therefore might be a useful site for design of novel inhibitors. PMID:22989235

  20. Properties of granular analogue model materials: A community wide survey

    NASA Astrophysics Data System (ADS)

    Klinkmüller, Matthias; Schreurs, Guido; Rosenau, Matthias; Kemnitz, Helga

    2016-04-01

    We report the material properties of 26 granular analogue materials used in 14 analogue modelling laboratories. We determined physical characteristics such as bulk density, grain size distribution, and grain shape, and performed ring shear tests to determine friction angles and cohesion, and uniaxial compression tests to evaluate the compaction behaviour. Mean grain size of the materials varied between (c. 100 and 400 micrometer). Analysis of grain shape factors show that the four different classes of granular materials (14 quartz sands, 5 dyed quartz sands, 4 heavy mineral sands and 3 size fractions of glass beads) can be broadly divided into two groups consisting of 12 angular and 14 rounded materials. Grain shape has an influence on friction angles, with most angular materials having higher internal friction angles (between c. 35° and 40°) than rounded materials, whereas well-rounded glass beads have the lowest internal friction angles (between c. 25° and 30°). We interpret this as an effect of intergranular sliding versus rolling . Most angular materials have also higher basal friction angles (tested for a specific foil) than more rounded materials, suggesting that angular grains scratch and wear the foil., Most materials have a cohesion in the order of 10-100 Pa except for well-rounded glass beads, which show a trend towards a quasi-cohesionless (C <10 Pa) Coulomb-type material. The uniaxial confined compression tests reveal that rounded grains generally show less compaction than angular grains. We interpret this to be related to the initial packing density reached during sieving which is higher for rounded grains than for angular grains. Ring-shear test data show that angular grains undergo a longer strain-hardening phase than more rounded materials. This might explain why analogue models consisting of angular grains accommodate deformation in a more distributed manner prior to strain localisation than models consisting of rounded grains. Also, models

  1. Charged analogues of Schwarzschild interior solution in terms of pressure

    NASA Astrophysics Data System (ADS)

    Bijalwan, Naveen

    2011-12-01

    Recently, Bijalwan (Astrophys. Space Sci., doi:10.1007/s10509-011-0691-0, 2011a) discussed charged fluid spheres with pressure while Bijalwan and Gupta (Astrophys. Space Sci. 317, 251-260, 2008) suggested using a monotonically decreasing function f to generate all possible physically viable charged analogues of Schwarzschild interior solutions analytically. They discussed some previously known and new solutions for Schwarzschild parameter u( =GM/c^{2a} ) le 0.142, a being radius of star. In this paper we investigate wide range of u by generating a class of solutions that are well behaved and suitable for modeling Neutron star charge matter. We have exploited the range u≤0.142 by considering pressure p= p( ω) and f = ( f0(1 - R2(1 - ω )/a2) +faR2(1 - ω )/a2 ), where ω = 1 -r2/R2 to explore new class of solutions. Hence, class of charged analogues of Schwarzschild interior is found for barotropic equation of state relating the radial pressure to the energy density. The analytical models thus found are well behaved with surface red shift z s ≤0.181, central red shift z c ≤0.282, mass to radius ratio M/ a≤0.149, total charge to total mass ratio e/ M≤0.807 and satisfy Andreasson's (Commun. Math. Phys. 288, 715-730, 2009) stability condition. Red-shift, velocity of sound and p/ c 2 ρ are monotonically decreasing towards the surface while adiabatic index is monotonically increasing. The maximum mass found to be 1.512 M Θ with linear dimension 14.964 km. Class of charged analogues of Schwarzschild interior discussed in this paper doesn't have neutral counter part. These solutions completely describe interior of a stable Neutron star charge matter since at centre the charge distribution is zero, e/ M≤0.807 and a typical neutral Neutron star has mass between 1.35 and about 2.1 solar mass, with a corresponding radius of about 12 km (Kiziltan et al., arXiv:1011.4291 [astro-ph.GA], 2010).

  2. Spectral Characterization of Phobos Analogues Under Simulated Environmental Conditions

    NASA Astrophysics Data System (ADS)

    Donaldson Hanna, K. L.; Bowles, N. E.; Edwards, C. S.; Glotch, T. D.; Greenhagen, B. T.; Pieters, C. M.; Thomas, I.

    2014-12-01

    The surface of Phobos holds many keys for understanding its formation and evolution as well as the history and dynamics of the Mars-Phobos system. Visible to near infrared (VNIR) observations suggests that Phobos' surface is compositionally heterogeneous with 'redder' and 'bluer' units that both appear to be anhydrous in nature. Lunar highland spectra have been identified as spectral analogues for the 'redder' and 'bluer' units while thermally metamorphosed CI/CM chondrites, lab-heated carbonaceous chondrites and highly space weathered mafic mineral assemblages have been identified as the best analogues for the 'bluer' surface units. Additionally, thermal infrared emissivity spectra indicate that if Phobos' surface is optically mature it may be rich in feldspar, which is consistent with VNIR observations of Phobos' surface being spectrally similar to lunar highland spectra. While remote observations provide key insights into the composition and evolution of planetary surfaces, a fundamentally important component to any remote compositional analysis of planetary surfaces is laboratory measurements of well-characterized samples measured under the appropriate environmental conditions. The vacuum environment of airless bodies creates a steep thermal gradient in the upper hundreds of microns of regolith. Lab studies of particulate rocks and minerals as well as selected lunar soils under vacuum and lunar-like conditions have identified significant effects of this thermal gradient on thermal infrared (TIR) spectral measurements. However recent lab measurements of carbonaceous chondrites demonstrated that simulated asteroid conditions do not affect the resulting emissivity spectra to the degree observed in lunar soils and is highly dependent on composition. Such lab studies demonstrate the high sensitivity of TIR emissivity spectra to environmental conditions under which they are measured and indicate that the near surface environment of all airless bodies do not

  3. Isoelectronic analogues of PN: Remarkably stable multiply charged cations

    SciTech Connect

    Wong, Ming Wah; Radom, L. )

    1990-01-25

    The structures and stabilities of PN and its 27 isoelectronic analogues, CS, SiO, BCl, AlF, BeAr, MgNe, Sn{sup +}, PO{sup +}, CCl{sup +}, SiF{sup +}, BAr{sup +}, AlNe{sup +}, SO{sup 2+}, NCl{sup 2+}, PF{sup 2+}, CAr{sup 2+}, SiNe{sup 2+}, OCl{sup 3+}, SF{sup 3+}, NAr{sup 3+}, PNe{sup 3+}, FCl{sup 4+}, OAr{sup 4+}, SNe{sup 4+}, FAr{sup 5+}, ClNe{sup 5+}, and ArNe{sup 6+}, have been examined by ab initio molecular orbital theory. The CASSCF/6-311G(MC)(d) level was used to determine the ground-state potential energy curves and spectroscopic constants for the 28 diatomic systems. Equilibrium structures were also obtained with the 6-311G(MC)(d) basis set at the MP3 and ST4CCD levels, and dissociation energies were determined at the MP4/6-311 + G(MC)(2df) and MP4/6-311 + G(MC)(3d2f) levels. For the neutral and monocation analogues of PN, the calculated equilibrium geometries (at MP3/6-311G(MC)(d)) and dissociation energies (at MP4/6-311 + G(MC)(3d2f)) are in very good agreement with available experimental values. All the dication analogues of PN, namely, SO{sup 2+}, NCl{sup 2+}, PF{sup 2+}, CAr{sup 2+}, and SiNe{sup 2+}, are predicted to be experimentally observable species. Of these, the SO{sup 2+}, NCl{sup 2+}, and CAr{sup 2+} dications are calculated to be kinetically stable species, with large barriers associated with the exothermic charge-separation reactions, while the PF{sup 2+} and SiNe{sup 2+} dications are predicted not only to be kinetically stable but also to be thermodynamically stable species.

  4. Protective Coatings

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Ameron International Protective Coatings Group developed a special coating for NASA that would withstand the high temperatures generated by the Space Shuttle rocket engines. The coating remains intact for at least 10 minutes, and insulates the launch pad so that it does not exceed 150 degrees and buckle. The NASA formulation was from Ameron's Engineered Siloxane (PSX) chemistry, which employs an inorganic silicon-oxygen structure which the company states is stronger and more reliable than organic polymers. Some of Ameron's PSX product line is based on the NASA technology, used for everything from industrial equipment to bridges.

  5. Protecting Antarctica

    NASA Astrophysics Data System (ADS)

    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.

  6. The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor

    PubMed Central

    Roth, Bryan L.; Gibbons, Simon; Arunotayanun, Warunya; Huang, Xi-Ping; Setola, Vincent; Treble, Ric; Iversen, Les

    2013-01-01

    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-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]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. PMID:23527166

  7. Memory amplification for trauma: Investigating the role of analogue PTSD symptoms in the laboratory.

    PubMed

    Oulton, Jacinta M; Takarangi, Melanie K T; Strange, Deryn

    2016-08-01

    Victims of trauma often remember their experience as being more traumatic later, compared to immediately after, the event took place. This finding-the "memory amplification effect"-is associated with increased re-experiencing symptoms. However, the effect has been found almost exclusively in field-based studies. We examined whether the effect could be replicated in the laboratory. In two studies, we exposed participants to negative photographs and assessed their memory for the photographs and analogue PTSD symptoms on two occasions. In Study 1, analogue symptoms at follow-up were positively associated with remembering more negative photos over time. In Study 2, we focused on "memory amplifiers": people whose memory of the photos amplified over time. Consistent with field research, analogue re-experiencing symptoms were associated with memory amplification. Overall, our findings confirm that analogue PTSD symptoms are also associated with an amplified memory for a trauma analogue. PMID:27328014

  8. Biodegradation of bisphenol A and its halogenated analogues by Cunninghamella elegans ATCC36112.

    PubMed

    Keum, Young Soo; Lee, Hye Ri; Park, Hee Won; Kim, Jeong-Han

    2010-11-01

    Bisphenol A and its halogenated analogues are commonly used industrial chemicals with strong toxicological effects over many organisms. In this study, metabolic fate of bisphenol A and its halogenated analogues were evaluated with Cunninghamella elegans ATCC36112. Bisphenol A and related analogues were rapidly transformed into several metabolites by C. elegans within 2-4 days. Detailed analysis of metabolites reveals that both phase I and II metabolism occurred in C. elegans. Cytochrome P450-dependent hydroxylation was observed in BPA. However, major reaction with bisphenol A and analogues with 1-2 halogen atoms were the formation of glucose-conjugate, not being inhibited by cytochrome P450 inhibitor. Overall metabolic rates decreased with increasing number of substitution at 2- and 6-position of BPA structures, which may be consequences of limited bioavailability or steric hindrance to conjugate-forming reaction. Information from the current study will provide detailed insights over the fungal metabolism of BPA and analogues. PMID:20455075

  9. Phosphonate analogues of cyclopropavir phosphates and their E-isomers. Synthesis and antiviral activity.

    PubMed

    Mhaske, Santosh B; Ksebati, Bashar; Prichard, Mark N; Drach, John C; Zemlicka, Jiri

    2009-06-01

    Z- and E-Phosphonate analogues 12 and 13 derived from cyclopropavir and the corresponding cyclic phosphonates 14 and 15 were synthesized and their antiviral activity was investigated. The 2,2-bis(hydroxymethylmethylenecyclopropane acetate (17) was transformed to tetrahydropyranyl acetate 18. Deacetylation gave intermediate 19 which was converted to bromide 20. Alkylation with diisopropyl methylphosphonate afforded after protecting group exchange (21 to 22) acetylated phosphonate intermediate 22. Addition of bromine gave the dibromo derivative 16 which was used in the alkylation-elimination procedure with 2-amino-6-chloropurine to give Z- and E-isomers 23 and 24. Hydrolytic dechlorination coupled with removal of all protecting groups gave the guanine phosphonates 12 and 13. Cyclization afforded the cyclic phosphonates 14 and 15. Z-Phosphonate 12 was a potent and non-cytotoxic inhibitor of human and murine cytomegalovirus (HCMV and MCMV) with EC(50) 2.2-2.7 and 0.13 microM, respectively. It was also an effective agent against Epstein-Barr virus (EBV, EC(50) 3.1 microM). The cyclic phosphonate 14 inhibited HCMV (EC(50) 2.4-11.5 microM) and MCMV (EC(50) 0.4 microM) but it was ineffective against EBV. Both phosphonates 12 and 14 were as active against two HCMV Towne strains with mutations in UL97 as they were against wild-type HCMV thereby circumventing resistance due to such mutations. Z-Phosphonate 12 was a moderate inhibitor of replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) but it was a potent agent against varicella zoster virus (VZV, EC(50) 2.9 microM). The cyclic phosphonate 14 lacked significant potency against these viruses. E-isomers 13 and 15 were devoid of antiviral activity. PMID:19410465

  10. Phosphonate Analogues of Cyclopropavir Phosphates and Their E-isomers. Synthesis and Antiviral Activity

    PubMed Central

    Mhaske, Santosh B.; Ksebati, Bashar; Prichard, Mark N.; Drach, John C.; Zemlicka, Jiri

    2009-01-01

    Z- and E-phosphonate analogues 12 and 13 derived from cyclopropavir and the corresponding cyclic phosphonates 14 and 15 were synthesized and their antiviral activity was investigated. The 2,2-bis(hydroxymethylmethylenecyclopropane acetate (17) was transformed to tetrahydropyranyl acetate 18. Deacetylation gave intermediate 19 which was converted to bromide 20. Alkylation with diisopropyl methylphosphonate afforded after protecting group exchange (21 to 22) acetylated phosphonate intermediate 22. Addition of bromine gave the dibromo derivative 16 which was used in the alkylation-elimination procedure with 2-amino-6-chloropurine to give Z- and E-isomers 23 and 24. Hydrolytic dechlorination coupled with removal of all protecting groups gave the guanine phosphonates 12 and 13. Cyclization afforded the cyclic phosphonates 14 and 15. Z-Phosphonate 12 was a potent and non-cytotoxic inhibitor of human and murine cytomegalovirus (HCMV and MCMV) with EC50 2.2-2.7 and 0.13 μM, respectively. It was also an effective agent against Epstein-Barr virus (EBV, EC50 3.1 μM). The cyclic phosphonate 14 inhibited HCMV (EC50 2.4-11.5 μM) and MCMV (EC50 0.4 μM) but it was ineffective against EBV. Both phosphonates 12 and 14 were as active against two HCMV Towne strains with mutations in UL97 as they were against wild-type HCMV thereby circumventing resistance due to such mutations. Z-Phosphonate 12 was a moderate inhibitor of replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) but it was a potent agent against varicella zoster virus (VZV, EC50 2.9 μM). The cyclic phosphonate 14 lacked significant potency against these viruses. E-isomers 13 and 15 were devoid of antiviral activity. PMID:19410465

  11. Affinity labeling of hepatitis C virus replicase with a nucleotide analogue: identification of binding site.

    PubMed

    Manvar, Dinesh; Singh, Kamlendra; Pandey, Virendra N

    2013-01-15

    We have used an ATP analogue 5'-[p-(fluorosulfonyl)benzoyl]adenosine (FSBA) to modify HCV replicase in order to identify the ATP binding site in the enzyme. FSBA inactivates HCV replicase activity in a concentration-dependent manner with a binding stoichiometry of 2 moles of FSBA per mole of enzyme. The enzyme activity is protected from FSBA in the presence of rNTP substrates or double-stranded RNA template primers that do not support ATP as the incoming nucleotide but not in the presence of polyrU.rA(26). HPLC analysis of tryptic peptides of FSBA-modified enzyme revealed the presence of two distinct peptides eluted at 23 and 36 min; these were absent in the control. Further we noted that both peptides were protected from FSBA modification in the presence of Mg·ATP. The LC/MS/MS analysis of the affinity-labeled tryptic peptides purified from HPLC, identified two major modification sites at positions 382 (Tyr), and 491 (Lys) and a minor site at position 38 (Tyr). To validate the functional significance of Tyr38, Tyr382, and Lys491 in catalysis, we individually substituted these residues by alanine and examined their ability to catalyze RdRp activity. We found that both Y382A and K491A mutants were significantly affected in their ability to catalyze RdRp activity while Y38A remained unaffected. We further observed that both Y382A and K491A mutants were not affected in their ability to bind template primer but were significantly affected in their ability to photo-cross-link ATP in the absence or presence of template primer. PMID:23268692

  12. A computational study of open-chain epothilone analogue

    NASA Astrophysics Data System (ADS)

    Kamel, Karol; Rusinska-Roszak, Danuta

    Molecular mechanics (MM/Ambers) calculations were applied to probe the conformational profile of open-chain epothilone analogue [Org Lett 2006, 8, 685], cytotoxic against some cell lines. Geometries of the most stable conformers were optimized at DFT level using the B3LYP functional and then compared to known both experimental and virtual conformers of epothilone. One of the most stable structures is III (1.47 kcal/mol above global minimum) which represents high similarity to the appropriate fragment of the Taylor's model of epothilone A, but two other conformers: XIV and XX, although they have almost the same conformation as the mother structure, are very unstable (6.7 and 12.4 kcal/mol above the global minimum).0

  13. Micromechanics of compaction in an analogue reservoir sandstone

    SciTech Connect

    DIGIOVANNI,ANTHONY A.; FREDRICH,JOANNE T.; HOLCOMB,DAVID J.; OLSSON,WILLIAM A.

    2000-02-28

    Energy production, deformation, and fluid transport in reservoirs are linked closely. Recent field, laboratory, and theoretical studies suggest that, under certain stress conditions, compaction of porous rocks may be accommodated by narrow zones of localized compressive deformation oriented perpendicular to the maximum compressive stress. Triaxial compression experiments were performed on Castlegate, an analogue reservoir sandstone, that included acoustic emission detection and location. Initially, acoustic emissions were focused in horizontal bands that initiated at the sample ends (perpendicular to the maximum compressive stress), but with continued loading progressed axially towards the center. This paper describes microscopy studies that were performed to elucidate the micromechanics of compaction during the experiments. The microscopy revealed that compaction of this weakly-cemented sandstone proceeded in two phases: an initial stage of porosity decrease accomplished by breakage of grain contacts and grain rotation, and a second stage of further reduction accommodated by intense grain breakage and rotation.

  14. Encoding complexity within supramolecular analogues of frustrated magnets.

    PubMed

    Cairns, Andrew B; Cliffe, Matthew J; Paddison, Joseph A M; Daisenberger, Dominik; Tucker, Matthew G; Coudert, François-Xavier; Goodwin, Andrew L

    2016-05-01

    The solid phases of gold(I) and/or silver(I) cyanides are supramolecular assemblies of inorganic polymer chains in which the key structural degrees of freedom-namely, the relative vertical shifts of neighbouring chains-are mathematically equivalent to the phase angles of rotating planar ('XY') spins. Here, we show how the supramolecular interactions between chains can be tuned to mimic different magnetic interactions. In this way, the structures of gold(I) and/or silver(I) cyanides reflect the phase behaviour of triangular XY magnets. Complex magnetic states predicted for this family of magnets-including collective spin-vortices of relevance to data storage applications-are realized in the structural chemistry of these cyanide polymers. Our results demonstrate how chemically simple inorganic materials can behave as structural analogues of otherwise inaccessible 'toy' spin models and also how the theoretical understanding of those models allows control over collective ('emergent') phenomena in supramolecular systems. PMID:27102677

  15. Analogue of cosmological particle creation in an ion trap.

    PubMed

    Schützhold, Ralf; Uhlmann, Michael; Petersen, Lutz; Schmitz, Hector; Friedenauer, Axel; Schätz, Tobias

    2007-11-16

    We study phonons in a dynamical chain of ions confined by a trap with a time-dependent (axial) potential strength and demonstrate that they behave in the same way as quantum fields in an expanding or contracting Universe. Based on this analogy, we present a scheme for the detection of the analogue of cosmological particle creation which should be feasible with present day technology. In order to test the quantum nature of the particle creation mechanism and to distinguish it from classical effects such as heating, we propose to measure the two-phonon amplitude via the 2nd red sideband transition and to compare it with the one-phonon amplitude (1st red sideband). PMID:18233131

  16. Analogue of Cosmological Particle Creation in an Ion Trap

    SciTech Connect

    Schuetzhold, Ralf; Uhlmann, Michael; Petersen, Lutz; Schmitz, Hector; Friedenauer, Axel; Schaetz, Tobias

    2007-11-16

    We study phonons in a dynamical chain of ions confined by a trap with a time-dependent (axial) potential strength and demonstrate that they behave in the same way as quantum fields in an expanding or contracting Universe. Based on this analogy, we present a scheme for the detection of the analogue of cosmological particle creation which should be feasible with present day technology. In order to test the quantum nature of the particle creation mechanism and to distinguish it from classical effects such as heating, we propose to measure the two-phonon amplitude via the 2nd red sideband transition and to compare it with the one-phonon amplitude (1st red sideband)

  17. High-pressure neutron scattering of Prussian blue analogue magnets

    NASA Astrophysics Data System (ADS)

    Pajerowski, Daniel

    Pressure sensitive magnetism is known to be useful in sensors, and while applications tend to use metallic alloys, molecule based magnets (MBMs) have been shown to have large inverse magnetostrictive (IMS) response. A promising group of MBMs are the Prussian blue analogues (PBAs), in which magnetic ordering can be tuned by external stimuli such as light, electric field, and pressure. Previously, high pressure neutron scattering of nickel hexacyanochromate hydrate has shown direct evidence for isomerization of the cyanide linkage with applied pressure. Other probes have suggested a similar effect in iron hexacyanochromate hydrate, although there has yet to be direct crystallographic evidence. Neutron diffraction is sensitive to organic elements, even while in the presence of metals, and we have performed experiments above 1 GPa to look for linkage isomerism in iron hexacyanochromate. These results are supported by bulk probes and calculations.

  18. Integration of inherent and induced chirality into subphthalocyanine analogue

    PubMed Central

    Zhao, Luyang; Qi, Dongdong; Wang, Kang; Wang, Tianyu; Han, Bing; Tang, Zhiyong; Jiang, Jianzhuang

    2016-01-01

    Conventional conjugated systems are characteristic of only either inherent or induced chirality because of synthetic challenge in combination of chiral segment into the main chromophore. In this work, chiral binaphthyl segment is directly fused into the central chromophore of a subphthalocyanine skeleton, resulting in a novel type of chiral subphthalocyanine analogue (R/S)-1 of integrated inherent and induced chirality. Impressively, an obviously enhanced optical activity is discerned for (R/S)-1 molecules, and corresponding enhancement mechanism is elucidated in detail. The synthesis strategy based on rational molecular design will open the door towards fabrication of chiral materials with giant optical activity, which will have great potential in chiroptical devices. PMID:27294871

  19. [The Biological Activity of the Sevanol and Its Analogues].

    PubMed

    Osmakov, D I; Koshelev, S G; Belozerova, O A; Kublitski, V S; Andreev, Ya A; Grishin, E V; Kozlov, S A

    2015-01-01

    Previously, from the plant Thymus armeniacus a new lignan sevanol was isolated, it's structure was elucidated and was shown that it effectively inhibits the acid-sensing channel ASIC3 and also exhibits a pronounced analgesic and anti-inflammatory effect. In this work biological activity of the sevanol analog obtained by chemical synthesis from simple precursors, the stereoisomer of sevanol and a precursor molecule represents a half of sevanol was measured in electrophysiological experiments on human ASIC3 channels expressed in Xenopus laevis oocytes. Measured inhibitory activity of a synthetic analogue coincided with the activity ofthe natural molecule. Stereoisomer showed inhibitory activity drop by about a third part, and the precursor molecule showed much less significant activity. In result the significance of functional groups and a spatial configuration of sevanol in order to biological activity was shown that is important to take into account for the optimal synthesis design as well as for new drugs development on its base. PMID:26762099

  20. [Antioxidant properties of 3-oxypyridine analogues: mexidol, emoxipin, proxipin].

    PubMed

    Klebanov, G I; Liubitskiĭ, O B; Vasil'eva, O V; Klimov, Iu V; Penzulaeva, O B; Tepliashin, A S; Tolstykh, M P; Promorenko, V K; Vladimirov, Iu A

    2001-01-01

    Using three chemiluminescent model systems of oxidation (suspension of phospholipid liposomes, a geous solution of haemoglobin-hydrogen peroxide-luminol and a geous solution 2,2'-azo-bis-(2-methylpropionamidine)dihydrochloride-luminol) the antioxidant activity and mechanism of antioxidant action of three 3-oxypyridine analogues: (mexidol, emoxipin and proxipin) were studied. These compounds were shown: a) to interact with catalitically active two valency iron ions (Fe2+), that causes elimination of ions from the model system; b) to scavenge reactive oxygen species and/or luminol radicals produced in the model systems. Their activity reduced in the following order: mexidol > emoxipin > proxipin. The antioxidant activity of 3-oxypyridines may underline known clinical effects of these compounds. PMID:11558311

  1. Characterizing the magnetic fields of the first τ Sco analogues

    NASA Astrophysics Data System (ADS)

    Petit, V.; Kochukhov, O.; Massa, D. L.; Marcolino, W. L. F.; Wade, G. A.; Ignace, R.

    2012-05-01

    The B0.2 V magnetic star τ Sco stands out from the larger population of massive OB stars due to its high X-ray activity, peculiar wind diagnostics and complex magnetic field. Recently, Petit et al. [1] presented the discovery of the first two τ Sco analogues - HD66665 and HD63425, identified by the striking similarity of their UV spectra to that of τ Sco. ESPaDOnS and Narval spectropolarimetric observations were obtained by the Magnetism in Massive Stars CFHT and TBL Large Programs, in order to characterize the stellar and magnetic properties of these stars. A magnetic field of similar surface strength was found on both stars, reinforcing the connection between the presence of a magnetic field and wind peculiarities. We present additional phaseresolved observations secured by the MiMeS collaboration for HD66665 in order to measure its magnetic geometry, and correlate that geometry with diagnostics of mass-loss.

  2. Two-dimensional inorganic analogues of graphene: transition metal dichalcogenides.

    PubMed

    Jana, Manoj K; Rao, C N R

    2016-09-13

    The discovery of graphene marks a major event in the physics and chemistry of materials. The amazing properties of this two-dimensional (2D) material have prompted research on other 2D layered materials, of which layered transition metal dichalcogenides (TMDCs) are important members. Single-layer and few-layer TMDCs have been synthesized and characterized. They possess a wide range of properties many of which have not been known hitherto. A typical example of such materials is MoS2 In this article, we briefly present various aspects of layered analogues of graphene as exemplified by TMDCs. The discussion includes not only synthesis and characterization, but also various properties and phenomena exhibited by the TMDCs.This article is part of the themed issue 'Fullerenes: past, present and future, celebrating the 30th anniversary of Buckminster Fullerene'. PMID:27501969

  3. Inhibition of plant and mammalian diamine oxidase by substrate analogues.

    PubMed

    Biegański, T; Osińska, Z; Masliński, C

    1982-04-01

    Imidazoles, aliphatic substrate analogues and the natural dipeptides, carnosine and anserine, were investigated as inhibitors of diamine oxidase from the pig kidney, human pregnancy plasma and pea seedlings. Imidazole, methylimidazoles, N-acetylimidazole, histamine and N tau-methylhistamine are relatively potent inhibitors of mammalian diamine oxidase showing no influence on plant enzymes. Anserine and carnosine are inhibitors of pig kidney and pea seedling enzymes. Ki values are 2 microM and 10 microM respectively. Investigated natural derivatives of putrescine and cadaverine have no influence on diamine oxidase of different origin. In conclusion, we present some evidence to suggest that mammalian diamine oxidase, despite a high reaction rate with putrescine, is better adapted to histamine oxidation, whereas for plant enzymes the diamines are preferred substrates. PMID:6805264

  4. Remarks on a gravitational analogue of the Casimir effect

    NASA Astrophysics Data System (ADS)

    Bezerra, V. B.; Mota, H. F.; Muniz, C. R.

    2016-06-01

    We consider the Casimir effect, by calculating the Casimir energy and its corrections for nonzero temperatures, of a massless scalar field in the spacetime with topology S3 × R1 (Einstein universe) containing an idealized cosmic string. The obtained results confirm the role played by the identifications imposed on the quantum field by boundary conditions arising from the topology of the gravitational field under consideration and illustrate a realization of a gravitational analogue of the Casimir effect. In this backgorund, we show that the vacuum energy can be written as a term which corresponds to the vacuum energy of the massless scalar field in the Einstein universe added by another term that formally corresponds to the vacuum energy of the electromagnetic field in the Einstein universe, multiplied by a parameter associated with the presence of the cosmic string, namely, λ = (1/α) ‑ 1, where α is a constant related to the cosmic string tension, Gμ.

  5. Hexaethylsubporphyrins: β-alkyl analogues in the subporphyrin family.

    PubMed

    Chandra, Brijesh; Kumar, B Sathish; Mondal, Navendu; Samanta, Anunay; Panda, Pradeepta K

    2015-12-14

    Two new subporphyrins were synthesized for the first time from a β-substituted pyrrole i.e. 3,4-diethylpyrrole via pyridine-tri-N-(3,4-diethylpyrrolyl)borane as building blocks. These β-hexaethylsubporphyrins are true contracted congeners of β-octaethylporphyrin (OEP). While the meso-triphenyl derivative of hexaethylsubporphyrin could be synthesized by following the reported method, the meso-free analogue could only be synthesized by condensation with trioxane, in the presence of catalytic methanesulfonic acid. These contracted macrocycles display interesting absorption, and emission behaviour including substituent dependent S2 fluorescence owing to the presence of flexible electron donating ethyl groups at their β-positions. The optical response and ultrafast S2 state dynamics of these systems suggest that it may be possible to tune the properties of the subporphyrin to develop efficient systems for solar energy capture and conversion processes. PMID:26524153

  6. Screening of bromotyramine analogues as antifouling compounds against marine bacteria.

    PubMed

    Andjouh, Sofyane; Blache, Yves

    2016-09-01

    Rapid and efficient synthesis of 23 analogues inspired by bromotyramine derivatives, marine natural products, by means of CuSO4-catalysed [3+2] alkyne-azide cycloaddition is described. The final target was then assayed for anti-biofilm activity against three Gram-negative marine bacteria, Pseudoalteromonas ulvae (TC14), Pseudoalteromonas lipolytica (TC8) and Paracoccus sp. (4M6). Most of the synthesised bromotyramine/triazole derivatives are more active than the parent natural products Moloka'iamine (A) and 3,5-dibromo-4-methoxy-β-phenethylamine (B) against biofilm formation by the three bacterial strains. Some of these compounds were shown to act as non-toxic inhibitors of biofilm development with EC50 < 200 μM without any effect on bacterial growth even at high concentrations (200 μM). PMID:27450150

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

    SciTech Connect

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

    2004-12-15

    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.

  8. Measurement of stimulated Hawking emission in an analogue system.

    PubMed

    Weinfurtner, Silke; Tedford, Edmund W; Penrice, Matthew C J; Unruh, William G; Lawrence, Gregory A

    2011-01-14

    Hawking argued that black holes emit thermal radiation via a quantum spontaneous emission. To address this issue experimentally, we utilize the analogy between the propagation of fields around black holes and surface waves on moving water. By placing a streamlined obstacle into an open channel flow we create a region of high velocity over the obstacle that can include surface wave horizons. Long waves propagating upstream towards this region are blocked and converted into short (deep-water) waves. This is the analogue of the stimulated emission by a white hole (the time inverse of a black hole), and our measurements of the amplitudes of the converted waves demonstrate the thermal nature of the conversion process for this system. Given the close relationship between stimulated and spontaneous emission, our findings attest to the generality of the Hawking process. PMID:21405217

  9. Synthesis of Dihydropyridine Analogues for Sperm Immobilizing Activity

    NASA Astrophysics Data System (ADS)

    Sadeghipour Roodsari, H. R.; Amini, M.; Naghibi Harat, Z.; Daneshgar, P.; Vosooghi, M.; Shafiee, A.

    In the present study, the activity of seven newly synthesized dihydropyridine analogues on the motility of sperm were determined and compared to nifedipine activity that was used as standard. Sperm motility reduced value for test compounds 6a-g shows a gradual increase proportional to the size elongation of alkyl ester groups. Consequently the size of alkyl is important in the activity of test compounds and finally increase in the lipophil size of hydrocarbon`s ester (R1) is inversely related to the activity of the synthetic compounds. As a result, the methyl ester of the test compounds with 50% of nifedipine activity (in two hours group) is the most active test compound.

  10. Novel C-Ring-Hydroxy-Substituted Controlled Deactivation Cannabinergic Analogues.

    PubMed

    Kulkarni, Shashank; Nikas, Spyros P; Sharma, Rishi; Jiang, Shan; Paronis, Carol A; Leonard, Michael Z; Zhang, Bin; Honrao, Chandrashekhar; Mallipeddi, Srikrishnan; Raghav, Jimit Girish; Benchama, Othman; Järbe, Torbjörn U C; Bergman, Jack; Makriyannis, Alexandros

    2016-07-28

    In pursuit of safer controlled-deactivation cannabinoids with high potency and short duration of action, we report the design, synthesis, and pharmacological evaluation of novel C9- and C11-hydroxy-substituted hexahydrocannabinol (HHC) and tetrahydrocannabinol (THC) analogues in which a seven atom long side chain, with or without 1'-substituents, carries a metabolically labile 2',3'-ester group. Importantly, in vivo studies validated our controlled deactivation approach in rodents and non-human primates. The lead molecule identified here, namely, butyl-2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-3-yl]-2-methylpropanoate (AM7499), was found to exhibit remarkably high in vitro and in vivo potency with shorter duration of action than the currently existing classical cannabinoid agonists. PMID:27367336

  11. Integration of inherent and induced chirality into subphthalocyanine analogue.

    PubMed

    Zhao, Luyang; Qi, Dongdong; Wang, Kang; Wang, Tianyu; Han, Bing; Tang, Zhiyong; Jiang, Jianzhuang

    2016-01-01

    Conventional conjugated systems are characteristic of only either inherent or induced chirality because of synthetic challenge in combination of chiral segment into the main chromophore. In this work, chiral binaphthyl segment is directly fused into the central chromophore of a subphthalocyanine skeleton, resulting in a novel type of chiral subphthalocyanine analogue (R/S)-1 of integrated inherent and induced chirality. Impressively, an obviously enhanced optical activity is discerned for (R/S)-1 molecules, and corresponding enhancement mechanism is elucidated in detail. The synthesis strategy based on rational molecular design will open the door towards fabrication of chiral materials with giant optical activity, which will have great potential in chiroptical devices. PMID:27294871

  12. Laval nozzle as an acoustic analogue of a massive field

    NASA Astrophysics Data System (ADS)

    Cuyubamba, M. A.

    2013-10-01

    We study a gas flow in the Laval nozzle, which is a convergent-divergent tube that has a sonic point in its throat. We show how to obtain the appropriate form of the tube, so that the acoustic perturbations of the gas flow in it satisfy any given wave-like equation. With the help of the proposed method we find the Laval nozzle, which is an acoustic analogue of the massive scalar field in the background of the Schwarzschild black hole. This gives us a possibility to observe in a laboratory the quasinormal ringing of the massive scalar field, which, for special set of the parameters, can have infinitely long-living oscillations in its spectrum.

  13. Synthesis and Conformational Analysis of Locked Carbocyclic Analogues of 1,3-Diazepinone Riboside, a High-Affinity Cytidine Deaminase Inhibitor

    PubMed Central

    2009-01-01

    Cytidine deaminase (CDA) catalyzes the deamination of cytidine via a hydrated transition-state intermediate that results from the nucleophilic attack of zinc-bound water at the active site. Nucleoside analogues where the leaving NH3 group is replaced by a proton and prevent conversion of the transition state to product are very potent inhibitors of the enzyme. However, stable carbocyclic versions of these analogues are less effective as the role of the ribose in facilitating formation of hydrated species is abolished. The discovery that a 1,3-diazepinone riboside (4) operated as a tight-binding inhibitor of CDA independent of hydration provided the opportunity to study novel inhibitors built as conformationally locked, carbocyclic 1,3-diazepinone nucleosides to determine the enzyme’s conformational preference for a specific form of sugar pucker. This work describes the synthesis of two target bicyclo[3.1.0]hexane nucleosides, locked as north (5) and south (6) conformers, as well as a flexible analogue (7) built with a cyclopentane ring. The seven-membered 1,3-diazepinone ring in all the three targets was built from the corresponding benzoyl-protected carbocyclic bis-allyl ureas by ring-closing metathesis. The results demonstrate CDA’s binding preference for a south sugar pucker in agreement with the high-resolution crystal structures of other CDA inhibitors bound at the active site. PMID:19618900

  14. Total Chemical Synthesis of a Heterodimeric Interchain Bis-Lactam-Linked Peptide: Application to an Analogue of Human Insulin-Like Peptide 3

    PubMed Central

    Karas, John; Shabanpoor, Fazel; Hossain, Mohammed Akhter; Wade, John D.; Scanlon, Denis B.

    2013-01-01

    Nonreducible cystine isosteres represent important peptide design elements in that they can maintain a near-native tertiary conformation of the peptide while simultaneously extending the in vitro and in vivo half-life of the biomolecule. Examples of these cystine mimics include dicarba, diselenide, thioether, triazole, and lactam bridges. Each has unique physicochemical properties that impact upon the resulting peptide conformation. Each also requires specific conditions for its formation via chemical peptide synthesis protocols. While the preparation of peptides containing two lactam bonds within a peptide is technically possible and reported by others, to date there has been no report of the chemical synthesis of a heterodimeric peptide linked by two lactam bonds. To examine the feasibility of such an assembly, judicious use of a complementary combination of amine and acid protecting groups together with nonfragment-based, total stepwise solid phase peptide synthesis led to the successful preparation of an analogue of the model peptide, insulin-like peptide 3 (INSL3), in which both of the interchain disulfide bonds were replaced with a lactam bond. An analogue containing a single disulfide-substituted interchain lactam bond was also prepared. Both INSL3 analogues retained significant cognate RXFP2 receptor binding affinity. PMID:24288548

  15. Characteristics of binding of insulin-like growth factor (IGF)-I and IGF-II analogues to the type 1 IGF receptor determined by BIAcore analysis.

    PubMed

    Forbes, Briony E; Hartfield, Perry J; McNeil, Kerrie A; Surinya, Kathy H; Milner, Steven J; Cosgrove, Leah J; Wallace, John C

    2002-02-01

    Insulin-like growth factor (IGF) binding to the type 1 IGF receptor (IGF1R) elicits mitogenic effects, promotion of differentiation and protection from apoptosis. This study has systematically measured IGF1R binding affinities of IGF-I, IGF-II and 14 IGF analogues to a recombinant high-affinity form of the IGF1R using BIAcore technology. The analogues assessed could be divided into two groups: (a) those designed to investigate binding of IGF-binding protein, which exhibited IGF1R-binding affinities similar to those of IGF-I or IGF-II; (b) those generated to probe IGF1R interactions with greatly reduced IGF1R-binding affinities. The relative binding affinities of IGF-I analogues and IGF-I for the IGF1R determined by BIAcore analysis agreed closely with existing data from receptor-binding assays using cells or tissue membranes, demonstrating that BIAcore technology is a powerful tool for measuring affinities of IGFs for IGF1R. In parallel studies, IGF1R-binding affinities were related to ability to protect against serum withdrawal-induced apoptosis in three different assays including Hoechst 33258 staining, cell survival, and DNA fragmentation assays using the rat pheochromocytoma cell line, PC12. In this model system, IGF-I and IGF-II at low nanomolar concentrations are able to prevent apoptosis completely. We conclude that ability to protect against apoptosis is directly related to ability to bind the IGF1R. PMID:11846798

  16. Reversible lipidization of somatostatin analogues for the liver targeting.

    PubMed

    Yuan, Liyun; Wang, Jeff; Shen, Wei-Chiang

    2008-10-01

    Tyr(3)-octreotide (TOC), a somatostatin analogue, is reversibly lipidized for passive delivery to the liver with the aim of increasing its association with hepatocytes. The reversibly lipidized TOC (REAL-TOC) was formed by the conjugation of the N-palmitoyl cysteinyl moiety to the cysteinyl residues of reduced TOC through disulfide linkages and characterized by matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF) analysis. The measured mass of REAL-TOC (M+H)(+) is 1752.31 Da (calculated mass: 1752.78), confirming that two molecules of N-palmitoyl cysteines are linked to TOC via disulfide bonds. TOC and REAL-TOC were radioiodinated and administered to mice. Their biodistribution and intrahepatic distribution were subsequently investigated. The area under the curve (AUC) of (125)I-REAL-TOC in the liver was 3.8-fold greater than that of (125)I-TOC, with 20.5% and 5.8% of the injected dose (ID)/g of (125)I-REAL-TOC remaining in the liver at 2 and 24h post injection, respectively. Within the liver, TOC was primarily distributed to parenchymal cells (PC). Nevertheless, TOC was quickly excreted out and only 2.4% ID per 100mg protein remained in the PC at 2h post injection. (125)I-REAL-TOC was retained in PC for up to 2h with a constant concentration of around 6% ID/100mg protein. (125)I-REAL-TOC was also highly associated with nonparenchymal cells (NPC) at significantly higher levels than (125)I-TOC at 10min, 1h and 2h post injection. Since somatostatin analogues have been evaluated for treating late-stage hepatocellular carcinoma (HCC), the reversibly lipidized conjugates may possess enhanced therapeutic efficacy due to the liver-targeting effect. PMID:18614343

  17. Synthesis and pharmacological studies of new pyrazole analogues of podophyllotoxin.

    PubMed

    Umesha, B; Basavarajuk, Y B

    2014-01-01

    The pyrazole analogues of podophyllotoxin were synthesized by the chalcone route. This route attracts the attention because of its simple operating conditions and easy availability ofthe chemicals. Initially, benzylide-neacetophenones (chalcones) were prepared in high yields by Claisen-Schmidt reaction of acetophenones with 4-(methylthio)benzaldehyde. The cyclopropyl ketones were prepared in good yields by the reaction of chalcones with trimethylsulfoxonium iodide. Tetralones were prepared in good yields by the Friedel-Craft's intramolecular cyclization reaction of cyclopropyle ketones in the presence of anhyd. stannic chloride and acetic anhydride. The tetralones on formylation to give substituted hydroxylmethylene tetralones. Condensation of substituted hydroxylmethylene tetralones with hydrazine hydrate afforded target compounds. The structures of the synthesized compounds were confirmed by IR, 'H-NMR and Mass spectral technique. The title compounds were screened for their antimitotic and antimicrobial activities. Among the synthesized compounds cyclopropyl ketones and pyrazole analogues of podophyllotoxin, compound 7-(Methytthio)-5-(4-(methylthio)phe- nyl)-4,5.-dihydro-2H-benzo[g]indazole is more active than 5-(4-(Methylthio)phenyl)-4,5-dihydro-2H-ben- zo[g]indazole, 7-Methyl-5-(4-(methylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole, 7-Methoxy-5-(4-(meth- ylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole and the key intermediate tetralones in 100, 200 and 400 ppm at 12, 18 and 24 hrs and also showed very good activity against screened bacteria and fungi compared to their standard. PMID:25898761

  18. A novel nucleic acid analogue shows strong angiogenic activity

    SciTech Connect

    Tsukamoto, Ikuko; Sakakibara, Norikazu; Maruyama, Tokumi; Igarashi, Junsuke; Kosaka, Hiroaki; Kubota, Yasuo; Tokuda, Masaaki; Ashino, Hiromi; Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro; Konishi, Ryoji

    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.

  19. Transitional lava flows as potential analogues for lunar impact melts

    NASA Astrophysics Data System (ADS)

    Neish, Catherine; Hughes, Scott; Hamilton, Christopher; Kobs Nawotniak, Shannon; Garry, William Brent; Skok, John Roma; Elphic, Richard; Carter, Lynn; Bandfield, Joshua; Osinski, Gordon; Lim, Darlene; Heldmann, Jennifer

    2015-11-01

    Lunar impact melt deposits are among the roughest surface materials on the Moon at the decimeter scale, even though they appear smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pāhoehoe and ´a´ā lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will inform us as to the circumstances under which they were formed. Although there is no perfect archetype for lunar impact melts on Earth, certain terrestrial environments lend themselves as functional analogues. Specifically, a variety of transitional lava flow types develop if the surface of a pāhoehoe-like flow is disrupted, producing ‘slabby’ or ‘rubbly’ flows that are extremely rough at the decimeter scale. We investigated the surface roughness of transitional lava flows at Craters of the Moon (COTM) National Monument, comparing radar imagery and high-resolution topographic profiles to similar data sets acquired by the Lunar Reconnaissance Orbiter for impact melt deposits on the Moon. Results suggest that the lava flows at COTM have similar radar properties to lunar impact melt deposits, but the terrestrial flows are considerably rougher at the meter scale. It may be that lunar impact melts represent a unique lava type not observed on Earth, whose surface texture is influenced by their high emplacement temperatures and/or cooling in a vacuum. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  20. Using analogues to quantify geological uncertainty in stochastic reserve modelling

    SciTech Connect

    Wells, B.; Brown, I.

    1995-08-01

    The petroleum industry seeks to minimize exploration risk by employing the best possible expertise, methods and tools. Is it possible to quantify the success of this process of risk reduction? Due to inherent uncertainty in predicting geological reality and due to changing environments for hydrocarbon exploration, it is not enough simply to record the proportion of successful wells drilled; in various parts of the world it has been noted that pseudo-random drilling would apparently have been as successful as the actual drilling programme. How, then, should we judge the success of risk reduction? For many years the E&P industry has routinely used Monte Carlo modelling to generate a probability distribution for prospect reserves. One aspect of Monte Carlo modelling which has received insufficient attention, but which is essential for quantifying risk reduction, is the consistency and repeatability with which predictions can be made. Reducing the subjective element inherent in the specification of geological uncertainty allows better quantification of uncertainty in the prediction of reserves, in both exploration and appraisal. Building on work reported at the AAPG annual conventions in 1994 and 1995, the present paper incorporates analogue information with uncertainty modelling. Analogues provide a major step forward in the quantification of risk, but their significance is potentially greater still. The two principal contributors to uncertainty in field and prospect analysis are the hydrocarbon life-cycle and the geometry of the trap. These are usually treated separately. Combining them into a single model is a major contribution to the reduction risk. This work is based in part on a joint project with Oryx Energy UK Ltd., and thanks are due in particular to Richard Benmore and Mike Cooper.

  1. Early Earth rock analogues for Martian subsurface processes

    NASA Astrophysics Data System (ADS)

    Bishop, J. L.; Grosch, E. G.; Maturilli, A.; Helbert, J.

    2015-12-01

    Sub-surface mafic-ultramafic crustal and hydrothermal environments on early Earth and Mars may have been very similar [1]. Hydrogen production from low-temperature alteration of ultramafic and basaltic rocks has been proposed to support early microbial life in Earth's earliest subsurface environments [1]. Similarly, evidence for microbial sulphate reduction has been reported from early Archean metabasaltic pillow lavas [2]. As such, Archean terrestrial rock environments preserved in greenstone belts may play an important role in understanding early Martian subsurface environments, which in turn may have led to preservation of early traces of life. In this context, the rock sequences of the Paleoarchean Barberton greenstone belt of South Africa provide unique Martian analogues as these rocks are exceptionally well preserved and record early Earth (and perhaps Martian-type) subsurface processes. In-situ exploration by rovers, remote sensing studies, and meteorite evidence has indicated the presence of altered gabbros, olivine-/pyroxene-bearing basalts and possible felsic porphyries on Mars. In this study we present a range of relevant 3.5 billion year old Archean greenstone belt analogue samples that include altered tholeiitic basalts, basaltic komatiites, serpentinized ultramafic komatiites and a felsic tonalite. The petrography and mineralogy of the samples are presented in terms of relic igneous phases and clay mineral alteration. We are acquiring visible/near-infrared reflectance and mid-IR emission spectra on these early Archean samples with the aim of using the hyperspectral data for ground truthing remote sensing data and mineral identification/environments on Mars.[1]. Grosch et al. (2014). Microscale mapping of alteration conditions and potential biosignatures in basaltic-ultramafic rocks on early Earth and beyond, Astrobiology 14 (3), 216-228. [2]. McLoughlin et al. (2012) Sulfur isotope evidence for a Paleoarchean subseafloor biosphere, Barberton, South

  2. The Arctic Mars Analogue Svalbard Expedition 2010. (Invited)

    NASA Astrophysics Data System (ADS)

    Steele, A.; Benning, L. G.; Fogel, M. L.; Amundsen, H.; Schmitz, N.; Amase 2010 Team

    2010-12-01

    The Arctic Mars Analogue Svalbard Expeditions (AMASE) 2010 was the latest of a series of expeditions that are NASA ASTEP and ESA funded and have as their primary goals 1) testing portable instruments for their robustness as field instruments for life detection, 2) assessing Mars analogue environments for abiosignatures and biosignatures, 3) refining protocols for contamination reduction, 4) defining a minimal instrument suite for Astrobiology science on Mars and 5) sample acquisition, collection and caching of suitable samples by rover platforms containing sample acquisition hardware: first Cliffbot, then Athena. As well as testing ESA instrumentation for the ExoMars mission and NASA instruments for Mars Science Laboratory, the goals and technologies used during this 2010 campaign are very similar to that proposed by the current MEPAG MAX-C mission concept and therefore set the stage for future sample return missions. As such the field-tested technologies, procedures and protocols can be used to address specific science objectives proposed for the 2018 Mars mission opportunity. As NASA and ESA enter a new era of collaboration, AMASE has provided and will continue to provide, a test bed for both current in-situ robotic missions and Mars Sample Return mission architectures. AMASE has proved to be a unique platform to build understanding and collaboration amongst scientists and engineers from Europe and the USA. AMASE 2010 team (other than those mentioned above): Ivar Midtkandal, Kjell Ove Storvik, Garret Huntress, Verena Starke, Pan Conrad, Francis McCubbin, Tor Viscor, Antonio Sensano, Laureline Josset, Jean-Luc Josset, Mihaela Glamoclija, Steve Squyres, Inge Loes Ten Kate, Kyong Hou, Jen Stern, Amy McAdam, Dave Blake, Dick Morris, Claire Cousins, Arnold Bauer, Carole Phillippon, Eckhard Steinmetz, Dave Potts, Dominique Tobler, Guillermo Lopez.

  3. Mapping Densities in Analogue Laboratory Turbulent Plumes Using Dye Concentration

    NASA Astrophysics Data System (ADS)

    Fisher, M. A.; Kobs-Nawotniak, S. E.

    2014-12-01

    Changing tephra concentration in volcanic eruption columns is difficult to measure in the field due to fluid opacity. The bulk fluid erupted may be higher density than the surrounding atmosphere at the vent and then transition to positive buoyancy through the ingestion and heating of ambient air; thus, the concentration of the plume fluid as it rises is critical to determining whether the material rises in a sustained plume or collapses into a pyroclastic density current. We evaluate the changing concentration of an analogue plume via tracer dye intensity and relate it to plume radius expansion and vent distance. To calibrate our concentration metric, we calculated the density and dye concentration of pre-determined tracer-water mixtures. The density of the solution was directly measured using a micropipette and high precision balance. The calculated density falls within the standard error of the measured density for each step. Five photographs were taken of each concentration using a mounted Ex-FH100 digital camera with identical lighting. Using a MATLAB script, the RGB (Red-Green-Blue) color value was extracted from five pixels located at the same coordinates in each image, confirming that there was no inherent error caused by the camera and that the RGB value was the same across an entire image. We created a color map to convert from the RGB color value of a pixel in an image to its corresponding concentration. This method algorithm can then be applied to an analogue volcanic tank model, using the color variations in the plume eddies to determine the tracer concentration, and thereby density distribution, in the plume.

  4. The uptake of HNO3 on meteoric smoke analogues

    NASA Astrophysics Data System (ADS)

    Frankland, Victoria L.; James, Alexander D.; Feng, Wuhu; Plane, John M. C.

    2015-05-01

    The uptake of HNO3, H2O, NO2 and NO was studied on meteoric smoke particle analogues using a low-pressure Knudsen cell operating at 295 K. The analogues used were olivine (MgFeSiO4) and a haematite/goethite (Fe2O3/FeO(OH)) mixture synthesised by the sol-gel process. For uptake on MgFeSiO4, the following uptake coefficients were obtained: γ(HNO3)=(1.8±0.3)×10-3, γ(H2O)=(4.0±1.3)×10-3, γ(NO2)=(5.7±0.2)×10-4 and γ(NO)<3×10-4. γ(HNO3) did not show a dependence on the mass of MgFeSiO4 in the Knudsen cell (when varied by a factor of 6) implying that, because of relatively efficient uptake, HNO3 is removed only by near-surface particles. This was corroborated by application of a surface uptake model. Saturating the MgFeSiO4 particles with water vapour before exposing them to NO2 increased γ(NO2) to (2.1±0.7)×10-3, but had a very small effect on γ(HNO3). For uptake on Fe2O3/FeO(OH), γ(HNO3)=(1.5±0.2)×10-3. These results were then included in a whole atmosphere chemistry-climate model, which shows that the heterogeneous removal on meteoric smoke particles in the winter polar vortex between 30 and 60 km appears to provide an important sink for HNO3.

  5. Inhibition of ATP Synthase by Chlorinated Adenosine Analogue

    PubMed Central

    Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

    2009-01-01

    8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing α and β subunits. Crystal structures of both α and β subunits that bind to the substrate, ADP, are known in tight binding (αdpβdp) and loose binding (αtpβtp) states. Molecular docking demonstrated that 8-Cl-ADP/8-Cl-ATP occupied similar binding modes as ADP/ATP in the tight and loose binding sites of ATP synthase, respectively, suggesting that the chlorinated nucleotide metabolites may be functional substrates and inhibitors of the enzyme. The computational predictions were consistent with our whole cell biochemical results. Oligomycin, an established pharmacological inhibitor of ATP synthase, decreased both ATP and 8-Cl-ATP formation from exogenous substrates, however, did not affect pyrimidine nucleoside analogue triphosphate accumulation. Synthesis of ATP from ADP was inhibited in cells loaded with 8-Cl-ATP. These biochemical studies are in consent with the computational modeling; in the αtpβtp state 8-Cl-ATP occupies similar binding as ANP, a non-hydrolyzable ATP mimic that is a known inhibitor. Similarly, in the substrate binding site (αdpβdp) 8-Cl-ATP occupies a similar position as ATP mimic ADP-BeF3 −. Collectively, our current work suggests that 8-Cl-ADP may serve as a substrate and the 8-Cl-ATP may be an inhibitor of ATP synthase. PMID:19477165

  6. Multidisciplinary integrated field campaign to an acidic Martian Earth analogue with astrobiological interest: Rio Tinto

    NASA Astrophysics Data System (ADS)

    Gómez, F.; Walter, N.; Amils, R.; Rull, F.; Klingelhöfer, A. K.; Kviderova, J.; 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.

    2011-07-01

    Recently reported results from latest Mars Orbiters and Rovers missions are transforming our opinion about the red planet. That dry and inhospitable planet reported in the past is becoming a wetter planet with high probabilities of water existence in the past. Nowadays, some results seem to indicate the presence of water beneath the Mars surface. But also mineralogy studies by NASA Opportunity Rover report iron oxides and hydroxides precipitates on Endurance Crater. Sedimentary deposits have been identified at Meridiani Planum. These deposits must have generated in a dune aqueous acidic and oxidizing environment. Similarities appear when we study Rio Tinto, and acidic river under the control of iron. The discovery of extremophiles on Earth widened the window of possibilities for life to develop in the Universe, and as a consequence on Mars and other planetary bodies with astrobiological interest. The compilation of data produced by the ongoing missions offers an interested view for life possibilities to exist: signs of an early wet Mars and rather recent volcanic activity as well as ground morphological characteristics that seem to be promoted by liquid water. The discovery of important accumulations of sulfates and the existence of iron minerals such as jarosite in rocks of sedimentary origin has allowed specific terrestrial models to come into focus. Río Tinto (Southwestern Spain, Iberian Pyritic Belt) is an extreme acidic environment, product of the chemolithotrophic activity of micro-organisms that thrive in the massive pyrite-rich deposits of the Iberian Pyritic Belt. Some particular protective environments should house the organic molecules and bacterial life forms in harsh environments such as Mars surface supporting microniches inside precipitated minerals or inside rocks. Terrestrial analogues could help us to afford the comprehension of habitability (on other planetary bodies). We are reporting here the multidisciplinary study of some endolithic niches

  7. Tyrosine analogues for probing proton-coupled electron transfer processes in peptides and proteins.

    PubMed

    Nara, Susheel J; Valgimigli, Luca; Pedulli, Gian Franco; Pratt, Derek A

    2010-01-20

    A series of amino acids analogous to tyrosine, but differing in the physicochemical properties of the aryl alcohol side chain, have been prepared and characterized. These compounds are expected to be useful in understanding the relationships between structure, thermodynamics, and kinetics in long-range proton-coupled electron transfer processes in peptides and proteins. Systematic changes in the acidity, redox potential, and O-H bond strength of the tyrosine side chain could be induced upon substituting the phenol for pyridinol and pyrimidinol moieties. Further modulation was possible by introducing methyl and t-butyl substitution in the position ortho to the phenolic hydroxyl. The unnatural amino acids were prepared by Pd-catalyzed cross-coupling of the corresponding halogenated aryl alcohol protected as their benzyl ethers with an organozinc reagent derived from N-Boc L-serine carboxymethyl ester. Subsequent debenzylation by catalytic hydrogenation yielded the tyrosine analogues in good yield. Spectrophotometric titrations revealed a decrease in tyrosine pK(a) of ca. 1.5 log units per included nitrogen atom, along with a corresponding increase in the oxidation (peak) potentials of ca. 200 mV, respectively. All told, the six novel amino acids described here have phenol-like side chains with pK(a)'s that span a range of 7.0 to greater than 10, and an oxidation (peak) potential range of greater than 600 mV at and around physiological pH. Radical equilibration EPR experiments were carried out to reveal that the O-H bond strengths increase systematically upon nitrogen incorporation (by ca. 0.5-1.0 kcal/mol), and radical stability and persistence increase systematically upon introduction of alkyl substitution in the ortho positions. The EPR spectra of the aryloxyl radicals derived from tyrosine and each of the analogues could be determined at room temperature, and each featured distinct spectral properties. The uniqueness of their spectra will be helpful in discerning

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

    SciTech Connect

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

    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.

  9. Protective Coatings

    NASA Technical Reports Server (NTRS)

    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.

  10. Synthetic multivalent ligands for cholera & cholera-like toxins: Protected cyclic neoglycopeptides.

    PubMed

    Kumar, Vajinder; Yadav, Narender; Kartha, K P Ravindranathan

    2016-08-01

    Synthesis of a set of novel glycopeptide analogues as potential cholera/cholera-like toxin inhibitors in their protected form is described. They include di-, tri-, tetra- and pentavalent scaffolds. The synthetic steps were achieved using a combination of solvent-free mechanochemical as well as the conventional solution-phase reactions. During the conventional DIC-HOBt-mediated peptide coupling followed for the preparation of certain glycopeptide analogues an interesting in situ Fmoc deprotection was observed which has been demonstrated to hold potential for synthesiszing glycopeptides/neoglycopeptides with extended polyamide chains. PMID:27309341

  11. New techniques in contraception: gossypol, vaccines and GnRH analogues.

    PubMed

    Aitken, R J

    1983-01-01

    Discussion focuses on 3 of the most promising lines of current contraceptive research -- gossypol, vaccines, and GnRH analogues, considering both the scientific principles behind their development and the ethical implications of their future application. 1) Chinese scientists confirmed the antispermatogenic effects of cotton seed oil in animal experiments; in 1971 the active agent was identifed as gossypol. The 1st clinical trials were initiated in 1972 and thus far more than 8000 volunteers have been treated with a variety of gossypol preparations including native gossypol, gossypol acetic acid, and gossypol formic acid. The conventional contraceptive regime involves a loading dose of 20mg/day for 60-75 days followed by a maintenance dose of 50 mg/week. An undisclosed number of pregnancies have occurred. Reversibility seems to be a major problem since around 10% of men remain infertile after the cessation of gossypol intake. Other hazards of gossypol ingestion include fatigue, gastrointestinal disorders, decreased libido, dizziness, and in 0.75% of cases hypokalaemic paralysis. The question arises as to whether it is right that 8000 Chinese men have been administered gossypol while ignorance concerning the toxicity and effectiveness of this compound prohibits its approval by any other government west of the Himalayas. 2) The development of a contraceptive vaccine would be appropriate to the needs of the Third World, the population of which will have doubled in 34 years to 6.6 billion. The advantages of vaccines are that they can be administered by paramedical personnel, they should provide a long-lasting protection against pregnancy, and they can take advantage of the service infrastructure existing in most developing countries for the administration of vaccines against disease. The zona pellucida and human chorionic gonadotropin (hCG) are not the only candidates for an antifertility vaccine but they are the most promising. A 3rd but less attractive possibility is

  12. Synthesis, biological activity, and conformational study of N-methylated allatostatin analogues inhibiting juvenile hormone biosynthesis.

    PubMed

    Xie, Yong; Zhang, Li; Zhang, Chuanliang; Wu, Xiaoqing; Deng, Xile; Yang, Xinling; Tobe, Stephen S

    2015-03-25

    An allatostatin (AST) neuropeptide mimic (H17) is a potential insect growth regulator, which inhibits the production of juvenile hormone (JH) by the corpora allata. To determine the effect of conformation of novel AST analogues and their ability to inhibit JH biosynthesis, eight insect AST analogues were synthesized using H17 as the lead compound by N-methylation scanning, which is a common strategy for improving the biological properties of peptides. A bioassay using JH production by corpora allata of the cockroach Diploptera punctata indicated that single N-methylation mimics (analogues 1-4) showed more activity than double N-methylation mimics (analogues 5-8). Especially, analogues 1 and 4 showed roughly equivalent activity to that of H17, with IC50 values of 5.17 × 10(-8) and 6.44 × 10(-8) M, respectively. Molecular modeling based on nuclear magnetic resonance data showed that the conformation of analogues 1 and 4 seems to be flexible, whereas analogues 2 and 3 showed a type IV β-turn. This flexible linear conformation was hypothesized to be a new important and indispensable structural element beneficial to the activity of AST mimics. PMID:25751662

  13. Presence and formation of cobalamin analogues in multivitamin-mineral pills.

    PubMed Central

    Kondo, H; Binder, M J; Kolhouse, J F; Smythe, W R; Podell, E R; Allen, R H

    1982-01-01

    Because the origin of cobalamin (vitamin B12) analogues in animal chows and animal and human blood and tissues is unknown, we investigated the possibility that multivitamin interactions might convert cobalamin to cobalamin analogues. We homogenized three popular multivitamin-mineral pills in water, incubated them at 37 degrees C for 2 h, and isolated the cobalamin. Using paper chromatography we observed that 20-90% of the cobalamin was present as cobalamin analogues. Studies using CN-[57Co]cobalamin showed that these analogues were formed due to the concerted action of vitamin C, thiamine, and copper on CN-cobalamin. These cobalamin analogues are absorbed from the gastrointestinal tract of mice and either fail to stimulate or actually inhibit cobalamin-dependent enzymes when injected parenterally. We conclude that CN-cobalamin can be converted to potentially harmful cobalamin analogues by multivitamin-mineral interactions and that these interactions may be responsible for the presence of cobalamin analogues in animal chows and animal and human blood and tissues. PMID:6126492

  14. Analogue Models Of Volcanic Spreading At Mt. Vesuvius

    NASA Astrophysics Data System (ADS)

    De Matteo, Ada; Castaldo, Raffaele; D'Auria, Luca; James, Michael; Lane, Steve; Massa, Bruno; Pepe, Susi; Tizzani, Pietro

    2015-04-01

    Somma-Vesuvius is a quiescent strato-volcano of the Neapolitan district, southern Italy, for which various geophysical and geological evidences (e.g. geodetic measurements, geological and structural data, seismic profiles interpretations and surface deformation analysis with Differential Interferometric Synthetic Aperture Radar (DInSAR)) indicate ongoing spreading deformation. In this research we investigate the spreading deformation and associated surface deformation pattern by performing analogue experiments and comparing the results with actual ground deformation as measured using DInSAR data recorded between 1992 and 2010. Somma-Vesuvius consists of a volcanic cone (Gran Cono) lying within an asymmetric caldera (Somma). The Somma caldera is the result of at least 7 Plinian eruptions, the last of which was the 79 CE. Pompeii eruption. The current cone of Mt. Vesuvius grew within the caldera in the following centuries as the effect of continued explosive and effusive activity of the volcano. The volcano lies on a substratum consisting of a Mesozoic carbonatic basement, overlapped by Holocene clastic sediments and volcanic rocks. Our analogue models were built to simulate the shape of the Somma-Vesuvius top a scale of about 1:100000, emplaced on a sand layer (brittle behaviour) laid on a silicone layer (ductile behaviour). Models are based on the Fluid-dynamics Dimensionless Analysis (FDA), according to the Buckingham-Π theorem. In this context, we considered few dimensionless parameters that allowed the setting of a reliable scaled model. To represent the complex Somma-Vesuvius geometry, an asymmetric model was built by setting a truncated cone (mimicking the topography of Somma edifice) topped by another small cone (mimicking the Gran Cono) shifted off the axis of the main cone. Different experiments were carried out in which the thickness of the basal sand layer and of the silicone one were varied. To quantify the vertical and horizontal displacements the

  15. Analogue modelling of salt diapirism induced by differential loading

    NASA Astrophysics Data System (ADS)

    Warsitzka, Michael; Kley, Jonas; Kukowski, Nina; Jähne, Fabian

    2010-05-01

    In salt tectonics, two general concepts exist to explain salt diapirism. First, the theory of active piercement by Trusheim (1960) states that salt rises up and pierces its overburden autonomously by buoyancy forces. Second, the theory of reactive piercement by Vendeville and Jackson (1992) considers a tectonic stress field responsible for initiation of salt uplift and has been tested in many analogue experiments. In this study, we investigated the hypothesis in which salt diapir formation is activated by sedimentary processes alone, i.e. without a tectonic trigger. Our models consisted of a viscous silicone layer simulating rock salt overlain by layers of sand that mimic brittle behaviour in natural overburden sediments. The experiments were monitored with a high-resolution strain analysis tool based on digital image correlation (particle image velocimetry, PIV). Deformation in the silicone was initiated by a lateral variation in the thickness or density of the overburden, which established a differential loading on the silicone layer. Subsequent sedimentation in certain time intervals forced the silicone to rise up and break through the initial sand layer by buoyancy forces. The model results support the hypothesis of active piercement of diapirs. Uplift of the silicone and creation of a pillow structure with a significant elevation can be achieved if the overburden does not exceed a critical thickness and if the load gradient in the overburden reaches a minimum value. Then, ongoing sedimentation in adjacent areas increases the lateral load gradient until the buoyancy force in the silicone is high enough to overcome the shear strength of the sand. Synkinematic sedimentation produces some typical strata geometries in the sand layer that can also be observed in nature, e.g. drag folds bordering the diapirs and layer thickening in the peripherical rim synclines. The creation of one diapir and its peripherical sinks induces a lateral migration of the deformation to

  16. Mitomycin C and porfiromycin analogues with substituted ethylamines at position 7.

    PubMed

    Iyengar, B S; Sami, S M; Remers, W A; Bradner, W T; Schurig, J E

    1983-01-01

    A series of 7-(2-substituted-ethyl)amino analogues of mitomycin C and porfiromycin was prepared and screened in standard antitumor systems. Certain of these analogues showed better activity than mitomycin C against P-388 leukemia, L-1210 leukemia, and/or B-16 melanocarcinoma in mice. Compounds also tested for their leukopenic effects in mice, the limiting toxicity of mitomycin C. Some of them were less leukopenic and some were more leukopenic than this clinical agent. No statistically significant correlations could be made between physicochemical properties and antitumor activities of the analogues. PMID:6827524

  17. Isolation and structural elucidation of a new tadalafil analogue in health supplements: bisprenortadalafil.

    PubMed

    Lee, Ji Hyun; Park, Han Na; Ganganna, Bogonda; Jeong, Ji Hye; Park, Sung-Kwan; Lee, Jongkook; Baek, Sun Young

    2016-06-01

    A new tadalafil analogue was found, along with nortadalafil, using HPLC-DAD during the inspection of a health product sold without official approval. The analogue was separated using a semi-preparative HPLC system and its structure was determined by a combination of mass spectrometry and NMR spectroscopy. The compound was identified as a tadalafil analogue in which the N-methyl group of tadalafil was replaced with a tadalafil precursor moiety. Nuclear Overhauser effect spectroscopy experiments suggested a cis-relationship between the substituents on a piperidine ring in the tadalafil moiety. PMID:27167568

  18. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

    PubMed Central

    Rabe, Patrick; Klapschinski, Tim A; Brock, Nelson L; Citron, Christian A; D’Alvise, Paul; Gram, Lone

    2014-01-01

    Summary 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 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 is presented and the bioactivity of the synthetic compounds is discussed. PMID:25161739

  19. Synthesis and Antimicrobial Evaluation of Nitazoxanide-Based Analogues: Identification of Selective and Broad Spectrum Activity

    PubMed Central

    Ballard, T. Eric; Wang, Xia; Olekhnovich, Igor; Koerner, Taylor; Seymour, Craig; Salamoun, Joseph; Warthan, Michelle; Hoffman, Paul S.; Macdonald, Timothy L.

    2011-01-01

    A library composed of Nitazoxanide-based analogues was synthesized and assayed for increased antibacterial efficacy against the pyruvate:ferredoxin oxidoreductase (PFOR) utilizing microorganisms Helicobacter pylori, Campylobacter jejuni and Clostridium difficile. Derivatives were found to recapitulate and improve activity against these organisms and select analogues were tested for their ability to disrupt the PFOR enzyme directly. The library was also screened for activity against staphylococci and resulted in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low μM MIC concentrations with low toxicity to human foreskin cells. PMID:21275058

  20. Hierarchically superstructured prussian blue analogues: spontaneous assembly synthesis and applications as pseudocapacitive materials.

    PubMed

    Yue, Yanfeng; Zhang, Zhiyong; Binder, Andrew J; Chen, Jihua; Jin, Xianbo; Overbury, Steven H; Dai, Sheng

    2015-01-01

    Hierarchically superstructured Prussian blue analogues (hexacyanoferrate, M=Ni(II) , Co(II) and Cu(II) ) are synthesized through a spontaneous assembly technique. In sharp contrast to macroporous-only Prussian blue analogues, the hierarchically superstructured porous Prussian blue materials are demonstrated to possess a high capacitance, which is similar to those of the conventional hybrid graphene/MnO2 nanostructured textiles. Because sodium or potassium ions are involved in energy storage processes, more environmentally neutral electrolytes can be utilized, making the superstructured porous Prussian blue analogues a great contender for applications as high-performance pseudocapacitors. PMID:25385481

  1. Peptide Receptor Radionuclide Therapy (PRRT) of Medullary and Nonmedullary Thyroid Cancer Using Radiolabeled Somatostatin Analogues.

    PubMed

    Salavati, Ali; Puranik, Ameya; Kulkarni, Harshad R; Budiawan, Hendra; Baum, Richard P

    2016-05-01

    As therapeutic options in advanced medullary and non-iodine avid differentiated (nonmedullary) thyroid cancers are limited and associated with significant toxicity, targeting of somatostatin receptors (SSTRs) for internal radiation therapy provides a promising option. Theranostics (therapy and diagnosis) using radiolabeled somatostatin analogues has proved to be a milestone in the management of SSTR-expressing tumors. Peptide receptor radionuclide therapy using (177)Lu-labeled or (90)Y-labeled somatostatin analogues may have a significant role in the management of medullary and nonmedullary thyroid cancers in those patients where PET/CT with (68)Ga-labeled somatostatin analogues demonstrates significant SSTR expression. PMID:27067502

  2. Expeditious synthesis of Mycobacterium tuberculosis sulfolipids SL-1 and Ac2SGL analogues.

    PubMed

    Sarpe, Vikram A; Kulkarni, Suvarn S

    2014-11-01

    M. tuberculosis sulfoglycolipids SL-1 and Ac2SGL are highly immunogenic and potential vaccine candidates. A short and efficient methodology is reported for the synthesis of SL-1 and Ac2SGL analogues via regioselective functionalization of α,α-D-trehalose employing a highly regioselective late stage sulfation, as a key step. The SL-1 analogues 3a and 4 were obtained in 10 and 9 steps in 13.4% and 23.9% overall yields, respectively. The Ac2SGL analogue 5 was synthesized in 5 steps in 18.4% yield. PMID:25322198

  3. Synthetic analogues of chymostatin. Inhibition of chymotrypsin and Streptomyces griseus proteinase A.

    PubMed Central

    Tomkinson, N P; Galpin, I J; Beynon, R J

    1992-01-01

    A series of analogues of chymostatin, including Z-Arg-Leu-Phe-aldehyde (Z-Arg-Leu-Phe-H), have been synthesized. Analysis of the inhibitory potential of these analogues permits identification of residues and interactions that are important for inhibitory activity. Moreover, the structure-function relationship for Z-Arg-Leu-Phe-H and chymostatin inhibition of chymotrypsin and Streptomyces griseus proteinase A (SGPA) was probed further with the aid of molecular mechanics. This analysis identified interactions that provide an explanation for the enhanced activity of the natural product, chymostatin, over the synthetic analogues in the inhibition of chymotrypsin but not SGPA. PMID:1530579

  4. Quality of casein based Mozzarella cheese analogue as affected by stabilizer blends.

    PubMed

    Jana, A H; Patel, H G; Suneeta, Pinto; Prajapati, J P

    2010-03-01

    Suitability of xanthan gum (XG)-locust bean gum (LBG), carrageenan (CAR)-LBG, and XG-CAR in 1:1 proportion at 0.42% in the formulation was assessed in the manufacture of Mozzarella cheese analogue. The stabilizer blends did not significantly influence the composition, texture profile, organoleptic, baking qualities and pizza-related characteristics of cheese analogues. Considering the influence of stabilizer blend on the sensory quality of analogue and sensory rating of pizza pie, XG-LBG blend (1:1) was preferred over XG-CAR and CAR-LBG. PMID:23572632

  5. Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors.

    PubMed

    Devreux, Vincent; Wiesner, Jochen; Goeman, Jan L; Van der Eycken, Johan; Jomaa, Hassan; Van Calenbergh, Serge

    2006-04-20

    A series of fosmidomycin analogues featuring restricted conformational mobility has been synthesized and evaluated as inhibitors of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase and as growth inhibitors of P. falciparum. The enantiomerically pure trans-cyclopropyl N-acetyl analogue 3b showed comparable inhibitory activity as fosmidomycin toward E. coli DOXP reductoisomerase and proved equally active when tested in vitro for P. falciparum growth inhibition. Conversely, the alpha-phenyl cis-cyclopropyl analogue 4 showed virtually no inhibition of the enzyme. PMID:16610809

  6. Hierarchically Superstructured Prussian Blue Analogues: Spontaneous Assembly Synthesis and Applications as Pseudocapacitive Materials

    DOE PAGESBeta

    Yue, Yanfeng; Zhang, Zhiyong; Binder, Andrew J.; Chen, Jihua; Jin, Xianbo; Overbury, Steven; Dai, Sheng

    2014-11-10

    Hierarchically superstructured Prussian blue analogues (hexa- conventional hybrid graphene/MnO2 nanostructured textiles. cyanoferrate, M = NiII, CoII and CuII) are synthesized through Because sodium or potassium ions are involved in energy stor- a spontaneous assembly technique. In sharp contrast to mac- age processes, more environmentally neutral electrolytes can roporous-only Prussian blue analogues, the hierarchically su- be utilized, making the superstructured porous Prussian blue perstructured porous Prussian blue materials are demonstrated analogues a great contender for applications as high-per- to possess a high capacitance, which is similar to those of the formance pseudocapacitors.

  7. Hierarchically Superstructured Prussian Blue Analogues: Spontaneous Assembly Synthesis and Applications as Pseudocapacitive Materials

    SciTech Connect

    Yue, Yanfeng; Zhang, Zhiyong; Binder, Andrew J.; Chen, Jihua; Jin, Xianbo; Overbury, Steven; Dai, Sheng

    2014-11-10

    Hierarchically superstructured Prussian blue analogues (hexa- conventional hybrid graphene/MnO2 nanostructured textiles. cyanoferrate, M = NiII, CoII and CuII) are synthesized through Because sodium or potassium ions are involved in energy stor- a spontaneous assembly technique. In sharp contrast to mac- age processes, more environmentally neutral electrolytes can roporous-only Prussian blue analogues, the hierarchically su- be utilized, making the superstructured porous Prussian blue perstructured porous Prussian blue materials are demonstrated analogues a great contender for applications as high-per- to possess a high capacitance, which is similar to those of the formance pseudocapacitors.

  8. Asymmetric gravitational spreading - Analogue experiments on the Svecofennian orogen

    NASA Astrophysics Data System (ADS)

    Nikkilä, Kaisa; Korja, Annakaisa; Koyi, Hemin; Eklund, Olav

    2015-04-01

    Over-thickened orogenic crust may suffer from rheological, gravitational and topographical unbalancing resulting in discharging via gravitational spreading. If the thickened orogen is also hot, then increased temperature may reduce the viscosity of the crust that may induce large-scale horizontal flow. The effect of flow on the crustal architecture has previously been modeled with symmetric two-way spreading or asymmetric one- or two-way spreading (like channel flow) experiments. Most models do not take into account of the contrasting mechanical properties of the juxtaposed terranes. We have made analogue experiments to study gravitational one-way spreading and the interplay between two crustal blocks with contrasting rheological properties. The models are 3 cm thick replicas of 60 km thick crust. They have three horizontal layers representing strong lower, weak middle and brittle upper crust. The models have cuts to study the effect of inherited crustal-scale weakness zones. The experiments have been conducted within a large centrifuge in the Hans Ramberg Tectonic Laboratory at Uppsala University. The analogue models propose that asymmetric, unilateral flow has different effect on the contrasting crustal units, in both horizontal and vertical directions. The laterally heterogeneous crust flows towards the direction of extension, and it rotates and extends the pre-existing weakness zones. The weakness zones facilitate exhumation and they increase strain rate. The weakness zones split the crust into subblocks, which stretch individually and which may show signatures of compression or rotation. The changes in thickness of the model reflect changes in the layers, which may thin or thicken depending on the mechanical properties of crustal layers. A consequence of this the total amount of flattening is less than the model extension. The results are compared to geophysical and geological data from Precambrian Svecofennian orogen in Fennoscandia. The comparison suggest

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

    NASA Technical Reports Server (NTRS)

    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

  10. Thalidomide analogue CC1069 inhibits development of rat adjuvant arthritis

    PubMed Central

    Oliver, S J; Freeman, S L; Corral, L G; Ocampo, C J; Kaplan, G

    1999-01-01

    The cytokine tumour necrosis factor-alpha (TNF-α) has been implicated in the aetiology of rheumatoid arthritis in humans as well as of experimental arthritis in rodents. Thalidomide, and to a greater extent the new thalidomide analogue CC1069, inhibit monocyte TNF-α production both in vitro and in vivo. The aim of the present study is to establish whether these drugs block production of TNF-α as well as IL-2 by rat leucocytes and whether this inhibition affects the development of rat adjuvant arthritis (AA). Cultured splenocytes were stimulated with either lipopolysaccharide (LPS) or concanavalin A (Con A) in the presence of thalidomide, CC1069, or solvent, and the production of TNF-α and IL-2 were compared. Next, adjuvant was injected into the base of the tail of rats without or with daily intraperitoneal injections with 100–200 mg/kg per day thalidomide or 50–200 mg/kg per day CC1069. Disease activity, including ankle swelling, hind limb radiographic and histological changes, weight gain, and ankle joint cytokine mRNA levels, were monitored. CC1069, but not the parent drug thalidomide, inhibited in vitro production of TNF-α and IL-2 by stimulated splenocytes in a dose-dependent manner. In vivo, a dose-dependent suppression of AA disease activity occurred in the CC1069-treated animals. In contrast, thalidomide-treated rats experienced comparable arthritis severity to placebo-treated animals. There was also a reduction in TNF-α and IL-2 mRNA levels in the ankle joints of CC1069-treated rats compared with thalidomide- and placebo-treated arthritic rats. Early initiation of CC1069 treatment suppressed AA inflammation more efficiently than delayed treatment. We conclude that thalidomide, which did not suppress TNF-α or IL-2 production in vitro by Lewis rat cells, did not suppress development of rat AA. However, the development of rat AA can be blocked by the thalidomide analogue CC1069, which is an efficient inhibitor of TNF-α production and IL-2 in vitro

  11. Synthesis of a des-B-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core.

    PubMed

    Kraft, Matthew B; Poudel, Yam B; Kedei, Noemi; Lewin, Nancy E; Peach, Megan L; Blumberg, Peter M; Keck, Gary E

    2014-09-24

    A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues. PMID:25207434

  12. Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core

    PubMed Central

    2015-01-01

    A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues. PMID:25207434

  13. Chemistry of group 9 dimetallaborane analogues of octaborane(12).

    PubMed

    Barik, Subrat Kumar; Roy, Dipak Kumar; Ghosh, Sundargopal

    2015-01-14

    We report the synthesis, isolation and structural characterization of several moderately air stable nido-metallaboranes that represent boron rich open cage systems. The reaction of [Cp*CoCl]2, (Cp* = η(5)-C5Me5), with [BH3·thf] in toluene at ice cold temperature, followed by thermolysis in boiling toluene produced [(Cp*Co)B9H13], 1 [(Cp*Co)2B8H12], 2 and [(Cp*Co)2B6H10] 3. Building upon our earlier reactivity studies on rhodaboranes, we continue to explore the reactivity of dicobalt analogues of octaborane(12) cluster 3 with [Fe2(CO)9] and [Ru3(CO)12] at ambient conditions that yielded novel fused clusters [Fe2(CO)6(Cp*Co)2B6H10], 4 and [Ru4(CO)11(Cp*Co)2B3H3], 5 respectively. In an attempt to synthesize a heterometallic metallaborane compound we performed the reaction of [(Cp*Rh)2B6H10], 6 with [Cp*IrH4] that yielded a Ir-Ir double bonded compound [(Cp*Ir)2H3][B(OH)4], 7. All the new compounds have been characterized by IR, (1)H, (11)B, (13)C NMR spectroscopy, and the molecular structures were unambiguously established by X-ray diffraction analysis. PMID:25385503

  14. Robenidine Analogues as Gram-Positive Antibacterial Agents.

    PubMed

    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. PMID:26765953

  15. Photophysical properties of pyrrolocytosine, a cytosine fluorescent base analogue.

    PubMed

    Nguyen, Quynh L; Spata, Vincent A; Matsika, Spiridoula

    2016-07-27

    The photophysical behavior of pyrrolocytosine (PC), a fluorescent base analogue of cytosine, has been investigated using theoretical approaches. The similarities between the PC and cytosine structures allow PC to maintain the pseudo-Watson-Crick base-pairing arrangement with guanine. Cytosine, similar to the other natural nucleobases, is practically non-fluorescent, because of ultrafast radiationless decay occurring through conical intersections. PC displays a much higher fluorescence quantum yield than cytosine, making it an effective fluorescent marker to study the structure, function, and dynamics of DNA/RNA complexes. Similar to 2-aminopurine, a constitutional isomer of adenine that base-pairs with thymine, PC's fluorescence is quenched when it is incorporated into a dinucleotide or a trinucleotide. In this work we examine the photophysical properties of isolated PC, microhydrated PC, as well as, complexes where PC is either base-stacked or hydrogen-bonded with guanine. Our results indicate that hydration affects the radiationless decay pathways in PC by destabilizing conical intersections. The calculations of dimers and trimers show that the radiative decay is affected by π stacking, while the presence of charge transfer states between PC and guanine may contribute to radiationless decay. PMID:27251599

  16. Assessment of capsiconinoid composition, nonpungent capsaicinoid analogues, in capsicum cultivars.

    PubMed

    Tanaka, Yoshiyuki; Hosokawa, Munetaka; Otsu, Keigo; Watanabe, Tatsuo; Yazawa, Susumu

    2009-06-24

    Capsiconinoid is a group of nonpungent capsaicinoid analogues produced in Capsicum fruits, which we recently identified. Capsiconinoids have agonist activity for transient receptor potential vanilloid type 1 (TRPV1), which is reported to be a receptor for capsaicin. It is, therefore, important to screen cultivars containing high levels of capsiconinoid for their use as a vegetable or dietary supplement. This study describes the quantitative analysis of capsiconinoid content in fruits of 35 Capsicum cultivars: 18 cultivars of C. annuum, 7 of C. baccatum, 5 of C. chinense, 4 of C. frutescens, and 1 of C. pubescens. Using high-performance liquid chromatography (HPLC), we found that 10 cultivars contained capsiconinoids. Capsiconinoid Baccatum (CCB) (C. baccatum var. praetermissum) showed the highest capsiconinoid content (3314 microg/g DW) and Charapita (C. chinense) had the second highest content. The other 8 cultivars had much lower capsiconinoid content than these two cultivars (<300 microg/g DW). Time-course analysis during fruit development clarified that capsiconinoid content in CCB fruits increased until 30 days after flowering (DAF) and then decreased rapidly until 40 DAF. PMID:19489540

  17. Combined treatment of somatostatin analogues with pegvisomant in acromegaly.

    PubMed

    Franck, S E; Muhammad, A; van der Lely, A J; Neggers, S J C M M

    2016-05-01

    Treatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups has recommended switching to combined treatment of LA-SSA and pegvisomant (PEGV) in patients with partial response to LA-SSAs. This combination of LA-SSA and PEGV, a growth hormone receptor antagonist, can normalize IGF-I levels in virtually all patients, requiring that the adequate dose of PEGV is used. The required PEGV dose varies significantly between individual acromegaly patients. One of the advantages of the combination therapy is that tumor size control or even tumor shrinkage can be observed in a vast majority of patients. The main side effects of the combination treatment are gastrointestinal symptoms, lipohypertrophy and transient elevated liver transaminases. In this review we provide an overview of the efficacy and safety of the combined treatment of LA-SSAs with PEGV. PMID:26661938

  18. BCN: a graphene analogue with remarkable adsorptive properties.

    PubMed

    Raidongia, Kalyan; Nag, Angshuman; Hembram, K P S S; Waghmare, Umesh V; Datta, Ranjan; Rao, C N R

    2010-01-01

    A new analogue of graphene containing boron, carbon and nitrogen (BCN) has been obtained by the reaction of high-surface-area activated charcoal with a mixture of boric acid and urea at 900 degrees C. X-ray photoelectron spectroscopy and electron energy-loss spectroscopy reveal the composition to be close to BCN. The X-ray diffraction pattern, high-resolution electron microscopy images and Raman spectrum indicate the presence of graphite-type layers with low sheet-to-sheet registry. Atomic force microscopy reveals the sample to consist of two to three layers of BCN, as in a few-layer graphene. BCN exhibits more electrical resistivity than graphene, but weaker magnetic features. BCN exhibits a surface area of 2911 m(2) g(-1), which is the highest value known for a B(x)C(y)N(z) composition. It exhibits high propensity for adsorbing CO(2) ( approximately 100 wt %) at 195 K and a hydrogen uptake of 2.6 wt % at 77 K. A first-principles pseudopotential-based DFT study shows the stable structure to consist of BN(3) and NB(3) motifs. The calculations also suggest the strongest CO(2) adsorption to occur with a binding energy of 3.7 kJ mol(-1) compared with 2.0 kJ mol(-1) on graphene. PMID:19946909

  19. Graphene analogues of BN: novel synthesis and properties.

    PubMed

    Nag, Angshuman; Raidongia, Kalyan; Hembram, Kailash P S S; Datta, Ranjan; Waghmare, Umesh V; Rao, C N R

    2010-03-23

    Enthused by the fascinating properties of graphene, we have prepared graphene analogues of BN by a chemical method with a control on the number of layers. The method involves the reaction of boric acid with urea, wherein the relative proportions of the two have been varied over a wide range. Synthesis with a high proportion of urea yields a product with a majority of 1-4 layers. The surface area of BN increases progressively with the decreasing number of layers, and the high surface area BN exhibits high CO(2) adsorption, but negligible H(2) adsorption. Few-layer BN has been solubilized by interaction with Lewis bases. We have used first-principles simulations to determine structure, phonon dispersion, and elastic properties of BN with planar honeycomb lattice-based n-layer forms. We find that the mechanical stability of BN with respect to out-of-plane deformation is quite different from that of graphene, as evident in the dispersion of their flexural modes. BN is softer than graphene and exhibits signatures of long-range ionic interactions in its optical phonons. Finally, structures with different stacking sequences of BN have comparable energies, suggesting relative abundance of slip faults, stacking faults, and structural inhomogeneities in multilayer BN. PMID:20128601

  20. The degree of biogenicity of micrites and terrestrial Mars analogues .

    NASA Astrophysics Data System (ADS)

    D'Elia, M.; Blanco, A.; Orofino, V.; Fonti, S.; Mastandrea, A.; Guido, A.; Tosti, F.; Russo, F.

    A number of indications, as the past presence of water, a denser atmosphere and a mild climate on early Mars, suggest that environmental conditions favorable to the emergence of life must have been present on that planet in the first hundred million years, or even more recently. If life actually existed on Mars, biomarkers could be still preserved with some degree of degradation. In previous laboratory works we have investigated the infrared spectral modifications induced by thermal processing on different carbonate samples, in the form of recent shells and fossils of different ages, whose biogenic origin is indisputable. The goal was to develop a method able to discriminate carbonate biogenic samples from their abiogenic counterparts. The method has been successfully applied to microbialites, i.e. bio-induced carbonates deposits, and particularly to stromatolites, the laminated fabric of microbialites, some of which can be ascribed among the oldest traces of biological activity known on Earth. This result is of valuable importance since such carbonates are linked to primitive living organisms which can be considered as good analogues for putative Martian life forms. In this work we show that, studying different parts of the same carbonate rock sample, we are able to distinguish, on the base of the degree of biogenicity, the various micrite types (i.e. detrital vs autochthonous).

  1. Upheaval Dome, An Analogue Site for Gale Center

    NASA Technical Reports Server (NTRS)

    Conrad, P. G.; Eignebrode, J. L.

    2011-01-01

    We propose Upheaval Dome in southeastern Utah as an impact analogue site on Earth to Mars Science Laboratory candidate landing site Gale Crater. The genesis of Upheaval Dome was a mystery for some time--originally thought to be a salt dome. The 5 km crater was discovered to possess shocked quartz and other shock metamorphic features just a few years ago, compelling evidence that the crater was formed by impact, although the structural geology caused Shoemaker and Herkenhoff to speculate an impact origin some 25 years earlier. The lithology of the crater is sedimentary. The oldest rocks are exposed in the center of the dome, upper Permian sandstones, and progressively younger units are well exposed moving outward from the center. These are Triassic sandstones, siltstones and shales, which are intruded by clastic dikes. There are also other clay-rich strata down section, as is the case with Gale Crater. There is significant deformation in the center of the crater, with folding and steeply tilted beds, unlike the surrounding Canyonlands area, which is relatively undeformed. The rock units are well exposed at Upheaval Dome, and there are shatter cones, impactite fragments, shocked quartz grains and melt rocks present. The mineral shock features suggest that the grains were subjected to dynamic pressures> 10 GPa.

  2. DNA information: from digital code to analogue structure.

    PubMed

    Travers, A A; Muskhelishvili, G; Thompson, J M T

    2012-06-28

    The digital linear coding carried by the base pairs in the DNA double helix is now known to have an important component that acts by altering, along its length, the natural shape and stiffness of the molecule. In this way, one region of DNA is structurally distinguished from another, constituting an additional form of encoded information manifest in three-dimensional space. These shape and stiffness variations help in guiding and facilitating the DNA during its three-dimensional spatial interactions. Such interactions with itself allow communication between genes and enhanced wrapping and histone-octamer binding within the nucleosome core particle. Meanwhile, interactions with proteins can have a reduced entropic binding penalty owing to advantageous sequence-dependent bending anisotropy. Sequence periodicity within the DNA, giving a corresponding structural periodicity of shape and stiffness, also influences the supercoiling of the molecule, which, in turn, plays an important facilitating role. In effect, the super-helical density acts as an analogue regulatory mode in contrast to the more commonly acknowledged purely digital mode. Many of these ideas are still poorly understood, and represent a fundamental and outstanding biological question. This review gives an overview of very recent developments, and hopefully identifies promising future lines of enquiry. PMID:22615471

  3. Biological targets for isatin and its analogues: Implications for therapy

    PubMed Central

    Medvedev, Alexei; Buneeva, Olga; Glover, Vivette

    2007-01-01

    Isatin and its metabolites are constituents of many natural substances. They are also components of many synthetic compounds exhibiting a wide range of effects, including antiviral activity, antitumor and antiangiogenic activity, antibacterial, antitubercular, antifungal, antiaptotic, anticonvulsant and anxyolytic activities. Isatin itself is an endogenous oxidized indole with a wide spectrum of behavioral and metabolic effects. It has a distinct and discontinuous distribution in the brain, peripheral tissues and body fluids and isatin binding sites are widely distributed also. Its output is increased during stress. Its most potent known in vitro actions are as an antagonist of atrial natriuretic peptide (ANP) function and NO signaling. As we understand more about its function and sites of action we may be able to develop new pharmacological agents to mimic or counteract its activity. We consider here the most promising biological targets for various isatin analogues and/or metabolites, which are employed for the development of various groups of therapeutics. It is also possible that the level of endogenous isatin may influence the in vivo pharmacological activity of compounds possessing the isatin moiety. PMID:19707325

  4. Detecting Pyrolysis Products from Bacteria in a Mars Soil Analogue

    NASA Technical Reports Server (NTRS)

    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.

  5. Onboard Detection of Active Canadian Sulfur Springs: A Europa Analogue

    NASA Technical Reports Server (NTRS)

    Castano, Rebecca; Wagstaff, Kiri; Gleeson, Damhnait; Pappalardo, Robert; Chien, Steve; Tran, Daniel; Scharenbroich, Lucas; Moghaddam, Baback; Tang, Benyang; Bue, Brian; Doggett, Thomas; Mandl, Dan; Frye, Stuart

    2008-01-01

    We discuss a current, ongoing demonstration of insitu onboard detection in which the Earth Observing-1 spacecraft detects surface sulfur deposits that originate from underlying springs by distinguishing the sulfur from the ice-rich glacial background, a good analogue for the Europan surface. In this paper, we describe the process of developing the onboard classifier for detecting the presence of sulfur in a hyperspectral scene, including the use of a training/testing set that is not exhaustively labeled, i.e.not all true positives are marked, and the selection of 12, out of 242, Hyperion instrument wavelength bands to use in the onboard detector. This study aims to demonstrate the potential for future missions to capture short-lived science events, make decisions onboard, identify high priority data for downlink and perform onboard change detection. In the future, such capability could help maximize the science return of downlink bandwidth-limited missions, addressing a significant constraint in all deep-space missions.

  6. Modern freshwater microbialite analogues for ancient dendritic reef structures

    NASA Technical Reports Server (NTRS)

    Laval, B.; Cady, S. L.; Pollack, J. C.; McKay, C. P.; Bird, J. S.; Grotzinger, J. P.; Ford, D. C.; Bohm, H. R.

    2000-01-01

    Microbialites are organosedimentary structures that can be constructed by a variety of metabolically distinct taxa. Consequently, microbialite structures abound in the fossil record, although the exact nature of the biogeochemical processes that produced them is often unknown. One such class of ancient calcareous structures, Epiphyton and Girvanella, appear in great abundance during the Early Cambrian. Together with Archeocyathids, stromatolites and thrombolites, they formed major Cambrian reef belts. To a large extent, Middle to Late Cambrian reefs are similar to Precambrian reefs, with the exception that the latter, including terminal Proterozoic reefs, do not contain Epiphyton or Girvanella. Here we report the discovery in Pavilion Lake, British Columbia, Canada, of a distinctive assemblage of freshwater calcite microbialites, some of which display microstructures similar to the fabrics displayed by Epiphyton and Girvanella. The morphologies of the modern microbialites vary with depth, and dendritic microstructures of the deep water (> 30 m) mounds indicate that they may be modern analogues for the ancient calcareous structures. These microbialites thus provide an opportunity to study the biogeochemical interactions that produce fabrics similar to those of some enigmatic Early Cambrian reef structures.

  7. Cetalox and analogues: synthesis via acid-mediated polyene cyclizations.

    PubMed

    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. PMID:18618391

  8. The Disk and Planets of Solar Analogue τCeti

    NASA Astrophysics Data System (ADS)

    Lawler, S. M.; Francesco, J. Di; Kennedy, G.; Sibthorpe, B.; Booth, M.; Vandenbussche, B.; Matthews, B.; Tuomi, M.

    2015-01-01

    τ Ceti is a nearby, mature star very similar to our Sun, with a massive Kuiper belt analogue tep{Greavesetal2004} and possible multiplanet system tep{Tuomietal2013} that has been compared to our Solar System. We present infrared and submillimeter observations of the debris disk from the Herschel Space Observatory and the James Clerk Maxwell Telescope (JCMT). We find the best model of the disk is a wide annulus ranging from 5-55 AU, inclined from face-on by 30°. tet{Tuomietal2013} report five possible super-Earths tightly nestled inside 1.4 AU, and we model this planetary system and place dynamical constraints on the inner edge of the disk. We find that due to the low masses and fairly circular orbits of the planets, the disk could reach as close to the star as 1.5 AU, with some stable orbits even possible between the two outermost planets. The photometric modelling cannot rule out a disk inner edge as close to the star as 1 AU, though 5-10 AU produces a better fit to the data. Dynamical modelling shows that the 5 planet system is stable with the addition of a Saturn-mass planet on an orbit outside 5 AU, where the Tuomi et al. analysis would not have detected a planet of this mass.

  9. Conformational behavior of insect pheromones and analogues. Part II

    NASA Astrophysics Data System (ADS)

    Koča, Jaroslav; Carlsen, Per H. J.

    1992-04-01

    The conformational potential energy surface paths of the sex pheromone, Ipsenol, to the Bark Beetle, Ips typographus, and of a series of analogues have been elucidated using the program DAISY. The following structures were calculated: 2-methyl-6-methylene-7-octen-4-ol (Ipsenol, ( II)), 2-methyl-6-methylene-2,7-octadiene-4-ol acetate ( III), 2-methyl-6-methylene-3,7-octadien-2-ol ( IV), 2-methyl-6-methylene-1,7-octadien-3-ol ( V), 5-(3-furanyl)-2-methyl-1-penten-3-ol ( VI) and 1-(3-furanyl)-4-methyl-3-penten-2-ol ( VII). As a measure of the conformational flexibility of the molecules the flexibility coefficients, f, were determined. The f values for the molecules were determined to be: II, 0.145; III, 0.144; IV, 1.240; V, 0.133; VI, 0.825; and VII, 0.451. The molecular mechanics method was used for energy calculations in conjunction with DAISY. Low-energy conformations (conformational channels) together with energy barriers for conformational changes are presented.

  10. Synthesis and metabolism of pheromones and pheromone analogues

    SciTech Connect

    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.

  11. Solar analogues and solar twins in the HARPS archive

    NASA Astrophysics Data System (ADS)

    Datson, Juliet; Flynn, Chris; Portinari, Laura

    2014-03-01

    We present 63 solar analogues and twins for which high signal-to-noise ratio (S/N) archival data are available for the High Accuracy Radial velocity Planet Searcher (HARPS) high-resolution spectrograph at the European Southern Observatory (ESO) 3.6-m telescope. We perform a differential analysis of these stellar spectra relative to the solar spectrum, similar to previous work using ESO 2.2-m/fiber-fed extended range optical spectrograph (FEROS) data, and expand our analysis by introducing a new method to test the temperature and metallicity calibration of Sun-like stars in the Geneva-Copenhagen Survey (GCS). The HARPS data are significantly better than the FEROS data, with improvements in S/N, spectral resolution and number of lines we can analyse. We confirm the offsets to the photometric scale found in our FEROS study. We confirm three solar twins found in the FEROS data as solar twins in the HARPS data, as well as identify six new twins.

  12. Stability studies of a somatostatin analogue in biodegradable implants.

    PubMed

    Rothen-Weinhold, A; Besseghir, K; Vuaridel, E; Sublet, E; Oudry, N; Gurny, R

    1999-02-15

    In recent years, peptides and proteins have received much attention as drug candidates. For many polypeptides, particularly hormones, it is desirable to release the drug continuously at a controlled rate over a period of weeks or even months, and thus a controlled release system is needed. Polylactic acid (PLA) is a biocompatible and biodegradable material with wide utility for many applications, including the design of controlled release systems for pharmaceutical agents. Pharmaceutical development of these delivery systems presents new problems in the area of stability assessment, especially for peptide drugs. In this study, we aimed to investigate the influence of different steps, during the manufacturing of an implant, on peptide stability in the polymeric matrix. Polylactic acid implants containing vapreotide, a somatostatin analogue, were prepared by extrusion. The effects of time, extrusion and temperature on the peptide stability were studied. The influence of various gamma sterilization doses, as well as the conditions under which the implants were irradiated, were also investigated. Peptide stability in the polymeric matrix was evaluated at various temperatures and at various time intervals up to 9 months. PMID:10205641

  13. Laboratory simulation on EUV photolysis of inorganic interstellar ice analogues

    NASA Astrophysics Data System (ADS)

    Chen, Y. J.; Nuevo, M.; Yih, T. S.; Ip, W. H.; Wu, C. Y.; Fung, H. S.; Lee, Y. Y.; Cheng, C.; Tsai, H. R.

    In this report we focused on the formation of large organic molecules from most simple cosmic inorganic ice analogues consisting of H 2 O CO 2 and NH 3 irradiated by extreme ultraviolet EUV photons We employed an ultra-high vacuum chamber equipped with a closed- cycle helium cryostat to simulate the environment of the space beyond the atmosphere The necessary intense simulation of solar radiation is provided by a synchrotron beam in the wide 4 -- 20eV range at National Synchrotron Radiation Research Center in Hsinchu Taiwan After exposure to 10 20 photon dose the icy sample was warmed up to room temperature under dynamic vacuum then we deposited another icy sample as well as last one and EUV irradiated and warmed up to room temperature again and again for six times the KBr substrate was then removed in an environment filled with argon gas After removed into laboratory the sample was washed with distilled water and hydrolyzed in a standard procedure the residue was then analyzed by HPLC The result shows that we could clearly identify 8 amino acids such as glycine Banaline Bserine ldots etc which were left over in the residue Associated with those basic amino acids are several other large molecules that could be tentatively identified as basic organic materials evolved from photolysis process

  14. An analogue experimental model of depth fluctuations in lava lakes

    NASA Astrophysics Data System (ADS)

    Witham, Fred; Woods, Andrew W.; Gladstone, Charlotte

    2006-07-01

    Lava lakes, consisting of molten degassing lava in summit craters of active basaltic volcanoes, sometimes exhibit complex cycles of filling and emptying on time-scales of hours to weeks such as recorded at Pu’u’O’o in Hawaii and Oldoinyo Lengai in Tanzania. Here we report on a new series of analogue laboratory experiments of two-phase flow in a reservoir-conduit-lava lake system which spontaneously generates oscillations in the depth of liquid within the lake. During the recharge phase, gas supplied from a subsurface reservoir of degassing magma drives liquid magma up the conduit, causing the lake to fill. As the magmastatic pressure in the lake increases, the upward supply of magma, driven by the gas bubbles, falls. Eventually the upflow becomes unstable, and liquid drains downwards from the lake, driven by the magmastatic pressure of the overlying lake, suppressing the ascent of any more bubbles from the chamber. At a later stage, once the lake has drained sufficiently, the descent speed of liquid through the conduit decreases below the ascent speed of the bubbles, and the recharge cycle resumes. Application of a quantitative model of the experiments to the natural system is broadly consistent with field data.

  15. Resonance IR: a coherent multidimensional analogue of resonance Raman.

    PubMed

    Boyle, Erin S; Neff-Mallon, Nathan A; Handali, Jonathan D; Wright, John C

    2014-05-01

    This work demonstrates the use of triply resonant sum frequency (TRSF) spectroscopy as a "resonance IR" analogue to resonance Raman spectroscopy. TRSF is a four-wave-mixing process where three lasers with independent frequencies interact coherently with a sample to generate an output at their triple summation frequency. The first two lasers are in the infrared and result in two vibrational excitations, while the third laser is visible and induces a two-quantum anti-Stokes resonance Raman transition. The signal intensity grows when the laser frequencies are all in resonance with coupled vibrational and electronic states. The method therefore provides electronic enhancement of IR-active vibrational modes. These modes may be buried beneath solvent in the IR spectrum and also be Raman-inactive and therefore inaccessible by other techniques. The method is presented on the centrosymmetric complex copper phthalocyanine tetrasulfonate. In this study, the two vibrational frequencies were scanned across ring-breathing modes, while the visible frequency was left in resonance with the copper phthalocyanine tetrasulfonate Q band, resulting in a two-dimensional infrared plot that also reveals coupling between vibrational states. TRSF has the potential to be a very useful probe of structurally similar biological motifs such as hemes, as well as synthetic transition-metal complexes. PMID:24707979

  16. Encoding complexity within supramolecular analogues of frustrated magnets

    NASA Astrophysics Data System (ADS)

    Cairns, Andrew B.; Cliffe, Matthew J.; Paddison, Joseph A. M.; Daisenberger, Dominik; Tucker, Matthew G.; Coudert, François-Xavier; Goodwin, Andrew L.

    2016-05-01

    The solid phases of gold(I) and/or silver(I) cyanides are supramolecular assemblies of inorganic polymer chains in which the key structural degrees of freedom—namely, the relative vertical shifts of neighbouring chains—are mathematically equivalent to the phase angles of rotating planar (‘XY’) spins. Here, we show how the supramolecular interactions between chains can be tuned to mimic different magnetic interactions. In this way, the structures of gold(I) and/or silver(I) cyanides reflect the phase behaviour of triangular XY magnets. Complex magnetic states predicted for this family of magnets—including collective spin-vortices of relevance to data storage applications—are realized in the structural chemistry of these cyanide polymers. Our results demonstrate how chemically simple inorganic materials can behave as structural analogues of otherwise inaccessible ‘toy’ spin models and also how the theoretical understanding of those models allows control over collective (‘emergent’) phenomena in supramolecular systems.

  17. Hydrogen adsorption in thin films of Prussian blue analogue

    SciTech Connect

    Yang, Dali; Ding, Vivian; Luo, Junhua; Currier, Robert P; Obrey, Steve; Zhao, Yusheng

    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.

  18. Effects of melatonin and its analogues on neural stem cells.

    PubMed

    Chu, Jiaqi; Tu, Yalin; Chen, Jingkao; Tan, Dunxian; Liu, Xingguo; Pi, Rongbiao

    2016-01-15

    Neural stem cells (NSCs) are multipotent cells which are capable of self-replication and differentiation into neurons, astrocytes or oligodendrocytes in the central nervous system (CNS). NSCs are found in two main regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ). The recent discovery of NSCs in the adult mammalian brain has fostered a plethora of translational and preclinical studies to investigate novel approaches for the therapy of neurodegenerative diseases. Melatonin is the major secretory product synthesized and secreted by the pineal gland and shows both a wide distribution within phylogenetically distant organisms from bacteria to humans and a great functional versatility. Recently, accumulated experimental evidence showed that melatonin plays an important role in NSCs, including its proliferation, differentiation and survival, which are modulated by many factors including MAPK/ERK signaling pathway, histone acetylation, neurotrophic factors, transcription factors, and apoptotic genes. The purpose of this review is to summarize the beneficial effects of melatonin on NSCs and further to discuss the potential usage of melatonin and its derivatives or analogues in the treatment of CNS neurodegenerative diseases. PMID:26499395

  19. Computational study of Met-Car analogue heterofullerenes

    NASA Astrophysics Data System (ADS)

    Domingos, H. S.

    2006-06-01

    Structural, chemical and electronic properties of a number of Met-Car analogue heterofullerenes were investigated using a combination of ab initio and semi-empirical quantum mechanical calculations.Met-Car clusters of known structure and chemistry were studied together with some new hypothetical configurations. In particular, the stability of clusters of the form Y8C12 (Y = Al, S, Si, Ti, As, Bi, Sb, P, N, B, Sn, Sc, Cr, V), XY7C12 (X, Y = B, N, Si) and Y8Z12 (Y, Z = N, B, Si) were investigated based on computed binding energies, Mulliken charges, bond orders and ionization potentials. The results indicate that some novel clusters are due for observation. Clusters of this type are known to form the building blocks of new polymerized solids and may exhibit some novel dielectric, magnetic and superconducting properties. Isomers of D3d symmetry, which are possible global energy minima for Cr, V and Sc carbide clusters, were also identified.

  20. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues.

    PubMed

    Stompor, Monika; Żarowska, Barbara

    2016-01-01

    The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group-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. PMID:27187329

  1. Dimerization of truncated melittin analogues results in cytolytic peptides.

    PubMed Central

    Rivett, D E; Kirkpatrick, A; Hewish, D R; Reilly, W; Werkmeister, J A

    1996-01-01

    A synthetic peptide with the sequence of the first 20 residues of melittin and terminating with an additional cysteine amide was found to have cytolytic activity similar to that of melittin. It was apparent from MS data that the cysteine-terminating peptides had formed disulphide dimers. A peptide in which the thiol was blocked by iodoacetate showed no activity, whereas the same peptide blocked by acetamidomethyl showed activity marginally less haemolytic than that of melittin. Cytolytic activity of melittin analogues comprising the full 26 residues could be obtained with wide sequence permutations providing that a general amphipathic helical structure was preserved. In contrast, the activity of the dimers was dependent not only on retention of an amphipathic helix but also on certain individual residues and a free positive charge. A free N-terminus was essential for haemolytic activity. In addition, a lysine or arginine residue at position 7 and a proline at position 14 were found to be necessary for activity, although it was apparent that additional residues are important for retention of the full lytic potential. PMID:8687396

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

    PubMed

    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. PMID:23848498

  3. Short acting insulin analogues in intensive care unit patients

    PubMed Central

    Bilotta, Federico; Guerra, Carolina; Badenes, Rafael; Lolli, Simona; Rosa, Giovanni

    2014-01-01

    Blood glucose control in intensive care unit (ICU) patients, addressed to actively maintain blood glucose concentration within defined thresholds, is based on two major therapeutic interventions: to supply an adequate calories load and, when necessary, to continuously infuse insulin titrated to patients needs: intensive insulin therapy (IIT). Short acting insulin analogues (SAIA) have been synthesized to improve the chronic treatment of patients with diabetes but, because of the pharmacokinetic characteristics that include shorter on-set and off-set, they can be effectively used also in ICU patients and have the potential to be associated with a more limited risk of inducing episodes of iatrogenic hypoglycemia. Medical therapies carry an intrinsic risk for collateral effects; this can be more harmful in patients with unstable clinical conditions like ICU patients. To minimize these risks, the use of short acting drugs in ICU patients have gained a progressively larger room in ICU and now pharmaceutical companies and researchers design drugs dedicated to this subset of medical practice. In this article we report the rationale of using short acting drugs in ICU patients (i.e., sedation and treatment of arterial hypertension) and we also describe SAIA and their therapeutic use in ICU with the potential to minimize iatrogenic hypoglycemia related to IIT. The pharmacodynamic and pharmachokinetic characteristics of SAIA will be also discussed. PMID:24936244

  4. Digitally Programmable Analogue Circuits for Sensor Conditioning Systems

    PubMed Central

    Zatorre, Guillermo; Medrano, Nicolás; Sanz, María Teresa; Aldea, Concepción; Calvo, Belén; Celma, Santiago

    2009-01-01

    This work presents two current-mode integrated circuits designed for sensor signal preprocessing in embedded systems. The proposed circuits have been designed to provide good signal transfer and fulfill their function, while minimizing the load effects due to building complex conditioning architectures. The processing architecture based on the proposed building blocks can be reconfigured through digital programmability. Thus, sensor useful range can be expanded, changes in the sensor operation can be compensated for and furthermore, undesirable effects such as device mismatching and undesired physical magnitudes sensor sensibilities are reduced. The circuits were integrated using a 0.35 μm standard CMOS process. Experimental measurements, load effects and a study of two different tuning strategies are presented. From these results, system performance is tested in an application which entails extending the linear range of a magneto-resistive sensor. Circuit area, average power consumption and programmability features allow these circuits to be included in embedded sensing systems as a part of the analogue conditioning components. PMID:22412331

  5. Synthesis and Properties of Group IV Graphane Analogues

    NASA Astrophysics Data System (ADS)

    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.

  6. Mechanism of cis-prenyltransferase reaction probed by substrate analogues

    SciTech Connect

    Lu, Yen-Pin; Liu, Hon-Ge; Teng, Kuo-Hsun; Liang, Po-Huang

    2010-10-01

    Research highlights: {yields} The extremely slow trans-OPPS reaction using 2-Fluoro-FPP supports the sequential mechanism with the carbocation intermediate. {yields} The similar UPPS reaction rate under single turnover supports the concerted mechanism, without the carbocation intermediate. {yields} The secondary kinetic isotope effect also supports associate transition state for UPPS reaction, without the carbocation intermediate. -- Abstract: Undecaprenyl pyrophosphate synthase (UPPS) is a cis-type prenyltransferases which catalyzes condensation reactions of farnesyl diphosphate (FPP) with eight isopentenyl pyrophosphate (IPP) units to generate C{sub 55} product. In this study, we used two analogues of FPP, 2-fluoro-FPP and [1,1-{sup 2}H{sub 2}]FPP, to probe the reaction mechanism of Escherichia coli UPPS. The reaction rate of 2-fluoro-FPP with IPP under single-turnover condition is similar to that of FPP, consistent with the mechanism without forming a farnesyl carbocation intermediate. Moreover, the deuterium secondary KIE of 0.985 {+-} 0.022 measured for UPPS reaction using [1,1-{sup 2}H{sub 2}]FPP supports the associative transition state. Unlike the sequential mechanism used by trans-prenyltransferases, our data demonstrate E. coli UPPS utilizes the concerted mechanism.

  7. Synthesis and Cytotoxicity Studies of Titanocene C Analogues

    PubMed Central

    Hogan, Megan; Claffey, James; Fitzpatrick, Eoin; Hickey, Thomas; Pampillón, Clara; Tacke, Matthias

    2008-01-01

    From the carbolithiation of 6-N,N-dimethylamino fulvene (3) and 2,4[bis(N,N-dimethylamino)methyl]-N-methylpyrrolyl lithium (2a), N-(N′,N′-dimethylaminomethyl)benzimidazolyl lithium (2b), or p-(N,N-dimethylamino)methylphenyl lithium (2c), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4' resulting in N,N-dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against a pig kidney epithelial cell line (LLC-PK), the IC50 values obtained were of 23, and 52  μM for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene in this paper, 5c with an IC50 value of 13 μM, was found to be approximately two times less cytotoxic than its analogue Titanocene C (IC50=5.5 μM) and almost four times less cytotoxic than cisplatin, which showed an IC50 value of 3.3 μM when tested on the LLC-PK cell line. PMID:18274663

  8. Synthesis and biological evaluations of a series of thaxtomin analogues.

    PubMed

    Zhang, Hongbo; Wang, Qingpeng; Ning, Xin; Hang, Hang; Ma, Jing; Yang, Xiande; Lu, Xiaolin; Zhang, Jiabao; Li, Yonghong; Niu, Congwei; Song, Haoran; Wang, Xin; Wang, Peng George

    2015-04-15

    Thaxtomins are a unique family of phytotoxins with unique 4-nitroindole and diketopiperazine fragments possessing potential herbicidal activities. This work presents the total synthesis of natural product thaxtomin C and its analogues. The extensive structure-activity relationship study screens four effective compounds, including thaxtomin A and thaxtomin C. It is indicated that 4-nitro indole fragment is essential for phytotoxicity, while benzyl and m-hydroxybenzyl substituents on the diketopiperazine ring are favorable for the efficacy. The N-methylations on indole and diketopiperazine show weak influence on the herbicidal activities. The four selected compounds show effective herbicidal activities against Brassica campestris, Amaranthus retroflexus, and Abutilon theophrasti, which are comparable or better than dichlobenil, even at a dosage of 187.5 g ha(-1). Moreover, these four compounds show good crop-selective properties to different crops and exhibit moderate protoporphyrinogen oxidase (PPO) enzyme inhibition. The antifungal results indicate that thaxtomin C displays inhibition to a wide range of fungi. PMID:25804187

  9. Synthesis and Biological Evaluation of Lactimidomycin and Its Analogues.

    PubMed

    Larsen, Brian J; Sun, Zhankui; Lachacz, Eric; Khomutnyk, Yaroslav; Soellner, Matthew B; Nagorny, Pavel

    2015-12-21

    The studies culminating in the total synthesis of the glutarimide-containing eukaryote translation elongation inhibitor lactimidomycin are described. The optimized synthetic route features a Zn(II)-mediated intramolecular Horner-Wadsworth-Emmons (HWE) reaction resulting in a highly stereoselective formation of the strained 12-membered macrolactone of lactimidomycin on a 423 mg scale. The presence of the E,Z-diene functionality was found to be key for effective macrocyclizations as a complete removal of these unsaturation units resulted in exclusive formation of the dimer rather than monocyclic enoate. The synthetic route features a late-stage installation of the glutarimide functionality via an asymmetric catalytic Mukaiyama aldol reaction, which allows for a quick generation of lactimidomycin homolog 55 containing two additional carbons in the glutarimide side chain. Similar to lactimidomycin, this analog was found to possess cytotoxicity against MDA-MB-231 breast cancer cells (GI50 =1-3 μM) using in vitro 2D and 3D assays. Although lactimidomycin was found to be the most potent compound in terms of anticancer activity, 55 as well as truncated analogues 50-52 lacking the glutarimide side-chain were found to be significantly less toxic against human mammary epithelial cells. PMID:26577990

  10. On the protection of "protected areas".

    PubMed

    Joppa, Lucas N; Loarie, Scott R; Pimm, Stuart L

    2008-05-01

    Tropical moist forests contain the majority of terrestrial species. Human actions destroy between 1 and 2 million km(2) of such forests per decade, with concomitant carbon release into the atmosphere. Within these forests, protected areas are the principle defense against forest loss and species extinctions. Four regions-the Amazon, Congo, South American Atlantic Coast, and West Africa-once constituted about half the world's tropical moist forest. We measure forest cover at progressively larger distances inside and outside of protected areas within these four regions, using datasets on protected areas and land-cover. We find important geographical differences. In the Amazon and Congo, protected areas are generally large and retain high levels of forest cover, as do their surroundings. These areas are protected de facto by being inaccessible and will likely remain protected if they continue to be so. Deciding whether they are also protected de jure-that is, whether effective laws also protect them-is statistically difficult, for there are few controls. In contrast, protected areas in the Atlantic Coast forest and West Africa show sharp boundaries in forest cover at their edges. This effective protection of forest cover is partially offset by their very small size: little area is deep inside protected area boundaries. Lands outside protected areas in the Atlantic Coast forest are unusually fragmented. Finally, we ask whether global databases on protected areas are biased toward highly protected areas and ignore "paper parks." Analysis of a Brazilian database does not support this presumption. PMID:18451028

  11. Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro

    NASA Astrophysics Data System (ADS)

    Dechristopher, Brian A.; Loy, Brian A.; Marsden, Matthew D.; Schrier, Adam J.; Zack, Jerome A.; Wender, Paul A.

    2012-09-01

    Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the step-economical syntheses of seven members of a new family of designed bryostatin analogues using a highly convergent Prins-macrocyclization strategy. We also demonstrate for the first time that such analogues effectively induce latent HIV activation in vitro with potencies similar to or better than bryostatin. Significantly, these analogues are up to 1,000-fold more potent in inducing latent HIV expression than prostratin, the current clinical candidate for latent virus induction. This study provides the first demonstration that designed, synthetically accessible bryostatin analogues could serve as superior candidates for the eradication of HIV/AIDS through induction of latent viral reservoirs in conjunction with current antiretroviral therapy.

  12. A Hypersaline Spring Analogue in Manitoba, Canada for Potential Ancient Spring Deposits on Mars

    NASA Astrophysics Data System (ADS)

    Berard, G.; Applin, D.; Stromberg, J.; Sharma, R.; Mann, P.; Grasby, S.; Bezys, R.; Horgan, B.; Londry, K.; Rice, M.; Last, B.; Last, F.; Badiou, P.; Goldsborough, G.; Bell, J. F.

    2012-03-01

    This study explores the characteristics of a spring complex, East German Creek, Manitoba (EGC), as a terrestrial analogue for similar environments on Mars. We focus on EGC's mineral precipitation patterns and potential for biosignature preservation.

  13. 20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

    PubMed

    Liu, Junhua; Wang, Xu; Liu, Peng; Deng, Rongxin; Lei, Min; Chen, Wantao; Hu, Lihong

    2013-07-15

    Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells. PMID:23683834

  14. Characterization of photophysical and base-mimicking properties of a novel fluorescent adenine analogue in DNA

    PubMed Central

    Dierckx, Anke; Dinér, Peter; El-Sagheer, Afaf H.; Kumar, Joshi Dhruval; Brown, Tom; Grøtli, Morten; Wilhelmsson, L. Marcus

    2011-01-01

    To increase the diversity of fluorescent base analogues with improved properties, we here present the straightforward click-chemistry-based synthesis of a novel fluorescent adenine-analogue triazole adenine (AT) and its photophysical characterization inside DNA. AT shows promising properties compared to the widely used adenine analogue 2-aminopurine. Quantum yields reach >20% and >5% in single- and double-stranded DNA, respectively, and show dependence on neighbouring bases. Moreover, AT shows only a minor destabilization of DNA duplexes, comparable to 2-aminopurine, and circular dichroism investigations suggest that AT only causes minimal structural perturbations to normal B-DNA. Furthermore, we find that AT shows favourable base-pairing properties with thymine and more surprisingly also with normal adenine. In conclusion, AT shows strong potential as a new fluorescent adenine analogue for monitoring changes within its microenvironment in DNA. PMID:21278417

  15. [Luliberin analogues exhibiting a cytotoxic effect on tumor cells in vitro].

    PubMed

    Burov, S V; Iablokova, T V; Dorosh, M Iu; Shkarubskaia, Z P; Blank, M; Epshteĭn, N; Fridkin, M

    2006-01-01

    Luliberin analogues modified at the N-terminus were synthesized to search for drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A synthetic scheme effective in the preparation of analogues containing fatty acid residues was proposed. The cytotoxic effect of the peptides was studied on a number of cell lines of human tumors in vitro. The dependence of the antitumor effect on the length of peptide chain, amino acid sequence, and structure of the N-terminal group was demonstrated. Modification with palmitic acid was found to result in highly active compounds in the case of analogues containing more than ten aa, whereas modifications with lauric, caproic, or trimethylacetic acid led to compounds with significantly lower activities. Analogues of luliberin containing a palmitic acid residue and effectively inhibiting the growth of tumor cells in vitro were synthesized. PMID:17042263

  16. Study of a CCP RF Dusty Plasma for the Production of Titan's Aerosols Analogues

    SciTech Connect

    Alcouffe, G.; Cernogora, G.; Ouni, F.; Correia, J. J.; Cavarroc, M.; Boufendi, L.; Szopa, C.

    2008-09-07

    The CCP-RF discharge PAMPRE experiment produces analogues of Titan's aerosols. Here are presented the plasma characteristics as a function of gas mixtures and dust formation. Electronic density, optical emission spectroscopy, and self-bias voltage measurements are presented.

  17. Martian Analogue Samples, Their Spectroscopic Biosignatures, and Degradation by the Cosmic Radiation Environment

    NASA Astrophysics Data System (ADS)

    Dartnell, L. R.

    2016-05-01

    Here we discuss the use of Raman and FTIR spectroscopy for the detection and characterisation of biosignatures in martian analogue samples, and their degradation by the cosmic ray environment in the martian near-subsurface.

  18. Synthesis and antiaggregant properties of Stabilized analogues of polyunsaturated fatty acid metabolites.

    PubMed

    Hachem, Ali; Roussel, Patrick; Ménager, Eric; Grée, Danielle; Le Floc'h, Yves; Grée, René; Cerletti, Chiara; Rolland, Yves; Simonet, Serge; Verbeuren, Tony

    2002-09-16

    New aromatic and heteroaromatic analogues of polyunsaturated fatty acid metabolites have been prepared using short and versatile strategies. Preliminary studies of their activity as inhibitors of platelet aggregation are reported. PMID:12182849

  19. Structure-activity studies on the potentiation of benzodiazepine receptor binding by ethylenediamine analogues and derivatives.

    PubMed Central

    Morgan, P. F.; Stone, T. W.

    1983-01-01

    The effect of ethylenediamine analogues on in vitro binding of [3H]-diazepam to crude cerebral cortical synaptosomal membranes in the rat was studied. Ethylenediamine significantly increased [3H]-diazepam binding to a maximum potentiation of 154% control (EC50 = 1.8 X 10(-4) M) and was the most active compound studied in terms of both potency and the maximum potentiation observed. Potentiation of [3H]-diazepam binding by ethylenediamine analogues is dependent on carbon-chain length, appears to require two terminal amino groups, and is not observed in the rigid analogues studied. Potentiation of [3H]-diazepam binding by ethylenediamine analogues is mediated largely by a change in receptor number and not receptor affinity. Results are discussed in terms of the possible nature of the ethylenediamine binding site. PMID:6317124

  20. Self-assembly of coordination molecular baskets as inorganic analogues of cyclotriveratrylenes (CTV).

    PubMed

    Li, Sheng-Hui; Huang, Hai-Ping; Yu, Shu-Yan; Li, Yi-Zhi; Huang, Hui; Sei, Yoshihisa; Yamaguchi, Kentaro

    2005-07-21

    A [3 + 3] modular self-assembly gives rise to the formation of basket-shaped, crown ether-functionalized, nano-sized trimetallo-macrocycles, which function as structural analogues of cyclotriveratrylenes (CTV). PMID:15995740

  1. Quantitative Assessment of Protein Interaction with Methyl-Lysine Analogues by Hybrid Computational and Experimental Approaches

    PubMed Central

    2011-01-01

    In cases where binding ligands of proteins are not easily available, structural analogues are often used. For example, in the analysis of proteins recognizing different methyl-lysine residues in histones, methyl-lysine analogues based on methyl-amino-alkylated cysteine residues have been introduced. Whether these are close enough to justify quantitative interpretation of binding experiments is however questionable. To systematically address this issue, we developed, applied, and assessed a hybrid computational/experimental approach that extracts the binding free energy difference between the native ligand (methyl-lysine) and the analogue (methyl-amino-alkylated cysteine) from a thermodynamic cycle. Our results indicate that measured and calculated binding differences are in very good agreement and therefore allow the correction of measured affinities of the analogues. We suggest that quantitative binding parameters for defined ligands in general can be derived by this method with remarkable accuracy. PMID:21991995

  2. Bonneville Basin Analogues for Large Lake Processes & Chronologies of Geomorphic Development on Mars

    NASA Astrophysics Data System (ADS)

    Nicoll, K.; Chan, M. A.; Parker, T. J.; Jewell, P. W.; Komatsu, G.; Okubo, C. H.

    2009-03-01

    We present an inventory of geomorphic analogues for Lake Bonneville and Mars, with focus on potential standing-water features. The goal is to understand water as a geomorphic agent at a variety of temporal and spatial scales.

  3. Restoration of estuarine wetlands via "managed realignment": the use of natural analogues.

    NASA Astrophysics Data System (ADS)

    Cundy, A.

    2003-04-01

    A proposed management response to rising sea-levels for low-relief coastal areas is the managed-realignment approach, where existing coastal defences are repositioned landward, and protective wetlands allowed to develop on the abandoned land. This technique has been applied with varying degrees of success at a number of coastal sites, and, in the U.K. at least, its use is increasing as coastal management authorities move away from hard engineering approaches towards more "natural" coastal and floodplain management. Studies of the response of low-lying coastal areas to the managed-realignment approach, and the subsequent restoration of intertidal wetlands, have tended to rely on short-term (< 5 years) studies of erosion and accretion, vegetation change, and changes in sediment chemistry. While the short-term response to breaching is important, it is essential to complement these studies with an understanding of the medium-term (decadal) response of low-lying coasts to sudden inundation to allow effective site selection and management. This medium-term response may be assessed using sedimentary and geomorphological studies at coastal sites which have been historically breached and flooded, which provide natural analogues for the managed realignment process. This paper illustrates this approach using data from two contrasting sites in southern England (Pagham Harbour and part of the Hamble estuary), which were flooded in the early 20th century following breaching of flood defences. Sediments at both sites retain a record of environmental change following marine inundation, and sedimentary studies, combined with documentary evidence, have been used to examine post-breaching marsh stability, variations in sediment accumulation rate, and vegetation colonisation and dieback over varying timescales. Historically-breached sites such as Pagham Harbour and the Hamble estuary are relatively common around European coasts, and these provide important natural laboratories within

  4. N-terminally glutamate-substituted analogue of gramicidin A as protonophore and selective mitochondrial uncoupler.

    PubMed

    Sorochkina, Alexandra I; Plotnikov, Egor Y; Rokitskaya, Tatyana I; Kovalchuk, Sergei I; Kotova, Elena A; Sychev, Sergei V; Zorov, Dmitry B; Antonenko, Yuri N

    2012-01-01

    Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA). The modified peptide [Glu1]gA exhibited high uncoupling activity in isolated mitochondria, in particular, abolishing membrane potential at the inner mitochondrial membrane with the same or even larger efficacy as gA. With mitochondria in cell culture, the depolarizing activity of [Glu1]gA was observed at concentrations by an order of magnitude lower than those of gA. On the contrary, [Glu1]gA was much less potent in forming proton channels in planar lipid bilayers than gA. Remarkably, at uncoupling concentrations, [Glu1]gA did not alter cell morphology and was nontoxic in MTT test, in contrast to gA showing high toxicity. The difference in the behavior of [Glu1]gA and gA in natural and artificial membranes could be ascribed to increased capability of [Glu1]gA to permeate through membranes and/or redistribute between different membranes. Based on the protective role of mild uncoupling, [Glu1]gA and some other proton-conducting gA analogues may be considered as prototypes of prospective therapeutic agents. PMID:22911866

  5. N-Terminally Glutamate-Substituted Analogue of Gramicidin A as Protonophore and Selective Mitochondrial Uncoupler

    PubMed Central

    Sorochkina, Alexandra I.; Plotnikov, Egor Y.; Rokitskaya, Tatyana I.; Kovalchuk, Sergei I.; Kotova, Elena A.; Sychev, Sergei V.; Zorov, Dmitry B.; Antonenko, Yuri N.

    2012-01-01

    Limited uncoupling of oxidative phosphorylation could be beneficial for cells by preventing excessive generation of reactive oxygen species. Typical uncouplers are weak organic acids capable of permeating across membranes with a narrow gap between efficacy and toxicity. Aimed at designing a nontoxic uncoupler, the protonatable amino acid residue Glu was substituted for Val at the N-terminus of the pentadecapeptide gramicidin A (gA). The modified peptide [Glu1]gA exhibited high uncoupling activity in isolated mitochondria, in particular, abolishing membrane potential at the inner mitochondrial membrane with the same or even larger efficacy as gA. With mitochondria in cell culture, the depolarizing activity of [Glu1]gA was observed at concentrations by an order of magnitude lower than those of gA. On the contrary, [Glu1]gA was much less potent in forming proton channels in planar lipid bilayers than gA. Remarkably, at uncoupling concentrations, [Glu1]gA did not alter cell morphology and was nontoxic in MTT test, in contrast to gA showing high toxicity. The difference in the behavior of [Glu1]gA and gA in natural and artificial membranes could be ascribed to increased capability of [Glu1]gA to permeate through membranes and/or redistribute between different membranes. Based on the protective role of mild uncoupling, [Glu1]gA and some other proton-conducting gA analogues may be considered as prototypes of prospective therapeutic agents. PMID:22911866

  6. Chemical modification of aldehyde dehydrogenase by a vinyl ketone analogue of an insect pheromone.

    PubMed

    Blatter, E E; Tasayco, M L; Prestwich, G; Pietruszko, R

    1990-12-01

    A major component of the sex pheromone from the tobacco budworm moth Heliothis virescens is a C16 straight-chain aldehyde with a single unsaturation at the eleventh position. The sex pheromones are inactivated when metabolized to their corresponding acids by insect aldehyde dehydrogenase. During this investigation it was demonstrated that the C16 aldehyde is a good substrate for human aldehyde dehydrogenase (EC 1.2.1.3) isoenzymes E1 and E2 with Km and Kcat. values at pH 7.0 of 2 microM and 0.4 mumol of NADH/min per mg and of 0.6 microM and 0.24 mumol of NADH/min per mg respectively. A vinyl ketone analogue of the pheromone inhibited insect pheromone metabolism; it also inactivated human aldehyde dehydrogenase. Total inactivation of both isoenzymes was achieved at stoichiometric (equal or less than the subunit number) concentrations of vinyl ketone, incorporating 2.1-2.6 molecules/molecule of enzyme. Substrate protection was observed in the presence of the parent aldehyde and 5'-AMP. Peptide maps of tryptic digests of the E2 isoenzyme modified with 3H-labelled vinyl ketone showed that incorporation occurred into a single peptide peak. The labelled peptide of E2 isoenzyme was further purified on h.p.l.c. and sequenced. The label was incorporated into cysteine-302 in the primary structure of E2 isoenzyme, thus indicating that cysteine-302 is located in the aldehyde substrate area of the active site of aldehyde dehydrogenase. Affinity labelling of aldehyde dehydrogenase with vinyl ketones may prove to be of general utility in biochemical studies of these enzymes. PMID:2268265

  7. The placental analogue and the pattern of sexual reproduction in the cheilostome bryozoan Bicellariella ciliata (Gymnolaemata)

    PubMed Central

    2012-01-01

    Background Matrotrophy or extraembryonic nutrition – transfer of nutrients from mother to embryo during gestation – is well known and thoroughly studied among vertebrates, but still poorly understood in invertebrates. The current paper focuses on the anatomy and ultrastructure of the oogenesis and placentotrophy as well as formation of the brood chamber (ovicell) in the cheilostome bryozoan Bicellariella ciliata (Linnaeus, 1758). Our research aimed to combine these aspects of the sexual reproduction into an integral picture, highlighting the role of the primitive placenta-like system in the evolution of bryozoan reproductive patterns. Results Follicular and nutrimentary provisioning of the oocyte occur during oogenesis. Small macrolecithal oocytes are produced, and embryos are nourished in the ovicell via a simple placental analogue (embryophore). Every brooding episode is accompanied by the hypertrophy of the embryophore, which collapses after larval release. Nutrients are released and uptaken by exocytosis (embryophore) and endocytosis (embryo). Embryos lack specialized area for nutrient uptake, which occurs through the whole epidermal surface. The volume increase between the ripe oocyte and the larva is ca. 10-fold. Conclusions The ovicell is a complex organ (not a special polymorph as often thought) consisting of an ooecium (protective capsule) and an ooecial vesicle (plugging the entrance to the brooding cavity) that develop from the distal and the fertile zooid correspondingly. Combination of macrolecithal oogenesis and extraembryonic nutrition allows attributing B. ciliata to species with reproductive pattern IV. However, since its oocytes are small, this species represents a previously undescribed variant of this pattern, which appears to represent a transitional state from the insipient matrotrophy (with large macrolecithal eggs) to substantial one (with small microlecithal ones). Altogether, our results substantially added and corrected the data

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

    NASA Astrophysics Data System (ADS)

    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 < 0.5 × 10-2 s-1, while other modelling clays demonstrated elastic-dominant power-law relationships. Based on these results, the elastic-dominant modelling clay is recommended as an analogue for basement cratons. Inherently cohesive synthetic sands produce fine-detailed fault and fracture patterns, and developed thrust, strike-slip, and extensional faults in simple 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.

  9. Synthesis and neurite growth evaluation of new analogues of honokiol, a neolignan with potent neurotrophic activity.

    PubMed

    Praveen Kumar, Vemula; Gajendra Reddy, R; Vo, Duc Duy; Chakravarty, Sumana; Chandrasekhar, Srivari; Grée, René

    2012-02-01

    A versatile synthetic route is reported towards the preparation of new analogues for potent neurotrophic agent biaryl-type lignan honokiol. A focused 24-membered library of derivatives containing five different groups at 5'-position of honokiol has been prepared in fair to good overall yields. Compared to the natural product, or to analogues with a short alkyl chain in this position, these new derivatives have lost most of the neurotrophic activity. PMID:22209461

  10. Hamamelitannin Analogues that Modulate Quorum Sensing as Potentiators of Antibiotics against Staphylococcus aureus.

    PubMed

    Vermote, Arno; Brackman, Gilles; Risseeuw, Martijn D P; Vanhoutte, Bieke; Cos, Paul; Van Hecke, Kristof; Breyne, Koen; Meyer, Evelyne; Coenye, Tom; Van Calenbergh, Serge

    2016-05-23

    The modulation of bacterial communication to potentiate the effect of existing antimicrobial drugs is a promising alternative to the development of novel antibiotics. In the present study, we synthesized 58 analogues of hamamelitannin (HAM), a quorum sensing inhibitor and antimicrobial potentiator. These efforts resulted in the identification of an analogue that increases the susceptibility of Staphylococcus aureus towards antibiotics in vitro, in Caenorhabditis elegans, and in a mouse mammary gland infection model, without showing cytotoxicity. PMID:27095479

  11. Chiral Vinylphosphonate and Phosphonate Analogues of the Immunosuppressive Agent FTY720

    PubMed Central

    Lu, Xuequan; Sun, Chaode; Valentine, William J.; E, Shuyu; Liu, Jianxiong; Tigyi, Gabor; Bittman, Robert

    2009-01-01

    The first enantioselective synthesis of chiral isosteric phosphonate analogues of FTY720 is described. One of these analogues, FTY720-(E)-vinylphosphonate (S)-5, but not its R enantiomer, elicited a potent anti-apoptotic effect in intestinal epithelial cells, suggesting that it exerts its action via the enantioselective activation of a receptor. (S)-5 failed to activate the sphingosine 1-phosphate type 1 (S1P1) receptor. PMID:19296586

  12. Quinlobelane: A water-soluble lobelane analogue and inhibitor of VMAT2

    PubMed Central

    Vartak, Ashish P.; Deaciuc, A. Gabriela; Dwoskin, Linda P.; Crooks, Peter A.

    2013-01-01

    Replacing the phenyl groups in the structure of the VMAT2 inhibitor, lobelane with either pyridyl, quinolyl or indolyl groups affords novel analogues with improved water solubility. The synthetic methodologies reported herein also underscore the paucity of hydrogenation methods that offer selectivity in the synthesis of the different classes of heteroaromatic lobelane analogues. The quinolyl group was the only replacement for the phenyl group in lobelane that retained VMAT2 inhibition. PMID:20494575

  13. Evaluation of the Interaction between Phosphohistidine Analogues and Phosphotyrosine Binding Domains

    PubMed Central

    McAllister, Tom E; Horner, Katherine A; Webb, Michael E

    2014-01-01

    We have investigated the interaction of peptides containing phosphohistidine analogues and their homologues with the prototypical phosphotyrosine binding SH2 domain from the eukaryotic cell signalling protein Grb2 by using a combination of isothermal titration calorimetry and a fluorescence anisotropy competition assay. These investigations demonstrated that the triazole class of phosphohistidine analogues are capable of binding too, suggesting that phosphohistidine could potentially be detected by this class of proteins in vivo. PMID:24771713

  14. Synthesis of chamaecypanone C analogues from in situ-generated cyclopentadienones and their biological evaluation.

    PubMed

    Dong, Suwei; Qin, Tian; Hamel, Ernest; Beutler, John A; Porco, John A

    2012-12-01

    A rhodium-catalyzed dehydrogenation protocol for the conversion of 3,5-diarylcyclopentenones to the corresponding 2,4-diarylcyclopentadienones has been developed. With this protocol, analogues of the cytotoxic agent chamaecypanone C have been synthesized via Diels-Alder cycloaddition between the cyclopentadienones and in situ-generated o-quinols. Biological evaluation of these analogues revealed a compound with higher activity as a microtubule inhibitor and cytotoxic agent in comparison with the parent structure. PMID:23110297

  15. Synthesis of Chamaecypanone C Analogues from in situ-Generated Cyclopentadienones and their Biological Evaluation

    PubMed Central

    Dong, Suwei; Qin, Tian; Hamel, Ernest; Beutler, John A.; Porco, John A.

    2012-01-01

    A rhodium-catalyzed dehydrogenation protocol has been developed for conversion of 3,5-diarylcyclopentenones to the corresponding 2,4-diarylcyclopentadienones. Using this protocol, analogues of the cytotoxic agent chamaecypanone C have been synthesized via Diels-Alder cycloaddition between the cyclopentadienones and in situ-generated ortho-quinols. Biological evaluation of these analogues revealed a compound with higher activity as a microtubule inhibitor and cytotoxic agent in comparison with the parent structure. PMID:23110297

  16. Insulin analogues in pregnancy and specific congenital anomalies: a literature review.

    PubMed

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

    2016-05-01

    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. We performed a literature search for studies of pregnant 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 in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26431249

  17. gamma-Substituted bis(pivaloyloxymethyl)ester analogues of fosmidomycin and FR900098.

    PubMed

    Kurz, Thomas; Behrendt, Christoph; Pein, Miriam; Kaula, Uwe; Bergmann, Bärbel; Walter, Rolf D

    2007-12-01

    The synthesis and in-vitro antimalarial activity of gamma-substituted bis(pivaloyloxymethyl)ester analogues of the drug candidate fosmidomycin have been investigated. In contrast to the high antimalarial activity of alpha-aryl substituted fosmidomycin analogues like alpha-phenylfosmidomycin, gamma-substituted derivatives display only weak to moderate activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. PMID:17994605

  18. Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.

    PubMed

    Balasubramanian, Ranganathan; Raghavan, Bhooma; Begaye, Adrian; Sackett, Dan L; Fecik, Robert A

    2009-01-22

    A stereoselective total synthesis of the cytotoxic natural products tubulysin U, tubulysin V, and its unnatural epimer epi-tubulysin V, is reported. Simplified analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N-Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological evaluation of these natural products and analogues provided key information with regard to structural and stereochemical requirements for antiproliferative activity and tubulin polymerization inhibition. PMID:19102699

  19. Protective effects of veskamide, enferamide, becatamide, and oretamide on H2O2-induced apoptosis of PC-12 cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Synthesis of piperlongumine analogues and discovery of nuclear factor erythroid 2-related factor 2 (Nrf2) activators as potential neuroprotective agents.

    PubMed

    Peng, Shoujiao; Zhang, Baoxin; Meng, Xianke; Yao, Juan; Fang, Jianguo

    2015-07-01

    The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells. PMID:26079183

  1. Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review.

    PubMed

    Chen, Da; Kannan, Kurunthachalam; Tan, Hongli; Zheng, Zhengui; Feng, Yong-Lai; Wu, Yan; Widelka, Margaret

    2016-06-01

    Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity. PMID:27143250

  2. Computer-aided rational design of novel EBF analogues with an aromatic ring.

    PubMed

    Wang, Shanshan; Sun, Yufeng; Du, Shaoqing; Qin, Yaoguo; Duan, Hongxia; Yang, Xinling

    2016-06-01

    Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-β-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized π-π and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1-D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. Graphical abstract The design strategy of new EBF analogues based on the OBP7 structure. PMID:27251400

  3. Synthesis, cytotoxicity and inhibition of NO production of ivangustin enantiomer analogues.

    PubMed

    Qin, Xiang-Yang; Chen, Bing-Yang; Fu, Jian-Jun; Shan, Lei; Lei, Xiao-Guang; Zhang, Wei-Dong

    2015-09-18

    The eight novel ivangustin enantiomer analogues possessing α-methylene-γ-butyrolactone moiety have been synthesized using (4S6R, 4S6S)-4-tert-butyldimethylsilyloxy-6-methylcyclohex-2-en-1-one (1) as starting material. These transformations were mainly carried out by aldol condensation reaction and one-pot annelation procedure. The stereochemistry of these synthesized analogues was determined by NOE analysis. Their cytoxicity was evaluated against the human cancer cell lines HCT-116 (colon), HL-60 (leukemia), QGY-7701 (liver), SMMC-7721 (liver), A549 (lung), MCF-7 (breast). The results showed that these analogues were more selective against the cell lines HL-60 and QGY-7701. Analogue 17 exhibited potent cytotoxicity and high selectivity toward HL-60 cell line with IC50 value of 1.02 μM, which suggested that it might be a promising anti-cancer lead compound. The inhibitory activities against NO production and the cytotoxicities in RAW 264.7 macrophages were determined at the same time. All of the analogues significantly inhibited the NO production with IC50 value in the range of 3.44-6.99 μM. Analogues 17, 22, 23 and 7 showed higher cytotoxicities, indicated their inhibitory activities against NO production may be influenced by the cytotoxicities. PMID:26280922

  4. Sensitivity of groundwater recharge using climatic analogues and HYDRUS-1D

    NASA Astrophysics Data System (ADS)

    Leterme, B.; Mallants, D.; Jacques, D.

    2012-08-01

    The sensitivity of groundwater recharge to different climate conditions was simulated using the approach of climatic analogue stations, i.e. stations presently experiencing climatic conditions corresponding to a possible future climate state. The study was conducted in the context of a safety assessment of a future near-surface disposal facility for low and intermediate level short-lived radioactive waste in Belgium; this includes estimation of groundwater recharge for the next millennia. Groundwater recharge was simulated using the Richards based soil water balance model HYDRUS-1D and meteorological time series from analogue stations. This study used four analogue stations for a warmer subtropical climate with changes of average annual precipitation and potential evapotranspiration from -42% to +5% and from +8% to +82%, respectively, compared to the present-day climate. Resulting water balance calculations yielded a change in groundwater recharge ranging from a decrease of 72% to an increase of 3% for the four different analogue stations. The Gijon analogue station (Northern Spain), considered as the most representative for the near future climate state in the study area, shows an increase of 3% of groundwater recharge for a 5% increase of annual precipitation. Calculations for a colder (tundra) climate showed a change in groundwater recharge ranging from a decrease of 97% to an increase of 32% for four different analogue stations, with an annual precipitation change from -69% to -14% compared to the present-day climate.

  5. Antizyme induction by polyamine analogues as a factor of cell growth inhibition.

    PubMed Central

    Mitchell, John L A; Leyser, Aviva; Holtorff, Michelle S; Bates, Jill S; Frydman, Benjamin; Valasinas, Aldonia L; Reddy, Venodhar K; Marton, Laurence J

    2002-01-01

    The polyamines spermidine and spermine and their diamine precursor putrescine are essential for mammalian cell growth and viability, and strategies are sought for reducing polyamine levels in order to inhibit cancer growth. Several structural analogues of the polyamines have been found to decrease natural polyamine levels and inhibit cell growth, probably by stimulating normal feedback mechanisms. In the present study, a large selection of spermine analogues has been tested for their effectiveness in inducing the production of antizyme, a key protein in feedback inhibition of putrescine synthesis and cellular polyamine uptake. Bisethylnorspermine, bisethylhomospermine, 1,19-bis-(ethylamino)-5,10,15-triazanonadecane, longer oligoamine constructs and many conformationally constrained analogues of these compounds were found to stimulate antizyme synthesis to different levels in rat liver HTC cells, with some producing far more antizyme than the natural polyamine spermine. Uptake of the tested compounds was found to be dependent on, and limited by, the polyamine transport system, for which all these have approximately equal affinity. These analogues differed in their ability to inhibit HTC cell growth during 3 days of exposure, and this ability correlated with their antizyme-inducing potential. This is the first direct evidence that antizyme is induced by several polyamine analogues. Selection of analogues with this potential may be an effective strategy for maximizing polyamine deprivation and growth inhibition. PMID:11972449

  6. Paired Magmatic-Metallogenic Belts in Myanmar - an Andean Analogue?

    NASA Astrophysics Data System (ADS)

    Gardiner, Nicholas; Robb, Laurence; Searle, Michael; Morley, Christopher

    2015-04-01

    contrasting minerals endowment. The Mogok-Mandalay-Mergui (MMM) Belt hosts crustal-melt S-type granites with significant tin-tungsten mineralization, and contains the historically major tungsten deposit of Mawchi. The Wuntho-Popa Arc comprises I-type granites and granodiorites with porphyry-type copper-gold and epithermal gold mineralization, and includes the world-class Monywa copper mine. Recent U-Pb radiometric age dating has shown the potential for the two belts to be both active from the Late Cretaceous to Eocene. The spatial juxtaposition of these two sub-parallel belts, the implication of contemporary magmatism, and their distinct but consistent metallogenic endowment bears strong similarities to the metallogenic belts of the South American Cordillera. Here we investigate whether they together represent the magmatic and metallogenic expression of an Andean-type setting in Myanmar during the subduction of Neo-Tethys. In this analogue the Wuntho-Popa Arc represents a proximal I-type magmatic belt sited immediately above the eastwards-verging Neo-Tethys subduction zone. Exhibiting porphyry-type copper-gold and epithermal gold mineralization, this would therefore be the Myanmar equivalent of the Andean coastal copper belts. Conversely, the parallel MMM Belt, comprised of more distal crustal-melt S-type tin granites, would have an analogue in the Bolivian tin belt.

  7. Adriatic indentation of the Eastern Alps - nature vs. analogue models

    NASA Astrophysics Data System (ADS)

    Favaro, S.; Scharf, A.; Schuster, R.; Handy, M. R.

    2013-12-01

    The Eastern Alps underwent late Oligocene-Miocene indentation by the Adriatic microplate, followed by rapid Miocene exhumation in the Tauern Window and orogen-parallel escape. Analogue models of indentation in the Eastern Alps indicate that exhumation of orogenic crust in front of the Adriatic indenter was coeval, with faults and post-nappe folds forming an asymmetrical conjugate pattern in front of the indenting block (Ratschbacher et al 1991, Rosenberg et al 2007). The amount and rate of exhumation is greatest at this location, but decrease laterally towards an unconfined boundary of the models that represents the retreating Carpathian subduction orogen. In nature, however, isotopic age patterns of deeply buried and exhumed basements rocks in the Tauern Window of the Eastern Alps indicate that cooling and possibly also exhumation were diachronous along strike of the orogen. In the westernmost Tauern Window, previous thermal modeling of fission-track ages (Fügenschuh et al 1997) revealed that rapid exhumation (≥ 1mm/a) lasted from 20-13 Ma and appears to have been triggered by sinistral transpression along the Guidicarie Belt beginning in Late Oligocene time. Rapid cooling (≥25°C/Ma) from 550 to 270°C lasted from 18-12 Ma (von Blanckenburg et al 1989; Fügenschuh et al 1997). In the easternmost part, however, rapid cooling from a similar peak temperature lasted from 23-20 Ma and ended no later than 17 Ma. Thus, rapid exhumation cannot have begun later than 23-21 Ma. Cooling patterns in the eastern central part of the Tauern Window are more complex and reflect the combined effects of doming and extensional exhumation. New Rb-Sr mica ages in post-nappe basement domes generally decrease from NW (muscovite: 26 Ma; biotite: 22 Ma) to SE (muscovite: 22 Ma; biotite: 18 Ma). We interpret these trends to show that doming began in the south-central part of the Tauern Window and then migrated to the SE while the entire basement nappe pile underwent orogen

  8. Occupant Protection Project

    NASA Technical Reports Server (NTRS)

    Bopp, Genie; Somers, Jeff; Granderson, Brad; Gernhardt, Mike; Currie, Nancy; Lawrence, Chuck

    2010-01-01

    Topics include occupant protection overview with a focus on crew protection during dynamic phases of flight; occupant protection collaboration; modeling occupant protection; occupant protection considerations; project approach encompassing analysis tools, injury criteria, and testing program development; injury criteria update methodology, unique effects of pressure suits and other factors; and a summary.

  9. 2009 Arctic Mars Analogue Svalbard Expedition (AMASE) Evolved Gas Studies

    NASA Astrophysics Data System (ADS)

    Mahaffy, P. R.; McAdam, A.; Eigenbrode, J.; Steele, A.

    2009-12-01

    The Arctic Mars Analogue Svalbard Expedition (AMASE) continued its multi-year campaign in August 2009 to study selected sedimentary and igneous environments in this geological diverse archipelago using a variety of measurement techniques and protocols that are candidates for future Mars missions. The X-ray diffraction mineralogical and evolved gas analysis (EGA) employed during the AMASE-2009 campaign closely mimicked similar experiments that are planned for the 2011 Mars Science Laboratory (MSL). Field instruments similar to those under development for the ESA ExoMars or other rover missions provided imaging, spectroscopic, and subsurface sounding data. A variety of microbiology and field life detection techniques rounded out the AMASE-2009 analytical tools. The evolved gas mass spectrometer utilized on AMASE-2009 was designed to model elements of the Sample Analysis at Mars (SAM) suite of instruments on MSL. Powdered rock samples were heated from ambient to 1000 C in a helium stream and evolved gases continuously analyzed by a mass spectrometer. A continued focus of AMASE-2009 was analysis of carbonates from the Spitsbergen Sverrefjell volcano [1]. The similarity of macromolecular carbon (MMC) associated with magnetite in carbonate globules found in an ice cave in Sverrefjell to those studied in the Mars meteorite ALH84001 has been a motivation for their intensive study. The MMC associated with these carbonates appears to have been formed abiotically [2] following the eruption of the Sverrefjell volcano into glacial ice. The AMASE-2008 EGA studies of microsampled carbonate layers are described and the ability and limitations of these in situ tools to distinguish biomarkers. [1] H. Amundsen, Nature 327, 692-695 (1987). [2] A. Steele et al., Meteoritics and Planetary Science 42, 1549-1566 (2007) Acknowledgement: Support of this work is from the NASA ASTEP program with A. Steele AMASE PI and H. Amundsen Expedition lead.

  10. Cytotoxic and antibacterial activities of the analogues of pogostone.

    PubMed

    Tang, Zheng-Wei; Peng, Cheng; Dai, Min; Han, Bo

    2015-10-01

    Six new (A5-A6, A8-A11) and six known (A1-A4, A7, PO) α-pyrone compounds were synthesized with dehydroacetate and aldehydes in tetrahydrofuran at room temperature. And their structures were determined by (1)H-NMR, (13)C-NMR and mass spectroscopy. In the bioscreening experiments, ten compounds (A1-A5, PO, A7-A10) exhibited antibacterial activities against Staphylococcus aureus ATCC 25923 with minimum inhibitory concentration (MIC) values of 4-512 mg/L, and nine compounds (A1-A5, PO, A7-A8, A10) exhibited antibacterial activities against Methicillin-resistant S. aureus (MRSA) ATCC 43300 with MIC values of 4-256 mg/L. Moreover, compound A10 showed the highest antibacterial activity against S. aureus ATCC 25923 and MRSA with MIC values of 4 mg/L, while the MIC values of Amoxicillin were 8 mg/L and >256 mg/L, respectively. Two compounds (A8 and PO) exhibited antibacterial activities against Escherichia coli ATCC 25922 with MIC values of 32-512 mg/L. However, only one compound (A8) exhibited significant antibacterial activity against Pseudomonas aeruginosa CVCC 3360 with MIC value of 256 mg/L. Moreover, A10 exhibited significant inhibition of proliferation in the four cell lines MCF-10, A549, A2780 and MFC, and showed stronger inhibitive activity of these four selected cell lines than cisplatin in the cytotoxic assay. Thus, this study suggests that pogostone analogues, especially A10, represented a kind of promising antibacterial and antineoplastic agents. PMID:26272659

  11. Design of potent substrate-analogue inhibitors of canine renin

    NASA Technical Reports Server (NTRS)

    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.

  12. Laboratory and Field Spectroscopy of Moon analogue material

    NASA Astrophysics Data System (ADS)

    Offringa, Marloes; Foing, Bernard H.

    2016-07-01

    Samples derived from terrestrial analogue sites are studied to gain insight into lunar processes in their geological context (Foing, Stoker, Ehrenfreund, 2011). For this study samples from the volcanic region of the Eifel, Germany collected during our latest field campaigns in November 2015 and February 2016 (Foing et al., 2010), are analyzed with a variety of spectrometers. The aim is to obtain a database of analyzed samples that could be used as a reference for future in situ measurements. We also use a documented set of Moon-Mars relevant minerals curated at VU Amsterdam. We are using systematically for all samples UV-VIS and NIR reflectance spectrometers, and sporadically a Fourier Transform Infrared (FTIR) spectrometer, an X-Ray Fluorescence (XRF) spectrometer and a Raman laser spectrometer on control samples. Calibration of the UV-VIS and NIR reflectance spectrometers is the main focus of this research in order to obtain the clearest spectra. The calibration of the UV-VIS and NIR reflectance spectrometers requires the use of a good light source as well as suitable optical fibers to create a signal that covers the widest range in wavelengths available. To eliminate noise towards the edges of this range, multiple measurements are averaged and data is processed by dividing the signal by reference spectra. Obtained spectra can be tested for accuracy by comparing them with stationary laboratory spectrometers such as the FTIR spectrometer. The Raman, UV-VIS and NIR are also used in combination with the ExoGeoLab mock-up lander during field campaigns (Foing, Stoker, Ehrenfreund, 2011) also brought again to Eifel in February 2016, to prove the applicability of the equipment in the field. Acknowledgements: we thank Dominic Doyle for ESTEC optical lab support, Euan Monaghan (Leiden U) for FTIR measurement support, Wim van Westrenen for access to VU samples, Oscar Kamps (Utrecht U./ESTEC), Aidan Cowley (EAC) and Matthias Sperl (DLR) for support discussions

  13. Platonic solids generate their four-dimensional analogues.

    PubMed

    Dechant, Pierre Philippe

    2013-11-01

    This paper shows how regular convex 4-polytopes - the analogues of the Platonic solids in four dimensions - can be constructed from three-dimensional considerations concerning the Platonic solids alone. Via the Cartan-Dieudonné theorem, the reflective symmetries of the Platonic solids generate rotations. In a Clifford algebra framework, the space of spinors generating such three-dimensional rotations has a natural four-dimensional Euclidean structure. The spinors arising from the Platonic solids can thus in turn be interpreted as vertices in four-dimensional space, giving a simple construction of the four-dimensional polytopes 16-cell, 24-cell, the F4 root system and the 600-cell. In particular, these polytopes have `mysterious' symmetries, that are almost trivial when seen from the three-dimensional spinorial point of view. In fact, all these induced polytopes are also known to be root systems and thus generate rank-4 Coxeter groups, which can be shown to be a general property of the spinor construction. These considerations thus also apply to other root systems such as A(1)\\oplus I(2)(n) which induces I(2)(n)\\oplus I(2)(n), explaining the existence of the grand antiprism and the snub 24-cell, as well as their symmetries. These results are discussed in the wider mathematical context of Arnold's trinities and the McKay correspondence. These results are thus a novel link between the geometries of three and four dimensions, with interesting potential applications on both sides of the correspondence, to real three-dimensional systems with polyhedral symmetries such as (quasi)crystals and viruses, as well as four-dimensional geometries arising for instance in Grand Unified Theories and string and M-theory. PMID:24132220

  14. An evaluation of indirubin analogues as phosphorylase kinase inhibitors.

    PubMed

    Begum, Jaida; Skamnaki, Vassiliki T; Moffatt, Colin; Bischler, Nicolas; Sarrou, Josephine; Skaltsounis, Alexios-Leandros; Leonidas, Demetres D; Oikonomakos, Nikos G; Hayes, Joseph M

    2015-09-01

    Phosphorylase kinase (PhK) has been linked with a number of conditions such as glycogen storage diseases, psoriasis, type 2 diabetes and more recently, cancer (Camus et al., 2012 [6]). However, with few reported structural studies on PhK inhibitors, this hinders a structure based drug design approach. In this study, the inhibitory potential of 38 indirubin analogues have been investigated. 11 of these ligands had IC50 values in the range 0.170-0.360μM, with indirubin-3'-acetoxime (1c) the most potent. 7-Bromoindirubin-3'-oxime (13b), an antitumor compound which induces caspase-independent cell-death (Ribas et al., 2006 [20]) is revealed as a specific inhibitor of PhK (IC50=1.8μM). Binding assay experiments performed using both PhK-holo and PhK-γtrnc confirmed the inhibitory effects to arise from binding at the kinase domain (γ subunit). High level computations using QM/MM-PBSA binding free energy calculations were in good agreement with experimental binding data, as determined using statistical analysis, and support binding at the ATP-binding site. The value of a QM description for the binding of halogenated ligands exhibiting σ-hole effects is highlighted. A new statistical metric, the 'sum of the modified logarithm of ranks' (SMLR), has been defined which measures performance of a model for both the "early recognition" (ranking earlier/higher) of active compounds and their relative ordering by potency. Through a detailed structure activity relationship analysis considering other kinases (CDK2, CDK5 and GSK-3α/β), 6'(Z) and 7(L) indirubin substitutions have been identified to achieve selective PhK inhibition. The key PhK binding site residues involved can also be targeted using other ligand scaffolds in future work. PMID:26364215

  15. Indenter growth in analogue models of Alpine-type deformation

    NASA Astrophysics Data System (ADS)

    Bonini, Marco; Sokoutis, Dimitrios; Talbot, Christopher J.; Boccaletti, Mario; Milnes, Alan G.

    1999-02-01

    A series of analogue experiments were carried out to simulate continental convergence, as seen in a profile through the Central Alps. A rigid indenter, representing the Adriatic plate, was driven laterally into a sand pack representing the brittle upper crust of Europe, detached and thickening above its subducting ductile lower crust. The rigid indenter advanced at the same steady rate in each experiment, but the dip of its front face was steepened in 15° increments from 15° to 90°. Where the rigid indenter face dipped at 45° or less, a sand wedge rose and was bound by a series of forekinks that nucleated at the toe of the indenter. Where the face of the rigid indenter dipped 60° or more, the wedge was defined by a single forekink and one or more backkinks that nucleated from a point advancing in front of the indenter toe. We interpret these results as indicating that slices of the sand pack and rising wedge are transferred across kink bands to build an "effective" indenter with a frontal dip closer to that dictated by the changing shear strength of the sand pile, which thickens vertically as it shortens laterally. One of our models (with a rigid indenter dipping 75°) simulates most of the major structures shown in recent syntheses of surface geology and deep seismic data in the Central Alps, without the isostatic lithospheric depression. This model accounts for the late collisional stage (Oligocene to Present) complex strain and metamorphic histories in the core of the orogenic wedge, the rapid rise and extrusion of small pips of Alpine eclogites, and the current passivity of the Insubric Line. It also emphasizes that lateral extension along gently dipping "thrusts" (orogen-normal horizontal escape) is confined to the extruded portion of the rising wedge.

  16. Redox Viscosity of Iron Rich Silicate Melts - Martian Mantle Analogues.

    NASA Astrophysics Data System (ADS)

    Dingwell, D. B.

    2004-12-01

    The dependence of shear viscosity on the oxidation state of ferrosilicate melts has been measured using the concentric cylinder method and a gas mixing furnace. Two different simple Fe-bearing systems have been studied to date: (i) anorthite-diopside eutectic composition (AnDi) with variable amount of Fe (up to 20 wt%) as a basalt analogue and (ii) sodium disilicate (NS2 up to 30 wt % Fe). In addition, the compositional range has been extended to include the more complex SNC meteorite composition, a composition more relevant to Mars. The measurements were performed under air, CO2 and CO2-CO mixture at 1 atm and in a temperature range of 1300 to 1350 \\ºC. The experimental procedure involve a continuous measurement of viscosity during stepwise reduction state. The melt was reduced by flowing CO2 and then successively reducing mixtures of CO2-CO through the alumina muffle tube. Gas flow rates were electronically controlled using Tylan mass flow controllers and oxygen fugacity was directly measured using a sensor and calculated with Nernst equation. The composition and oxidation state of the melt was monitored by obtaining a melt sample after each redox equilibrium step. The melts were sampled by dipping an alumina rod into the sample and drawing out a drop of liquid, which was then plunged into water for quenching. The resulting glasses were analyzed by electron microprobe, and the volumetric potassium dichromate titration were employed to determine FeO. In addition, the redox dependence of viscosity of our samples have been compared with data from literature (Mysen et al. 1985, Dingwell and Virgo, 1988; Dingwell 1989, Dingwell 1991). The viscosity of all melts investigated herein decreases with melt reduction. The viscosity decrease is, in general, a nonlinear function of oxidation state expressed as Fe2+/Fetot and can be fitted using logarithmic equation.

  17. Two-dimensional graphene analogues for biomedical applications.

    PubMed

    Chen, Yu; Tan, Chaoliang; Zhang, Hua; Wang, Lianzhou

    2015-05-01

    The increasing demand of clinical biomedicine and fast development of nanobiotechnology has substantially promoted the generation of a variety of organic/inorganic nanosystems for biomedical applications. Biocompatible two-dimensional (2D) graphene analogues (e.g., nanosheets of transition metal dichalcogenides, transition metal oxides, g-C3N4, Bi2Se3, BN, etc.), which are referred to as 2D-GAs, have emerged as a new unique family of nanomaterials that show unprecedented advantages and superior performances in biomedicine due to their unique compositional, structural and physicochemical features. In this review, we summarize the state-of-the-art progress of this dynamically developed material family with a particular focus on biomedical applications. After the introduction, the second section of the article summarizes a range of synthetic methods for new types of 2D-GAs as well as their surface functionalization. The subsequent section provides a snapshot on the use of these biocompatible 2D-GAs for a broad spectrum of biomedical applications, including therapeutic (photothermal/photodynamic therapy, chemotherapy and synergistic therapy), diagnostic (fluorescent/magnetic resonance/computed tomography/photoacoustic imaging) and theranostic (concurrent diagnostic imaging and therapy) applications, especially on oncology. In addition, we briefly present the biosensing applications of these 2D-GAs for the detection of biomacromolecules and their in vitro/in vivo biosafety evaluations. The last section summarizes some critical unresolved issues, possible challenges/obstacles and also proposes future perspectives related to the rational design and construction of 2D-GAs for biomedical engineering, which are believed to promote their clinical translations for benefiting the personalized medicine and human health. PMID:25519856

  18. Glycosylphosphatidylinositol Anchor Analogues Sequester Cholesterol and Reduce Prion Formation*

    PubMed Central

    Bate, Clive; Tayebi, Mourad; Williams, Alun

    2010-01-01

    A hallmark of prion diseases is the conversion of the host-encoded prion protein (PrPC where C is cellular) into an alternatively folded, disease-related isoform (PrPSc, where Sc is scrapie), the accumulation of which is associated with synapse degeneration and ultimately neuronal death. The formation of PrPSc is dependent upon the presence of PrPC in specific, cholesterol-sensitive membrane microdomains, commonly called lipid rafts. PrPC is targeted to these lipid rafts because it is attached to membranes via a glycosylphosphatidylinositol anchor. Here, we show that treatment of prion-infected neuronal cell lines (ScN2a, ScGT1, or SMB cells) with synthetic glycosylphosphatidylinositol analogues, glucosamine-phosphatidylinositol (glucosamine-PI) or glucosamine 2-O-methyl inositol octadecyl phosphate, reduced the PrPSc content of these cells in a dose-dependent manner. In addition, ScGT1 cells treated with glucosamine-PI did not transmit infection following intracerebral injection to mice. Treatment with glucosamine-PI increased the cholesterol content of ScGT1 cell membranes and reduced activation of cytoplasmic phospholipase A2 (PLA2), consistent with the hypothesis that the composition of cell membranes affects key PLA2-dependent signaling pathways involved in PrPSc formation. The effect of glucosamine-PI on PrPSc formation was also reversed by the addition of platelet-activating factor. Glucosamine-PI caused the displacement of PrPC from lipid rafts and reduced expression of PrPC at the cell surface, putative sites for PrPSc formation. We propose that treatment with glucosamine-PI modifies local micro-environments that control PrPC expression and activation of PLA2 and subsequently inhibits PrPSc formation. PMID:20427265

  19. COMMUNITY BASED ENVIRONMENTAL PROTECTION

    EPA Science Inventory

    Community Based Environmental Protection intends to make environmental protection spring from the needs and values of the community of interest. Real community involvement in protecting the environment requires a process in which the environmental needs of communities and ecosyst...

  20. Protection of Organic Matter from Enzyme Degradation by Mineral Mesopores

    NASA Astrophysics Data System (ADS)

    Zimmerman, A. R.; Chorover, J. D.; Brantley, S. L.

    2003-12-01

    Mineral mesopores (2-50 nm diameter) may sequester organic matter (natural and pollutant) and protect it from microbial and fungal enzymatic degradation in soils and sediments. Synthetic mesoporous alumina and silica minerals with uniform pore sizes and shapes were used to test the role of mesopores in protecting organic matter from enzymatic degradation. A model humic compound, L-3-4-dihydroxyphenylalanine (L-DOPA), was sorbed to the internal surfaces of mesoporous alumina (8.2 nm diameter pores) and mesoporous silica (3.4 nm diameter pores) as well as to the external surfaces of nonporous alumina and silica analogues. A fungal derived enzyme, laccase, was added to these sorbate-sorbent pairs in aqueous solution and activity was monitored by oxygen consumption. Though enzyme activity was suppressed in both cases by mineral-enzyme interaction (enzyme inhibition likely due to adsorption of the enzyme), both the rate and total extent of enzyme-mediated degradation of mesopore-sorbed L-DOPA was 3-40 times lower than that of the externally-sorbed analogue. These results provide, for the first time, direct evidence for the viability of the proposed mesopore protection mechanism for the sequestration and preservation of sedimentary organic matter and organic contaminants. Mesopore adsorption/desorption phenomena may also help explain the slow degradation of organic contaminants in soil and sediment and may prove useful as delivery vehicles for organic compounds to agricultural, medical or environmental systems.