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Sample records for atr inhibitors cgk733

  1. The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation

    Directory of Open Access Journals (Sweden)

    Sunnerhagen Per

    2009-11-01

    Full Text Available Abstract The ataxia telangiectasia mutated (ATM and the ATM- related (ATR kinases play a central role in facilitating the resistance of cancer cells to genotoxic treatment regimens. The components of the ATM and ATR regulated signaling pathways thus provide attractive pharmacological targets, since their inhibition enhances cellular sensitivity to chemo- and radiotherapy. Caffeine as well as more specific inhibitors of ATM (KU55933 or ATM and ATR (CGK733 have recently been shown to induce cell death in drug-induced senescent tumor cells. Addition of these agents to cancer cells previously rendered senescent by exposure to genotoxins suppressed the ATM mediated p21 expression required for the survival of these cells. The precise molecular pharmacology of these agents however, is not well characterized. Herein, we report that caffeine, CGK733, and to a lesser extent KU55933, inhibit the proliferation of otherwise untreated human cancer and non-transformed mouse fibroblast cell lines. Exposure of human cancer cell lines to caffeine and CGK733 was associated with a rapid decline in cyclin D1 protein levels and a reduction in the levels of both phosphorylated and total retinoblastoma protein (RB. Our studies suggest that observations based on the effects of these compounds on cell proliferation and survival must be interpreted with caution. The differential effects of caffeine/CGK733 and KU55933 on cyclin D1 protein levels suggest that these agents will exhibit dissimilar molecular pharmacological profiles.

  2. In Vivo and In Vitro Effects of ATM/ATR Signaling Pathway on Proliferation, Apoptosis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells.

    Science.gov (United States)

    Wang, Ming; Liu, Gang; Shan, Guo-Ping; Wang, Bing-Bing

    2017-08-01

    The study investigated the ability of ataxia-telangiectasia mutated (ATM)/Rad3-related (ATR) signaling pathway to influence the proliferation, apoptosis, and radiosensitivity of nasopharyngeal carcinoma (NPC) cells. NPC tissues and corresponding adjacent normal tissues were collected from 143 NPC patients. The NPC CNE2 cells were assigned into a control group, X-ray group, CGK-733 group, and X-ray+CGK-733 group. The mRNA levels of ATM and ATR were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and the protein levels of ATM and ATR using western blotting. The positive expression of ATM and ATR in tissues and nude mouse tumor tissues was determined by immunohistochemistry. Cell proliferation, migration, invasion, and apoptosis rates were analyzed by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, scratch test, transwell assay, and flow cytometry, respectively. A nude mouse model of NPC was established to observe tumor volume and growth. The mRNA levels of ATR and ATM and the expression of ATR and ATM protein in NPC tissues were significantly higher than those in adjacent normal tissues. The colony formation assay showed that the colony-forming rate decreased, showing radiation dose-dependent and CGK-733 concentration-dependent manners. Expression of ATM, ATR, Chk1, and Chk2 was evidently increased in the X-ray, CGK-733, and X-ray+CGK-733groups compared with the control group, and the aforementioned expression was highest in the X-ray+CGK-733 group among the four groups. The cell proliferation, invasion, and migration were decreased, tumor volume decreased and cell apoptosis increased in the X-ray, CGK-733, and X-ray+CGK-733 groups compared with the control group; the X-ray+CGK-733 group exhibited lowest cell proliferation, invasion and migration, smallest tumor volume, and highest cell apoptosis among the four groups. Inhibition of ATM/ATR signaling pathway reduces proliferation and enhances apoptosis and

  3. Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation.

    Science.gov (United States)

    Yang, Lina; Liu, Yuanyuan; Sun, Chao; Yang, Xinrui; Yang, Zhen; Ran, Juntao; Zhang, Qiuning; Zhang, Hong; Wang, Xinyu; Wang, Xiaohu

    2015-11-01

    Non-small cell lung cancer (NSCLC) exhibits radioresistance to conventional rays, due to its DNA damage repair systems. NSCLC may potentially be sensitized to radiation treatment by reducing those factors that continuously enhance the repair of damaged DNA. In the present study, normal lung fibroblast MRC-5 and lung cancer A549 cells were treated with NU7026 and CGK733, which are inhibitors of the DNA-dependent protein kinase catalytic subunit (PKcs) and ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR), respectively, followed by exposure to X-rays and carbon ion irradiation. The cytotoxic activity, cell survival rate, DNA damage repair ability, cell cycle arrest and apoptosis rate of the treated cells were analyzed with MTT assay, colony formation assay, immunofluorescence and flow cytometry, respectively. The transcription and translation levels of the ATM, ATR and DNA-PKcs genes were detected by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results indicated that the radiosensitivity and DNA repair ability of A549 cells were reduced, and the percentages of apoptotic cells and those arrested at the G2/M phase of the cell cycle were significantly increased, following ionizing radiation with inhibitor-pretreatment. The expression levels of ATM, ATR, DNA-PKcs and phosphorylated histone H2AX, a biomarker for DNA double-strand breaks, were all upregulated at the transcriptional or translational level in A549 cells treated with carbon ion irradiation, compared with the control and X-rays-treated cells. In addition, the treatment with 5-50 µM NU7026 or CGK733 did not produce any obvious cytotoxicity in MRC-5 cells, and the effect of the DNA-PKcs-inhibitor on enhancing the radiosensitivity of A549 cells was stronger than that observed for the ATM and ATR-inhibitor. These findings demonstrated a minor role for ATM and ATR in radiation-induced cell death, since the upregulation of

  4. ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression.

    Science.gov (United States)

    Fallone, F; Britton, S; Nieto, L; Salles, B; Muller, C

    2013-09-12

    Tumor cells adaptation to severe oxygen deprivation (hypoxia) plays a major role in tumor progression. The transcription factor HIF-1 (hypoxia-inducible factor 1), whose α-subunit is stabilized under hypoxic conditions is a key component of this process. Recent studies showed that two members of the phosphoinositide 3-kinase-related kinases (PIKKs) family, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase), regulate the hypoxic-dependent accumulation of HIF-1. These proteins initiate cellular stress responses when DNA damage occurs. In addition, it has been demonstrated that extreme hypoxia induces a replicative stress resulting in regions of single-stranded DNA at stalled replication forks and the activation of ATR (ataxia telangiectasia and Rad3 related protein), another member of the PIKKs family. Here, we show that even less severe hypoxia (0.1% O2) also induces activation of ATR through replicative stress. Importantly, in using either transiently silenced ATR cells, cells expressing an inactive form of ATR or cells exposed to an ATR inhibitor (CGK733), we demonstrate that hypoxic ATR activation positively regulates the key transcription factor HIF-1 independently of the checkpoint kinase Chk1. We show that ATR kinase activity regulates HIF-1α at the translational level and we find that the elements necessary for the regulation of HIF-1α translation are located within the coding region of HIF-1α mRNA. Finally, by using three independent cellular models, we clearly show that the loss of ATR expression and/or kinase activity results in the decrease of HIF-1 DNA binding under hypoxia and consequently affects protein expression levels of two HIF-1 target genes, GLUT-1 and CAIX. Taken together, our data show a new function for ATR in cellular adaptation to hypoxia through regulation of HIF-1α translation. Our work offers new prospect for cancer therapy using ATR inhibitors with the potential to decrease cellular adaptation in hypoxic

  5. Rationally Designed PI3Kα Mutants to Mimic ATR and Their Use to Understand Binding Specificity of ATR Inhibitors.

    Science.gov (United States)

    Lu, Yipin; Knapp, Mark; Crawford, Kenneth; Warne, Robert; Elling, Robert; Yan, Kelly; Doyle, Michael; Pardee, Gwynn; Zhang, Li; Ma, Sylvia; Mamo, Mulugeta; Ornelas, Elizabeth; Pan, Yue; Bussiere, Dirksen; Jansen, Johanna; Zaror, Isabel; Lai, Albert; Barsanti, Paul; Sim, Janet

    2017-06-02

    ATR, a protein kinase in the PIKK family, plays a critical role in the cell DNA-damage response and is an attractive anticancer drug target. Several potent and selective inhibitors of ATR have been reported showing significant antitumor efficacy, with most advanced ones entering clinical trials. However, due to the absence of an experimental ATR structure, the determinants contributing to ATR inhibitors' potency and specificity are not well understood. Here we present the mutations in the ATP-binding site of PI3Kα to progressively transform the pocket to mimic that of ATR. The generated PI3Kα mutants exhibit significantly improved affinity for selective ATR inhibitors in multiple chemical classes. Furthermore, we obtained the X-ray structures of the PI3Kα mutants in complex with the ATR inhibitors. The crystal structures together with the analysis on the inhibitor affinity profile elucidate the roles of individual amino acid residues in the binding of ATR inhibitors, offering key insights for the binding mechanism and revealing the structure features important for the specificity of ATR inhibitors. The ability to obtain structural and binding data for these PI3Kα mutants, together with their ATR-like inhibitor binding profiles, makes these chimeric PI3Kα proteins valuable model systems for structure-based inhibitor design. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells.

    Science.gov (United States)

    Min, Ahrum; Im, Seock-Ah; Jang, Hyemin; Kim, Seongyeong; Lee, Miso; Kim, Debora Keunyoung; Yang, Yaewon; Kim, Hee-Jun; Lee, Kyung-Hun; Kim, Jin Won; Kim, Tae-Yong; Oh, Do-Youn; Brown, Jeff; Lau, Alan; O'Connor, Mark J; Bang, Yung-Jue

    2017-04-01

    Ataxia telangiectasia and Rad3-related (ATR) can be considered an attractive target for cancer treatment due to its deleterious effect on cancer cells harboring a homologous recombination defect. The aim of this study was to investigate the potential use of the ATR inhibitor, AZD6738, to treat gastric cancer.In SNU-601 cells with dysfunctional ATM, AZD6738 treatment led to an accumulation of DNA damage due to dysfunctional RAD51 foci formation, S phase arrest, and caspase 3-dependent apoptosis. In contrast, SNU-484 cells with functional ATM were not sensitive to AZD6738. Inhibition of ATM in SNU-484 cells enhanced AZD6738 sensitivity to a level comparable with that observed in SNU-601 cells, showing that activation of the ATM-Chk2 signaling pathway attenuates AZD6738 sensitivity. In addition, decreased HDAC1 expression was found to be associated with ATM inactivation in SNU-601 cells, demonstrating the interaction between HDAC1 and ATM can affect sensitivity to AZD6738. Furthermore, in an in vivo tumor xenograft mouse model, AZD6738 significantly suppressed tumor growth and increased apoptosis.These findings suggest synthetic lethality between ATR inhibition and ATM deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM deficiency are warranted to develop novel treatment strategies for gastric cancer. Mol Cancer Ther; 16(4); 566-77. ©2017 AACR. ©2017 American Association for Cancer Research.

  7. Small-molecule inhibitors of Ataxia Telangiectasia and Rad3 related kinase (ATR) sensitize lymphoma cells to UVA radiation

    DEFF Research Database (Denmark)

    Biskup, Edyta; Naym, David Gram; Gniadecki, Robert

    2016-01-01

    and require more aggressive therapies. OBJECTIVE: The aim of this project was to investigate whether inhibition of Ataxia Telangiectasia and Rad3 related kinase (ATR) may enhance efficacy of phototherapy. METHODS: CTCL cell lines (MyLa2000, SeAx and Mac2a) served as in vitro cell models. ATR and Chk1 were...

  8. Atlantic Test Range (ATR)

    Data.gov (United States)

    Federal Laboratory Consortium — ATR controls fully-instrumented and integrated test ranges that provide full-service support for cradle-to-grave testing. Airspace and surface target areas are used...

  9. ATR Kinase Inhibition Protects Non-cycling Cells from the Lethal Effects of DNA Damage and Transcription Stress*

    Science.gov (United States)

    Kemp, Michael G.; Sancar, Aziz

    2016-01-01

    ATR (ataxia telangiectasia and Rad-3-related) is a protein kinase that maintains genome stability and halts cell cycle phase transitions in response to DNA lesions that block DNA polymerase movement. These DNA replication-associated features of ATR function have led to the emergence of ATR kinase inhibitors as potential adjuvants for DNA-damaging cancer chemotherapeutics. However, whether ATR affects the genotoxic stress response in non-replicating, non-cycling cells is currently unknown. We therefore used chemical inhibition of ATR kinase activity to examine the role of ATR in quiescent human cells. Although ATR inhibition had no obvious effects on the viability of non-cycling cells, inhibition of ATR partially protected non-replicating cells from the lethal effects of UV and UV mimetics. Analyses of various DNA damage response signaling pathways demonstrated that ATR inhibition reduced the activation of apoptotic signaling by these agents in non-cycling cells. The pro-apoptosis/cell death function of ATR is likely due to transcription stress because the lethal effects of compounds that block RNA polymerase movement were reduced in the presence of an ATR inhibitor. These results therefore suggest that whereas DNA polymerase stalling at DNA lesions activates ATR to protect cell viability and prevent apoptosis, the stalling of RNA polymerases instead activates ATR to induce an apoptotic form of cell death in non-cycling cells. These results have important implications regarding the use of ATR inhibitors in cancer chemotherapy regimens. PMID:26940878

  10. ATR Power Supplies

    Energy Technology Data Exchange (ETDEWEB)

    Bruno, Don [Brookhaven National Lab. (BNL), Upton, NY (United States)

    1996-09-10

    The ATR (AGS to RHIC Transfer Line) is fed beam from two synchrotron rings. The first synchrotron ring is the Booster which receives protons from a 200MeV Linac and can achieve a proton energy of 1.5GeV. The Booster can also receive heavy ions from a 15.5MV Tandem Van de Graaff. The Booster is about 1/8 of a mile in circumference. The Booser then Feeds the AGS (Alternating Gradient Synchrotron) wich can achieve a proton energy of 29.5 Gev. The AGS is about 1/2 of a mile in circumference. The AGS then kicks the beam out to the ATR line which will eventually feed RHIC (Relativistic Heavy Ion Collider) beam starting with the sextant test in December of 1996. The ATR line is about 1/2 mile long. The ATR line is made up of the upgraded U-line, new W, X and Y lines (see Figure 1). The test in November and December of 1995 transported beam from the AGS to the end of the W-line into a beam stop. During the normal operation of RHIC there will be a switching magnet at the end of the W-line which will bend beam into the X-Line and then into the Y-line so that the two beams in RHIC will be rotating in opposite directions.

  11. PUREX new substation ATR

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, D.E.

    1997-05-12

    This document is the acceptance test report (ATR) for the New PUREX Main and Minisubstations. It covers the factory and vendor acceptance and commissioning test reports. Reports are presented for the Main 5 kV substation building, the building fire system, switchgear, and vacuum breaker; the minisubstation control building and switch gear; commissioning test; electrical system and loads inspection; electrical utilities transformer and cable; and relay setting changes based on operational experience.

  12. Inhibitors

    Science.gov (United States)

    ... and exercise, immune tolerance therapy, and needs of older adults with hemophilia and an inhibitor. For more information, visit https://www.hemophilia.org/Events-Educational-Programs/Inhibitor-Education/Inhibitor-Education-Summits The NHF’s Inhibitor Education Summits ...

  13. ATR Performance Estimation Seed Program

    Science.gov (United States)

    2015-09-28

    19b. TELEPHONE NUMBER (Include area code) 09/28/2015 Research Performance Report July 2014 - June 2015 ATR Performance Estimation Seed Program Cook...Report: ATR Performance Estimation Seed Program Daniel A. Cook Georgia Tech Research Institute Sensors and Electromagnetic Applications Laboratory...term seed program to expand the Navy’s efforts in performance prediction for MCM. The team included individuals from ARL/PSU, APL-UW, GTRI, and NSWC

  14. Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities

    Directory of Open Access Journals (Sweden)

    Kumar Sanjiv

    2016-01-01

    Full Text Available ATR and CHK1 maintain cancer cell survival under replication stress and inhibitors of both kinases are currently undergoing clinical trials. As ATR activity is increased after CHK1 inhibition, we hypothesized that this may indicate an increased reliance on ATR for survival. Indeed, we observe that replication stress induced by the CHK1 inhibitor AZD7762 results in replication catastrophe and apoptosis, when combined with the ATR inhibitor VE-821 specifically in cancer cells. Combined treatment with ATR and CHK1 inhibitors leads to replication fork arrest, ssDNA accumulation, replication collapse, and synergistic cell death in cancer cells in vitro and in vivo. Inhibition of CDK reversed replication stress and synthetic lethality, demonstrating that regulation of origin firing by ATR and CHK1 explains the synthetic lethality. In conclusion, this study exemplifies cancer-specific synthetic lethality between two proteins in the same pathway and raises the prospect of combining ATR and CHK1 inhibitors as promising cancer therapy.

  15. Cantharidin Overcomes Imatinib Resistance by Depleting BCR-ABL in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Sun, Xiaoyan; Cai, Xueting; Yang, Jie; Chen, Jiao; Guo, Caixia; Cao, Peng

    2016-12-01

    Cantharidin (CTD) is an active compound isolated from the traditional Chinese medicine blister beetle and displayed anticancer properties against various types of cancer cells. However, little is known about its effect on human chronic myeloid leukemia (CML) cells, including imatinib-resistant CML cells. The objective of this study was to investigate whether CTD could overcome imatinib resistance in imatinib-resistant CML cells and to explore the possible underlying mechanisms associated with the effect. Our results showed that CTD strongly inhibited the growth of both imatinib-sensitive and imatinib-resistant CML cells. CTD induced cell cycle arrest at mitotic phase and triggered DNA damage in CML cells. The ATM/ATR inhibitor CGK733 abrogated CTD-induced mitotic arrest but promoted the cytotoxic effects of CTD. In addition, we demonstrated that CTD downregulated the expression of the BCR-ABL protein and suppressed its downstream signal transduction. Real-time quantitative PCR revealed that CTD inhibited BCR-ABL at transcriptional level. Knockdown of BCR-ABL increased the cell-killing effects of CTD in K562 cells. These findings indicated that CTD overcomes imatinib resistance through depletion of BCR-ABL. Taken together, CTD is an important new candidate agent for CML therapy.

  16. ATR Spent Fuel Options Study

    Energy Technology Data Exchange (ETDEWEB)

    Connolly, Michael James [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bean, Thomas E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Brower, Jeffrey O. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Luke, Dale E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Patterson, M. W. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Robb, Alan K. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Sindelar, Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Rebecca E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Tonc, Vincent F. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Tripp, Julia L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Winston, Philip L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-01-01

    The Advanced Test Reactor (ATR) is a materials and fuels test nuclear reactor that performs irradiation services for the U.S. Department of Energy (DOE) Office of Nuclear Energy (NE), Naval Reactors, the National Nuclear Security Administration (NNSA), and other research programs. ATR achieved initial criticality in 1967 and is expected to operate in support of needed missions until the year 2050 or beyond. It is anticipated that ATR will generate approximately 105 spent nuclear fuel (SNF) elements per year through the year 2050. Idaho National Laboratory (INL) currently stores 2,008 ATR SNF elements in dry storage, 976 in wet storage, and expects to have 1,000 elements in wet storage before January 2017. A capability gap exists at INL for long-term (greater than the year 2050) management, in compliance with the Idaho Settlement Agreement (ISA), of ATR SNF until a monitored retrievable geological repository is open. INL has significant wet and dry storage capabilities that are owned by the DOE Office of Environmental Management (EM) and operated and managed by Fluor Idaho, which include the Idaho Nuclear Technology and Engineering Center’s (INTEC’s) CPP-666, CPP-749, and CPP-603. In addition, INL has other capabilities owned by DOE-NE and operated and managed by Battelle Energy Alliance, LLC (BEA), which are located at the Materials and Fuel Complex (MFC). Additional storage capabilities are located on the INL Site at the Naval Reactors Facility (NRF). Current INL SNF management planning, as defined in the Fluor Idaho contract, shows INTEC dry fuel storage, which is currently used for ATR SNF, will be nearly full after transfer of an additional 1,000 ATR SNF from wet storage. DOE-NE tasked BEA with identifying and analyzing options that have the potential to fulfill this capability gap. BEA assembled a team comprised of SNF management experts from Fluor Idaho, Savannah River Site (SRS), INL/BEA, and the MITRE Corp with an objective of developing and analyzing

  17. Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer.

    Science.gov (United States)

    Abdel-Fatah, Tarek M A; Middleton, Fiona K; Arora, Arvind; Agarwal, Devika; Chen, Tao; Moseley, Paul M; Perry, Christina; Doherty, Rachel; Chan, Stephen; Green, Andrew R; Rakha, Emad; Ball, Graham; Ellis, Ian O; Curtin, Nicola J; Madhusudan, Srinivasan

    2015-03-01

    ATR-CHEK1 signalling is critical for genomic stability. ATR-CHEK1 signalling may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. We investigated ATR, CHEK1 and phosphorylated CHEK1 (Ser345) protein (pCHEK1) levels in 1712 breast cancers. ATR and CHEK1 mRNA expression was evaluated in 1950 breast cancers. Pre-clinically, biological consequences of ATR gene knock down or ATR inhibition by the small molecule inhibitor (VE-821) were investigated in MCF7 and MDA-MB-231 breast cancer cell lines and in non-tumorigenic breast epithelial cells (MCF10A). High ATR and high cytoplasmic pCHEK1 levels were significantly associated with higher tumour stage, higher mitotic index, pleomorphism and lymphovascular invasion. In univariate analyses, high ATR and high cytoplasmic pCHEK1 levels were associated with poor breast cancer specific survival (BCSS). In multivariate analysis, high ATR level remains an independent predictor of adverse outcome. At the mRNA level, high CHEK1 remains associated with aggressive phenotypes including lymph node positivity, high grade, Her-2 overexpression, triple negative, aggressive molecular phenotypes and adverse BCSS. Pre-clinically, CHEK1 phosphorylation at serine(345) following replication stress was impaired in ATR knock down and in VE-821 treated breast cancer cells. Doxycycline inducible knockdown of ATR suppressed growth, which was restored when ATR was re-expressed. Similarly, VE-821 treatment resulted in a dose dependent suppression of cancer cell growth and survival (MCF7 and MDA-MB-231) but was less toxic in non-tumorigenic breast epithelial cells (MCF10A). We provide evidence that ATR and CHEK1 are promising biomarkers and rational drug targets for personalized therapy in breast cancer. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  18. APOBEC3A and APOBEC3B Activities Render Cancer Cells Susceptible to ATR Inhibition.

    Science.gov (United States)

    Buisson, Rémi; Lawrence, Michael S; Benes, Cyril H; Zou, Lee

    2017-09-01

    The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like APOBEC3A and APOBEC3B have emerged as key mutation drivers in cancer. Here, we show that APOBEC3A and APOBEC3B activities impose a unique type of replication stress by inducing abasic sites at replication forks. In contrast to cells under other types of replication stress, APOBEC3A-expressing cells were selectively sensitive to ATR inhibitors (ATRi), but not to a variety of DNA replication inhibitors and DNA-damaging drugs. In proliferating cells, APOBEC3A modestly elicited ATR but not ATM. ATR inhibition in APOBEC3A-expressing cells resulted in a surge of abasic sites at replication forks, revealing an ATR-mediated negative feedback loop during replication. The surge of abasic sites upon ATR inhibition associated with increased accumulation of single-stranded DNA, a substrate of APOBEC3A, triggering an APOBEC3A-driven feed-forward loop that ultimately drove cells into replication catastrophe. In a panel of cancer cell lines, ATRi selectively induced replication catastrophe in those harboring high APOBEC3A and/or APOBEC3B activities, showing that APOBEC3A and APOBEC3B activities conferred susceptibility to ATRi. Our results define an APOBEC-driven replication stress in cancer cells that may offer an opportunity for ATR-targeted therapy. Cancer Res; 77(17); 4567-78. ©2017 AACR. ©2017 American Association for Cancer Research.

  19. ATR Commissioning Software Task Force Report

    Energy Technology Data Exchange (ETDEWEB)

    D' Ottavio, Ted [Brookhaven National Lab. (BNL), Upton, NY (United States); Kewisch, Jorg [Brookhaven National Lab. (BNL), Upton, NY (United States); Saltmarsh, Chris [Brookhaven National Lab. (BNL), Upton, NY (United States); Sathe, Smita [Brookhaven National Lab. (BNL), Upton, NY (United States); Satogata, Todd [Brookhaven National Lab. (BNL), Upton, NY (United States); Shea, Don [Brookhaven National Lab. (BNL), Upton, NY (United States); Tepikian, Steve [Brookhaven National Lab. (BNL), Upton, NY (United States); Trahern, Garry [Brookhaven National Lab. (BNL), Upton, NY (United States)

    1994-12-16

    The Beam Injection Tests Software Task Force was charged with studying the software needed for the ATR tests, seen as a stepping stone or template for the larger scope of the full RHIC control system. This report outlines our avenues of exploration so far, presents the current analysis and implementation work in progress, and gives recommendations for the future on the ATR and longer time scales.

  20. Cancer cells with alternative lengthening of telomeres do not display a general hypersensitivity to ATR inhibition

    Directory of Open Access Journals (Sweden)

    Katharina I Deeg

    2016-08-01

    Full Text Available Telomere maintenance is a hallmark of cancer as it provides cancer cells with cellular immortality. A significant fraction of tumors uses the alternative lengthening of telomeres (ALT pathway to elongate their telomeres and to gain an unlimited proliferation potential. Since the ALT pathway is unique to cancer cells, it represents a potentially valuable, currently unexploited target for anticancer therapies. Recently, it was proposed that ALT renders cells hypersensitive to ataxia telangiectasia- and RAD3-related (ATR protein inhibitors (Flynn et al., Science 347, 273. Here, we measured the response of various ALT or telomerase positive cell lines to the ATR inhibitor VE-821. In addition, we compared the effect of the inhibitor on cell viability in isogenic cell lines, in which ALT was active or suppressed. In these experiments a general ATR inhibitor sensitivity of cells with ALT could not be confirmed. We rather propose that the observed variations in sensitivity reflect differences between cell lines that are unrelated to ALT.

  1. MIR-ATR sensor for process monitoring

    Science.gov (United States)

    Geörg, Daniel; Schalk, Robert; Methner, Frank-Jürgen; Beuermann, Thomas

    2015-06-01

    A mid-infrared attenuated total reflectance (MIR-ATR) sensor has been developed for chemical reaction monitoring. The optical setup of the compact and low-priced sensor consists of an IR emitter as light source, a zinc selenide (ZnSe) ATR prism as boundary to the process, and four thermopile detectors, each equipped with an optical bandpass filter. The practical applicability was tested during esterification of ethanol and formic acid to ethyl formate and water as a model reaction with subsequent distillation. For reference analysis, a Fourier transform mid-infrared (FT-MIR) spectrometer with diamond ATR module was applied. On-line measurements using the MIR-ATR sensor and the FT-MIR spectrometer were performed in a bypass loop. The sensor was calibrated by multiple linear regression in order to link the measured absorbance in the four optical channels to the analyte concentrations. The analytical potential of the MIR-ATR sensor was demonstrated by simultaneous real-time monitoring of all four chemical substances involved in the esterification and distillation process. The temporal courses of the sensor signals are in accordance with the concentration values achieved by the commercial FT-MIR spectrometer. The standard error of prediction for ethanol, formic acid, ethyl formate, and water were 0.38 mol L  -  1, 0.48 mol L  -  1, 0.38 mol L  -  1, and 1.12 mol L  -  1, respectively. A procedure based on MIR spectra is presented to simulate the response characteristics of the sensor if the transmission ranges of the filters are varied. Using this tool analyte specific bandpass filters for a particular chemical reaction can be identified. By exchanging the optical filters, the sensor can be adapted to a wide range of processes in the chemical, pharmaceutical, and beverage industries.

  2. ATR promotes cilia signalling: links to developmental impacts.

    Science.gov (United States)

    Stiff, Tom; Casar Tena, Teresa; O'Driscoll, Mark; Jeggo, Penny A; Philipp, Melanie

    2016-04-15

    Mutations in ATR(ataxia telangiectasia and RAD3-related) cause Seckel syndrome (ATR-SS), a microcephalic primordial dwarfism disorder. Hitherto, the clinical manifestation of ATR deficiency has been attributed to its canonical role in DNA damage response signalling following replication fork stalling/collapse. Here, we show that ATR regulates cilia-dependent signalling in a manner that can be uncoupled from its function during replication. ATR-depleted or patient-derived ATR-SS cells form cilia of slightly reduced length but are dramatically impaired in cilia-dependent signalling functions, including growth factor and Sonic hedgehog signalling. To better understand the developmental impact of ATR loss of function, we also used zebrafish as a model. Zebrafish embryos depleted of Atr resembled ATR-SS morphology, showed a modest but statistically significant reduction in cilia length and other morphological features indicative of cilia dysfunction. Additionally, they displayed defects in left-right asymmetry including ambiguous expression of southpaw, incorrectly looped hearts and randomized localization of internal organs including the pancreas, features typically conferred by cilia dysfunction. Our findings reveal a novel role for ATR in cilia signalling distinct from its canonical function during replication and strengthen emerging links between cilia function and development. © The Author 2016. Published by Oxford University Press.

  3. Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication

    Directory of Open Access Journals (Sweden)

    Antonio Postigo

    2017-05-01

    Full Text Available In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.

  4. An add-on cap for ATR-IR spectroscopy studies

    DEFF Research Database (Denmark)

    2014-01-01

    The invention relates to a cap (300B) for an attenuated total reflectance infrared (ATR-IR) spectrometer, the ATR-IR spectrometer comprising an ATR-IR plate (200). The cap (300B) comprises an ATR- IR plate facing cap surface. When the ATR-IR plate facing cap surface is placed on the sample surface...

  5. HCLK2 is required for activity of the DNA damage response kinase ATR

    DEFF Research Database (Denmark)

    Rendtlew Danielsen, Jannie M; Larsen, Dorthe Helena; Schou, Kenneth Bødtker

    2008-01-01

    of ATR kinase activity. We show that HCLK2 forms a complex with ATR-ATRIP and the ATR activator TopBP1. We demonstrate that HCLK2-induced ATR kinase activity toward substrates requires TopBP1 and vice versa and provides evidence that HCLK2 facilitates efficient ATR-TopBP1 association. Consistent with its...... in the same pathway as TopBP1 but that the two proteins regulate different steps in ATR activation....

  6. Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair.

    Science.gov (United States)

    Lima, Michelle; Bouzid, Hana; Soares, Daniele G; Selle, Frédéric; Morel, Claire; Galmarini, Carlos M; Henriques, João A P; Larsen, Annette K; Escargueil, Alexandre E

    2016-05-03

    Trabectedin (Yondelis®, ecteinascidin-743, ET-743) is a marine-derived natural product approved for treatment of advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Lurbinectedin is a novel anticancer agent structurally related to trabectedin. Both ecteinascidins generate DNA double-strand breaks that are processed through homologous recombination repair (HRR), thereby rendering HRR-deficient cells particularly sensitive. We here characterize the DNA damage response (DDR) to trabectedin and lurbinectedin in HeLa cells. Our results show that both compounds activate the ATM/Chk2 (ataxia-telangiectasia mutated/checkpoint kinase 2) and ATR/Chk1 (ATM and RAD3-related/checkpoint kinase 1) pathways. Interestingly, pharmacological inhibition of Chk1/2, ATR or ATM is not accompanied by any significant improvement of the cytotoxic activity of the ecteinascidins while dual inhibition of ATM and ATR strongly potentiates it. Accordingly, concomitant inhibition of both ATR and ATM is an absolute requirement to efficiently block the formation of γ-H2AX, MDC1, BRCA1 and Rad51 foci following exposure to the ecteinascidins. These results are not restricted to HeLa cells, but are shared by cisplatin-sensitive and -resistant ovarian carcinoma cells. Together, our data identify ATR and ATM as central coordinators of the DDR to ecteinascidins and provide a mechanistic rationale for combining these compounds with ATR and ATM inhibitors.

  7. ATR FTIR Mapping of Leather Fiber Panels

    Science.gov (United States)

    Tondi, G.; Grünewald, T.; Petutschnigg, A.; Schnabel, T.

    2015-01-01

    Leather fiber panels are very promising materials for many applications, not only for the easy availability of the constituents but also for their outstanding fi re-retardant properties. These innovative composite panels can be an excellent material for building insulation, and in recent times, the interest of industries in this composite board has considerably arisen. For this reason the discrimination of the components in the leather fiber panels is becoming fundamental in order to ensure their homogeneous properties. A method to characterize the surface of these materials is then required. An ATR FTIR mapping system for the leather fiber panels has been performed with a Perkin-Elmer microscope coupled with a Frontier FTIR spectrometer. The system has successfully allowed transforming the optical image to a chemical one. This technique can be considered as a right tool for routine controls of the surface quality, especially when the leather shavings cannot be optically distinguished.

  8. Encefalomenigocele atrésico parietal

    Directory of Open Access Journals (Sweden)

    Liliana Rivera Oliva

    2011-09-01

    Full Text Available El encefalocele es una anomalía congénita rara, en la que una porción del encéfalo protruye a través de un orificio craneal (evaginación, generalmente situado en la línea media. Clínicamente se caracteriza por una masa epicraneal, de consistencia blanda, muchas veces acompañada de trastornos psicomotores, convulsiones y trastornos de la visión. Se presenta el caso de un recién nacido con diagnóstico de encefalomeningocele atrésico parietal, intervenido quirúrgicamente y con evolución satisfactoria.

  9. The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function.

    Science.gov (United States)

    Xue, Lian; Furusawa, Yoshiya; Okayasu, Ryuichi; Miura, Masahiko; Cui, Xing; Liu, Cuihua; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Yajima, Hirohiko; Yu, Dong

    2015-01-01

    DNA double strand break (DSB) repair pathway choice following ionizing radiation (IR) is currently an appealing research topic, which is still largely unclear. Our recent paper indicated that the complexity of DSBs is a critical factor that enhances DNA end resection. It has been well accepted that the RPA-coated single strand DNA produced by resection is a signaling structure for ATR activation. Therefore, taking advantage of high linear energy transfer (LET) radiation to effectively produce complex DSBs, we investigated how the complexity of DSB influences the function of ATR pathway on the G2/M checkpoint regulation. Human skin fibroblast cells with or without ATM were irradiated with X rays or heavy ion particles, and dual-parameter flow cytometry was used to quantitatively assess the mitotic entry at early period post radiation by detecting the cells positive for phosphor histone H3. In ATM-deficient cells, ATR pathway played a pivotal role and functioned in a dose- and LET-dependent way to regulate the early G2/M arrest even as low as 0.2Gy for heavy ion radiation, which indicated that ATR pathway could be rapidly activated and functioned in an ATM-independent, but DSB complexity-dependent manner following exposure to IR. Furthermore, ATR pathway also functioned more efficiently in ATM-proficient cells to block G2 to M transition at early period of particle radiation exposure. Accordingly, in contrast to ATM inhibitor, ATR inhibitor had a more effective radiosensitizing effect on survival fraction following heavy ion beams as compared with X ray radiation. Taken together, our results reveal that the complexity of DSBs is a crucial factor for the activation of ATR pathway for G2/M checkpoint regulation, and ATM-dependent end resection is not essential for the activation. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

    DEFF Research Database (Denmark)

    Toledo Lazaro, Luis Ignacio; Altmeyer, Matthias; Rask, Maj-Britt

    2013-01-01

    origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing...... induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells...

  11. LWRS ATR Irradiation Testing Readiness Status

    Energy Technology Data Exchange (ETDEWEB)

    Kristine Barrett

    2012-09-01

    The Light Water Reactor Sustainability (LWRS) Program was established by the U.S. Department of Energy Office of Nuclear Energy (DOE-NE) to develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of the current reactors. The LWRS Program is divided into four R&D Pathways: (1) Materials Aging and Degradation; (2) Advanced Light Water Reactor Nuclear Fuels; (3) Advanced Instrumentation, Information and Control Systems; and (4) Risk-Informed Safety Margin Characterization. This report describes an irradiation testing readiness analysis in preparation of LWRS experiments for irradiation testing at the Idaho National Laboratory (INL) Advanced Test Reactor (ATR) under Pathway (2). The focus of the Advanced LWR Nuclear Fuels Pathway is to improve the scientific knowledge basis for understanding and predicting fundamental performance of advanced nuclear fuel and cladding in nuclear power plants during both nominal and off-nominal conditions. This information will be applied in the design and development of high-performance, high burn-up fuels with improved safety, cladding integrity, and improved nuclear fuel cycle economics

  12. ATR National Scientific User Facility 2009 Annual Report

    Energy Technology Data Exchange (ETDEWEB)

    Todd R. Allen; Mitchell K. Meyer; Frances Marshall; Mary Catherine Thelen; Jeff Benson

    2010-11-01

    This report describes activities of the ATR NSUF from FY-2008 through FY-2009 and includes information on partner facilities, calls for proposals, users week and education programs. The report also contains project information on university research projects that were awarded by ATR NSUF in the fiscal years 2008 & 2009. This research is university-proposed researcher under a user facility agreement. All intellectual property from these experiments belongs to the university per the user agreement.

  13. FLUX SENSOR EVALUATIONS AT THE ATR CRITICAL FACILITY

    Energy Technology Data Exchange (ETDEWEB)

    Troy Unruh; Joy Rempe; David Nigg; George Imel; Jason Harris; Eric Bonebrake

    2010-11-01

    The Advanced Test Reactor (ATR) and the ATR Critical (ATRC) facilities lack real-time methods for detecting thermal neutron flux and fission reaction rates for irradiation capsules. Direct measurements of the actual power deposited into a test are now possible without resorting to complicated correction factors. In addition, it is possible to directly measure minor actinide fission reaction rates and to provide time-dependent monitoring of the fission reaction rate or fast/thermal flux during transient testing. A joint Idaho State University /Idaho National Laboratory ATR National Scientific User Facility (ATR NSUF) project was recently initiated to evaluate new real-time state-of-the-art in-pile flux detection sensors. Initially, the project is comparing the accuracy, response time, and long duration performance of French Atomic Energy Commission (CEA)-developed miniature fission chambers, specialized self-powered neutron detectors (SPNDs) by the Argentinean National Energy Commission (CNEA), specially developed commercial SPNDs, and back-to-back fission (BTB) chambers developed by Argonne National Laboratory (ANL). As discussed in this paper, specialized fixturing and software was developed by INL to facilitate these joint ISU/INL evaluations. Calculations were performed by ISU to assess the performance of and reduce uncertainties in flux detection sensors and compare data obtained from these sensors with existing integral methods employed at the ATRC. Ultimately, project results will be used to select the detector that can provide the best online regional ATRC power measurement. It is anticipated that project results may offer the potential to increase the ATRC’s current power limit and its ability to perform low-level irradiation experiments. In addition, results from this effort will provide insights about the viability of using these detectors in the ATR. Hence, this effort complements current activities to improve ATR software tools, computational

  14. Homeostatic regulation of meiotic DSB formation by ATM/ATR

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Tim J.; Wardell, Kayleigh; Garcia, Valerie; Neale, Matthew J., E-mail: m.neale@sussex.ac.uk

    2014-11-15

    Ataxia–telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage-sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed.

  15. Monitoring Theophylline Concentrations in Saline Using Terahertz ATR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Kei Takeya

    2016-03-01

    Full Text Available To assess the possibility of terahertz technology for the determination of drug concentration in blood, we endeavored to apply a terahertz (THz attenuated total reflection (ATR method to measure the levels of theophylline in saline. A change in reflected THz wave amplitude was observed in a theophylline concentration-dependent manner. This result was obtained with simple measurements of comparisons of the amplitude of the reflected wave, and suggests that it is possible to monitor concentration changes of drugs in liquid material using THz ATR measurements.

  16. HMGA2 Inhibits Apoptosis through Interaction with ATR-CHK1 Signaling Complex in Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Suchitra Natarajan

    2013-03-01

    Full Text Available The non-histone chromatin binding protein high mobility group AT-hook 2 (HMGA2 is expressed in stem cells and many cancer cells, including tumor initiating cells, but not translated in normal human somatic cells. The presence of HMGA2 is correlated with advanced neoplastic disease and poor prognosis for patients. We had previously demonstrated a role of HMGA2 in DNA repair pathways. In the present study, we employed different human tumor cell models with endogenous and exogenous expression of HMGA2 and show that upon DNA damage, the presence of HMGA2 caused an increased and sustained phosphorylation of the ataxia telangiectasia and Rad3-related kinase (ATR and its downstream target checkpoint kinase 1 (CHK1. The presence of activated pCHK1Ser296 coincided with prolonged G2/M block and increased tumor cell survival, which was enhanced further in the presence of HMGA2. Our study, thus, identifies a novel relationship between the ATR-CHK1 DNA damage response pathway and HMGA2, which may support the DNA repair function of HMGA2 in cancer cells. Furthermore, our data provide a rationale for the use of inhibitors to ATR or CHK1 and HMGA2 in the treatment of HMGA2-positive human cancer cells.

  17. Validation of HELIOS for ATR Core Follow Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Bays, Samuel E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Swain, Emily T. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Crawford, Douglas S. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Nigg, David W. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-03-01

    This work summarizes the validation analyses for the HELIOS code to support core design and safety assurance calculations of the Advanced Test Reactor (ATR). Past and current core safety assurance is performed by the PDQ-7 diffusion code; a state of the art reactor physics simulation tool from the nuclear industry’s earlier days. Over the past twenty years, improvements in computational speed have enabled the use of modern neutron transport methodologies to replace the role of diffusion theory for simulation of complex systems, such as the ATR. More exact methodologies have enabled a paradigm-shift away from highly tuned codes that force compliance with a bounding safety envelope, and towards codes regularly validated against routine measurements. To validate HELIOS, the 16 ATR operational cycles from late-2009 to present were modeled. The computed power distribution was compared against data collected by the ATR’s on-line power surveillance system. It was found that the ATR’s lobe-powers could be determined with ±10% accuracy. Also, the ATR’s cold startup shim configuration for each of these 16 cycles was estimated and compared against the reported critical position from the reactor log-book. HELIOS successfully predicted criticality within the tolerance set by the ATR startup procedure for 13 out of the 16 cycles. This is compared to 12 times for PDQ (without empirical adjustment). These findings, as well as other insights discussed in this report, suggest that HELIOS is highly suited for replacing PDQ for core safety assurance of the ATR. Furthermore, a modern verification and validation framework has been established that allows reactor and fuel performance data to be computed with a known degree of accuracy and stated uncertainty.

  18. Application of ATR-spectroscopy aboard landers: the MATROS experiment

    Science.gov (United States)

    Grigoriev, A.; Coradini, A.; Korablev, O.; Korzhenevskaya, T.; Korolev, Yu.; Gusev, M.; Garbuz, A.; Moshkin, E.; Piccioni, G.; Bellucci, G.; Dibs/Pasteur Team

    We propose to implement the technique of Attenuated Total Reflection (ATR) spectroscopy for in situ studies of planets and small bodies. This method is well-known in laboratory practice (especially in microbiological studies), but so far was not used in space. During descend in an atmosphere an ATR-spectrometer allows investigation of suspended particles -- both solid and liquid. After landing, it can be used for mineralogical studies; on potentially habitable bodies (Mars, Europe) ATR-spectroscopy can be focused on direct detection of living cells. The primary goal of Exo-Mars Pasteur program (2009) is the search for Martian life. We propose for Pasteur the MATROS (Martian Attenuated Total Reflection Optical Spectroscopy) investigation in synergy with DIBS (Drill-Integrated spectrometer) and MIMA (Infrared spectrometer) -- two experiments rated as ``very good'' during preliminary selection. MATROS will perform mineralogical analysis and search for primitive forms of Martian life. Soil samples will be provided from the drill's distribution system. MATROS' hardware consists of a dedicated Mineralogical-Biological Unit (MBU) with multiple hermetic lid and an internal source of radiation (micro-globar). The spectrum of this globar at the output of MATROS modified by ATR absorption will be analyzed by DIBS near infrared spectrometer (0.7-2.8 μ m) and by MIMA Fourier-spectrometer (2.5-20 μ m). Thus the ATR absorption spectra will be measured in the spectral range as wide as 0.7-20 μ m. The measuring sequence is as follows: first, MBU is sterilized by heating up to 100C or more. Then, a sample (actually a bit of mineral powder) will be put into the MBU and analyzed to obtain mineralogical information, including possibly the oxidation degree. After this, some water will be added, and a modification of the ATR spectrum may indicate the presence of clay minerals. Finally, we set up the conditions optimal for culturing of anaerobic autotrophic bacteria (proper temperature

  19. Activation of the ATR kinase by the RPA-binding protein ETAA1

    DEFF Research Database (Denmark)

    Haahr, Peter; Hoffmann, Saskia; Tollenaere, Maxim A X

    2016-01-01

    Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway...... in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults. Mechanistically......, this requires a conserved domain in ETAA1 that potently and directly stimulates ATR kinase activity independently of TopBP1. Simultaneous loss of ETAA1 and TopBP1 gives rise to synthetic lethality characterized by massive genome instability and abrogation of ATR-dependent signalling. Our findings demonstrate...

  20. Key features for ATA / ATR database design in missile systems

    Science.gov (United States)

    Özertem, Kemal Arda

    2017-05-01

    Automatic target acquisition (ATA) and automatic target recognition (ATR) are two vital tasks for missile systems, and having a robust detection and recognition algorithm is crucial for overall system performance. In order to have a robust target detection and recognition algorithm, an extensive image database is required. Automatic target recognition algorithms use the database of images in training and testing steps of algorithm. This directly affects the recognition performance, since the training accuracy is driven by the quality of the image database. In addition, the performance of an automatic target detection algorithm can be measured effectively by using an image database. There are two main ways for designing an ATA / ATR database. The first and easy way is by using a scene generator. A scene generator can model the objects by considering its material information, the atmospheric conditions, detector type and the territory. Designing image database by using a scene generator is inexpensive and it allows creating many different scenarios quickly and easily. However the major drawback of using a scene generator is its low fidelity, since the images are created virtually. The second and difficult way is designing it using real-world images. Designing image database with real-world images is a lot more costly and time consuming; however it offers high fidelity, which is critical for missile algorithms. In this paper, critical concepts in ATA / ATR database design with real-world images are discussed. Each concept is discussed in the perspective of ATA and ATR separately. For the implementation stage, some possible solutions and trade-offs for creating the database are proposed, and all proposed approaches are compared to each other with regards to their pros and cons.

  1. Recent ATR and fusion algorithm improvements for multiband sonar imagery

    Science.gov (United States)

    Aridgides, Tom; Fernández, Manuel

    2009-05-01

    An improved automatic target recognition processing string has been developed. The overall processing string consists of pre-processing, subimage adaptive clutter filtering, normalization, detection, data regularization, feature extraction, optimal subset feature selection, feature orthogonalization and classification processing blocks. The objects that are classified by the 3 distinct ATR strings are fused using the classification confidence values and their expansions as features, and using "summing" or log-likelihood-ratio-test (LLRT) based fusion rules. The utility of the overall processing strings and their fusion was demonstrated with new high-resolution three-frequency band sonar imagery. The ATR processing strings were individually tuned to the corresponding three-frequency band data, making use of the new processing improvement, data regularization; this improvement entails computing the input data mean, clipping the data to a multiple of its mean and scaling it, prior to feature extraction and resulted in a 3:1 reduction in false alarms. Two significant fusion algorithm improvements were made. First, a nonlinear exponential Box-Cox expansion (consisting of raising data to a to-be-determined power) feature LLRT fusion algorithm was developed. Second, a repeated application of a subset Box-Cox feature selection / feature orthogonalization / LLRT fusion block was utilized. It was shown that cascaded Box-Cox feature LLRT fusion of the ATR processing strings outperforms baseline "summing" and single-stage Box-Cox feature LLRT algorithms, yielding significant improvements over the best single ATR processing string results, and providing the capability to correctly call the majority of targets while maintaining a very low false alarm rate.

  2. Preliminary Discrimination of Butter Adulteration by ATR-FTIR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Lucian Cuibus

    2015-05-01

    Full Text Available The Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR  was applied for the discrimination of butter samples adulterated with solid fraction of palm oil. For FTIR fingerprinting of butter samples, with or without controlled additions of palm oil as adulterant was firstly obtained, using a Shimatsu Prestige 21 Spectrophotometer, including a horizontal diamond ATR accessory with reflection in the MIR region (3873-690 cm-1.The spiked butter samples including 0 level and seven increasing concentrations of palm fats, up to 50% were fingerprinted and the calibration curve was obtained (n=19. In parallel, the validation was realized using different set of spiked butter samples ranging 1-44.4 % of palm fat (n=7. Finally, an independent set of commercial samples was analized (n=14.Partial least squares (PLS model was used for statistical data processing in accordance with standard method. The value of the correlation coefficient (R2= 0.977 between actual and predicted values was statistically significant (p<0.001, considering the superposition of  "actual vs predicted” curves. This combined FTIR-PLS evaluation revealed that 3 out of  samples of butter were suspected of adulteration with palm oil, presented values 14 ranging 4-12%.In conclusion, ATR-FTIR methodology may offer an rapid evaluation of  butter samples authenticity. The low value for detection limit (3%palm oil in butter and the low limit of quantification (9.8% palm oil in butter confirms that ATR-FTIR spectroscopy  is a sensitive method to identify the adulteration of butter with  palm oil.   

  3. AGR-2 Data Qualification Report for ATR Cycle 154B

    Energy Technology Data Exchange (ETDEWEB)

    Binh Pham; Jeff Einerson

    2014-01-01

    This report provides the data qualification status of Advanced Gas Reactor-2 (AGR-2) fuel irradiation experimental data from Advanced Test Reactor (ATR) Cycle 154B as recorded in the Nuclear Data Management and Analysis System (NDMAS). This is the last cycle of AGR-2 irradiation, as the test train was pulled from the ATR core during the outage portion of ATR Cycle 155A. The AGR-2 data streams addressed in this report include thermocouple (TC) temperatures, sweep gas data (flow rates including new Fission Product Monitoring (FPM) downstream flows from Fission Product Monitoring System (FPMS) detectors, pressure, and moisture content), and FPMS data (release rates and release-to-birth rate ratios [R/Bs]) for each of the six capsules in the AGR-2 experiment. The final data qualification status for these data streams is determined by a Data Review Committee (DRC) comprised of AGR technical leads, Sitewide Quality Assurance (QA), and NDMAS analysts. The Data Review Committee reviewed the data acquisition process, considered whether the data met the requirements for data collection as specified in QA-approved Very High Temperature Reactor (VHTR) data collection plans, examined the results of NDMAS data testing and statistical analyses, and confirmed the qualification status of the data as given in this report.

  4. Natural convection heat transfer analysis of ATR fuel elements

    Energy Technology Data Exchange (ETDEWEB)

    Langerman, M.A.

    1992-05-01

    Natural convection air cooling of the Advanced Test Reactor (ATR) fuel assemblies is analyzed to determine the level of decay heat that can be removed without exceeding the melting temperature of the fuel. The study was conducted to assist in the level 2 PRA analysis of a hypothetical ATR water canal draining accident. The heat transfer process is characterized by a very low Rayleigh number (Ra {approx} 10{sup {minus}5}) and a high temperature ratio. Since neither data nor analytical models were available for Ra < 0.1, an analytical approach is presented based upon the integral boundary layer equations. All assumptions and simplifications are presented and assessed and two models are developed from similar foundations. In one model, the well-known Boussinesq approximations are employed, the results from which are used to assess the modeling philosophy through comparison to existing data and published analytical results. In the other model, the Boussinesq approximations are not used, thus making the model more general and applicable to the ATR analysis.

  5. Immune Response of A Novel ATR-AP205-001 Conjugate Anti-hypertensive Vaccine.

    Science.gov (United States)

    Hu, Xiajun; Deng, Yihuan; Chen, Xiao; Zhou, Yanzhao; Zhang, Hongrong; Wu, Hailang; Yang, Shijun; Chen, Fen; Zhou, Zihua; Wang, Min; Qiu, Zhihua; Liao, Yuhua

    2017-10-03

    We developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals. In this study, we focused on the immunological effect and safety of the VLP-based vaccine. By comparing to the depolymerized dimeric vaccine ATR-Dimer-001, we found that ATR-AP205-001 reached subcapsular sinus of lymph node shortly after administration, followed by accumulation on follicle dendritic cells via follicle B cell transportation, while ATR-Dimer-001 vaccine showed no association with FDCs. ATR-AP205-001 vaccine strongly activated dendritic cells, which promoted T cells differentiation to follicular helper T cells. ATR-AP205-001 vaccine induced powerful germinal center reaction, which was translated to a boost of specific antibody production and long-lasting B cell memory, far superior to ATR-Dimer-001 vaccine. Moreover, neither cytotoxic T cells, nor Th1/Th17 cell-mediated inflammation was observed in ATR-AP205-001 vaccine, similar to ATR-Dimer-001 vaccine. We concluded that ATR-AP205-001 vaccine quickly induced potent humoral immunity through collaboration of B cells, follicular dendritic cells and follicular helper T cells, providing an effective and safe intervention for hypertension in the future clinical application.

  6. Transcriptional Regulation of the Daptomycin Gene Cluster in Streptomyces roseosporus by an Autoregulator, AtrA*

    Science.gov (United States)

    Mao, Xu-Ming; Luo, Shuai; Zhou, Ri-Cheng; Wang, Feng; Yu, Pin; Sun, Ning; Chen, Xiao-Xia; Tang, Yi; Li, Yong-Quan

    2015-01-01

    Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus. To reveal the transcriptional regulatory mechanism of daptomycin biosynthesis, we used the biotinylated dptE promoter (dptEp) as a probe to affinity isolate the dptEp-interactive protein AtrA, a TetR family transcriptional regulator, from the proteome of mycelia. AtrA bound directly to dptEp to positively regulate gene cluster expression and daptomycin production. Meanwhile, both ΔatrA and ΔadpA mutants showed bald phenotype and null production of daptomycin. AdpA positively regulated atrA expression by direct interaction with atrA promoter (atrAp), and removal of ArpA in S. roseosporus, a homolog of the A-factor receptor, resulted in accelerated morphological development and increased daptomycin production, suggesting that atrA was the target of AdpA to mediate the A-factor signaling pathway. Furthermore, AtrA was positively autoregulated by binding to its own promoter atrAp. Thus, for the first time at the transcriptional level, we have identified an autoregulator, AtrA, that directly mediates the A-factor signaling pathway to regulate the proper production of daptomycin. PMID:25648897

  7. Transcriptional regulation of the daptomycin gene cluster in Streptomyces roseosporus by an autoregulator, AtrA.

    Science.gov (United States)

    Mao, Xu-Ming; Luo, Shuai; Zhou, Ri-Cheng; Wang, Feng; Yu, Pin; Sun, Ning; Chen, Xiao-Xia; Tang, Yi; Li, Yong-Quan

    2015-03-20

    Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus. To reveal the transcriptional regulatory mechanism of daptomycin biosynthesis, we used the biotinylated dptE promoter (dptEp) as a probe to affinity isolate the dptEp-interactive protein AtrA, a TetR family transcriptional regulator, from the proteome of mycelia. AtrA bound directly to dptEp to positively regulate gene cluster expression and daptomycin production. Meanwhile, both ΔatrA and ΔadpA mutants showed bald phenotype and null production of daptomycin. AdpA positively regulated atrA expression by direct interaction with atrA promoter (atrAp), and removal of ArpA in S. roseosporus, a homolog of the A-factor receptor, resulted in accelerated morphological development and increased daptomycin production, suggesting that atrA was the target of AdpA to mediate the A-factor signaling pathway. Furthermore, AtrA was positively autoregulated by binding to its own promoter atrAp. Thus, for the first time at the transcriptional level, we have identified an autoregulator, AtrA, that directly mediates the A-factor signaling pathway to regulate the proper production of daptomycin. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Analysis of the ATR fuel element swaging process

    Energy Technology Data Exchange (ETDEWEB)

    Richins, W.D.; Miller, G.K.

    1995-12-01

    This report documents a detailed evaluation of the swaging process used to connect fuel plates to side plates in Advanced Test Reactor (ATR) fuel elements. The swaging is a mechanical process that begins with fitting a fuel plate into grooves in the side plates. Once a fuel plate is positioned, a lip on each of two side plate grooves is pressed into the fuel plate using swaging wheels to form the joints. Each connection must have a specified strength (measured in terms, of a pullout force capacity) to assure that these joints do not fail during reactor operation. The purpose of this study is to analyze the swaging process and associated procedural controls, and to provide recommendations to assure that the manufacturing process produces swaged connections that meet the minimum strength requirement. The current fuel element manufacturer, Babcock and Wilcox (B&W) of Lynchburg, Virginia, follows established procedures that include quality inspections and process controls in swaging these connections. The procedures have been approved by Lockheed Martin Idaho Technologies and are designed to assure repeatability of the process and structural integrity of each joint. Prior to July 1994, ATR fuel elements were placed in the Hydraulic Test Facility (HTF) at the Idaho National Engineering Laboratory (AGNAIL), Test Reactor Area (TRA) for application of Boehmite (an aluminum oxide) film and for checking structural integrity before placement of the elements into the ATR. The results presented in this report demonstrate that the pullout strength of the swaged connections is assured by the current manufacturing process (with several recommended enhancements) without the need for- testing each element in the HTF.

  9. Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection

    DEFF Research Database (Denmark)

    Carson, Christian T; Orazio, Nicole I; Lee, Darwin V

    2009-01-01

    The protein kinases ataxia-telangiectasia mutated (ATM) and ATM-Rad3 related (ATR) are activated in response to DNA damage, genotoxic stress and virus infections. Here we show that during infection with wild-type adenovirus, ATR and its cofactors RPA32, ATRIP and TopBP1 accumulate at viral...... during virus infection, which is independent of Mre11 nuclease activity and recruitment of RPA/ATR/ATRIP/TopBP1. Unlike other damage scenarios, we found that ATM and ATR signaling are not dependent on each other during infection. We identify a region of the viral E4orf3 protein responsible...

  10. UCSB ATR-­NSUF Irradiation DMC Sample Inspection Report

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, Tarik A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Quintana, Matthew Estevan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Romero, Tobias J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-02-23

    A variety of tensile samples of Ferritic and Oxide Dispersion Strengthened (ODS or nanoferritic) steels were placed the ATR reactor over 2 Years achieving doses of roughly 4-6 dpa at temperatures of roughly 290°C. After irradiation, samples were shipped from the MFC hot cells at Idaho National Laboratory (INL) to the Wing 9 hot cells in the CMR facility at Los Alamos National Laboratory. Samples were cleaned to removed alpha contamination from the MFC hot cells, and then, as needed removed from their irradiation containers, sorted and inspected. This report will summarize the inspection of the Disc Multipurpose Coupon (DMC) inspection from packet 7-1.

  11. The role of ATR kinase during mammalian gametogenesis

    OpenAIRE

    Pacheco Piñol, Sarai

    2015-01-01

    ATR és una proteïna cinasa essencial per a la viabilitat cel·lular que participa en els mecanismes de resposta al dany en el DNA per tal de mantenir la integritat del genoma. Aquesta proteïna es activada en resposta a regions de cadena simple del DNA (ssDNA) generades per la resecció dels trencaments de doble cadena (DSBs) i controla la progressió de les forques de replicació durant la fase S del cicle cel·lular. Durant la meiosi, un tipus de divisió cel·lular especialitzada per la qual les c...

  12. The use of ATR-FTIR imaging to study coated oil capsules

    NARCIS (Netherlands)

    Heussen, P.C.M.; Dalen, van G.; Nootenboom, P.; Smit, I.; Duynhoven, van J.P.M.

    2012-01-01

    Fourier transform infrared (FTIR) spectroscopic imaging using a large Internal Reflection Element (IRE), also called Attenuated Total Reflection (ATR) crystal, can be used for the identification and localisation of chemical compounds in solid food products. In this study ATR-FTIR imaging, by means

  13. S phase block following MEC1ATR inactivation occurs without severe dNTP depletion

    Directory of Open Access Journals (Sweden)

    Caroline Earp

    2015-12-01

    Full Text Available Inactivation of Mec1, the budding yeast ATR, results in a permanent S phase arrest followed by chromosome breakage and cell death during G2/M. The S phase arrest is proposed to stem from a defect in Mec1-mediated degradation of Sml1, a conserved inhibitor of ribonucleotide reductase (RNR, causing a severe depletion in cellular dNTP pools. Here, the casual link between the S phase arrest, Sml1, and dNTP-levels is examined using a temperature sensitive mec1 mutant. In addition to S phase arrest, thermal inactivation of Mec1 leads to constitutively high levels of Sml1 and an S phase arrest. Expression of a novel suppressor, GIS2, a conserved mRNA binding zinc finger protein, rescues the arrest without down-regulating Sml1 levels. The dNTP pool in mec1 is reduced by ∼17% and GIS2 expression restores it, but only partially, to ∼93% of a control. We infer that the permanent S phase block following Mec1 inactivation can be uncoupled from its role in Sml1 down-regulation. Furthermore, unexpectedly modest effects of mec1 and GIS2 on dNTP levels suggest that the S phase arrest is unlikely to result from a severe depletion of dNTP pool as assumed, but a heightened sensitivity to small changes in its availability.

  14. Modern approaches in deep learning for SAR ATR

    Science.gov (United States)

    Wilmanski, Michael; Kreucher, Chris; Lauer, Jim

    2016-05-01

    Recent breakthroughs in computational capabilities and optimization algorithms have enabled a new class of signal processing approaches based on deep neural networks (DNNs). These algorithms have been extremely successful in the classification of natural images, audio, and text data. In particular, a special type of DNNs, called convolutional neural networks (CNNs) have recently shown superior performance for object recognition in image processing applications. This paper discusses modern training approaches adopted from the image processing literature and shows how those approaches enable significantly improved performance for synthetic aperture radar (SAR) automatic target recognition (ATR). In particular, we show how a set of novel enhancements to the learning algorithm, based on new stochastic gradient descent approaches, generate significant classification improvement over previously published results on a standard dataset called MSTAR.

  15. Structural Analysis of Spiropyran Polimers using ATR Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Delgado Macui, R; Rojas Lopez, M; Gayou, V L; Orduna Diaz, A [Centro de Investigacion en BiotecnologIa Aplicada del IPN, San Juan de los Molinos km. 1.5 Tepetitla de Lardizabal, A.P. 90700, Tlaxcala (Mexico)

    2006-01-01

    We have used infrared spectroscopy in attenuated total reflection (ATR) mode to analyze the interactions between the polymeric base and solvent with a photochromic material (spyropiran). We used cellulose acetate as polymeric base and the spyropiran; 1,3,3 trimethyl indoline-5-nitro benzopyrane. Thin films with different weight concentrations of SP were deposited in the polymeric base. The infrared spectra show bands whose frequencies are associated to several molecular bondings. It was observed a decreasing in intensity of absorbance for C = O stretching mode of the acetate group at 1720 cm{sup -1} and for C = C stretching mode for the main chain at 823 and 982 cm{sup -1} both associated to the presence of SP in polymeric films.

  16. Feature Fusion Based on Convolutional Neural Network for SAR ATR

    Directory of Open Access Journals (Sweden)

    Chen Shi-Qi

    2017-01-01

    Full Text Available Recent breakthroughs in algorithms related to deep convolutional neural networks (DCNN have stimulated the development of various of signal processing approaches, where the specific application of Automatic Target Recognition (ATR using Synthetic Aperture Radar (SAR data has spurred widely attention. Inspired by the more efficient distributed training such as inception architecture and residual network, a new feature fusion structure which jointly exploits all the merits of each version is proposed to reduce the data dimensions and the complexity of computation. The detailed procedure presented in this paper consists of the fused features, which make the representation of SAR images more distinguishable after the extraction of a set of features from DCNN, followed by a trainable classifier. In particular, the obtained results on the 10-class benchmark data set demonstrate that the presented architecture can achieve remarkable classification performance to the current state-of-the-art methods.

  17. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

    Science.gov (United States)

    Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

    2017-02-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21CIP/WAF1)-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21CIP/WAF1)-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21CIP/WAF1)-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21CIP/WAF1)-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

  18. Mutation of serine 1333 in the ATR HEAT repeats creates a hyperactive kinase.

    Directory of Open Access Journals (Sweden)

    Jessica W Luzwick

    Full Text Available Subcellular localization, protein interactions, and post-translational modifications regulate the DNA damage response kinases ATR, ATM, and DNA-PK. During an analysis of putative ATR phosphorylation sites, we found that a single mutation at S1333 creates a hyperactive kinase. In vitro and in cells, mutation of S1333 to alanine (S1333A-ATR causes elevated levels of kinase activity with and without the addition of the protein activator TOPBP1. S1333 mutations to glycine, arginine, or lysine also create a hyperactive kinase, while mutation to aspartic acid decreases ATR activity. S1333A-ATR maintains the G2 checkpoint and promotes completion of DNA replication after transient exposure to replication stress but the less active kinase, S1333D-ATR, has modest defects in both of these functions. While we find no evidence that S1333 is phosphorylated in cultured cells, our data indicate that small changes in the HEAT repeats can have large effects on kinase activity. These mutants may serve as useful tools for future studies of the ATR pathway.

  19. Evaluation of the AtrAedes™ Lure for Collection of Culex quinquefasciatus in Gravid Traps.

    Science.gov (United States)

    Irish, S R; Batengana, B M; Eiras, A E; Cameron, M M

    2015-03-01

    The typical attractant used in gravid trapping of Culex quinquefasciatus is an aged infusion of organic materials, which can change in attractiveness over time. A standardized chemical attractant dispenser derived from grass infusion, the AtrAedes™ lure, has been produced for the surveillance of the dengue vector Aedes aegypti. A study using this lure in combination with the Centers for Disease Control and Prevention gravid traps was conducted in Tanga, Tanzania. The addition of the lure to traps baited with either grass infusion or tap water did not result in significant increases in trap catch. Grass infusion-baited traps (with and without the AtrAedes lure) collected significantly more Cx. quinquefasciatus than traps baited with AtrAedes + tap water, tap water alone, or AtrAedes alone. The catches of the traps baited with AtrAedes + tap water, tap water alone, and AtrAedes alone were not significantly different from each other. Although the placement of the lure in the base of the trap may have decreased trap catches, it seems that the AtrAedes is not as effective as grass infusion for collecting Cx. quinquefasciatus in Tanzania.

  20. Roles of ATR1 paralogs YMR279c and YOR378w in boron stress tolerance

    OpenAIRE

    BOZDAĞ, Gönensin Ozan; Uluışık, İrem; Gülcüler, Gülce Sıla; Karakaya, Hüseyin Çağlar; KOÇ, Ahmet

    2011-01-01

    Boron is a necessary nutrient for plants and animals, however excess of it causes toxicity. Previously, Atr1 and Arabidopsis Bor1 homolog were identified as the boron efflux pump in yeast, which lower the cytosolic boron concentration and help cells to survive in the presence of toxic amount of boron. In this study, we analyzed ATR1 paralogs, YMR279c and YOR378w, to understand whether they participate in boron stress tolerance in yeast. Even though these genes share homology with ATR1, neithe...

  1. Identification of a Novel System for Boron Transport: Atr1 Is a Main Boron Exporter in Yeast▿ †

    Science.gov (United States)

    Kaya, Alaattin; Karakaya, Huseyin C.; Fomenko, Dmitri E.; Gladyshev, Vadim N.; Koc, Ahmet

    2009-01-01

    Boron is a micronutrient in plants and animals, but its specific roles in cellular processes are not known. To understand boron transport and functions, we screened a yeast genomic DNA library for genes that confer resistance to the element in Saccharomyces cerevisiae. Thirty boron-resistant transformants were isolated, and they all contained the ATR1 (YML116w) gene. Atr1 is a multidrug resistance transport protein belonging to the major facilitator superfamily. C-terminal green fluorescent protein-tagged Atr1 localized to the cell membrane and vacuole, and ATR1 gene expression was upregulated by boron and several stress conditions. We found that atr1Δ mutants were highly sensitive to boron treatment, whereas cells overexpressing ATR1 were boron resistant. In addition, atr1Δ cells accumulated boron, whereas ATR1-overexpressing cells had low intracellular levels of the element. Furthermore, atr1Δ cells showed stronger boron-dependent phenotypes than mutants deficient in genes previously reported to be implicated in boron metabolism. ATR1 is widely distributed in bacteria, archaea, and lower eukaryotes. Our data suggest that Atr1 functions as a boron efflux pump and is required for boron tolerance. PMID:19414602

  2. ATR-FTIR as a potential tool for controlling high quality vinegar categories

    DEFF Research Database (Denmark)

    Ríos-Reina, Rocío; Callejón, Raquel M.; Oliver-Pozo, Celia

    2017-01-01

    Characterization of wine vinegars qualified with a Protected Designation of Origin (PDO) is crucial to certify their quality and authenticity. Spectroscopic techniques as Fourier transform mid infrared spectroscopy (FTIR) with Attenuated Total Reflectance (ATR) has been applied to investigate its...

  3. Montana Weigh-in-Motion (WIM) and Automatic Traffic Recorder (ATR) Strategy Final Report

    Science.gov (United States)

    2017-03-01

    The objective of this project was to review the Montana Department of Transportations (MDTs) permanent Weigh-in-Motion (WIM) and Automated Traffic Recorder (ATR) data collection programs to ensure they are efficiently providing the best possibl...

  4. Encefalomenigocele atrésico parietal Parietal atresic encephalomeningocele

    Directory of Open Access Journals (Sweden)

    Liliana Rivera Oliva

    2011-09-01

    Full Text Available El encefalocele es una anomalía congénita rara, en la que una porción del encéfalo protruye a través de un orificio craneal (evaginación, generalmente situado en la línea media. Clínicamente se caracteriza por una masa epicraneal, de consistencia blanda, muchas veces acompañada de trastornos psicomotores, convulsiones y trastornos de la visión. Se presenta el caso de un recién nacido con diagnóstico de encefalomeningocele atrésico parietal, intervenido quirúrgicamente y con evolución satisfactoria.The encephalocele is a uncommon congenital anomaly where a portion of encephalon protrudes through a cranial orifice (evagination, generally located in the middle line. Clinically, it is characterized by a soft epicranial mass often accompanied or psychomotor disorders, convulsions and vision disorders. This is the case of a newborn diagnosed with parietal atresic encephalomeningocele operated on with a satisfactory evolution.

  5. Experimental active control of sound in the ATR 42

    Science.gov (United States)

    Paonessa, A.; Sollo, A.; Paxton, M.; Purver, M.; Ross, C. F.

    Passenger comfort is becoming day by day an important issue for the market of the regional turboprop aircraft and also for the future high speed propeller driven aircraft. In these aircraft the main contribution to the passenger annoyance is due to the propeller noise blade passing frequency (BPF) and its harmonics. In the recent past a detailed theoretical and experimental work has been done by Alenia Aeronautica in order to reduce the noise level in the ATR aircraft passenger cabin by means of conventional passive treatments: synchrophasing of propellers, dynamic vibration absorbers, structural reinforcements, damping materials. The application of these treatments has been introduced on production aircraft with a remarkable improvement of noise comfort but with a significant weight increase. For these reasons, a major technology step is required for reaching passenger comfort comparable to that of jet aircraft with the minimum weight increase. The most suitable approach to this problem has been envisaged in the active noise control which consists in generating an anti-sound field in the passenger cabin to reduce the noise at propeller BPF and its harmonics. The attenuation is reached by means of a control system which acquires information about the cabin noise distribution and the propeller speed during flight and simultaneously generates the signals to drive the speakers.

  6. Neutron dosimetry and damage calculations for the ATR-A1 irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Ratner, R.T. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-09-01

    Neutron fluence measurements and radiation damage calculations are reported for the collaborative US/Japan ATR-A1 irradiation in the Advanced Test Reactor (ATR) at Idaho National Engineering Laboratory (INEL). The maximum total neutron fluence at midplane was 9.4 {times} 10{sup 21} n/cm{sup 2} (5.5 {times} 10{sup 21} n/cm{sup 2} above 0.1 MeV), resulting in about 4.6 dpa in vanadium.

  7. ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres

    Directory of Open Access Journals (Sweden)

    Adrian S. Tong

    2015-11-01

    Full Text Available The yeast homologs of the ATM and ATR DNA damage response kinases play key roles in telomerase-mediated telomere maintenance, but the role of ATM/ATR in the mammalian telomerase pathway has been less clear. Here, we demonstrate the requirement for ATM and ATR in the localization of telomerase to telomeres and telomere elongation in immortal human cells. Stalled replication forks increased telomerase recruitment in an ATR-dependent manner. Furthermore, increased telomerase recruitment was observed upon phosphorylation of the shelterin component TRF1 at an ATM/ATR target site (S367. This phosphorylation leads to loss of TRF1 from telomeres and may therefore increase replication fork stalling. ATM and ATR depletion reduced assembly of the telomerase complex, and ATM was required for telomere elongation in cells expressing POT1ΔOB, an allele of POT1 that disrupts telomere-length homeostasis. These data establish that human telomerase recruitment and telomere elongation are modulated by DNA-damage-transducing kinases.

  8. Achilles Tendon Reflex (ATR) in response to short exposures of microgravity and hypergravity

    Science.gov (United States)

    Fujii, M.; Jaweed, M.

    1992-01-01

    Previous studies indicate that latency and amplitude of the Achilles tendon reflex (ATR) are reduced after exposure to microgravity for 28 days. The objective of this study was to quantitatively measure the latency of ATR during brief (20 sec) exposure to microgravity in KC-135 parabolic flights. Methods: The ATR was elicited in ten men during parabolic flight with the ankle held neutrally, planarflexed, and dorsiflexed. During flight, the ATR was elicited during the zero G and 1.8 G phases. Postflight testing was performed flying back to the airfield. Latencies to onset of the ATR were calculated and analyses of variance were performed to determine the effect of gravity and ankle position on latency. Result: The mean latencies for zero-G, 1.8-G and postflight with the ankle in the neutral position were 32.7 plus or minus 0.5 ms, and 33.1 plus or minus 0.7 ms respectively, which were not significantly different. There was a trend toward prolongation of latencies postflight. The mean latency for those who were motion sick was 32.1 plus or minus 0.1 ms compared to 34.0 plus or minus 0.3 ms for those who were not sick. Conclusions: These studies indicate that neither the level of gravity nor ankle position significantly affected the latency of the ATR.

  9. Structural elucidation and functional characterization of the Hyaloperonospora arabidopsidis effector protein ATR13.

    Directory of Open Access Journals (Sweden)

    Lauriebeth Leonelli

    2011-12-01

    Full Text Available The oomycete Hyaloperonospora arabidopsidis (Hpa is the causal agent of downy mildew on the model plant Arabidopsis thaliana and has been adapted as a model system to investigate pathogen virulence strategies and plant disease resistance mechanisms. Recognition of Hpa infection occurs when plant resistance proteins (R-genes detect the presence or activity of pathogen-derived protein effectors delivered to the plant host. This study examines the Hpa effector ATR13 Emco5 and its recognition by RPP13-Nd, the cognate R-gene that triggers programmed cell death (HR in the presence of recognized ATR13 variants. Herein, we use NMR to solve the backbone structure of ATR13 Emco5, revealing both a helical domain and a disordered internal loop. Additionally, we use site-directed and random mutagenesis to identify several amino acid residues involved in the recognition response conferred by RPP13-Nd. Using our structure as a scaffold, we map these residues to one of two surface-exposed patches of residues under diversifying selection. Exploring possible roles of the disordered region within the ATR13 structure, we perform domain swapping experiments and identify a peptide sequence involved in nucleolar localization. We conclude that ATR13 is a highly dynamic protein with no clear structural homologues that contains two surface-exposed patches of polymorphism, only one of which is involved in RPP13-Nd recognition specificity.

  10. In-situ ATR-FTIR for characterization of thin biorelated polymer films

    Energy Technology Data Exchange (ETDEWEB)

    Müller, M., E-mail: mamuller@ipfdd.de [Leibniz Institute of Polymer Research Dresden (IPF Dresden), Hohe Straße 6, 01069 Dresden (Germany); Technical University of Dresden (TUD), Department of Chemistry and Food Chemistry, 01062 Dresden (Germany); Torger, B. [Leibniz Institute of Polymer Research Dresden (IPF Dresden), Hohe Straße 6, 01069 Dresden (Germany); Technical University of Dresden (TUD), Department of Chemistry and Food Chemistry, 01062 Dresden (Germany); Bittrich, E. [Leibniz Institute of Polymer Research Dresden (IPF Dresden), Hohe Straße 6, 01069 Dresden (Germany); Kaul, E.; Ionov, L. [Leibniz Institute of Polymer Research Dresden (IPF Dresden), Hohe Straße 6, 01069 Dresden (Germany); Technical University of Dresden (TUD), Department of Chemistry and Food Chemistry, 01062 Dresden (Germany); Uhlmann, P. [Leibniz Institute of Polymer Research Dresden (IPF Dresden), Hohe Straße 6, 01069 Dresden (Germany); Stamm, M. [Leibniz Institute of Polymer Research Dresden (IPF Dresden), Hohe Straße 6, 01069 Dresden (Germany); Technical University of Dresden (TUD), Department of Chemistry and Food Chemistry, 01062 Dresden (Germany)

    2014-04-01

    We present and review in-situ-attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic data from thin biorelated polymer films useful for the modification and functionalization of polymer and inorganic materials and discuss their applications related to life sciences. A special ATR mirror attachment operated by the single-beam-sample-reference (SBSR) concept and housing a homebuilt thermostatable flow cell was used, which allows for appropriate background compensation and signal to noise ratio. ATR-FTIR data on the reactive deposition of dopamine on inorganic model surfaces are shown. Information on the structure and deposition pathway for such bioinspired melanin-like films is provided. ATR-FTIR data on thermosensitive polymer brushes of poly(N-isopropylacrylamide) (PNIPAAM) is then presented. The thermotropic hydration and hydrogen bonding behavior of PNIPAAM brush films is described. Finally, ATR-FTIR data on biorelated polyelectrolyte multilayers (PEM) are given together with details on PEM growth and detection. Applications of these latter films for biopassivation/activation and local drug delivery are addressed.

  11. The essential kinase ATR: ensuring faithful duplication of a challenging genome.

    Science.gov (United States)

    Saldivar, Joshua C; Cortez, David; Cimprich, Karlene A

    2017-10-01

    One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.

  12. Seeded growth fabrication of Cu-on-Si electrodes for in situ ATR-SEIRAS applications

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui-Feng [Shanghai Key Laboratory for Molecular Catalysis and Innovative Materials and Department of Chemistry, Fudan University, Shanghai 200433 (China); Yan, Yan-Gang [Shanghai Key Laboratory for Molecular Catalysis and Innovative Materials and Department of Chemistry, Fudan University, Shanghai 200433 (China); Huo, Sheng-Juan [Shanghai Key Laboratory for Molecular Catalysis and Innovative Materials and Department of Chemistry, Fudan University, Shanghai 200433 (China); Cai, Wen-Bin [Shanghai Key Laboratory for Molecular Catalysis and Innovative Materials and Department of Chemistry, Fudan University, Shanghai 200433 (China); Department of Enviromental Engineering, Shanghai University of Electric Power, Shanghai 200090 (China); E-mail: wbcai@fudan.edu.cn; Xu, Qun-Jie [Department of Enviromental Engineering, Shanghai University of Electric Power, Shanghai 200090 (China); Osawa, Masatoshi [Catalysis Research Center, Hokkaido University, Sapporo 001-0021 (Japan)

    2007-05-25

    A seeded-growth approach has been developed to fabricate a Cu nanoparticle film (simplified hereafter with nanofilm) on Si for electrochemical ATR surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS). The approach comprises an initial activation of the reflecting plane of hemicylindrical Si prism by introducing a Cu seed layer in a CuSO{sub 4}-HF solution and the subsequent electroless deposition of the Cu nanofilms from an electroless Cu plating bath. The as-deposited Cu nanofilm exhibited strong SEIRA effect for the CO probe and interfacial free H{sub 2}O. ATR-SEIRAS was also applied to characterize the adsorbed geometries of pyridine at the Cu/electrolyte interface. Only vibrational bands assignable to the A {sub 1} symmetry modes were detected in the entire potential window investigated, suggestive of an end-on adsorption via the ring N-atom on a Cu electrode.

  13. ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response.

    Science.gov (United States)

    Blackford, Andrew N; Jackson, Stephen P

    2017-06-15

    In vertebrate cells, the DNA damage response is controlled by three related kinases: ATM, ATR, and DNA-PK. It has been 20 years since the cloning of ATR, the last of the three to be identified. During this time, our understanding of how these kinases regulate DNA repair and associated events has grown profoundly, although major questions remain unanswered. Here, we provide a historical perspective of their discovery and discuss their established functions in sensing and responding to genotoxic stress. We also highlight what is known regarding their structural similarities and common mechanisms of regulation, as well as emerging non-canonical roles and how our knowledge of ATM, ATR, and DNA-PK is being translated to benefit human health. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 10 CFR 830 Major Modification Determination for Replacement of ATR Primary Coolant Pumps and Motors

    Energy Technology Data Exchange (ETDEWEB)

    Noel Duckwitz

    2011-05-01

    The continued safe and reliable operation of the ATR is critical to the Department of Energy (DOE) Office of Nuclear Energy (NE) mission. While ATR is safely fulfilling current mission requirements, a variety of aging and obsolescence issues challenge ATR engineering and maintenance personnel’s capability to sustain ATR over the long term. First documented in a series of independent assessments, beginning with an OA Environmental Safety and Health Assessment conducted in 2003, the issues were validated in a detailed Material Condition Assessment (MCA) conducted as a part of the ATR Life Extension Program in 2007.Accordingly, near term replacement of aging and obsolescent original ATR equipment has become important to ensure ATR capability in support of NE’s long term national missions. To that end, a mission needs statement has been prepared for a non-major system acquisition which is comprised of three interdependent subprojects. The first project will replace the existent diesel-electrical bus (E-3), switchgear, and the 50-year-old obsolescent marine diesels with commercial power that is backed with safety related emergency diesel generators, switchgear, and uninterruptible power supply (UPS). The second project, the subject of this major modification determination, will replace the four, obsolete, original primary coolant pumps (PCPs) and motors. Completion of this and the two other age-related projects (replacement of the ATR diesel bus [E-3] and switchgear and replacement of the existent emergency firewater injection system) will resolve major age-related operational issues plus make a significant contribution in sustaining the ATR safety and reliability profile. The major modification criteria evaluation of the project pre-conceptual design identified several issues that lead to the conclusion that the project is a major modification: 1. Evaluation Criteria #3 (Change of existing process). The proposed strategy for equipping the replacement PCPs with VFDs

  15. Status of ATR-A1 irradiation experiment on vanadium alloys and low-activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Strain, R.V.; Gomes, I.; Smith, D.L. [Argonne National Lab., IL (United States); Matsui, H. [Tohoku Univ. (Japan)

    1996-10-01

    The ATR-A1 irradiation experiment was a collaborative U.S./Japan effort to study at low temperature the effects of neutron damage on vanadium alloys. The experiment also contained a limited quantity of low-activation ferritic steel specimens from Japan as part of the collaboration agreement. The irradiation started in the Advanced Test Reactor (ATR) on November 30, 1995, and ended as planned on May 5, 1996. Total exposure was 132.9 effective full power days (EFPDs) and estimated neutron damage in the vanadium was 4.7 dpa. The vehicle has been discharged from the ATR core and is scheduled to be disassembled in the next reporting period.

  16. Measured Thermal and Fast Neutron Fluence Rates for ATF-1 Holders During ATR Cycle 157D

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Larry Don [Idaho National Lab. (INL), Idaho Falls, ID (United States); Miller, David Torbet [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-03-01

    This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 157D which were measured by the Radiation Measurements Laboratory (RML) as requested by the Power Reactor Programs (ATR Experiments) Radiation Measurements Work Order. This report contains measurements of the fluence rates corresponding to the particular elevations relative to the 80-ft. core elevation. The data in this report consist of (1) a table of the ATR power history and distribution, (2) a hard copy listing of all thermal and fast neutron fluence rates, and (3) plots of both the thermal and fast neutron fluence rates. The fluence rates reported are for the average power levels given in the table of power history and distribution.

  17. Detection and quantification of soymilk in cow-buffalo milk using Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR).

    Science.gov (United States)

    Jaiswal, Pranita; Jha, Shyam Narayan; Borah, Anjan; Gautam, Anuj; Grewal, Manpreet Kaur; Jindal, Gaurav

    2015-02-01

    Milk consumption is steadily increasing, especially in India and China, due to rising income. To bridge the gap between supply and demand, unscrupulous milk vendors add milk-like products from vegetable sources (soymilk) to milk without declaration. A rapid detection technique is required to enforce the safety norms of food regulatory authorities. Fourier Transform Infrared (FTIR) spectroscopy has demonstrated potential as a rapid quality monitoring method and was therefore explored for detection of soymilk in milk. In the present work, spectra of milk, soymilk (SM), and milk adulterated with known quantity of SM were acquired in the wave number range of 4000-500cm(-1) using Attenuated Total Reflectance (ATR)-FTIR. The acquired spectra revealed differences amongst milk, SM and adulterated milk (AM) samples in the wave number range of 1680-1058cm(-1). This region encompasses the absorption frequency of amide-I, amide-II, amide-III, beta-sheet protein, α-tocopherol and Soybean Kunitz Trypsin Inhibitor. Principal component analysis (PCA) showed clustering of samples based on SM concentration at 5% level of significance and thus SM could be detected in milk using ATR-FTIR. The SM was best predicted in the range of 1472-1241cm(-1) using multiple linear regression with coefficient of determination (R(2)) of 0.99 and 0.92 for calibration and validation, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. SAR image dataset of military ground targets with multiple poses for ATR

    Science.gov (United States)

    Belloni, Carole; Balleri, Alessio; Aouf, Nabil; Merlet, Thomas; Le Caillec, Jean-Marc

    2017-10-01

    Automatic Target Recognition (ATR) is the task of automatically detecting and classifying targets. Recognition using Synthetic Aperture Radar (SAR) images is interesting because SAR images can be acquired at night and under any weather conditions, whereas optical sensors operating in the visible band do not have this capability. Existing SAR ATR algorithms have mostly been evaluated using the MSTAR dataset.1 The problem with the MSTAR is that some of the proposed ATR methods have shown good classification performance even when targets were hidden,2 suggesting the presence of a bias in the dataset. Evaluations of SAR ATR techniques are currently challenging due to the lack of publicly available data in the SAR domain. In this paper, we present a high resolution SAR dataset consisting of images of a set of ground military target models taken at various aspect angles, The dataset can be used for a fair evaluation and comparison of SAR ATR algorithms. We applied the Inverse Synthetic Aperture Radar (ISAR) technique to echoes from targets rotating on a turntable and illuminated with a stepped frequency waveform. The targets in the database consist of four variants of two 1.7m-long models of T-64 and T-72 tanks. The gun, the turret position and the depression angle are varied to form 26 different sequences of images. The emitted signal spanned the frequency range from 13 GHz to 18 GHz to achieve a bandwidth of 5 GHz sampled with 4001 frequency points. The resolution obtained with respect to the size of the model targets is comparable to typical values obtained using SAR airborne systems. Single polarized images (Horizontal-Horizontal) are generated using the backprojection algorithm.3 A total of 1480 images are produced using a 20° integration angle. The images in the dataset are organized in a suggested training and testing set to facilitate a standard evaluation of SAR ATR algorithms.

  19. APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress.

    Science.gov (United States)

    Willis, Jeremy; Patel, Yogin; Lentz, Barry L; Yan, Shan

    2013-06-25

    The base excision repair pathway is largely responsible for the repair of oxidative stress-induced DNA damage. However, it remains unclear how the DNA damage checkpoint is activated by oxidative stress at the molecular level. Here, we provide evidence showing that hydrogen peroxide (H2O2) triggers checkpoint kinase 1 (Chk1) phosphorylation in an ATR [ataxia-telangiectasia mutated (ATM) and Rad3-related]-dependent but ATM-independent manner in Xenopus egg extracts. A base excision repair protein, Apurinic/apyrimidinic (AP) endonuclease 2 (APE2, APN2, or APEX2), is required for the generation of replication protein A (RPA)-bound single-stranded DNA, the recruitment of a checkpoint protein complex [ATR, ATR-interacting protein (ATRIP), and Rad9] to damage sites, and H2O2-induced Chk1 phosphorylation. A conserved proliferating cell nuclear antigen interaction protein box of APE2 is important for the recruitment of APE2 to H2O2-damaged chromatin. APE2 3'-phosphodiesterase and 3'-5' exonuclease activity is essential for single-stranded DNA generation in the 3'-5' direction from single-stranded breaks, referred to as single-stranded break end resection. In addition, APE2 associates with Chk1, and a serine residue (S86) in the Chk1-binding motif of APE2 is essential for Chk1 phosphorylation, indicating a Claspin-like but distinct role for APE2 in ATR-Chk1 signaling. Our data indicate that APE2 plays a vital and previously unexpected role in ATR-Chk1 checkpoint signaling in response to oxidative stress. Thus, our findings shed light on a distinct mechanism of how an ATR-Chk1-dependent DNA damage checkpoint is mediated by APE2 in the oxidative stress response.

  20. 10 CFR 830 Major Modification Determination for the ATR Diesel Bus (E-3) and Switchgear Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Noel Duckwtiz

    2011-05-01

    Near term replacement of aging and obsolescent original ATR equipment has become important to ensure ATR capability in support of NE’s long term national missions. To that end, a mission needs statement has been prepared for a non-major system acquisition which is comprised of three interdependent subprojects. The first project, subject of this determination, will replace the existent diesel-electrical bus (E-3) and associated switchgear. More specifically, INL proposes transitioning ATR to 100% commercial power with appropriate emergency backup to include: • Provide commercial power as the normal source of power to the ATR loads currently supplied by diesel-electric power. • Provide backup power to the critical ATR loads in the event of a loss of commercial power. • Replace obsolescent critical ATR power distribution equipment, e.g., switchgear, transformers, motor control centers, distribution panels. Completion of this and two other age-related projects (primary coolant pump and motor replacement and emergency firewater injection system replacement) will resolve major age related operational issues plus make a significant contribution in sustaining the ATR safety and reliability profile. The major modification criteria evaluation of the project pre-conceptual design identified several issues make the project a major modification: 1. Evaluation Criteria #2 (Footprint change). The addition of a new PC-4 structure to the ATR Facility to house safety-related SSCs requires careful attention to maintaining adherence to applicable engineering and nuclear safety design criteria (e.g., structural qualification, fire suppression) to ensure no adverse impacts to the safety-related functions of the housed equipment. 2. Evaluation Criteria #3 (Change of existing process). The change to the strategy for providing continuous reliable power to the safety-related emergency coolant pumps requires careful attention and analysis to ensure it meets a project primary object

  1. Alterations in ATR in nasal NK/T-cell lymphoma and chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Liu, Angen; Takakuwa, Tetsuya; Luo, Wen-Juan; Fujita, Shigeki; Aozasa, Katsuyuki

    2006-07-01

    Nasal natural killer (NK)/T-cell lymphoma (NKTCL) and chronic active Epstein-Barr virus infection (CAEBV) are relatively frequent, especially in Asia, and are poor in prognosis. Both diseases are proliferative diseases of NK/T cells that show highly complicated karyotypes, suggesting the involvement of chromosomal instability. ATR is an important gene for DNA damage response and chromosomal stability. To evaluate the role of ATR gene alterations in the pathogenesis of NKTCL and CAEBV, the whole coding region of the ATR gene was examined in cell lines derived from NKTCL and CAEBV, as well as tumor samples from patients. ATR alterations were detected in two of eight NKTCL and in one of three CAEBV lines. Most aberrant transcripts observed were deletions resulting from aberrant splicing. ATR alterations were also detected in four of 10 NKTCL clinical samples. Both NKTCL and CAEBV cell lines with ATR alterations showed a delay or abrogation in repair of ionizing radiation-induced DNA double-strand breaks and ultraviolet-induced DNA single-strand breaks, and both exhibited a defect in p53 accumulation. These findings show that alterations in the ATR gene result in an abnormal response to DNA double-strand break and single-strand break repair, suggesting a role for ATR gene alterations in NKTCL lymphomagenesis.

  2. ATR-FTIR Spectroscopy in the Undergraduate Chemistry Laboratory: Part II--A Physical Chemistry Laboratory Experiment on Surface Adsorption

    Science.gov (United States)

    Schuttlefield, Jennifer D.; Larsen, Sarah C.; Grassian, Vicki H.

    2008-01-01

    Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is a useful technique for measuring the infrared spectra of solids and liquids as well as probing adsorption on particle surfaces. The use of FTIR-ATR spectroscopy in organic and inorganic chemistry laboratory courses as well as in undergraduate research was presented…

  3. Cyclohexene photo-oxidation over vanadia catalyst analyzed by time resolvedATR-FT-IT spectroscopy

    NARCIS (Netherlands)

    Mul, Guido; Wasylenko, W.; Sameh Hamdy, M.; Frei, H.

    2008-01-01

    Vanadia was incorporated in the 3-D mesoporous material TUD-1 with a loading of 2% w/w vanadia. The performance in the selective photo-oxidation of liquid cyclohexene was investigated using ATR-FT-IR spectroscopy. Under continuous illumination at 458 nm a significant amount of product,

  4. ATM/ATR-mediated phosphorylation of PALB2 promotes RAD51 function

    DEFF Research Database (Denmark)

    Ahlskog, Johanna K; Larsen, Brian D; Achanta, Kavya

    2016-01-01

    DNA damage activates the ATM and ATR kinases that coordinate checkpoint and DNA repair pathways. An essential step in homology-directed repair (HDR) of DNA breaks is the formation of RAD51 nucleofilaments mediated by PALB2-BRCA2; however, roles of ATM and ATR in this critical step of HDR are poorly...... understood. Here, we show that PALB2 is markedly phosphorylated in response to genotoxic stresses such as ionizing radiation and hydroxyurea. This response is mediated by the ATM and ATR kinases through three N-terminal S/Q-sites in PALB2, the consensus target sites for ATM and ATR Importantly, a phospho......-deficient PALB2 mutant is unable to support proper RAD51 foci formation, a key PALB2 regulated repair event, whereas a phospho-mimicking PALB2 version supports RAD51 foci formation. Moreover, phospho-deficient PALB2 is less potent in HDR than wild-type PALB2. Further, this mutation reveals a separation in PALB2...

  5. Hydroxyl accessibility in wood by deuterium exchange and ATR-FTIR spectroscopy

    DEFF Research Database (Denmark)

    Tarmian, Asghar; Burgert, Ingo; Thybring, Emil Engelund

    2017-01-01

    The accessibility of wood hydroxyls to water is commonly studied by infrared spectroscopy after deuteration where water-interacting hydroxyls have their H exchanged for D. In this study, the hydroxyl accessibility is determined with ATR-FTIR spectroscopy after deuteration of specimens with liquid D...

  6. 78 FR 42898 - Airworthiness Directives; ATR-GIE Avions de Transport Régional Airplanes

    Science.gov (United States)

    2013-07-18

    ... investigation into an ATR 72 accident in August 2005 have shown that overruling standard operational procedures... proposed AD was prompted by reports of airplane incidents and accidents that have occurred because of low.... ADDRESSES: You may send comments by any of the following methods: Federal eRulemaking Portal: Go to http...

  7. Dynamic generation of artificial HRSAR imagery for ATR development and cockpit simulation

    Science.gov (United States)

    Seidel, Heiko; Stahl, Christoph; Knappe, Peter; Hurst, Peter

    2004-09-01

    Following the tendency of increasingly using imaging sensors in military aircraft, future combat airplane pilots will need onboard artificial intelligence for aiding them in image interpretation and target designation. This document presents a system which is able to simulate high-resolution artificial SAR imagery and thereby facilitates automatic target recognition (ATR) algorithm development. The system provides a comprehensive interface that allows dynamically requesting imagery depending on the location and heading of a simulated carrier platform. Landscapes, structures and target signatures are generated based on digital terrain data and target models. An assessment of dissimilar database preparations for sensor simulation was done with respect to the different properties of SAR imaging compared to optical imaging. The document presents selected results for specific landscape elements. Post-processing algorithms for overcoming weaknesses of digital terrain databases and improving image realism are presented. Simulated sensor imagery is useful in a wide range of applications, two of which are training of ATR algorithms and sensor simulation in flight simulation environments. Using an existing ATR method as an example, the applicability and the influences of synthetic imagery on ATR training are shown and first approaches on how to validate the correctness of the imagery are explained. The integration of the system into a flight simulator in the context of interfacing and control topics serves as a concluding example.

  8. An in situ ATR-IR spectroscopy study of aluminas under aqueous phase reforming conditions

    NARCIS (Netherlands)

    Koichumanova, Kamila; Gupta, K.B. Sai Sankar; Lefferts, Leonardus; Mojet, Barbara; Seshan, Kulathuiyer

    2015-01-01

    High temperature/pressure in situ Attenuated Total Reflection Infrared (ATR-IR) spectroscopy was used to investigate the phase transformation of support γ-Al2O3 into boehmite (AlO(OH)) under the hydrothermal conditions of aqueous phase reforming (APR). Activation energy barriers of boehmite

  9. Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice

    DEFF Research Database (Denmark)

    Lopez-Contreras, Andres J; Specks, Julia; Barlow, Jacqueline H

    2015-01-01

    of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile...

  10. Roles of ATR1 paralogs YMR279c and YOR378w in boron stress tolerance.

    Science.gov (United States)

    Bozdag, Gonensin Ozan; Uluisik, Irem; Gulculer, Gulce Sila; Karakaya, Huseyin C; Koc, Ahmet

    2011-06-17

    Boron is a necessary nutrient for plants and animals, however excess of it causes toxicity. Previously, Atr1 and Arabidopsis Bor1 homolog were identified as the boron efflux pump in yeast, which lower the cytosolic boron concentration and help cells to survive in the presence of toxic amount of boron. In this study, we analyzed ATR1 paralogs, YMR279c and YOR378w, to understand whether they participate in boron stress tolerance in yeast. Even though these genes share homology with ATR1, neither their deletion rendered cells boron sensitive nor their expression was significantly upregulated by boron treatment. However, expression of YMR279, but not YOR378w, from the constitutive GAPDH promoter on a high copy plasmid provided remarkable boron resistance by decreasing intracellular boron levels. Thus our results suggest the presence of a third boron exporter, YMR279c, which functions similar to ATR1 and provides boron resistance in yeast. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. 76 FR 70044 - Airworthiness Directives; ATR-GIE Avions de Transport Régional Airplanes

    Science.gov (United States)

    2011-11-10

    ... require parts costing $960, for a cost of $6,060 per product. We have no way of determining the number of... condition on an aviation product. The MCAI describes the unsafe condition as: One ATR operator has... condition on these products. DATES: This AD becomes effective December 15, 2011. The Director of the Federal...

  12. Measured thermal and fast neutron fluence rates for ATF-1 holders during ATR cycle 160A

    Energy Technology Data Exchange (ETDEWEB)

    Walker, B. J. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Miller, D. T. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-06-06

    This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 160A which were measured by the Radiation Measurements Laboratory (RML).

  13. An add-on system including a micro-reactor for an atr-ir spectrometer

    DEFF Research Database (Denmark)

    2014-01-01

    The invention relates to an add-on system for an attenuated total reflectance infrared (ATR-IR) spectrometer, the add-on system allowing for time-resolved in situ IR measurements of heterogeneous mixtures. The add-on device comprises a micro-reactor (300A) forming a sample cavity (305) when...

  14. An add-on system for photochemical ATR-IR spectroscopy studies

    DEFF Research Database (Denmark)

    2014-01-01

    The invention relates to an add-on system for a unit mainly adapted for attenuated total reflectance infrared (ATR-IR) spectroscopy. The add-on system enables time-resolved in-situ measurements of different sample types in an easy, simple and inexpensive way. The add-on system includes a cap (300G...

  15. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis.

    Science.gov (United States)

    Enriquez-Rios, Vanessa; Dumitrache, Lavinia C; Downing, Susanna M; Li, Yang; Brown, Eric J; Russell, Helen R; McKinnon, Peter J

    2017-01-25

    The DNA damage response (DDR) orchestrates a network of cellular processes that integrates cell-cycle control and DNA repair or apoptosis, which serves to maintain genome stability. DNA-PKcs (the catalytic subunit of the DNA-dependent kinase, encoded by PRKDC), ATM (ataxia telangiectasia, mutated), and ATR (ATM and Rad3-related) are related PI3K-like protein kinases and central regulators of the DDR. Defects in these kinases have been linked to neurodegenerative or neurodevelopmental syndromes. In all cases, the key neuroprotective function of these kinases is uncertain. It also remains unclear how interactions between the three DNA damage-responsive kinases coordinate genome stability, particularly in a physiological context. Here, we used a genetic approach to identify the neural function of DNA-PKcs and the interplay between ATM and ATR during neurogenesis. We found that DNA-PKcs loss in the mouse sensitized neuronal progenitors to apoptosis after ionizing radiation because of excessive DNA damage. DNA-PKcs was also required to prevent endogenous DNA damage accumulation throughout the adult brain. In contrast, ATR coordinated the DDR during neurogenesis to direct apoptosis in cycling neural progenitors, whereas ATM regulated apoptosis in both proliferative and noncycling cells. We also found that ATR controls a DNA damage-induced G2/M checkpoint in cortical progenitors, independent of ATM and DNA-PKcs. These nonoverlapping roles were further confirmed via sustained murine embryonic or cortical development after all three kinases were simultaneously inactivated. Thus, our results illustrate how DNA-PKcs, ATM, and ATR have unique and essential roles during the DDR, collectively ensuring comprehensive genome maintenance in the nervous system. The DNA damage response (DDR) is essential for prevention of a broad spectrum of different human neurologic diseases. However, a detailed understanding of the DDR at a physiological level is lacking. In contrast to many in

  16. Protein phosphatase 5 is necessary for ATR-mediated DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yoonsung [Department of Pharmacology, DNA Repair Research Center, Chosun University School of Medicine, 375 Seosuk-Dong, Gwangju 501-759 (Korea, Republic of); Cheong, Hyang-Min [Department of Life Science, College of Natural Science, Chung-Ang University, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Lee, Jung-Hee [Department of Pharmacology, DNA Repair Research Center, Chosun University School of Medicine, 375 Seosuk-Dong, Gwangju 501-759 (Korea, Republic of); Song, Peter I. [Department of Dermatology, University of Arkansas for Medical Science, 4301 West Markham, Slot 576, Little Rock, AR 72205 (Korea, Republic of); Lee, Kwang-Ho [Department of Life Science, College of Natural Science, Chung-Ang University, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Kim, Sang-Yong [Division of Endocrinology, Department of Internal Medicine, Chosun University School of Medicine, 375 Seosuk-Dong, Gwangju 501-759 (Korea, Republic of); Jun, Jae Yeoul [Department of Physiology, Chosun University School of Medicine, 375 Seosuk-Dong, Gwangju 501-759 (Korea, Republic of); You, Ho Jin, E-mail: hjyou@chosun.ac.kr [Department of Pharmacology, DNA Repair Research Center, Chosun University School of Medicine, 375 Seosuk-Dong, Gwangju 501-759 (Korea, Republic of)

    2011-01-07

    Research highlights: {yields} Serine/threonine protein phosphatase 5 (PP5) has been shown to participate in ataxia telangiectasia-mutated (ATM)- and ATR (ATM- and Rad3-related)-mediated checkpoint pathways, which plays an important role in the DNA damage response and maintenance of genomic stability. {yields} However, it is not clear exactly how PP5 participates in this process. {yields} Our results indicate that PP5 is more closely related with ATR-mediated pathway than ATM-mediated pathway in DNA damage repair. -- Abstract: Several recent studies have shown that protein phosphatase 5 (PP5) participates in cell cycle arrest after DNA damage, but its roles in DNA repair have not yet been fully characterized. We investigated the roles of PP5 in the repair of ultraviolet (UV)- and neocarzinostatin (NCS)-induced DNA damage. The results of comet assays revealed different repair patterns in UV- and NCS-exposed U2OS-PS cells. PP5 is only essential for Rad3-related (ATR)-mediated DNA repair. Furthermore, the phosphorylation of 53BP1 and BRCA1, important mediators of DNA damage repair, and substrates of ATR and ATM decreased in U2OS-PS cells exposed to UV radiation. In contrast, the cell cycle arrest proteins p53, CHK1, and CHK2 were normally phosphorylated in U2OS and U2OS-PS cells exposed to UV radiation or treated with NCS. In view of these results, we suggest that PP5 plays a crucial role in ATR-mediated repair of UV-induced DNA damage.

  17. Knockdown of REV3 synergizes with ATR inhibition to promote apoptosis induced by cisplatin in lung cancer cells.

    Science.gov (United States)

    Jiang, He-Guo; Chen, Ping; Su, Jin-Yu; Wu, Ming; Qian, Hai; Wang, Yi; Li, Jian

    2017-12-01

    It has been demonstrated that REV3, the catalytic subunit of the translesion synthesis (TLS) polymerase ζ, play an important role in DNA damage response (DDR) induced by cisplatin, and Ataxia-telangietasia mutated and Rad-3-related (ATR) knase is a central player in activating cell cycle checkpoint, stabilizing replication forks, regulating DDR, and promoting repair of DNA damage caused by cisplatin. Cancer cells deficient in either one of REV3 and ATR are more sensitive to cisplatin. However, whether co-inhibition of REV3 and ATR can further increase sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin is not clear. In this study, we show that REV3 knockdown combined with ATR inhibition further enhance cytotoxicity of cisplatin in NSCLC cells, including cisplatin-sensitive and -resistant cell lines, compared to individual knockdown of REV3 or ATR, which are accompanied by markedly caspase-dependent apoptosis response, pronounced DNA damage accumulation and severe impediment of interstrand crosslink (ICL), and double strand break (DSB) repair. Our results suggest that REV3 knockdown synergize strongly with ATR inhibition to significantly increase sensitivity of cisplatin in NSCLC cells by inhibiting ICL and DSB repair. Thus simultaneously targeting REV3 and ATR may represent one approach to overcome cisplatin resistance and improve chemotherapeutic efficacy in NSCLC treatment. © 2017 Wiley Periodicals, Inc.

  18. Advanced Test Reactor National Scientific User Facility (ATR NSUF) Monthly Report November 2014

    Energy Technology Data Exchange (ETDEWEB)

    Soelberg, Renae [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-11-01

    Advanced Test Reactor National Scientific User Facility (ATR NSUF) Monthly Report November 2014 Highlights Rory Kennedy and Sarah Robertson attended the American Nuclear Society Winter Meeting and Nuclear Technology Expo in Anaheim, California, Nov. 10-13. ATR NSUF exhibited at the technology expo where hundreds of meeting participants had an opportunity to learn more about ATR NSUF. Dr. Kennedy briefed the Nuclear Engineering Department Heads Organization (NEDHO) on the workings of the ATR NSUF. • Rory Kennedy, James Cole and Dan Ogden participated in a reactor instrumentation discussion with Jean-Francois Villard and Christopher Destouches of CEA and several members of the INL staff. • ATR NSUF received approval from the NE-20 office to start planning the annual Users Meeting. The meeting will be held at INL, June 22-25. • Mike Worley, director of the Office of Innovative Nuclear Research (NE-42), visited INL Nov. 4-5. Milestones Completed • Recommendations for the Summer Rapid Turnaround Experiment awards were submitted to DOE-HQ Nov. 12 (Level 2 milestone due Nov. 30). Major Accomplishments/Activities • The University of California, Santa Barbara 2 experiment was unloaded from the GE-2000 at HFEF. The experiment specimen packs will be removed and shipped to ORNL for PIE. • The Terrani experiment, one of three FY 2014 new awards, was completed utilizing the Advanced Photon Source MRCAT beamline. The experiment investigated the chemical state of Ag and Pd in SiC shell of irradiated TRISO particles via X-ray Absorption Fine Structure (XAFS) spectroscopy. Upcoming Meetings/Events • The ATR NSUF program review meeting will be held Dec. 9-10 at L’Enfant Plaza. In addition to NSUF staff and users, NE-4, NE-5 and NE-7 representatives will attend the meeting. Awarded Research Projects Boise State University Rapid Turnaround Experiments (14-485 and 14-486) Nanoindentation and TEM work on the T91, HT9, HCM12A and 9Cr ODS specimens has been completed at

  19. Meteorological Conditions Associated with the ATR72 Aircraft Accident near Roselawn, Indiana, on 31 October 1994.

    Science.gov (United States)

    Marwitz, J.; Politovich, M.; Bernstein, B.; Ralph, F.; Neiman, P.; Ashenden, R.; Bresch, J.

    1997-01-01

    An ATR72 commuter aircraft crashed near Roselawn, Indiana, on 31 October 1994 killing all 68 people on board. Available weather data, including those from a Next Generation Radar, a radar wind profiler, a Geostationary Operational Environmental Satellite, and pilot reports of icing have been examined in combination with analysis fields from the Rapid Update Cycle model and forecast fields from the Pennsylvania State University/National Center for Atmospheric Research MM5 numerical model. Synthesis of this information provides a relatively complete and consistent picture of the ambient meteorological conditions in the region of the ATR72 holding pattern at 3.1 km above mean sea level. Of particular interest is the evidence that these conditions favored the development of supercooled drizzle drops within a strong frontal zone, as indicated by cloud-top temperatures of 10° to 15°C, weak radar reflectivity, and strong, vertical wind shear within the cloud and warm front.

  20. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    Directory of Open Access Journals (Sweden)

    Stephanie Munk

    2017-10-01

    Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

  1. ATR Activates the S-M Checkpoint during Unperturbed Growth to Ensure Sufficient Replication Prior to Mitotic Onset

    Directory of Open Access Journals (Sweden)

    John Kenneth Eykelenboom

    2013-11-01

    Full Text Available Cells must accurately replicate and segregate their DNA once per cell cycle in order to successfully transmit genetic information. During S phase in the presence of agents that cause replication stress, ATR-dependent checkpoints regulate origin firing and the replication machinery as well as prevent untimely mitosis. Here, we investigate the role of ATR during unperturbed growth in vertebrate cells. In the absence of ATR, individual replication forks progress more slowly, and an increased number of replication origins are activated. These cells also enter mitosis early and divide more rapidly, culminating in chromosome bridges and laggards at anaphase, failed cytokinesis, and cell death. Interestingly, cell death can be rescued by prolonging mitosis with partial inhibition of the mitotic cyclin-dependent kinase 1. Our data indicate that one of the essential roles of ATR during normal growth is to minimize the level of unreplicated DNA before the onset of mitosis.

  2. Analysis of European honeybee (Apis mellifera) wings using ATR-FTIR and Raman spectroscopy: A pilot study

    Czech Academy of Sciences Publication Activity Database

    Machovič, Vladimír; Lapčák, L.; Havelcová, Martina; Borecká, Lenka; Novotná, M.; Novotná, M.; Javůrková, I.; Langrová, I.; Hájková, Š.; Brožová, A.; Titěra, D.

    2017-01-01

    Roč. 48, č. 1 (2017), s. 22-29 ISSN 1211-3174 Institutional support: RVO:67985891 Keywords : honeybee wings * ATR-FTIR * Raman spectroscopy * protein * lipid * chitin Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry

  3. Determination of methyl ester contents in biodiesel blends by FTIR-ATR and FTNIR spectroscopies.

    Science.gov (United States)

    Oliveira, Jefferson S; Montalvão, Rafael; Daher, Leila; Suarez, Paulo A Z; Rubim, Joel C

    2006-07-15

    Partial last square regression (PLS) and artificial neural network (ANN) combined to FTIR-ATR and FTNIR spectroscopies have been used to design calibration models for the determination of methyl ester content (%, w/w) in biodiesel blends (methyl ester+diesel). Methyl esters were obtained by the methanolysis of soybean, babassu, dende, and soybean fried oils. Two sets of samples have been used: Group I, binary mixtures (diesel+one kind of methyl ester), corresponding to 96 biodiesel blends (0-100%, w/w), and Group II, quaternary mixtures (diesel+three types of methyl esters), corresponding to 60 biodiesel blends (0-100%, w/w). The PLS results have shown that the FTNIR model for Group I is more precise and accurate (+/-0.02 and +/-0.06%, w/w). In the case of Group II the PLS models (FTIR-ATR and FTNIR) have shown the same accuracies, while the ANN/FTNIR models has presented better performance than the ANN/FTIR-ATR models. The best accuracy was achieved by the ANN/FTNIR model for diesel determination (0.14%, w/w) while the worthiest was that of dende ANN/FTIR-ATR model (0.6%, w/w). Precisions in Group II analysis ranged from 0.06 to 0.53% (w/w) and coefficients of variation were better than 3% indicating that these models are suitable for the determination of diesel-biodiesel blends composed of methyl esters derived from different vegetable oils.

  4. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    DEFF Research Database (Denmark)

    Munk, Stephanie; Sigurðsson, Jón Otti; Xiao, Zhenyu

    2017-01-01

    The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM)-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essentia....... They analyze changes in the SUMO and phosphoproteome after MMC and hydroxyurea treatments and find that the DNA damage response kinases ATR and ATM globally regulate SUMOylation upon replication stress and fork breakage....

  5. Diamond-coated ATR prism for infrared absorption spectroscopy of surface-modified diamond nanoparticles

    Czech Academy of Sciences Publication Activity Database

    Remeš, Zdeněk; Kozak, Halyna; Rezek, Bohuslav; Ukraintsev, Egor; Babchenko, Oleg; Kromka, Alexander; Girard, H.A.; Arnault, J.-C.; Bergonzo, P.

    2013-01-01

    Roč. 270, APR (2013), s. 411-417 ISSN 0169-4332 R&D Projects: GA ČR GAP108/12/0910; GA ČR GPP205/12/P331; GA MŠk LH12236; GA MŠk LH12186 Institutional support: RVO:68378271 Keywords : ATR FTIR * CVD * hydrogenation * microwave * nanocrystalline diamond * nanopowder Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.538, year: 2013

  6. Atrésie choanale : A propos de 29 cas | Zainine | Journal Tunisien d ...

    African Journals Online (AJOL)

    Introduction : L'atrésie choanale est une malformation congénitale rare, dont la fréquence est estimée à 1 cas pour 5000 à 8000 naissances. plusieurs hypothèses embryologiques ont été proposées pour expliquer son origine. Le diagnostic de cette malformation est avant tout clinique. Objectifs : analyser les ...

  7. ATR-FTIR spectroscopy and chemometrics: An interesting tool to discriminate and characterize counterfeit medicines.

    Science.gov (United States)

    Custers, D; Cauwenbergh, T; Bothy, J L; Courselle, P; De Beer, J O; Apers, S; Deconinck, E

    2015-08-10

    Counterfeit medicines pose a huge threat to public health worldwide. High amounts of counterfeit pharmaceuticals enter the European market and therefore detection of these products is essential. Attenuated Total Reflection Fourier-Transform infrared spectroscopy (ATR-FTIR) might be useful for the screening of counterfeit medicines since it is easy to use and little sample preparation is required. Furthermore, this approach might be helpful to customs to obtain a first evaluation of suspected samples. This study proposes a combination of ATR-FTIR and chemometrics to discriminate and classify counterfeit medicines. A sample set, containing 209 samples in total, was analyzed using ATR-FTIR and the obtained spectra were used as fingerprints in the chemometric data-analysis which included Principal Component Analysis (PCA), k-Nearest Neighbours (k-NN), Classification and Regression Trees (CART) and Soft Independent Modelling of Class Analogy (SIMCA). First it was verified whether the mentioned techniques are capable to distinguish samples containing different active pharmaceutical ingredients (APIs). PCA showed a clear tendency of discrimination based on the API present; k-NN, CART and SIMCA were capable to create suitable prediction models based on the presence of different APIs. However k-NN performs the least while SIMCA performs the best. Secondly, it was tested whether these three models could be expanded to discriminate between genuine and counterfeit samples as well. k-NN was not able to make the desired discrimination and therefore it was not useful. CART performed better but also this model was less suited. SIMCA, on the other hand, resulted in a model with a 100% correct discrimination between genuine and counterfeit drugs. This study shows that chemometric analysis of ATR-FTIR fingerprints is a valuable tool to discriminate genuine from counterfeit samples and to classify counterfeit medicines. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Assessing and calibrating the ATR-FTIR approach as a carbonate rock characterization tool

    Science.gov (United States)

    Henry, Delano G.; Watson, Jonathan S.; John, Cédric M.

    2017-01-01

    ATR-FTIR (attenuated total reflectance Fourier transform infrared) spectroscopy can be used as a rapid and economical tool for qualitative identification of carbonates, calcium sulphates, oxides and silicates, as well as quantitatively estimating the concentration of minerals. Over 200 powdered samples with known concentrations of two, three, four and five phase mixtures were made, then a suite of calibration curves were derived that can be used to quantify the minerals. The calibration curves in this study have an R2 that range from 0.93-0.99, a RMSE (root mean square error) of 1-5 wt.% and a maximum error of 3-10 wt.%. The calibration curves were used on 35 geological samples that have previously been studied using XRD (X-ray diffraction). The identification of the minerals using ATR-FTIR is comparable with XRD and the quantitative results have a RMSD (root mean square deviation) of 14% and 12% for calcite and dolomite respectively when compared to XRD results. ATR-FTIR is a rapid technique (identification and quantification takes < 5 min) that involves virtually no cost if the machine is available. It is a common tool in most analytical laboratories, but it also has the potential to be deployed on a rig for real-time data acquisition of the mineralogy of cores and rock chips at the surface as there is no need for special sample preparation, rapid data collection and easy analysis.

  9. FTIR-ATR spectroscopy applied to quality control of grape-derived spirits.

    Science.gov (United States)

    Anjos, Ofélia; Santos, António J A; Estevinho, Letícia M; Caldeira, Ilda

    2016-08-15

    The Fourier transform infrared (FTIR) spectroscopic method with attenuated total reflectance (ATR) was used for predicting the alcoholic strength, the methanol, acetaldehyde and fusel alcohols content of grape-derived spirits. FTIR-ATR spectrum in the mid-IR region (4000-400 cm(-1)) was used for the quantitative estimation by applying partial least square (PLS) regression models and the results were correlated with those obtained from reference methods. In the developed method, a cross-validation with 50% of the samples was used for PLS analysis along with a validation test set with 50% of the remaining samples. Good correlation models with a great accuracy were obtained for methanol (r(2)=99.4; RPD=12.8), alcoholic strength (r(2)=97.2; RPD=6.0), acetaldehyde (r(2)=98.2; RPD=7.5) and fusel alcohols (r(2) from 97.4 to 94.1; RPD from 6.2 to 4.1). These results corroborate the hypothesis that FTIR-ATR is a useful technique for the quality control of grape-derived spirits, whose practical application may improve the efficiency and quickness of the current laboratory analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Predicting the physical properties of tablets from ATR-FTIR spectra using partial least squares regression.

    Science.gov (United States)

    Taylor, Michael; Elhissi, Abdelbary M A

    2011-04-01

    The formulation of a new tablet is a time-consuming activity involving the preparation and testing of many different formulations with the aim of identifying one with the desired properties. In complex formulations it may not be clear which excipient is responsible for eliciting a particular property. To investigate partial least squares (PLS) regression analysis of ATR-FTIR spectra of tablets as a predictive and investigative tool in the formulation of novel tablet formulations. Magnesium stearate, lactose, acetylsalicylic acid and Ac-Di-Sol. ATR-FTIR spectra of a simple aspirin tablet formulation with varying amounts of the lubricant magnesium stearate were obtained. PLS models were built using the spectral data as the multivariate variable and various physical properties of the tablets as the univariate variables. PLS models that allowed good predications to be made for samples not included in the training set were obtained for tablet hardness and disintegration time. It was clear from PLS model regression coefficients that magnesium stearate was responsible for the variation in the tablets' physical properties. PLS regression in combination with ATR-FTIR spectroscopy has been shown to be a useful approach for the prediction of the physical properties of tablets.

  11. Fast quantitative determination of microbial rhamnolipids from cultivation broths by ATR-FTIR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Hausmann Rudolf

    2008-10-01

    Full Text Available Abstract Background Vibrational spectroscopic techniques are becoming increasingly important and popular because they have the potential to provide rapid and convenient solutions to routine analytical problems. Using these techniques, a variety of substances can be characterized, identified and also quantified rapidly. Results The rapid ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy in time technique has been applied, which is suitable to quantify the concentrations of microbial rhamnolipids in a typical cultivation process. While the usually applied HPLC analysis requires an extensive and time consuming multi step extraction protocol for sample preparation, the ATR-FTIR-method allows the quantification of the rhamnolipids within 20 minutes. Accuracies between 0.5 g/l – 2.1 g/l for the different analytes were determined by cross validation of the calibration set. Even better accuracies between 0.28 g/l – 0.59 g/l were found for independent test samples of an arbitrarily selected cultivation. Conclusion ATR-FTIR was found to be suitable for the rapid analysis of rhamnolipids in a biotechnological process with good reproducibility in sample determination and sufficient accuracy. An improvement in accuracy through continuous expansion and validation of the reference spectra set seems very likely.

  12. Diamond-coated ATR prism for infrared absorption spectroscopy of surface-modified diamond nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Remes, Z., E-mail: remes@fzu.cz [Institute of Physics of the ASCR, v.v.i., Cukrovarnicka 10, Praha 6 (Czech Republic); Kozak, H.; Rezek, B.; Ukraintsev, E.; Babchenko, O.; Kromka, A. [Institute of Physics of the ASCR, v.v.i., Cukrovarnicka 10, Praha 6 (Czech Republic); Girard, H.A.; Arnault, J.-C.; Bergonzo, P. [CEA, LIST, Diamond Sensors Laboratory, F-91191 Gif-sur-Yvette (France)

    2013-04-01

    Linear antenna microwave chemical vapor deposition process was used to homogeneously coat a 7 cm long silicon prism by 85 nm thin nanocrystalline diamond (NCD) layer. To show the advantages of the NCD-coated prism for attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) of nanoparticles, we apply diamond nanoparticles (DNPs) of 5 nm nominal size with various surface modifications by a drop-casting of their methanol dispersions. ATR-FTIR spectra of as-received, air-annealed, plasma-oxidized, and plasma-hydrogenated DNPs were measured in the 4000–1500 cm{sup −1} spectral range. The spectra show high spectral resolution, high sensitivity to specific DNP surface moieties, and repeatability. The NCD coating provides mechanical protection against scratching and chemical stability of the surface. Moreover, unlike on bare Si surface, NCD hydrophilic properties enable optically homogeneous coverage by DNPs with some aggregation on submicron scale as evidenced by scanning electron microscopy and atomic force microscopy. Compared to transmission FTIR regime with KBr pellets, direct and uniform deposition of DNPs on NCD-ATR prism significantly simplifies and speeds up the analysis (from days to minutes). We discuss prospects for in situ monitoring of surface modifications and molecular grafting.

  13. Submission of FeCrAl Feedstock for Support of AFC ATR-2 Irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Barrett, Kristine E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Sun, Zhiqian [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-09-16

    The Advanced Test Reactor (ATR) is currently being used to test accident tolerant fuel (ATF) forms destined for commercial nuclear power plant deployment. One irradiation program using the ATR for ATF concepts, Accident Tolerant Fuel-2 (ATF-2), is a water loop irradiation test using miniaturized fuel pins as test articles. This complicated testing configuration requires a series of pre-test experiments and verification including a flowing loop autoclave test and a sensor qualification test (SQT) prior to full test train deployment within the ATR. In support of the ATF-2 irradiation program, Oak Ridge National Laboratory (ORNL) has supplied two different Generation II FeCrAl alloys in rod stock form to Idaho National Laboratory (INL). These rods will be machined into dummy pins for deployment in the autoclave test and SQT. Post-test analysis of the dummy pins will provide initial insight into the performance of Generation II FeCrAl alloys in the ATF-2 irradiation experiment as well as within a commercial nuclear reactor.

  14. MELT WIRE SENSORS AVAILABLE TO DETERMINE PEAK TEMPERATURES IN ATR IRRADIATION TESTING

    Energy Technology Data Exchange (ETDEWEB)

    K. L. Davis; D. Knudson; J. Daw; J. Palmer; J. L. Rempe

    2012-07-01

    In April 2007, the Department of Energy (DOE) designated the Advanced Test Reactor (ATR) a National Scientific User Facility (NSUF) to advance US leadership in nuclear science and technology. By attracting new users from universities, laboratories, and industry, the ATR will support basic and applied nuclear research and development and help address the nation's energy security needs. In support of this new program, the Idaho National Laboratory (INL) has developed in-house capabilities to fabricate, test, and qualify new and enhanced temperature sensors for irradiation testing. Although most efforts emphasize sensors capable of providing real-time data, selected tasks have been completed to enhance sensors provided in irradiation locations where instrumentation leads cannot be included, such as drop-in capsule and Hydraulic Shuttle Irradiation System (HSIS) or 'rabbit' locations. To meet the need for these locations, the INL has developed melt wire temperature sensors for use in ATR irradiation testing. Differential scanning calorimetry and environmental testing of prototypical sensors was used to develop a library of 28 melt wire materials, capable of detecting peak irradiation temperatures ranging from 85 to 1500°C. This paper will discuss the development work and present test results.

  15. Cyclohexene Photo-oxidation over Vanadia Catalyst Analyzed by Time Resolved ATR-FT-IR Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Frei, Heinz; Mul, Guido; Wasylenko, Walter; Hamdy, M. Sameh; Frei, Heinz

    2008-06-04

    Vanadia was incorporated in the 3-dimensional mesoporous material TUD-1 with a loading of 2percent w/w vanadia. The performance in the selective photo-oxidation of liquid cyclohexene was investigated using ATR-FT-IR spectroscopy. Under continuous illumination at 458 nm a significant amount of product, i.e. cyclohexenone, was identified. This demonstrates for the first time that hydroxylated vanadia centers in mesoporous materials can be activated by visible light to induce oxidation reactions. Using the rapid scan method, a strong perturbation of the vanadyl environment could be observed in the selective oxidation process induced by a 458 nm laser pulse of 480 ms duration. This is proposed to be caused by interaction of the catalytic centre with a cyclohexenyl hydroperoxide intermediate. The restoration of the vanadyl environment could be kinetically correlated to the rate of formation of cyclohexenone, and is explained by molecular rearrangement and dissociation of the peroxide to ketone and water. The ketone diffuses away from the active center and ATR infrared probing zone, resulting in a decreasing ketone signal on the tens of seconds time scale after initiation of the photoreaction. This study demonstrates the high potential of time resolved ATR FT-IR spectroscopy for mechanistic studies of liquid phase reactions by monitoring not only intermediates and products, but by correlating the temporal behavior of these species to molecular changes of the vanadyl catalytic site.

  16. [ALK inhibitor].

    Science.gov (United States)

    Mano, Hiroyuki

    2011-01-01

    While lung cancer is the leading cause of cancer deaths worldwide, the molecular mechanism underlying its carcinogenesis is mainly unknown. We have discovered a small, fusion-type tyrosine kinase EML4-ALK that is generated through a tiny inversion within the short arm of human chromosome 2. Transgenic mice expressing EML4-ALK in lung developed hundreds of lung cancer nodules soon after birth, but such nodules were readily eradicated upon treatment with an ALK inhibitor. Clinical trials for EML4-ALK-positive lung cancer with an ALK inhibitor is ongoing, with its interim results being highly promising.

  17. The ATM- and ATR-related SCD domain is over-represented in proteins involved in nervous system development.

    Science.gov (United States)

    Cara, Lukas; Baitemirova, Medina; Follis, Jack; Larios-Sanz, Maia; Ribes-Zamora, Albert

    2016-01-08

    ATM and ATR are cellular kinases with a well-characterized role in the DNA-damage response. Although the complete set of ATM/ATR targets is unknown, they often contain clusters of S/TQ motifs that constitute an SCD domain. In this study, we identified putative ATM/ATR targets that have a conserved SCD domain across vertebrates. Using this approach, we have identified novel putative ATM/ATR targets in pathways known to be under direct control of these kinases. Our analysis has also unveiled significant enrichment of SCD-containing proteins in cellular pathways, such as vesicle trafficking and actin cytoskeleton, where a regulating role for ATM/ATR is either unknown or poorly understood, hinting at a much broader and overarching role for these kinases in the cell. Of particular note is the overrepresentation of conserved SCD-containing proteins involved in pathways related to neural development. This finding suggests that ATM/ATR could be directly involved in controlling this process, which may be linked to the adverse neurological effects observed in patients with mutations in ATM.

  18. ATR preferentially interacts with common fragile site FRA3B and the binding requires its kinase activity in response to aphidicolin treatment.

    Science.gov (United States)

    Wan, Cheng; Kulkarni, Atul; Wang, Yuh-Hwa

    2010-04-01

    The instability of common fragile sites (CFSs) contributes to the development of a variety of cancers. The ATR-dependent DNA damage checkpoint pathway has been implicated in maintaining CFS stability, but the mechanism is incompletely understood. The goal of our study was to elucidate the action of the ATR protein in the CFS-specific ATR-dependent checkpoint response. Using a chromatin immunoprecipitation assay, we demonstrated that ATR protein preferentially binds (directly or through complexes) to fragile site FRA3B as compared to non-fragile site regions, under conditions of mild replication stress. Interestingly, the amount of ATR protein that bound to three regions of FRA3B peaked at 0.4microM aphidicolin (APH) treatment and decreased again at higher concentrations of APH. The total amounts of cellular ATR and several ATR-interacting proteins remained unchanged, suggesting that ATR binding to the fragile site is guided initially by the level of replication stress signals generated at FRA3B due to APH treatment and then sequestered from FRA3B regions by successive signals from other non-fragile site regions, which are produced at the higher concentrations of APH. This decrease in ATR binding to fragile site FRA3B at the higher concentrations of APH may account for the increasing number of chromosome gaps and breaks observed under the same conditions. Furthermore, inhibition of ATR kinase activity by treatment with 2-aminopurine (2-AP) or by over-expression of a kinase-dead ATR mutant showed that the kinase activity is required for the binding of ATR to fragile DNAs in response to APH treatment. Our results provide novel insight into the mechanism for the regulation of fragile site stability by ATR. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Angiogenesis Inhibitors

    Science.gov (United States)

    ... blood vessels “feed” growing tumors with oxygen and nutrients , allowing the cancer cells to invade nearby tissue , to move throughout ... any angiogenesis inhibitors currently being used to treat cancer in humans? Yes. The U.S. Food and Drug Administration (FDA) has approved bevacizumab to ...

  20. Ataxia-telangiectasia mutated and the Mre11-Rad50-NBS1 complex: promising targets for radiosensitization.

    Science.gov (United States)

    Kuroda, Shinji; Urata, Yasuo; Fujiwara, Toshiyoshi

    2012-01-01

    Radiotherapy plays a central part in cancer treatment, and use of radiosensitizing agents can greatly enhance this modality. Although studies have shown that several chemotherapeutic agents have the potential to increase the radiosensitivity of tumor cells, investigators have also studied a number of molecularly targeted agents as radiosensitizers in clinical trials based on reasonably promising preclinical data. Recent intense research into the DNA damage-signaling pathway revealed that ataxia-telangiectasia mutated (ATM) and the Mre11-Rad50-NBS1 (MRN) complex play central roles in DNA repair and cell cycle checkpoints and that these molecules are promising targets for radiosensitization. Researchers recently developed three ATM inhibitors (KU-55933, CGK733, and CP466722) and an MRN complex inhibitor (mirin) and showed that they have great potential as radiosensitizers of tumors in preclinical studies. Additionally, we showed that a telomerase-dependent oncolytic adenovirus that we developed (OBP-301 [telomelysin]) produces profound radiosensitizing effects by inhibiting the MRN complex via the adenoviral E1B55kDa protein. A recent Phase I trial in the United States determined that telomelysin was safe and well tolerated in humans, and this agent is about to be tested in combination with radiotherapy in a clinical trial based on intriguing preclinical data demonstrating that telomelysin and ionizing radiation can potentiate each other. In this review, we highlight the great potential of ATM and MRN complex inhibitors, including telomelysin, as radiosensitizing agents.

  1. ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G; Lukas, Jiri

    2004-01-01

    The ATR and Chk1 kinases are essential to maintain genomic integrity. ATR, with Claspin and the Rad9-Rad1-Hus1 complex, activates Chk1 after DNA damage. Chk1-mediated phosphorylation of the Cdc25A phosphatase is required for the mammalian S-phase checkpoint. Here, we show that during physiological...... S phase the regulation of the Chk1-Cdc25A pathway depends on ATR, Claspin, Rad9, and Hus1. Human cells with chemically or genetically ablated ATR showed inhibition of Chk1-dependent phosphorylation of Cdc25A, and they accumulated Cdc25A without external DNA damage. Furthermore, si......RNA-mediated depletion of Claspin, Rad9 and Hus1 also stabilized Cdc25A. ATR ablation also inhibited the activatory phosphorylation of Chk1 on serine 345. Thus, the ATR-Chk1-Cdc25A pathway represents an integral part of physiological S-phase progression, and interference with this mechanism undermines viability...

  2. ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

    Science.gov (United States)

    Ray, Alo; Blevins, Chessica; Wani, Gulzar; Wani, Altaf A

    2016-01-01

    Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation.

  3. Identification of two novel regulatory genes involved in pristinamycin biosynthesis and elucidation of the mechanism for AtrA-p-mediated regulation in Streptomyces pristinaespiralis.

    Science.gov (United States)

    Wang, Wenfang; Tian, Jinzhong; Li, Lei; Ge, Mei; Zhu, Hong; Zheng, Guosong; Huang, He; Ruan, Lijun; Jiang, Weihong; Lu, Yinhua

    2015-09-01

    In this study, using a transposon-based strategy, two novel regulatory genes were identified as being involved in the biosynthesis of both pristinamycin I (PI) and II (PII) in Streptomyces pristinaespiralis, including a TetR-family regulatory gene atrA-p (SSDG_00466) and an orphan histidine kinase gene SSDG_02492. The mechanism by which AtrA-p exerted a positive role in pristinamycin production was elucidated. We showed that deletion of atrA-p resulted in a delayed production of both PI and PII as well as reduced PII production. Transcriptional analysis integrated with electrophoretic mobility shift assays (EMSAs) demonstrated that AtrA-p played a positive role in pristinamycin production by directly activating the transcription of two cluster-situated regulatory genes, spbR and papR5, which encode a γ-butyrolactone receptor protein and a TetR-family repressor, respectively. The precise AtrA-p-binding sites upstream of these two targets were determined, which allowed the identification of a relatively conserved binding motif comprising two 5-nt inverted repeats separated by a variable 5-nt sequence (5'-GGAAT-n5-ATTCC-3') possibly required for the regulation of AtrA-like regulators in Streptomyces. Base substitutions of the AtrA-p-binding sites on the genome caused similar decreases in spbR and papR5 transcription as those observed in ∆atrA-p. Taken together, herein, a novel mechanism for AtrA-dependent regulation of antibiotic biosynthesis was revealed in S. pristinaespiralis, which is distinct from those of its homologs, AtrA-c from Streptomyces coelicolor, AtrA-g from Streptomyces griseus, and AtrA from Streptomyces roseosporus that perform their effects in antibiotic biosynthesis directly via pathway-specific activator genes or the biosynthetic structural genes.

  4. Drosophila dSmad2 and Atr-I transmit activin/TGFbeta signals.

    Science.gov (United States)

    Das, P; Inoue, H; Baker, J C; Beppu, H; Kawabata, M; Harland, R M; Miyazono, K; Padgett, R W

    1999-02-01

    Much is known about the three subfamilies of the TGFbeta superfamily in vertebrates-the TGFbetas, dpp/BMPs, and activins. Signalling in each subfamily is dependent on both shared and unique cell surface receptors and Smads. In invertebrates, mutants for BMP pathway components have been extensively characterized, but thus far, evidence for an activin- or TGFbeta-like pathway has been lacking, preventing the use of the extensive genetic tools available for studying several key issues of TGFbeta signalling. Here we report the identification of dSmad2, a new Drosophila Smad which is most related to the activin/TGFbeta-pathway Smads, Smad2 and Smad3. We show that dSmad2 induces activin responsive genes in Xenopus animal cap assays. dSMAD2 is phosphorylated by ATR-I and PUNT, but not by activated THICK VEINS, and translocates to the nucleus upon activation. Furthermore, we show that dSMAD2 complexes with MEDEA only in the presence of ATR-I and PUNT. dSmad2 is expressed in the imaginal disks and in the outer proliferation centre of the larval brain, suggesting that it may have important proliferative and patterning roles during Drosophila development. Our data provide evidence for the existence of an activin/TGFbeta pathway in Drosophila. We show that dSmad2 participates in this pathway, and that it functions with Atr-I and punt. We show that Medea also participates in this pathway, indicating the conservation of roles for Co-Smads in diverse phyla. Expression patterns of dSmad2 suggest that it functions in imaginal disks and in the brain, in tissues that undergo extensive patterning and proliferation.

  5. Root discrimination of closely related crop and weed species using FT MIR-ATR spectroscopy

    Directory of Open Access Journals (Sweden)

    Catharina eMeinen

    2015-09-01

    Full Text Available Root discrimination of species is a pre-condition for studying belowground competition processes between crop and weed species. In this experiment, we tested Fourier transform mid-infrared (FT MIR-attenuated total reflection (ATR spectroscopy to discriminate roots of closely related crop and weed species grown in the greenhouse: maize/barnyard grass, barley/wild oat, wheat/blackgrass (Poaceae, and sugar beet/common lambsquarters (Chenopodiaceae. Fresh (moist and dried root segments as well as ground roots were analyzed by FT MIR-ATR spectroscopy. Root absorption spectra showed species specific peak distribution and peak height. A clear separation according to species was not possible with fresh root segments. Dried root segments (including root basis, middle section and root tip of maize/barnyard grass and sugar beet/common lambsquarters formed completely separated species clusters. Wheat and blackgrass separated in species specific clusters when root tips were removed from cluster analysis. A clear separation of dried root segments according to species was not possible in the case of barley and wild oat. Cluster analyses of ground roots revealed a 100 % separation of all tested crop and weed species combinations. Spectra grouped in Poaceae and Chenopodiaceae clusters. Within the Poaceae cluster, C3 and C4 species differed significantly in heterogeneity. Thus, root spectra reflected the degree of kinship. To quantify species proportion in root mixtures, a two- and a three-species model for species quantification in root mixtures of maize, barnyard grass, and wild oat was calculated. The models showed low standard errors of prediction (RMSEP and high residual predictive deviation (RPD values in an external test set validation. Hence, FT MIR-ATR spectroscopy seems to be a promising tool for root research even between closely related plant species.

  6. AGR-3/4 Final Data Qualification Report for ATR Cycles 151A through 155B-1

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Binh T. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-03-01

    This report provides the qualification status of experimental data for the entire Advanced Gas Reactor 3/4 (AGR 3/4) fuel irradiation. AGR-3/4 is the third in a series of planned irradiation experiments conducted in the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) for the AGR Fuel Development and Qualification Program, which supports development of the advanced reactor technology under the INL ART Technology Development Office (TDO). The main objective of AGR-3/4 irradiation is to provide a known source of fission products for subsequent transport through compact matrix and structural graphite materials due to the presence of designed-to-fail fuel particles. Full power irradiation of the AGR 3/4 test began on December 14, 2011 (ATR Cycle 151A), and was completed on April 12, 2014 (end of ATR Cycle 155B) after 369.1 effective full power days of irradiation. The AGR-3/4 test was in the reactor core for eight of the ten ATR cycles between 151A and 155B. During the unplanned outage cycle, 153A, the experiment was removed from the ATR northeast flux trap (NEFT) location and stored in the ATR canal. This was to prevent overheating of fuel compacts due to higher than normal ATR power during the subsequent Powered Axial Locator Mechanism cycle, 153B. The AGR 3/4 test was inserted back into the ATR NEFT location during the outage of ATR Cycle 154A on April 26, 2013. Therefore, the AGR-3/4 irradiation data received during these 2 cycles (153A and 153B) are irrelevant and their qualification status isnot included in this report. Additionally, during ATR Cycle 152A the ATR core ran at low power for a short enough duration that the irradiation data are not used for physics and thermal calculations. However, the qualification status of irradiation data for this cycle is still covered in this report. As a result, this report includes data from 8 ATR Cycles: 151A, 151B, 152A, 152B, 154A, 154B, 155A, and 155B, as recorded in the Nuclear Data Management and

  7. Shear Punch Testing on ATR Irradiated MA956 FeCrAl Alloy

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, Tarik A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Quintana, Matthew Estevan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Romero, Tobias J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-13

    The shear punch testing of irradiated and control MA956 (FeCrAl) Alloy from the NSUF-ATR-UCSB irradiation is presented. This is the first data taken on a new shear punch fixture design to test three 1.5mm punches from each 8mm x 0.5mm Disc Multipurpose Coupon (DMC). Samples were irradiated to 6.1dpa at a temperature of 315°C and 6.2 dpa at 400°C.

  8. Characterisation Of Polysacharides And Lipids From Selected Green Algae Species By FTIR-ATR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Bartošová Alica

    2015-06-01

    Full Text Available Fourier transform infrared (FTIR spectroscopy was used in this study to identify and determine spectral features of Chromochloris zofingiensis (Dönz Fucíková et L.A. Lewis (SAG 211-14, Gottingen, Germany, Acutodesmus obliguus (Turpin Hegewald (SAG 276-1, Gottingen, Germany and Chlorella sorokiniana (K. Brandt Pröschold et Darienko (SAG 211-40c, Gottingen, Germany. Polysaccharides and lipids from these three algae species were determined using Fourier Transformed Infrared Spectroscopy (FTIR with ATR accessory with diamante crystal in spectral range from 400 – 4000 cm−1 and resolution 4.

  9. Radar automatic target recognition (ATR) and non-cooperative target recognition (NCTR)

    CERN Document Server

    Blacknell, David

    2013-01-01

    The ability to detect and locate targets by day or night, over wide areas, regardless of weather conditions has long made radar a key sensor in many military and civil applications. However, the ability to automatically and reliably distinguish different targets represents a difficult challenge. Radar Automatic Target Recognition (ATR) and Non-Cooperative Target Recognition (NCTR) captures material presented in the NATO SET-172 lecture series to provide an overview of the state-of-the-art and continuing challenges of radar target recognition. Topics covered include the problem as applied to th

  10. Binding of a biosynthetic intermediate to AtrA modulates the production of lidamycin by Streptomyces globisporus.

    Science.gov (United States)

    Li, Xingxing; Yu, Tengfei; He, Qing; McDowall, Kenneth J; Jiang, Bingya; Jiang, Zhibo; Wu, Linzhuan; Li, Guangwei; Li, Qinglian; Wang, Songmei; Shi, Yuanyuan; Wang, Lifei; Hong, Bin

    2015-06-01

    The control of secondary production in streptomycetes involves the funneling of environmental and physiological signals to the cluster-situated (transcriptional) regulators (CSRs) of the biosynthetic genes. For some systems, the binding of biosynthetic products to the CSR has been shown to provide negative feedback. Here we show for the production of lidamycin (C-1027), a clinically relevant antitumor agent, by Streptomyces globisporus that negative feedback can extend to a point higher in the regulatory cascade. We show that the DNA-binding activity of the S. globisporus orthologue of AtrA, which was initially described as a transcriptional activator of actinorhodin biosynthesis in S. coelicolor, is inhibited by the binding of heptaene, a biosynthetic intermediate of lidamycin. Additional experiments described here show that S. globisporus AtrA binds in vivo as well as in vitro to the promoter region of the gene encoding SgcR1, one of the CSRs of lidamycin production. The feedback to the pleiotropic regulator AtrA is likely to provide a mechanism for coordinating the production of lidamycin with that of other secondary metabolites. The activity of AtrA is also regulated by actinorhodin. As AtrA is evolutionarily conserved, negative feedback of the type described here may be widespread within the streptomycetes. © 2015 John Wiley & Sons Ltd.

  11. Comparison of pharmaceutical formulations: ATR-FTIR spectroscopic imaging to study drug-carrier interactions.

    Science.gov (United States)

    Ewing, Andrew V; Biggart, Gordon D; Hale, Carwyn R; Clarke, Graham S; Kazarian, Sergei G

    2015-11-10

    Attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopic imaging has been used in combination with UV detection to study the release of a model poorly water-soluble drug, indomethacin, when formulated with selected drug carriers. Firstly, formulations of indomethacin and nicotinamide in varying weight ratios were studied since novel tablet dosage forms containing multi-drugs are of industrial interest. The in situ spectroscopic imaging measurements of the dissolving tablets showed that as the loading of indomethacin was increased, the rate of drug release changed from one that expressed first-order drug release to one which showed zero-order drug release. Two drug release mechanisms have been identified from the recorded spectroscopic images and UV dissolution profiles. To further validate these mechanisms, specific formulations containing the model drug and two other excipients, urea and mannitol, were studied. The formulations with urea showed similar first-order release, indicative of the drug-carrier interactions. Whereas, the indomethacin/mannitol formulations showed a zero-order release curve explained by disintegration of the tablet. ATR-FTIR spectroscopic imaging provided highly chemically specific information as well as the spatial distribution of the components during the dissolution process which has demonstrated the potential of this combined analytical setup to determine the mechanisms of drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Independent Review of AFC 2A, 2B, and 2E ATR Irradiation Tests

    Energy Technology Data Exchange (ETDEWEB)

    M. Cappiello; R. Hobbins; K. Penny; L. Walters

    2014-01-01

    As part of the Department of Energy Advanced Fuel Cycle program, a series of fuels development irradiation tests have been performed in the Advanced Test Reactor (ATR) at the Idaho National Laboratory. These tests are providing excellent data for advanced fuels development. The program is focused on the transmutation of higher actinides which best can be accomplished in a sodium-cooled fast reactor. Because a fast test reactor is no longer available in the US, a special test vehicle is used to achieve near-prototypic fast reactor conditions (neutron spectra and temperature) for use in ATR (a water-cooled thermal reactor). As part of the testing program, there were many successful tests of advanced fuels including metals and ceramics. Recently however, there have been three experimental campaigns using metal fuels that experienced failure during irradiation. At the request of the program, an independent review committee was convened to review the post-test analyses performed by the fuels development team, to assess the conclusions of the team for the cause of the failures, to assess the adequacy and completeness of the analyses, to identify issues that were missed, and to make recommendations for improvements in the design and operation of future tests. Although there is some difference of opinion, the review committee largely agreed with the conclusions of the fuel development team regarding the cause of the failures. For the most part, the analyses that support the conclusions are sufficient.

  13. In vivo interstitial glucose characterization and monitoring in the skin by ATR-FTIR spectroscopy

    Science.gov (United States)

    Skrebova Eikje, Natalja

    2011-03-01

    Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related 1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise measurements of interstitial glucose levels may be more important clinically.

  14. Rapid detection of melamine adulteration in dairy milk by SB-ATR-Fourier transform infrared spectroscopy.

    Science.gov (United States)

    Jawaid, Sana; Talpur, Farah N; Sherazi, S T H; Nizamani, Shafi M; Khaskheli, Abid A

    2013-12-01

    Melamine is a nitrogenous chemical substance used principally as a starting material for the manufacture of synthetic resins. Due to its very high proportion of nitrogen melamine has been added illegitimately to foods and feeds to increase the measured protein content, which determines the value of the product. These issues prompted private as well as governmental laboratories to develop methods for the analysis of melamine in a wide variety of food products and ingredients. Owing to this fact present study is aimed to use single bounce attenuated total reflectance (SB-ATR) Fourier transform infrared spectroscopy (FTIR) method as an effective rapid tool for the detection and quantification of melamine in milk (liquid and powder). Partial least-squares (PLS) models were established for correlating spectral data to melamine concentration with R(2)>0.99, and RMSEC 0.370. Linear calibration curves were obtained over the calibration range of 25-0.0625%. The LOD and LOQ of the method was 0.00025% (2.5 ppm) and 0.0015% (15 ppm) respectively. Proposed SB-ATR-FTIR method requires little or no sample preparation with an assay time of 1-2 min. Copyright © 2013. Published by Elsevier Ltd.

  15. Analytical characterization of polymers used in conservation and restoration by ATR-FTIR spectroscopy.

    Science.gov (United States)

    Chércoles Asensio, Ruth; San Andrés Moya, Margarita; de la Roja, José Manuel; Gómez, Marisa

    2009-12-01

    In the last few decades many new polymers have been synthesized that are now being used in cultural heritage conservation. The physical and chemical properties and the long-term behaviors of these new polymers are determined by the chemical composition of the starting materials used in their synthesis along with the nature of the substances added to facilitate their production. The practical applications of these polymers depend on their composition and form (foam, film, sheets, pressure-sensitive adhesives, heat-seal adhesives, etc.). Some materials are used in restoration works and others for the exhibition, storage and transport of works of art. In all cases, it is absolutely necessary to know their compositions. Furthermore, many different materials that are manufactured for other objectives are also used for conservation and restoration. The technical information about the materials provided by the manufacturer is usually incomplete, so it is necessary to analytically characterize such materials. FTIR spectrometry is widely used for polymer identification, and, more recently, ATR-FTIR has been shown to give excellent results. This paper reports the ATR-FTIR analysis of samples of polymeric materials used in the conservation of artworks. These samples were examined directly in the solid material without sample preparation.

  16. Analysis code for large rupture accidents in ATR. SENHOR/FLOOD/HEATUP

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-08-01

    In the evaluation of thermo-hydraulic transient change, the behavior of core reflooding and the transient change of fuel temperature in the events which are classified in large rupture accidents of reactor coolant loss, that is the safety evaluation event of the ATR, the analysis codes for thermo-hydraulic transient change at the time of large rupture SENHOR, for core reflooding characteristics FLOOD and for fuel temperature HEATUP are used, respectively. The analysis code system for loss of coolant accident comprises the analysis code for thermo-hydraulic transient change at the time of medium and small ruptures LOTRAC in addition to the above three codes. Based on the changes with time lapse of reactor thermal output and steam drum pressure obtained by the SENHOR, average reflooding rate is analyzed by the FLOOD, and the time of starting the turnaround of fuel cladding tube temperature and the heat transfer rate after the turnaround are determined. Based on these data, the detailed temperature change of fuel elements is analyzed by the HEATUP, and the highest temperature and the amount of oxidation of fuel cladding tubes are determined. The SENHOR code, the FLOOD code and the HEATUP code and various models for these codes are explained. The example of evaluation and the sensitivity analysis of the ATR plant are reported in the Appendix. (K.I.)

  17. New particle formation events measured on board the ATR-42 aircraft during the EUCAARI campaign

    Directory of Open Access Journals (Sweden)

    S. Crumeyrolle

    2010-07-01

    Full Text Available Aerosol properties were studied during an intensive airborne measurement campaign that took place at Rotterdam in Netherlands in May 2008 within the framework of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI. The objective of this study is to illustrate seven events of new particle formation (NPF observed with two Condensation Particle Counters (CPCs operated on board the ATR-42 research aircraft in airsectors around Rotterdam, and to provide information on the spatial extent of the new particle formation phenomenon based on 1-s resolution measurements of ultra-fine particle (in the size range 3–10 nm diameter, denoted N3-10 hereafter concentrations. The results show that particle production occurred under the influence of different air mass origins, at different day times and over the North Sea as well as over the continent. The number concentration of freshly nucleated particles (N3-10 varied between 5000 and 100 000 cm−3 within the boundary layer (BL. Furthermore the vertical extension for all nucleation events observed on the ATR-42 never exceeded the upper limit of the BL. The horizontal extent of N3-10 could not be delimited due to inflexible flight plans which could not be modified to accommodate real-time results. However, the NPF events were observed over geographically large areas; typically the horizontal extension was about 100 km and larger.

  18. Centromeric DNA replication reconstitution reveals DNA loops and ATR checkpoint suppression.

    Science.gov (United States)

    Aze, Antoine; Sannino, Vincenzo; Soffientini, Paolo; Bachi, Angela; Costanzo, Vincenzo

    2016-06-01

    Half of the human genome is made up of repetitive DNA. However, mechanisms underlying replication of chromosome regions containing repetitive DNA are poorly understood. We reconstituted replication of defined human chromosome segments using bacterial artificial chromosomes in Xenopus laevis egg extract. Using this approach we characterized the chromatin assembly and replication dynamics of centromeric alpha-satellite DNA. Proteomic analysis of centromeric chromatin revealed replication-dependent enrichment of a network of DNA repair factors including the MSH2-6 complex, which was required for efficient centromeric DNA replication. However, contrary to expectations, the ATR-dependent checkpoint monitoring DNA replication fork arrest could not be activated on highly repetitive DNA due to the inability of the single-stranded DNA binding protein RPA to accumulate on chromatin. Electron microscopy of centromeric DNA and supercoil mapping revealed the presence of topoisomerase I-dependent DNA loops embedded in a protein matrix enriched for SMC2-4 proteins. This arrangement suppressed ATR signalling by preventing RPA hyper-loading, facilitating replication of centromeric DNA. These findings have important implications for our understanding of repetitive DNA metabolism and centromere organization under normal and stressful conditions.

  19. Focusing, imaging, and ATR for the Gotcha 2008 wide angle SAR collection

    Science.gov (United States)

    Gianelli, Christopher D.; Xu, Luzhou

    2013-05-01

    The following work discusses IAA's approach to tackling the wide angle, circular spotlight, synthetic aperture radar (SAR) problem from the 2008 Gotcha wide angle SAR data set, which is publicly released, with unlimited distribution. This data set comes with a MATLAB image formation routine and attendant graphical user inter- face (GUI). We begin by introducing a simple approach to focusing the collected phase history data that utilizes point targets (quadrahedral targets) present in the scene. Two SAR imaging algorithms are then presented, namely, the data-independent backprojection (BP) algorithm and the data-adaptive sparse learning via itera- tive minimization (SLIM) algorithm. These imaging approaches are compared using the 2008 Gotcha wide angle SAR data to perform both a clutter discrimination experiment, as well as an automatic target recognition (ATR) experiment. The ATR system is composed of a target pose and target center estimation preprocessing system, and includes a novel target feature for the final classification stage. Empirical results obtained by applying the focusing approach and imaging algorithms to the 2008 Gotcha wide angle SAR data set are presented and described. The results presented highlight the benefit of applying the SLIM algorithm over its data-independent counterpart, as well as the utility of the novel target feature.

  20. Mebendazole crystal forms in tablet formulations. An ATR-FTIR/chemometrics approach to polymorph assignment.

    Science.gov (United States)

    Calvo, Natalia L; Kaufman, Teodoro S; Maggio, Rubén M

    2016-04-15

    Structural polymorphism of active pharmaceutical ingredients (API) is a relevant concern for the modern pharmaceutical industry, since different polymorphic forms may display dissimilar properties, critically affecting the performance of the corresponding drug products. Mebendazole (MEB) is a widely used broad spectrum anthelmintic drug of the benzimidazole class, which exhibits structural polymorphism (Forms A-C). Form C, which displays the best pharmaceutical profile, is the recommended one for clinical use. The polymorphs of MEB were prepared and characterized by spectroscopic, calorimetric and microscopic means. The polymorphs were employed to develop a suitable chemometrics-assisted sample display model based on the first two principal components of their ATR-FTIR spectra in the 4000-600 cm(-1) region. The model was internally and externally validated employing the leave-one-out procedure and an external validation set, respectively. Its suitability for revealing the polymorphic identity of MEB in tablets was successfully assessed analyzing commercial tablets under different physical forms (whole, powdered, dried, sieved and aged). It was concluded that the ATR-FTIR/PCA (principal component analysis) association is a fast, efficient and non-destructive technique for assigning the solid-state forms of MEB in its drug products, with minimum sample pre-treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. In-column ATR-FTIR spectroscopy to monitor affinity chromatography purification of monoclonal antibodies

    Science.gov (United States)

    Boulet-Audet, Maxime; Kazarian, Sergei G.; Byrne, Bernadette

    2016-07-01

    In recent years many monoclonal antibodies (mAb) have entered the biotherapeutics market, offering new treatments for chronic and life-threatening diseases. Protein A resin captures monoclonal antibody (mAb) effectively, but the binding capacity decays over repeated purification cycles. On an industrial scale, replacing fouled Protein A affinity chromatography resin accounts for a large proportion of the raw material cost. Cleaning-in-place (CIP) procedures were developed to extend Protein A resin lifespan, but chromatograms cannot reliably quantify any remaining contaminants over repeated cycles. To study resin fouling in situ, we coupled affinity chromatography and Fourier transform infrared (FTIR) spectroscopy for the first time, by embedding an attenuated total reflection (ATR) sensor inside a micro-scale column while measuring the UV 280 nm and conductivity. Our approach quantified the in-column protein concentration in the resin bed and determined protein conformation. Our results show that Protein A ligand leached during CIP. We also found that host cell proteins bound to the Protein A resin even more strongly than mAbs and that typical CIP conditions do not remove all fouling contaminants. The insights derived from in-column ATR-FTIR spectroscopic monitoring could contribute to mAb purification quality assurance as well as guide the development of more effective CIP conditions to optimise resin lifespan.

  2. ATR-IR study of skin components: Lipids, proteins and water. Part I: Temperature effect

    Science.gov (United States)

    Olsztyńska-Janus, S.; Pietruszka, A.; Kiełbowicz, Z.; Czarnecki, M. A.

    2018-01-01

    In this work we report the studies of the effect of temperature on skin components, such as lipids, proteins and water. Modifications of lipids structure induced by increasing temperature (from 20 to 90 °C) have been studied using ATR-IR (Attenuated Total Reflectance Infrared) spectroscopy, which is a powerful tool for characterization of the molecular structure and properties of tissues, such as skin. Due to the small depth of penetration (0.6-5.6 μm), ATR-IR spectroscopy probes only the outermost layer of the skin, i.e. the stratum corneum (SC). The assignment of main spectral features of skin components allows for the determination of phase transitions from the temperature dependencies of band intensities [e.g. νas(CH2) and νs(CH2)]. The phase transitions were determined by using two methods: the first one was based on the first derivative of the Boltzmann function and the second one employed tangent lines of sigmoidal, aforementioned dependencies. The phase transitions in lipids were correlated with modifications of the structure of water and proteins.

  3. Classification of Edible Oils Based on ATR-FTIR Spectral Information During a Long Heating Treatment.

    Science.gov (United States)

    Mahboubifar, Marjan; Hemmateenejad, Bahram; Yousefinejad, Saeed

    2017-03-01

    Identification of oil type and its QC are important concerns in food control laboratories. Classifying edible oils that have not been used (i.e., unheated) with the aid of vibrational spectroscopy has previously been reported. However, the classification of used (i.e., heat-treated) oils needs special attention. The effect of long heating times on the classification of four kinds of edible oils (canola, corn, frying, and sunflower) based on attenuated total reflectance (ATR)-FTIR spectra was surveyed. The sampling was done on the oils during a 36 h heating process (at 170°C). The ATR-FTIR spectra of the samples were collected in the range of 4000-550 cm-1. Interval extended canonical variates analysis (ECVA), as a variable selection and classification tool, was used to determine the best intervals during the heating procedure for classification. Principal component analysis discriminate analysis, partial least-squares discriminate analysis, and ECVA were performed on the selected intervals and on the total heating time. The effect of autoscaling and mean-centering, as data preprocessing methods, was also investigated. The ECVA method resulted in the best performances for classification, with a 94% cross-validated nonerror rate (one misclassification) for the heating process times of 24-27 and 33-36 h.

  4. Identification and classification of textile fibres using ATR-FT-IR spectroscopy with chemometric methods.

    Science.gov (United States)

    Peets, Pilleriin; Leito, Ivo; Pelt, Jaan; Vahur, Signe

    2017-02-15

    The possibility of classification of single- and two-component textile materials using ATR-FT-IR spectra and chemometric methods, principal component analysis (PCA) and discriminant analysis, was assessed. Altogether 89 textile samples belonging to 26 different types (11 one- and 15 two-component textiles) were investigated. It was found that PCA classification using only two or three principal components (PCs) enables identifying different one- and two-component textiles, although with two important limitations: it was not always possible to distinguish between the cellulose-based fibres (cotton, linen and in some cases viscose) and it was only partly possible to distinguish between silk and wool. The statistical discriminant analysis can use as many PCs as there are sample classes and due to that can discriminate between single-component fibres, including viscose from linen and cotton as well as silk from wool. Besides that, in both of these cases, involving optical microscopy as an additional technique enabled unequivocal identification of the fibres. The possibilities of semi-quantitative analysis of mixed fibres (cotton-polyester, wool-polyester and wool-polyamide) with PCA were investigated and it was found that approximate quantitative composition is obtainable if for the mixed fibre sample a number of spectra are averaged in order to minimize the effect of structural inhomogeneity. For approximate content determination 25 spectra of selected two-component samples were registered for calibration and the averaged spectrum for each sample was computed. Due to the structural inhomogeneity of mixed textiles, obtaining accurate quantitative composition from real samples is not possible with ATR-FT-IR. The main problems with ATR-FT-IR-PCA classification are (1) difficulties in getting high quality spectra from some textiles (e.g. polyacrylic), (2) inhomogeneity of the textile fibres in the case of two-component fibres and (3) intrinsic similarity between the

  5. Assessment of XM-19 as a Substitute for AISI 348 in ATR Service

    Energy Technology Data Exchange (ETDEWEB)

    F. A. Garner; L. R. Greenwood; R. E. Mizia; C. R. Tyler

    2007-11-01

    It has been proposed that XM-19 alloy be considered as a possible replacement steel for AISI 348 in the construction of Advanced Test Reactor (ATR) capsules. AISI 348 works well, but is currently very difficult to obtain commercially. The superior and desirable mechanical properties of XM-19 alloy have been proven in non-nuclear applications, but no data are available regarding its use in radiation environments. While most 300 series alloys will meet the conditions required in ATR , it cannot be confidently assumed that XM-19 can be substituted without prior qualification in a radiation test. Compared to AISI 348, XM-19 will have an enhanced tendency for phase instabilities due to its higher levels of Ni and, especially, Si. However, transmutation of important elemental components in the highly thermalized ATR spectrum may have a very pronounced effect on its performance during irradiation. Not only will strong transmutation of Mn to Fe reduce the ductility and strength advantages provided by the higher initial Mn content of XM-19, but the extensive loss of Mn will also release from solution much of the N upon which the higher strength of XM-19 depends. In addition, the combined influence of transmutation and Inverse Kirkendall processes may lead to gas-bubble-covered grain boundaries, producing a very fragile alloy after significant irradiation has accumulated. At present, there are no radiation data available to substantiate this possible scenario. An alternate proposal is therefore advanced. Since the response of AISI 348 and 347 to radiation are expected to be relatively indistinguishable, the AISI 347 might serve as an acceptable replacement. While AISI 348 is usually chosen for nuclear service in order to reduce the overall radioactivity arising from relatively small amounts of highly transmutable elements such as cobalt, these elements have very little effect on the radiation performance of the steel. In the proposed application, however, the activity

  6. An essential function for the ATR-activation-domain (AAD of TopBP1 in mouse development and cellular senescence.

    Directory of Open Access Journals (Sweden)

    Zhong-Wei Zhou

    Full Text Available ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins - Dpb11(TopBP1, Ddc1(Rad9 and Dna2 - all interact with and activate Mec1(ATR. Each contains an ATR activation domain (ADD that interacts directly with the Mec1(ATR:Ddc2(ATRIP complex. Any of the Dpb11(TopBP1, Ddc1(Rad9 or Dna2 ADDs is sufficient to activate Mec1(ATR in vitro. All three can also independently activate Mec1(ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development.

  7. In Situ ATR-FTIR Study on the Selective Photo-oxidation of Cyclohexane over Anatase TiO2

    NARCIS (Netherlands)

    Almeida, A.; Moulijn, J.A.; Mul, Guido

    2008-01-01

    Anatase-catalyzed photo-oxidation of cyclohexane was analyzed by in situ ATR-FTIR spectroscopy. A set of seven UV-LEDs (375 nm), with a photon flux of 9 × 10-9 Einstein·cm-2·s-1 (at the catalyst surface) was used to initiate the photoreaction. Surface-adsorbed cyclohexanone and water are the primary

  8. Using paint to investigate fires: an ATR-IR study of the degradation of paint samples upon heating.

    Science.gov (United States)

    Roberts, Kelly; Almond, Matthew J; Bond, John W

    2013-03-01

    Fire investigation is a challenging area for the forensic investigator. The aim of this work was to use spectral changes to paint samples to estimate the temperatures to which a paint has been heated. Five paint samples (one clay paint, two car paints, one metallic paint, and one matt emulsion) have been fully characterized by a combination of attenuated total reflectance Fourier transform infrared (ATR-IR), Raman, X-ray fluorescence spectroscopy and powder X-ray diffraction. The thermal decomposition of these paints has been investigated by means of ATR-IR and thermal gravimetric analysis. Clear temperature markers are observed in the ATR-IR spectra namely: loss of ν(C = O) band, >300°C; appearance of water bands on cooling, >500°C; alterations to ν(Si-O) bands due to dehydration of silicate clays, >700°C; diminution of ν(CO3 ) and δ(CO3 ) modes of CaCO3 , >950°C. We suggest the possible use of portable ATR-IR for nondestructive, in situ analysis of paints. © 2012 American Academy of Forensic Sciences.

  9. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) in the discrimination of normal and oral cancer blood plasma

    Science.gov (United States)

    Pachaiappan, Rekha; Prakasarao, Aruna; Singaravelu, Ganesan

    2017-02-01

    Oral cancer is the most frequent type of cancer that occurs with 75000 to 80000 new cases reported every year in India. The carcinogens from tobacco and related products are the main cause for the oral cancer. ATR-FTIR method is label free, fast and cost-effective diagnostic method would allow for rapid diagnostic results in earlier stages by the minimal chemical changes occur in the biological metabolites available in the blood plasma. The present study reports the use of ATR-FTIR data with advanced statistical model (LDA-ANN) in the diagnosis of oral cancer from normal with better accuracy. The infrared spectra were acquired on ATR-FTIR Jasco spectrophotometer at 4 cm-1 resolution, 30 scans, in the 1800-900 cm-1 spectral range. Each sample had 5 spectra recorded from each blood plasma sample. The spectral data were routed through the multilayer perception of artificial neural network to evaluate for the statistical efficacy. Among the spectral data it was found that amide II (1486 cm-1) and lipid (1526 cm-1) affords about 90 % in the discrimination between groups using LDA. These preliminary results indicate that ATR-FTIR is useful to differentiate normal subject from oral cancer patients using blood plasma.

  10. Stability of indomethacin with relevance to the release from amorphous solid dispersions studied with ATR-FTIR spectroscopic imaging.

    Science.gov (United States)

    Ewing, Andrew V; Clarke, Graham S; Kazarian, Sergei G

    2014-08-18

    This work presents the use of attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and spectroscopic imaging to study the stability and dissolution behaviour of amorphous solid dispersions (ASDs). ASDs are employed to improve the bioavailability of drugs which are poorly soluble in aqueous solutions. Selecting the appropriate polymeric excipients for use in pharmaceutical tablets is crucial to control drug stability and subsequent release. In this study, indomethacin was used as a model poorly-aqueous soluble drug since the amorphous-form has improved dissolution properties over its crystalline forms. ASDs of indomethacin/polyethylene glycol (PEG) and indomethacin/hydroxypropyl methylcellulose (HPMC) in a 1:3 wt ratio were compared. Firstly, ATR-FTIR spectroscopy was employed to monitor the stability of indomethacin in the ASDs over 96 h. While the indomethacin/HPMC ASD showed the ability to maintain the amorphous indomethacin form for longer periods of time, ATR-FTIR spectra revealed that indomethacin in the drug/PEG ASD crystallised to the stable γ-form, via the α-form. Secondly, ATR-FTIR spectroscopic imaging was used to study the dissolution of ASD tablets in a phosphate buffer (pH 7.5). Crystallisation of amorphous indomethacin was characterised in the spectra collected during the dissolution of the indomethacin/PEG ASD which consequently hindered release into the surrounding solution. In contrast, release of amorphous indomethacin was more effective from HPMC. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway

    NARCIS (Netherlands)

    D.O. Warmerdam (Daniël); E.K. Brinkman (Eva); J.A. Marteijn (Jurgen); R.H. Medema (Rene); R. Kanaar (Roland); V.A.J. Smits (Veronique)

    2013-01-01

    textabstractIn response to UV light, single-stranded DNA intermediates coated with replication protein A (RPA) are generated, which trigger the ATR-Chk1 checkpoint pathway. Recruitment and/or activation of several checkpoint proteins at the damaged sites is important for the subsequent cell cycle

  12. ATR-FTIR Spectroscopy Highlights the Problem of Distinguishing Between Exophiala dermatitidis and E. phaeomuriformis Using MALDI-TOF MS

    NARCIS (Netherlands)

    Ergin, C.; Gok, Y.; Baygu, Y.; Gumral, R.; Ozhak-Baysan, B.; Dogen, A.; Ogunc, D.; Ilkit, M.; Seyedmousavi, S.

    2016-01-01

    The present study compared two chemical-based methods, namely, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, to understand the misidentification of Exophiala

  13. Characterization of southern yellow pine bark layers by Attenuated Total Reflectance (ATR) and Fourier Transform Infrared (FT-IR) Spectroscopy

    Science.gov (United States)

    Thomas L. Eberhardt

    2009-01-01

    The outer bark (rhytidome) of the southern yellow pines is a complex structure comprised of alternating layers of obliterated phloem and periderm tissues, with the latter comprised of three layers, those being phellem, phellogen, and phelloderm. An attenuated total reflectance (ATR) sampling accessory, coupled with a Fourier transform infrared (FTIR) spectrometer,...

  14. Measured thermal and fast neutron fluence rates for ATF-1 holders during ATR cycle 158B/159A

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Larry Don [Idaho National Lab. (INL), Idaho Falls, ID (United States); Miller, David Torbet [Idaho National Lab. (INL), Idaho Falls, ID (United States); Walker, Billy Justin [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-11-01

    This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 158B/159A which were measured by the Radiation Measurements Laboratory (RML).

  15. Characterization of poly(L-lactide/Propylene glycol) based polyurethane films using ATR-FTIR spectroscopy

    Science.gov (United States)

    Manap, Siti Munirah; Ahmad, Azizan; Anuar, Farah Hannan

    2016-11-01

    A polyurethane films consisting of PLLA, PPG and PLLA-PPG were prepared using solution casting method. Three types of polyurethane were prepared: PPLA:PMDI, PPG:PMDI and PLLA-PPG:PMDI in the presence of polymeric diphenylmethane diisocyanate (PMDI) as the coupling agent and catalyst, Sn(Oct)2. The aim of this research was to improve the physicals properties of PLLA and PPG homopolymers through copolymerization between the two polymers. The homopolymers and polyurethane films were characterized using ATR-FTIR spectroscopy. Chemical reaction between PLLA, PPG and PMDI before and after the reaction were confirmed by observing the shifting of wavenumber for the carbonyl and ether group. Other than that, the additional band for N-H after the reaction indicated that the reaction was successful.

  16. Unidirectional excitation of graphene plasmon in attenuated total reflection (ATR) configuration

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Wei [Hubei University of Education, Wuhan (China). School of Physics and Mechanical and Electrical Engineering; Wu, Yue-Chao [Nanyang Technological University, Singapore (Singapore). Div. of Physics and Applied Physics; Liu, Fang-Li [Maryland Univ., College Park, MD (United States). Joint Quantum Institute

    2016-08-01

    Graphene plasmon has been attracting interests from both theoretical and experimental research due to its gate tunability and potential applications in the terahertz frequency range. Here, we propose an effective scheme to unidirectionally excite the graphene plasmon by exploiting magneto-optical materials in the famous attenuated total reflection (ATR) configuration. We show that the graphene plasmon dispersion relation in such a device is asymmetric in different exciting directions, thus making it possible to couple the incident light unidirectionally to the propagating plasmon. The split of absorption spectrum of graphene clearly indicates that under a magnetic field for one single frequency, graphene plasmon can only be excited in one direction. The possible gate tunablity of excitation direction and the further application of the proposed scheme, such as optical isolator, also are discussed.

  17. Usage of FTIR-ATR as Non-Destructive Analysis of Selected Toxic Dyes

    Science.gov (United States)

    Bartošová, Alica; Blinová, Lenka; Sirotiak, Maroš; Michalíková, Anna

    2017-06-01

    The degradation of the environment which is due to the discharge of polluting wastewater from industrial sources poses a real problem in several countries. Textile industries use large volumes of water in their operations, discharging thus large volume of wastewater into the environment, most of which is untreated. The wastewater contains a variety of chemicals from various stages of process operations, including desizing, scouring, bleaching and dyeing. The main purpose of this paper is to introduce Infrared Spectrometry with Fourier transformation as a non-destructive method for study, identifation and rapid determination of selected representatives of cationic (Methylene Blue), azo (Congo Red, Eriochrome Black T) and nitroso (Naphthol Green B) dyes. In conjunction with the ATR technique, FTIR offers a reliable detection method of dyes without extraction by other dangerous substances. Spectral interpretation of dye spectra revealed valuable information about the identification and characterization of each group of dyes.

  18. Analysis of H2O in silicate glass using attenuated total reflectance (ATR) micro-FTIR spectroscopy

    Science.gov (United States)

    Lowenstern, Jacob B.; Pitcher, Bradley W.

    2013-01-01

    We present a calibration for attenuated total reflectance (ATR) micro-FTIR for analysis of H2O in hydrous glass. A Ge ATR accessory was used to measure evanescent wave absorption by H2O within hydrous rhyolite and other standards. Absorbance at 3450 cm−1 (representing total H2O or H2Ot) and 1630 cm−1 (molecular H2O or H2Om) showed high correlation with measured H2O in the glasses as determined by transmission FTIR spectroscopy and manometry. For rhyolite, wt%H2O=245(±9)×A3450-0.22(±0.03) and wt%H2Om=235(±11)×A1630-0.20(±0.03) where A3450 and A1630 represent the ATR absorption at the relevant infrared wavelengths. The calibration permits determination of volatiles in singly polished glass samples with spot size down to ~5 μm (for H2O-rich samples) and detection limits of ~0.1 wt% H2O. Basaltic, basaltic andesite and dacitic glasses of known H2O concentrations fall along a density-adjusted calibration, indicating that ATR is relatively insensitive to glass composition, at least for calc-alkaline glasses. The following equation allows quantification of H2O in silicate glasses that range in composition from basalt to rhyolite: wt%H2O=(ω×A3450/ρ)+b where ω = 550 ± 21, b = −0.19 ± 0.03, ρ = density, in g/cm3, and A3450 is the ATR absorbance at 3450 cm−1. The ATR micro-FTIR technique is less sensitive than transmission FTIR, but requires only a singly polished sample for quantitative results, thus minimizing time for sample preparation. Compared with specular reflectance, it is more sensitive and better suited for imaging of H2O variations in heterogeneous samples such as melt inclusions. One drawback is that the technique can damage fragile samples and we therefore recommend mounting of unknowns in epoxy prior to polishing. Our calibration should hold for any Ge ATR crystals with the same incident angle (31°). Use of a different crystal type or geometry would require measurement of several H2O-bearing standards to provide a crystal

  19. HPV 5 and 8 E6 abrogate ATR activity resulting in increased persistence of UVB induced DNA damage.

    Directory of Open Access Journals (Sweden)

    Nicholas A Wallace

    Full Text Available The role of the E6 oncoprotein from high-risk members of the α human papillomavirus genus in anogenital cancer has been well established. However, far less is known about the E6 protein from the β human papillomavirus genus (β-HPVs. Some β-HPVs potentially play a role in non-melanoma skin cancer development, although they are not required for tumor maintenance. Instead, they may act as a co-factor that enhances the carcinogenic potential of UV damage. Indeed, the E6 protein from certain β-HPVs (HPV 5 and 8 promotes the degradation of p300, a histone acetyl transferase involved in UV damage repair. Here, we show that the expression of HPV 5 and 8 E6 increases thymine dimer persistence as well as the likelihood of a UVB induced double strand break (DSB. Importantly, we provide a mechanism for the increased DNA damage by showing that both extended thymine dimer persistence as well as elevated DSB levels are dependent on the ability of HPV 8 E6 to promote p300 degradation. We further demonstrate that HPV 5 and 8 E6 expression reduces the mRNA and protein levels of ATR, a PI3 kinase family member that plays a key role in UV damage signaling, but that these levels remain unperturbed in cells expressing a mutated HPV 8 E6 incapable of promoting p300 degradation. We confirm that the degradation of p300 leads to a reduction in ATR protein levels, by showing that ATR levels rebound when a p300 mutant resistant to HPV 8 mediated degradation and HPV 8 E6 are co-transfected. Conversely, we show that ATR protein levels are reduced when p300 is targeted for degradation by siRNA. Moreover, we show the reduced ATR levels in HPV 5 and 8 E6 expressing cells results in delayed ATR activation and an attenuated ability of cells to phosphorylate, and as a result accumulate, p53 in response to UVB exposure, leading to significantly reduced cell cycle arrest. In conclusion, these data demonstrate that β-HPV E6 expression can enhance the carcinogenic potential of

  20. ATR technique, an appropriate method for determining the degree of conversion in dental giomers

    Science.gov (United States)

    Prejmerean, Cristina; Prodan, Doina; Vlassa, Mihaela; Streza, Mihaela; Buruiana, Tinca; Colceriu, Loredana; Prejmerean, Vasile; Cuc, Stanca; Moldovan, Marioara

    2016-12-01

    Dental light-curing giomers were developed to combine the favourable properties of diacrylic resin composites (DRCs) and glass-ionomer cements (GICs) in a single material and to eliminate their inherent drawbacks. Giomers are characterized by their aesthetic appearance, high mechanical properties, adhesion to dental tissues as well as fluoride release and recharge abilities. The qualities of the giomers are greatly influenced by the level of conversion of the component resins. Infrared spectroscopy is one of the most largely used techniques for the determination of the degree of conversion in resin-based dental materials. However different results were obtained due to the performances of the used methods. The present work presents the determination of conversion degree in a series of dental copolymers and their corresponding giomers using transmission Fourier transform infrared spectroscopy (FTIR) and an attenuated total reflection technique (ATR) technique, respectively, the main aim being the study of the influence of the materials composition and of the light curing modes upon the achieved conversion in the cured giomers. Beautifil II commercial giomer was used as a control. A halogen lamp and a diode-blue LED lamp were used for the curing of the materials. The results showed that the composition of the resins greatly influenced the conversion. The highest conversions (up to 79%) were obtained in the case of the experimental giomers which contained the experimental Bis-GMA urethane analogue, followed by the Beautifil II giomer (61%) and experimental giomers based on commercial Bis-GMA (up to 50%), respectively. The resins light-cured by using the diode-blue LED lamp presented slightly higher conversions than the resins cured by halogen lamp. The study demonstrates the possibility to evaluate easily and reproducibly the conversion in light-curing composite materials with complex chemical composition and structure, particularly in the case of giomers by using the

  1. Rapid detection of NBOME's and other NPS on blotter papers by direct ATR-FTIR spectrometry.

    Science.gov (United States)

    Coelho Neto, José

    2015-07-01

    Blotter paper is among the most common forms of consumption of new psychotropic substances (NPS), formerly referred as designer drugs. In many cases, users are misled to believe they are taking LSD when, in fact, they are taking newer and less known drugs like the NBOMEs or other substituted phenethylamines. We report our findings in quick testing of blotter papers for illicit substances like NBOMEs and other NPS by taking ATR-FTIR spectra directly from blotters seized on the streets, without any sample preparation. Both sides (front and back) of each blotter were tested. Collected data were analyzed by single- and multi-component spectral matching and submitted to chemometric discriminant analysis. Our results showed that, on 66.7% of the cases analyzed, seized blotters contained one or more types of NBOMEs, confirming the growing presence of this novel substances on the market. Matching IR signals were detected on both or just one side of the blotters and showed variable strength. Although no quantitative analysis was made, detection of these substances by the proposed approach serves as indication of variable and possibly higher dosages per blotter when compared to LSD, which showed to be below the detection limit of the applied method. Blotters containing a mescaline-like compound, later confirmed by GC-MS and LC-MS to be MAL (methallylescaline), a substance very similar to mescaline, were detected among the samples tested. Validity of direct ATR-FTIR testing was confirmed by checking the obtained results against independent GC-MS or LC-MS results for the same cases/samples. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Cutaneous approach towards clinical and pathophysiological aspects of hyperglycemia by ATR FTIR spectroscopy

    Science.gov (United States)

    Eikje, Natalja Skrebova; Sota, Takayuki; Aizawa, Katsuo

    2007-07-01

    Attempts were made to non-invasively detect glucose-specific spectral signals in the skin by ATR-FTIR spectroscopy. In vivo spectra were collected from the inner wrists of healthy, prediabetes and diabetes subjects in the 750-4000 cm -1 region, with a closer assessment of the glucose-related region between 1000 and 1180 cm -1. Spectra in vivo showed glucose-specific peaks at 1030, 1080, 1118 and 1151 cm -1, as a variety of glucose solutions are found in vitro. Based on the differences of intensities at 1030 and 1118 cm -1 two spectral patterns were seen: I 1118 > I 1030 for a diabetes and I 1030> I 1118 for non-diabetes subjects. The peak at 1030 cm -1 was used to assess glucose concentrations in the skin due to its good correlation with glucose concentrations in vitro. Calculated mean values of the peak at 1030 cm -1 showed evidence of correlation with blood glucose levels when grouped as = 200 mg/dL, though there was no constant correlation between them when compared before/after OGTT or at the fasting/postprandial states. Absorbances at 1030 cm -1 were not only increased in a dose-dependent manner in a diabetes patient, but were also generally higher than in non-diabetes subjects at 30 min OGTT assessment. Also we could monitor absorbances at 1030 cm -1 and determine their changes in the skin tissue at different times of OGTT. We assume that our approach to in vivo measurement and monitoring of glucose concentrations at 1030 cm -1 may be one of the indicators to assess glucose activity level and its changes in the skin tissue, and has further implications in the study of clinical and pathophysiological aspects of hyperglycemia in diabetes and non-diabetes subjects by ATR-FTIR spectroscopy.

  3. Rapid classification and quantification of cocaine in seized powders with ATR-FTIR and chemometrics.

    Science.gov (United States)

    Eliaerts, Joy; Dardenne, Pierre; Meert, Natalie; Van Durme, Filip; Samyn, Nele; Janssens, Koen; De Wael, Karolien

    2017-10-01

    Traditionally, fast screening for the presence of cocaine in unknown powders is performed by means of colour tests. The major drawbacks of these tests are subjective colour evaluation depending on the operator ('50 shades of blue') and a lack of selectivity. An alternative fast screening technique is Fourier Transform InfraRed (FTIR) spectrometry. This technique provides spectra that are difficult to interpret without specialized expertise and shows a lack of sensitivity for the detection of cocaine in mixtures. To overcome these limitations, a portable FTIR spectrometer using Attenuated Total Reflectance (ATR) sampling was combined with a multivariate technique, called Support Vector Machines (SVM). Representative street drug powders (n = 482), seized during the period January 2013 to July 2015, and reference powders (n = 33) were used to build and validate a classification model (n = 515) and a quantification model (n = 378). Both models were compared with the conventional chromatographic techniques. The SVM classification model showed a high sensitivity, specificity, and efficiency (99%). The SVM quantification model determined cocaine content with a root mean squared error of prediction (RMSEP) of 6% calculated over a wide working range from 4 to 99 w%. In conclusion, the developed models resulted in a clear output (cocaine detected or cocaine not detected) and a reliable estimation of the cocaine content in a wide variety of mixtures. The ATR-FTIR technique combined with SVM is a straightforward, user-friendly, and fast approach for routine classification and quantification of cocaine in seized powders. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Defining the Contribution of MC1R Physiological Ligands to ATR Phosphorylation at Ser435, a Predictor of DNA Repair in Melanocytes.

    Science.gov (United States)

    Jarrett, Stuart G; Wolf Horrell, Erin M; Boulanger, Mary C; D'Orazio, John A

    2015-12-01

    The melanocortin 1 receptor (MC1R), a GS-coupled receptor that signals through cAMP and protein kinase A (PKA), regulates pigmentation, adaptive tanning, and melanoma resistance. MC1R-cAMP signaling promotes PKA-mediated phosphorylation of ataxia telangiectasia and rad3-related (ATR) at Ser435 (ATR-pS435), a modification that enhances nucleotide excision repair (NER) by facilitating recruitment of the XPA protein to sites of UV-induced DNA damage. High-throughput methods were developed to quantify ATR-pS435, measure XPA-photodamage interactions, and assess NER function. We report that melanocyte-stimulating hormone (α-MSH) or ACTH induce ATR-pS435, enhance XPA's association with UV-damaged DNA and optimize melanocytic NER. In contrast, MC1R antagonists agouti signaling protein (ASIP) or human β-defensin 3 (HBD3) interfere with ATR-pS435 generation, impair the XPA-DNA interaction, and reduce DNA repair. Although ASIP and HBD3 each blocked α-MSH-mediated induction of the signaling pathway, only ASIP depleted basal ATR-pS435. Our findings confirm that ASIP diminishes agonist-independent MC1R basal signaling whereas HBD3 is a neutral MC1R antagonist that blocks activation by melanocortins. Furthermore, our data suggest that ATR-pS435 may be a useful biomarker for the DNA repair-deficient MC1R phenotype.

  5. Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

    Science.gov (United States)

    Saha, Janapriya; Wang, Minli; Hada, Megumi; Cucinotta, Francis A.

    2011-01-01

    The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the

  6. Variability and robustness of scatterers in HRR/ISAR ground target data and its influence on the ATR performance

    Science.gov (United States)

    Schumacher, R.; Schimpf, H.; Schiller, J.

    2011-06-01

    The most challenging problem of Automatic Target Recognition (ATR) is the extraction of robust and independent target features which describe the target unambiguously. These features have to be robust and invariant in different senses: in time, between aspect views (azimuth and elevation angle), between target motion (translation and rotation) and between different target variants. Especially for ground moving targets in military applications an irregular target motion is typical, so that a strong variation of the backscattered radar signal with azimuth and elevation angle makes the extraction of stable and robust features most difficult. For ATR based on High Range Resolution (HRR) profiles and / or Inverse Synthetic Aperture Radar (ISAR) images it is crucial that the reference dataset consists of stable and robust features, which, among others, will depend on the target aspect and depression angle amongst others. Here it is important to find an adequate data grid for an efficient data coverage in the reference dataset for ATR. In this paper the variability of the backscattered radar signals of target scattering centers is analyzed for different HRR profiles and ISAR images from measured turntable datasets of ground targets under controlled conditions. Especially the dependency of the features on the elevation angle is analyzed regarding to the ATR of large strip SAR data with a large range of depression angles by using available (I)SAR datasets as reference. In this work the robustness of these scattering centers is analyzed by extracting their amplitude, phase and position. Therefore turntable measurements under controlled conditions were performed targeting an artificial military reference object called STANDCAM. Measures referring to variability, similarity, robustness and separability regarding the scattering centers are defined. The dependency of the scattering behaviour with respect to azimuth and elevation variations is analyzed. Additionally generic types

  7. Status Report on the Fabrication of Fuel Cladding Chemical Interaction Test Articles for ATR Irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howard, Richard H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-09-28

    FeCrAl alloys are a promising new class of alloys for light water reactor (LWR) applications due to their superior oxidation and corrosion resistance in high temperature environments. The current R&D efforts have focused on the alloy composition and processing routes to generate nuclear grade FeCrAl alloys with optimized properties for enhanced accident tolerance while maintaining properties needed for normal operation conditions. Therefore, the composition and processing routes must be optimized to maintain the high temperature steam oxidation (typically achieved by increasing the Cr and Al content) while still exhibiting properties conducive to normal operation in a LWR (such as radiation tolerance where reducing Cr content is favorable). Within this balancing act is the addition of understanding the influence on composition and processing routes on the FeCrAl alloys for fuel-cladding chemical interactions (FCCI). Currently, limited knowledge exists on FCCI for the FeCrAl-UO2 clad-fuel system. To overcome the knowledge gaps on the FCCI for the FeCrAl-UO2 clad-fuel system a series of fueled irradiation tests have been developed for irradiation in the Advanced Test Reactor (ATR) housed at the Idaho National Laboratory (INL). The first series of tests has already been reported. These tests used miniaturized 17x17 PWR fuel geometry rodlets of second-generation FeCrAl alloys fueled with industrial Westinghouse UO2 fuel. These rodlets were encapsulated within a stainless steel housing.To provide high fidelity experiments and more robust testing, a new series of rodlets have been developed deemed the Accident Tolerant Fuel Experiment #1 Oak Ridge National Laboratory FCCI test (ATF-1 ORNL FCCI). The main driving factor, which is discussed in detail, was to provide a radiation environment where prototypical fuel-clad interface temperatures are met while still maintaining constant contact between industrial fuel and the candidate cladding alloys

  8. ATR-FTIR Spectroscopy on intact dried leaves of sage (Salvia officinalis L. – chemotaxonomic discrimination and essential oil composition

    Directory of Open Access Journals (Sweden)

    Gudi, Gennadi

    2016-07-01

    Full Text Available Sage (Salvia officinalis L. is cultivated worldwide for its aromatic leaves which are used as herbal spice and for phytopharmaceutical applications. Fast analytical strategies for essential oil analysis, performed directly on plant material would reduce the delay between sampling and analytical results. This would enhance product quality by improving technical control of cultivation. The attenuated total reflectance Fourier transform infrared (ATR-FTIR spectroscopy method described here provides a reliable calibration model for quantification of essential oil components (EOC and its main constituents (e.g. -thujone and -thujone directly on dried, intact leaves of sage. Except for drying no further sample preparation is required for ATR-FTIR and the measurement time of less than 5 min per sample contrasts with the most common alternative of hydro-distillation followed by GC analysis which can take several hours per sample.

  9. Thermal behaviors of stainless steel tube based GeO2 ATR hollow fibers for transmitting CO2 laser radiations

    Science.gov (United States)

    Wang, Xu; Wang, Lin; Fu, Xiaohong; Jing, Chengbin; Yue, Fangyu; Yang, Pingxiong; Chu, Junhao

    2017-10-01

    The stainless steel (SUS) capillary tube attenuated total reflective (ATR) GeO2 hollow waveguide has advantages of low fabrication cost, strong mechanic strength and low transmission loss. It can find laser power delivery applications such as laser surgery, and material processing. However, the temperature rise of the operating waveguide may affect the laser delivery stability and the laser surgery safety. The thermal behaviors of the SUS ATR hollow fiber transmitting CO2 laser were investigated theoretically and experimentally in this work. Both theoretic simulations and experimental results disclose the periodic oscillatory behavior of the fiber temperature. The influence of input laser power on fiber temperature has been quantitatively discussed. A maximum input laser power of 23 W is predicted for laser surgery in which case the fiber temperature had better be lower than 47 °C to avoid tissue scalds. An input laser power smaller than 137 W is suggested preventing the fiber from being overheated (150 °C).

  10. AGR-2 Final Data Qualification Report for U.S. Capsules - ATR Cycles 147A Through 154B

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Binh T. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Very High-Temperature Reactor Technology Development Office; Einerson, Jeffrey J. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Very High-Temperature Reactor Technology Development Office

    2014-07-01

    This report provides the data qualification status of AGR-2 fuel irradiation experimental data in four U.S. capsules from all 15 Advanced Test Reactor (ATR) Cycles 147A, 148A, 148B, 149A, 149B, 150A, 150B, 151A, 151B, 152A, 152B, 153A, 153B, 154A, and 154B, as recorded in the Nuclear Data Management and Analysis System (NDMAS). Thus, this report covers data qualification status for the entire AGR-2 irradiation and will replace four previously issued AGR-2 data qualification reports (e.g., INL/EXT-11-22798, INL/EXT-12-26184, INL/EXT-13-29701, and INL/EXT-13-30750). During AGR-2 irradiation, two cycles, 152A and 153A, occurred when the ATR core was briefly at low power, so AGR-2 irradiation data are not used for physics and thermal calculations. Also, two cycles, 150A and 153B, are Power Axial Locator Mechanism (PALM) cycles when the ATR power is higher than during normal cycles. During the first PALM cycle, 150A, the experiment was temporarily moved from the B-12 location to the ATR water canal and during the second PALM cycle, 153B, the experiment was temporarily moved from the B-12 location to the I-24 location to avoid being overheated. During the “Outage” cycle, 153A, seven flow meters were installed downstream from seven Fission Product Monitoring System (FPMS) monitors to measure flows from the monitors and these data are included in the NDMAS database.

  11. Raman and IR-ATR spectroscopy studies of heteroepitaxial structures with a GaN:C top layer

    Science.gov (United States)

    Cerqueira, M. F.; Vieira, L. G.; Alves, A.; Correia, R.; Huber, M.; Andreev, A.; Bonanni, A.; Vasilevskiy, M. I.

    2017-09-01

    This work, motivated by the technologically important task of determination of carbon dopant location in the GaN crystal lattice, employed Raman spectroscopy, with both resonant and non-resonant excitation, and infrared (IR) spectroscopy, in the attenuated total reflection (ATR) configuration, to study lattice vibration modes in a set of carbon-doped GaN (GaN:C) epilayers grown by metalorganic vapour phase epitaxy. We analyse Raman and IR-ATR spectra from the point of view of possible effects of the carbon doping, namely: (i) local vibration mode of C atoms in the nitrogen sublattice (whose frequency we theoretically estimate as 768 cm-1 using an isotope defect model), and (ii) shift in the positions of longitudinal modes owing to the phonon-plasmon coupling. We find only indirect hints of the doping effect on the resonant Raman spectra. However, we show theoretically and confirm experimentally that the IR-ATR spectroscopy can be a much more sensitive tool for this purpose, at least for the considered structures. A weak perturbation of the dielectric function of GaN:C, caused by the substitutional carbon impurity, is shown to produce a measurable dip in the ATR reflectivity spectra at  ≈770 cm-1 for both p- and s-polarizations. Moreover, it influences a specific (guided-wave type) mode observed at  ≈737 cm-1, originating from the GaN layer, which appears in the narrow frequency window where the real parts of the two components of the dielectric tensor of the hexagonal crystal have opposite signs. This interpretation is supported by our modelling of the whole multilayer structure, using a transfer matrix formalism.

  12. ATR-FTIR spectroscopic characterization of coexisting carbonate surface complexes on hematite

    Science.gov (United States)

    Bargar, J.R.; Kubicki, J.D.; Reitmeyer, R.; Davis, J.A.

    2005-01-01

    The speciation of carbonate adsorbed to hematite in air-equilibrated aqueous solutions has been studied using ATR-FTIR spectroscopy. Samples were measured over a range of pH conditions, at 0.1 M NaCl and at low ionic strength, and in H2O and D2O solutions to permit a multispecies analysis of the data. Second-derivative analyses and fits to the spectra indicate the presence of two major and two minor surface-bound carbonate species. The two major complexes coexist at near-neutral pH and low ionic strength. One of these two complexes is relatively sensitive to ionic strength, being displaced at 0.1 M NaCl, whereas the other is not. Comparison of experimental to DFT/MO-calculated frequencies suggest these two major species to be (a) a monodentate binuclear inner-sphere carbonate surface complex, and (b) a fully or partially solvated carbonate (CO32-) species that is symmetry broken and appears to reside in the structured vicinal water layers at the hematite-water interface, retained by hydrogen bonding and/or other forces. Minor carbonate complexes include diffuse layer CO32- and an unidentified inner-sphere species. Both of the dominant species observed here are likely to be significant controls of the surface charge and sorptive properties of Fe-oxides. Copyright ?? 2005 Elsevier Ltd.

  13. Reagent-free simultaneous determination of glucose and cholesterol in whole blood by FTIR-ATR

    Science.gov (United States)

    Li, Zhigang; Lv, Hong; Li, Tianhe; Si, Guangyuan; Wang, Qiaoyun; Lv, Jiangtao; Hu, Xiaofei

    2017-05-01

    Reagent-free determination of multiple analytes is an active and promising field of research in clinical analysis. In this work, the determination of glucose and cholesterol in whole blood using Fourier transform infrared (FTIR) spectroscopy equipped with an attenuated total reflectance (ATR) accessory was performed. A comprehensive sample selection rule in multi space based on SPXY was proposed, termed C-SPXY. The core idea is to make full use of different derivative spectra space to construct the calibration set which preserves the more effective information. On this basis, a partial least squares (PLS) regression fusion modeling method was also presented aiming at improving prediction accuracy of glucose and cholesterol concentration in whole blood samples. Compared with other methods based on single spectra space, the proposed fusion model based on multi spectra space C-SPXY method provides smaller RMSEP values. Experimental results demonstrate that the proposed method and model provides superior predictive power and holds a good application prospect in the field of clinical analysis.

  14. Analysis code for medium and small rupture accidents in ATR. LOTRAC/HEATUP

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-08-01

    In the evaluation of thermo-hydraulic and fuel temperature transient changes in the events which are classified in medium and small rupture accidents of reactor coolant loss that is the safety evaluation event of the ATR, the analysis code for synthetic thermo-hydraulic transient change at the time of medium and small ruptures LOTRAC and the detailed analysis code for fuel temperature HEATUP are used, respectively. By using the LOTAC, the thermo-hydraulic behavior of reactor cooling facility and the temperature behavior of fuel at the time of blow-down are analyzed, and also the characteristics of changing reactor thermal output is analyzed, considering the functioning characteristics of emergency core cooling system. Based on the data of thermo-hydraulic behavior obtained by the LOTRAC, the time of beginning the turn-around of fuel cladding tube temperature obtained by the data of ECCS pouring characteristics, the heat transfer rate after the turn-around and so on, the detailed temperature change of fuel elements is analyzed by the HEATUP, and the highest temperature and the amount of oxidation of fuel cladding tubes are determined. The LOTRAC code, the HEATUP code, various analysis models, and rupture simulation experiment are reported. (K.I.)

  15. Tungstate (VI) sorption on hematite: An in situ ATR-FTIR probe on the mechanism.

    Science.gov (United States)

    Rakshit, Sudipta; Sallman, Bryan; Davantés, Athénais; Lefèvre, Grégory

    2017-02-01

    Owing to the suspected toxicity and carcinogenicity of tungstate (VI) oxyanions [i.e. mono tungstate and several polytungstate, generally represented by W (VI)], the environmental fate of W (VI) has been widely studied. Sorption is regarded as a major mechanism by which W (VI) species are retained in the solid/water interface. Iron (hydr)oxides have been considered important environmental sinks for W (VI) species. Here we report sorption mechanisms of W (VI) on a common iron oxide mineral-hematite under environmentally relevant solution properties using in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic probes. Initial W (VI) loadings varied from 10 to 200 μM at fixed pH values ranged from 4.6 to 8.1. For pH envelop (pHs = 4.6, 5.0, 5.5, 6.0, 6.5, 7.5, and 8.1) experiments, fixed W (VI) concentrations (i.e. 10 & 200 μM) were used to understand the effects of pH. The results indicated that at acidic pH values (pH hematite surface and the strength of the interaction increases with decreasing pH. In addition, initial W (VI) concentration affected the sorption mechanisms of W (VI) on hematite. Our study will aid the molecular level understanding of W (VI) retention on iron oxide surfaces. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Effects of Near Infrared Radiation on DNA. DLS and ATR-FTIR Study.

    Science.gov (United States)

    Szymborska-Małek, Katarzyna; Komorowska, Małgorzata; Gąsior-Głogowska, Marlena

    2018-01-05

    We presume that the primary effect of Near Infrared (NIR) radiation on aqueous solutions of biological molecules concerns modification of hydrogen bonded structures mainly the global and the hydration shell water molecules. Since water has a significant influence on the DNA structure, we expect that the thermal stability of DNA could be modified by NIR radiation. The herring sperm DNA was exposed to NIR radiation (700-1100nm) for 5, 10, and 20min periods. The temperature dependent infrared measurements were done for the thin films formed on the diamond ATR crystal from evaporated DNA solutions exposed and unexposed to NIR radiation. For the NIR-treated samples (at room temperature) the B form was better conserved than in the control sample independently of the irradiation period. Above 50°C a considerable increase in the A form was only observed for 10min NIR exposed samples. The hydrodynamic radius, (Rh), studied by the dynamic light scattering, showed drastic decrease with the increasing irradiation time. Principal components analysis (PCA) allowed to detect the spectral features correlated with the NIR effect and thermal stability of the DNA films. Obtained results strongly support the idea that the photoionization of water by NIR radiation in presence of DNA molecules is the main factor influencing on its physicochemical properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. ATR discrimination-SNR for HRR assuming χ2 model of RCS variability

    Science.gov (United States)

    Holt, Craig R.; Schmidt, Steven L.; Attili, Joseph B.

    2001-10-01

    A discrimination SNR for predicting classification performance is developed as an analogy to the RADAR equation that is used to predict detection performance. It assumes a statistical model for the target radar cross-section (RCS) and that the resulting likelihood classifier is employed. The relationship between the probability of classification errors and the dB value of the discrimination SNR is obtained. A specific form for the likelihood classifier and the discrimination SNR is developed assuming that the variability of the target RCS is described by a (chi) 2 - distribution. The form of this (chi) 2 - based classifier is novel and significantly different from the more common Gaussian based mean-square-error classifier. It is shown that the discrimination SNR has an intuitive interpretation in terms of the number of radar samples, the average contrast between targets and the contrast-noise. The use of this tool is illustrated using compact range High Range Resolution (HRR) Doppler measurements from the U.S. Army National Ground Intelligence Center (NGIC). The sensitivity of ATR performance to radar parameters is quantified using the discrimination SNR with gains measured in meaningful dB units.

  18. The Conference Proceedings of the 2003 Air Transport Research Society (ATRS) World Conference, Volume 5

    Science.gov (United States)

    Bowen, Brent (Editor); Gudmundsson, Sveinn (Editor); Oum, Tae (Editor)

    2003-01-01

    The UNO Aviation Institute Monograph Series began in 1994 as a key component of the education outreach and information transfer missions of the Aviation Institute and the NASA Nebraska Space Grant & EPSCoR Programs. The series is an outlet for aviation materials to be indexed and disseminated through an efficient medium. Publications are welcome in all aspects of aviation. Publication formats may include, but are not limited to, conference proceedings, bibliographies, research reports, manuals, technical reports, and other documents that should be archived and indexed for future reference by the aviation and world wide communities. The Conference proceedings of the 2003 Air Transport Research Society (ATRS) world conference, volume 5 is presented. The topics include: 1) The Temporal Configuration of Airline Networks in Europe; 2) Determination and Applications of Environmental Costs at Different Sized Airports-Aircraft Noise and Engine Emissions; 3) Cost Effective Measures to Reduce CO2 Emissions in the Air Freight Sector; 4) An Assessment of the Sustainability of Air Transport System: Quantification of Indicators; 5) Regulation, Competition and Network Evolution in Aviation; 6) Regulation in the Air: Price and Frequency Cap; 7) Industry Consolidation and Future Airline Network Structures in Europe; 8) Application of Core Theory to the U.S. Airline Industry; 9) Air Freight Transshipment Route Choice Analysis; 10) A Fuzzy Approach of the Competition on Air Transport Market; and 11) Developing Passenger Demand Models for International Aviation from/to Egypt: A Case Study of Cairo Airport and Egyptair.

  19. Quantitative monitoring of membrane permeation via in-situ ATR FT-IR spectroscopy

    Science.gov (United States)

    Beckingham, Bryan; Miller, Daniel

    Ion conducting membranes are of interest for various energy applications including fuel cells and artificial photosynthesis systems. Within the context of artificial photosynthesis, membranes are desired that facilitate the ion transport necessary to feed the electrochemical reactions while meeting various additional selectivity and permeability demands depending on the CO2 reduction products. Herein, we demonstrate the use of in-situ ATR FT-IR spectroscopy to quantitatively resolve the concentration of single and multicomponent mixtures of various CO2 reduction products including methanol, formate and acetate. We then apply this methodology to the in-situ monitoring of the permeation of single and multicomponent mixtures across commercially available membranes. Membrane permeabilities and selectivities calculated from the single component time-resolved concentration curves are compared to the multicomponent permeation experiments. This material is based upon work performed at the Joint Center for Artificial Photosynthesis, a DOE Energy Innovation Hub, supported through the Office of Science of the U.S. Department of Energy under Award Number DE-SC000493.

  20. Probing the Mec1ATR Checkpoint Activation Mechanism with Small Peptides.

    Science.gov (United States)

    Wanrooij, Paulina H; Tannous, Elias; Kumar, Sandeep; Navadgi-Patil, Vasundhara M; Burgers, Peter M

    2016-01-01

    Yeast Mec1, the ortholog of human ATR, is the apical protein kinase that initiates the cell cycle checkpoint in response to DNA damage and replication stress. The basal activity of Mec1 kinase is activated by cell cycle phase-specific activators. Three distinct activators stimulate Mec1 kinase using an intrinsically disordered domain of the protein. These are the Ddc1 subunit of the 9-1-1 checkpoint clamp (ortholog of human and Schizosaccharomyces pombe Rad9), the replication initiator Dpb11 (ortholog of human TopBP1 and S. pombe Cut5), and the multifunctional nuclease/helicase Dna2. Here, we use small peptides to determine the requirements for Mec1 activation. For Ddc1, we identify two essential aromatic amino acids in a hydrophobic environment that when fused together are proficient activators. Using this increased insight, we have been able to identify homologous motifs in S. pombe Rad9 that can activate Mec1. Furthermore, we show that a 9-amino acid Dna2-based peptide is sufficient for Mec1 activation. Studies with mutant activators suggest that binding of an activator to Mec1 is a two-step process, the first step involving the obligatory binding of essential aromatic amino acids to Mec1, followed by an enhancement in binding energy through interactions with neighboring sequences. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Effects of Near Infrared Radiation on DNA. DLS and ATR-FTIR Study

    Science.gov (United States)

    Szymborska-Małek, Katarzyna; Komorowska, Małgorzata; Gąsior-Głogowska, Marlena

    2018-01-01

    We presume that the primary effect of Near Infrared (NIR) radiation on aqueous solutions of biological molecules concerns modification of hydrogen bonded structures mainly the global and the hydration shell water molecules. Since water has a significant influence on the DNA structure, we expect that the thermal stability of DNA could be modified by NIR radiation. The herring sperm DNA was exposed to NIR radiation (700-1100 nm) for 5, 10, and 20 min periods. The temperature dependent infrared measurements were done for the thin films formed on the diamond ATR crystal from evaporated DNA solutions exposed and unexposed to NIR radiation. For the NIR-treated samples (at room temperature) the B form was better conserved than in the control sample independently of the irradiation period. Above 50 °C a considerable increase in the A form was only observed for 10 min NIR exposed samples. The hydrodynamic radius, (Rh), studied by the dynamic light scattering, showed drastic decrease with the increasing irradiation time. Principal components analysis (PCA) allowed to detect the spectral features correlated with the NIR effect and thermal stability of the DNA films. Obtained results strongly support the idea that the photoionization of water by NIR radiation in presence of DNA molecules is the main factor influencing on its physicochemical properties.

  2. A further insight into the adsorption mechanism of protein on hydroxyapatite by FTIR-ATR spectrometry

    Science.gov (United States)

    Lin, Zhongyu; Hu, Ren; Zhou, Jianzhang; Ye, Yiwen; Xu, Zhaoxi; Lin, Changjian

    2017-02-01

    The adsorption mechanism of bovine serum albumin (BSA) on hydroxyapatite (HA) for different time intervals has been studied by Fourier transform infrared (FTIR)-attenuated total internal reflectance (ATR) spectrometry in this paper. The difference spectra obtained in HA and BSA frequency regions demonstrate that the binding of Pdbnd O, from the phosphate (PO43 -) of HA, to the hydrogen of methyl (- CH3), methene (- CH2) and amideII (- CNH) in the protein appears to be much faster and stronger than that of the Psbnd O group. In addition, Ca2 + must serve as a key role in the interaction of BSA with HA. The binding of Ca2 + to the oxygen of the peptide bond seems to induce a significant reconformation of polypeptide backbones from β-pleated sheet to α-helix and β-turn of helical circles. This alteration seems to have been accompanied by much hydrogen of polypeptides driven to bind PO43 - and OH- of the HA actively and much -C = O and Hsbnd Nsbnd groups of the peptide bond freed from inter-chain hydrogen bonding to react on Ca2 + and combine strongly with the HA surface. This might be well expected to promote the HA biomineralization.

  3. Quantitative analysis of anti-inflammatory drugs using FTIR-ATR spectrometry

    Science.gov (United States)

    Hassib, Sonia T.; Hassan, Ghaneya S.; El-Zaher, Asmaa A.; Fouad, Marwa A.; Taha, Enas A.

    2017-11-01

    Four simple, accurate, sensitive and economic Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopic (ATR-FTIR) methods have been developed for the quantitative estimation of some non-steroidal anti-inflammatory drugs. The first method involves the determination of Etodolac by direct measurement of the absorbance at 1716 cm- 1. In the second method, the second derivative of the IR spectra of Tolfenamic acid and its reported degradation product (2-chlorobenzoic acid) was used and the amplitudes were measured at 1084.27 cm- 1 and 1056.02 cm- 1 for Tolfenamic acid and 2-chlorobenzoic acid, respectively. The third method used the first derivative of the IR spectra of Bumadizone and its reported degradation product, N,N-diphenylhydrazine and the amplitudes were measured at 2874.98 cm- 1 and 2160.32 cm- 1 for Bumadizone and N,N-diphenylhydrazine, respectively. The fourth method depends on measuring the amplitude of Diacerein at 1059.18 cm- 1 and of rhein, its reported degradation product, at 1079.32 cm- 1 in their first derivative spectra. The four methods were successfully applied on the pharmaceutical formulations by extracting the active constituent in chloroform and the extract was directly measured in liquid phase mode using a specific cell. Moreover, validation of these methods was carried out following International Conference of Harmonisation (ICH) guidelines.

  4. In situ ATR-FTIR study of the early stages of fly ash geopolymer gel formation.

    Science.gov (United States)

    Rees, Catherine A; Provis, John L; Lukey, Grant C; van Deventer, Jannie S J

    2007-08-14

    The kinetics of geopolymer formation are monitored using a novel in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic technique. Reaction rates are determined from the intensity variation of the bands related to the geopolymer gel network and the unreacted fly ash particles. Comparison with deuterated geopolymer samples provides critical information regarding peak assignments. An initial induction (lag) period is observed to occur for hydroxide-activated geopolymers, followed by gel evolution according to an approximately linear reaction profile. The length of the lag period is reduced by increasing the concentration of NaOH. An increase in the rate of network formation also occurs with increasing NaOH concentration up to a maximum point, beyond which an increased NaOH concentration leads to a reduced rate of network formation. This trend is attributed to the competing effects of increased alkalinity and stronger ion pairing with an increase in NaOH concentration. In situ analysis also shows that the rate of fly ash dissolution is similar for all moderate- to high-alkali geopolymer slurries, which is attributed to the very highly water-deficient nature of these systems and is contrary to predictions from classical glass dissolution chemistry. This provides for the first time detailed kinetic information describing fly ash geopolymer formation kinetics.

  5. Application of FTIR-ATR Spectroscopy to Determine the Extent of Lipid Peroxidation in Plasma during Haemodialysis.

    Science.gov (United States)

    Oleszko, Adam; Olsztyńska-Janus, Sylwia; Walski, Tomasz; Grzeszczuk-Kuć, Karolina; Bujok, Jolanta; Gałecka, Katarzyna; Czerski, Albert; Witkiewicz, Wojciech; Komorowska, Małgorzata

    2015-01-01

    During a haemodialysis (HD), because of the contact of blood with the surface of the dialyser, the immune system becomes activated and reactive oxygen species (ROS) are released into plasma. Particularly exposed to the ROS are lipids and proteins contained in plasma, which undergo peroxidation. The main breakdown product of oxidized lipids is the malondialdehyde (MDA). A common method for measuring the concentration of MDA is a thiobarbituric acid reactive substances (TBARS) method. Despite the formation of MDA in plasma during HD, its concentration decreases because it is removed from the blood in the dialyser. Therefore, this research proposes the Fourier Transform Infrared Attenuated Total Reflectance (FTIR-ATR) spectroscopy, which enables determination of primary peroxidation products. We examined the influence of the amount of hydrogen peroxide added to lipid suspension that was earlier extracted from plasma specimen on lipid peroxidation with use of TBARS and FTIR-ATR methods. Linear correlation between these methods was shown. The proposed method was effective during the evaluation of changes in the extent of lipid peroxidation in plasma during a haemodialysis in sheep. A measurement using the FTIR-ATR showed an increase in plasma lipid peroxidation after 15 and 240 minutes of treatment, while the TBARS concentration was respectively lower.

  6. Validation of ATR FT-IR to identify polymers of plastic marine debris, including those ingested by marine organisms.

    Science.gov (United States)

    Jung, Melissa R; Horgen, F David; Orski, Sara V; Rodriguez C, Viviana; Beers, Kathryn L; Balazs, George H; Jones, T Todd; Work, Thierry M; Brignac, Kayla C; Royer, Sarah-Jeanne; Hyrenbach, K David; Jensen, Brenda A; Lynch, Jennifer M

    2018-02-01

    Polymer identification of plastic marine debris can help identify its sources, degradation, and fate. We optimized and validated a fast, simple, and accessible technique, attenuated total reflectance Fourier transform infrared spectroscopy (ATR FT-IR), to identify polymers contained in plastic ingested by sea turtles. Spectra of consumer good items with known resin identification codes #1-6 and several #7 plastics were compared to standard and raw manufactured polymers. High temperature size exclusion chromatography measurements confirmed ATR FT-IR could differentiate these polymers. High-density (HDPE) and low-density polyethylene (LDPE) discrimination is challenging but a clear step-by-step guide is provided that identified 78% of ingested PE samples. The optimal cleaning methods consisted of wiping ingested pieces with water or cutting. Of 828 ingested plastics pieces from 50 Pacific sea turtles, 96% were identified by ATR FT-IR as HDPE, LDPE, unknown PE, polypropylene (PP), PE and PP mixtures, polystyrene, polyvinyl chloride, and nylon. Published by Elsevier Ltd.

  7. Rapid detection of gelatin in dental materials using attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR)

    Science.gov (United States)

    Irfanita, N.; Jaswir, I.; Mirghani, M. E. S.; Sukmasari, S.; Ardini, Y. D.; Lestari, W.

    2017-08-01

    The presence of gelatin is not limited to food products but has also been found in pharmaceuticals. Most dental materials available in Malaysia are imported from other countries and might contain gelatin which is a protein derived either from porcine, bovine or other animal sources. Authentication of gelatin is crucial due to religious and health concerns. Therefore, this study aimed to detect gelatin in dental materials using ATR-FTIR. Forty two samples of dental material were purchased from dental suppliers and detection was done using ATR-FTIR. The spectrum from each sample was compared against standard bovine and porcine gelatin. Experimental dental paste containing bovine and porcine gelatin at concentrations of 5, 10, 15 and 20% were also prepared for quantification analysis. The results showed that gelatin was present in nine out of forty two samples of dental materials but the species of origin was not confirmed. Meanwhile, in the experimental bovine and porcine dental paste, it was seen that as the concentration increased, the intensity of the absorption of Amide group also increased. Thus, ATR-FTIR can be utilized as a reliable tool to detect gelatin in dental materials and other pharmaceuticals.

  8. ATR-FT-IR spectroscopy in the region of 550-230 cm -1 for identification of inorganic pigments

    Science.gov (United States)

    Vahur, Signe; Teearu, Anu; Leito, Ivo

    2010-03-01

    A comprehensive study of ATR-FT-IR spectra of 40 inorganic pigments of different colours widely used in historical paintings has been carried out in the low wave number spectral range (550-230 cm -1). The infrared spectra were recorded from mixtures of pigment and linseed oil. It is demonstrated that this spectral range - essentially devoid of absorption peaks of the common binder materials - can be well used for identification of inorganic pigments in paint samples thereby markedly extending the possibilities of pigment identification/confirmation by ATR-IR spectroscopy into the realm of pigments having no absorptions in the mid-IR region. In some cases the method can be used alone for pigment identification and in many cases it provides useful additional evidence for pigment identification using other instrumental techniques (electron microprobe analysis, XRF, optical microscopy). Together with earlier work this study provides a comprehensive overview of the pigment identification possibilities using ATR-FT-IR as well as a collection of reference spectra and is expected to be a useful reference for conservation practitioners.

  9. Structural transformation of synthetic hydroxyapatite under simulated in vivo conditions studied with ATR-FTIR spectroscopic imaging

    Science.gov (United States)

    Sroka-Bartnicka, Anna; Borkowski, Leszek; Ginalska, Grazyna; Ślósarczyk, Anna; Kazarian, Sergei G.

    2017-01-01

    Hydroxyapatite and carbonate-substituted hydroxyapatite are widely used in bone tissue engineering and regenerative medicine. Both apatite materials were embedded into recently developed ceramic/polymer composites, subjected to Simulated Body Fluid (SBF) for 30 days and characterized using ATR-FTIR spectroscopic imaging to assess their behaviour and structures. The specific aim was to detect the transition phases between both types of hydroxyapatite during the test and to analyze the surface modification caused by SBF. ATR-FTIR spectroscopic imaging was successfully applied to characterise changes in the hydroxyapatite lattice due to the elastic properties of the scaffolds. It was observed that SBF treatment caused a replacement of phosphates in the lattice of non-substituted hydroxyapatite by carbonate ions. A detailed study excluded the formation of pure A type carbonate apatite. In turn, CO32- content in synthetic carbonate-substituted hydroxyapatite decreased. The usefulness of ATR-FTIR spectroscopic imaging studies in the evaluation of elastic and porous β-glucan hydroxyapatite composites has been demonstrated.

  10. Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Hiroyuki; Xie, Yihu; de Lange, Titia; Pavletich, Nikola P. (Rockefeller); (SKI)

    2010-09-20

    We reported previously that the stability of all mammalian phosphatidylinositol 3-kinase-related protein kinases (PIKKs) depends on their interaction with Tel2, the ortholog of yeast Tel2 and Caenorhabditis elegans Clk-2. Here we provide evidence that Tel2 acts with Hsp90 in the maturation of PIKK complexes. Quantitative immunoblotting showed that the abundance of Tel2 is low compared with the PIKKs, and Tel2 preferentially bound newly synthesized ATM, ATR, mTOR, and DNA-PKcs. Tel2 complexes contained, in addition to Tti1-Tti2, the Hsp90 chaperone, and inhibition of Hsp90 interfered with the interaction of Tel2 with the PIKKs. Analysis of in vivo labeled nascent protein complexes showed that Tel2 and Hsp90 mediate the formation of the mTOR TORC1 and TORC2 complexes and the association of ATR with ATRIP. The structure of yeast Tel2, reported here, shows that Tel2 consists of HEAT-like helical repeats that assemble into two separate {alpha}-solenoids. Through mutagenesis, we identify a surface patch of conserved residues involved in binding to the Tti1-Tti2 complex in vitro. In vivo, mutation of this conserved patch affects cell growth, levels of PIKKs, and ATM/ATR-mediated checkpoint signaling, highlighting the importance of Tti1-Tti2 binding to the function of Tel2. Taken together, our data suggest that the Tel2-Tti1-Tti2 complex is a PIKK-specific cochaperone for Hsp90.

  11. Improving precursor adsorption characteristics in ATR-FTIR spectroscopy with a ZrO{sub 2} nanoparticle coating

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jaeseo [Korea Research Institute of Standards and Science, Center for Vacuum Technology (Korea, Republic of); Mun, Jihun [University of Science and Technology, Department of Advanced Device Technology (Korea, Republic of); Shin, Jae-Soo; Kim, Jongho; Park, Hee Jung [Daejeon University, Department of Advanced Materials Engineering (Korea, Republic of); Kang, Sang-Woo, E-mail: swkang@kriss.re.kr [Korea Research Institute of Standards and Science, Center for Vacuum Technology (Korea, Republic of)

    2017-02-15

    Nanoparticles were applied to a crystal surface to increase its precursor adsorption efficiency in an attenuated total reflection Fourier transform infrared (ATR-FTIR) spectrometer. Nanoparticles with varying dispersion stabilities were employed and the resulting precursor adsorption characteristics were assessed. The size of the nanoparticles was <100 nm (TEM). In order to vary the dispersion stability, ZrO{sub 2} nanoparticles were dispersed in aqueous solutions of different pH. The ZrO{sub 2} dispersion solutions were analyzed using scanning electron microscopy (SEM) while particle distribution measurements were analyzed using electrophoretic light scattering (ELS) and dynamic light scattering (DLS) techniques. ZrO{sub 2} nanoparticles dispersed in solutions of pH 3 and 11 exhibited the most stable zeta potentials (≥+30 or ≤−30 mV); these observations were confirmed by SEM analysis and particle distribution measurements. Hexamethyldisilazane (HMDS) was used as a precursor for ATR-FTIR spectroscopy. Consequently, when ZrO{sub 2} nanoparticle solutions with the best dispersion stabilities (pH 3 and 11) were applied to the adsorption crystal surface, the measurement efficiency of ATR-FTIR spectroscopy improved by ∼200 and 300%, respectively.

  12. Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML.

    Science.gov (United States)

    Morgado-Palacin, Isabel; Day, Amanda; Murga, Matilde; Lafarga, Vanesa; Anton, Marta Elena; Tubbs, Anthony; Chen, Hua Tang; Ergan, Aysegul; Anderson, Rhonda; Bhandoola, Avinash; Pike, Kurt G; Barlaam, Bernard; Cadogan, Elaine; Wang, Xi; Pierce, Andrew J; Hubbard, Chad; Armstrong, Scott A; Nussenzweig, André; Fernandez-Capetillo, Oscar

    2016-09-13

    Among the various subtypes of acute myeloid leukemia (AML), those with chromosomal rearrangements of the MLL oncogene (AML-MLL) have a poor prognosis. AML-MLL tumor cells are resistant to current genotoxic therapies because of an attenuated response by p53, a protein that induces cell cycle arrest and apoptosis in response to DNA damage. In addition to chemicals that damage DNA, efforts have focused on targeting DNA repair enzymes as a general chemotherapeutic approach to cancer treatment. Here, we found that inhibition of the kinase ATR, which is the primary sensor of DNA replication stress, induced chromosomal breakage and death of mouse AML(MLL) cells (with an MLL-ENL fusion and a constitutively active N-RAS independently of p53. Moreover, ATR inhibition as a single agent exhibited antitumoral activity, both reducing tumor burden after establishment and preventing tumors from growing, in an immunocompetent allograft mouse model of AML(MLL) and in xenografts of a human AML-MLL cell line. We also found that inhibition of ATM, a kinase that senses DNA double-strand breaks, also promoted the survival of the AML(MLL) mice. Collectively, these data indicated that ATR or ATM inhibition represent potential therapeutic strategies for the treatment of AML, especially MLL-driven leukemias. Copyright © 2016, American Association for the Advancement of Science.

  13. Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) for Rapid Determination of Microbial Cell Lipid Content: Correlation with Gas Chromatography-Mass Spectrometry (GC-MS).

    Science.gov (United States)

    Millan-Oropeza, Aaron; Rebois, Rolando; David, Michelle; Moussa, Fathi; Dazzi, Alexandre; Bleton, Jean; Virolle, Marie-Joelle; Deniset-Besseau, Ariane

    2017-10-01

    There is a growing interest worldwide for the production of renewable oil without mobilizing agriculture lands; fast and reliable methods are needed to identify highly oleaginous microorganisms of potential industrial interest. The aim of this study was to demonstrate the relevance of attenuated total reflection (ATR) spectroscopy to achieve this goal. To do so, the total lipid content of lyophilized samples of five Streptomyces strains with varying lipid content was assessed with two classical quantitative but time-consuming methods, gas chromatography-mass spectrometry (GC-MS) and ATR Fourier transform infrared (ATR FT-IR) spectroscopy in transmission mode with KBr pellets and the fast ATR method, often questioned for its lack of reliability. A linear correlation between these three methods was demonstrated allowing the establishment of equations to convert ATR values expressed as CO/amide I ratio, into micrograms of lipid per milligram of biomass. The ATR method proved to be as reliable and quantitative as the classical GC-MS and FT-IR in transmission mode methods but faster and more reproducible than the latter since it involves far less manipulation for sample preparation than the two others. Attenuated total reflection could be regarded as an efficient fast screening method to identify natural or genetically modified oleaginous microorganisms by the scientific community working in the field of bio-lipids.

  14. Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector.

    Science.gov (United States)

    Zhang, Chao; Wang, Bing; Li, Lei; Li, Yawei; Li, Pengzhi; Lv, Guohua

    2017-09-01

    Surgery followed by radiotherapy is the standard treatment for chordomas, which are a rare but low-grade type of bone cancer arising from remnants of the embryonic notochord. However, disease recurrence following radiotherapy is common, most likely due to endogenous DNA repair mechanisms that promote cell survival upon radiation strikes. The ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3 related (ATM/ATR)-mediated pathway has a critical role in DNA repair mechanisms; however, it has rarely been investigated in chordomas. In the present study, the expression of signal molecules related to the ATM/ATR pathway in chordoma tissues and adjacent normal tissues were initially examined using immunohistochemistry and western blot analysis. Chordoma U-CH1 and U-CH2 cells were subsequently used to investigate cell responses to ionizing radiation and the potential protective actions mediated by the ATM/ATR pathway. Phosphorylated (p)-ATM, p-ATR, γ-H2A histone family, member X (H2AX) and RAD51 were significantly upregulated in chordoma tissues relative to adjacent normal tissues (PATM, γ-H2AX and RAD51 expression in U-CH1 cells (PATM, p-ATR and RAD51 levels in U-CH2 cells (PATM/ATR pathway, in which RAD51 serves as an important downstream effector. Thus, RAD51 presents a promising therapeutic target for improving the outcome of radiotherapy treatment in chordomas.

  15. Alpha glucosidase inhibitors

    National Research Council Canada - National Science Library

    Kalra, Sanjay

    2014-01-01

    Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action...

  16. Proton pump inhibitors

    Science.gov (United States)

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by glands in ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a ...

  17. An Approach for Routine Analytical Detection of Beeswax Adulteration Using FTIR-ATR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Svečnjak Lidija

    2015-12-01

    Full Text Available Although beeswax adulteration represents one of the main beeswax quality issues, there are still no internationally standardised analytical methods for routine quality control. The objective of this study was to establish an analytical procedure suitable for routine detection of beeswax adulteration using FTIR-ATR spectroscopy. For the purpose of this study, reference IR spectra of virgin beeswax, paraffin, and their mixtures containing different proportions of paraffin (5 - 95%, were obtained. Mixtures were used for the establishment of calibration curves. To determine the prediction strength of IR spectral data for the share of paraffin in mixtures, the Partial Least Squares Regression method was used. The same procedure was conducted on beeswax-beef tallow mixtures. The model was validated using comb foundation samples of an unknown chemical background which had been collected from the international market (n = 56. Selected physico-chemical parameters were determined for comparison purposes. Results revealed a strong predictive power (R2 = 0.999 of IR spectra for the paraffin and beef tallow share in beeswax. The results also revealed that the majority of the analysed samples (89% were adulterated with paraffin; only 6 out of 56 (11% samples were identified as virgin beeswax, 28% of the samples exhibited a higher level of paraffin adulteration (>46% of paraffin, while the majority of the analysed samples (50% were found to be adulterated with 5 - 20% of paraffin. These results indicate an urgent need for routine beeswax authenticity control. In this study, we demonstrated that the analytical approach defining the standard curves for particular adulteration levels in beeswax, based on chemometric modelling of specific IR spectral region indicative for adulteration, enables reliable determination of the adulterant proportions in beeswax.

  18. Application of FTIR-ATR spectroscopy coupled with multivariate analysis for rapid estimation of butter adulteration.

    Science.gov (United States)

    Fadzlillah, Nurrulhidayah Ahmad; Rohman, Abdul; Ismail, Amin; Mustafa, Shuhaimi; Khatib, Alfi

    2013-01-01

    In dairy product sector, butter is one of the potential sources of fat soluble vitamins, namely vitamin A, D, E, K; consequently, butter is taken into account as high valuable price from other dairy products. This fact has attracted unscrupulous market players to blind butter with other animal fats to gain economic profit. Animal fats like mutton fat (MF) are potential to be mixed with butter due to the similarity in terms of fatty acid composition. This study focused on the application of FTIR-ATR spectroscopy in conjunction with chemometrics for classification and quantification of MF as adulterant in butter. The FTIR spectral region of 3910-710 cm⁻¹ was used for classification between butter and butter blended with MF at various concentrations with the aid of discriminant analysis (DA). DA is able to classify butter and adulterated butter without any mistakenly grouped. For quantitative analysis, partial least square (PLS) regression was used to develop a calibration model at the frequency regions of 3910-710 cm⁻¹. The equation obtained for the relationship between actual value of MF and FTIR predicted values of MF in PLS calibration model was y = 0.998x + 1.033, with the values of coefficient of determination (R²) and root mean square error of calibration are 0.998 and 0.046% (v/v), respectively. The PLS calibration model was subsequently used for the prediction of independent samples containing butter in the binary mixtures with MF. Using 9 principal components, root mean square error of prediction (RMSEP) is 1.68% (v/v). The results showed that FTIR spectroscopy can be used for the classification and quantification of MF in butter formulation for verification purposes.

  19. The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum.

    Science.gov (United States)

    Goh, Choon Fu; Craig, Duncan Q M; Hadgraft, Jonathan; Lane, Majella E

    2017-02-01

    Drug permeation through the intercellular lipids, which pack around and between corneocytes, may be enhanced by increasing the thermodynamic activity of the active in a formulation. However, this may also result in unwanted drug crystallisation on and in the skin. In this work, we explore the combination of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the skin. Ex vivo permeation studies of saturated solutions of diclofenac sodium (DF Na) in two vehicles, propylene glycol (PG) and dimethyl sulphoxide (DMSO), were carried out in porcine ear skin. Tape stripping and ATR-FTIR spectroscopy were conducted simultaneously to collect spectral data as a function of skin depth. Multivariate data analysis was applied to visualise and categorise the spectral data in the region of interest (1700-1500cm-1) containing the carboxylate (COO-) asymmetric stretching vibrations of DF Na. Spectral data showed the redshifts of the COO- asymmetric stretching vibrations for DF Na in the solution compared with solid drug. Similar shifts were evident following application of saturated solutions of DF Na to porcine skin samples. Multivariate data analysis categorised the spectral data based on the spectral differences and drug crystallisation was found to be confined to the upper layers of the skin. This proof-of-concept study highlights the utility of ATR-FTIR spectroscopy in combination with multivariate data analysis as a simple and rapid approach in the investigation of drug deposition in the skin. The approach described here will be extended to the study of other actives for topical application to the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families

    Directory of Open Access Journals (Sweden)

    Pichette Roxane

    2006-09-01

    Full Text Available Abstract Background Ataxia telangiectasia-mutated and Rad3-related (ATR is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. Methods ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD, haplotype analyses, and tagging SNP (tSNP identification. Expression analyses were carried out using real-time PCR. Results The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. Conclusion Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association

  1. Validation of a χ2 model of HRR target RCS variability and verification of the resulting ATR performance model

    Science.gov (United States)

    Holt, Craig R.; Attili, Joseph B.; Schmidt, Steven L.

    2001-10-01

    A (chi) 2 model for radar cross section (RCS) variability of High Range Resolution (HRR) measurements is validated using compact range data from the U.S. Army National Ground Intelligence Center (NGIC). It is shown that targets can be represented by a mean template and by a variance template, or in this case, an effective number of degrees-of-freedom for the (chi) 2-distribution. The analysis also includes comparison of the measured tails of the RCS distribution to that predicated by the (chi) 2-distribution. The likelihood classifier is obtained, and a Monte Carlo performance model is developed to validate the statistical model at the level of ATR performance.

  2. Analysis of European Honeybee (Apis Mellifera Wings Using ATR-FTIR and Raman Spectroscopy: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Machovič V.

    2017-03-01

    Full Text Available The infrared (ATR-FTIR and Raman spectroscopy was used for the structural characterization of honeybee wings. Protein, chitin, and lipid characteristic spectral features were detected using both methods. The protein secondary structure was predominantly composed of the β-sheet molecular conformation with β-turns or coil contributions. The vibration modes of the side-chain aromatic amino acid residues (tyrosine, phenylalanine, tryptophan occurred in the wing spectra. The results of discriminant analysis showed that the infrared spectroscopy of the wing in combination with a multivariate analysis seemed promising for a resolution of the chemical structure of the wings based on lipid, proteins, and chitin content.

  3. Differentiation and identification of fungi by ATR-FTIR method in a leather collection relating back to Seljuk period

    Directory of Open Access Journals (Sweden)

    Mohsen Mohammadi Achachluei

    2013-01-01

    Full Text Available Introduction: Biodegradation is one of the main degrading factors of leather artifacts. Determination of fungi and other microorganisms has vital importance for conservation of valuable objects made from organic materials. Usual classic techniques for identification of pathogens and fungi have some difficulties, but FTIR spectroscopy has been introduced as useful technique for characterization and determination of microorganisms. Materials and methods: In this study, historic leathers were related to the Seljuk period. The leathers were sampled in laboratory and fungi were cultivated in SDA medium. Genuses of fungi were identified according to macroscopic, microscopic and morphologic characteristics. Microorganisms were analyzed by ATR-FTIR spectrometer and differences of spectral properties were assessed. Spectral properties were assessed according to form and absorption region of peaks. Cluster analysis was used for evaluation of different regions and areas on the measured spectra.Results: Results showed the presence of Penicillium sp. (9 samples, 33.3%, Aspergillus sp. (5 samples, 18.5%, Cladosporium sp. (4 samples, 14.8%, Rhizoctonia sp. (2 samples, 7.4%, Trichophyton sp. (1 sample, 3.7% and also one sample of yeast (3.7%. Two species of fungi remained unidentified (7.4% and there was not any growth in 3 samples (11.1%. Spectral properties indicated to structural differences between microorganisms (fungi, yeast, bacteria. It showed characteristics of fungi genus and species in some cases.Discussion and conclusion: Active fungi induce decomposition, hydrolysis and decay of leather and its vegetable tannins. The decay leads to aesthetic change and health problems. Therefore, it is necessary to remove of fungi and appropriate treatment of leather artifacts. Application of ATR-FTIR spectroscopy had good results for identification of fungi, yeast and bacteria. Assessments showed the potential of ATR-FTIR spectroscopy for easy and rapid

  4. Microstructural examination of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Gelles, D.S. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-09-01

    Microstructural examination results are reported for four heats of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment to {approximately}4 dpa at {approximately}200 and 300 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment or composition.

  5. Tip-enhanced near-field optical microscope with side-on and ATR-mode sample excitation for super-resolution Raman imaging of surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Heilman, A. L.; Gordon, M. J. [Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, California 93106-5080 (United States)

    2016-06-14

    A tip-enhanced near-field optical microscope with side-on and attenuated total reflectance (ATR) excitation and collection is described and used to demonstrate sub-diffraction-limited (super-resolution) optical and chemical characterization of surfaces. ATR illumination is combined with an Au optical antenna tip to show that (i) the tip can quantitatively transduce the optical near-field (evanescent waves) above the surface by scattering photons into the far-field, (ii) the ATR geometry enables excitation and characterization of surface plasmon polaritons (SPPs), whose associated optical fields are shown to enhance Raman scattering from a thin layer of copper phthalocyanine (CuPc), and (iii) SPPs can be used to plasmonically excite the tip for super-resolution chemical imaging of patterned CuPc via tip-enhanced Raman spectroscopy (TERS). ATR-illumination TERS is also quantitatively compared with the more conventional side-on illumination scheme. In both cases, spatial resolution was better than 40 nm and tip on/tip off Raman enhancement factors were >6500. Furthermore, ATR illumination was shown to provide similar Raman signal levels at lower “effective” pump powers due to additional optical energy delivered by SPPs to the active region in the tip-surface gap.

  6. ON-LINE MONITORING OF I&C TRANSMITTERS AND SENSORS FOR CALIBRATION VERIFICATION AND RESPONSE TIME TESTING WAS SUCCESSFULLY IMPLEMENTED AT ATR

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, Phillip A.; O' Hagan, Ryan; Shumaker, Brent; Hashemian, H. M.

    2017-03-01

    The Advanced Test Reactor (ATR) has always had a comprehensive procedure to verify the performance of its critical transmitters and sensors, including RTDs, and pressure, level, and flow transmitters. These transmitters and sensors have been periodically tested for response time and calibration verification to ensure accuracy. With implementation of online monitoring techniques at ATR, the calibration verification and response time testing of these transmitters and sensors are verified remotely, automatically, hands off, include more portions of the system, and can be performed at almost any time during process operations. The work was done under a DOE funded SBIR project carried out by AMS. As a result, ATR is now able to save the manpower that has been spent over the years on manual calibration verification and response time testing of its temperature and pressure sensors and refocus those resources towards more equipment reliability needs. More importantly, implementation of OLM will help enhance the overall availability, safety, and efficiency. Together with equipment reliability programs of ATR, the integration of OLM will also help with I&C aging management goals of the Department of Energy and long-time operation of ATR.

  7. Sobre el iuspositivismo que hemos de dejar atrás. Una crítica iusnaturalista a "Dejemos atrás el positivismo jurídico" de Atienza y de Ruiz Manero

    Directory of Open Access Journals (Sweden)

    JOSÉ CHÁVEZ-FERNÁNDEZ

    2011-01-01

    Full Text Available A través de la confrontación de las tesis más relevantes que Atienza y Ruiz Manero proponen en su artículo "Dejemos atrás el positivismo jurídico", el autor pretende mostrar-a partir de la respuesta a las preguntas "¿qué iuspositivismo hemos de dejar atrás?", "¿por qué?" y "¿cómo?"- que existen en el iuspositivismo debilidades explicativas graves respecto de la realidad jurídica, y que estas están vinculadas tanto al escepticismo ético como a la negación de la existencia de un Derecho natural en sentido propio, es decir, de raigambre antropológico-metafísica. Por otro lado, se tratará de evidenciar que dichas debilidades explicativas le son comunes también a los intentos pragmático-constructivistas de superación del iuspositivismo por lo que, en última instancia, ninguno de dichos esquemas conceptuales puede dar cuenta cabal de una realidad como los derechos humanos que se presentan como deudas ético-jurídicas inexcusables fundamentadas en la dignidad ontológica de todos los seres humanos.

  8. In-situ monitoring of blood glucose level for dialysis machine by AAA-battery-size ATR Fourier spectroscopy

    Science.gov (United States)

    Hosono, Satsuki; Sato, Shun; Ishida, Akane; Suzuki, Yo; Inohara, Daichi; Nogo, Kosuke; Abeygunawardhana, Pradeep K.; Suzuki, Satoru; Nishiyama, Akira; Wada, Kenji; Ishimaru, Ichiro

    2015-07-01

    For blood glucose level measurement of dialysis machines, we proposed AAA-battery-size ATR (Attenuated total reflection) Fourier spectroscopy in middle infrared light region. The proposed one-shot Fourier spectroscopic imaging is a near-common path and spatial phase-shift interferometer with high time resolution. Because numerous number of spectral data that is 60 (= camera frame rare e.g. 60[Hz]) multiplied by pixel number could be obtained in 1[sec.], statistical-averaging improvement realize high-accurate spectral measurement. We evaluated the quantitative accuracy of our proposed method for measuring glucose concentration in near-infrared light region with liquid cells. We confirmed that absorbance at 1600[nm] had high correlations with glucose concentrations (correlation coefficient: 0.92). But to measure whole-blood, complex light phenomenon caused from red blood cells, that is scattering and multiple reflection or so, deteriorate spectral data. Thus, we also proposed the ultrasound-assisted spectroscopic imaging that traps particles at standing-wave node. Thus, if ATR prism is oscillated mechanically, anti-node area is generated around evanescent light field on prism surface. By elimination complex light phenomenon of red blood cells, glucose concentration in whole-blood will be quantify with high accuracy. In this report, we successfully trapped red blood cells in normal saline solution with ultrasonic standing wave (frequency: 2[MHz]).

  9. A new integrated TLC/MU-ATR/SERS advanced approach for the identification of trace amounts of dyes in mixtures.

    Science.gov (United States)

    Sciutto, Giorgia; Prati, Silvia; Bonacini, Irene; Litti, Lucio; Meneghetti, Moreno; Mazzeo, Rocco

    2017-10-23

    The present research is focused on the setting up of an advanced analytical system for the detection of synthetic dyes. The system is based on the combination of an innovative thin layer chromatography (TLC) plate coupled with enhanced infrared (MU-ATR, metal underlayer attenuated total reflection) and Surface Enhanced Raman (SERS) spectroscopy. In particular, a TLC plate made of silver iodide (AgI) applied onto a gold coated glass slide (AgI@Au) is proposed as an efficient stationary phase for the separation of dyes mixtures. The separated dyes are then identified by means of both enhanced FTIR and SERS, performed directly on the same eluted spots. The use of a mid-IR transparent inorganic salt as stationary phase coupled with the underneath gold layer avoids spectral interferences, enhancing the signal obtained from ATR analyses. At the same time, SERS spectra can be recorded as the TLC plate may act as a SERS active substrate due to the photoreduction of AgI to metallic Ag caused by the exposure to the laser during the Raman analysis. Different mixtures of synthetic dyes of known composition, widely used in dyeing processes, have been tested and the method resulted to be effective in identifying trace amounts in the order of tens nanograms. Moreover, the method has been further evaluated on a real case study represented by dyes extracted from dyed wool. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without {alpha}-thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Villard, L.; Lossi, A.M.; Fontes, M. [and others

    1996-03-01

    We have previously reported the isolation of a gene from Xq13 that codes for a putative regulator of transcription (XNP) and has now been shown to be the gene involved in the X-linked {alpha}-thalassemia with mental retardation (ATR-X) syndrome. The widespread expression and numerous domains present in the putative protein suggest that this gene could be involved in other phenotypes. The predominant expression of the gene in the developing brain, as well as its association with neuron differentiation, indicates that mutations of this gene might result in a mental retardation (MR) phenotype. In this paper we present a family with a splice junction mutation in XNP that results in the skipping of an exon and in the introduction of a stop codon in the middle of the XNP-coding sequence. Only the abnormal transcript is expressed in two first cousins presenting the classic ATR-X phenotype (with {alpha}-thalassemia and HbH inclusions). In a distant cousin presenting a similar dysmorphic MR phenotype but not having thalassemia, {approximately}30% of the XNP transcripts are normal. These data demonstrate that the mode of action of the XNP gene product on globin expression is distinct from its mode of action in brain development and facial morphogenesis and suggest that other dysmorphic mental retardation phenotypes, such as Juberg-Marsidi or some sporadic cases of Coffin-Lowry, could be due to mutations in XNP. 20 refs., 5 figs., 2 tabs.

  11. Simultaneous ATR-FTIR Based Determination of Malaria Parasitemia, Glucose and Urea in Whole Blood Dried onto a Glass Slide.

    Science.gov (United States)

    Roy, Supti; Perez-Guaita, David; Andrew, Dean W; Richards, Jack S; McNaughton, Don; Heraud, Philip; Wood, Bayden R

    2017-05-16

    New diagnostic tools that can detect malaria parasites in conjunction with other diagnostic parameters are urgently required. In this study, Attenuated Total Reflection Fourier transform infrared (ATR-FTIR) spectroscopy in combination with Partial Least Square Discriminant Analysis (PLS-DA) and Partial Least Square Regression (PLS-R) have been applied as a point-of-care test for identifying malaria parasites, blood glucose, and urea levels in whole blood samples from thick blood films on glass slides. The specificity for the PLS-DA was found to be 98% for parasitemia levels >0.5%, but a rather low sensitivity of 70% was achieved because of the small number of negative samples in the model. In PLS-R the Root Mean Square Error of Cross Validation (RMSECV) for parasite concentration (0-5%) was 0.58%. Similarly, for glucose (0-400 mg/dL) and urea (0-250 mg/dL) spiked samples, relative RMSECVs were 16% and 17%, respectively. The method reported here is the first example of multianalyte/disease diagnosis using ATR-FTIR spectroscopy, which in this case, enabled the simultaneous quantification of glucose and urea analytes along with malaria parasitemia quantification using one spectrum obtained from a single drop of blood on a glass microscope slide.

  12. ATR FT-IR spectroscopy on Vmh2 hydrophobin self-assembled layers for Teflon membrane bio-functionalization

    Energy Technology Data Exchange (ETDEWEB)

    Portaccio, M., E-mail: marianna.portaccio@unina2.it [Dipartimento di Medicina Sperimentale – Seconda Università di Napoli, Via S.M. di Costantinopoli, 16-80134 Napoli (Italy); Gravagnuolo, A.M., E-mail: alfredomaria.gravagnuolo@unina.it [Dipartimento di Scienze Chimiche, Università “Federico II”, Via Cintia, 21- 80126 Napoli (Italy); Longobardi, S., E-mail: sara.longobardi@unina.it [Dipartimento di Scienze Chimiche, Università “Federico II”, Via Cintia, 21- 80126 Napoli (Italy); Giardina, P., E-mail: paola.giardina@unina.it [Dipartimento di Scienze Chimiche, Università “Federico II”, Via Cintia, 21- 80126 Napoli (Italy); Rea, I., E-mail: ilaria.rea@na.imm.cnr.it [Institute for Microelectronics and Microsystems, CNR, Via P. Castellino, 111-80131 Napoli (Italy); De Stefano, L., E-mail: luca.destefano@na.imm.cnr.it [Institute for Microelectronics and Microsystems, CNR, Via P. Castellino, 111-80131 Napoli (Italy); Cammarota, M., E-mail: marcella.cammarota@unina2.it [Dipartimento di Medicina Sperimentale – Seconda Università di Napoli, Via S.M. di Costantinopoli, 16-80134 Napoli (Italy); Lepore, M., E-mail: maria.lepore@unina2.it [Dipartimento di Medicina Sperimentale – Seconda Università di Napoli, Via S.M. di Costantinopoli, 16-80134 Napoli (Italy)

    2015-10-01

    Graphical abstract: - Highlights: • Hydrophobin self-assembled layers on Teflon in different preparation conditions were investigated. • ATR collection data geometry allowed samples examination without any particular preparation. • Amide content, lipid/amide and carbohydrate/amide ratios of the protein layer were estimated. • Secondary structure of protein was determined for the examined samples. • FT-IR demonstrated to be of extreme relevance in monitoring hydrophobin self-assembled layers preparation. - Abstract: Surface functionalization by layers of hydrophobins, amphiphilic proteins produced by fungi offers a promising and green strategy for fabrication of biomedical and bioanalytical devices. The layering process of the Vmh2 hydrophobin from Pleurotus ostreatus on Teflon membrane has been investigated by Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) spectroscopy. In particular, protein layers obtained with hydrophobin purified with two different procedures and in various coating conditions have been examined. The layers have been characterized by quantifying the amide I and amide II band area together with the lipid/amide ratio and carbohydrate/amide ratio. This characterization can be very useful in evaluating the best purification strategy and coating conditions. Moreover the analysis of the secondary structure of the layered protein using the deconvolution procedure of amide I band indicate the prevalent contribution from β-sheet state. The results inferred by infrared spectroscopy have been also confirmed by scanning electron microscopy imaging.

  13. Characterization of Satsuma mandarin (Citrus unshiu Marc.) nectar-to-honey transformation pathway using FTIR-ATR spectroscopy.

    Science.gov (United States)

    Svečnjak, Lidija; Prđun, Saša; Rogina, Josip; Bubalo, Dragan; Jerković, Igor

    2017-10-01

    Samples of Satsuma mandarin (Citrus unshiu Marc.) nectar, honey sac content and honey were analyzed by FTIR-ATR spectroscopy and reference methods. The spectral analysis allowed detection of the major chemical constituents in C. unshiu nectar-to-honey transformation pathway thus providing information on the intensity and location of the compositional changes occurring during this process. The preliminary results showed that in average more than one-third of sugar-related nectar-to-honey conversion takes place directly in the honey sac; the average sugar content (w/w) was 17.93% (nectar), 47.03% (honey sac) and 79.63% (honey). FTIR-ATR results showed great spectral similarity of analyzed honey samples and small degree variations in both sugar and water content in nectar samples. The spectral data revealed distinctive differences in the chemical composition of individual honey sac contents with the most intensive and complex absorption envelope in the spectral region between 1175 and 950cm -1 (glucose, fructose and sucrose absorption bands). Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Cocaine profiling: Implementation of a predictive model by ATR-FTIR coupled with chemometrics in forensic chemistry.

    Science.gov (United States)

    Materazzi, Stefano; Gregori, Adolfo; Ripani, Luigi; Apriceno, Azzurra; Risoluti, Roberta

    2017-05-01

    In this study, a strategy based on Infrared Spectroscopy with Fourier Transformed and Attenuated Total Reflectance associated with chemometrics (ATR-FTIR) is proposed to identify the chemical "fingerprint" of cocaine samples. To this end, standard mixtures of cocaine and cuttings at differents ratio were investigated in order to develop a multivariate classification model to simultaneously predict the composition of the samples and to obtain a profile of adulteration of cocaine seizures. In addition, the application of a Partial Least Squares (PLS) and Principal Component Regression (PCR) calibration approaches were found to be a useful tool to predict the content of cocaine, caffeine, procaine, lidocaine and phenacetin in drug seizures. The achieved results on real confiscated samples, in cooperation with the Italian Scientific Investigation Department (Carabinieri-RIS) of Rome, allow to consider ATR-FTIR followed to chemometrics as a promising forensic tool in such situations involving profile comparisons and supporting forensic investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Prediction of peroxide value in omega-3 rich microalgae oil by ATR-FTIR spectroscopy combined with chemometrics.

    Science.gov (United States)

    Cebi, Nur; Yilmaz, Mustafa Tahsin; Sagdic, Osman; Yuce, Hande; Yelboga, Emrah

    2017-06-15

    Our work explored, for the first time, monitoring peroxide value (PV) of omega-3 rich algae oil using ATR-FTIR spectroscopic technique. The PV of the developed method was compared by that obtained by standard method of Association of Official Analytical Chemists (AOAC). In this study, peak area integration (PAI), Partial Least Squares Regression (PLSR), and Principal Component Regression (PCR) were used as the calibration techniques. PV obtained by the AOAC method and by FTIR-ATR technique were well correlated considering the peak area related to trans double bonds and chemometrics techniques of PLSR and PCR. Calibration model was established using the band with a peak point at 966cm-1 (990-940cm-1) related to CH out of plane deformation vibration of trans double bond. Algae oil oxidation could be successfully quantified using PAI, PLSR and PCR techniques. Additionally, hierarchical cluster analysis was performed and significant discrimination was observed coherently with oxidation process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. ATR-IR fingerprinting as a powerful method for identification of traditional medicine samples: a report of 20 herbal patterns

    Directory of Open Access Journals (Sweden)

    A. Sakhteman

    2015-06-01

    Full Text Available Background and objectives: Attenuated total reflectance-inferared (ATR-IR spectra can be used as a non-invasive fingerprinting approach in quality control of herbal samples. Methods: Twenty versatile herbal samples were subjected to attenuated total reflectance-inferared (ATR-IR spectroscopy followed by different clustering methods in order to determine by which method more reasonable classifications would be obtained. Results: All classification methods (K-means, HCA, PCA and SOM were able to discriminate the two medicinal seeds, Hyocyamus niger and Peganum harmala from other herbal samples. Similarly, the starch samples were clustered in a reasonable method. In HCA, one cluster included three types of starch samples: Zea mays, Oryza sativa and Triticum aestivum. All the four classification methods were able to separate Solanum tuberosum starch from other starch samples. HCA and SOM, were able to classify leaf samples Origanum vulgare and Melissa officinalis belonging to Lamiaceae family, in one category. Crocus sativus and its adulterant Carthamus tinctorius flowers were identified by PCA, HCA and SOM as different categories. Conclusion: The result of this study can be utilized for identification and quality control of traditionally used medicinal plant samples in an unknown sample powder. Such data could be the basis for preparing a data bank on Iranian medicinal samples which in turn is used as a simple, fast and reliable method for characterization of herbal powders in Pharmacopoeias.

  17. Characterization of postmortem biochemical changes in rabbit plasma using ATR-FTIR combined with chemometrics: A preliminary study

    Science.gov (United States)

    Zhang, Ji; Li, Bing; Wang, Qi; Li, Chengzhi; Zhang, Yinming; Lin, Hancheng; Wang, Zhenyuan

    2017-02-01

    Postmortem interval (PMI) determination is one of the most challenging tasks in forensic medicine due to a lack of accurate and reliable methods. It is especially difficult for late PMI determination. Although many attempts with various types of body fluids based on chemical methods have been made to solve this problem, few investigations are focused on blood samples. In this study, we employed an attenuated total reflection (ATR)-Fourier transform infrared (FTIR) technique coupled with principle component analysis (PCA) to monitor biochemical changes in rabbit plasma with increasing PMI. Partial least square (PLS) model was used based on the spectral data for PMI prediction in an independent sample set. Our results revealed that postmortem chemical changes in compositions of the plasma were time-dependent, and various components including proteins, lipids and nucleic acids contributed to the discrimination of the samples at different time points. A satisfactory prediction within 48 h postmortem was performed by the combined PLS model with a good fitting between actual and predicted PMI of 0.984 and with an error of ± 1.92 h. In consideration of the simplicity and portability of ATR-FTIR, our preliminary study provides an experimental and theoretical basis for application of this technique in forensic practice.

  18. Hepatitis B virus X protein via the p38MAPK pathway induces E2F1 release and ATR kinase activation mediating p53 apoptosis.

    Science.gov (United States)

    Wang, Wen-Horng; Hullinger, Ronald L; Andrisani, Ourania M

    2008-09-12

    Hepatitis B virus (HBV) X protein (pX) is implicated in hepatocellular carcinoma (HCC) pathogenesis by an unknown mechanism. Deletions or mutations of genes involved in the p53 pathway are often associated with HBV-mediated HCC, indicating rescue from p53 apoptosis is a likely mechanism in HBV-HCC pathogenesis. Herein, we determined the mechanism by which pX sensitizes hepatocytes to p53-mediated apoptosis. Although it is well established that the Rb/E2F/ARF pathway stabilizes p53, and the DNA damage-activated ATM/ATR kinases activate p53, the mechanism that coordinates these two pathways has not been determined. We demonstrate that the p38MAPK pathway activated by pX serves this role in p53 apoptosis. Specifically, the activated p38MAPK pathway stabilizes p53 via E2F1-mediated ARF expression, and also activates the transcriptional function of p53 by activating ATR. Knockdown of p53, E2F1, ATR, or p38MAPKalpha abrogates pX-mediated apoptosis, demonstrating that E2F1, ATR, and p38MAPKalpha are all essential in p53 apoptosis in response to pX. Specifically, in response to pX expression, the p38MAPK pathway activates Cdk4 and Cdk2, leading to phosphorylation of Rb, release of E2F1, and transcription of ARF. The p38MAPK pathway also activates ATR, leading to phosphorylation of p53 on Ser-18 and Ser-23, transcription of pro-apoptotic genes Bax, Fas, and Noxa, and apoptosis. In conclusion, pX sensitizes hepatocytes to p53 apoptosis via activation of the p38MAPK pathway, which couples p53 stabilization and p53 activation, by E2F1 induction and ATR activation, respectively.

  19. Hepatitis B Virus X Protein via the p38MAPK Pathway Induces E2F1 Release and ATR Kinase Activation Mediating p53 Apoptosis*S⃞

    Science.gov (United States)

    Wang, Wen-Horng; Hullinger, Ronald L.; Andrisani, Ourania M.

    2008-01-01

    Hepatitis B virus (HBV) X protein (pX) is implicated in hepatocellular carcinoma (HCC) pathogenesis by an unknown mechanism. Deletions or mutations of genes involved in the p53 pathway are often associated with HBV-mediated HCC, indicating rescue from p53 apoptosis is a likely mechanism in HBV-HCC pathogenesis. Herein, we determined the mechanism by which pX sensitizes hepatocytes to p53-mediated apoptosis. Although it is well established that the Rb/E2F/ARF pathway stabilizes p53, and the DNA damage-activated ATM/ATR kinases activate p53, the mechanism that coordinates these two pathways has not been determined. We demonstrate that the p38MAPK pathway activated by pX serves this role in p53 apoptosis. Specifically, the activated p38MAPK pathway stabilizes p53 via E2F1-mediated ARF expression, and also activates the transcriptional function of p53 by activating ATR. Knockdown of p53, E2F1, ATR, or p38MAPKα abrogates pX-mediated apoptosis, demonstrating that E2F1, ATR, and p38MAPKα are all essential in p53 apoptosis in response to pX. Specifically, in response to pX expression, the p38MAPK pathway activates Cdk4 and Cdk2, leading to phosphorylation of Rb, release of E2F1, and transcription of ARF. The p38MAPK pathway also activates ATR, leading to phosphorylation of p53 on Ser-18 and Ser-23, transcription of pro-apoptotic genes Bax, Fas, and Noxa, and apoptosis. In conclusion, pX sensitizes hepatocytes to p53 apoptosis via activation of the p38MAPK pathway, which couples p53 stabilization and p53 activation, by E2F1 induction and ATR activation, respectively. PMID:18606816

  20. Interactions of Human Mismatch Repair Proteins MutSα and MutLα with Proteins of the ATR-Chk1 Pathway*

    Science.gov (United States)

    Liu, Yiyong; Fang, Yanan; Shao, Hongbing; Lindsey-Boltz, Laura; Sancar, Aziz; Modrich, Paul

    2010-01-01

    At clinically relevant doses, chemotherapeutic SN1 DNA methylating agents induce an ATR-mediated checkpoint response in human cells that is dependent on functional MutSα and MutLα. Deficiency of either mismatch repair activity renders cells highly resistant to this class of drug, but the mechanisms linking mismatch repair to checkpoint activation have remained elusive. In this study we have systematically examined the interactions of human MutSα and MutLα with proteins of the ATR-Chk1 pathway using both nuclear extracts and purified proteins. Using nuclear co-immunoprecipitation, we have detected interaction of MutSα with ATR, TopBP1, Claspin, and Chk1 and interaction of MutLα with TopBP1 and Claspin. We were unable to detect interaction of MutSα or MutLα with Rad17, Rad9, or replication protein A in the extract system. Use of purified proteins confirmed direct interaction of MutSα with ATR, TopBP1, and Chk1 and of MutLα with TopBP1. MutSα-Claspin and MutLα-Claspin interactions were not demonstrable with purified proteins, suggesting that extract interactions are indirect or depend on post-translational modification. Use of a modified chromatin immunoprecipitation assay showed that proliferating cell nuclear antigen, ATR, TopBP1, and Chk1 are recruited to chromatin in a MutLα- and MutSα-dependent fashion after N-methyl-N′-nitro-N-nitrosoguanidine treatment. However, chromatin enrichment of replication protein A, Claspin, Rad17-RFC, and Rad9-Rad1-Hus1 was not detected in these experiments. Although our failure to observe enrichment of the latter activities could be due to sensitivity limitations, these observations may indicate a novel mechanism for ATR activation. PMID:20029092

  1. DPP-4 inhibitors

    DEFF Research Database (Denmark)

    Deacon, Carolyn F.

    2016-01-01

    Dipeptidyl peptidase (DPP)-4 inhibitors inhibit the activity of the enzyme responsible for the initial rapid degradation of the incretin hormones, thereby enhancing their antihyperglycemic effects.......Dipeptidyl peptidase (DPP)-4 inhibitors inhibit the activity of the enzyme responsible for the initial rapid degradation of the incretin hormones, thereby enhancing their antihyperglycemic effects....

  2. Development of C-lignin with G/S-lignin and lipids in orchid seed coats – an unexpected diversity exposed by ATR-FT-IR spectroscopy

    DEFF Research Database (Denmark)

    Barsberg, Søren Talbro; Lee, Y-I; Rasmussen, Hanne Nina

    2018-01-01

    Cite this article: Barsberg ST, Lee Y-I, Rasmussen HN. Development of C-lignin with G/S-lignin and lipids in orchid seed coats – an unexpected diversity exposed by ATR-FT-IR spectroscopy. Seed Science Research https:// doi.org/10.1017/S0960258517000344......Cite this article: Barsberg ST, Lee Y-I, Rasmussen HN. Development of C-lignin with G/S-lignin and lipids in orchid seed coats – an unexpected diversity exposed by ATR-FT-IR spectroscopy. Seed Science Research https:// doi.org/10.1017/S0960258517000344...

  3. Encapsulation-Induced Stress Helps Saccharomyces cerevisiae Resist Convertible Lignocellulose Derived Inhibitors

    Directory of Open Access Journals (Sweden)

    Johan O. Westman

    2012-09-01

    Full Text Available The ability of macroencapsulated Saccharomyces cerevisiae CBS8066 to withstand readily and not readily in situ convertible lignocellulose-derived inhibitors was investigated in anaerobic batch cultivations. It was shown that encapsulation increased the tolerance against readily convertible furan aldehyde inhibitors and to dilute acid spruce hydrolysate, but not to organic acid inhibitors that cannot be metabolized anaerobically. Gene expression analysis showed that the protective effect arising from the encapsulation is evident also on the transcriptome level, as the expression of the stress-related genes YAP1, ATR1 and FLR1 was induced upon encapsulation. The transcript levels were increased due to encapsulation already in the medium without added inhibitors, indicating that the cells sensed low stress level arising from the encapsulation itself. We present a model, where the stress response is induced by nutrient limitation, that this helps the cells to cope with the increased stress added by a toxic medium, and that superficial cells in the capsules degrade convertible inhibitors, alleviating the inhibition for the cells deeper in the capsule.

  4. A new Density Functional Theory (DFT) based method for supporting the assignment of vibrational signatures of mannan and cellulose—Analysis of palm kernel cake hydrolysis by ATR-FT-IR spectroscopy as a case study

    DEFF Research Database (Denmark)

    Barsberg, Søren Talbro; Sanadi, Anand Ramesh; Jørgensen, Henning

    2011-01-01

    Attenuated Total Reflectance (ATR) FT-IR spectroscopy gives in situ information on molecular concentration, organization and interactions in plant cell walls. We demonstrate its potential for further developments by a case study which combines ATR-FT-IR spectroscopy with a recently published DFT ...

  5. Dynamic dependence on ATR and ATM for double-strand break repair in human embryonic stem cells and neural descendants.

    Directory of Open Access Journals (Sweden)

    Bret R Adams

    2010-04-01

    Full Text Available The DNA double-strand break (DSB is the most toxic form of DNA damage. Studies aimed at characterizing DNA repair during development suggest that homologous recombination repair (HRR is more critical in pluripotent cells compared to differentiated somatic cells in which nonhomologous end joining (NHEJ is dominant. We have characterized the DNA damage response (DDR and quality of DNA double-strand break (DSB repair in human embryonic stem cells (hESCs, and in vitro-derived neural cells. Resolution of ionizing radiation-induced foci (IRIF was used as a surrogate for DSB repair. The resolution of gamma-H2AX foci occurred at a slower rate in hESCs compared to neural progenitors (NPs and astrocytes perhaps reflective of more complex DSB repair in hESCs. In addition, the resolution of RAD51 foci, indicative of active homologous recombination repair (HRR, showed that hESCs as well as NPs have high capacity for HRR, whereas astrocytes do not. Importantly, the ATM kinase was shown to be critical for foci formation in astrocytes, but not in hESCs, suggesting that the DDR is different in these cells. Blocking the ATM kinase in astrocytes not only prevented the formation but also completely disassembled preformed repair foci. The ability of hESCs to form IRIF was abrogated with caffeine and siRNAs targeted against ATR, implicating that hESCs rely on ATR, rather than ATM for regulating DSB repair. This relationship dynamically changed as cells differentiated. Interestingly, while the inhibition of the DNA-PKcs kinase (and presumably non-homologous endjoining [NHEJ] in astrocytes slowed IRIF resolution it did not in hESCs, suggesting that repair in hESCs does not utilize DNA-PKcs. Altogether, our results show that hESCs have efficient DSB repair that is largely ATR-dependent HRR, whereas astrocytes critically depend on ATM for NHEJ, which, in part, is DNA-PKcs-independent.

  6. Efficacy of metformin in human single hair fibre by ATR-FTIR spectroscopy coupled with statistical analysis.

    Science.gov (United States)

    Sundaramoorthi, Kamatchi; Sethu, Gunasekaran; Ethirajulu, Sailatha; Raja Marthandam, Pavithra

    2017-03-20

    Diabetes mellitus is chronic metabolic disorder, resulting from insulin deficiency, characterized by hyperglycemia altered metabolism of carbohydrates, proteins and lipids and an increased risk of vascular complications. There are different classes of anti-diabetic drugs in allopathic system of medicine. Metformin (dimethyl biguanide) is a blood glucose lowering agent used in the treatment of non-insulin dependent diabetes mellitus. Almost in all diseases the blood serves as the primary metabolic transport system in the body. Its composition is the preferred indicator with respect to the pathophysiological condition of the patient. Instead of analyzing blood to diagnose diabetes, hair could be used to detect diabetes using FTIR-ATR technique. The most important components of hair are fibrous proteins (keratins), melanins, glycogen, and lipids. Hair follicles are located 3-4mm below the surface of the skin and are surrounded by rich blood capillary system. In the present study, ten diabetic subjects were considered to evaluate the efficacy of metformin hydrochloride for the treatment of diabetes mellitus using FTIR-ATR spectroscopy. The spectra of diabetic hair fibre samples have been recorded in the mid infrared region of 4000-450cm -1 . The hair samples of the diabetic subjects before medication were taken as pre-treatment samples. The hair samples of diabetic subjects referred to medication with metformin for a period of three month were taken as post-treatment sample. Some remarkable spectral differences were elucidated between pre- and post-treatment hair fibre samples. A comparative study on the FTIR-ATR hair spectra of patients (pre- and post-treatment) along with the healthy subjects has been made. The absorption values of some of the specific bands of biomolecules present in the hair samples viz., protein, lipids and glucose for both the pre- and post-treatment subjects are noted. It was observed that, these biomarkers are significantly different between

  7. Targeting Ongoing DNA Damage in Multiple Myeloma: Effects of DNA Damage Response Inhibitors on Plasma Cell Survival

    Directory of Open Access Journals (Sweden)

    Ana Belén Herrero

    2017-05-01

    Full Text Available Human myeloma cell lines (HMCLs and a subset of myeloma patients with poor prognosis exhibit high levels of replication stress (RS, leading to DNA damage. In this study, we confirmed the presence of DNA double-strand breaks (DSBs in several HMCLs by measuring γH2AX and RAD51 foci and analyzed the effect of various inhibitors of the DNA damage response on MM cell survival. Inhibition of ataxia telangiectasia and Rad3-related protein (ATR, the main kinase mediating the response to RS, using the specific inhibitor VE-821 induced more cell death in HMCLs than in control lymphoblastoid cells and U266, an HMCL with a low level of DNA damage. The absence of ATR was partially compensated by ataxia telangiectasia-mutated protein (ATM, since chemical inhibition of both kinases using VE-821 and KU-55933 significantly increased the death of MM cells with DNA damage. We found that ATM and ATR are involved in DSB repair by homologous recombination (HR in MM. Inhibition of both kinases resulted in a stronger inhibition that may underlie cell death induction, since abolition of HR using two different inhibitors severely reduced survival of HMCLs that exhibit DNA damage. On the other hand, inhibition of the other route involved in DSB repair, non-homologous end joining (NHEJ, using the DNA-PK inhibitor NU7441, did not affect MM cell viability. Interestingly, we found that NHEJ inhibition did not increase cell death when HR was simultaneously inhibited with the RAD51 inhibitor B02, but it clearly increased the level of cell death when HR was inhibited with the MRE11 inhibitor mirin, which interferes with recombination before DNA resection takes place. Taken together, our results demonstrate for the first time that MM cells with ongoing DNA damage rely on an intact HR pathway, which thereby suggests therapeutic opportunities. We also show that inhibition of HR after the initial step of end resection might be more appropriate for inducing MM cell death, since it

  8. Targeting Ongoing DNA Damage in Multiple Myeloma: Effects of DNA Damage Response Inhibitors on Plasma Cell Survival.

    Science.gov (United States)

    Herrero, Ana Belén; Gutiérrez, Norma Carmen

    2017-01-01

    Human myeloma cell lines (HMCLs) and a subset of myeloma patients with poor prognosis exhibit high levels of replication stress (RS), leading to DNA damage. In this study, we confirmed the presence of DNA double-strand breaks (DSBs) in several HMCLs by measuring γH2AX and RAD51 foci and analyzed the effect of various inhibitors of the DNA damage response on MM cell survival. Inhibition of ataxia telangiectasia and Rad3-related protein (ATR), the main kinase mediating the response to RS, using the specific inhibitor VE-821 induced more cell death in HMCLs than in control lymphoblastoid cells and U266, an HMCL with a low level of DNA damage. The absence of ATR was partially compensated by ataxia telangiectasia-mutated protein (ATM), since chemical inhibition of both kinases using VE-821 and KU-55933 significantly increased the death of MM cells with DNA damage. We found that ATM and ATR are involved in DSB repair by homologous recombination (HR) in MM. Inhibition of both kinases resulted in a stronger inhibition that may underlie cell death induction, since abolition of HR using two different inhibitors severely reduced survival of HMCLs that exhibit DNA damage. On the other hand, inhibition of the other route involved in DSB repair, non-homologous end joining (NHEJ), using the DNA-PK inhibitor NU7441, did not affect MM cell viability. Interestingly, we found that NHEJ inhibition did not increase cell death when HR was simultaneously inhibited with the RAD51 inhibitor B02, but it clearly increased the level of cell death when HR was inhibited with the MRE11 inhibitor mirin, which interferes with recombination before DNA resection takes place. Taken together, our results demonstrate for the first time that MM cells with ongoing DNA damage rely on an intact HR pathway, which thereby suggests therapeutic opportunities. We also show that inhibition of HR after the initial step of end resection might be more appropriate for inducing MM cell death, since it prevents the

  9. X-linked [alpha]-thalassemia/mental retardation (ATR-X) syndrome: Localization to Xq12-q21. 31 by X inactivation and linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gibbons, R.J.; Buckle, V.J.; Higgs, D.R.; Suthers, G.K. (John Radcliffe Hospital, Oxford (United Kingdom)); Wilkie, A.O.M. (Univ. of Hospital of Wales, Cardiff (United Kingdom))

    1992-11-01

    The authors have examined seven pedigrees that include individuals with a recently described X-linked form of severe mental retardation associated with [alpha]-thalassemia (ATR-X syndrome). Using hematologic and molecular approaches, they have shown that intellectually normal female carriers of this syndrome may be identified by the presence of rare cells containing HbH (hemoglobin H) inclusions in their peripheral blood and by an extremely skewed pattern of X inactivation seen in cells from a variety of tissues. Linkage analysis has localized the ATR-X locus to an interval of approximately 11 cM between the loci DXS106 and DXYS1X (Xq12-q21.31), with a peak LOD score of 5.4 (recombination fraction of 0) at DCS72. These findings provide the basis for genetic counseling, assessment of carrier risk, and prenatal diagnosis of the ATR-X syndrome. Furthermore, they represent an important step in developing strategies to understand how the mutant ATR-X allele causes mental handicap, dysmorphism, and down-regulation of the [alpha]-globin genes. 54 refs., 6 figs., 4 tabs.

  10. Study of fibrinogen adsorption on hydroxyapatite and TiO2 surfaces by electrochemical piezoelectric quartz crystal impedance and FTIR-ATR spectroscopy.

    Science.gov (United States)

    Yang, Qin; Zhang, Youyu; Liu, Meiling; Ye, Min; Zhang, YuQin; Yao, Shouzhuo

    2007-07-30

    The electrochemical piezoelectric quartz crystal impedance (EQCI), a combined technique of piezoelectric quartz crystal impedance (PQCI), electrochemical impedance (EI), and Fourier transform infrared spectroscopy-attenuated total internal reflectance spectroscopy (FTIR-ATR) were used to in situ study the adsorption process of fibrinogen onto the surface of biomaterials-TiO2 and hydroxyapatite (Ca5(PO4)3OH, HAP). The equivalent circuit parameters, the resonance frequencies and the half peak width of the conductance spectrum of the two biomaterial-modified piezoelectric quartz crystal (PQC) resonances as well as the FTIR-ATR spectra of fibrinogen during fibrinogen adsorption on TiO2 and HAP particles modified electrode surface were obtained. The adsorption kinetics and mechanism of fibrinogen were investigated and discussed as well. The results suggested that two consecutive steps occurred during the adsorption of fibrinogen onto TiO2 and hydroxyapatite (HAP) surface. The fibrinogen molecules were firstly adsorbed onto the surface, and then the rearrangement of adsorbed fibrinogen or multi-layered adsorption occurred. The FTIR-ATR spectroscopy investigations showed that the secondary structure of fibrinogen molecules was altered during the adsorption and the adsorption kinetics of fibrinogen related with the variety of biomaterials. These experimental results suggest a way for enriching biological analytical science and developing new applications of analytical techniques, such as PQCI, EI, and FTIR-ATR.

  11. Measuring Heterogeneous Reaction Rates with ATR-FTIR Spectroscopy to Evaluate Chemical Fates in an Atmospheric Environment: A Physical Chemistry and Environmental Chemistry Laboratory Experiment

    Science.gov (United States)

    Roberts, Jason E.; Zeng, Guang; Maron, Marta K.; Mach, Mindy; Dwebi, Iman; Liu, Yong

    2016-01-01

    This paper reports an undergraduate laboratory experiment to measure heterogeneous liquid/gas reaction kinetics (ozone-oleic acid and ozone-phenothrin) using a flow reactor coupled to an attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometer. The experiment is specially designed for an upper-level undergraduate Physical…

  12. Comparison of ATR-FTIR spectra of porcine vaginal and buccal mucosa with ear skin and penetration analysis of drug and vehicle components into pig ear.

    Science.gov (United States)

    Schwarz, Julia C; Pagitsch, Elisabeth; Valenta, Claudia

    2013-12-18

    In the present study, porcine buccal and vaginal mucosae were successfully characterised by ATR-FTIR for the first time and compared to porcine ear skin. By analysing typical bands of the spectra, the structure of proteins and the lipid matrix were elucidated. According to the body site, differences in membrane permeability were detected when analysing the CH2-stretching and -scissoring vibrations. The results indicated a higher permeability for porcine vaginal and buccal tissue compared to skin. Furthermore, the influence of a lecithin-based microemulsion on the barrier properties of the above mentioned tissues was investigated by ATR-FTIR; the results revealed structural changes in all tissues. In addition, the ATR-FTIR technique was employed to semi-quantitatively analyse compounds directly on skin. To this end, tape stripping experiments were performed with a deuterated liposomal drug delivery system containing the model drug flufenamic acid. While the amount of penetrated deuterated liposomes was determined directly on skin samples by ATR-FTIR, the drug amount was analysed by HPLC after extraction of the tape strips since higher sensitivity was achieved in this fashion. Thus, it was possible to monitor the skin penetration of drug and vehicle simultaneously. Interestingly, the results indicated an independent drug penetration after release from the liposomal carrier system. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. PLS models for determination of SARA analysis of Colombian vacuum residues and molecular distillation fractions using MIR-ATR

    Directory of Open Access Journals (Sweden)

    Jorge A. Orrego-Ruiz

    2014-06-01

    Full Text Available In this work, prediction models of Saturates, Aromatics, Resins and Asphaltenes fractions (SARA from thirty-seven vacuum residues of representative Colombian crudes and eighteen fractions of molecular distillation process were obtained. Mid-Infrared (MIR Attenuated Total Reflection (ATR spectroscopy in combination with partial least squares (PLS regression analysis was used to estimate accurately SARA analysis in these kind of samples. Calibration coefficients of prediction models were for saturates, aromatics, resins and asphaltenes fractions, 0.99, 0.96, 0.97 and 0.99, respectively. This methodology permits to control the molecular distillation process since small differences in chemical composition can be detected. Total time elapsed to give the SARA analysis per sample is 10 minutes.

  14. Rapid evaluation and quantitative analysis of thyme, origano and chamomile essential oils by ATR-IR and NIR spectroscopy

    Science.gov (United States)

    Schulz, Hartwig; Quilitzsch, Rolf; Krüger, Hans

    2003-12-01

    The essential oils obtained from various chemotypes of thyme, origano and chamomile species were studied by ATR/FT-IR as well as NIR spectroscopy. Application of multivariate statistics (PCA, PLS) in conjunction with analytical reference data leads to very good IR and NIR calibration results. For the main essential oil components (e.g. carvacrol, thymol, γ-terpinene, α-bisabolol and β-farnesene) standard errors are in the range of the applied GC reference method. In most cases the multiple coefficients of determination ( R2) are >0.97. Using the IR fingerprint region (900-1400 cm -1) a qualitative discrimination of the individual chemotypes is possible already by visual judgement without to apply any chemometric algorithms.The described rapid and non-destructive methods can be applied in industry to control very easily purifying, blending and redistillation processes of the mentioned essential oils.

  15. Fabrication Control Plan for ORNL RH-LOCA ATF Test Specimens to be Irradiated in the ATR

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Howard, Richard [Idaho National Lab. (INL), Idaho Falls, ID (United States); Teague, Michael [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-06-01

    The purpose of this fabrication plan is (1) to summarize the design of a set of rodlets that will be fabricated and then irradiated in the Advanced Test Reactor (ATR) and (2) provide requirements for fabrication and acceptance criteria for inspections of the Light Water Reactor (LWR) – Accident Tolerant Fuels (ATF) rodlet components. The functional and operational (F&OR) requirements for the ATF program are identified in the ATF Test Plan. The scope of this document only covers fabrication and inspections of rodlet components detailed in drawings 604496 and 604497. It does not cover the assembly of these items to form a completed test irradiation assembly or the inspection of the final assembly, which will be included in a separate INL final test assembly specification/inspection document. The controls support the requirements that the test irradiations must be performed safely and that subsequent examinations must provide valid results.

  16. The Conference Proceedings of the 2001 Air Transport Research Society (ATRS) of the WCTR Society. Volume 1

    Science.gov (United States)

    Lee, Yeong-Heok (Editor); Bowen, Brent D. (Editor); Tarry, Scott E. (Editor)

    2001-01-01

    The ATRS held its Annual conference at Jeju Island, Korea in July 2001. The conference was a success with nearly 140 participants including 70 presenters. This report contains presentations from Volume 1 on the following: Airline and Travel Agent Relationships in Asia;Benchmarking Aviation Safety in the Commercial Airline Industry;Impact of Frequent Flyer Program on the Demand for Air Travel; Application of Genetic Algorithm on Airline Schedule;The Effects of Dual Carrier Designation and Partial Liberalization: The Case of Canada;Defense of Air Carriers and Air Agencies in FAA Enforcement proceedin gs - Damage Control Before the Case Arises; Cost Incentives for Airline Mergers? - An examination on the cost impact of U.S. airline mergers and acquisitions;Airport Regulation, Airline Competition and Canada's Airport System; Airline Competition: The Case of Israel's Domestic Doupoly; Non-Financial Indicators of Airline Distress: A Conceptual Approach;and Airport Privatization: An Empirical Analysis of Financial and Operational Efficiency.

  17. A Simple Approach to Distinguish Classic and Formaldehyde-Free Tannin Based Rigid Foams by ATR FT-IR

    Directory of Open Access Journals (Sweden)

    Gianluca Tondi

    2015-01-01

    Full Text Available Tannin based rigid foams (TBRFs have been produced with formaldehyde since 1994. Only recently several methods have been developed in order to produce these foams without using formaldehyde. TBRFs with and without formaldehyde are visually indistinguishable; therefore a method for determining the differences between these foams had to be found. The attenuated total reflectance infrared spectroscopy (ATR FT-IR investigation of the TBRFs presented in this paper allowed discrimination between the formaldehyde-containing (classic and formaldehyde-free TBRFs. The spectra of the formaldehyde-free TBRFs, indeed, present decreased band intensity related to the C–O stretching vibration of (i the methylol groups and (ii the furanic rings. This evidence served to prove the chemical difference between the two TBRFs and explained the slightly higher mechanical properties measured for the classic TBRFs.

  18. Fast and calibration free determination of first order reaction kinetics in API synthesis using in-situ ATR-FTIR.

    Science.gov (United States)

    Rehbein, Moritz C; Husmann, Sascha; Lechner, Christian; Kunick, Conrad; Scholl, Stephan

    2017-09-28

    In early stages of drug development only sparse amounts of the key substances are available, which is problematic for the determination of important process data like reaction kinetics. Therefore, it is important to perform experiments as economically as possible, especially in regards to limiting compounds. Here we demonstrate the use of a temperature step experiment enabling the determination of complete reaction kinetics in a single non-isothermal experiment. In contrast to the traditionally used HPLC, the method takes advantage of the high measuring rate and the low amount of labor involved in using in-situ ATR-FTIR to determine time-dependent concentration-equivalent data. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A distrofia miotônica ou miotonia atrófica: estudo sintético-crítico

    Directory of Open Access Journals (Sweden)

    Enzo Azzi

    1953-03-01

    Full Text Available O autor, baseado em algumas observações clínicas pessoais, individualiza os elementos principais (atróficos, miotônicos, neurendócrino-vegetativos que se referem à distrofia miotônica, insistindo sôbre a riqueza dos sintomas infundíbulo-hipofisários observados (distrofia adiposogenital, policitemia, perturbações do sono, constante hipoplasia da sela turca que falam em favor de uma meiopragia diencéfalo-hipofisária como mecanismo fisiopatogênico da doença. O autor discute também o problema das relações entre distrofia miotônica e miotonia de Thomsen, concluindo, com base em um de seus casos, pela identidade fundamental das duas formas e, portanto, pela sua unificação.

  20. Mirando atrás: Las representaciones de zoomorfos retrospicientes en el arte paleolítico europeo

    Directory of Open Access Journals (Sweden)

    LOMBO MONTAÑÉS, A., HERNANDO ÁLVAREZ, C., BEA, M.

    2014-01-01

    Full Text Available Se presenta el estudio de conjunto de las representaciones paleolíticas de zoomorfos con la cabeza vuelta hacia atrás. Su análisis detallado permite enunciar algunas hipótesis de carácter tecnológico (orientación, cronológico y contextual (asociación temática, al tiempo que nos acerca a su significación. Las grafías zoomorfas retrospicientes forman un pequeño grupo característico dentro del repertorio gráfico del arte paleolítico, tratándose de un motivo gráfico que además de reflejar actitudes animales reales debió convertirse, muy posiblemente, en un elemento clave de trasmisión gráfica, debido a su amplia dispersión geográfica.

  1. Tensile and impact properties of vanadium-base alloys irradiated at low temperatures in the ATR-A1 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Nowicki, L.J.; Billone, M.C.; Chung, H.M.; Smith, D.L. [Argonne National Lab., IL (United States)

    1998-03-01

    Subsize tensile and Charpy specimens made from several V-(4-5)Cr-(4-5)Ti alloys were irradiated in the ATR-A1 experiment to study the effects of low-temperature irradiation on mechanical properties. These specimens were contained in lithium-bonded subcapsules and irradiated at temperatures between {approx}200 and 300 C. Peak neutron damage was {approx}4.7 dpa. Postirradiation testing of these specimens has begun. Preliminary results from a limited number of specimens indicate a significant loss of work-hardening capability and dynamic toughness due to the irradiation. These results are consistent with data from previous low-temperature neutron irradiation experiments on these alloys.

  2. Structural ATR-IR analysis of cellulose fibers prepared from a NaOH complex aqueous solution

    Science.gov (United States)

    Yang, Y. P.; Zhang, Y.; Lang, Y. X.; Yu, M. H.

    2017-06-01

    In this study, regenerated cellulose fibers were successfully prepared from cellulose/NaOH/thiourea/urea aqueous solution through an efficient extrusion dissolution method. The microstructure of the regenerated cellulose fibers were analysed by using attenuated total reflection infrared (ATR-IR) spectroscopy and the corresponding two-dimensional (2D) correlation spectroscopy. The results showed that the fibers demonstrate a typical crystalline cellulose II and a relatively high crystallinity. Improved crystal structure and tensile strength were obtained in the regenerated cellulose fibers due to improved multi-roller drawing process. The total crystalline index (TCI) and tensile strength of the fibers at different spinning stages were determined in the range of 0.46-0.54 and 1.06-2.30 cN/dtex, respectively. The described cellulose regeneration pathway provided an environmentally friendly and simple method, which could have a significant influence on current cellulose regeneration industries.

  3. Improvement in the corrosion resistance of carbon steel in acidic condition using naphthalen-2-ylnaphthalene-2-carboxammide inhibitor.

    Science.gov (United States)

    Kannan, Perumal; Rao, Toleti Subba; Rajendran, Nallaiyan

    2017-09-18

    In the present investigation, the anti corrosive performance of synthesized Naphthalen-2-yl Naphthalene-2-Carboxammide (NNC) in 1 N HCl solution as corrosion inhibitor on carbon steel was studied at room temperature. Potentiodynamic polarization study revealed the mixed behavior of the inhibitor NNC along with inhibition efficiency. The inhibition efficiency of NNC increases with increasing inhibitor concentration. The electrochemical noise analysis (ENA) and electrochemical impedance spectroscopy (EIS) studies have showed that noise resistance (Rn) and charge transfer resistance (Rct) values were increased with addition of inhibitor concentrations. The synthesized and adsorbed bonds of inhibitor with the metal atom were characterized by ATR-FTIR spectroscopy. The adsorption isotherm explored that the adsorption of NNC obeyed Langmuir adsorption to bond with metal surface at carbon steel/HCl solution interface. The thermodynamic properties were calculated to discuss the adsorption mechanism of corrosion inhibition. Atomic force microscope (AFM) study showed a less corroded and roughness surface morphology, which is due to the formation of protective film layer on the surface. Quantum chemical parameters were calculated and correlated with respect to inhibitive performance of NNC. The study revealed that the adsorption nature of inhibitor has both physisorption and chemisorption phenomena. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Current status of poly(ADP-ribose polymerase inhibitors and future directions

    Directory of Open Access Journals (Sweden)

    Ohmoto A

    2017-10-01

    Full Text Available Akihiro Ohmoto,1 Shinichi Yachida1,2 1Laboratory of Clinical Genomics, National Cancer Center Research Institute, Tokyo, 2Department of Cancer Genome Informatics, Graduate School of Medicine, Faculty of Medicine, Osaka University, Osaka, Japan Abstract: Inhibitors of poly(ADP-ribose polymerases (PARPs, which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer. Clinical trials of various combinations of PARP inhibitors with cytotoxic or molecular-targeted agents are also underway. In particular, expanded applications of PARP inhibitors are anticipated following recent reports that defects in homologous recombination repair (HRR are associated with mutations in repair genes other than BRCA1/BRCA2, such as ATM, ATR, PALB2, RAD51, CHEK1 and CHEK2, as well as with epigenetic loss of BRCA1 function through promoter methylation or overexpression of the BRCA2-interacting transcriptional repressor EMSY. Current topics of interest include selection of the best agent in each clinical context, identification of new treatment targets for HRR-proficient cases, and development of PARP inhibitor-based regimens that are less toxic and that prolong overall survival as well as progression-free survival. In addition, potential long-term side effects and suitable biomarkers for predicting efficacy and mechanisms of clinical resistance are in discussion. This review summarizes representative preclinical and clinical data for PARP inhibitors and discusses

  5. [Acquired coagulant factor inhibitors].

    Science.gov (United States)

    Nogami, Keiji

    2015-02-01

    Acquired coagulation factor inhibitors are an autoimmune disease causing bleeding symptoms due to decreases in the corresponding factor (s) which result from the appearance of autoantibodies against coagulation factors (inhibitor). This disease is quite different from congenital coagulation factor deficiencies based on genetic abnormalities. In recent years, cases with this disease have been increasing, and most have anti-factor VIII autoantibodies. The breakdown of the immune control mechanism is speculated to cause this disease since it is common in the elderly, but the pathology and pathogenesis are presently unclear. We herein describe the pathology and pathogenesis of factor VIII and factor V inhibitors. Characterization of these inhibitors leads to further analysis of the coagulation process and the activation mechanisms of clotting factors. In the future, with the development of new clotting examination method (s), we anticipate that further novel findings will be obtained in this field through inhibitor analysis. In addition, detailed elucidation of the coagulation inhibitory mechanism possibly leading to hemostatic treatment strategies for acquired coagulation factor disorders will be developed.

  6. Cathepsin D inhibitors

    Directory of Open Access Journals (Sweden)

    M. Gacko

    2007-11-01

    Full Text Available Inhibitors of cathepsin D belong to chemical compounds that estrify carboxyl groups of the Asp33 and Asp231residues of its catalytic site, penta-peptides containing statin, i.e. the amino acid similar in structure to the tetraedric indirectproduct, and polypeptides found in the spare organs of many plants and forming permanent noncovalent complexes withcathepsin. Cathepsin D activity is also inhibited by alpha2-macroglobulin and antibodies directed against this enzyme.Methods used to determine the activity and concentration of these inhibitors and their analytical, preparative and therapeuticapplications are discussed.

  7. AGR-3/4 Data Qualification Report for ATR Cycles 151A, 151B, 152A, 152B, 154A, and 154B

    Energy Technology Data Exchange (ETDEWEB)

    Binh T. Pham

    2014-02-01

    This data report provides the qualification status of Advanced Gas Reactor-3/4 (AGR-3/4) fuel irradiation experimental data from Advanced Test Reactor (ATR) Cycles 151A, 151B, 152A, 152B, 154A, and 154B, as recorded in the Nuclear Data Management and Analysis System (NDMAS). Of these cycles, ATR Cycle 152A is a low power cycle that occurred when the ATR core was briefly at low power. The irradiation data are not used for physics and thermal calculation, but the qualification status of these cycle data is still covered in this report. On the other hand, during ATR Cycles 153A (unplanned Outage cycle) and 153B (Power Axial Locator Mechanism [PALM] cycle), the AGR-3/4 was pulled out from the ATR core and stored in the canal to avoid being overheated. Therefore, qualification of the AGR-3/4 irradiation data from these 2 cycles was excluded in this report. By the end of ATR Cycle 154B, AGR-3/4 was irradiated for a total of 264.1 effective full power days. The AGR-3/4 data streams addressed in this report include thermocouple (TC) temperatures, sweep gas data (flow rates, pressure, and moisture content), and Fission Product Monitoring System (FPMS) data (release rates and release-to-birth rate ratios [R/Bs]) for each of the twelve capsules in the AGR-3/4 experiment. The final data qualification status for these data streams is determined by a Data Review Committee (DRC) composed of AGR technical leads, Sitewide Quality Assurance (QA), and NDMAS analysts. The DRC convened on February 12, 2014, reviewed the data acquisition process, and considered whether the data met the requirements for data collection as specified in QA-approved Very High Temperature Reactor (VHTR) Technology Development Office (TDO) data collection plans. The DRC also examined the results of NDMAS data testing and statistical analyses, and confirmed the qualification status of the data as given in this report.

  8. Overview of aerosol properties associated with air masses sampled by the ATR-42 during the EUCAARI campaign (2008)

    Science.gov (United States)

    Crumeyrolle, S.; Schwarzenboeck, A.; Sellegri, K.; Burkhart, J. F.; Stohl, A.; Gomes, L.; Quennehen, B.; Roberts, G.; Weigel, R.; Roger, J. C.; Villani, P.; Pichon, J. M.; Bourrianne, T.; Laj, P.

    2012-04-01

    Within the frame of the European Aerosol Cloud Climate and Air Quality Interactions (EUCAARI) project the Météo-France aircraft ATR-42 performed 22 research flights, over central Europe and the North Sea during the intensive observation period in May 2008. For the campaign, the ATR-42 was equipped in order to study aerosol physical, chemical and optical properties, as well as cloud microphysics. During the campaign, continental air masses from Eastern and Western Europe were encountered, along with polar and Scandinavian air masses. For the 22 research flights, retroplume analyses along the flight tracks were performed with FLEXPART in order to classify air masses into five sectors of origin which allows for a qualitative evaluation of emission influence on the respective air parcel. In the polluted boundary layer (BL), typical concentrations of particles with diameters larger than 10 nm (N10) are of the order of 5000-6000 cm-3, whereas N10 concentrations of clean air masses were lower than 1300 cm-3. The detection of the largest particle number concentrations occurred in air masses coming from Polar and Scandinavian regions for which an elevated number of nucleation mode (25-28 nm) particles was observed and attributed to new particle formation over open sea. In the free troposphere (FT), typical observed N10 are of the order of 900 cm-3 in polluted air masses and 400-600 cm-3 in clean air masses, respectively. In both layers, the chemical composition of submicron aerosol particles is dominated by organic matter and nitrate in polluted air masses, while, sulphate and ammonium followed by organics dominate the submicron aerosols in clean air masses. The highest CCN/CN ratios were observed within the polar air masses while the CCN concentration values are the highest within the polluted air masses. Within the five air mass sectors defined and the two layers (BL and FT), observations have been distinguished into anticyclonic (first half of May 2008) and cyclonic

  9. Investigation of aged Asian dust particles by the combined use of quantitative ED-EPMA and ATR-FTIR imaging

    Directory of Open Access Journals (Sweden)

    Y.-C. Song

    2013-03-01

    Full Text Available In our previous works, it was demonstrated that the combined use of quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA, which is also known as low-Z particle EPMA, and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR imaging has great potential for a detailed characterization of individual aerosol particles. In this study, extensively chemically modified (aged individual Asian dust particles collected during an Asian dust storm event on 11 November 2002 in Korea were characterized by the combined use of low-Z particle EPMA and ATR-FTIR imaging. Overall, 109 individual particles were classified into four particle types based on their morphology, elemental concentrations, and molecular species and/or functional groups of individual particles available from the two analytical techniques: Ca-containing (38%, NaNO3-containing (30%, silicate (22%, and miscellaneous particles (10%. Among the 41 Ca-containing particles, 10, 8, and 14 particles contained nitrate, sulfate, and both, respectively, whereas only two particles contained unreacted CaCO3. Airborne amorphous calcium carbonate (ACC particles were observed in this Asian dust sample for the first time, where their IR peaks for the insufficient symmetric environment of CO32− ions of ACC were clearly differentiated from those of crystalline CaCO3. This paper also reports the first inland field observation of CaCl2 particles probably converted from CaCO3 through the reaction with HCl(g. HCl(g was likely released from the reaction of sea salt with NOx/HNO3, as all 33 particles of marine origin contained NaNO3 (no genuine sea salt particle was encountered. Some silicate particles with minor amounts of calcium were observed to be mixed with nitrate, sulfate, and water. Among 24 silicate particles, 10 particles are mixed with water, the presence of which could facilitate atmospheric heterogeneous reactions of silicate particles including swelling

  10. Gli1 protein regulates the S-phase checkpoint in tumor cells via Bid protein, and its inhibition sensitizes to DNA topoisomerase 1 inhibitors.

    Science.gov (United States)

    Tripathi, Kaushlendra; Mani, Chinnadurai; Barnett, Reagan; Nalluri, Sriram; Bachaboina, Lavanya; Rocconi, Rodney P; Athar, Mohammed; Owen, Laurie B; Palle, Komaraiah

    2014-11-07

    Aberrant expression of hedgehog molecules, particularly Gli1, is common in cancers of many tissues and is responsible for their aggressive behavior and chemoresistance. Here we demonstrate a novel and tumor-specific role for aberrant Gli1 in the regulation of the S-phase checkpoint that suppresses replication stress and resistance to chemotherapy. Inhibition of Gli1 in tumor cells induced replication stress-mediated DNA damage response, attenuated their clonogenic potential, abrogated camptothecin (CPT)-induced Chk1 phosphorylation, and potentiated its cytotoxicity. However, in normal fibroblasts, Gli1 siRNAs showed no significant changes in CPT-induced Chk1 phosphorylation. Further analysis of ataxia telangiectasia and Rad3-related protein (ATR)/Chk1 signaling cascade genes in tumor cells revealed an unexpected mechanism whereby Gli1 regulates ATR-mediated Chk1 phosphorylation by transcriptional regulation of the BH3-only protein Bid. Consistent with its role in DNA damage response, Bid down-regulation in tumor cells abolished CPT-induced Chk1 phosphorylation and sensitized them to CPT. Correspondingly, Gli1 inhibition affected the expression of Bid and the association of replication protein A (RPA) with the ATR- interacting protein (ATRIP)-ATR complex, and this compromised the S-phase checkpoint. Conversely, complementation of Bid in Gli1-deficient cells restored CPT-induced Chk1 phosphorylation. An in silico analysis of the Bid promoter identified a putative Gli1 binding site, and further studies using luciferase reporter assays confirmed Gli1-dependent promoter activity. Collectively, our studies established a novel connection between aberrant Gli1 and Bid in the survival of tumor cells and their response to chemotherapy, at least in part, by regulating the S-phase checkpoint. Importantly, our data suggest a novel drug combination of Gli1 and Top1 inhibitors as an effective therapeutic strategy in treating tumors that expresses Gli1. © 2014 by The American

  11. Gli1 Protein Regulates the S-phase Checkpoint in Tumor Cells via Bid Protein, and Its Inhibition Sensitizes to DNA Topoisomerase 1 Inhibitors*

    Science.gov (United States)

    Tripathi, Kaushlendra; Mani, Chinnadurai; Barnett, Reagan; Nalluri, Sriram; Bachaboina, Lavanya; Rocconi, Rodney P.; Athar, Mohammed; Owen, Laurie B.; Palle, Komaraiah

    2014-01-01

    Aberrant expression of hedgehog molecules, particularly Gli1, is common in cancers of many tissues and is responsible for their aggressive behavior and chemoresistance. Here we demonstrate a novel and tumor-specific role for aberrant Gli1 in the regulation of the S-phase checkpoint that suppresses replication stress and resistance to chemotherapy. Inhibition of Gli1 in tumor cells induced replication stress-mediated DNA damage response, attenuated their clonogenic potential, abrogated camptothecin (CPT)-induced Chk1 phosphorylation, and potentiated its cytotoxicity. However, in normal fibroblasts, Gli1 siRNAs showed no significant changes in CPT-induced Chk1 phosphorylation. Further analysis of ataxia telangiectasia and Rad3-related protein (ATR)/Chk1 signaling cascade genes in tumor cells revealed an unexpected mechanism whereby Gli1 regulates ATR-mediated Chk1 phosphorylation by transcriptional regulation of the BH3-only protein Bid. Consistent with its role in DNA damage response, Bid down-regulation in tumor cells abolished CPT-induced Chk1 phosphorylation and sensitized them to CPT. Correspondingly, Gli1 inhibition affected the expression of Bid and the association of replication protein A (RPA) with the ATR- interacting protein (ATRIP)-ATR complex, and this compromised the S-phase checkpoint. Conversely, complementation of Bid in Gli1-deficient cells restored CPT-induced Chk1 phosphorylation. An in silico analysis of the Bid promoter identified a putative Gli1 binding site, and further studies using luciferase reporter assays confirmed Gli1-dependent promoter activity. Collectively, our studies established a novel connection between aberrant Gli1 and Bid in the survival of tumor cells and their response to chemotherapy, at least in part, by regulating the S-phase checkpoint. Importantly, our data suggest a novel drug combination of Gli1 and Top1 inhibitors as an effective therapeutic strategy in treating tumors that expresses Gli1. PMID:25253693

  12. Inhibitors of histone demethylases

    DEFF Research Database (Denmark)

    Lohse, Brian; Kristensen, Jesper L; Kristensen, Line H

    2011-01-01

    Methylated lysines are important epigenetic marks. The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression. Despite the relative recent discovery of these enzymes a number of inhibitors have already appeared. Most of the i...

  13. Protease inhibitors and beyond.

    Science.gov (United States)

    1997-03-01

    A new generation of protease inhibitors is entering studies. Abbott Lab's ABT-378 and Pharmacia/Upjohn's PNU-140690 are beginning clinical studies and both are designed to overcome resistance problems. Several companies are developing new compounds to inhibit reverse transcriptase, such as Bristol-Myers Squibb's lobucavir and Hoechst/Bayer's HBY097. Calanolide A, which will soon begin trials, has a different resistance pattern than other non-nucleoside reverse transcriptase inhibitors, which may be an important advantage. Several groups are developing compounds to inhibit the HIV zinc finger, such as Parke-Davis' compound, CI-1012; and a Dutch company who is developing Azodicarbonamide, a drug currently in phase I/II trials for people with advanced disease in Europe. HIV drugs to date have not been successful in blocking viral fusion. However, three new fusion inhibitors are showing promise within the laboratory: Pentafuside (currently in phase I trials), Fuji ImmunoPharmaceuticals' FP-21399 (currently in phase I trials), and ISIS Pharmaceuticals' ISIS 5320. A new class of drugs known as integrase inhibitors has been of interest to pharmaceutical companies for the past several years; only one drug, Aronex Pharmaceuticals' Zintevir, has reached phase I/II trials.

  14. Transglutaminase inhibitor from milk

    NARCIS (Netherlands)

    Jong, G.A.H. de; Wijngaards, G.; Koppelman, S.J.

    2003-01-01

    Cross-linking experiments of skimmed bovine milk with bacterial transglutaminase isolated from Streptoverticillium mobaraense showed only some degree of formation of high-molecular-weight casein polymers. Studies on the nature of this phenomenon revealed that bovine milk contains an inhibitor of

  15. HIV protease inhibitor resistance

    NARCIS (Netherlands)

    Wensing, Annemarie M.J.; Fun, Axel; Nijhuis, Monique

    2017-01-01

    HIV protease is pivotal in the viral replication cycle and directs the formation of mature infectious virus particles. The development of highly specific HIV protease inhibitors (PIs), based on thorough understanding of the structure of HIV protease and its substrate, serves as a prime example of

  16. Phosphodiesterase 4 inhibitors.

    Science.gov (United States)

    Zebda, Rema; Paller, Amy S

    2018-03-01

    Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US Food and Drug Administration-approved for children older than 2 years and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety. Copyright © 2017. Published by Elsevier Inc.

  17. Proton-pump inhibitors

    African Journals Online (AJOL)

    Proton-pump inhibitors (PPIs) work by binding irreversibly to the. H+/K+-ATPase pump of the parietal cell, leading to inhibition of acid production in approximately 70% of active pumps.1The result is a dramatic increase in gastric pH mitigating the deleterious effects of acid in gastro-oesophageal reflux disease (GORD) and.

  18. Role of Bi promotion and solvent in platinum-catalyzed alcohol oxidation probed by in situ X-ray absorption and ATR-IR spectroscopy

    DEFF Research Database (Denmark)

    Mondelli, C.; Grunwaldt, Jan-Dierk; Ferri, D.

    2010-01-01

    the catalysts under working conditions using in situ X-ray absorption spectroscopy (XAS) and attenuated total reflection infrared spectroscopy (ATR-IR), aiming at uncovering the roles of the metal promoter and the reaction medium. XAS confirms that Bi is oxidized more easily than Pt, maintaining the catalytic....... This behaviour is not observed in the presence of Bi, whose geometric effect (site blocking) is interpreted as additionally limiting the adsorption of toluene and the premature deactivation of Pt. ATR-IR spectroscopy during CO adsorption on Pt and during reaction indicates that Bi is located rather on extended...... surfaces than on step or kink sites. Side products, CO and benzoate species, appearing during the reaction reveal that the geometric suppression of undesired reactions does not occur to the same extent on Pt-based catalysts as on Pd, suggesting that decarbonylation of the produced aldehyde on Pt may occur...

  19. In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing.

    Science.gov (United States)

    Wan, Boyong; Zordan, Christopher A; Lu, Xujin; McGeorge, Gary

    2016-10-01

    Complete dissolution of the active pharmaceutical ingredient (API) is critical in the manufacturing of liquid-filled soft-gelatin capsules (SGC). Attenuated total reflectance UV spectroscopy (ATR-UV) and Raman spectroscopy have been investigated for in-line monitoring of API dissolution during manufacturing of an SGC product. Calibration models have been developed with both techniques for in-line determination of API potency. Performance of both techniques was evaluated and compared. The ATR-UV methodology was found to be able to monitor the dissolution process and determine the endpoint, but was sensitive to temperature variations. The Raman technique was also capable of effectively monitoring the process and was more robust to the temperature variation and process perturbations by using an excipient peak for internal correction. Different data preprocessing methodologies were explored in an attempt to improve method performance.

  20. Understanding the Crystallinity Indices Behavior of Burned Bones and Teeth by ATR-IR and XRD in the Presence of Bioapatite Mixed with Other Phosphate and Carbonate Phases

    Directory of Open Access Journals (Sweden)

    Giampaolo Piga

    2016-01-01

    Full Text Available We have critically investigated the ATR-IR spectroscopy data behavior of burned human teeth as opposed to the generally observed behavior in human bones that were subjected to heat treatment, whether deliberate or accidental. It is shown that the deterioration of the crystallinity index (CI behavior sometimes observed in bones subjected to high temperature appears to be of higher frequency in the case of bioapatite from teeth. This occurs because the formation of the β-tricalcium phosphate (β-TCP phase, otherwise known as whitlockite, clearly ascertained by the X-ray diffraction (XRD patterns collected on the same powdered specimens investigated by ATR-IR. These results point to the need of combining more than one physicochemical technique even if apparently well suitable, in order to verify whether the assumed conditions assessed by spectroscopy are fully maintained in the specimens after temperature and/or mechanical processing.

  1. Current status of poly(ADP-ribose) polymerase inhibitors and future directions.

    Science.gov (United States)

    Ohmoto, Akihiro; Yachida, Shinichi

    2017-01-01

    Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer. Clinical trials of various combinations of PARP inhibitors with cytotoxic or molecular-targeted agents are also underway. In particular, expanded applications of PARP inhibitors are anticipated following recent reports that defects in homologous recombination repair (HRR) are associated with mutations in repair genes other than BRCA1/BRCA2, such as ATM, ATR, PALB2, RAD51, CHEK1 and CHEK2, as well as with epigenetic loss of BRCA1 function through promoter methylation or overexpression of the BRCA2-interacting transcriptional repressor EMSY. Current topics of interest include selection of the best agent in each clinical context, identification of new treatment targets for HRR-proficient cases, and development of PARP inhibitor-based regimens that are less toxic and that prolong overall survival as well as progression-free survival. In addition, potential long-term side effects and suitable biomarkers for predicting efficacy and mechanisms of clinical resistance are in discussion. This review summarizes representative preclinical and clinical data for PARP inhibitors and discusses their potential for future applications to treat various malignancies.

  2. A Feasibility Study to Determine Cooling Time and Burnup of ATR Fuel Using a Nondestructive Technique and Three Types of Gamma-ray Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Jorge Navarro; Rahmat Aryaeinejad,; David W. Nigg

    2011-05-01

    A Feasibility Study to Determine Cooling Time and Burnup of ATR Fuel Using a Nondestructive Technique1 Rahmat Aryaeinejad, Jorge Navarro, and David W Nigg Idaho National Laboratory Abstract Effective and efficient Advanced Test Reactor (ATR) fuel management require state of the art core modeling tools. These new tools will need isotopic and burnup validation data before they are put into production. To create isotopic, burn up validation libraries and to determine the setup for permanent fuel scanner system a feasibility study was perform. The study consisted in measuring short and long cooling time fuel elements at the ATR canal. Three gamma spectroscopy detectors (HPGe, LaBr3, and HPXe) and two system configurations (above and under water) were used in the feasibility study. The first stage of the study was to investigate which detector and system configuration would be better suited for different scenarios. The second stage of the feasibility study was to create burnup and cooling time calibrations using experimental isotopic data collected and ORIGEN 2.2 burnup data. The results of the study establish that a better spectra resolution is achieve with an above the water configuration and that three detectors can be used in the permanent fuel scanner system for different situations. In addition it was conclude that a number of isotopic ratios and absolute measurements could be used to predict ATR fuel burnup and cooling times. 1This work was supported by the U.S. Depart¬ment of Energy (DOE) under Battelle Energy Alliance, LLC Contract No. DE-AC07-05ID14517.

  3. Bacterial and abiotic decay in waterlogged archaeological Picea abies (L.) Karst studied by confocal Raman imaging and ATR-FTIR spectroscopy

    DEFF Research Database (Denmark)

    Pedersen, Nanna Bjerregaard; Gierlinger, Notburga; Thygesen, Lisbeth Garbrecht

    2015-01-01

    Waterlogged archaeological Norway spruce [Picea abies (L.) Karst] poles were studied by means of confocal Raman imaging (CRI) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) analysis to determine lignin and polysaccharide composition and distribution in the cell...... wall. The waterlogged archaeological wood (WAW) was submerged under anoxic conditions for approximately 400 years and solely decayed by erosion bacteria (EB). CRI showed that decayed tracheids contain a residual material (RM) with heterogeneous lignin distribution; within the same tracheid RM often...

  4. Evaluation of Salmon Adhesion on PET-Metal Interface by ATR, FT-IR, and Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    E. Zumelzu

    2015-01-01

    Full Text Available The material employed in this study is an ecoefficient, environmentally friendly, chromium (VI-free (noncarcinogenic metal polymer. The originality of the research lies in the study of the effect of new production procedures of salmon on metal packaging with multilayer polyethylene terephthalate (PET polymer coatings. Our hypothesis states that the adhesion of postmortem salmon muscles to the PET polymer coating produces surface and structural changes that affect the functionality and limit the useful life of metal containers, compromising therefore their recycling capacity as ecomaterials. This work is focused on studying the effects of the biochemical changes of postmortem salmon on the PET coating and how muscle degradation favors adhesion to the container. The experimental design considered a series of laboratory tests of containers simulating the conditions of canned salmon, chemical and physical tests of food-contact canning to evaluate the adhesion, and characterization of changes in the multilayer PET polymer by electron microscopy, ATR, FT-IR, and Raman spectroscopy analyses. The analyses determined the effect of heat treatment of containers on the loss of freshness of canned fish and the increased adhesion to the container wall, and the limited capability of the urea treatment to remove salmon muscle from the container for recycling purposes.

  5. Colloidal carriers of isotretinoin for topical acne treatment: skin uptake, ATR-FTIR and in vitro cytotoxicity studies.

    Science.gov (United States)

    Gürbüz, Aslı; Özhan, Gül; Güngör, Sevgi; Erdal, M Sedef

    2015-09-01

    Acne vulgaris is the chronical, multifactorial and complex disease of the pilosebaceous unit in the skin. The main goal of the topical therapy in acne is to target the drug to epidermal and deep dermal regions by minimizing systemic absorption . Isotretinoin, a retinoic acid derivative, is the most effective drug in acne pathogenesis. Because systemic treatment may cause many side effects, topical isotretinoin treatment is an option in the management of acne. However, due to its high lipophilic character, isotretinoin tends to accumulate in the upper stratum corneum, thus its penetration into the lower layers is limited, which restricts the efficiency of topical treatment. Microemulsions are fluid, isotropic, colloidal drug carriers that have been widely studied as drug delivery systems. The percutaneous transport of active agents can be enhanced by microemulsions when compared with their conventional formulations. The purpose of this study was to evaluate microemulsions as alternative topical carriers for isotretinoin with an objective to improve its skin uptake. After in vitro permeation studies, the dermal penetration of isotretinoin from microemulsions was investigated by tape stripping procedure. Confocal laser scanning microscopy provided insight about the localization of the drug in the skin. The interaction between the microemulsion components and stratum corneum lipids is studied by ATR-FTIR spectroscopy. The relative safety of the microemulsions was assessed in mouse embryonic fibroblasts using MTT viability test. The results indicate that microemulsion-based novel colloidal carriers have a potential for enhanced skin delivery and localization of isotretinoin.

  6. Determination of surface concentrations of individual molecule-layers used in nanoscale biosensors by in situ ATR-FTIR spectroscopy

    KAUST Repository

    Punzet, Manuel

    2012-01-01

    For the development of nanowire sensors for chemical and medical detection purposes, the optimal functionalization of the surface is a mandatory component. Quantitative ATR-FTIR spectroscopy was used in situ to investigate the step-by-step layer formation of typical functionalization protocols and to determine the respective molecule surface concentrations. BSA, anti-TNF-α and anti-PSA antibodies were bound via 3-(trimethoxy)butylsilyl aldehyde linkers to silicon-oxide surfaces in order to investigate surface functionalization of nanowires. Maximum determined surface concentrations were 7.17 × 10 -13 mol cm -2 for BSA, 1.7 × 10 -13 mol cm -2 for anti-TNF-α antibody, 6.1 × 10 -13 mol cm -2 for anti-PSA antibody, 3.88 × 10 -13 mol cm -2 for TNF-α and 7.0 × 10 -13 mol cm -2 for PSA. Furthermore we performed antibody-antigen binding experiments and determined the specific binding ratios. The maximum possible ratio of 2 was obtained at bulk concentrations of the antigen in the μg ml -1 range for TNF-α and PSA. © 2012 The Royal Society of Chemistry.

  7. Application of FTIR-ATR to Moscatel dessert wines for prediction of total phenolic and flavonoid contents and antioxidant capacity.

    Science.gov (United States)

    Silva, Sandra D; Feliciano, Rodrigo P; Boas, Luís V; Bronze, Maria R

    2014-05-01

    Fourier transform infrared spectroscopy (FTIR) attenuated total reflectance (ATR) was applied for the determination of total phenolic and flavonoid contents and antioxidant capacity (DPPH and FRAP assays) in Moscatel dessert wines (n=56). Prediction models were developed for the referred parameters using Partial Least Squares (PLS) considering the spectral region 1800-900cm(-1). The determination coefficients (r(2)) values in the calibration models ranged from 0.670 to 0.870. Cross validation (leave-one-out technique) was applied to the data. Root mean square errors of calibration (RMSEC) and cross validation (RMSECV) as well as the relative errors of prediction (REP) were calculated. Minimum errors of prediction were obtained for total flavonoid content (0.2%) and maximum values (22%) for antioxidant capacity measured by FRAP. The proposed method may be used for rapid screening of total phenolic and flavonoid contents in Moscatel dessert wines. The implemented methodologies may also be used to get rough estimates for DPPH and FRAP antioxidant capacities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Perfluoroalkylated Substance Effects in Xenopus laevis A6 Kidney Epithelial Cells Determined by ATR-FTIR Spectroscopy and Chemometric Analysis

    Science.gov (United States)

    2016-01-01

    The effects of four perfluoroalkylated substances (PFASs), namely, perfluorobutanesulfonate (PFBS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), and perfluorononanoic acid (PFNA) were assessed in Xenopus laevis A6 kidney epithelial cells by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and chemometric analysis. Principal component analysis–linear discriminant analysis (PCA-LDA) was used to visualize wavenumber-related alterations and ANOVA-simultaneous component analysis (ASCA) allowed data processing considering the underlying experimental design. Both analyses evidenced a higher impact of low-dose PFAS-treatments (10–9 M) on A6 cells forming monolayers, while there was a larger influence of high-dose PFAS-treatments (10–5 M) on A6 cells differentiated into dome structures. The observed dose–response PFAS-induced effects were to some extent related to their cytotoxicity: the EC50-values of most influential PFAS-treatments increased (PFOS < PFNA < PFOA ≪ PFBS), and higher-doses of these chemicals induced a larger impact. Major spectral alterations were mainly attributed to DNA/RNA, secondary protein structure, lipids, and fatty acids. Finally, PFOS and PFOA caused a decrease in A6 cell numbers compared to controls, whereas PFBS and PFNA did not significantly change cell population levels. Overall, this work highlights the ability of PFASs to alter A6 cells, whether forming monolayers or differentiated into dome structures, and the potential of PFOS and PFOA to induce cell death. PMID:27078751

  9. Total sulfur determination in residues of crude oil distillation using FT-IR/ATR and variable selection methods.

    Science.gov (United States)

    Müller, Aline Lima Hermes; Picoloto, Rochele Sogari; de Azevedo Mello, Paola; Ferrão, Marco Flores; de Fátima Pereira dos Santos, Maria; Guimarães, Regina Célia Lourenço; Müller, Edson Irineu; Flores, Erico Marlon Moraes

    2012-04-01

    Total sulfur concentration was determined in atmospheric residue (AR) and vacuum residue (VR) samples obtained from petroleum distillation process by Fourier transform infrared spectroscopy with attenuated total reflectance (FT-IR/ATR) in association with chemometric methods. Calibration and prediction set consisted of 40 and 20 samples, respectively. Calibration models were developed using two variable selection models: interval partial least squares (iPLS) and synergy interval partial least squares (siPLS). Different treatments and pre-processing steps were also evaluated for the development of models. The pre-treatment based on multiplicative scatter correction (MSC) and the mean centered data were selected for models construction. The use of siPLS as variable selection method provided a model with root mean square error of prediction (RMSEP) values significantly better than those obtained by PLS model using all variables. The best model was obtained using siPLS algorithm with spectra divided in 20 intervals and combinations of 3 intervals (911-824, 823-736 and 737-650 cm(-1)). This model produced a RMSECV of 400 mg kg(-1) S and RMSEP of 420 mg kg(-1) S, showing a correlation coefficient of 0.990. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. FT-IR/ATR univariate and multivariate calibration models for in situ monitoring of sugars in complex microalgal culture media.

    Science.gov (United States)

    Girard, Jean-Michel; Deschênes, Jean-Sébastien; Tremblay, Réjean; Gagnon, Jonathan

    2013-09-01

    The objective of this work is to develop a quick and simple method for the in situ monitoring of sugars in biological cultures. A new technology based on Attenuated Total Reflectance-Fourier Transform Infrared (FT-IR/ATR) spectroscopy in combination with an external light guiding fiber probe was tested, first to build predictive models from solutions of pure sugars, and secondly to use those models to monitor the sugars in the complex culture medium of mixotrophic microalgae. Quantification results from the univariate model were correlated with the total dissolved solids content (R(2)=0.74). A vector normalized multivariate model was used to proportionally quantify the different sugars present in the complex culture medium and showed a predictive accuracy of >90% for sugars representing >20% of the total. This method offers an alternative to conventional sugar monitoring assays and could be used at-line or on-line in commercial scale production systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Development of an LS-DYNA Model of an ATR42-300 Aircraft for Crash Simulation

    Science.gov (United States)

    Jackson, Karen E.; Fasanella, Edwin L.

    2004-01-01

    This paper describes the development of an LS-DYNA simulation of a vertical drop test of an ATR42-300 twin-turboprop high-wing commuter-class airplane. A 30-ft/s drop test of this aircraft was performed onto a concrete impact surface at the FAA Technical Center on July 30, 2003. The purpose of the test was to evaluate the structural response of a commuter-class aircraft when subjected to a severe, but survivable, impact. The aircraft was configured with crew and passenger seats, anthropomorphic test dummies, forward and aft luggage, instrumentation, and onboard data acquisition systems. The wings were filled with approximately 8,700 lb. of water to represent the fuel and the aircraft weighed a total of 33,200 lb. The model, which consisted of 57,643 nodes and 62,979 elements, was developed from direct measurements of the airframe geometry, over a period of approximately 8 months. The seats, dummies, luggage, fuel, and other ballast were represented using concentrated masses. Comparisons were made of the structural deformation and failure behavior of the airframe, as well as selected acceleration time history responses.

  12. UV-vis and FTIR-ATR characterization of 9-fluorenon-2-carboxyester/(2-hydroxypropyl)-beta-cyclodextrin inclusion complex.

    Science.gov (United States)

    Stancanelli, R; Ficarra, R; Cannavà, C; Guardo, M; Calabrò, M L; Ficarra, P; Ottanà, R; Maccari, R; Crupi, V; Majolino, D; Venuti, V

    2008-08-05

    In this work, the usefulness of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) as a tool to form an inclusion complex with 9-fluorenonic derivative (AG11) has been investigated, in pure water, by UV absorption. Phase-solubility diagrams allowed the determination of the association constant between AG11 and HP-beta-CyD. At the same time, solid binary systems between AG11 and HP-beta-CyD have been prepared in 1:1 stoichiometry by co-precipitation method. In order to confirm the complexation, FTIR spectroscopy in ATR geometry measurements have been performed and the results have been compared with the free compounds and the corresponding physical mixture in the same molar ratio. The nature of the interactions between AG11 and HP-beta-CyD has been elucidated also by applying mathematical procedures such as deconvolution and curve fitting. Improvement of the aqueous solubility is expected to improve the bioavailability of the drug in oral administration.

  13. Raman and ATR FTIR spectroscopy in reactive crystallization: Simultaneous monitoring of solute concentration and polymorphic state of the crystals

    Science.gov (United States)

    Qu, Haiyan; Alatalo, Hannu; Hatakka, Henry; Kohonen, Jarno; Louhi-Kultanen, Marjatta; Reinikainen, Satu-Pia; Kallas, Juha

    2009-06-01

    Batch-reactive crystallization of the two polymorphs of L-glutamic acid was studied using in-line Raman and ATR FTIR spectroscopy. It was observed that the barrier to the nucleation of the stable β-form was higher, and thus the occurrence of β-form nucleation requires a higher supersaturation level. The local supersaturation level inside the reactive crystallizer is significantly affected by the feeding manner of the reactant. When the reactant was fed to a poorly mixed zone, such as the surface of the liquid, a high local supersaturation level was generated near the feeding point. This high local supersaturation level drastically increased with the increase in the concentrations of the reactants. As a consequence, the fraction of the β-form increased with the increase in reactants concentrations. On the other hand, feeding the reactant to a well-mixed zone near the impeller can avoid the occurrence of high local supersaturation, and therefore the dependence of the polymorphic composition of the final product on the concentration of the reactants can be reduced. The information obtained from the spectroscopy leads to improved understanding of the precipitation process and offers great potential for process optimization and control of crystalline quality.

  14. The Dimeric Architecture of Checkpoint Kinases Mec1ATR and Tel1ATM Reveal a Common Structural Organization.

    Science.gov (United States)

    Sawicka, Marta; Wanrooij, Paulina H; Darbari, Vidya C; Tannous, Elias; Hailemariam, Sarem; Bose, Daniel; Makarova, Alena V; Burgers, Peter M; Zhang, Xiaodong

    2016-06-24

    The phosphatidylinositol 3-kinase-related protein kinases are key regulators controlling a wide range of cellular events. The yeast Tel1 and Mec1·Ddc2 complex (ATM and ATR-ATRIP in humans) play pivotal roles in DNA replication, DNA damage signaling, and repair. Here, we present the first structural insight for dimers of Mec1·Ddc2 and Tel1 using single-particle electron microscopy. Both kinases reveal a head to head dimer with one major dimeric interface through the N-terminal HEAT (named after Huntingtin, elongation factor 3, protein phosphatase 2A, and yeast kinase TOR1) repeat. Their dimeric interface is significantly distinct from the interface of mTOR complex 1 dimer, which oligomerizes through two spatially separate interfaces. We also observe different structural organizations of kinase domains of Mec1 and Tel1. The kinase domains in the Mec1·Ddc2 dimer are located in close proximity to each other. However, in the Tel1 dimer they are fully separated, providing potential access of substrates to this kinase, even in its dimeric form. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. The Dimeric Architecture of Checkpoint Kinases Mec1ATR and Tel1ATM Reveal a Common Structural Organization*

    Science.gov (United States)

    Sawicka, Marta; Wanrooij, Paulina H.; Darbari, Vidya C.; Tannous, Elias; Hailemariam, Sarem; Bose, Daniel; Makarova, Alena V.; Burgers, Peter M.; Zhang, Xiaodong

    2016-01-01

    The phosphatidylinositol 3-kinase-related protein kinases are key regulators controlling a wide range of cellular events. The yeast Tel1 and Mec1·Ddc2 complex (ATM and ATR-ATRIP in humans) play pivotal roles in DNA replication, DNA damage signaling, and repair. Here, we present the first structural insight for dimers of Mec1·Ddc2 and Tel1 using single-particle electron microscopy. Both kinases reveal a head to head dimer with one major dimeric interface through the N-terminal HEAT (named after Huntingtin, elongation factor 3, protein phosphatase 2A, and yeast kinase TOR1) repeat. Their dimeric interface is significantly distinct from the interface of mTOR complex 1 dimer, which oligomerizes through two spatially separate interfaces. We also observe different structural organizations of kinase domains of Mec1 and Tel1. The kinase domains in the Mec1·Ddc2 dimer are located in close proximity to each other. However, in the Tel1 dimer they are fully separated, providing potential access of substrates to this kinase, even in its dimeric form. PMID:27129217

  16. The Conference Proceedings of the 2001 Air Transport Research Society (ATRS) of the WCTR Society. Volume 2

    Science.gov (United States)

    Lee, Yeong-Heok (Editor); Bowen, Brent D. (Editor); Tarry, Scott E. (Editor)

    2001-01-01

    The ATRS held its 5th Annual conference at the City University of Hong Kong Campus in July 2001. The conference was a success with nearly 140 participants including 70 presenters. Titles that comprise Volume 2 include: Intelligent Airport Gate Assignment System; A Study on the Effects of the Personality Compatibility to the Job Performance; ITS/CVO Application for Air cargo Transportation in Korea; An Airport as a Logistics and Economic Hub: The Case of Incheon International Airport; The Impact Of Aviation Safety over the Consumer's Behavior; The Integration of China and Taiwan Air Networks for Direct Air Cargo Services; Quality perception and carrier choice in Civil Aviation; Future Trends in Business Travel Decision Making; Cooperation Among German Airports in Europe; Inbound and Outbound Air Passenger Traffic Forecasting between the United States and Selected Asian countries; An Evaluation of Alternative Facilities for Airport Redevelopment using Fuzzy Linguistic Approach; Economic Analysis of Airline Alliances; The Aviation Cooperation between the two Koreas Preparing for the Reunification of the Peninsula; and A Study on the Air Transport Cooperation in Northeast Asia between China, Japan and Korea.

  17. In situ monitoring of an escherichia coli fermentation using a diamond composition ATR probe and mid-infrared spectroscopy

    Science.gov (United States)

    Doak; Phillips

    1999-05-01

    A diamond composition ATR probe was used in situ to obtain IR spectra on replicate Escherichia coli fermentations involving a complex medium. The probe showed excellent stability over a 6-month operating period and was unaffected by either agitation or aeration. The formation of an unknown was observed from IR spectra obtained during the sterilization; subsequent experiments proved this to be a reaction product between yeast extract and the phosphates used as buffer salts. Partial-least-squares-based calibration/prediction models were developed for both glucose and acetate using in-process samples. The resulting models had prediction errors of +/-0.26 and +/-0.75 g/L for glucose and acetic acid, respectively, errors which were statistically equivalent to the estimated experimental errors in the reference measurements. Relative concentration profiles for the unknown formed during sterilization could be generated either by tracking peak height at an independent wavelength or by self-modeling curve resolution of the spectral region overlapping that of glucose. These profiles indicated that this compound was metabolized simultaneously with glucose; upon depletion of the glucose, when the microorganism switched to consumption of acetic acid, utilization continued but at a lower rate. The data presented provide an extensive characterization of the performance characteristics of this in situ analysis and clearly demonstrate its utility not just in the quantitative measurement of multiple known species but in the qualitative evaluation of unknown species.

  18. ;Host-guest; interactions in Captisol®/Coumestrol inclusion complex: UV-vis, FTIR-ATR and Raman studies

    Science.gov (United States)

    Venuti, Valentina; Stancanelli, Rosanna; Acri, Giuseppe; Crupi, Vincenza; Paladini, Giuseppe; Testagrossa, Barbara; Tommasini, Silvana; Ventura, Cinzia Anna; Majolino, Domenico

    2017-10-01

    The ability of Captisol® (sulphobutylether-β-cyclodextrin, SBE-β-CD), to form inclusion complexes, both in solution and in the solid state, has been tested in order to improve some unfavorable chemical-physical characteristics, such as poor solubility in water, of a bioflavonoid, Coumestrol (Coum), well known for its anti-oxidant, anti-inflammatory, anti-fungal and anti-viral activity. In pure water, a phase-solubility study was carried out to evaluate the enhancement of the solubility of Coum and, therefore, the occurred complexation with the macrocycle. The stoichiometry and the stability constant of the SBE-β-CD/Coum complex were calculated with the phase solubility method and through the Job's plot. After that, the solid SBE-β-CD/Coum complex was prepared utilizing a kneading method. The spectral changes induced by complexation on characteristic vibrational band of Coum were complementary investigated by Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) and Raman spectroscopy, putting into evidence the guest chemical groups involved in the ;host-guest; interactions responsible of the formation and stabilization of the complex. Particular attention was paid to the Cdbnd O and Osbnd H stretching vibrations, whose temperature-evolution respectively furnished the enthalpy changes associated to the binding of host and guest in solid phase and to the reorganization of the hydrogen bond scheme upon complexation. From the whole set of results, an inclusion geometry is also proposed.

  19. Adsorption/oxidation of CO on highly dispersed Pt catalyst studied by combined electrochemical and ATR-FTIRAS methods

    Energy Technology Data Exchange (ETDEWEB)

    Sato, T.; Kunimatsu, K. [Clean Energy Research Center, University of Yamanashi, 4 Takeda, Kofu 400-8510 (Japan); Uchida, H. [Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4 Takeda, Kofu 400-8510 (Japan); Watanabe, M. [Clean Energy Research Center, University of Yamanashi, 4 Takeda, Kofu 400-8510 (Japan)], E-mail: m-watanabe@yamanashi.ac.jp

    2007-12-20

    Elecrochemical ATR-FTIRAS measurements were conducted for the first time to investigate nature of CO adsorbed under potential control on a highly dispersed Pt catalyst with average particle size of 2.6 nm supported on carbon black (Pt/C) and carbon un-supported Pt black catalyst (Pt-B). Each catalyst was uniformly dispersed by 10 {mu}g Pt/cm{sup 2} and fixed by Nafion film of 0.05 {mu}m thick on a gold film chemically deposited on a Si ATR prism window. Adsorption of CO was conducted at 0.05 V on the catalysts in 1 and 100% CO atmospheres, for which CO coverage, {theta}{sub CO}, was 0.69 and 1, respectively. Two well-defined {nu}(CO) bands free from band anomalies assigned to atop CO (CO(L)) and symmetrically bridge bonded CO (CO(B){sub sym.}) were observed. It was newly found that the CO(L) band was spitted into two well-defined peaks, particularly in 1% CO, from very early stage of adsorption, which was interpreted in terms of simultaneous occupation of terrace and step-edge sites, denoted as CO(L){sub terrace} and CO(L){sub edge}, respectively. This simultaneous occupation was commonly observed in our work both on Pt/C and Pt-B. A new band was also observed around 1950 cm{sup -1} in addition to the bands of CO(L) and CO(B){sub sym.}, which was assigned to asymmetric bridge CO, CO(B){sub asym.}, adsorbed on (1 0 0) terraces, based on our previous ECSTM observation of CO adsorption structures on (1 0 0) facet. The CO(B){sub asym.} on the Pt/C, particularly in 100% CO atmosphere, results in growth of a sharp band at 3650 cm{sup -1} accompanied by a concomitant development of a band around 3500 cm{sup -1}. The former and the latter are assigned to {nu}(OH) vibrations of non-hydrogen bonded and hydrogen bonded water molecules adsorbed on Pt, respectively, interpreted in term of results from a bond scission of the existing hydrogen bonded networks by CO(L)s and from a promotion of new hydrogen bonding among water molecules presumably by CO(B){sub asym.}. It was found

  20. An ATR-FTIR study of sulphate sorption on magnetite; rate of adsorption, surface speciation, and effect of calcium ions.

    Science.gov (United States)

    Roonasi, Payman; Holmgren, Allan

    2009-05-01

    The adsorption of sulphate on magnetite was studied in-situ using ATR-FTIR spectroscopy. Synthetic magnetite particles were deposited on a ZnSe internal reflection element and the spectra of sulphate adsorbed at pH 4-8.5 were recorded. Two different ionic strengths were used viz. 0.01 M and 0.1 M NaCl. The spectra of adsorbed sulphate on magnetite coated ZnSe were compared with the spectra of sulphate solutions at the same pH values and in contact with uncoated ZnSe. The spectrum of adsorbed sulphate at pH 4 showed three maxima at 979, 1044, and 1115 cm(-1) indicating a monodentate adsorption in which the T(d) symmetry of SO(4)(2-) is lowered to C(3v). At pH 6.5, sulphate adsorbed as an outer-sphere complex with two weak bands appearing at 1102 and 980 cm(-1). Moreover, spectra of the adsorbed sulphate at pH 4 were recorded as a function of time and sulphate concentration. The equilibrium absorbance at different concentrations fitted a Langmuir type adsorption isotherm. The Langmuir affinity constant K at pH 4 was determined from the slope and intercept of the Langmuir plot to be K=1.2344x10(4) M(-1) and the Gibbs free energy of adsorption DeltaG(ads)(0) was estimated from this value to be -33.3 kJ/mol. Kinetic analysis indicated that adsorption at pH 4 is fast, whilst the desorption kinetic at the same pH is very slow. In addition, the effect of Ca ions on sulphate adsorption was also studied. It was shown that Ca ions increased the sulphate adsorption on magnetite at pH 8.5.

  1. Sorption of phosphate onto mesoporous γ-alumina studied with in-situ ATR-FTIR spectroscopy

    Directory of Open Access Journals (Sweden)

    Zheng Ting-Ting

    2012-04-01

    Full Text Available Abstract Background Due to the extensive use of phosphates in industry, agriculture and households, the phosphate - γ-alumina interactions are important for understanding its detrimental contribution to eutrophication in lakes and rivers. In situ Fourier transform infrared (FTIR spectroscopy can provide more detailed information on the adsorbate-adsorbent interaction and the formation of hydrogen bonds. Results In situ ATR-FTIR spectroscopy was used to identify phosphate complexes adsorbed within the three-dimensional network of mesoporous γ-alumina at pH 4.1 and 9.0. The integrated intensity between 850 cm-1 and 1250 cm-1 was used as a relative measure of the amount of adsorbed phosphate. The integrated intensity proved to be about 3 times higher at pH 4.1 as compared with the corresponding intensity at pH 9.0. The adsorption of phosphate at the two pH conditions could be well described by the Langmuir adsorption isotherm at low concentrations and the empirical Freundlich adsorption isotherm for the whole concentration range, viz. 5 – 2000 μM. Conclusions From the band shape of infrared spectra at pH 4.1 and pH 9.0, it was proposed that the symmetry of the inner-sphere surface complex formed between phosphate and γ-alumina was C1 at the lower pH value, whilst the higher value (9.0 implied a surface complex with C2v or C1 symmetry. The difference in adsorbed amount of phosphate at the two pH values was ascribed to the reduced fraction of ≡ AlOH2+ surface sites and the increased fraction of ≡ AlO- sites upon increasing pH from 4 to 9.

  2. Evaluating and Modeling the Internal Diffusion Behaviors of Microencapsulated Rejuvenator in Aged Bitumen by FTIR-ATR Tests

    Directory of Open Access Journals (Sweden)

    Junfeng Su

    2016-11-01

    Full Text Available Microencapsulated rejuvenator has been attracted much attention for self-healing bitumen. The diffusion coefficient is one of the key parameters to estimate the feasibility of rejuvenator to age bitumen. The objective of this research was to evaluate diffusion behaviors of microencapsulated rejuvenator in aged bitumen by a FTIR-ATR method. Various microcapsule samples were mixed in bitumen to form thin films. The core material of microcapsules used as rejuvenator was diphenylsilane (DPS, its fairly specific absorption band at 843 cm−1 was selected as a marker band to calculate the diffusion coefficient (D. The microstructure parameters, including contents, mean size and mean shell thickness of microcapsules, were considered to understand the diffusion behaviors under different temperatures (20, 30, 40 and 50 °C in bitumen. The results showed that a larger mean size of microcapsules did not greatly affect the D values under the same temperature. In contrast, a higher mean shell thickness decreased the D values because of the decrement of damage probability of microcapsules under the same content. With the same microcapsule sample in bitumen, the D values presented a trend of linear increase when the content of microcapsules was increased. All these results indicated that the microstructure affected the diffusion behaviors based on the concentration of released rejuvenator. A preliminary model of diffusion behaviors of microencapsulated rejuvenator in bitumen was given based on the Arrhenius equation considering the microstructure of microcapsules, the amount of released rejuvenator and the age degree of bitumen. This model may be a guide to the construction and application of self-healing bitumen using microcapsules.

  3. [Cytoplasmic kinase inhibitors].

    Science.gov (United States)

    Mano, Hiroyuki

    2010-10-01

    Protein kinases play essential roles in the regulation of cell proliferation. Point mutations or/and fusions of protein kinases are frequently identified in human cancers, and targeting such activated kinases provides us with a chance to eradicate tumor cells. This was first proved by imatinib mesylate that inhibits ABL tyrosine kinase and, thereby, efficiently kills malignant cells in chronic myeloid leukemia. In addition, other clinical trials are ongoing for kinase inhibitors against EML4--ALK in lung cancer, JAK2 in myeloproliferative disorders and BRAF in malignant melanoma. Early reports indeed reveal that such targeting compounds are promising drugs for human cancers with activated kinases.

  4. ATR-p53 restricts homologous recombination in response to replicative stress but does not limit DNA interstrand crosslink repair in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Bianca M Sirbu

    Full Text Available Homologous recombination (HR is required for the restart of collapsed DNA replication forks and error-free repair of DNA double-strand breaks (DSB. However, unscheduled or hyperactive HR may lead to genomic instability and promote cancer development. The cellular factors that restrict HR processes in mammalian cells are only beginning to be elucidated. The tumor suppressor p53 has been implicated in the suppression of HR though it has remained unclear why p53, as the guardian of the genome, would impair an error-free repair process. Here, we show for the first time that p53 downregulates foci formation of the RAD51 recombinase in response to replicative stress in H1299 lung cancer cells in a manner that is independent of its role as a transcription factor. We find that this downregulation of HR is not only completely dependent on the binding site of p53 with replication protein A but also the ATR/ATM serine 15 phosphorylation site. Genetic analysis suggests that ATR but not ATM kinase modulates p53's function in HR. The suppression of HR by p53 can be bypassed under experimental conditions that cause DSB either directly or indirectly, in line with p53's role as a guardian of the genome. As a result, transactivation-inactive p53 does not compromise the resistance of H1299 cells to the interstrand crosslinking agent mitomycin C. Altogether, our data support a model in which p53 plays an anti-recombinogenic role in the ATR-dependent mammalian replication checkpoint but does not impair a cell's ability to use HR for the removal of DSB induced by cytotoxic agents.

  5. Planificación en fútbol según el modelo ATR en comparación con los modelos tradicionales

    OpenAIRE

    García Prada, Oscar

    2013-01-01

    El presente trabajo busca el desarrollo de una planificación en fútbol comparando los diferentes modelos de planificación. Se basa en la contraposición entre los modelos tradicionales y los contemporáneos, siendo el modelo ATR el más adecuado para la planificación de una temporada de fútbol. El trabajo se desarrolla desde un marco teórico englobando las diferentes características y fases en el desarrollo de una planificación así como los pasos a seguir para su correcto desarrol...

  6. Formation of carboxy- and amide-terminated alkyl monolayers on silicon(111) investigated by ATR-FTIR, XPS, and X-ray scattering: Construction of photoswitchable surfaces

    DEFF Research Database (Denmark)

    Rück-Braun, Karola; Petersen, Michael Åxman; Michalik, Fabian

    2013-01-01

    zigzag-like substitution pattern for the ester- and carboxy-terminated monolayer. Hydrolysis of the remaining H-Si(111) bonds at the surface furnished HO-Si(111) groups according to XPS and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) studies. The amide-terminated alkyl...... acid end-group. X-ray photoelectron spectroscopy (XPS) and grazing incidence X-ray diffraction (GIXD) indicate a surface coverage of about 50% of the initially H-terminated sites. In agreement, GIXD implies a rectangular unit mesh of 6.65 and 7.68 Å side lengths, containing two molecules in a regular...

  7. Revisiting the Brønsted acid catalysed hydrolysis kinetics of polymeric carbohydrates in ionic liquids by in situ ATR-FTIR spectroscopy

    DEFF Research Database (Denmark)

    Kunov-Kruse, Andreas Jonas; Riisager, Anders; Shunmugavel, Saravanamurugan

    2013-01-01

    A new versatile method to measure rates and determine activation energies for the Brønsted acid catalysed hydrolysis of cellulose and cellobiose (and other polymeric carbohydrates) in ionic liquids is demonstrated by following the C–O stretching band of the glycoside bond with in situ ATR......-FTIR. An activation energy in excellent agreement with the literature was determined for cellulose hydrolysis, whereas a distinctly lower activation energy was determined for cellobiose hydrolysis. The methodology also allowed to independently determine activation energies for the formation of 5-hydroxymethylfurfural...

  8. Methyl Jasmonate Induces Papain Inhibitor(s) in Tomato Leaves.

    Science.gov (United States)

    Bolter, C. J.

    1993-12-01

    Leaves of 18- to 24-d-old tomato (Lycopersicon esculentum) plants exposed to gaseous methyl jasmonate (MJ) for 24 h at 30[deg]C in continuous light contained high levels of soluble protein that inhibited papain. Chromatographic analysis demonstrated that the active protein had a molecular mass of 80 to 90 kD. Induction of papain inhibitor was directly related to the concentration of air-borne MJ up to a maximum of 0.1 [mu]L MJ per treatment and depended on the duration of exposure up to 18 h. Inhibitor activity in plants treated for less than 18 h increased with time after treatment. Levels remained constant for up to 4 d after treatment, after which time activity decreased. The youngest leaf, leaf 5, consistently lost activity at a faster rate than older, lower leaves. Inhibitor concentration in all leaves was reduced to minimum levels by 11 d after MJ treatment, but did not return to control levels. Treatment with MJ in the dark did induce inhibitor activity, but at a significantly lower rate. Polyclonal antibodies raised to purified potato tuber skin cysteine proteinase inhibitors (CPI) cross-reacted with the tomato inhibitor, suggesting that the tomato papain inhibitor and the potato CPI are closely related. No papain inhibitor activity was observed in extracts from wounded tomato leaves, nor was there any immunoreactivity with antibodies raised to potato tuber skin CPI.

  9. Characterization of microRNA-125b expression in MCF7 breast cancer cells by ATR-FTIR spectroscopy.

    Science.gov (United States)

    Ozek, Nihal Simsek; Tuna, Serkan; Erson-Bensan, A Elif; Severcan, Feride

    2010-12-01

    MicroRNAs (miRNAs), are ~22 nucleotides long, non-coding RNAs that control gene expression post-transcriptionally by binding to their target mRNA's 3'UTRs (untranslated regions). Due to their roles in various important regulatory processes and pathways, miRNAs have been implicated in disease mechanisms such as tumorigenesis when their expression is deregulated. To date, a significant number of miRNAs and their target messenger RNAs (mRNAs) have been identified and verified. It is generally accepted that miRNAs can potentially bind to many mRNAs, which brings the requirement of validation of these interactions. While understanding that such individual interactions is crucial to delineate the role of a specific miRNA, we took a holistic approach and analyzed global changes in the cell due to expression of a miRNA in a model cell line system. Our model consisted of MCF7 cells stably transfected with miR-125b (MCF7-125b) and empty vector (MCF7-EV). MiR-125b is one of the known down-regulated miRNAs in breast cancers. In this study we examined the global structural changes in MCF7 cells lacking and expressing miR-125b by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) Spectroscopy and investigated the dynamic changes by more sensitive spin-labelling Electron Spin Resonance (ESR) spectroscopy. Our results revealed less RNA, protein, lipid, and glycogen content in MCF7-125b compared to MCF7-EV cells. Membrane fluidity and proliferation rate were shown to be lower in MCF7-125b cells. Based on these changes, MCF7-125b and MCF7-EV cells were discriminated successfully by cluster analysis. Here, we provide a novel means to understand the global effects of miRNAs in cells. Potential applications of this approach are not only limited to research purposes. Such a strategy is also promising to pioneer the development of future diagnostic tools for deregulated miRNA expression in patient samples.

  10. Kinetic and Conformational Insights of Protein Adsorption onto Montmorillonite Revealed Using in Situ ATR-FTIR/2D-COS.

    Science.gov (United States)

    Schmidt, Michael P; Martínez, Carmen Enid

    2016-08-09

    Protein adsorption onto clay minerals is a process with wide-ranging impacts on the environmental cycling of nutrients and contaminants. This process is influenced by kinetic and conformational factors that are often challenging to probe in situ. This study represents an in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic investigation of the adsorption of a model protein (bovine serum albumin (BSA)) onto a clay mineral (montmorillonite) at four concentrations (1.50, 3.75, 7.50, and 15.0 μM) under environmentally relevant conditions. At all concentrations probed, FTIR spectra show that BSA readily adsorbs onto montmorillonite. Adsorption kinetics follow an Elovich model, suggesting that primary limitations on adsorption rates are surface-related heterogeneous energetic restrictions associated with protein rearrangement and lateral protein-protein interaction. BSA adsorption onto montmorillonite fits the Langmuir model, yielding K = 5.97 × 10(5) M(-1). Deconvolution and curve fitting of the amide I band at the end of the adsorption process (∼120 min) shows a large extent of BSA unfolding upon adsorption at 1.50 μM, with extended chains and turns increasing at the expense of α-helices. At higher concentrations/surface coverages, BSA unfolding is less pronounced and a more compact structure is assumed. Two-dimensional correlation spectroscopic (2D-COS) analysis reveals three different pathways corresponding to adsorbed conformations. At 1.50 μM, adsorption increases extended chains, followed by a loss in α-helices and a subsequent increase in turns. At 3.75 μM, extended chains decrease and then aggregated strands increase and side chains decrease, followed by a decrease in turns. With 7.50 and 15.0 μM BSA, the loss of side-chain vibrations is followed by an increase in aggregated strands and a subsequent decrease in turns and extended chains. Overall, the BSA concentration and resultant surface coverage have a profound

  11. Proteinase inhibitors in Brazilian leguminosae

    Directory of Open Access Journals (Sweden)

    C. A. M. Sampaio

    1991-01-01

    Full Text Available Serine proteinase inhitors, in the seeds of several Leguminosae from the Pantanal region (West Brazil, were studied using bovine trypsin, a digestive enzyme, Factor XIIa and human plasma Kallikrein, two blood clotting factors. The inhibitors were purified from Enterolobium contortisiliquum (Mr=23,000, Torresea cearensis (Mr = 13,000, Bauhinia pentandra (Mr = 20,000 and Bauhinia bauhinioides (Mr = 20,000. E. contortisiliquum inhibitor inactivates all three enzymes, whereas the T. cearensis inhibitor inactivates trypsin and Factor XSSa, but does nor affect plasma kallikrein; both Bauhinia inhibitors, on the other hand, inactivate trypsin and plasma kallikrein but only the Bpentandra inhibitor affects Factor XIIa. Ki values were calculated between 10 [raised to the power of] -7 and 10 [raised to the power of] -8 M.

  12. Formación de investigadores en medicina familiar: El modelo de tutorización en investigación Asesor-Tutor-Residente (ATR Researchers training on family medicine: The tutoring model in investigation advisory-tutor-resident (ATR

    Directory of Open Access Journals (Sweden)

    E. Raúl Ponce Rosas

    2003-04-01

    Full Text Available El tutor de la medicina de familia, los principios y características de la tutoría y la relación tutor-residente son elementos fundamentales para el desarrollo adecuado de los cursos de especialización de esta disciplina. La tutoría o tutorización en medicina familiar es la base de la docencia y se centra en la figura de una relación humana de enseñanza individualizada tutor-residente en la práctica asistencial, docente y de investigación. Los modelos de tutorización en medicina de familia proporcionan herramientas útiles para establecer una adecuada relación tutor-residente. En este trabajo se describe el modelo de tutorización en investigación Asesor-Tutor-Residente, que se lleva a cabo en el Curso de Especialización de Medicina Familiar en la Facultad de Medicina de la UNAM, México. El modelo de tutorización en investigación Asesor-Tutor-Residente (ATR, es un paradigma de capacitación teórico-práctico en esta importante y fundamental área de la medicina de familia. El modelo ATR pretende motivar e interesar a tutores y residentes para hacer investigación con base en la demostración y la supervisión formativa a través de la asesoría continua, reflexiva, planeada y sistematizada.The tutor of the family medicine, the principles and characteristics of the tutorship, and the relationship tutor-resident they are fundamental elements for the appropriate development of the courses of specialization of this discipline. The tutorship or tutoring in family medicine are the base of the teaching and it is centered in the figure of a human relationship of teaching individualized tutor-resident in the assistance, educational practice and investigation. The tutoring models in family medicine provide useful tools to establish an appropriate relationship tutor-resident. In this work is describe the tutoring model in investigation "advisory-tutor-resident" (ATR that is carried out in the Course of Specialization of Family Medicine in

  13. Kaposi sarcoma herpes virus latency associated nuclear antigen protein release the G2/M cell cycle blocks by modulating ATM/ATR mediated checkpoint pathway.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available The Kaposi's sarcoma-associated herpesvirus infects the human population and maintains latency stage of viral life cycle in a variety of cell types including cells of epithelial, mesenchymal and endothelial origin. The establishment of latent infection by KSHV requires the expression of an unique repertoire of genes among which latency associated nuclear antigen (LANA plays a critical role in the replication of the viral genome. LANA regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. The present study demonstrates the disruption of the host G2/M cell cycle checkpoint regulation as an associated function of LANA. DNA profile of LANA expressing human B-cells demonstrated the ability of this nuclear antigen in relieving the drug (Nocodazole induced G2/M checkpoint arrest. Caffeine suppressed nocodazole induced G2/M arrest indicating involvement of the ATM/ATR. Notably, we have also shown the direct interaction of LANA with Chk2, the ATM/ATR signalling effector and is responsible for the release of the G2/M cell cycle block.

  14. Estimation of the age of human bloodstains under the simulated indoor and outdoor crime scene conditions by ATR-FTIR spectroscopy.

    Science.gov (United States)

    Lin, Hancheng; Zhang, Yinming; Wang, Qi; Li, Bing; Huang, Ping; Wang, Zhenyuan

    2017-10-16

    Estimation of the age of human bloodstains is of great importance in forensic practices, but it is a challenging task because of the lack of a well-accepted, reliable, and established method. Here, the attenuated total reflection (ATR)-Fourier transform infrared (FTIR) technique combined with advanced chemometric methods was utilized to determine the age of indoor and outdoor bloodstains up to 107 days. The bloodstain storage conditions mimicked crime scene scenarios as closely as possible. Two partial least squares regression models-indoor and outdoor models with 7-85 days-exhibited good performance for external validation, with low values of predictive root mean squared error (5.83 and 4.77) and high R(2) values (0.94 and 0.96) and residual predictive deviation (4.08 and 5.14), respectively. Two partial least squares-discriminant analysis classification models were built and demonstrated excellent distinction between fresh (age ≤1 d) and older (age >1 d) bloodstains, which is highly valuable for forensic investigations. These findings demonstrate that ATR-FTIR spectroscopy coupled with advanced chemometric methods can be employed as a rapid and non-destructive tool for age estimation of bloodstains in real-world forensic investigation.

  15. Observations of surface-mediated reduction of Pu(VI) to Pu(IV) on hematite nanoparticles by ATR FT-IR

    Energy Technology Data Exchange (ETDEWEB)

    Emerson, Hilary P. [Florida International Univ., Applied Research Center, Miami, FL (United States); Powell, Brian A. [Clemson Univ., Dept. of Enviromental Engineering and Earth Sciences, Anderson, SC (United States)

    2015-07-01

    Previous studies have shown that mineral surfaces may facilitate the reduction of plutonium though the mechanisms of the reduction are still unknown. The objective of this study is to use batch sorption and attenuated total reflectance Fourier transform infrared spectroscopy experiments to observe the surface-mediated reduction of plutonium on hematite nanoparticles. These techniques allow for in situ measurement of reduction of plutonium with time and may lead to a better understanding of the mechanisms of surface mediated reduction of plutonium. For the first time, ATR FT-IR peaks for Pu(VI) sorbed to hematite are measured at ∝ 916 cm{sup -1}, respectively. The decrease in peak intensity with time provides a real-time, direct measurement of Pu(VI) reduction on the hematite surface. In this work pseudo first order rate constants estimated at the high loadings (22 mg{sub Pu}/g{sub hematite}, 1.34 x 10{sup -6} M{sub Pu}/m{sup 2}) for ATR FT-IR are approximately 10 x slower than at trace concentrations based on previous work. It is proposed that the reduced rate constant at higher Pu loadings occurs after the reduction capacity due to trace Fe(II) has been exhausted and is dependent on the oxidation of water and possibly electron shuttling based on the semiconducting nature of hematite. Therefore, the reduction rate at higher loadings is possibly due to the thermodynamic favorability of Pu(IV)-hydroxide complexes.

  16. SUV2, which encodes an ATR-related cell cycle checkpoint and putative plant ATRIP, is required for aluminium-dependent root growth inhibition in Arabidopsis.

    Science.gov (United States)

    Sjogren, Caroline A; Larsen, Paul B

    2017-09-01

    A suppressor mutagenesis screen was conducted in order to identify second site mutations that could reverse the extreme hypersensitivity to aluminium (Al) seen for the Arabidopsis mutant, als3-1. From this screen, it was found that a loss-of-function mutation in the previously described SUV2 (SENSITIVE TO UV 2), which encodes a putative plant ATRIP homologue that is a component of the ATR-dependent cell checkpoint response, reversed the als3-1 phenotype. This included prevention of hallmarks associated with als3-1 including Al-dependent terminal differentiation of the root tip and transition to endoreduplication. From this analysis, SUV2 was determined to be required for halting cell cycle progression and triggering loss of the quiescent centre (QC) following exposure to Al. In conjunction with this, SUV2 was found to have a similar role as ATR, ALT2 and SOG1 in Al-dependent stoppage of root growth, all of which are required for promotion of expression of a suite of genes that likely are part of an Al-dependent DNA damage transcriptional response. This work argues that these Al response factors work together to detect Al-dependent damage and subsequently activate a DNA damage response pathway that halts the cell cycle and subsequently promotes QC differentiation and entrance into endocycling. © 2017 John Wiley & Sons Ltd.

  17. Combined use of quantitative ED-EPMA, Raman microspectrometry, and ATR-FTIR imaging techniques for the analysis of individual particles.

    Science.gov (United States)

    Jung, Hae-Jin; Eom, Hyo-Jin; Kang, Hyun-Woo; Moreau, Myriam; Sobanska, Sophie; Ro, Chul-Un

    2014-08-21

    In this work, quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA) (called low-Z particle EPMA), Raman microspectrometry (RMS), and attenuated total reflectance Fourier transform infrared spectroscopic (ATR-FTIR) imaging were applied in combination for the analysis of the same individual airborne particles for the first time. After examining individual particles of micrometer size by low-Z particle EPMA, consecutive examinations by RMS and ATR-FTIR imaging of the same individual particles were then performed. The relocation of the same particles on Al or Ag foils was successfully carried out among the three standalone instruments for several standard samples and an indoor airborne particle sample, resulting in the successful acquisition of quality spectral data from the three single-particle analytical techniques. The combined application of the three techniques to several different standard particles confirmed that those techniques provided consistent and complementary chemical composition information on the same individual particles. Further, it was clearly demonstrated that the three different types of spectral and imaging data from the same individual particles in an indoor aerosol sample provided richer information on physicochemical characteristics of the particle ensemble than that obtainable by the combined use of two single-particle analytical techniques.

  18. A rapid ATR-FTIR spectroscopic method for detection of sibutramine adulteration in tea and coffee based on hierarchical cluster and principal component analyses.

    Science.gov (United States)

    Cebi, Nur; Yilmaz, Mustafa Tahsin; Sagdic, Osman

    2017-08-15

    Sibutramine may be illicitly included in herbal slimming foods and supplements marketed as "100% natural" to enhance weight loss. Considering public health and legal regulations, there is an urgent need for effective, rapid and reliable techniques to detect sibutramine in dietetic herbal foods, teas and dietary supplements. This research comprehensively explored, for the first time, detection of sibutramine in green tea, green coffee and mixed herbal tea using ATR-FTIR spectroscopic technique combined with chemometrics. Hierarchical cluster analysis and PCA principle component analysis techniques were employed in spectral range (2746-2656cm -1 ) for classification and discrimination through Euclidian distance and Ward's algorithm. Unadulterated and adulterated samples were classified and discriminated with respect to their sibutramine contents with perfect accuracy without any false prediction. The results suggest that existence of the active substance could be successfully determined at the levels in the range of 0.375-12mg in totally 1.75g of green tea, green coffee and mixed herbal tea by using FTIR-ATR technique combined with chemometrics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Sensing cocaine in saliva with attenuated total reflection infrared (ATR-IR) spectroscopy combined with a one-step extraction method

    Science.gov (United States)

    Hans, Kerstin M.-C.; Gianella, Michele; Sigrist, Markus W.

    2012-03-01

    On-site drug tests have gained importance, e.g., for protecting the society from impaired drivers. Since today's drug tests are majorly only positive/negative, there is a great need for a reliable, portable and preferentially quantitative drug test. In the project IrSens we aim to bridge this gap with the development of an optical sensor platform based on infrared spectroscopy and focus on cocaine detection in saliva. We combine a one-step extraction method, a sample drying technique and infrared attenuated total reflection (ATR) spectroscopy. As a first step we have developed an extraction technique that allows us to extract cocaine from saliva to an almost infrared-transparent solvent and to record ATR spectra with a commercially available Fourier Transform-infrared spectrometer. To the best of our knowledge this is the first time that such a simple and easy-to-use one-step extraction method is used to transfer cocaine from saliva into an organic solvent and detect it quantitatively. With this new method we are able to reach a current limit of detection around 10 μg/ml. This new extraction method could also be applied to waste water monitoring and controlling caffeine content in beverages.

  20. MRN- and 9-1-1-Independent Activation of the ATR-Chk1 Pathway during the Induction of the Virulence Program in the Phytopathogen Ustilago maydis.

    Science.gov (United States)

    Tenorio-Gómez, María; de Sena-Tomás, Carmen; Pérez-Martín, Jose

    2015-01-01

    DNA damage response (DDR) leads to DNA repair, and depending on the extent of the damage, to further events, including cell death. Evidence suggests that cell differentiation may also be a consequence of the DDR. During the formation of the infective hypha in the phytopathogenic fungus Ustilago maydis, two DDR kinases, Atr1 and Chk1, are required to induce a G2 cell cycle arrest, which in turn is essential to display the virulence program. However, the triggering factor of DDR in this process has remained elusive. In this report we provide data suggesting that no DNA damage is associated with the activation of the DDR during the formation of the infective filament in U. maydis. We have analyzed bulk DNA replication during the formation of the infective filament, and we found no signs of impaired DNA replication. Furthermore, using RPA-GFP fusion as a surrogate marker of the presence of DNA damage, we were unable to detect any sign of DNA damage at the cellular level. In addition, neither MRN nor 9-1-1 complexes, both instrumental to transmit the DNA damage signal, are required for the induction of the above mentioned cell cycle arrest, as well as for virulence. In contrast, we have found that the claspin-like protein Mrc1, which in other systems serves as scaffold for Atr1 and Chk1, was required for both processes. We discuss possible alternative ways to trigger the DDR, independent of DNA damage, in U. maydis during virulence program activation.

  1. Combining Mass Spectrometry and ATR-FTIR Spectroscopy to Study Phase, Diffusion and Composition of Secondary Organic Aerosol from the Ozonolysis of α-pinene

    Science.gov (United States)

    Perraud, V. M.; Finlayson-Pitts, B. J.; Waring-Kidd, C.

    2014-12-01

    Secondary organic aerosol (SOA) is ubiquitous in the atmosphere and composes a large fraction of the total aerosol budget. Recent reports from field measurements and laboratory studies show that some SOA particles are better represented by a semi-solid low viscosity tar-like material rather than a ideal liquid often assumed in regional and global models. Characterizing the phase of SOA is crucial to understanding how particles interact with trace gases and how it ultimately impacts their growth and evolution in the atmosphere. We report here laboratory studies carried out in the unique UCI large-volume, slow-flow, aerosol flow reactor. Particles from the ozonolysis of a-pinene were formed at various relative humidities (RH from < 3% to 90%) and collected onto a custom ATR-FTIR impactor. The observed impaction pattern provided insights into changes in phase/viscosity of the SOA as a function of relative humidity. In addition, attenuated total reflectance FTIR and mass spectrometry measurements provided information on simultaneous changes on composition. Application of ATR-FTIR combined with PTR-MS provided additional data on the volatility of the SOA at room temperature and diffusion coefficients of two key components pinonaldehyde and acetic acid present in the SOA. Implication for modeling the growth and ultimately the lifetime of SOA in the atmosphere will be discussed.

  2. Surface characterization of poly(L-lactic acid)-methoxy poly(ethylene glycol) diblock copolymers by static and dynamic contact angle measurements, FTIR, and ATR-FTIR.

    Science.gov (United States)

    Mert, O; Doganci, E; Erbil, H Y; Demir, A S

    2008-02-05

    The surface composition and surface free energy properties of two types of amphiphilic and semicrystalline diblock copolymers consisting of poly(L-lactic acid) coupled to (methoxy poly(ethylene glycol) (PLLA-MePEG) having differing block lengths of PEG were investigated by using static and dynamic contact angle measurements, transmission Fourier infrared spectroscopy (FTIR), and attenuated total reflection spectroscopy (ATR-FTIR) and compared with results obtained from PLLA and MePEG homopolymers. The contact angle results were evaluated by using the van Oss-Good method (acid-base method), and it was determined that the Lewis base surface tension coefficient (gamma-) of the copolymers increased with an increase of the PEG molar content at the copolymer surface. This result is in good agreement with the transmission FTIR and ATR-FTIR results but not proportional to them, indicating that the surfaces of the copolymers are highly mobile and that the molecular rearrangement takes place upon contact with a polar liquid drop. The dynamic contact angle measurements showed that the strong acid-base interaction between the oxygen atoms in the copolymer backbone of the relatively more hydrophilic PEG segments with the Lewis acidic groups of the polar and hydrogen-bonding water molecules enabled the surface molecules to restructure (conformational change) at the contact area, so that the PEG segments moved upward, whereas the apolar methyl pendant groups of PLLA segments buried downward.

  3. A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions

    Science.gov (United States)

    Shimizu, Kiminori; Paul, Sanjoy; Ohba, Ayumi; Gonoi, Tohru; Watanabe, Akira; Gomi, Katsuya

    2017-01-01

    Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B). PMID:28052140

  4. A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions.

    Directory of Open Access Journals (Sweden)

    Daisuke Hagiwara

    2017-01-01

    Full Text Available Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E, deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A and putative drug efflux pump (Cdr1B.

  5. ATR-FTIR sensor development for continuous on-line monitoring of chlorinated aliphatic hydrocarbons in a fixed-bed bioreactor.

    Science.gov (United States)

    Acha, V; Meurens, M; Naveau, H; Agathos, S N

    2000-06-05

    This article describes the continuous on-line monitoring of a dechlorination process by a novel attenuated total reflection-Fourier transform infrared (ATR-FTIR) sensor. This optical sensor was developed to measure noninvasively part-per-million (ppm) concentrations of trichloroethylene (TCE), tetrachloroethylene (PCE), and carbon tetrachloride (CT) in the aqueous effluent of a fixed-bed dechlorinating bioreactor, without any prior sample preparation. The sensor was based on an ATR internal reflection element (IRE) coated with an extracting hydrophobic polymer, which prevented water molecules from interacting with the infrared (IR) radiation. The selective diffusion of chlorinated compound molecules from aqueous solution into the polymer made possible their detection by the IR beam. With the exclusion of water the detection limits were lowered, and measurements in the low ppm level became possible. The best extracting polymer was polyisobutylene (PIB) in the form of a 5.8-microm thick film, which afforded a detection limit of 2, 3, and 2. 5 mg/L (ppm) for TCE, PCE, and CT, respectively. Values of the enrichment factors between the polymer coating and the water matrix of these chloro-organics were determined experimentally and were compared individually with predictions obtained from the slopes of absorbance/concentration curves for the three analytes. Before coupling the ATR-FTIR sensor to the dechlorinating bioreactor, preliminary spectra of the chlorinated compounds were acquired on a laboratory scale configuration in stop-flow and flow-through closed-loop modes. In this way, it was possible to study the behavior and direct response of the optical sensor to any arbitrary concentration change of the analytes. Subsequently, the bioreactor was monitored with the infrared sensor coupled permanently to it. The sensor tracked the progression of the analytes' spectra over time without perturbing the dechlorinating process. To calibrate the ATR-FTIR sensor, a total of 13

  6. Efectividad de un programa de ejercicios y pedaleo hacia atrás en atletas afectados de Síndrome de Dolor Femoropatelar en el Centro de alto rendimiento de Madrid.

    OpenAIRE

    Gracia Pera, María Bruis

    2014-01-01

    ¿Los atletas tratados con Síndrome de dolor femoropatelar que reciban un plan de prevención mediante el pedaleo hacia atrás disminuirán la recurrencia? El objetivo de dicho estudio es la reducción de la recurrencia en los atletas diagnosticados de Síndrome de dolor femoropatelar (PFPS) mediante la incorporación del pedaleo hacia atrás en el plan de prevención. Metodología: estudio experimental, controlado, aleatorio y simple ciego. Se elegirá una muestra de 20 pacientes diagnosticados d...

  7. [Progress on matrix metalloproteinase inhibitors].

    Science.gov (United States)

    Lingling, Jia; Qianbing, Wan

    2017-04-01

    Continuing advances in dentin bonding technology and adhesives revolutionized bonding of resin-based composite restorations. However, hybrid layers created by contemporary dentin adhesives present imperfect durability, and degradation of collagen matrix by endogenous enzymes is a significant factor causing destruction of hybrid layers. Bond durability can be improved by using enzyme inhibitors to prevent collagen degradation and to preserve integrity of collagen matrix. This review summarizes progress on matrix metalloproteinase inhibitors (including chlorhexidine, ethylenediaminetetraacetic acid, quaternary ammonium salt, tetracycline and its derivatives, hydroxamic acid inhibitors, bisphosphonate derivative, and cross-linking agents) and suggests prospects for these compounds.

  8. Angiogenesis Inhibitors in NSCLC

    Directory of Open Access Journals (Sweden)

    Anna Manzo

    2017-09-01

    Full Text Available Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC. Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL that demonstrated an improvement of about two months in progression-free survival (PFS in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS also. Afterwards, other antiangiogenic agents, including sunitinib, sorafenib, and vandetanib have been unsuccessfully tested in first and successive lines. Recently, two new antiangiogenic agents (ramucirumab and nintedanib produced a significant survival benefit in second-line setting. In the REVEL study, ramucirumab plus docetaxel prolonged the median OS of patients with any histology NSCLC when compared with docetaxel alone (10.4 versus 9.1 months, hazard ratio (HR 0.857, p = 0.0235. In the LUME-Lung 1 study, nintedanib plus docetaxel prolonged the median PFS of patients with any tumor histology (p = 0.0019, and improved OS (12.6 versus 10.3 months in patients with adenocarcinoma. As a result, it became a new option for the second-line treatment of patients with advanced NSCLC and adenocarcinoma histology. Identifying predictive biomarkers to optimize the benefit of antiangiogenic drugs remains an ongoing challenge.

  9. Thrombin inhibitors from different animals.

    Science.gov (United States)

    Tanaka-Azevedo, A M; Morais-Zani, K; Torquato, R J S; Tanaka, A S

    2010-01-01

    Venous and arterial thromboembolic diseases are still the most frequent causes of death and disability in high-income countries. Clinical anticoagulants are inhibitors of enzymes involved in the coagulation pathway, such as thrombin and factor X(a). Thrombin is a key enzyme of blood coagulation system, activating the platelets, converting the fibrinogen to the fibrin net, and amplifying its self-generation by the activation of factors V, VIII, and XI. Thrombin has long been a target for the development of oral anticoagulants. Furthermore, selective inhibitors of thrombin represent a new class of antithrombotic agents. For these reasons, a number of specific thrombin inhibitors are under evaluation for possible use as antithrombotic drugs. This paper summarizes old and new interests of specific thrombin inhibitors described in different animals.

  10. Thrombin Inhibitors from Different Animals

    Directory of Open Access Journals (Sweden)

    A. M. Tanaka-Azevedo

    2010-01-01

    Full Text Available Venous and arterial thromboembolic diseases are still the most frequent causes of death and disability in high-income countries. Clinical anticoagulants are inhibitors of enzymes involved in the coagulation pathway, such as thrombin and factor Xa. Thrombin is a key enzyme of blood coagulation system, activating the platelets, converting the fibrinogen to the fibrin net, and amplifying its self-generation by the activation of factors V, VIII, and XI. Thrombin has long been a target for the development of oral anticoagulants. Furthermore, selective inhibitors of thrombin represent a new class of antithrombotic agents. For these reasons, a number of specific thrombin inhibitors are under evaluation for possible use as antithrombotic drugs. This paper summarizes old and new interests of specific thrombin inhibitors described in different animals.

  11. Selective Serotonin Reuptake Inhibitors (SSRIs)

    Science.gov (United States)

    ... Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. http://www.uptodate.com/home. Accessed June 2, 2016. Mental health medications. National Institute of Mental Health. http://www. ...

  12. Formulary management of ACE inhibitors.

    Science.gov (United States)

    Gerbrandt, K R; Yedinak, K C

    1996-12-01

    An increasing number of ACE inhibitors have become available in recent years. Because these agents are all similar, careful scrutiny is required in order to determine specific advantages of particular agents when making formulary decisions. Differences between agents with regard to structure and tissue specificity have been identified, but the clinical relevance of these differences is not clear. ACE inhibitors vary greatly with regard to bioconversion, distribution and elimination. Disease states such as congestive heart failure (CHF) and hepatic or renal insufficiency may affect the disposition of specific ACE inhibitors. These agents may differ substantially in duration of action, and ACE inhibitors that are given once daily may optimise patient compliance and decrease costs. ACE inhibitors have been extensively studied in patients with hypertension, CHF or nephropathy, and following myocardial infarction (MI). Differences in efficacy between agents are often a result of variations in study design, or because nonequipotent dosages were compared. It is likely that the benefits of ACE inhibitors are class effects, and it is probably reasonable to use an agent even if large scale clinical trials have not been performed with that particular drug. Few differences have been found between ACE inhibitors with regard to adverse effects or drug interactions, and these factors are of minor importance when making formulary decisions. Cost and availability may vary among agents, and will depend on geographical location and institution-specific purchasing contracts. ACE inhibitors have shown positive effects on quality of life when compared with agents of other classes. Quality-of-life studies that have directly compared ACE inhibitors have produced conflicting results. In the setting of hypertension, cost-effectiveness evaluations typically find that the newer, longer-acting ACE inhibitors provide the greatest financial benefit. Differences in cost effectiveness in the post

  13. Interaction of Zn(II) with hematite nanoparticles and microparticles: Part 2. ATR-FTIR and EXAFS study of the aqueous Zn(II)/oxalate/hematite ternary system.

    Science.gov (United States)

    Ha, Juyoung; Trainor, Thomas P; Farges, François; Brown, Gordon E

    2009-05-19

    Sorption of Zn(II) to hematite nanoparticles (HN) (av diam=10.5 nm) and microparticles (HM) (av diam=550 nm) was studied in the presence of oxalate anions (Ox2-(aq)) in aqueous solutions as a function of total Zn(II)(aq) to total Ox2-(aq) concentration ratio (R=[Zn(II)(aq)]tot/[Ox2-(aq)]tot) at pH 5.5. Zn(II) uptake is similar in extent for both the Zn(II)/Ox/HN and Zn(II)/Ox/HM ternary systems and the Zn(II)/HN binary system at [Zn(II)(aq)](tot)system than for the Zn(II)/Ox/HM ternary and the Zn(II)/HN and Zn(II)/HM binary systems at [Zn(II)(aq)]tot>4 mM. In contrast, Zn(II) uptake for the Zn(II)/HM binary system is a factor of 2 greater than that for the Zn(II)/Ox/HM and Zn(II)/Ox/HN ternary systems and the Zn(II)/HN binary system at [Zn(II)(aq)]totternary system at both R values examined (0.16 and 0.68), attenuated total reflectance Fourier transform infrared (ATR-FTIR) results are consistent with the presence of inner-sphere oxalate complexes and outer-sphere ZnOx(aq) complexes, and/or type A ternary complexes. In addition, extended X-ray absorption fine structure (EXAFS) spectroscopic results suggest that type A ternary surface complexes (i.e., >O2-Zn-Ox) are present. In the Zn(II)/Ox/HN ternary system at R=0.15, ATR-FTIR results indicate the presence of inner-sphere oxalate and outer-sphere ZnOx(aq) complexes; the EXAFS results provide no evidence for inner-sphere Zn(II) complexes or type A ternary complexes. In contrast, ATR-FTIR results for the Zn/Ox/HN sample with R = 0.68 are consistent with a ZnOx(s)-like surface precipitate and possibly type B ternary surface complexes (i.e., >O2-Ox-Zn). EXAFS results are also consistent with the presence of ZnOx(s)-like precipitates. We ascribe the observed increase of Zn(II)(aq) uptake in the Zn(II)/Ox/HN ternary system at [Zn(II)(aq)]tot>or=4 mM relative to the Zn(II)/Ox/HM ternary system to formation of a ZnOx(s)-like precipitate at the hematite nanoparticle/water interface.

  14. Tratamiento del maxilar posterior atrófico mediante técnica de reconstrucción tridimensional con elevación de seno y abordaje «en tunel»

    Directory of Open Access Journals (Sweden)

    Andrés Restoy

    2015-01-01

    Conclusiones: El tratamiento del sector posterior maxilar atrófico mediante reconstrucción tridimensional con autoinjerto óseo, elevación sinusal y abordaje por tunelización es una técnica que proporciona resultados predecibles y estables, permitiendo la rehabilitación con coronas sobre implantes dentales de dimensiones adecuadas.

  15. Effect of pH on the Nitrite Hydrogenation Mechanism over Pd/Al(2)O(3) and Pt/Al(2)O(3): Details obtained with ATR-IR Spectroscopy

    NARCIS (Netherlands)

    Ebbesen, S.D.; Mojet, Barbara; Lefferts, Leonardus

    2011-01-01

    It is well-known that activity and selectivity to N2 during nitrite hydrogenation over noble metal catalysts in water depend on the pH of the solution, but mechanistic understanding is lacking. Attenuated total reflection infrared (ATR-IR) spectroscopy is an ideal tool to perform detailed studies on

  16. Manejo estomatológico del liquen plano oral atrófico. Revisión de literatura y presentación de un caso

    OpenAIRE

    Harris Ricardo, Jonathan; Corporación Universitaria Rafael Núñez, Cartagena, Colombia; Díaz-Caballero, Antonio; Universidad de Cartagena, Cartagena, Colombia; Fortich Mesa, Natalia; Corporación Universitaria Rafael Núñez, Cartagena, Colombia

    2011-01-01

    El liquen plano oral es una enfermedad de carácter autoinmune mucocutánea crónica y etiología desconocida. Las lesiones se presentan en la cavidad oral, la piel, las uñas y también pueden tener expresiones en los folículos pilosos de la cabeza. Presenta diversas formas clínicas entre las que se encuentra el patrón reticular, atrófico y erosivo. Este último es la forma clínica más asociada con una transformación maligna de las lesiones bucales. El diagnóstico es clínico-patológico y el tratami...

  17. Study of Barley Grain Molecular Structure for Ruminants Using DRIFT, FTIR-ATR and Synchrotron Radiation Infrared Microspectroscopy (SR-IMS): A Review

    Science.gov (United States)

    Yu, Peiqiang

    2012-05-01

    Barley inherent structures are highly associated with nutrient utilization and availability in both humans and animals. Barley has different degradation kinetics compared with other cereal grains. It has a relatively higher degradation rate and extent, which often cause digestive disorder in the rumen. Therefore understanding barley inherent structure at cellular and molecular levels and processing-induced structure changes is important, because we can manipulate barley inherent structures and digestive behaviors. Several molecular spectroscopy techniques can be used to detect barley inherent structures at cellular and molecular levels. This article reviews several applications of the IR molecular spectral bioanalytical techniques - DRIFT, FT/IR-ATR and SR-IMS for barley chemistry, molecular structure and molecular nutrition research

  18. Evaluation of Corrosion of the Dummy “EE” Plate 19 in YA Type ATR Fuel Element During Reactor PALM Cycles

    Energy Technology Data Exchange (ETDEWEB)

    Brower, Jeffrey Owen [Idaho National Lab. (INL), Idaho Falls, ID (United States); Glazoff, Michael Vasily [Idaho National Lab. (INL), Idaho Falls, ID (United States); Eiden, Thomas John [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rezvoi, Aleksey Victor [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-08-01

    Advanced Test Reactor (ATR) Cycle 153B-1 was a 14-day, high-power, powered axial locator mechanism (PALM) operating cycle that completed on April 12, 2013. Cycle 153B-1 was a typical operating cycle for the ATR and did not result in any unusual plant transients. ATR was started up and shut down as scheduled. The PALM drive physically moves the selected experiments into and out of the core to simulate reactor startup and heat up, and shutdown and cooldown transients, while the reactor remains in steady state conditions. However, after the cycle was over, several thousand of the flow-assisted corrosion pits and “horseshoeing” defects were readily observable on the surface of the several YA-type fuel elements (these are “dummy” plates that contain no fuel). In order understand these corrosion phenomena a thermal-hydraulic model of coolant channel 20 on a YA-M fuel element was generated. The boundaries of the model were the aluminum EE plate of a YA-M fuel element and a beryllium reflector block with 13 horizontal saw cuts which represented regions of zero flow. The heat generated in fuel plates 1 through 18 was modeled to be passing through the aluminum EE plate. The coolant channel 20 width was set at 0.058 in. (58 mils). It was established that the horizontal saw cuts had a significant effect on the temperature of the coolant. The flow, which was expected to vary linearly with gradual heating of the coolant as it passed through the channel, was extremely turbulent. The temperature rise, which was expected to be a smooth “S” curve, was represented by a series temperature rise “humps,” which occurred at each horizontal saw cut in the beryllium reflector block. Each of the 13 saw cuts had a chamfered edge which resulted in the coolant flow being re-directed as a jet across the coolant channel into the surface of the EE plate, which explained the temperature rise and the observed sscalloping and possibly pitting degradation on the YA-M fuel elements. In

  19. Fourier transform infrared-attenuated total reflectance (FTIR-ATR spectroscopy and chemometric techniques for the determination of adulteration in petrodiesel/biodiesel blends

    Directory of Open Access Journals (Sweden)

    Armando Guerrero Peña

    2014-06-01

    Full Text Available We propose an analytical method based on fourier transform infrared-attenuated total reflectance (FTIR-ATR spectroscopy to detect the adulteration of petrodiesel and petrodiesel/palm biodiesel blends with African crude palm oil. The infrared spectral fingerprints from the sample analysis were used to perform principal components analysis (PCA and to construct a prediction model using partial least squares (PLS regression. The PCA results separated the samples into three groups, allowing identification of those subjected to adulteration with palm oil. The obtained model shows a good predictive capacity for determining the concentration of palm oil in petrodiesel/biodiesel blends. Advantages of the proposed method include cost-effectiveness and speed; it is also environmentally friendly.

  20. 2DCOS and PCMW2D analysis of FT-IR/ATR spectra measured at variable temperatures on-line to a polyurethane polymerization

    Science.gov (United States)

    Schuchardt, Patrick; Unger, Miriam; Siesler, Heinz W.

    2018-01-01

    In the present communication the potential of 2DCOS analysis and the spin-off technique perturbation-correlation moving window 2D (PCMW2D) analysis is illustrated with reference to spectroscopic changes observed in a data set recorded by in-line fiber-coupled FT-IR spectroscopy in the attenuated total reflection (ATR) mode during a polyurethane solution polymerization at different temperatures. In view of the chemical functionalities involved, hydrogen bonding plays an important role in this polymerization reaction. Based on the 2DCOS and PCMW2D analysis, the sequence of hydrogen bonding changes accompanying the progress of polymerization and precipitation of solid polymer can be determined. Complementary to the kinetic data derived from the original variable-temperature spectra in a previous publication the results provide a more detailed picture of the investigated solution polymerization.

  1. MRN- and 9-1-1-Independent Activation of the ATR-Chk1 Pathway during the Induction of the Virulence Program in the Phytopathogen Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    María Tenorio-Gómez

    Full Text Available DNA damage response (DDR leads to DNA repair, and depending on the extent of the damage, to further events, including cell death. Evidence suggests that cell differentiation may also be a consequence of the DDR. During the formation of the infective hypha in the phytopathogenic fungus Ustilago maydis, two DDR kinases, Atr1 and Chk1, are required to induce a G2 cell cycle arrest, which in turn is essential to display the virulence program. However, the triggering factor of DDR in this process has remained elusive. In this report we provide data suggesting that no DNA damage is associated with the activation of the DDR during the formation of the infective filament in U. maydis. We have analyzed bulk DNA replication during the formation of the infective filament, and we found no signs of impaired DNA replication. Furthermore, using RPA-GFP fusion as a surrogate marker of the presence of DNA damage, we were unable to detect any sign of DNA damage at the cellular level. In addition, neither MRN nor 9-1-1 complexes, both instrumental to transmit the DNA damage signal, are required for the induction of the above mentioned cell cycle arrest, as well as for virulence. In contrast, we have found that the claspin-like protein Mrc1, which in other systems serves as scaffold for Atr1 and Chk1, was required for both processes. We discuss possible alternative ways to trigger the DDR, independent of DNA damage, in U. maydis during virulence program activation.

  2. Técnicas FT-IR (PAS, UATR e Objetiva ATR Aplicadas à Caracterização de EPDM Modificada com Plasma

    Directory of Open Access Journals (Sweden)

    Renata Patrícia dos Santos

    2014-06-01

    Full Text Available Técnicas FT-IR (UATR, PAS e MIC, com objetiva ATR foram escolhidas para a caracterização da superfície da borracha de EPDM vulcanizada, após tratamento em plasma de Ar/O2 e N2/H2/Ar gerado em micro-ondas. Após tratamento, grupos oxigenados foram detectados por UATR e MIC/FT-IR, com objetiva ATR para as duas misturas gasosas, e possíveis grupos nitrogenados foram inseridos na superfície das amostras tratadas com plasma de N2/H2/Ar. A análise MIC/FT-IR sugeriu a formação de grupos em uma camada mais externa, para as amostras tratadas com plasma de N2/H2/Ar, sendo possível observar a redução na intensidade das bandas da absorção do CH2 e CH3, o que pode estar relacionado ao fato de o nitrogênio ser um gás menos permeável que o oxigênio. Diferentes velocidades, 0,05 cm.s-1 e 0,2 cm.s-1, foram utilizadas na análise PAS para avaliar a superfície após tratamento, e apenas para a velocidade 0,05 cm.s-1 com plasma de Ar/O2 alterações espectroscópicas foram detectadas. A redução na medida de ângulo de contato e o aumento na resistência ao descascamento da colagem indicaram melhoras nas propriedades adesivas da superfície. Falhas de adesão foram observadas entre a interface do filme de adesivo de PU e da borracha de EPDM, e confirmados por UATR/FT-IR.

  3. Degradation patterns of natural and synthetic textiles on a soil surface during summer and winter seasons studied using ATR-FTIR spectroscopy

    Science.gov (United States)

    Ueland, Maiken; Howes, Johanna M.; Forbes, Shari L.; Stuart, Barbara H.

    2017-10-01

    Textiles are a valuable source of forensic evidence and the nature and condition of textiles collected from a crime scene can assist investigators in determining the nature of the death and aid in the identification of the victim. Until now, much of the knowledge of textile degradation in forensic contexts has been based on the visual inspection of material collected from soil environments. The purpose of the current study was to investigate the potential of a more quantitative approach to the understanding of forensic textile degradation through the application of infrared spectroscopy. Degradation patterns of natural and synthetic textile materials as they were subjected to a natural outdoor environment in Australia were investigated. Cotton, polyester and polyester - cotton blend textiles were placed on a soil surface during the summer and winter seasons and were analysed over periods 1 and 1.5 years, respectively, and examined using attenuated total reflectance (ATR) spectroscopy. Statistical analysis of the spectral data obtained for the cotton material correlated with visual degradation and a difference in the onset of degradation between the summer and winter season was revealed. The synthetic material did not show any signs of degradation either visually or statistically throughout the experimental period and highlighted the importance of material type in terms of preservation. The cotton section from the polyester - cotton blend samples was found to behave in a similar manner to that of the 100% cotton samples, however principal component analysis (PCA) demonstrated that the degradation patterns were less distinct in both the summer and winter trial for the blend samples. These findings indicated that the presence of the synthetic material may have inhibited the degradation of the natural material. The use of statistics to analyse the spectral data obtained for textiles of forensic interest provides a better foundation for the interpretation of the data

  4. Formación de investigadores en medicina familiar: El modelo de tutorización en investigación Asesor-Tutor-Residente (ATR

    Directory of Open Access Journals (Sweden)

    E. Raúl Ponce Rosas

    Full Text Available El tutor de la medicina de familia, los principios y características de la tutoría y la relación tutor-residente son elementos fundamentales para el desarrollo adecuado de los cursos de especialización de esta disciplina. La tutoría o tutorización en medicina familiar es la base de la docencia y se centra en la figura de una relación humana de enseñanza individualizada tutor-residente en la práctica asistencial, docente y de investigación. Los modelos de tutorización en medicina de familia proporcionan herramientas útiles para establecer una adecuada relación tutor-residente. En este trabajo se describe el modelo de tutorización en investigación Asesor-Tutor-Residente, que se lleva a cabo en el Curso de Especialización de Medicina Familiar en la Facultad de Medicina de la UNAM, México. El modelo de tutorización en investigación Asesor-Tutor-Residente (ATR, es un paradigma de capacitación teórico-práctico en esta importante y fundamental área de la medicina de familia. El modelo ATR pretende motivar e interesar a tutores y residentes para hacer investigación con base en la demostración y la supervisión formativa a través de la asesoría continua, reflexiva, planeada y sistematizada.

  5. In situ observation on the dynamic process of evaporation and crystallization of sodium nitrate droplets on a ZnSe substrate by FTIR-ATR.

    Science.gov (United States)

    Zhang, Qing-Nuan; Zhang, Yun; Cai, Chen; Guo, Yu-Cong; Reid, Jonathan P; Zhang, Yun-Hong

    2014-04-17

    Sodium nitrate is a main component of aging sea salt aerosol, and its phase behavior has been studied repeatedly with wide ranges observed in the efflorescence relative humidity (RH) in particular. Studies of the efflorescence dynamics of NaNO3 droplets deposited on a ZnSe substrate are reported, using an in situ Fourier transform infrared attenuated total reflection (FTIR-ATR) technique. The time-dependence of the infrared spectra of NaNO3 aerosols accompanying step changes in RH have been measured with high signal-to-noise ratio. From the IR difference spectra recorded, changes of the time-dependent absorption peak area of the O-H stretching band (ν-OH, ∼3400 cm(-1)) and the nitrate out-of-plane bending band (ν2-NO3(-), ∼836 cm(-1)) are obtained. From these measurements, changes in the IR signatures can be attributed to crystalline and solution phase nitrate ions, allowing the volume fraction of the solution droplets that have crystallized to be determined. Then, using these clear signatures of the volume fraction of droplets that have yet to crystallize, the homogeneous and heterogeneous nucleation kinetics can be studied from conventional measurements using a steady decline in RH. The nucleation rate measurements confirm that the rate of crystallization in sodium nitrate droplets is considerably less than in ammonium sulfate droplets at any particular degree of solute supersaturation, explaining the wide range of efflorescence RHs observed for sodium nitrate in previous studies. We demonstrate that studying nucleation kinetics using the FTIR-ATR approach has many advantages over brightfield imaging studies on smaller numbers of larger droplets or measurements made on single levitated particles.

  6. Positron emitter labeled enzyme inhibitors

    Science.gov (United States)

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1987-05-22

    This invention involved a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide in activators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  7. PROTEIN INHIBITORS SYNTHESISED BY MICROORGANISMS

    Directory of Open Access Journals (Sweden)

    O. V. Matseliukh

    2013-12-01

    Full Text Available In a review the literature data on protein inhibitors of peptidases synthesised by different types of microorganisms are systematized. It is shown that at the present time on the basis of amino acid sequence homology protein inhibitors are grouped into 77 families, 29 of which include inhibitors of microorganisms. The mechanism of inhibition of peptidases by proteins may be related to their catalytic mechanism of action or include unrelated blocking of the active site or its surroundings. The structural elements of the protein inhibitors are responsible for binding to the peptidases, mostly include the N- or C-terminal sequences, the unprotected polypeptide loops (chains, which are acting independently or in combination with other elements. The basic properties, structural features and, where it is established, the functions of the protein inhibitors of peptidases are considered. Since some of these proteins effectively inhibit such peptidases as subtilisin, chymotrypsin, pancreatic elastase, their practical use in the treatment of diseases such as emphysema, arthritis, pancreatitis, thrombosis, hypertension, muscular dystrophy, cancer. It is suggested that the role of a bacterial homologue of Escherichia coli alphaacroglobulin, which is a periplasmic protein, is to protect the periplasmic space from the action of bacteria own proteases. Based on the specific properties of alpha-2-macroglobulin to bind endopeptidases active molecules, they are used in biotechnology to isolate endopeptidases from crude biological preparations and titration of its active centers. Some free–living bacteria are able to synthesize protein inhibitors to protect from the effects of its own enzymes, while the presence of these proteins in pathogens may play a certain role both in the infectious process and in the protection of the host proteases.

  8. Proton pump inhibitors and gastroenteritis

    NARCIS (Netherlands)

    R.J. Hassing (Robert); A. Verbon (Annelies); H. de Visser (Herman); A. Hofman (Albert); B.H.Ch. Stricker (Bruno)

    2016-01-01

    textabstractAn association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam

  9. Evaluation of Erosion of the Dummy “EE” Plate 19 in YA Type ATR Fuel Element During Reactor PALM Cycles

    Energy Technology Data Exchange (ETDEWEB)

    Brower, Jeffrey O. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor; Glazoff, Michael V. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor; Eiden, Thomas J. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor; Rezvoi, Aleksey V. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor

    2016-08-01

    Advanced Test Reactor (ATR) Cycle 153B-1 was a 14-day, high-power, powered axial locator mechanism (PALM) operating cycle that completed on April 12, 2013. Cycle 153B-1 was a typical operating cycle for the ATR, and did not result in any unusual plant transients. ATR was started up and shut down as scheduled. The PALM drive physically moves the selected experiments into and out of the core to simulate reactor startup and heat up, and shutdown and cooldown transients, while the reactor remains in steady-state conditions. However, after the cycle was over, when the fuel elements were removed from the core and inspected, several thousand flow-assisted erosion pits and “horseshoeing” defects were readily observed on the surface of the several YA-type fuel elements (these are aluminum “dummy” plates that contain no fuel). In order to understand these erosion phenomena, a thermal-hydraulic model of coolant channel 20 on a YA-M fuel element was generated. The boundaries of the model were the aluminum EE plate of a YA-M fuel element and a beryllium reflector block with 13 horizontal saw cuts which represented regions of zero flow. The heat generated in fuel plates 1 through 18 was modeled to be passing through the aluminum EE plate. The coolant channel 20 width was set at 0.058 in. (58 mils). It was established that the horizontal saw cuts had a significant effect on the temperature of the coolant. The flow, which was expected to vary linearly with gradual heating of the coolant as it passed through the channel, was extremely turbulent. The temperature rise, which was expected to be a smooth “S” curve, was represented by a series temperature rise “humps,” which occurred at each horizontal saw cut in the beryllium reflector block. Each of the 13 saw cuts had a chamfered edge which resulted in the coolant flow being re-directed as a jet across the coolant channel into the surface of the EE plate, which explained the temperature rise and the observed

  10. Nicotinamide phosphoribosyltransferase inhibitors, design, preparation and SAR

    DEFF Research Database (Denmark)

    Christensen, Mette Knak; Erichsen, Kamille Dumong; Olesen, Uffe Hogh

    2013-01-01

    Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. Using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described and compounds optimize...

  11. FTIR-ATR-based prediction and modelling of lignin and energy contents reveals independent intra-specific variation of these traits in bioenergy poplars

    Directory of Open Access Journals (Sweden)

    Taylor Gail

    2011-04-01

    Full Text Available Abstract Background There is an increasing demand for renewable resources to replace fossil fuels. However, different applications such as the production of secondary biofuels or combustion for energy production require different wood properties. Therefore, high-throughput methods are needed for rapid screening of wood in large scale samples, e.g., to evaluate the outcome of tree breeding or genetic engineering. In this study, we investigated the intra-specific variability of lignin and energy contents in extractive-free wood of hybrid poplar progenies (Populus trichocarpa × deltoides and tested if the range was sufficient for the development of quantitative prediction models based on Fourier transform infrared spectroscopy (FTIR. Since lignin is a major energy-bearing compound, we expected that the energy content of wood would be positively correlated with the lignin content. Results Lignin contents of extractive-free poplar wood samples determined by the acetyl bromide method ranged from 23.4% to 32.1%, and the calorific values measured with a combustion calorimeter varied from 17260 to 19767 J g-1. For the development of calibration models partial least square regression and cross validation was applied to correlate FTIR spectra determined with an attenuated total reflectance (ATR unit to measured values of lignin or energy contents. The best models with high coefficients of determination (R2 (calibration = 0.91 and 0.90; R2 (cross-validation = 0.81 and 0.79 and low root mean square errors of cross validation (RMSECV = 0.77% and 62 J g-1 for lignin and energy determination, respectively, were obtained after data pre-processing and automatic wavenumber restriction. The calibration models were validated by analyses of independent sets of wood samples yielding R2 = 0.88 and 0.86 for lignin and energy contents, respectively. Conclusions These results show that FTIR-ATR spectroscopy is suitable as a high-throughput method for lignin and energy

  12. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    current barriers of kinase inhibitors, including poor selectivity and emergence of drug resistance. In spite of the small number of identified allosteric inhibitors in comparison with that of inhibitors targeting the ATP pocket, encouraging results, such as the FDA-approval of the first small...

  13. Study of the interface solid/solutions containing PEO-PPO block copolymers and asphaltenes by FTIR/ATR; Estudo de solucoes de copolimeros em bloco de PEO-PPO contendo asfaltenos por FTIR/DTA

    Energy Technology Data Exchange (ETDEWEB)

    Aguiar, Janaina I.S.; Neto, Jessica S.G.; Mansur, Claudia R.E. [Universidade Federal do Rio de Janeiro, Instituto de Macromoleculas, Laboratorio de Macromoleculas e Coloides na Industria de Petroleo, Rio de Janeiro, RJ (Brazil)], E-mails: janaina_333@hotmail.com, kinha_dac_dm@hotmail.com; celias@ima.ufrj.br

    2011-07-01

    The formation of water/oil emulsions can cause problems in various stages of production, processing and refining of petroleum. In this study, the technique of Fourier transform infrared spectroscopy (FTIR) using the method of attenuated total reflectance (ATR) was applied to study the solid-solutions of block copolymers based on poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) interface and its interaction in this interface with asphaltenic fractions of petroleum. The solid is the crystal of the ATR. Initially, we determined the critical micelle concentration values of the copolymers, which were consistent those obtained by a tensiometer. Bottle Test was also performed to correlate the efficiency of PEO-PPO copolymers in the breaking of water/oil emulsions with its adsorption at the interfaces solutions. (author)

  14. Proteasome inhibitors with photocontrolled activity.

    Science.gov (United States)

    Hansen, Mickel J; Velema, Willem A; de Bruin, Gerjan; Overkleeft, Herman S; Szymanski, Wiktor; Feringa, Ben L

    2014-09-22

    Proteasome inhibitors are widely used in cancer treatment as chemotherapeutic agents. However, their employment often results in severe side effects, due to their non-specific cytotoxicity towards healthy tissue. This problem might be overcome by using a photopharmacological approach, that is, by attaining external, dynamic, spatiotemporal photocontrol over the activity of a cytotoxic agent, achieved by the introduction of a photoswitchable moiety into its molecular structure. Here we describe the design, synthesis, and activity of photoswitchable proteasome inhibitors. Substantial differences in proteasome inhibitory activity in cell extracts were observed before and after irradiation with light. The presented results show potential for the development of chemotherapeutic agents that can be switched on and off with light, constituting a new strategy for spatiotemporally modulating proteasomal activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Small-molecule arginase inhibitors.

    Science.gov (United States)

    Ivanenkov, Yan A; Chufarova, Nina V

    2014-01-01

    Arginase is an enzyme that metabolizes L-arginine to L-ornithine and urea. In addition to its fundamental role in the hepatic ornithine cycle, it also influences the immune systems in humans and mice. Arginase participates in many inflammatory disorders by decreasing the synthesis of nitric oxide and inducing fibrosis and tissue regeneration. L-arginine deficiency, which is modulated by myeloid cell arginase, suppresses T-cell immune response. This mechanism plays a fundamental role in inflammation-associated immunosuppression. Pathogens can synthesize their own arginase to elude immune reaction. Small-molecule arginase inhibitors are currently described as promising therapeutics for the treatment of several diseases, including allergic asthma, inflammatory bowel disease, ulcerative colitis, cardiovascular diseases (atherosclerosis and hypertension), diseases associated with pathogens (e.g., Helicobacter pylori, Trypanosoma cruzi, Leishmania, Mycobacterium tuberculosis and Salmonella), cancer and induced or spontaneous immune disorders. This article summarizes recent patents in the area of arginase inhibitors and discusses their properties.

  16. Proteasome inhibitors in cancer therapy

    Directory of Open Access Journals (Sweden)

    Wioletta Romaniuk

    2015-12-01

    Full Text Available Proteasomes are multisubunit enzyme complexes. They contain three enzymatic active sites which are termed chymotrypsin-like, trypsin-like, and caspase-like. The elementary function of the proteasomes is degradation of damaged proteins. Proteasome inhibition leads to accumulation of damaged protein, which leads to caspase activation and cell death. This relationship is used in cancer therapy. Bortezomib is the first proteasome inhibitor approved by the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma. Carfilzomib belongs to the second generation of drugs, which was approved by the US FDA in 2012. Currently in the study phase there are four new inhibitors: ixazomib (MLN9780/MLN2238, delanzomib (CEP-18770, oprozomib (ONX0912/PR-047 and marizomib (NPI-0052.

  17. Natural Inhibitors of Maillard Browning

    Science.gov (United States)

    2013-12-01

    incorporated into pre-selected candidate ration components for evaluation via storage, sensory and chemical analysis. The concentration of inhibitor was...inhibiting Maillard browning, also known as non-enzymatic browning, a complex reaction which can lead to darkening of color, off- odors , off-flavors...nutritional intake, and decrease waste due to non-consumption of sensory degraded ration components. 1.1 Maillard Browning Maillard browning, also

  18. Proton Pump Inhibitors and Gastritis

    OpenAIRE

    Suzuki, Masayuki; Suzuki, Hidekazu; Hibi, Toshifumi

    2008-01-01

    Proton pump inhibitors (PPIs) are novel compounds that strongly inhibit the H+/K+-ATPase in the gastric parietal cells to cause profound suppression of acid secretion. Acid-generating ATPase, also known as vacuolar-type ATPase, is located in the lysozomes of leukocytes and osteoclasts and its activity is also reportedly influenced by treatment with PPIs. This concept is supported by the results of studies using autoradiography in which 3H-Lansoprazole uptake sites were clearly detected in the...

  19. Effect of pH on the Nitrite Hydrogenation Mechanism over Pd/Al2O3 and Pt/Al2O3: Details Obtained with ATR-IR Spectroscopy

    DEFF Research Database (Denmark)

    Ebbesen, Sune Dalgaard; Mojet, Barbara L.; Lefferts, Leon

    2011-01-01

    on catalytic surfaces in water. In this paper, the influence of pH was studied on adsorption and subsequent hydrogenation of nitrite in water between pH 5 and 9 over Pd/Al2O3 and Pt/Al2O3, using ATR-IR spectroscopy. On both catalysts, pH clearly influenced the surface coverage and reaction rates...

  20. Characterization of Developmental Immature Fiber ( im) Mutant and Texas Marker-1 (TM-1) Cotton Fibers Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy.

    Science.gov (United States)

    Liu, Yongliang; Kim, Hee-Jin

    2017-07-01

    The immature fiber ( im) mutant is one type of cotton fiber mutant with unique characteristics of non-fluffy cotton bolls. Compared to its near-isogenic wild type Texas Marker-1 (TM-1), im fiber has a thin secondary cell wall and is less mature. In this work, we applied the previously proposed principal component analysis (PCA) and simple algorithms to analyze the attenuated total reflection Fourier transform infrared (ATR FT-IR) spectra of developmental im and TM-1 fibers. The results from these approaches could not effectively and consistently indicate the inherent difference between TM-1 and im fibers at the same developmental stage. The difference between TM-1 and corresponding im fibers was detected when comparing the normalized intensity variations of the 730 cm-1 bands. The 730 cm-1 band intensities in developmental im fibers are temporally lower than those in developmental TM-1 fibers although they became similar when the TM-1 and im fibers are fully mature. The observation might imply the likelihood of temporal reduction of amorphous regions in developmental im fibers rather than in developmental TM-1 fibers.

  1. Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR FT-IR) Applied to Study the Distribution of Ink Components in Printed Newspapers.

    Science.gov (United States)

    Gómez, Nuria; Molleda, Cristina; Quintana, Ester; Carbajo, José M; Rodríguez, Alejandro; Villar, Juan C

    2016-09-01

    A new method was developed to study how the oil and cyan pigments of cold-set ink are distributed in newspaper thickness. The methodology involved laboratory printing followed by delamination of the printed paper. The unprinted side, printed side, and resulting layers were analyzed using attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR). Three commercial newspapers and black and cyan cold-set inks were chosen for the study. Attenuated total reflection Fourier transform infrared spectroscopy enabled the proportion of oil and cyan pigment on the printed surface and throughout the sheet thickness to be measured. Oil percentage was evaluated as the area increment of the region from 2800 cm(-1) to 3000 cm(-1) The relative amount of cyan pigment was determined as the area of the absorption band at 730 cm(-1) The ink oil was found mainly below half the paper thickness, whereas the pigment was detected at the layers closer to the printed surface, at a depth penetration of less than 15 µm (20% of thickness). Distribution of these two components in paper thickness depended on the type of cold-set ink, the amount of ink transferred, and the newspaper properties. © The Author(s) 2016.

  2. ATM/ATR-related checkpoint signals mediate arsenite-induced G{sub 2}/M arrest in primary aortic endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsou, Tsui-Chun; Tsai, Feng-Yuan; Yeh, Szu-Ching; Chang, Louis W. [National Health Research Institutes, Division of Environmental Health and Occupational Medicine, Miaoli County (Taiwan)

    2006-12-15

    Epidemiological studies have demonstrated a high association of inorganic arsenic exposure with vascular disease. Our recent in vitro studies have linked this vascular damage to vascular endothelial dysfunction induced by arsenic exposure. However, cell-cycle arrest induced by arsenic and its involvement in vascular dysfunction remain to be clarified. In this study, we employed primary porcine aortic endothelial cells to investigate regulatory mechanisms of G{sub 2}/M phase arrest induced by arsenite. Our study revealed that lower concentrations of arsenite (1 and 3 {mu}M) increased cell proliferation, whereas higher concentrations of arsenite (10, 20, and 30 {mu}M) inhibited cell proliferation together with correlated increases in G{sub 2}/M phase arrest. We found that this arsenite-induced G{sub 2}/M phase arrest was accompanied by accumulation and/or phosphorylation of checkpoint-related molecules, including p53, Cdc25B, Cdc25C, and securin. Inhibition of activations of these checkpoint-related molecules by caffeine significantly attenuated the 30-{mu}M arsenite-induced G{sub 2}/M phase arrest by 93%. Our data suggest that the DNA damage responsive kinases ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) play critical roles in arsenite-induced G{sub 2}/M phase arrest in aortic endothelial cells possibly via regulation of checkpoint-related signaling molecules including p53, Cdc25B, Cdc25C, and securin. (orig.)

  3. Elevated levels of the polo kinase Cdc5 override the Mec1/ATR checkpoint in budding yeast by acting at different steps of the signaling pathway.

    Directory of Open Access Journals (Sweden)

    Roberto Antonio Donnianni

    2010-01-01

    Full Text Available Checkpoints are surveillance mechanisms that constitute a barrier to oncogenesis by preserving genome integrity. Loss of checkpoint function is an early event in tumorigenesis. Polo kinases (Plks are fundamental regulators of cell cycle progression in all eukaryotes and are frequently overexpressed in tumors. Through their polo box domain, Plks target multiple substrates previously phosphorylated by CDKs and MAPKs. In response to DNA damage, Plks are temporally inhibited in order to maintain the checkpoint-dependent cell cycle block while their activity is required to silence the checkpoint response and resume cell cycle progression. Here, we report that, in budding yeast, overproduction of the Cdc5 polo kinase overrides the checkpoint signaling induced by double strand DNA breaks (DSBs, preventing the phosphorylation of several Mec1/ATR targets, including Ddc2/ATRIP, the checkpoint mediator Rad9, and the transducer kinase Rad53/CHK2. We also show that high levels of Cdc5 slow down DSB processing in a Rad9-dependent manner, but do not prevent the binding of checkpoint factors to a single DSB. Finally, we provide evidence that Sae2, the functional ortholog of human CtIP, which regulates DSB processing and inhibits checkpoint signaling, is regulated by Cdc5. We propose that Cdc5 interferes with the checkpoint response to DSBs acting at multiple levels in the signal transduction pathway and at an early step required to resect DSB ends.

  4. In-Situ ATR-FTIR and Surface Complexation Modeling Study of the Adsorption of Dimethylarsenic Acid and p-Arsanilic Acid on Iron Oxides

    Science.gov (United States)

    Goldberg, S. R.; Al-Abadleh, H.; Mitchell, W.

    2010-12-01

    Arsenic is an element that exists naturally in many rocks and minerals around the world, accumulates in petroleum, shale, and coal deposits as a result of biogeochemical processes, and is found in fly ash from fuel combustion. Arsenic compounds in their organic and inorganic forms pose both health and environmental risks. The environmental fate of arsenic compounds is controlled to a large extent by their surface interactions with inorganic and organic surfaces. We report results from applying the triple layer surface complexation model to adsorption isotherm and pH-envelope experimental data of dimethylarsenic acid, DMA, and p-arsanilic acid, p-AsA on the iron oxides, hematite and goethite. Ligand exchange reactions were based on the interpretation of ATR-FTIR spectra of DMA and p-AsA surface complexes. Surface coverage of the organoarsenicals was quantified in-situ from the spectral component at 840 cm-1. The best model fit to the DMA adsorption data was obtained using an outer-sphere complex, whereas for p-AsA, best model fit was obtained using two monodentate inner-sphere surface complexes. The significance of the results is discussed in relation to improving modeling tools used by environmental regulators. Accurate predictive modeling tools are needed for effective design of arsenic removal technologies using iron oxide minerals.

  5. In situ ATR-FTIR and surface complexation modeling studies on the adsorption of dimethylarsinic acid and p-arsanilic acid on iron-(oxyhydr)oxides.

    Science.gov (United States)

    Mitchell, William; Goldberg, Sabine; Al-Abadleh, Hind A

    2011-06-15

    Arsenic is an element that exists naturally in many rocks and minerals around the world. It also accumulates in petroleum, shale, oil sands, and coal deposits as a result of biogeochemical processes, and it has been found in fly ash from the combustion of solid biofuels. Arsenic compounds in their organic and inorganic forms pose both a health and an environmental risk, and continue to be a challenge to the energy industry. The environmental fate and removal technologies of arsenic compounds are controlled to a large extent by their surface interactions with inorganic and organic adsorbents. We report thermodynamic binding constants, K(binding), from applying the triple-layer surface complexation model to adsorption isotherm and pH envelope data for dimethylarsinic acid (DMA) and p-arsanilic acid (p-AsA) on hematite and goethite. Ligand exchange reactions were constructed based on the interpretation of ATR-FTIR spectra of DMA and p-AsA surface complexes. Surface coverage of adsorbates was quantified in situ from the spectral component at 840 cm(-1). The best fit to the DMA adsorption data was obtained using outer-sphere complex formation, whereas for p-AsA, the best fit was obtained using two monodentate inner-sphere surface complexes. The significance of the results is discussed in relation to improving modeling tools used by environmental regulators and the energy sector for optimum control of arsenic content in fuels. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. ATR-FTIR spectroscopy study of the influence of pH and contact time on the adhesion of Shewanella putrefaciens bacterial cells to the surface of hematite.

    Science.gov (United States)

    Elzinga, Evert J; Huang, Jen-How; Chorover, Jon; Kretzschmar, Ruben

    2012-12-04

    Attachment of live cells of Shewanella putrefaciens strain CN-32 to the surface of hematite (α-Fe(2)O(3)) was studied with in situ ATR-FTIR spectroscopy at variable pH (4.5-7.7) and contact times up to 24 h. The IR spectra indicate that phosphate based functional groups on the cell wall play an important role in mediating adhesion through formation of inner-sphere coordinative bonds to hematite surface sites. The inner-sphere attachment mode of microbial P groups varies with pH, involving either a change in protonation or in coordination to hematite surface sites as pH is modified. At all pH values, spectra collected during the early stages of adhesion show intense IR bands associated with reactive P-groups, suggestive of preferential coordination of P-moieties at the hematite surface. Spectra collected after longer sorption times show distinct frequencies from cell wall protein and carboxyl groups, indicating that bacterial adhesion occurring over longer time scales is to a lesser degree associated with preferential attachment of P-based bacterial functional groups to the hematite surface. The results of this study demonstrate that pH and reaction time influence cell-mineral interactions, implying that these parameters play an important role in determining cell mobility and biofilm formation in aqueous geochemical environments.

  7. Glyphosate complexation to aluminium(III). An equilibrium and structural study in solution using potentiometry, multinuclear NMR, ATR-FTIR, ESI-MS and DFT calculations.

    Science.gov (United States)

    Purgel, Mihály; Takács, Zoltán; Jonsson, Caroline M; Nagy, Lajos; Andersson, Ingegärd; Bányai, István; Pápai, Imre; Persson, Per; Sjöberg, Staffan; Tóth, Imre

    2009-11-01

    The stoichiometries and stability constants of a series of Al(3+)-N-phosponomethyl glycine (PMG/H(3)L) complexes have been determined in acidic aqueous solution using a combination of precise potentiometric titration data, quantitative (27)Al and (31)P NMR spectra, ATR-FTIR spectrum and ESI-MS measurements (0.6M NaCl, 25 degrees C). Besides the mononuclear AlH(2)L(2+), Al(H(2)L)(HL), Al(HL)(2)(-) and Al(HL)L(2-), dimeric Al(2)(HL)L(+) and trinuclear Al(3)H(5)L(4)(2+) complexes have been postulated. (1)H and (31)P NMR data show that different isomers co-exist in solution and the isomerization reactions are slow on the (31)P NMR time scale. The geometries of monomeric and dimeric complexes likely double hydroxo bridged and double phosphonate bridged isomers have been optimized using DFT ab initio calculations starting from rational structural proposals. Energy calculations using the PCM solvation method also support the co-existence of isomers in solutions.

  8. UV but not X rays stimulate homologous recombination between sister chromatids and homologs in a Saccharomyces cerevisiae mec1 (ATR) hypomorphic mutant.

    Science.gov (United States)

    Fasullo, Michael; Sun, Mingzeng

    2008-12-15

    MEC1, the essential yeast ATM/ATR homolog, prevents replication fork collapse and is required for the cellular response to DNA damage. We had previously observed higher rates of spontaneous SCE, heteroallelic recombination and translocations in mec1-21 mutants, which still retain some G2 checkpoint function, compared to mec1 null mutants, which are completely defective in checkpoint function, and wild type. However, the types of DNA lesions that are more recombinogenic in mec1-21, compared to wild type, are unknown. Here, we measured DNA damage-associated SCE, homolog (heteroallelic) recombination, and homology-directed translocations in mec1-21, and characterized types of DNA damage-associated chromosomal rearrangements that occur in mec1-21. Although frequencies of UV-associated recombination were higher in mec1-21, the mutant was defective in double-strand break-associated SCE and heteroallelic recombination. Over-expression of Rad53 in mec1-21 reduced UV-associated recombination but did not suppress the defect in X-ray-associated recombination. Both X ray and UV exposure increased translocation frequencies in mec1-21, but the majority of the UV-associated products were non-reciprocal translocations. We suggest that although recombinational repair of double-stand breaks is less efficient in mec1 mutants, recombinants may be generated by other mechanisms, such as break-induced replication.

  9. Kinetic Parameters during Bis-GMA and TEGDMA Monomer Polymerization by ATR-FTIR: The Influence of Photoinitiator and Light Curing Source

    Directory of Open Access Journals (Sweden)

    Aline B. Denis

    2016-01-01

    Full Text Available This study aimed to analyze the kinetic parameters of two monomers using attenuated total reflectance Fourier transform infrared (ATR-FTIR: 2,2-bis-[4-(2-hydroxy-3-methacryloxypropyl-1-oxy-phenyl] propane (Bis-GMA and triethylene glycol dimethacrylate (TEGDMA. The following were calculated to evaluate the kinetic parameters: maximum conversion rate (Rpmax, time at the maximum polymerization rate (tmax, conversion at Rpmax, and total conversion recorded at the maximum conversion point after 300 s. Camphorquinone (CQ and phenyl propanedione (PPD were used in this study as photoinitiators, whereas N,N-dimethyl-p-toluidine (DMPT amine was used as a coinitiator. LED apparatus and halogen lamp were used in turn to evaluate the effect that light source had on the monomer kinetics. The mass concentration ratio for the three resin preparations was 0.7 : 0.3 for Bis-GMA and TEGDMA: R1 (CQ + DMPT, R2 (PPD + DMPT, and R3 (PPD + CQ + DMPT. The PPD association with the CQ photoinitiator altered the polymerization kinetics compared to a resin containing only the CQ photoinitiator. The light sources exhibited no significant differences for tmax of R1 and R3. Resins containing only the PPD initiator exhibited a higher tmax than those containing only CQ. However, the Rpmax decreased for resins containing the PPD photoinitiator.

  10. Study of Chemical Intermediates by Means of ATR-IR Spectroscopy and Hybrid Hard- and Soft-Modelling Multivariate Curve Resolution-Alternating Least Squares

    Directory of Open Access Journals (Sweden)

    Junxiu Ma

    2017-01-01

    Full Text Available 3,5-Diamino-1,2,4-triazole (DAT became a significant energetic materials intermediate, and the study of its reaction mechanism has fundamental significance in chemistry. The aim of this study is to investigate the ability of online attenuated total reflection infrared (ATR-IR spectroscopy combined with the novel approach of hybrid hard- and soft-modelling multivariate curve resolution-alternating least squares (HS-MCR analysis to monitor and detect changes in structural properties of compound during 3,5-diamino-1,2,4-triazole (DAT synthesis processes. The subspace comparison method (SCM was used to obtain the principal components number, and then the pure IR spectra of each substance were obtained by independent component analysis (ICA and HS-MCR. The extent of rotation ambiguity was estimated from the band boundaries of feasible solutions calculated using the MCR-BANDS procedure. There were five principal components including two intermediates in the process in the results. The reaction rate constants of DAT formation reaction were also obtained by HS-MCR. HS-MCR was used to analyze spectroscopy data in chemical synthesis process, which not only increase the information domain but also reduce the ambiguities of the obtained results. This study provides the theoretical basis for the optimization of synthesis process and technology of energetic materials and provides a strong technical support of research and development of energy material with extraordinary damage effects.

  11. Synthesis, physicochemical and spectroscopic characterization of copper(II)-polysaccharide pullulan complexes by UV-vis, ATR-FTIR, and EPR.

    Science.gov (United States)

    Mitić, Zarko; Cakić, Milorad; Nikolić, Goran M; Nikolić, Ružica; Nikolić, Goran S; Pavlović, Radmila; Santaniello, Enzo

    2011-02-15

    Bioactive copper(II) complexes with polysaccharides, like pullulan and dextran, are important in both veterinary and human medicine for the treatment of hypochromic microcitary anemia and hypocupremia. In aqueous alkaline solutions, Cu(II) ion forms complexes with the exopolysaccharide pullulan and its reduced low-molecular derivative. The metal content and the solution composition depend on pH, temperature, and time of the reaction. The complexing process begins in a weak alkali solution (pH >7) and involves OH groups of pullulan monomer (glucopyranose) units. Complexes of Cu(II) ion with reduced low-molecular pullulan (RLMP, M(w) 6000 g mol(-1)) were synthesized in water solutions, at the boiling temperature and at different pH values ranging from 7.5 to 12. The Cu(II) complex formation with RLMP was analyzed by UV-vis spectrophotometry and other physicochemical methods. Spectroscopic characterizations (ATR-FTIR, FT-IRIS, and EPR) and spectra-structure correlation of Cu(II)-RLMP complexes were also carried out. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Quantitative assessment of copper proteinates used as animal feed additives using ATR-FTIR spectroscopy and powder X-ray diffraction (PXRD) analysis.

    Science.gov (United States)

    Cantwell, Caoimhe A; Byrne, Laurann A; Connolly, Cathal D; Hynes, Michael J; McArdle, Patrick; Murphy, Richard A

    2017-08-01

    The aim of the present work was to establish a reliable analytical method to determine the degree of complexation in commercial metal proteinates used as feed additives in the solid state. Two complementary techniques were developed. Firstly, a quantitative attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic method investigated modifications in vibrational absorption bands of the ligand on complex formation. Secondly, a powder X-ray diffraction (PXRD) method to quantify the amount of crystalline material in the proteinate product was developed. These methods were developed in tandem and cross-validated with each other. Multivariate analysis (MVA) was used to develop validated calibration and prediction models. The FTIR and PXRD calibrations showed excellent linearity (R2 > 0.99). The diagnostic model parameters showed that the FTIR and PXRD methods were robust with a root mean square error of calibration RMSEC ≤3.39% and a root mean square error of prediction RMSEP ≤7.17% respectively. Comparative statistics show excellent agreement between the MVA packages assessed and between the FTIR and PXRD methods. The methods can be used to determine the degree of complexation in complexes of both protein hydrolysates and pure amino acids.

  13. DNA damage induces a kinetochore-based ATM/ATR-independent SAC arrest unique to the first meiotic division in mouse oocytes.

    Science.gov (United States)

    Lane, Simon I R; Morgan, Stephanie L; Wu, Tianyu; Collins, Josie K; Merriman, Julie A; ElInati, Elias; Turner, James M; Jones, Keith T

    2017-10-01

    Mouse oocytes carrying DNA damage arrest in meiosis I, thereby preventing creation of embryos with deleterious mutations. The arrest is dependent on activation of the spindle assembly checkpoint, which results in anaphase-promoting complex (APC) inhibition. However, little is understood about how this checkpoint is engaged following DNA damage. Here, we find that within minutes of DNA damage checkpoint proteins are assembled at the kinetochore, not at damage sites along chromosome arms, such that the APC is fully inhibited within 30 min. Despite this robust response, there is no measurable loss in k-fibres, or tension across the bivalent. Through pharmacological inhibition we observed that the response is dependent on Mps1 kinase, aurora kinase and Haspin. Using oocyte-specific knockouts we find the response does not require the DNA damage response kinases ATM or ATR. Furthermore, checkpoint activation does not occur in response to DNA damage in fully mature eggs during meiosis II, despite the divisions being separated by just a few hours. Therefore, mouse oocytes have a unique ability to sense DNA damage rapidly by activating the checkpoint at their kinetochores. © 2017. Published by The Company of Biologists Ltd.

  14. Determination of trans Fat in Selected Fast Food Products and Hydrogenated Fats of India Using Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) Spectroscopy.

    Science.gov (United States)

    Khan, Mohd Umar; Hassan, Mohammad Fahimul; Rauf, Abdul

    2017-01-01

    This paper reports the application of a simple and rapid method for the determination of trans fatty acid (TFA) content in some of the selected Indian fast food products and hydrogenated fats using Fourier transform infrared (FTIR) spectroscopy in conjunction with second derivative procedure. FTIR spectroscopy has been successfully applied to trans measurement using the absorbance bands at or near 966 cm-1 in the FTIR spectra. It was found from the analysis that TFA content of fast food product was ranging from 1.57% to 3.83% of the total fat while for hydrogenated fats, comparatively large quantity of TFA was detected in the range of 3.31% to 4.73%. Since GC-FID is most widely used method for the determination of fatty acid (FA) composition, this method was used for the sake of comparison. Value of regression coefficient was found very close to one (0.99503) with standard deviation of 0.10247 showing a good agreement between GC-FID and proposed ATR-FTIR method.

  15. Effects of metal ions on entero-soluble poly(methacrylic acid-methyl methacrylate) coating: a combined analysis by ATR-FTIR spectroscopy and computational approaches.

    Science.gov (United States)

    Cilurzo, Francesco; Gennari, Chiara G M; Selmin, Francesca; Vistoli, Giulio

    2010-04-05

    Poly(methacrylic acid-methyl methacrylate)s (HPMMs) are pH-dependent polymers which ionize and form salts (PMMs) in neutral conditions. Despite their wide use in tablet coating, the interactions of PMMs with electrolytes present in biorelevant media and luminal fluids have been scantly investigated. The data generated in the current work provide the basic information on the effect of bivalent cations, namely, Ca2+, Zn2+ and Mn2+, on the HPMMs' solubility and, consequently, on the performances (disintegration and drug dissolution) of acetaminophen gastroresistant tablets when exposed to fluid containing such salts. The interactions between polymers and metal ions were analyzed by ATR-FTIR spectroscopy and in silico combining molecular dynamics simulations to explore the conformational profiles of several oligomers with different M(w), taken as model of the polymers, with ab initio and semiempirical calculations in the gas phase. The computational results agree with the experimental data in terms of spatial disposition of the bications with respect to PMMs (Ca2+ and Mn2+ as bidentate form and Zn2+ as monodentate ligand) and interaction strength (Zn2+ > Mn(2+) > Ca2+). The tablet disintegration and dissolution rate of acetaminophen were strongly affected by the interactions of the dissolving copolymer with the metal ions which led to coating insolubilization. These preliminary results underline that the ingestion of metal ions at high concentrations could affect the drug liberation from gastroresistant dosage forms.

  16. Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as a Forensic Method to Determine the Composition of Inks Used to Print the United States One-cent Blue Benjamin Franklin Postage Stamps of the 19th Century.

    Science.gov (United States)

    Brittain, Harry G

    2016-01-01

    Through the combined use of infrared (IR) absorption spectroscopy and attenuated total reflectance (ATR) sampling, the composition of inks used to print the many different types of one-cent Benjamin Franklin stamps of the 19th century has been established. This information permits a historical evaluation of the formulations used at various times, and also facilitates the differentiation of the various stamps from each other. In two instances, the ink composition permits the unambiguous identification of stamps whose appearance is identical, and which (until now) have only been differentiated through estimates of the degree of hardness or softness of the stamp paper, or through the presence or absence of a watermark in the paper. In these instances, the use of ATR Fourier transform infrared spectroscopy (FT-IR) spectroscopy effectively renders irrelevant two 100-year-old practices of stamp identification. Furthermore, since the use of ATR sampling makes it possible to obtain the spectrum of a stamp still attached to its cover, it is no longer necessary to identify these blue Franklin stamps using their cancellation dates. © The Author(s) 2015.

  17. A novel mutation in the putative DNA helicase XH2 is responsible for male-to-female sex reversal associated with an atypical form of the ATR-X syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Ion, A.; Telvi, L.; Galacteros, F.; McElreavey, K. [Institut Pasteur, Paris (France)] [and others

    1996-06-01

    We describe a pedigree presenting X-linked severe mental retardation associated with multiple congenital abnormalities and 46,XY gonadal dysgenesis, leading in one family member to female gender assignment. Female carriers are unaffected. The dysmorphic features are similar to those described in the {alpha}-thalassemia and mental retardation (ATR-X) syndrome, although there is no clinical evidence of {alpha}-thalassemia in this family. In addition, the family had other clinical features not previously observed in the ATR-X syndrome, including partial optic-nerve atrophy and partial ocular albinism. Mutations in a putative DNA helicase, termed XH2, have been reported to give rise to the ATR-X syndrome. We screened the YCH2 gene for mutations in affected members of the family and identified a 4-bp deletion at an intron/exon boundary that removes an invariant 3{prime} splice-acceptor site. The mutation cosegregates with the syndrome. The genomic deletion causes missplicing of the pre-mRNA, which results in the loss of 8 bp of coding sequence, thereby generating a frameshift and a downstream premature stop codon. Our finding increases the range of clinical features associated with mutations in the XH2 gene. 17 refs., 4 figs., 2 tabs.

  18. Uso de plasma rico en plaquetas autólogo en el tratamiento quirúrgico de pseudoartrosis atrófica de fémur y tibia

    Directory of Open Access Journals (Sweden)

    Julio C Vejarano-Solano

    2013-04-01

    Full Text Available Objetivo: Describir y evaluar los resultados del tratamiento quirúrgico de pseudoartrosis atrófica de fémur o tibia mediante el uso de plasma rico en plaquetas (PRP autólogo. Material y métodos: Estudio descriptivo longitudinal de 20 casos (19 pacientes de pseudoartrosis atrófica de fémur o tibia tratados quirúrgicamente con PRP autólogo en el Hospital Nacional Cayetano Heredia de Lima, desde enero del 2008 hasta enero del 2012. El PRP fue preparado en el banco de sangre del hospital a partir de una unidad de sangre autóloga. Se evaluó el tiempo de consolidación ósea mediante radiografías seriadas y se registraron las complicaciones. Resultados: Se incluyeron 12 varones y 7 mujeres, con edad promedio de 33,8 años (15 a 67 años. Se evidenció consolidación en el 95% de los pacientes, el tiempo promedio para la consolidación fue 25 semanas. Se observó un caso de persistencia de infección con cultivo positivo a E. coli y un caso de refractura. Conclusiones: El PRP autólogo tiene un efecto beneficioso en la reparación del tejido óseo en casos de pseudoartrosis atrófica.

  19. Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro

    NARCIS (Netherlands)

    Walker, J.B.; Hughes, B.; James, I.; Haddock, P.; Kluft, C.; Bajzar, L.

    2003-01-01

    Two competitive inhibitors of TAFIa (activated thrombin-activable fibrinolysis inhibitor), 2-guanidinoethyl-mercaptosuccinic acid and potato tuber carboxypeptidase inhibitor, variably affect fibrinolysis of clotted human plasma. Depending on their concentration, the inhibitors shortened, prolonged,

  20. Emerging therapies for atopic dermatitis: JAK inhibitors.

    Science.gov (United States)

    Cotter, David G; Schairer, David; Eichenfield, Lawrence

    2018-03-01

    The Janus kinase-signal transducer and activator of transcription pathway is a conserved master regulator of immunity and myeloproliferation. Advanced understanding of this pathway has led to development of targeted inhibitors of Janus kinases (Jakinibs). As a class, JAK inhibitors effectively treat a multitude of hematologic and inflammatory diseases. Given such success, use of JAK inhibitors for mitigation of atopic dermatitis is under active investigation. Herein, we review the evolving data on the safety and efficacy of JAK inhibitors in treatment of atopic dermatitis. Although it is still early in the study of JAK inhibitors for atopic dermatitis, evidence identifies JAK inhibitors as effective alternatives to conventional therapies. Nonetheless, multiple large safety and efficacy trials are needed before widespread use of JAK inhibitors can be advocated for atopic dermatitis. Copyright © 2017. Published by Elsevier Inc.

  1. Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori1

    Science.gov (United States)

    Bravo, Luis Eduardo; Bravo, Juan Carlos; Realpe, José Luis; Zarama, Guillermo; Piazuelo, MarÍa Blanca; Correa, Pelayo

    2014-01-01

    RESUMEN Introducción El mapeo de las diferentes regiones del estómago y el número de fragmentos de mucosa gástrica disponibles para evaluación histopatológica son fuentes importantes de variación en el momento de clasificar y hacer la gradación de la gastritis crónica. Objetivos Estimar la sensibilidad del número de fragmentos de mucosa gástrica necesarios para establecer los diagnósticos de gastritis atrófica con metaplasia intestinal (MI), displasia y estado de infección por Helicobacter pylori. Además evaluar la variabilidad intra-observador en la clasificación de estas lesiones precursoras del cáncer gástrico. Materiales y métodos En una cohorte de 6 años de seguimiento se evaluaron 1,958 procedimientos de endoscopia realizados por dos gastroenterólogos. En cada procedimiento y de cada participante se obtuvieron 5 biopsias de mucosa gástrica que representaban antro, incisura angularis y cuerpo. Un único patólogo hizo la interpretación histológica de las 5 biopsias y proporcionó un diagnóstico definitivo global que se utilizó como patrón de referencia. Cada fragmento de mucosa gástrica examinado condujo a un diagnóstico individual para cada biopsia que se comparó con el patrón de referencia. La variabilidad intra-observador se evaluó en 127 personas que corresponden a una muestra aleatoria de 20% del total de endoscopias hechas a los 72 meses de seguimiento. Resultados La sensibilidad del diagnóstico de MI y displasia gástrica aumentó de manera significativa con el número de fragmentos de mucosa gástrica evaluados El sitio anatómico de mayor sensibilidad para el diagnóstico de MI y displasia fue la incisura angularis. Para descubrir H. pylori se logró alta sensibilidad con el estudio de un solo fragmento de mucosa gástrica (95.9%) y fue independiente del sitio de obtención de la biopsia. El acuerdo intra-observador para el diagnóstico de gastritis crónica fue 86.1% con valor kappa de 0.79 IC 95% (0.76-0.85). Las

  2. Attenuated total reflectance-mid infrared spectroscopy (ATR-MIR) coupled with independent components analysis (ICA): A fast method to determine plasticizers in polylactide (PLA).

    Science.gov (United States)

    Kassouf, Amine; Ruellan, Alexandre; Jouan-Rimbaud Bouveresse, Delphine; Rutledge, Douglas N; Domenek, Sandra; Maalouly, Jacqueline; Chebib, Hanna; Ducruet, Violette

    2016-01-15

    Compliance of plastic food contact materials (FCMs) with regulatory specifications in force, requires a better knowledge of their interaction phenomena with food or food simulants in contact. However these migration tests could be very complex, expensive and time-consuming. Therefore, alternative procedures were introduced based on the determination of potential migrants in the initial material, allowing the use of mathematical modeling, worst case scenarios and other alternative approaches, for simple and fast compliance testing. In this work, polylactide (PLA), plasticized with four different plasticizers, was considered as a model plastic formulation. An innovative analytical approach was developed, based on the extraction of qualitative and quantitative information from attenuated total reflectance (ATR) mid-infrared (MIR) spectral fingerprints, using independent components analysis (ICA). Two novel chemometric methods, Random_ICA and ICA_corr_y, were used to determine the optimal number of independent components (ICs). Both qualitative and quantitative information, related to the identity and the quantity of plasticizers in PLA, were retrieved through a direct and fast analytical method, without any prior sample preparations. Through a single qualitative model with 11 ICs, a clear and clean classification of PLA samples was obtained, according to the identity of plasticizers incorporated in their formulations. Moreover, a quantitative model was established for each formulation, correlating proportions estimated by ICA and known concentrations of plasticizers in PLA. High coefficients of determination (higher than 0.96) and recoveries (higher than 95%) proved the good predictability of the proposed models. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Reforma legislativa da televisão no Chile ante o futuro digital: um passo à frente, outro atrás

    Directory of Open Access Journals (Sweden)

    Lucas Sierra

    2010-05-01

    Full Text Available Este trabalho analisa criticamente a proposta de reforma à legislação televisiva que o Governo chileno enviou ao Congresso com vistas à futura tecnologia digital. A reforma é conformada por dois projetos de lei: um se refere à Lei 18.838, a Lei Geral de Televisão, e o outro à Lei 19.132, relativa à Televisão Nacional de Chile. Ambos os projetos são analisados aqui. O primeiro, sustenta-se, propõe um avanço interessante: a incorporação da categoria de serviços “intermediários” de telecomunicações à futura radiodifusão televisiva digital. Este é um passo no sentido da convergência que a tecnologia digital impulsiona entre os distintos serviços de telecomunicações. Este avanço, contudo, se vê limitado por outras propostas do projeto, como, por exemplo, o estabelecimento de “campanhas de utilidade ou interesse público” obrigatórias para os canais, o que representa uma intervenção estatal injustificada. O segundo projeto, sobre a Televisão Nacional de Chile, também é criticado. A razão fundamental é que ele estende e torna menos nítido o objetivo desta empresa estatal, lançando uma sombra de dúvida sobre o critério de subsidiariedade estatal que inspira nossa regulação econômica, ao mesmo tempo em que se propõe a romper o pé de igualdade que existe entre a televisão estatal e a privada. Em síntese, conclui-se, esta reforma legislativa dá um passo adiante, mas também um atrás.

  4. In situ ATR-IR spectroscopy study of adsorbed protein: Visible light denaturation of bovine serum albumin on TiO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Bouhekka, A., E-mail: Ahmed.Bouhekka@unige.ch [Departement de Chimie Physique, 30 Quai Ernest-Ansermet, CH-1211 Geneve 4 (Switzerland); Laboratoire de Physique des Couches Minces et Materiaux pour l' Electronique, Universite d' Oran Es-Senia, 31100 Oran (Algeria); Departement de Physique, Universite Hassiba Ben Bouali, 02000 Chlef (Algeria); Buergi, T., E-mail: Thomas.Buergi@unige.ch [Departement de Chimie Physique, 30 Quai Ernest-Ansermet, CH-1211 Geneve 4 (Switzerland)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer We study the behavior of BSA protein adsorbed on TiO{sub 2} using in situ IR spectroscopy. Black-Right-Pointing-Pointer We examine the secondary structure changes during light exposure. Black-Right-Pointing-Pointer Visible light illumination creates random coil in the secondary structure of BSA. Black-Right-Pointing-Pointer The denaturation of BSA adsorbed on TiO{sub 2} under visible light irradiation is irreversible. - Abstract: In this work in situ Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy in a flow-through cell was used to study the effect of visible light irradiation on bovine serum albumin (BSA) adsorbed on porous TiO{sub 2} films. The experiments were performed in water at concentrations of 10{sup -6} mol/l at room temperature. The curve fitting method of the second derivative spectra allowed us to explore details of the secondary structure of pure BSA in water and conformation changes upon adsorption as well as during and after illumination by visible light. The results clearly show that visible light influences the conformation of adsorbed BSA. The appearance of a shift of the amide I band, in the original spectra, from 1653 cm{sup -1} to 1648 cm{sup -1}, is interpreted by the creation of random coil in the secondary structure of adsorbed BSA. The second derivative analysis of infrared spectra permits direct quantitative analysis of the secondary structural components of BSA, which show that the percentage of {alpha}-helix decreases during visible light illumination whereas the percentage of random coil increases.

  5. Targeting telomerase with radiolabeled inhibitors.

    Science.gov (United States)

    Waghorn, Philip A; Jackson, Mark R; Gouverneur, Veronique; Vallis, Katherine A

    2017-01-05

    The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, 123 I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An 123 I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC 50 of 1.58 μM (MST-312 IC 50 : 0.23 μM). Clonogenic assays showed a dose dependant effect of 123 I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  6. Vanadium Compounds as PTP Inhibitors

    Directory of Open Access Journals (Sweden)

    Elsa Irving

    2017-12-01

    Full Text Available Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs and protein tyrosine phosphatases (PTPs. Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential.

  7. Proteasome inhibitor patents (2010 - present).

    Science.gov (United States)

    Metcalf, Rainer; Scott, Latanya M; Daniel, Kenyon G; Dou, Q Ping

    2014-04-01

    Over the past 3 years, numerous patents and patent applications have been submitted and published involving compounds designed to inhibit the proteasome. Proteasome inhibition has been of great interest in cancer research since disruption of proteolysis leads to a significant buildup of cytotoxic proteins and activation of apoptotic pathways, particularly in rapidly proliferating cells. The current standards in proteasome inhibition are the only FDA-approved inhibitors, bortezomib and carfilzomib. Although these drugs are quite effective in treating multiple myeloma and other blood tumors, there are shortcomings, including toxicities and resistance. Most of the current patents attempt to improve on existing compounds, by increasing bioavailability and selectivity, while attempting to reduce toxicity. A general categorization of similar compounds was employed to evaluate and compare drug design strategies. This review focuses on novel compounds and subsequent analogs developed for proteasome inhibition, used in preventing and treating human cancers. A comprehensive description and categorization of patents related to each type of compound and its derivatives, as well as their uses and efficacies as anticancer agents is included. A review of combination therapy patents has also been included. Although there are many diverse chemical scaffolds being published, there are few patented proteasome inhibitors whose method of inhibition is genuinely novel. Most patents utilize a destructive chemical warhead to attack the catalytic threonine residue of the proteasome active sites. Few patents try to depart from this, emphasizing the need for developing new mechanisms of action and specific targeting.

  8. Proton pump inhibitors and osteoporosis

    DEFF Research Database (Denmark)

    Andersen, Bjarne Nesgaard; Johansen, Per Birger; Abrahamsen, Bo

    2016-01-01

    PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months and a di......PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months...... and a discussion of these findings and how this has influenced our understanding of this association, the clinical impact and the underlying pathophysiology. RECENT FINDINGS: New studies have further strengthened existing evidence linking use of PPIs to osteoporosis. Short-term use does not appear to pose a lower...... risk than long-term use. There is a continued lack of conclusive studies identifying the pathogenesis. Direct effects on calcium absorption or on osteoblast or osteoclast action cannot at present plausibly explain the mechanism. SUMMARY: The use of PPIs is a risk factor for development of osteoporosis...

  9. Laura: Soybean variety lacking Kunitz trypsin inhibitor

    Directory of Open Access Journals (Sweden)

    Srebrić Mirjana

    2010-01-01

    Full Text Available Grain of conventional soybean varieties requires heat processing to break down trypsin inhibitor's activity before using as food or animal feed. At the same time, protein denaturation and other qualitative changes occur in soybean grain, especially if the temperature of heating is not controlled. Two types of trypsin inhibitor were found in soybean grain the Kunitz trypsin inhibitor and the Bowman-Birk inhibitor. Mature grain of soybean Laura is lacking Kunitz trypsin inhibitor. Grain yield of variety Laura is equal to high yielding varieties from the maturity group I, where it belongs. Lacking of Kunitz-trypsin inhibitor makes soybean grain suitable for direct feeding in adult non ruminant animals without previous thermal processing. Grain of variety Laura can be processed for a shorter period of time than conventional soybeans. This way we save energy, and preserve valuable nutritional composition of soybean grain, which is of interest in industrial processing.

  10. An inhibitor of phospholipase D in saliva

    Science.gov (United States)

    Dawson, Rex M. C.; Hemington, Norma

    1974-01-01

    1. Bovine, dog and human saliva contain substances which inhibit the soluble phospholipase D present in grass leaf or celery stalk. 2. The inhibitor in bovine saliva is of high molecular weight and exhibits considerable stability to heat, acids and alkalis. 3. The inhibitor has been purified free from salivary mucoprotein. 4. It is suggested that the inhibitor could protect the upper alimentary tract of a herbage-eating animal from the necrotic action of phospholipase D. PMID:4376946

  11. Histone deacetylase inhibitors in cancer therapy.

    Science.gov (United States)

    Lane, Andrew A; Chabner, Bruce A

    2009-11-10

    Epigenetic processes are implicated in cancer causation and progression. The acetylation status of histones regulates access of transcription factors to DNA and influences levels of gene expression. Histone deacetylase (HDAC) activity diminishes acetylation of histones, causing compaction of the DNA/histone complex. This compaction blocks gene transcription and inhibits differentiation, providing a rationale for developing HDAC inhibitors. In this review, we explore the biology of the HDAC enzymes, summarize the pharmacologic properties of HDAC inhibitors, and examine results of selected clinical trials. We consider the potential of these inhibitors in combination therapy with targeted drugs and with cytotoxic chemotherapy. HDAC inhibitors promote growth arrest, differentiation, and apoptosis of tumor cells, with minimal effects on normal tissue. In addition to decompaction of the histone/DNA complex, HDAC inhibition also affects acetylation status and function of nonhistone proteins. HDAC inhibitors have demonstrated antitumor activity in clinical trials, and one drug of this class, vorinostat, is US Food and Drug Administration approved for the treatment of cutaneous T-cell lymphoma. Other inhibitors in advanced stages of clinical development, including depsipeptide and MGCD0103, differ from vorinostat in structure and isoenzyme specificity, and have shown activity against lymphoma, leukemia, and solid tumors. Promising preclinical activity in combination with cytotoxics, inhibitors of heat shock protein 90, and inhibitors of proteasome function have led to combination therapy trials. HDAC inhibitors are an important emerging therapy with single-agent activity against multiple cancers, and have significant potential in combination use.

  12. [Development of new antiatherosclerotic agents--ACAT inhibitors and CETP inhibitors].

    Science.gov (United States)

    Miyazaki, A; Horiuchi, S

    1999-12-01

    Development of new antiatherosclerotic agents were reviewed focusing on ACAT inhibitors and CETP inhibitors. ACAT inhibitors enhance intracellular degradation of VLDL in hepatocytes. Cholesterol absorption in small intestine is inhibited by ACAT inhibitors. Thus, ACAT inhibitors reduce plasma cholesterol levels. In atherosclerotic lesions, ACAT inhibitors suppress foam cell formation (cholesteryl ester accumulation) in macrophages. Since ACAT inhibitors have multiple anti-atherogenic effects, they are considered future drugs controlling hypercholesterolemia and atherosclerosis. CETP inhibitors are expected to increase HDL and decrease LDL. Although the patients with CETP deficiency show high level of HDL, recent studies showed that they are not necessarily resistant to atherosclerosis. The strategy to inhibit CETP for suppressing atherosclerosis has not been established.

  13. Development of immune checkpoint inhibitors.

    Science.gov (United States)

    Kitano, Shigehisa

    2017-01-01

    Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4. In 2011, the US Food and Drug Administration approved the use of ipilimumab for the treatment of advanced metastatic melanoma. Then, nivolumab, which is a humanized mAb that blocks programmed death-1 (PD-1), was approved for use in the treatment of advanced melanoma in 2014 and of advanced non-small-cell lung carcinoma (NSCLC) in 2015 in Japan. Pembrolizumab, which is another anti-PD-1 antibody, was approved for use in the treatment of advanced melanoma and advanced NSCLC as the first-line therapy in 2016 in Japan. Thereafter, nivolumab was also approved for use in the treatment of advanced renal cell cancer in August 2016, of Hodgkin's lymphoma in December 2016, and of head and neck cancer in March 2017 in Japan. Moreover, phase III trials of anti-PD-1 mAb and anti-PD-ligand 1 mAb for use in the treatment of cancers, such as gastric, ovarian, bladder, and esophageal cancers, are ongoing. Several clinical trials have investigated new agents, alone and in combination, for use in the treatment of various cancers. Current advances in tumor immunology have unveiled the importance of immunosuppressive cells, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, especially in a tumor microenvironment (TME). Some data from basic research in mouse models and the immunomonitoring of cancer patients

  14. Calcineurin inhibitor minimisation versus continuation of calcineurin inhibitor treatment for liver transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Wettergren, Andre; Chan, An-Wen

    2012-01-01

    The therapeutic success of liver transplantation has been largely attributable to the development of effective immunosuppressive treatment regimens. In particular, calcineurin inhibitors were essential in reducing acute rejection and improving early survival. Currently, more than 90% of all liver...... transplant recipients are treated with the calcineurin inhibitor cyclosporine or tacrolimus. Unfortunately, calcineurin inhibitors cause adverse events, such as nephrotoxicity, and because of this, minimisation (reduction and withdrawal) regimens of calcineurin inhibitor have been developed and studied...

  15. Determinação quantitativa da concentração de silicone em antiespumantes por espectroscopia FT-IR / ATR e calibração multivariada Quantitative determination of silicone in antifoaming products by FT-IR / ATR spectroscopy and multivariate calibration

    Directory of Open Access Journals (Sweden)

    Marcelo H. F. Garcia

    2004-12-01

    Full Text Available Neste trabalho apresentamos uma alternativa para a dosagem do teor de silicone (polidimetilsiloxano em antiespumantes por meio da técnica de espectroscopia no infravermelho com transformada de Fourier (FT-IR, com a utilização do acessório de reflectância total atenuada (ATR. Os espectros foram registrados na faixa espectral de 2500 a 780 cm-1, com resolução de 4 cm-1 e 128 varreduras. A calibração de um modelo linear por meio da utilização do método de mínimos quadrados parciais (PLS aplicado aos espectros foi capaz de determinar satisfatoriamente a concentração de silicone nas amostras. Este método é de extrema importância para indústrias produtoras de antiespumantes siliconados, uma vez que o desempenho de tais produtos geralmente é avaliado em função da viscosidade dos mesmos. Muitas vezes no processo de fabricação de tais produtos ocorre uma homogeneização incompleta do silicone no solvente, o que leva a resultados de viscosidade que não são representativos das amostras analisadas. A determinação da concentração do teor de silicone é uma importante ferramenta para o Controle Estatístico de Processo (CEP, pois evita o desperdício de matérias-primas empregadas na fabricação dos antiespumantes.This work presents an alternative method to determine the concentration of silicone (polydimethylsiloxane in antifoaming products using Fourier Transformed Infrared Spectroscopy (FT-IR with the attenuated total reflectance (ATR accessory. The spectra were recorded in the range from 2500 to 780 cm-1, with a resolution of 4 cm-1 and 128 scans. With calibration of a linear model using PLS regression method applied to spectral data we were able to determine the silicone concentration in the samples. This method may be useful for antifoaming producers since the performance of such products generally is evaluated as a function of their viscosity. Moreover, during manufacturing an incomplete homogenization of silicone in the

  16. Integrin Inhibitors in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Maylein C. Juan-Rivera

    2018-02-01

    Full Text Available Prostate cancer (PCa is the most frequently diagnosed cancer and the third highest cause of cancer-related deaths in men in the U.S. The development of chemotherapeutic agents that can bind PCa tumor cells with high specificity is critical in order to increase treatment effectiveness. Integrin receptors and their corresponding ligands have different expression patterns in PCa cells. They have been identified as promising targets to inhibit pathways involved in PCa progression. Currently, several compounds have proven to target specific integrins and their subunits in PCa cells. In this article, we review the role of integrins inhibitors in PCa and their potential as therapeutic targets for PCa treatments. We have discussed the following: natural compounds, monoclonal antibodies, statins, campothecins analog, aptamers, d-aminoacid, and snake venom. Recent studies have shown that their mechanisms of action result in decrease cell migration, cell invasion, cell proliferation, and metastasis of PCa cells.

  17. Protein C inhibitor (plasminogen activator inhibitor-3) and the risk of venous thrombosis

    NARCIS (Netherlands)

    Meijers, JCM; Marquart, JA; Bertina, RM; Rosendaal, FR; Bouma, Bonno N.

    Protein C inhibitor (PCI), also known as plasminogen activator inhibitor-3, is a serine proteinase inhibitor that can inhibit enzymes in blood coagulation, fibrinolysis and fertility. The role of PCI in regulating the blood coagulation mechanism is not known, as it can inhibit both procoagulant

  18. Intellectual property issues of immune checkpoint inhibitors.

    Science.gov (United States)

    Storz, Ulrich

    2016-01-01

    Immune checkpoint inhibitors are drugs that interfere with tumor escape responses. Some members of this class are already approved, and expected to be blockbusters in the future. Many companies have developed patent activities in this field. This article focuses on the patent landscape, and discusses key players and cases related to immune checkpoint inhibitors.

  19. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase...

  20. [Interaction between clopidogrel and proton pump inhibitors

    NARCIS (Netherlands)

    Harmsze, A.M.; Boer, A. de; Boot, H.; Deneer, V.H.; Heringa, M.; Mol, P.G.; Schalekamp, T.; Verduijn, M.M.; Verheugt, F.W.A.; Comte, M. le

    2011-01-01

    The drug interaction between proton pump inhibitors and clopidogrel has been the subject of much study in recent years. Contradictory results regarding the effect of proton pump inhibitors on platelet reactivity and on clinical outcome in clopidogrel-treated patients have been reported in

  1. Biological and molecular mechanisms of sulfur mustard analog-induced toxicity in JB6 and HaCaT cells: Possible role of ATM/ATR-cell cycle checkpoint pathway

    Science.gov (United States)

    Tewari-Singh, Neera; Gu, Mallikarjuna; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2010-01-01

    Effective medical treatment and preventive measures for chemical warfare agent sulfur mustard (HD)-caused incapacitating skin toxicity are lacking, owing to limited knowledge of its mechanism of action. The proliferating basal epidermal cells are primary major sites of attack during HD-caused skin injury. Therefore, employing mouse JB6 and human HaCaT epidermal cells, here we investigated the molecular mechanism of HD analog, 2-chloroethyl ethyl sulfide (CEES)-induced skin cytotoxicity. As compared to control, up to 1 mM CEES treatment of these cells for 2, 4 and 24 h, caused dose-dependent decreases in cell viability and proliferation as measured by DNA synthesis, together with S and G2-M phase arrest in cell cycle progression. Mechanistic studies showed phosphorylation of DNA damage sensors and checkpoint kinases, ATM at ser1981 and ATR at ser428 within 30 min of CEES exposure, and modulation of S and G2-M phase-associated cell cycle regulatory proteins which are downstream targets of ATM and ATR kinases. Hoechst-propidium iodide (PI) staining demonstrated that CEES-induced cell death was both necrotic and apoptotic in nature and latter was induced at 4 and 24 h of CEES treatment in HaCaT and JB6 cells, respectively. An increase in caspase-3 activity and both caspase-3 and PARP cleavage coinciding with CEES-caused apoptosis in both cell lines suggested the involvement of caspase pathway. Together, our findings suggest a DNA damaging effect of CEES that activates ATM/ATR-cell cycle checkpoint signaling as well as caspase-PARP pathways leading to cell cycle arrest and apoptosis/necrosis in both JB6 and HaCaT cells. The identified molecular targets, quantitative biomarkers and epidermal cell models in this study, have the potential and usefulness in rapid development of effective prophylactic and therapeutic interventions against HD-induced skin toxicity. PMID:20469912

  2. Potential physiological role of plant glycosidase inhibitors

    DEFF Research Database (Denmark)

    Bellincampi, D.; Carmadella, L.; Delcour, J.A.

    2004-01-01

    Carbohydrate-active enzymes including glycosidases, transglycosidases, glycosyltransferases, polysaccharide lyases and carbohydrate esterases are responsible for the enzymatic processing of carbohydrates in plants. A number of carbohydrate-active enzymes are produced by microbial pathogens...... and insects responsible of severe crop losses. Plants have evolved proteinaceous inhibitors to modulate the activity of several of these enzymes. The continuing discovery of new inhibitors indicates that this research area is still unexplored and may lead to new exciting developments. To date, the role...... of the inhibitors is not completely understood. Here we review recent results obtained on the best characterised inhibitors, pointing to their possible biological role in vivo. Results recently obtained with plant transformation technology indicate that this class of inhibitors has potential biotechnological...

  3. En pos del <> a través del <>. El cuarto de atrás de Carmen Martín Gaite y Don Julián de Juan Goytisolo.

    OpenAIRE

    Valle Collado, Mélanie

    2008-01-01

    En este trabajo, se analiza El cuarto de atrás de Carmen Martín Gaite y Don Julián de Juan Goytisolo en relación con el concepto de metaficción. Consideramos que los autores consiguieron rescatar y transmitir su experiencia del pasado sin caer en los tópicos ni las ideas impuestas porque, en ellas, se aventuraron en un nuevo modelo formal (fuera del realismo social). En el primer apartado, veremos cómo las obras muestran su proceso de gestación y qué papel desarrolla la inte...

  4. Tratamiento del maxilar posterior atrófico mediante técnica de reconstrucción tridimensional con elevación de seno y abordaje «en tunel»

    OpenAIRE

    Restoy, Andrés; Pizarro, Víctor L.; Ordóñez, Vanesa; Lara, Juan; Doussinague, Beatriz R.; Domínguez-Mompell, José Luis

    2015-01-01

    Objetivos: En defectos maxilares con importante componente vertical, es necesaria la reconstrucción del proceso alveolar previamente a la rehabilitación con implantes para evitar una longitud desproporcionada de las coronas protésicas. En este artículo se revisa el tratamiento del maxilar posterior atrófico mediante elevación de seno y técnica de reconstrucción alveolar tridimensional simultánea con autoinjerto óseo. Se utilizó como vía de abordaje un túnel mucoso subperióstico a través de un...

  5. Soy Protein Isolate and Glycerol Hydrogen Bonding Using Two-Dimensional Correlation (2D-COS) Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy.

    Science.gov (United States)

    Yan, Zhiwei; Li, Qian; Zhang, Pudun

    2017-11-01

    It is a trend to substitute bioplastics for petroleum-based plastics in food packaging. Glycerol-plasticized soy protein isolate (SPI) is promising as a replacement for traditional petroleum-based plastics. Hydrogen bonding (H-bonding) plays a key role in plasticization of SPI film. However, few publications are concerned with the interactions of SPI and glycerol at the molecular level. In this paper, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy was applied to investigate the effect of H-bonding on the secondary structures of glycerol-plasticized SPI films and thus on the plasticization. An "S" profile of the H-bonding between SPI and glycerol with an abrupt jump in the glycerol range of 10-30% was achieved. For more in-depth investigation of the H-bonding, two-dimensional correlation spectroscopy (2D-COS) and perturbation-correlation moving-window two-dimensional (PCMW2D) analyses were applied to the amide I and II bands of SPI films spectra series. The conformation change sequences under the effect of H-bonding were revealed. When glycerol was involved, it entered into the β-sheet and the H-bonds of the SPI peptide backbone (C = O···H-N-) were replaced by the new H-bonds between SPI and glycerol (C = O···H-O-). The transformations of parallel β-sheet to β-turn in the range of 0-20% and anti-parallel β-sheet to β-turn in the range of 20-35% were obtained. In the 35-60% concentration range, the β-sheet was first changed to a transition state conformation, then together with the β-turn, to the random coil. The 2D-COS results clearly suggest that the conformations of SPI gradually change from the ordered to the less ordered and disordered, which significantly improve the plasticity of SPI film.

  6. AGR-2 Data Qualification Report for ATR Cycles 151B-2, 152A, 152B, 153A, 153B and 154A

    Energy Technology Data Exchange (ETDEWEB)

    Binh T. Pham; Jeffrey J. Einerson

    2013-09-01

    This report documents the data qualification status of AGR-2 fuel irradiation experimental data from Advanced Test Reactor (ATR) Cycles 152A, 152B, 153A, 153B, and 154A, as recorded in the Nuclear Data Management and Analysis System (NDMAS). The AGR-2 data streams addressed include thermocouple (TC) temperatures, sweep gas data (flow rate, pressure, and moisture content), and fission product monitoring system (FPMS) data for each of the six capsules in the experiment. A total of 13,400,520 every minute instantaneous TC and sweep gas data records were received and processed by NDMAS for this period. Of these data, 8,911,791 records (66.5% of the total) were determined to be Qualified based on NDMAS accuracy testing and data validity assessment. For temperature, there were 4,266,081 records (74% of the total TC data) that were Failed due to TC instrument failures. For sweep gas flows, there were 222,648 gas flow records (2.91% of the flow data) that were Failed. The inlet gas flow failures due to gas flow cross-talk and leakage problems that occurred after Cycle 150A were corrected by using the same gas mixture in all six capsules and the Leadout. For FPMS data, NDMAS received and processed preliminary release rate and release-to-birth rate ratio (R/B) data for three reactor cycles (Cycles 149B, 150B, and 151A) . This data consists of 45,983 release rate records and 45,235 R/B records for the 12 radionuclides reported. The qualification status of these FPMS data has been set to In Process until receipt of Quality Assurance-approved data generator reports. All of the above data have been processed and tested using a SAS®-based enterprise application software system, stored in a secure Structured Query Language database, made available on the NDMAS Web portal (http://ndmas.inl.gov), and approved by the INL STIM for release to both internal and appropriate external Very High Temperature Reactor Program participants.

  7. ATR alterations in Hodgkin's lymphoma

    NARCIS (Netherlands)

    Liu, Angen; Takakuwa, Tetsuya; Fujita, Shigeki; Luo, Wen-Juan; Tresnasari, Kristianti; Van den Berg, Anke; Poppema, Sibrand; Aozasa, Katsuyuki

    Hodgkin's lymphoma (HL) is characterized by the presence of neoplastic Hodgkin and Reed-Sternberg cells (HRSC) in a background of inflammatory cells. Free radicals and oxidative stress generated in the inflammatory lesions could cause DNA damage, thus providing a basis for lymphomagenesis.

  8. Automatic Traffic Recorder (ATR) Stations

    Data.gov (United States)

    Department of Homeland Security — The data included in the GIS Traffic Stations Version database have been assimilated from station description files provided by FHWA for Weigh-in-Motion (WIM), and...

  9. Development of natural cellulase inhibitor mediated intensified biological pretreatment technology using Pleurotus florida for maximum recovery of cellulose from paddy straw under solid state condition.

    Science.gov (United States)

    Naresh Kumar, Manickam; Ravikumar, Rajarathinam; Thenmozhi, Senniyappan; Kirupa Sankar, Muthuvelu

    2017-11-01

    Inhibitor mediated intensified bio-pretreatment (IMBP) technology using natural cellulase inhibitor (NCI) for maximum cellulose recovery from paddy straw was studied. Pretreatment was carried out under solid state condition. Supplementation of 8% NCI in pretreatment medium improves cellulose recovery and delignification by 1.2 and 1.5-fold respectively, compared to conventional bio-pretreatment due to inhibition of 61% of cellulase activity in IMBP. Further increase in NCI concentration showed negative effect on Pleurotus florida growth and suppress the laccase productivity by 1.1-fold. Laccase activity in IMBP was found to be 2.0U/mL on 19thday, which is higher than (1.5U/mL) conventional bio-pretreatment. Physico-chemical modifications in paddy straw before and after pretreatment were analysed by SEM, ATR-FTIR, XRD and TGA. According to these findings, the IMBP technology can be a viable eco-friendly technology for sustainable production of bioethanol with maximum cellulose recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Ghrelin- and preproghrelin-immunoreactive cells in atrophic body gastritis Células imunorreativas a grelina e preprogrelina na gastrite atrófica do corpo

    Directory of Open Access Journals (Sweden)

    Letícia F Moreira

    2011-10-01

    hiperplasia endócrina associada à gastrite atrófica do corpo (GAC. MATERIAL E MÉTODOS: Biópsias endoscópicas de 54 pacientes com GAC foram processadas para imuno-histoquímica, e anticorpos específicos contra grelina, preprogrelina e cromogranina foram utilizados. As células imunorreativas foram examinadas na hiperplasia endócrina presente na mucosa atrófica e nas áreas de metaplasia intestinal e pseudoantral. RESULTADOS: Ocorreu expressão de grelina em número variável de células endócrinas hiperplásicas em todos os pacientes estudados. Diferença estatisticamente significativa foi encontrada entre a frequência de nódulos hiperplásicos com mais de 50% de células imunomarcadas por cromogranina e grelina ou por cromogranina e preprogrelina. O número médio de nódulos hiperplásicos por paciente demonstrado pela cromogranina foi de 8,6. A maioria desses nódulos apresentou células imunorreativas para grelina e preprogrelina, respectivamente, 5,1 e 5,6, em média. A presença da expressão imuno-histoquímica de grelina e preprogrelina foi incomum em glândulas exibindo metaplasia intestinal, respectivamente, em quatro (9,5% e nove (21,4% casos e foram frequentes nas áreas de metaplasia pseudoantral em, respectivamente, 37 (72,5% e 26 (50,9% casos. CONCLUSÃO: Células imunorreativas a grelina e preprogrelina estão presentes na hiperplasia endócrina associada à GAC. Entretanto, mais estudos são necessários para saber até que ponto esses hormônios estão atuando como moduladores do crescimento e a evolução desses nódulos hiperplásicos.

  11. AZT as a telomerase inhibitor

    Directory of Open Access Journals (Sweden)

    Daniel E Gomez

    2012-09-01

    Full Text Available Telomerase is a highly specialized reverse transcriptase and the maintenance of telomeric length is determined by this specific enzyme. The human holoenzyme telomerase is a ribonucleoprotein composed by a catalytic subunit, hTERT, an RNA component, hTR, and a group of associated proteins. Telomerase is normally expressed in embryonic cells and is repressed during adulthood. The enzyme is reexpressed in around 85% of solid tumors. This observation makes it a potential target for developing drugs that could be developed for therapeutic purposes. The identification of the hTERT as a functional catalytic reverse transcriptase prompted studies of inhibiting telomerase with the HIV reverse transcriptase inhibitor azidothymidine (AZT. Previously, we have demonstrated that AZT binds preferentially to telomeres, inhibits telomerase and enhances tumor cell senescence and apoptosis after AZT treatment in breast mammary adenocarcinoma cells. Since then, several studies have considered AZT for telomerase inhibition and have led to potential clinical strategies for anticancer therapy. This review covers present thinking of the inhibition of telomerase by AZT and future treatment protocols using the drug.

  12. ALK inhibitors, a pharmaceutical perspective

    Directory of Open Access Journals (Sweden)

    Arturo eGalvani

    2012-02-01

    Full Text Available In 2007, the ALK tyrosine kinase, already known to be translocated and activated in Anaplastic Large Cell Lymphoma, and a few other rare cancers, was described as a potential therapeutic target for a subset of non small-cell lung cancer (NSCLC patients. Clinical proof of concept, culminating in the recent approval by the FDA of the Pfizer drug Xalkori (crizotinib, formerly known as PF-02341066 followed in record time. The drug was approved together with a companion diagnostic, the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular, Inc. for detection of eligible patients. This remarkable example of the coming of age of personalized medicine in cancer therapy is hopefully only an auspice of things to come in this rapidly developing field. Perhaps unsurprisingly, however, the appearance of clinical acquired resistance to crizotinib has already been observed early on in clinical testing, with the identification of several ALK secondary point mutations which diminish drug efficacy, and which open the way for development of second-generation inhibitors. It is also emerging that acquired resistance to crizotinib may also occur through ALK-independent mechanisms, which still need to be elucidated in detail.

  13. Novel Toxoplasma gondii inhibitor chemotypes.

    Science.gov (United States)

    Sanford, A G; Schulze, T T; Potluri, L P; Hemsley, R M; Larson, J J; Judge, A K; Zach, S J; Wang, X; Charman, S A; Vennerstrom, J L; Davis, P H

    2018-04-01

    We profiled three novel T. gondii inhibitors identified from an antimalarial phenotypic high throughput screen (HTS) campaign: styryl 4-oxo-1,3-benzoxazin-4-one KG3, tetrahydrobenzo[b]pyran KG7, and benzoquinone hydrazone KG8. These compounds inhibit T. gondii in vitro with IC 50 values ranging from 0.3 to 2μM, comparable to that of 0.25 to 1.5μM for the control drug pyrimethamine. KG3 had no measurable cytotoxicity against five mammalian cell lines, whereas KG7 and KG8 inhibited the growth of 2 of 5 cell lines with KG8 being the least selective for T. gondii. None of the compounds were mutagenic in an Ames assay. Experimental gLogD 7.4 and calculated PSA values for the three compounds were well within the ranges predicted to be favorable for good ADME, even though each compound had relatively low aqueous solubility. All three compounds were metabolically unstable, especially KG3 and KG7. Multiple IP doses of 5mg/kg KG7 and KG8 increased survival in a T. gondii mouse model. Despite their liabilities, we suggest that these compounds are useful starting points for chemical prospecting, scaffold-hopping, and optimization. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Vascular calcification: Inducers and inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Donghyun, E-mail: dhlee@cau.ac.kr [Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756 (Korea, Republic of)

    2011-09-15

    Highlights: {center_dot} Types of vascular calcification processes. {center_dot} Inducers of vascular calcification. {center_dot} Inhibitors of vascular calcifications. {center_dot} Clinical utility for vascular calcification therapy. {center_dot} Implications for the development of new tissue engineering strategies. - Abstract: Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.

  15. Development of green vapour corrosion inhibitor

    Science.gov (United States)

    Asmara, Y. P.; Suraj, V.; Siregar, J. P.; Kurniawan, T.; Bachtiar, D.; Mohamed, N. M. Z. N.

    2017-10-01

    Corrosion control using inhibitor is an effective method to protect carbon steel from corrosion. Due to environmental toxicity of chemical inorganic corrosion inhibitors (synthetic), green inhibitors are potentially to develop. In atmospheric conditions, green vapour corrosion inhibitors are the best solutions to replace the uses of inorganic corrosion inhibitors. This research used chemical acid extraction from the key lime (citrus aurantiifolia) leaves and seeds. They are used as the main ingredients to produce this effective green corrosion inhibitor. The experiments investigated effects of corrosion inhibition on corrosion rate of low carbon steel in 3% NaCl solution using both fog salt chamber and electrochemical cell. Using salt fog chamber to represent atmospheric conditions, and corrosion rates are evaluated visually and calculated using weight loss methods. Corrosion rate on electrochemical cell were calculated using linear polarization resistance (LPR) methods. All of the experiments were set in natural conditions at pH 7. Using weight loss for three days exposure time, the efficiency of the inhibitor reached 82.39%.

  16. Histone Deacetylase Inhibitors as Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Tomas Eckschlager

    2017-07-01

    Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  17. Histone Deacetylase Inhibitors as Anticancer Drugs.

    Science.gov (United States)

    Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

    2017-07-01

    Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  18. An Updated Review of Tyrosinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Te-Sheng Chang

    2009-05-01

    Full Text Available Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are desirable. These phenomena have encouraged researchers to seek new potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys tyrosinase inhibitors newly discovered from natural and synthetic sources. The inhibitory strength is compared with that of a standard inhibitor, kojic acid, and their inhibitory mechanisms are discussed.

  19. Contemporary protease inhibitors and cardiovascular risk

    DEFF Research Database (Denmark)

    Lundgren, Jens; Mocroft, Amanda; Ryom, Lene

    2018-01-01

    PURPOSE OF REVIEW: To review the evidence linking use of HIV protease inhibitors with excess risk of cardiovascular disease (CVD) in HIV+ populations. RECENT FINDINGS: For the two contemporary most frequently used protease inhibitors, darunavir and atazanavir [both pharmacologically boosted...... with ritonavir (/r)], darunavir/r has been shown to be associated with increased CVD risk. The effect is cumulative with longer exposure increasing risk and an effect size comparable to what has been observed for previously developed protease inhibitors. Biological mechanisms may be overlapping and include...... on individualization of care based on underlying risk of CVD....

  20. Calcineurin inhibitors in heart transplantation.

    Science.gov (United States)

    Keogh, Anne

    2004-05-01

    The use of calcineurin inhibitors (CNIs; cyclosporine and tacrolimus) has dramatically increased medium-term life expectancy after heart transplantation but has had only limited impact on long-term outcomes for heart transplant recipients. The original oil-based formulation of cyclosporine has been superceded by a microemulsion formulation (Neoral), which has more predictable pharmacokinetics and allows more precise dose-tailoring. Cyclosporine microemulsion and tacrolimus (Prograf) have a similar efficacy in the prevention of acute rejection of heart transplants, but their use is accompanied by nephrotoxicity and by cardiovascular side effects. The efficacy of immunosuppression can be improved by adjunctive therapy, such as azathioprine, mycophenolate mofetil (MMF; Cellcept), corticosteroids, and induction therapy. One of the most important predictors of patient mortality at >5 years after heart transplantation is cardiac allograft vasculopathy (CAV)/late graft failure, which accounts for 31% of deaths. Neither cyclosporine nor tacrolimus have been shown to prevent the development of CAV. In terms of efficacy, MMF provides a modest advantage over azathioprine in preventing CAV, and the combination of cyclosporine plus MMF results in significantly lower mortality than cyclosporine plus azathioprine. Overall, CNIs have multiple cardiovascular side effects, such as hypertension, hyperlipidemia and new-onset diabetes after transplantation, although cyclosporine and tacrolimus have somewhat different cardiovascular side-effect profiles. The challenge in choosing the best immunosuppressive regimen is to balance efficacy and safety to optimize graft and patient survival over the course of many decades. Because cyclosporine and tacrolimus have similar efficacy against acute rejection the choice of CNI for heart transplant recipients should be based on the relative risk of cardiovascular and renal side effects.

  1. Predicting the Performance of Organic Corrosion Inhibitors

    Directory of Open Access Journals (Sweden)

    David A. Winkler

    2017-12-01

    Full Text Available The withdrawal of effective but toxic corrosion inhibitors has provided an impetus for the discovery of new, benign organic compounds to fill that role. Concurrently, developments in the high-throughput synthesis of organic compounds, the establishment of large libraries of available chemicals, accelerated corrosion inhibition testing technologies, and the increased capability of machine learning methods have made discovery of new corrosion inhibitors much faster and cheaper than it used to be. We summarize these technical developments in the corrosion inhibition field and describe how data-driven machine learning methods can generate models linking molecular properties to corrosion inhibition that can be used to predict the performance of materials not yet synthesized or tested. We briefly summarize the literature on quantitative structure–property relationships models of small organic molecule corrosion inhibitors. The success of these models provides a paradigm for rapid discovery of novel, effective corrosion inhibitors for a range of metals and alloys in diverse environments.

  2. Kinase inhibitors for advanced medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Martin Schlumberger

    2012-01-01

    Full Text Available The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.

  3. Electrochemical Behaviour of Environmentally Friendly Inhibitor of ...

    African Journals Online (AJOL)

    Electrochemical Behaviour of Environmentally Friendly Inhibitor of Aloe Secundiflora Extract in Corrosion Control of Carbon Steel in Soft Water Media. ... corrosion control in neutral and aerated soft water solutions have been investigated using electrochemical impedance spectroscopy and Tafel polarization techniques.

  4. Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2014-06-01

    Full Text Available Acetylcholinesterase (AChE inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE. Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a “cholinergic anti-inflammatory pathway” which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system.

  5. Small-Molecule Inhibitors of Urea Transporters

    Science.gov (United States)

    Verkman, Alan S.; Esteva-Font, Cristina; Cil, Onur; Anderson, Marc O.; Li, Fei; Li, Min; Lei, Tianluo; Ren, Huiwen; Yang, Baoxue

    2015-01-01

    Urea transporter (UT) proteins, which include isoforms of UT-A in kidney tubule epithelia and UT-B in vasa recta endothelia and erythrocytes, facilitate urinary concentrating function. Inhibitors of urea transporter function have potential clinical applications as sodium-sparing diuretics, or ‘urearetics,’ in edema from different etiologies, such as congestive heart failure and cirrhosis, as well as in syndrome of inappropriate antidiuretic hormone (SIADH). High-throughput screening of drug-like small molecules has identified UT-A and UT-B inhibitors with nanomolar potency. Inhibitors have been identified with different UT-A versus UT-B selectivity profiles and putative binding sites on UT proteins. Studies in rodent models support the utility of UT inhibitors in reducing urinary concentration, though testing in clinically relevant animal models of edema has not yet been done. PMID:25298345

  6. The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, J; Kluft, C

    1997-01-01

    proteases. We studied the influence of chemical anti-inhibitors (chloramine T, flufenamate, sodium lauryl sulfate, and methylamine) on fibrinolytic serine proteases and fibrinolytic enzyme inhibitors using the physiological substrate fibrin as plasmin substrate. Low concentrations of chloramine T (0.01 mmol....../l) prevent the inhibition of plasminogen activators. Higher concentrations (1 mmol/l) reduce the inhibition of plasmin, but simultaneously quench the plasminogen activator activity. Flufenamate eliminates most fibrinolytic enzyme inhibitors, but increases the activity of plasmin (apparent recovery 140......Fibrinolytic enzyme inhibitors hamper the determination of the specific fibrinolytic serine protease activity. Reportedly, chemical anti-inhibitors eliminate the influence of fibrinolytic inhibitors, but it remains unclear to what extent they change the specific activity of fibrinolytic serine...

  7. Monoamine Oxidase B Inhibitors in Parkinson's Disease.

    Science.gov (United States)

    Dezsi, Livia; Vecsei, Laszlo

    2017-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials. A literature search was conducted in PubMed for 'PD treatment', 'MAO-B inhibitors', 'selegiline', 'rasagiline', 'safinamide' and 'clinical trials' with 'MAO-B inhibitors' in 'Parkinson' disease'. MAO-B inhibitors have a favorable pharmacokinetic profile, improve the dopamine deficient state and may have neuroprotective properties. Safinamide exhibits an anti-glutamatergic effect as well. When applied as monotherapy, MAO-B inhibitors provide a modest, but significant improvement of motor function and delay the need for levodopa. Rasagiline and safinamide were proven safe and effective when added to a dopamine agonist in early PD. As add-on to levodopa, MAO-B inhibitors significantly reduced off-time and were comparable in efficacy to COMT inhibitors. Improvements were achieved as regards certain non-motor symptoms as well. Due to the efficacy shown in clinical trials and their favorable side-effect profile, MAO-B inhibitors are valuable drugs in the treatment of PD. They are recommended as monotherapy in the early stages of the disease and as add-on therapy to levodopa in advanced PD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Update on TNF Inhibitors in Dermatology.

    Science.gov (United States)

    Sobell, Jeffrey M

    2016-06-01

    Emerging data describe new potential indications for tumor necrosis factor (TNF) inhibitors in dermatology, including pediatric psoriasis and hidradenitis suppurativa. New biosimilar TNF agents are in late stages of development and may be available in the United States in the near future. Biosimilar agents are similar but not identical to available TNF inhibitors, and approval requires extensive analytic, toxicity, pharmacokinetic, pharmacodynamic, and clinical testing. Semin Cutan Med Surg 35(supp6):S104-S106. 2016 published by Frontline Medical Communications.

  9. Emerging Corrosion Inhibitors for Interfacial Coating

    Directory of Open Access Journals (Sweden)

    Mona Taghavikish

    2017-12-01

    Full Text Available Corrosion is a deterioration of a metal due to reaction with environment. The use of corrosion inhibitors is one of the most effective ways of protecting metal surfaces against corrosion. Their effectiveness is related to the chemical composition, their molecular structures and affinities for adsorption on the metal surface. This review focuses on the potential of ionic liquid, polyionic liquid (PIL and graphene as promising corrosion inhibitors in emerging coatings due to their remarkable properties and various embedment or fabrication strategies. The review begins with a precise description of the synthesis, characterization and structure-property-performance relationship of such inhibitors for anti-corrosion coatings. It establishes a platform for the formation of new generation of PIL based coatings and shows that PIL corrosion inhibitors with various heteroatoms in different form can be employed for corrosion protection with higher barrier properties and protection of metal surface. However, such study is still in its infancy and there is significant scope to further develop new structures of PIL based corrosion inhibitors and coatings and study their behaviour in protection of metals. Besides, it is identified that the combination of ionic liquid, PIL and graphene could possibly contribute to the development of the ultimate corrosion inhibitor based coating.

  10. Aromatase inhibitors in the treatment of endometriosis

    Directory of Open Access Journals (Sweden)

    Radosław Słopień

    2016-03-01

    Full Text Available Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia, pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs. A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body’s oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis.

  11. Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hyeon-Ok [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Hong, Sung-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Kim, Chang Soon [Department of Microbiological Engineering, Kon-Kuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143–701 (Korea, Republic of); Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Park, In-Chul, E-mail: parkic@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Lee, Jin Kyung, E-mail: jklee@kirams.re.kr [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of)

    2015-08-15

    Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.

  12. Small molecule HIV entry inhibitors: Part II. Attachment and fusion inhibitors: 2004-2010.

    Science.gov (United States)

    Singh, Inder Pal; Chauthe, Siddheshwar Kisan

    2011-03-01

    The first US FDA approved HIV entry inhibitor drug Enfuvirdine belongs to the fusion inhibitor category. Earlier efforts in this area were focused on peptides and monoclonal antibodies; recently, the focus has shifted towards the development of small molecule HIV attachment and fusion inhibitors. They can be used for prophylactic purposes and also hold potential for the development of HIV microbicides. In a previous paper ('Small molecule HIV entry inhibitors: Part I'), we reviewed patents and patent applications for small molecule chemokine receptor antagonists from major pharmaceutical companies. In this paper, the development of small molecule HIV attachment and fusion inhibitors is discussed in detail. It covers patents and patent applications for small molecule HIV attachment and fusion inhibitors published between 2004 and 2010 and related literature with a focus on recent developments based on lead generation and lead modification. To augment the potency of currently available antiretroviral drug combinations and to fight drug-resistant virus variants, more effective drugs which target additional steps in the viral replication cycle are urgently needed. HIV attachment and fusion processes are such targets. Inhibitors of these targets will provide additional options for the treatment of HIV drug-resistant strains. Small molecule HIV attachment inhibitors such as BMS-378806 and analogs from Bristol Myers Squibb, N-aryl piperidine derivatives from Propharmacon, and NBD-556 and NBD-557 from New York Blood Center may have potential as vaginal microbicidal agents and can be an economical alternative to monoclonal antibodies.

  13. Polyphenol oxidase inhibitor(s) from German cockroach (Blattella germanica) extract

    Science.gov (United States)

    An extract from German cockroach appears effective in inhibiting browning on apples and potatoes. Successful identification of inhibitor(s) of PPO from German cockroach would be useful to the fruit and vegetable segments of the food industry, due to the losses they incur from enzymatic browning. Ide...

  14. Monoamine Reuptake Inhibitors in Parkinson's Disease

    Science.gov (United States)

    Huot, Philippe; Fox, Susan H.; Brotchie, Jonathan M.

    2015-01-01

    The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia. PMID:25810948

  15. Janus kinase inhibitors: jackpot or potluck?

    Directory of Open Access Journals (Sweden)

    Pavithran Keechilat

    2012-06-01

    Full Text Available The reports of a unique mutation in the Janus kinase-2 gene (JAK2 in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN: primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

  16. Protease Inhibitors from Plants with Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Yoonkyung Park

    2009-06-01

    Full Text Available Antimicrobial proteins (peptides are known to play important roles in the innate host defense mechanisms of most living organisms, including plants, insects, amphibians and mammals. They are also known to possess potent antibiotic activity against bacteria, fungi, and even certain viruses. Recently, the rapid emergence of microbial pathogens that are resistant to currently available antibiotics has triggered considerable interest in the isolation and investigation of the mode of action of antimicrobial proteins (peptides. Plants produce a variety of proteins (peptides that are involved in the defense against pathogens and invading organisms, including ribosome-inactivating proteins, lectins, protease inhibitors and antifungal peptides (proteins. Specially, the protease inhibitors can inhibit aspartic, serine and cysteine proteinases. Increased levels of trypsin and chymotrypsin inhibitors correlated with the plants resistance to the pathogen. Usually, the purification of antimicrobial proteins (peptides with protease inhibitor activity was accomplished by salt-extraction, ultrafiltration and C18 reverse phase chromatography, successfully. We discuss the relation between antimicrobial and anti-protease activity in this review. Protease inhibitors from plants potently inhibited the growth of a variety of pathogenic bacterial and fungal strains and are therefore excellent candidates for use as the lead compounds for the development of novel antimicrobial agents.

  17. [Interaction between clopidogrel and proton pump inhibitors].

    Science.gov (United States)

    Harmsze, Ankie M; de Boer, Anthonius; Boot, Henk; Deneer, Vera H M; Heringa, Mette; Mol, Peter G M; Schalekamp, Tom; Verduijn, Monique M; Verheugt, Freek W A; le Comte, Marianne

    2011-01-01

    The drug interaction between proton pump inhibitors and clopidogrel has been the subject of much study in recent years. Contradictory results regarding the effect of proton pump inhibitors on platelet reactivity and on clinical outcome in clopidogrel-treated patients have been reported in literature. Concomitant use of omeprazole and clopidogrel was found to decrease the exposure (AUC) to clopidogrel's active metabolite by 50% and to sharply increase platelet reactivity, as a result of inhibition by omeprazole of CYP2C19, a cytochrome P450 (CYP) enzyme. Pantoprazole has a much weaker effect on clopidogrel's pharmacokinetics and on platelet reactivity during concomitant use. The influence of the other proton pump inhibitors when used simultaneously with clopidogrel has not yet been investigated in adequately randomized studies. Regulatory agencies state that the combination of clopidogrel and the CYP2C19 inhibitors omeprazole and esomeprazole should be avoided. To date, there is no conclusive evidence of a clinically-relevant interaction between any of the proton pump inhibitors and clopidogrel.

  18. Combination of polarized TIRF and ATR spectroscopies for determination of the second and fourth order parameters of molecular orientation in thin films and construction of an orientation distribution based on the maximum entropy method.

    Science.gov (United States)

    Runge, Anne F; Saavedra, S Scott; Mendes, Sergio B

    2006-04-06

    This article describes two mathematical formalisms for the determination of the second and fourth order parameters of molecular films using optical spectroscopy. Method A uses polarized total internal reflection fluorescence (TIRF) to calculate the second and fourth order parameters, {P2(cos theta)} and {P4(cos theta)}, using an independently determined value for the angle between the absorption and emission dipoles, gamma. Method B uses {P2(cos theta)} obtained from attenuated total reflectance (ATR) data, along with polarized TIRF measurements to calculate {P4(cos theta)} and {cos2 gamma}. The choice of a specific method should rely on experimental considerations. We also present a method to separate the contributions of substrate surface roughness and dipole orientation with respect to the molecular axis from the spectroscopically determined second and fourth order parameters. Finally, a maximum entropy approach for construction of an orientation distribution from order parameters is compared with the commonly used delta and Gaussian distributions.

  19. Novel peptide-based protease inhibitors

    DEFF Research Database (Denmark)

    Roodbeen, Renée

    This thesis describes the design and synthesis of peptide-based serine protease inhibitors. The targeted protease, urokinase-type plasminogen activator (uPA) activates plasminogen, which plays a major role in cancer metastasis. The peptide upain-2 (S 1 ,S 12-cyclo-AcCSWRGLENHAAC-NH2) is a highly......, the disulfide bridge was replaced with amide bonds of various lengths. The novel peptides did not retain their inhibitory activity, but formed the basis for another strategy. Second, bicyclic peptides were obtained by creating head-to-tail cyclized peptides that were made bicyclic by the addition of a covalent...... bond across the ring. The second bridge was made by a disulfide bridge, amide bond formation or via ring-closing metathesis. A, with upain-2 equipotent, bicyclic inhibitor was obtained and its binding to uPA was studied by ITC, NMR and X-ray. The knowledge of how selective inhibitors bind uPA has been...

  20. Ablation of burned skin with ultra-short pulses laser to promote healing: evaluation by optical coherence tomography, histology, {mu}ATR-FTIR and Nonlinear Microscopy; Ablacao de pele queimada com laser de pulsos ultra-curtos para promocao da cicatrizacao: avaliacao por tomografia por coerencia optica, histologia, {mu}ATR-FTIR e microscopia nao-linear

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Moises Oliveira dos

    2012-07-01

    Burns cause changes in the anatomical structure of the skin associated with trauma. The severity of the burn injury is divided into first, second and third-degree burns. The third-degree burns have been a major focus of research in search of more conservative treatments and faster results in repair for a functional and cosmetically acceptable. The conventional treatment is the use of topical natural or synthetic skin graft. An alternative therapy is the laser ablation process for burned tissue necrosis removal due to the no mechanical contact, fast application and access to difficult areas. The purpose of this study is to evaluate the feasibility of using high intensity femtosecond lasers as an adjunct treatment of burned patients. For this study, 65 Wistar rats were divided into groups of five animals: healthy skin, burned skin, two types of treatment (surgical debridement or femtosecond laser ablation) and four different times in the healing process monitoring. Three regions of the back of the animals were exposed to steam source causing third-degree burn. On the third day after the burn, one of the regions was ablated with high intensity ultrashort laser pulses ({lambda} = 785 nm, 90 fs, 2 kHz and 10 {mu}J/ pulse), the other received surgical debridement, and the last was considered the burn control. The regions were analyzed by optical coherence tomography (OCT), histology, attenuated total reflectance infrared spectroscopy using Fourier transform ({mu}-ATR-FTIR), two-photon excitation fluorescence microscopy (TPEFM) and second harmonic generation technique (SHG) on days 3, 5, 7 and 14 pos-treatments. The results showed that with the laser irradiation conditions used it was possible to remove debris from third degree burn. The techniques used to characterize the tissue allowed to verify that all treatments promoted wound healing. On the fourteenth day, the regeneration curve showed that the attenuation coefficient of laser ablated tissue converges to the values

  1. Conservation of Moroccan manuscript papers aged 150, 200 and 800 years. Analysis by infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and scanning electron microscopy energy dispersive spectrometry (SEM-EDS).

    Science.gov (United States)

    Hajji, Latifa; Boukir, Abdellatif; Assouik, Jamal; Lakhiari, Hamid; Kerbal, Abdelali; Doumenq, Pierre; Mille, Gilbert; De Carvalho, Maria Luisa

    2015-02-05

    The preservation of manuscripts and archive materials is a serious problem for librarians and restorers. Paper manuscript is subjected to numerous degradation factors affecting their conservation state. This research represents an attempt to evaluate the conservation restoration process applied in Moroccan libraries, especially the alkaline treatment for strengthening weakened paper. In this study, we focused on six samples of degraded and restored paper taken from three different Moroccan manuscripts aged 150, 200 and 800 years. In addition, the Japanese paper used in restoration has been characterized. A modern paper was also analyzed as reference. A three-step analytical methodology based on infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectrometry (SEM-EDS) analysis was developed before and after restoration in order to determine the effect of the consolidation treatment on the paper structure. The results obtained by XRD and ATR-FTIR disclosed the presence of barium sulfate (BaSO4) in all restored paper manuscripts. The presence of calcium carbonate (CaCO3) in all considered samples was confirmed by FTIR spectroscopy. The application of de-acidification treatment causes significant changes connected with the increase of intensity mostly in the region 1426 cm(-1), assigned to the asymmetric and symmetric CO stretching mode of calcite, indicating the effectiveness of de-acidification procedure proved by the rise of the alkaline reserve content allowing the long term preservation of paper. Observations performed by SEM magnify the typical paper morphology and the structure of fibbers, highlighting the effect of the restoration process, manifested by the reduction of impurities. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Detect changes in lipid-related structure of brown- and yellow-seeded Brassica Carinata seed during rumen fermentation in relation to basic chemical profile using ATR-FT/IR molecular spectroscopy with chemometrics

    Science.gov (United States)

    Xin, Hangshu; Yu, Peiqiang

    2014-12-01

    In this experiment, brown- and yellow-seeded Brassica carinata were selected to use as a model to investigate whether there were any changes in lipid-related structure make-up (including CH3 and CH2 asymmetric and symmetric stretching bands ca. 3010-2765 cm-1, unsaturated lipid band ca. 3043-2987 cm-1 and carbonyl Cdbnd O ester band ca. 1789-1701 cm-1) of oilseed tissue during rumen in situ incubation using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FT/IR). Correlations of lipid spectral characteristics with basic chemical profile and multivariate analyses for clarifying structural differences within lipid regions between two carinata seeds were also measured. The results showed that most spectral parameters in both carinata seeds were reduced as incubation time increased. However, the extent of changes in peak intensity of carbonyl Cdbnd O ester group of brown-seeded carinata was not in fully accordance with that of yellow-seeded carinata. Additionally, these lipid structure features were highly correlated with the concentrations of OM (positively), CP (positively), NDF (negatively) and EE (positively) in carinata seeds after 0, 12, 24 and 48 h of incubation. Based on the results from multivariate analyses, neither AHCA nor PCA could produce any distinctions in rumen residues between brown- and yellow-seeded carinata in spectra at lipid regions. It was concluded that besides for original feed samples, spectroscopic technique of ATR-FT/IR could also be used for rumen degradation residues in detecting changes in lipid-related molecular structure make-up. Further studies are needed to explore more details in lipid metabolism during ruminal fermentation with the combined consideration on both metabolic basis and molecular structural basis.

  3. Characterization of silver halide fiber optics and hollow silica waveguides for use in the construction of a mid-infrared attenuated total reflection fourier transform infrared (ATR FT-IR) spectroscopy probe.

    Science.gov (United States)

    Damin, Craig A; Sommer, André J

    2013-11-01

    Advances in fiber optic materials have allowed for the construction of fibers and waveguides capable of transmitting infrared radiation. An investigation of the transmission characteristics associated with two commonly used types of infrared-transmitting fibers/waveguides for prospective use in a fiber/waveguide-coupled attenuated total internal reflection (ATR) probe was performed. Characterization of silver halide polycrystalline fiber optics and hollow silica waveguides was done on the basis of the transmission of infrared light using a conventional fiber optic coupling accessory and an infrared microscope. Using the fiber optic coupling accessory, the average percent transmission for three silver halide fibers was 18.1 ± 6.1% relative to a benchtop reflection accessory. The average transmission for two hollow waveguides (HWGs) using the coupling accessory was 8.0 ± 0.3%. (Uncertainties in the relative percent transmission represent the standard deviations.) Reduced transmission observed for the HWGs was attributed to the high numerical aperture of the coupling accessory. Characterization of the fibers/waveguides using a zinc selenide lens objective on an infrared microscope indicated 24.1 ± 7.2% of the initial light input into the silver halide fibers was transmitted. Percent transmission obtained for the HWGs was 98.7 ± 0.1%. Increased transmission using the HWGs resulted from the absence or minimization of insertion and scattering losses due to the hollow air core and a better-matched numerical aperture. The effect of bending on the transmission characteristics of the fibers/waveguides was also investigated. Significant deviations in the transmission of infrared light by the solid-core silver halide fibers were observed for various bending angles. Percent transmission greater than 98% was consistently observed for the HWGs at the bending angles. The combined benefits of high percent transmission, reproducible instrument responses, and increased bending

  4. Human tyrosinase inhibitor in rum distillate wastewater.

    Science.gov (United States)

    Takara, Kensaku; Iwasaki, Hironori; Ujihara, Kunihiro; Wada, Koji

    2008-01-01

    An inhibitor of human tyrosinase activity in rum distillate wastewater was isolated and identified as (S)-(+)-imperanene (1). (S)-(+)-Imperanene significantly inhibited tyrosinase isolated from HMV-II cells (IC(50) 1.85 mM). Inhibition kinetics studies revealed that imperanene is a competitive inhibitor of tyrosinase when L-3,4-dihydroxyphenylalanine is used as the substrate. The inhibitory activities of 1, O-beta-D-glucopyranosyl imperanene (2) and O-beta-D-glucopyranosyl-3-methoxyl imperanene (3) were 1>2>3.

  5. Does plasminogen activator inhibitor-1 drive lymphangiogenesis?

    DEFF Research Database (Denmark)

    Bruyère, Françoise; Melen-Lamalle, Laurence; Blacher, Silvia

    2010-01-01

    The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis...... by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two...... as a potential therapeutic target to counteract pathological lymphangiogenesis....

  6. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang

    2014-01-01

    plasminogen activator (uPA). We used X-ray crystal structure analysis, site-directed mutagenesis, liquid state NMR, surface plasmon resonance analysis, and isothermal titration calorimetry and wild type and engineered variants of murine and human uPA. We demonstrate that Arg6 inserts into the S1 specificity......Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase-type...

  7. 2-Aminobenzimidazoles as potent Aurora kinase inhibitors.

    Science.gov (United States)

    Zhong, Min; Bui, Minna; Shen, Wang; Baskaran, Subramanian; Allen, Darin A; Elling, Robert A; Flanagan, W Michael; Fung, Amy D; Hanan, Emily J; Harris, Shannon O; Heumann, Stacey A; Hoch, Ute; Ivy, Sheryl N; Jacobs, Jeffrey W; Lam, Stuart; Lee, Heman; McDowell, Robert S; Oslob, Johan D; Purkey, Hans E; Romanowski, Michael J; Silverman, Jeffrey A; Tangonan, Bradley T; Taverna, Pietro; Yang, Wenjin; Yoburn, Josh C; Yu, Chul H; Zimmerman, Kristin M; O'Brien, Tom; Lew, Willard

    2009-09-01

    This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.

  8. Rational design of protein kinase inhibitors

    Directory of Open Access Journals (Sweden)

    Yarmoluk S. M.

    2013-07-01

    Full Text Available Modern methodological approaches to rational design of low molecular weight compounds with specific activity in relation to predetermined biomolecular targets are considered by example of development of high effective protein kinase inhibitors. The application of new computational methods that allow to significantly improve the quality of computational experiments (in, particular, accuracy of low molecular weight compounds activity prediction without increase of computational and time costs are highlighted. The effectiveness of strategy of rational design is demonstrated by examples of several own investigations devoted to development of new inhibitors that are high effective and selective towards protein kinases CK2, FGFR1 and ASK1.

  9. Synergistic apoptosis induction in leukemic cells by the phosphatase inhibitor salubrinal and proteasome inhibitors.

    Directory of Open Access Journals (Sweden)

    Hannes C A Drexler

    Full Text Available Cells adapt to endoplasmic reticulum (ER-stress by arresting global protein synthesis while simultaneously activating specific transcription factors and their downstream targets. These processes are mediated in part by the phosphorylation-dependent inactivation of the translation initiation factor eIF2alpha. Following restoration of homeostasis protein synthesis is resumed when the serine/threonine-protein phosphatase PP1 dephosphorylates and reactivates eIF2alpha. Proteasome inhibitors, used to treat multiple myeloma patients evoke ER-stress and apoptosis by blocking the ER-associated degradation of misfolded proteins (ERAD, however, the role of eIF2alpha phosphorylation in leukemic cells under conditions of proteasome inhibitor-mediated ER stress is currently unclear.Bcr-Abl-positive and negative leukemic cell lines were used to investigate the functional implications of PP1-related phosphatase activities on eIF2alpha phosphorylation in proteasome inhibitor-mediated ER stress and apoptosis. Rather unexpectedly, salubrinal, a recently identified PP1 inhibitor capable to protect against ER stress in various model systems, strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines. Salubrinal treatment did not affect the phosphorlyation status of eIF2alpha. Furthermore, the proapoptotic effect of salubrinal occurred independently from the chemical nature of the proteasome inhibitor, was recapitulated by a second unrelated phosphatase inhibitor and was unaffected by overexpression of a dominant negative eIF2alpha S51A variant that can not be phosphorylated. Salubrinal further aggravated ER-stress and proteotoxicity inflicted by the proteasome inhibitors on the leukemic cells since characteristic ER stress responses, such as ATF4 and CHOP synthesis, XBP1 splicing, activation of MAP kinases and eventually apoptosis were efficiently abrogated by the translational inhibitor cycloheximide.Although PP1

  10. Proton pump inhibitors affect the gut microbiome

    NARCIS (Netherlands)

    Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Feenstra, Ettje T.; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

    BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or

  11. Thiosemicarbazones as inhibitors of tyrosinase enzyme.

    Science.gov (United States)

    Soares, Mariana A; Almeida, Mariana A; Marins-Goulart, Carla; Chaves, Otávio A; Echevarria, Aurea; de Oliveira, Márcia C C

    2017-08-01

    In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. Thiosemicarbazones Thio-1, Thio-2, Thio-3 and Thio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44mM, respectively) than Thio-5, Thio-6, Thio-7 and Thio-8. For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu2+ ions. Inside the active protein pocket, Thio-2 - the best studied inhibitor - is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force. Thio-2, containing a substituent on the aromatic ring similar to the substrate l-DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver-Burk plot. The same results were observed in the UV-Vis curves. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Vildagliptin: the first innovative DDP-4 inhibitor

    OpenAIRE

    Edvin Villkhauer

    2010-01-01

    A review of the main stages of investigation undertaken by Novartis Pharmaceuticals in search of a new molecule for the treatment of type 2 diabetes mellitus, dipeptidyl peptidase-4 (DPP-4) inhibitor (Vildaglyptin). The data on specificity and selectivity of the action of this molecule are presented along with the results of its comparison with another agent of this group (sitagliptin).

  13. TLC bioautographic method for detecting lipase inhibitors.

    Science.gov (United States)

    Hassan, Abdel Moniem Sadek

    2012-01-01

    Bioautographic assays using TLC play an important role in the search for active compounds from plants. A TLC bioautographic assay has previously been established for the detection of acetylcholinesterase inhibitors but not for lipases. Development of a TLC bioautographic method for detecting lipase inhibitors in plant extracts. After migration of the plant extracts, the TLC plate was sprayed with α-naphtyl acetate and enzyme solutions before incubation at 37°C for 20 min. Finally, the solution of Fast Blue B salt was sprayed onto the TLC plate giving a purple background colouration. Lipase inhibitors were visualised as white spots on the TLC plates. Orlistat (a known lipase inhibitor) inhibited lipase down to 0.01 µg. Methanolic extracts of Camellia sinensis (L.) kuntz and Rosmarinus officinalis L after migration on TLC gave enzymatic inhibition when applied in amounts of 82 and 56 µg, respectively. On the other hand the methanolic extract of Morus alba leaves did not exhibit any lipase inhibitory activity. The screening test was able to detect lipase inhibition by pure reference substances and by compounds present in complex matrices, such as plant extracts. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases

    Summary

    The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based

  15. Are phosphodiesterase 4 inhibitors just more theophylline?

    Science.gov (United States)

    Boswell-Smith, Victoria; Cazzola, Mario; Page, Clive P

    2006-06-01

    Theophylline has been relegated to a second- or even third-line therapy in the treatment of asthma and chronic obstructive pulmonary disease (COPD), behind glucocorticosteroids and beta2-agonists, although recent findings have suggested that theophylline possesses anti-inflammatory and immunomodulatory effects in addition to its well-recognized effects as a bronchodilator. In part, theophylline has fallen out of favor because of its adverse side-effect profile, and this has led to the search for more effective and safer drugs based on the knowledge that theophylline is orally active and that it is a nonselective phosphodiesterase (PDE) inhibitor. This has led to the development of selective PDE4 inhibitors, originally designed for depression, for the treatment of both COPD and asthma. Such drugs have shown clinical efficacy in the treatment of respiratory disease while having a considerably safer side-effect profile in comparison with theophylline, particularly because there are no reported drug interactions with PDE4 inhibitors, a feature that complicates the use of theophylline. In addition, it is also becoming increasingly apparent that theophylline is not working solely through PDE inhibition, as formerly assumed, and that this drug has other relevant pharmacologic activities that are likely to contribute to its efficacy, such as adenosine receptor antagonism and induction of histone deacetylase. Thus, the introduction of PDE4 inhibitors represents an entirely new class of drugs for the treatment of respiratory disease.

  16. Viral safety of C1-inhibitor NF

    NARCIS (Netherlands)

    Terpstra, F. G.; Kleijn, M.; Koenderman, A. H. L.; Over, J.; van Engelenburg, F. A. C.; Schuitemaker, H.; van 't Wout, A. B.

    2007-01-01

    We studied the efficacy of virus reduction by three process steps (polyethylene glycol 4000 (PEG) precipitation, pasteurization, and 15nm virus filtration) in the manufacturing of C1-inhibitor NF. The potential prion removing capacity in this process was estimated based on data from the literature.

  17. Developing ER Stress Inhibitors for Treating ALS

    Science.gov (United States)

    2015-11-01

    in response to thapsigargin, an inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase ( SERCA ) channels which initiates ER stress by preventing...O’Regan, J. P., Deng, H. X., and et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral

  18. Deconstructing Lipid Kinase Inhibitors by Chemical Proteomics.

    Science.gov (United States)

    McCloud, Rebecca L; Franks, Caroline E; Campbell, Sean T; Purow, Benjamin W; Harris, Thurl E; Hsu, Ku-Lung

    2018-01-16

    Diacylglycerol kinases (DGKs) regulate lipid metabolism and cell signaling through ATP-dependent phosphorylation of diacylglycerol to biosynthesize phosphatidic acid. Selective chemical probes for studying DGKs are currently lacking and are needed to annotate isoform-specific functions of these elusive lipid kinases. Previously, we explored fragment-based approaches to discover a core fragment of DGK-α (DGKα) inhibitors responsible for selective binding to the DGKα active site. Here, we utilize quantitative chemical proteomics to deconstruct widely used DGKα inhibitors to identify structural regions mediating off-target activity. We tested the activity of a fragment (RLM001) derived from a nucleotide-like region found in the DGKα inhibitors R59022 and ritanserin and discovered that RLM001 mimics ATP in its ability to broadly compete at ATP-binding sites of DGKα as well as >60 native ATP-binding proteins (kinases and ATPases) detected in cell proteomes. Equipotent inhibition of activity-based probe labeling by RLM001 supports a contiguous ligand-binding site composed of C1, DAGKc, and DAGKa domains in the DGKα active site. Given the lack of available crystal structures of DGKs, our studies highlight the utility of chemical proteomics in revealing active-site features of lipid kinases to enable development of inhibitors with enhanced selectivity against the human proteome.

  19. Curcumin derivatives as HIV-1 protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R. [Univ. of California, San Francisco, CA (United States)

    1993-12-31

    Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

  20. Safety aspects of HIV-protease inhibitors

    NARCIS (Netherlands)

    J.P. Dieleman (Jeanne)

    2002-01-01

    textabstractThe objectives of this thesis were to provide more insight into the risk and risk factors of adverse drug reactions associated with HIV-protease inhibitor treatment under non-experimental everyday circumstances. By recognition of risk factors, patients at risk can be identified

  1. Curbing indoor mold growth with mold inhibitors

    Science.gov (United States)

    Carol A. Clausen; Vina W. Yang

    2004-01-01

    Environmentally acceptable mold inhibitors are needed to curb the growth of mold fungi in woodframe housing when moisture management measures fail. Excess indoor moisture can lead to rapid mold establishment which, in turn, can have deleterious affects on indoor air quality. Compounds with known mold inhibitory properties and low mammalian toxicity, such as food...

  2. Natural peptides and proteins: potent tyrosinase inhibitors

    Directory of Open Access Journals (Sweden)

    R. Hariri*

    2017-11-01

    Full Text Available Background and objectives: Tyrosinase is a copper containing oxidase which is crucial for controlling the production of melanin in creatures such as bacteria, fungi, plants and mammals. It is involved in the first two steps of melanin biosynthesis and leads to pigmentation and different types of cancer such as melanoma. Also, it is responsible for browning of fruits and vegetables. Therefore, safe and efficient tyrosinase inhibitors are useful in the field of clinical medicine, cosmetics, agricultural and food industries. Conventional tyrosinase inhibitors such as hydroquinone, kojic acid, and arbutin have suffered from several problems such as melanocytes cytotoxicity, irritation, low permeability through the skin, contact allergy and low stability. Considering these difficulties, researchers have developed various naturally occurring anti-tyrosinase agents and in this regard, peptides and proteins have attracted lots of attention. Methods: In this work, anti-tyrosinase peptides and proteins obtained from natural resources were reviewed using credible databases. Results: Literature survey revealed that development of anti-tyrosinase activity of naturally occurring peptides and proteins started from 1974. Mushrooms (e.g. Agaricushortensis, bacteria (e.g. Lactobacillus helveticus and Oscillatoria agardhii, plants (e.g. Pseudostellaria heterophylla, rice bran,silk and egg yolk have been found as the most potent inhibitors. Conclusion: Literature review depicted that natural peptides and proteins can be consumed efficiently as tyrosinase inhibitors with much lower side effects. In this respect, new horizon will be opened to safe anti-tyrosinase agents.

  3. Structure-Based Design of Ricin Inhibitors

    Directory of Open Access Journals (Sweden)

    Jon D. Robertus

    2011-10-01

    Full Text Available Ricin is a potent cytotoxin easily purified in large quantities. It presents a significant public health concern due to its potential use as a bioterrorism agent. For this reason, extensive efforts have been underway to develop antidotes against this deadly poison. The catalytic A subunit of the heterodimeric toxin has been biochemically and structurally well characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA inhibitors have been identified; the most promising leads belonging to the pterin family. Development of these lead compounds into potent drug candidates is a challenging prospect for numerous reasons, including poor solubility of pterins, the large and highly polar secondary binding pocket of RTA, as well as the enzyme’s near perfect catalytic efficiency and tight binding affinity for its natural substrate, the eukaryotic ribosome. To date, the most potent RTA inhibitors developed using this approach are only modest inhibitors with apparent IC50 values in the 10−4 M range, leaving significant room for improvement. This review highlights the variety of techniques routinely employed in structure-based drug design projects, as well as the challenges faced in the design of RTA inhibitors.

  4. Protease inhibitor mediated resistance to insects

    NARCIS (Netherlands)

    Outchkourov, N.S.

    2003-01-01

    Protease inhibitors (PIs) are among the defensive molecules that plants produce in order to defend themselves against herbivores. A major aim of this thesis is to develop novel insect resistance traits usingheterologous, non-plant PIs. Prerequisite for the success of the

  5. TNF-Alpha Inhibitors for Chronic Urticaria

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Thomsen, Simon Francis

    2013-01-01

    had a durable response with a mean of 11 months. Six patients (30%) experienced side effects and five patients had mild recurrent upper respiratory infections, whereas one patient experienced severe CNS toxicity that could be related to treatment with TNF-alpha inhibitor. Adalimumab and etanercept may...

  6. Aromatase inhibitors in stimulated IVF cycles

    DEFF Research Database (Denmark)

    Papanikolaou, Evangelos G; Polyzos, Nikolaos P; Al Humaidan, Peter Samir Heskjær

    2011-01-01

    Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are ava...

  7. The Glycosylation of Plasminogen Activator Inhibitor-1

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand; Pedersen, Katrine Egelund; Christensen, Anni

    Plasminogen activator inhibitor type-1 (PAI-1) has three potential sites for N-linked glycosylation, including Asn209Tyr210Thr211, Asn265Met266Thr267, and Asn329Glu330Ser331. Using a HEK293 expression system, we have made mutants with Asp or Gln substitutions of the Asn residue in each of these s...

  8. Therapeutic substitution post-patent expiry: the cases of ACE inhibitors and proton pump inhibitors.

    Science.gov (United States)

    Vandoros, Sotiris

    2014-05-01

    This paper examines whether there is a switch in total (originator and generic) consumption after generic entry from molecules that face generic competition towards other molecules of the same class, which are still in-patent. Data from six European countries for the time period 1991 to 2006 are used to study the cases of angiotensin-converting enzyme inhibitors and proton pump inhibitors. Empirical evidence shows that patent expiry of captopril and enalapril led to a switch in total (off-patent originator and generic) consumption towards other in-patent angiotensin-converting enzyme inhibitors, whereas patent expiry of omeprazole led to a switch in consumption towards other proton pump inhibitors. This phenomenon makes generic policies ineffective and results in an increase in pharmaceutical expenditure due to the absence of generic alternatives in the market of in-patent molecules. Copyright © 2013 John Wiley & Sons, Ltd.

  9. ROS inhibitor N-acetyl-l-cysteine antagonizes the activity of proteasome inhibitors

    Science.gov (United States)

    Halasi, Marianna; Wang, Ming; Chavan, Tanmay S.; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L.

    2015-01-01

    NAC (N-acetyl-l-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H2O2. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis. PMID:23772801

  10. Peptidyl cyclopropenones: Reversible inhibitors, irreversible inhibitors, or substrates of cysteine proteases?

    OpenAIRE

    Cohen, Meital; Bretler, Uriel; Albeck, Amnon

    2013-01-01

    Peptidyl cyclopropenones were previously introduced as selective cysteine protease reversible inhibitors. In the present study we synthesized one such peptidyl cyclopropenone and investigated its interaction with papain, a prototype cysteine protease. A set of kinetics, biochemical, HPLC, MS, and 13C-NMR experiments revealed that the peptidyl cyclopropenone was an irreversible inhibitor of the enzyme, alkylating the catalytic cysteine. In parallel, this cyclopropenone also behaved as an alter...

  11. Environmental life cycle analysis of potato sprout inhibitors

    NARCIS (Netherlands)

    Kerstholt, R.P.V.; Ree, C.M.; Moll, H.C.

    Potato sprout inhibitors are generally applied to suppress sprouting during winter storage. This study presents the compared environmental profiles of the two sprout inhibitors available on the Dutch market: A traditional chemical product with isopropyl-3-chlorophenylcarbamate (CIPC) and

  12. Glycosidase inhibitors: update and perspectives on practical use

    National Research Council Canada - National Science Library

    Asano, Naoki

    2003-01-01

    .... Since then, over 100 glycosidase inhibitors have been isolated from plants and microorganisms. Modifying or blocking biological processes by specific glycosidase inhibitors has revealed the vital functions of glycosidases in living systems...

  13. Extraction and Characterization of Cathepsin Inhibitor from Milkfish

    Directory of Open Access Journals (Sweden)

    Tati Nurhayati

    2015-06-01

    Full Text Available Proteolytic enzyme is distributed acros all organism including fish. Cysteine proteases are the largest group of proteolytic enzyme. Lysosomal cathepsin, one of cysteine protease enzyme, cause softening and degradation of myofibril protein and it’s activity is regulated by endogenous inhibitors. The purposes of this study were to optimize the extraction cathepsin inhibitors from the skin, muscles, and viscera of fish, to partially purify the cathepsin inhibitors of selected sources, and to study the characteristics of the cathepsin inhibitor. The cathepsin inhibitor could be extracted from muscle fish and partially purified using ammonium sulfate of 70%. The purified cathepsin inhibitor had optimum temperature at 40°C and the optimum at pH 8. Metal ions decreased the activity of the protease inhibitor, except 1 mM of metal ion Mn2+ and Na+. Keywords: Cathepsin, characterization, partial purification, protease inhibitor

  14. Cellular growth kinetics distinguish a cyclophilin inhibitor from an HSP90 inhibitor as a selective inhibitor of hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Rudolf K F Beran

    Full Text Available During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA and heat-shock protein 90 (HSP90 which have each been reported to inhibit replication of hepatitis C virus (HCV. By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino-17-demethoxygeldanamycin (17-AAG to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA, exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth.

  15. Role of inhibitors and biodegradable material in mitigation of ...

    African Journals Online (AJOL)

    uku

    2011-05-02

    May 2, 2011 ... reduce ammonia volatilization loss from urea fertilizer. Coating with urease inhibitors can improve the bioavailability of N, resulting in increased dry matter yield and N uptake. Such increases result from delayed urea hydrolysis by urease inhibitors and coating materials. The value of inhibitors in mitigating.

  16. Enzyme inhibitors of marine microbial origin with pharmaceutical importance.

    Science.gov (United States)

    Imada, Chiaki

    2004-01-01

    Several enzyme inhibitors with various industrial uses were isolated from bacteria and actinomycetes living in the marine environment. These inhibitors are useful in medicine and agriculture. All the compounds, except the monoamine oxidase inhibitors, are novel, and their activities have been characterized.

  17. Protein C inhibitor may modulate human sperm-oocyte interactions

    NARCIS (Netherlands)

    Elisen, M. G.; van Kooij, R. J.; Nolte, M. A.; Marquart, J. A.; Lock, T. M.; Bouma, B. N.; Meijers, J. C.

    1998-01-01

    Protein C inhibitor (PCI) is a heparin-binding plasma serine protease inhibitor that was originally identified as an inhibitor of activated protein C. PCI has a broad protease specificity, inhibiting several proteases in hemostasis and fibrinolysis by acting as a suicide substrate. Recently it has

  18. Replacing sulfa drugs with novel DHPS inhibitors.

    Science.gov (United States)

    Hammoudeh, Dalia I; Zhao, Ying; White, Stephen W; Lee, Richard E

    2013-07-01

    More research effort needs to be invested in antimicrobial drug development to address the increasing threat of multidrug-resistant organisms. The enzyme DHPS has been a validated drug target for over 70 years as the target for the highly successful sulfa drugs. The use of sulfa drugs has been compromised by the widespread presence of resistant organisms and the adverse side effects associated with their use. Despite the large amount of structural information available for DHPS, few recent publications address the possibility of using this knowledge for novel drug design. This article reviews the relevant papers and patents that report promising new small-molecule inhibitors of DHPS, and discuss these data in light of new insights into the DHPS catalytic mechanism and recently determined crystal structures of DHPS bound to potent small-molecule inhibitors. This new functional understanding confirms that DHPS deserves further consideration as an antimicrobial drug target.

  19. Raltegravir: first in class HIV integrase inhibitor

    Directory of Open Access Journals (Sweden)

    Zelalem Temesgen

    2008-06-01

    Full Text Available Zelalem Temesgen1, Dawd S Siraj21Mayo Clinic, Rochester, MN, USA; 2East Carolina University Greenville, NC, USAAbstract: On October 16, 2007, the US Food and Drug Administration (FDA approved raltegravir for treatment of human immunodeficiency virus (HIV-1 infection in combination with other antiretroviral agents in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Raltegravir is first in a novel class of antiretroviral drugs known as integrase inhibitors. It has demonstrated potent anti HIV activity in both antiretroviral treatment-naïve and experienced patients. The most common adverse events reported with raltegravir during phase 2 and 3 clinical trials were diarrhea, nausea, and headache. Laboratory abnormalities include mild elevations in liver transaminases and creatine phosphokinase.Keywords: raltegravir, HIV, antiretroviral agents, integrase inhibitors

  20. Are leukotriene inhibitors useful for bronchiolitis?

    Science.gov (United States)

    Pérez-Gutiérrez, Fernanda; Otárola-Escobar, Isidora; Arenas, Deidyland

    2016-12-16

    Bronchiolitis is a prevalent disease in children under two years of age, which carries significant morbidity and mortality. However, there is controversy regarding the optimal therapeutic management. Leukotriene inhibitors have been proposed as an alternative, although its efficacy is not clear yet. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified two systematic reviews comprising six trials addressing the question of this article. We extracted data, combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded leukotriene inhibitors might not decrease mortality levels on bronchiolitis patients and it is not clear whether they decrease length of hospital stay. They might reduce recurrent wheezing, but the certainty of the evidence is low, and they increase adverse effects.

  1. Potent peptidic fusion inhibitors of influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

    2017-09-28

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

  2. SGLT2 Inhibitors: Benefit/Risk Balance.

    Science.gov (United States)

    Scheen, André J

    2016-10-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin showed remarkable reductions in cardiovascular/all-cause mortality and in hospitalization for heart failure in patients with previous cardiovascular disease. Positive renal outcomes were also shown with empagliflozin. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. Concern about a risk of ketoacidosis and bone fractures has been recently raised, which deserves caution and further evaluation.

  3. Rho-kinase inhibitors from adlay seeds.

    Science.gov (United States)

    Amen, Yhiya; Zhu, Qinchang; Tran, Hai-Bang; Afifi, Mohamed S; Halim, Ahmed F; Ashour, Ahmed; Fujimoto, Ryoji; Goto, Takahiro; Shimizu, Kuniyoshi

    2017-07-19

    Rho-kinase enzymes are one of the most important targets recently identified in our bodies. Several lines of evidence indicate that these enzymes are involved in many diseases and cellular disorders. ROCK inhibitors may have clinical applications for cancer, hypertension, glaucoma, etc. Our study aims to identify the possible involvement of Rho-kinase inhibition to the multiple biological activities of adlay seeds and provide a rationale for their folkloric medicines. Hence, we evaluated Rho-kinase I and II inhibitory activity of the ethanol extract and 28 compounds derived from the seeds. A molecular docking assay was designed to estimate the binding affinity of the tested compounds with the target enzymes. The results of our study suggest a possible involvement of Rho-kinase inhibition to the multiple biological activities of the seeds. Furthermore, the results obtained with the tested compounds revealed some interesting skeletons as a scaffold for design and development of natural Rho-kinase inhibitors.

  4. Caffeine as a Potential Quorum Sensing Inhibitor

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2013-04-01

    Full Text Available Quorum sensing enables bacteria to control the gene expression in response to the cell density. It regulates a variety of bacterial physiological functions such as biofilm formation, bioluminescence, virulence factors and swarming which has been shown contribute to bacterial pathogenesis. The use of quorum sensing inhibitor would be of particular interest in treating bacterial pathogenicity and infections. In this work, we have tested caffeine as quorum sensing inhibitor by using Chromobacterium violaceum CV026 as a biosensor. We verified that caffeine did not degrade the N-acyl homoserine lactones tested. In this work, it is shown that caffeine could inhibit N-acyl homoserine lactone production and swarming of a human opportunistic pathogen, namely Pseudomonas aeruginosa PA01. To the best of our knowledge, this is the first documentation providing evidence on the presence of anti-quorum sensing activity in caffeine. Our work will allow caffeine to be explored as anti-infective drugs.

  5. Natural products inhibitors of the enzyme acetylcholinesterase

    Directory of Open Access Journals (Sweden)

    José M. Barbosa Filho

    Full Text Available Alzheimer's disease (AD is a progressive, neurodegenerative pathology that primarily affects the elderly population, and is estimated to account for 50-60% of dementia cases in persons over 65 years of age. The main symptoms associated with AD involve cognitive dysfunction, primarily memory loss. Other features associated with the later stages of AD include language deficits, depression, behavioural problems including agitation, mood disturbances and psychosis. One of the most promising approaches for treating this disease is to enhance the acetylcholine level in the brain using acetylcholinesterase (AChE inhibitors. The present work reviews the literature on plants and plant-derived compounds inhibitors of enzyme acetylcholinesterase. The review refers to 309 plant extracts and 260 compounds isolated from plants, which are classified in appropriate chemical groups and model tested, and cites their activity. For this purpose 175 references were consulted.

  6. Inhibitors of the Cellular Trafficking of Ricin

    Directory of Open Access Journals (Sweden)

    Daniel Gillet

    2012-01-01

    Full Text Available Throughout the last decade, efforts to identify and develop effective inhibitors of the ricin toxin have focused on targeting its N-glycosidase activity. Alternatively, molecules disrupting intracellular trafficking have been shown to block ricin toxicity. Several research teams have recently developed high-throughput phenotypic screens for small molecules acting on the intracellular targets required for entry of ricin into cells. These screens have identified inhibitory compounds that can protect cells, and sometimes even animals against ricin. We review these newly discovered cellular inhibitors of ricin intoxication, discuss the advantages and drawbacks of chemical-genetics approaches, and address the issues to be resolved so that the therapeutic development of these small-molecule compounds can progress.

  7. Cathepsin D inactivates cysteine proteinase inhibitors, cystatins.

    Science.gov (United States)

    Lenarcic, B; Kos, J; Dolenc, I; Lucovnik, P; Krizaj, I; Turk, V

    1988-07-29

    The formation of inactive complexes in excess molar amounts of human cathepsins H and L with their protein inhibitors human stefin A, human stefin B and chicken cystatin at pH 5.6 has been shown by measurement of enzyme activity coupled with reverse-phase HPLC not to involve covalent cleavage of the inhibitors. Inhibition must be the direct result of binding. On the contrary the interaction of cystatins with aspartic proteinase cathepsin D at pH 3.5 for 60 min followed by HPLC resulted in their inactivation accompanied by peptide bond cleavage at several sites, preferentially those involving hydrophobic amino acid residues. The released peptides do not inhibit papain and cathepsin L. These results explain reported elevated levels of cysteine proteinases and lead to the proposal that cathepsin D exerts an important function, through inactivation of cystatins, in the increased activities of cysteine proteinases in human diseases including muscular distrophy.

  8. Classification of Cytochrome P450 1A2 Inhibitors and Non-Inhibitors by Machine Learning Techniques

    DEFF Research Database (Denmark)

    Vasanthanathan, Poongavanam; Taboureau, Olivier; Oostenbrink, Chris

    2009-01-01

    of CYP1A2 inhibitors and non-inhibitors. Training and test sets consisted of about 400 and 7000 compounds, respectively. Various machine learning techniques, like binary QSAR, support vector machine (SVM), random forest, kappa nearest neighbors (kNN), and decision tree methods were used to develop...... to be applicable for virtual screening of CYP1A2 inhibitors or non-inhibitors, or can be used as simple filters in the drug discovery process....

  9. Immune checkpoint inhibitor-related myocarditis.

    Science.gov (United States)

    Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

    2017-10-17

    Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart. Evidence from studies using genetically engineered mouse models suggests that CTLA-4 signaling terminates proliferation and promotes anergy during the primary response to cardiac self-peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic state. Patients affected by immune checkpoint inhibitor-related myocarditis often experience rapid onset of profound hemodynamic compromise progressing to cardiogenic shock. Early diagnosis is mandatory to address specific therapy and correct the timing of circulatory support. However, the diagnosis of myocarditis is challenging due to the heterogeneity of clinical presentations. Owing to its early onset, nonspecific symptomatology and fulminant progression, especially when these drugs are used in combination, oncologists should be vigilant for immune checkpoint inhibitor-related myocarditis. With many questions yet to be answered, from basic immune biology to clinical management, future research should aim to optimize the use of these drugs by identifying predictive biomarkers of either a response to therapy or the risks of myocarditis development. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Acrosin inhibitor detecting along the boar epididymis

    Czech Academy of Sciences Publication Activity Database

    Maňásková-Postlerová, Pavla; Cozlová, Nina; Dorosh, Andriy; Šulc, Miroslav; Guyonet, B.; Jonáková, Věra

    2016-01-01

    Roč. 82, Jan 2016 (2016), s. 733-739 ISSN 0141-8130 R&D Projects: GA ČR(CZ) GAP503/12/1834; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GA14-05547S Institutional support: RVO:86652036 ; RVO:61388971 Keywords : Acrosin inhibitor * Boar epididymis * Spermatozoa Subject RIV: CE - Biochemistry Impact factor: 3.671, year: 2016

  11. BCR ABL Kinase Inhibitors for Cancer Therapy

    OpenAIRE

    Dhara Patel; Maulik P. Suthar; Vipul Patel; Rajesh Singh

    2010-01-01

    BCR-ABL tyrosine kinase inhibitors have started era of molecular targeted therapy and marked a greatest milestone in cancer drug discovery. Despite of impressive cytogenetic response rates achieved with several agents in patients with chronic myelogenous leukemia (CML) in chronic phase, those with advanced stage CML frequently obtain more modest responses that are in many instances of short duration. Several mechanisms of resistance to imatinib are also observed among patients that develop cl...

  12. Adverse Effects of COX-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Jagdish N. Sharma

    2005-01-01

    Full Text Available Cyclooxygenase-2 selective inhibitors (COXIBs were developed with the prime object of minimizing gastrointestinal adverse effects, which are seen with the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs. Their long-term use is limited by the development of hypertension, edema, and congestive heart failure in a significant proportion of patients. NSAIDs block the activity of both COX isozymes, COX-1 and COX-2, which mediate the enzymatic conversion of arachidonate to prostaglandin H2 (PGH2 and other prostaglandin (PG metabolites. It is well established that the cardiovascular profile of COX-2 inhibitors can be accounted for by inhibition of COX-dependent PG synthesis. Following the COX-mediated synthesis of PGH2 from arachidonate, PGH2 is metabolized to one of at least five bioactive PGs, including PGE2, PGI2, PGF2, PGD2, or thromboxane A2 (TXA2. These prostanoids have pleiotropic cardiovascular effects, altering platelet function and renal function, and they are acting either as vasodilators or vasoconstrictors. Although COX-1 and COX-2 exhibit similar biochemical activity in converting arachidonate to PGH2in vitro, the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX-1 and COX-2, tissue distribution, and availability of the prostanoid synthases. PGs have been established as being critically involved in mitigating hypertension, helping to maintain medullary blood flow (MBF, promoting urinary salt excretion, and preserving the normal homeostasis of thrombosis, and the researchers found that the use of COX-2 inhibitors caused many serious complications in altering the normal body homeostasis. The purpose of the present research is to explain briefly the side effects of COX-2 inhibitors on the renal and cardiovascular system.

  13. Morphology and Mechanism of Benign Inhibitors

    Science.gov (United States)

    2012-07-01

    University of Cincinnati. Samples were mounted and coated with 2–3 nm of tungsten using a dual ion beam sputter coater (South Bay Technologies, Inc.) to...inhibitor precursor solution on the metal surface for 30 s, the wafer is accelerated to 2000 rpm and held for 1 minute to spin off the excess solution. To...24 hours before further characterization. The coating procedure was carried out using a Laurell single-wafer spin processor (WS-400A-6NPP-Lite

  14. Corrosion protection with eco-friendly inhibitors

    Science.gov (United States)

    Shahid, Muhammad

    2011-12-01

    Corrosion occurs as a result of the interaction of a metal with its environment. The extent of corrosion depends on the type of metal, the existing conditions in the environment and the type of aggressive ions present in the medium. For example, CO3-2 and NO-3 produce an insoluble deposit on the surface of iron, resulting in the isolation of metal and consequent decrease of corrosion. On the other hand, halide ions are adsorbed selectively on the metal surface and prevent formation of the oxide phase on the metal surface, resulting in continuous corrosion. Iron, aluminum and their alloys are widely used, both domestically and industrially. Linear alkylbenzene and linear alkylbenzene sulfonate are commonly used as detergents. They have also been found together in waste water. It is claimed that these chemicals act as inhibitors for stainless steel and aluminum. Release of toxic gases as a result of corrosion in pipelines may lead in certain cases to air pollution and possible health hazards. Therefore, there are two ways to look at the relationship between corrosion and pollution: (i) corrosion of metals and alloys due to environmental pollution and (ii) environmental pollution as a result of corrosion protection. This paper encompasses the two scenarios and possible remedies for various cases, using 'green' inhibitors obtained either from plant extracts or from pharmaceutical compounds. In the present study, the effect of piperacillin sodium as a corrosion inhibitor for mild steel was investigated using a weight-loss method as well as a three-electrode dc electrochemical technique. It was found that the corrosion rate decreased as the concentration of the inhibitor increased up to 9×10-4 M 93% efficiency was exhibited at this concentration.

  15. FAITH - Fast Assembly Inhibitor Test for HIV

    Czech Academy of Sciences Publication Activity Database

    Hadravová, Romana; Rumlová, Michaela; Ruml, T.

    2015-01-01

    Roč. 486, Dec (2015), s. 78-87 ISSN 0042-6822 R&D Projects: GA ČR(CZ) GA14-15326S; GA MŠk LO1302; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : retrovirus * HIV * assembly * assay * inhibitor Subject RIV: EE - Microbiology, Virology Impact factor: 3.200, year: 2015 http://www.sciencedirect.com/science/article/pii/S0042682215003864

  16. Identification of Neutrophil Exocytosis Inhibitors (Nexinhibs), Small Molecule Inhibitors of Neutrophil Exocytosis and Inflammation

    Science.gov (United States)

    Johnson, Jennifer L.; Ramadass, Mahalakshmi; He, Jing; Brown, Steven J.; Zhang, Jinzhong; Abgaryan, Lusine; Biris, Nikolaos; Gavathiotis, Evripidis; Rosen, Hugh; Catz, Sergio D.

    2016-01-01

    Neutrophils constitute the first line of cellular defense in response to bacterial and fungal infections and rely on granular proteins to kill microorganisms, but uncontrolled secretion of neutrophil cargos is injurious to the host and should be closely regulated. Thus, increased plasma levels of neutrophil secretory proteins, including myeloperoxidase and elastase, are associated with tissue damage and are hallmarks of systemic inflammation. Here, we describe a novel high-throughput screening approach to identify small molecule inhibitors of the interaction between the small GTPase Rab27a and its effector JFC1, two central regulators of neutrophil exocytosis. Using this assay, we have identified small molecule inhibitors of Rab27a-JFC1 binding that were also active in cell-based neutrophil-specific exocytosis assays, demonstrating the druggability of Rab GTPases and their effectors. These compounds, named Nexinhibs (neutrophil exocytosis inhibitors), inhibit exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. Furthermore, the compounds are reversible and potent inhibitors of the extracellular production of superoxide anion by preventing the up-regulation of the granule membrane-associated subunit of the NADPH oxidase at the plasma membrane. Nexinhibs also inhibit the up-regulation of activation signature molecules, including the adhesion molecules CD11b and CD66b. Importantly, by using a mouse model of endotoxin-induced systemic inflammation, we show that these inhibitors have significant activity in vivo manifested by decreased plasma levels of neutrophil secretory proteins and significantly decreased tissue infiltration by inflammatory neutrophils. Altogether, our data present the first neutrophil exocytosis-specific inhibitor with in vivo anti-inflammatory activity, supporting its potential use as an inhibitor of systemic

  17. Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

    Science.gov (United States)

    Oldenburg, Johannes; Mahlangu, Johnny N; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U; Young, Guy; Santagostino, Elena; Kruse-Jarres, Rebecca; Negrier, Claude; Kessler, Craig; Valente, Nancy; Asikanius, Elina; Levy, Gallia G; Windyga, Jerzy; Shima, Midori

    2017-08-31

    Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C. A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (Phemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).

  18. Therapeutic Innovations: Tyrosine Kinase Inhibitors in Cancer

    Directory of Open Access Journals (Sweden)

    Nikolaos Dervisis

    2016-01-01

    Full Text Available Conventional cytotoxic chemotherapy involving DNA-interacting agents and indiscriminate cell death is no longer the future of cancer management. While chemotherapy is not likely to completely disappear from the armamentarium; the use of targeted therapies in combination with conventional treatment is becoming the standard of care in human medicine. Tyrosine kinases are pivotal points of functional cellular pathways and have been implicated in malignancy, inflammatory, and immune-mediated diseases. Pharmaceutical interventions targeting aberrant tyrosine kinase signaling has exploded and is the second most important area of drug development. The “Valley of Death” between drug discovery and approval threatens to blunt the enormous strides in cancer management seen thus far. Kinase inhibitors, as targeted small molecules, hold promise in the treatment and diagnosis of cancer. However, there are still many unanswered questions regarding the use of kinase inhibitors in the interpretation and management of cancer. Comparative oncology has the potential to address restrictions and limitations in the advancement in kinase inhibitor therapy.

  19. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  20. Model for metabolic resistance against ALS inhibitors

    Directory of Open Access Journals (Sweden)

    Richter, Otto

    2014-02-01

    Full Text Available Due to herbicide selection pressure metabolic resistance has evolved in many weed species. In this paper we analyse the interaction between the branched chain amino acid (BBC pathway and detoxifying pathways for herbicide breakdown. The four phase detoxification pathway of herbicides comprising the action of P450, GST, glycosyltransferase and ABC transporter is modelled by a system of coupled enzyme kinetic reactions represented by nonlinear differential equations. The herbicide under consideration inhibits the enzyme ALS, which is the key enzyme for the biosynthesis of branched amino acids. For the kinetics of ALS a Monod approach is employed with a binding site for the inhibitor. Synthetic and detoxification pathways are coupled. The model is used to study the production of branched amino acids under the action of ALS inhibitors for different structures and modes of action of the detoxification pathway. The model is capable of generating typical dose response curves and their shift in dependence of the activity pattern of the enzymes of the detoxification pathway of the inhibitor.

  1. The most abundant protease inhibitor in potato tuber (Cv. Elkana) is a serine protease inhibitor from the Kunitz Family.

    NARCIS (Netherlands)

    Pouvreau, L.A.M.; Gruppen, H.; Koningsveld, van G.A.; Broek, van den L.A.M.; Voragen, A.G.J.

    2003-01-01

    The gene of the most abundant protease inhibitor in potato cv. Elkana was isolated and sequenced. The deduced amino acid sequence of this gene showed 98% identity with potato serine protease inhibitor (PSPI), a member of the Kunitz family. Therefore, the most abundant protease inhibitor was

  2. Reconstrução do seio maxilar atrófico com enxerto autólogo de crista ilíaca: avaliação por tomografia computadorizada e radiografia panorâmica

    Directory of Open Access Journals (Sweden)

    André Luíz Zétola

    Full Text Available OBJETIVOS: As dificuldades para a utilização de implantes dentários osteointegrados em pacientes portadores de atrofia do seio maxilar justificaram o emprego de enxerto autólogo não vascularizado de crista ilíaca isolado ou associado à hidroxiapatita (HA em 14 pacientes submetidos a 25 procedimentos no Hospital das Nações, Curitiba, Paraná, portadores de atrofia do sinus maxilar. O objetivo foi avaliar comparativamente a precisão da tomografia computadorizada e da radiografia panorâmica, através da quantificação da neoformação óssea nesta estrutura. MÉTODOS: Foram selecionadas pacientes edentados, com altura óssea residual do rebordo gengival ao soalho do seio maxilar menor que 5mm. O enxerto medular de crista ilíaca fragmentada isolado ou misturado com HA foi colocado através da parede lateral no soalho atrófico da cuba maxilar por via submucosa. A avaliação quantitativa e qualitativa foi feita através da radiografia panorâmica e tomografia computadorizada, sendo utilizado na análise estatística a distribuição t de Student (prevalência de 0,05 para análise das variâncias, considerado que a leitura dos laudos radiológicos foi feita por dois especialistas, medindo a distância entre os pontos inferiores e superiores do enxerto no soalho do seio maxilar. RESULTADOS: Tivemos um ganho médio de 14,8mm em todos os procedimentos, com um erro maior que 3mm em 16 procedimentos (64% e incorporação satisfatória do enxerto ósseo suficiente para futuro implante dentário. CONCLUSÕES: A tomografia computadorizada foi o método de escolha na avaliação qualitativa e quantitativa da incorporação de enxerto autólogo não vascularizado em seio maxilar atrófico.

  3. Using ATR-FT/IR to detect carbohydrate-related molecular structure features of carinata meal and their in situ residues of ruminal fermentation in comparison with canola meal

    Science.gov (United States)

    Xin, Hangshu; Yu, Peiqiang

    2013-10-01

    There is no information on the co-products from carinata bio-fuel and bio-oil processing (carinata meal) in molecular structural profiles mainly related to carbohydrate biopolymers in relation to ruminant nutrition. Molecular analyses with Fourier transform infrared spectroscopy (FT/IR) technique with attenuated total reflectance (ATR) and chemometrics enable to detect structural features on a molecular basis. The objectives of this study were to: (1) determine carbohydrate conformation spectral features in original carinata meal, co-products from bio-fuel/bio-oil processing; and (2) investigate differences in carbohydrate molecular composition and functional group spectral intensities after in situ ruminal fermentation at 0, 12, 24 and 48 h compared to canola meal as a reference. The molecular spectroscopic parameters of carbohydrate profiles detected were structural carbohydrates (STCHO, mainly associated with hemi-cellulosic and cellulosic compounds; region and baseline ca. 1483-1184 cm-1), cellulosic compounds (CELC, region and baseline ca. 1304-1184 cm-1), total carbohydrates (CHO, region and baseline ca. 1193-889 cm-1) as well as the spectral ratios calculated based on respective spectral intensity data. The results showed that the spectral profiles of carinata meal were significantly different from that of canola meal in CHO 2nd peak area (center at ca. 1091 cm-1, region: 1102-1083 cm-1) and functional group peak intensity ratios such as STCHO 1st peak (ca. 1415 cm-1) to 2nd peak (ca. 1374 cm-1) height ratio, CHO 1st peak (ca. 1149 cm-1) to 3rd peak (ca. 1032 cm-1) height ratio, CELC to total CHO area ratio and STCHO to CELC area ratio, indicating that carinata meal may not in full accord with canola meal in carbohydrate utilization and availability in ruminants. Carbohydrate conformation and spectral features were changed by significant interaction of meal type and incubation time and almost all the spectral parameters were significantly decreased (P canola

  4. Structure-Based Search for New Inhibitors of Cholinesterases

    Directory of Open Access Journals (Sweden)

    Barbara Malawska

    2013-03-01

    Full Text Available Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer’s disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological evaluation of selected candidates confirmed that the designed compounds were acetylcholinesterase inhibitors with IC50 values in the mid-nanomolar to low micromolar range, and some of them were also butyrylcholinesterase inhibitors.

  5. Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

    Science.gov (United States)

    Thakur, Rupamoni; Mukherjee, Ashis K

    2017-06-01

    Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. xtraction and Characterization of Cathepsin Inhibitor from Milkfish

    Directory of Open Access Journals (Sweden)

    Tati Nurhayati

    2015-06-01

    Full Text Available Abstract Proteolytic enzyme is distributed acros all organism including fish. Cysteine proteases are the largest group of proteolytic enzyme. Lysosomal cathepsin, one of cysteine protease enzyme, cause softening and degradation of myofibril protein and it’s activity is regulated by endogenous inhibitors. The purposes of this study were to optimize the extraction cathepsin inhibitors from the skin, muscles, and viscera of fish, to partially purify the cathepsin inhibitors of selected sources, and to study the characteristics of the cathepsin inhibitor. The cathepsin inhibitor could be extracted from muscle fish and partially purified using ammonium sulfate of 70%. The purified cathepsin inhibitor had optimum temperature at 40°C and the optimum at pH 8. Metal ions decreased the activity of the protease inhibitor, except 1 mM of metal ion Mn2+ and Na+.

  7. Evaluation of Encapsulated Inhibitor for Autonomous Corrosion Protection

    Science.gov (United States)

    Johnsey, M. N.; Li, W.; Buhrow, J. W.; Calle, L. M.; Pearman, B. P.; Zhang, X.

    2015-01-01

    This work concerns the development of smart coating technologies based on microencapsulation for the autonomous control of corrosion. Microencapsulation allows the incorporation of corrosion inhibitors into coating which provides protection through corrosion-controlled release of these inhibitors.One critical aspect of a corrosion protective smart coating is the selection of corrosion inhibitor for encapsulation and comparison of the inhibitor function before and after encapsulation. For this purpose, a systematic approach is being used to evaluate free and encapsulated corrosion inhibitors by salt immersion. Visual, optical microscope, and Scanning Electron Microscope (with low-angle backscatter electron detector) are used to evaluate these inhibitors. It has been found that the combination of different characterization tools provide an effective method for evaluation of early stage localized corrosion and the effectiveness of corrosion inhibitors.

  8. De El cuarto de atrás de Carmen Martín Gaite a La meitat de l’ànima de Carme Riera: Notas sobre la memoria histórica en la novela contemporánea / From Carmen Martín Gaite’s El cuarto de atrás to Carme Riera’s La meitat de l’ànima: Some notes on historical memory in contemporary fiction

    Directory of Open Access Journals (Sweden)

    Mario Santana

    2011-01-01

    Full Text Available Resumen: La novela española contemporánea ha dado una relevancia especial al interés por recuperar y transmitir la memoria colectiva del pasado reciente. Si bien la denominada “novela de memoria” (HERZBERGER, 1995 ya es una constante en la producción narrativa desde los primeros años de la transición a la democracia, este ensayo propone que en la última década ha ido ganando popularidad una “novela de la memoria histórica” con rasgos estructurales y temáticos que la convierten en una modalidad diferenciada. A partir del concepto de memoria heteropática (SILVERMAN, 1996 y del estudio de las semejanzas y diferencias entre dos novelas paradigmáticas de uno y otro modelo narrativo —El cuarto de atrás de Carmen Martín Gaite (1978 y La meitat de l’ànima de Carme Riera (2004, respectivamente—, se identifican algunos de los rasgos más distintivos de la novela de la memoria histórica y en especial su articulación literaria de la memoria como proyecto colectivo y ciudadano.Summary: The recovery and transmission of collective memory about the recent past plays an important role in contemporary Spanish fiction. While the production of “novels of memory” (HERZBERGER, 1995 has been consistent since the beginning of the transition to democracy, this essay proposes that in the last decade has gained popularity a “novel of historical memory”, which has distinctive estructural and thematic features and deserves to be studied as a differentiated modality. Using as a point of departure the notion of heteropathic memory (SILVERMAN, 1996 and through the analysis of the parallels and differences between two novels representative of both models —Carmen Martín Gaite’s El cuarto de atrás (1978 and Carme Riera’s La meitat de l’ànima (2004, respectively—, the essay identifies some of the most distinctive features of the novel of historical memory and, in particular, the literary articulation of memory as a collective and

  9. The "SWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both?

    Science.gov (United States)

    Nissan, Moriah H; Solit, David B

    2011-12-01

    Activating mutations in the BRAF gene are among the most prevalent kinase mutations in human cancer. BRAF mutations are most frequent in patients with melanoma where they occur in approximately 50% of patients with advanced disease. Remarkable clinical activity has recently been reported with highly selective RAF inhibitors in melanoma patients whose tumors harbor V600E BRAF mutations. The response rates of RAF inhibitors in patients with BRAF-mutant melanomas far exceed the activity level of any prior therapy studied in this disease. The results suggest that we have entered an era of personalized therapy for patients with metastatic melanoma in which treatment selection will be guided by BRAF mutational status. This review will discuss the strengths, weaknesses, opportunities and threats ("SWOT") of developing RAF and MEK selective inhibitors as anti-cancer therapies, recent insights into the mechanisms of intrinsic and acquired resistance to these agents, and current efforts to develop mechanism-based combination therapies.

  10. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort

    Science.gov (United States)

    Schwarz, John; Astermark, Jan; Menius, Erika D.; Carrington, Mary; Donfield, Sharyne M.; Gomperts, Edward D.; Nelson, George W.; Oldenburg, Johannes; Pavlova, Anna; Shapiro, Amy D.; Winkler, Cheryl A.; Berntorp, Erik

    2012-01-01

    Background Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in hemophilia A. It has been suggested that differences in the distribution of factor VIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Design and Methods Data from the HIGS Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1+H2) and inhibitor risk among individuals of genetically-determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and HLA were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Results H3 was associated with higher inhibitor risk among those genetically-identified (N=49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N=223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Conclusion H3 was not an independent predictor of inhibitor risk. Further, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. PMID:22958194

  11. Using ATR-FT/IR molecular spectroscopy to detect effects of blend DDGS inclusion level on the molecular structure spectral and metabolic characteristics of the proteins in hulless barley

    Science.gov (United States)

    Zhang, Xuewei; Yu, Peiqiang

    2012-09-01

    The objectives of this study were to investigate the effects of inclusion of a bioethanol co-product of blend DDGS (wheat:corn = 70%:30%) on protein molecular structure spectral and metabolic characteristics in hulless barley-based feed using ATR-FT/IR molecular spectroscopy. Hulless barley grain with the blend DDGS were mixed in the five ratios. The results showed that when blend DDGS was included at an increased ratio, predicted truly absorbed protein supply was highly and linearly increased (P samples but decreased (P samples. The ratio of α-helix to β-sheet peak height was quadratically changed with increasing inclusion rate of blend DDGS in the original samples, but no difference among the in situ 48 h residue samples, indicating completion of protein degradation. No correlation was found between protein 2nd structures and protein nutrient profiles not only for the original combination samples (except NPN) but also for in situ 48 h residue samples. This study may provide information on how protein molecular structure and metabolic characteristic changes after feed combination and how more effectively utilize hulless barley and blend co-products for dairy and beef cattle.

  12. Detect changes in protein structure of carinata meal during rumen fermentation in relation to basic chemical profile and comparison with canola meal using ATR-FT/IR molecular spectroscopy with chemometrics

    Science.gov (United States)

    Xin, Hangshu; Yu, Peiqiang

    2013-08-01

    As far as we know, no study has been carried out on whether protein structure changes in the feed during rumen fermentation from other research team. This study was conducted to characterize protein structure spectral changes in carinata meal during ruminal fermentation using Fourier transform infrared spectroscopy (FT/IR) technique with ATR. The objectives were to find out whether (1) protein internal structure (in terms of protein amide profile and protein secondary structure profile) changed after in situ ruminal fermentation at 0, 12, 24 and 48 h in carinata meal and conventional canola meal was used as a reference; (2) there was any correlation between protein spectral parameters and basic chemical profile in in situ rumen residue samples; and (3) the protein structural chemical make-up of carinata meal differed from canola meal during 48 h rumen incubation. The results showed that protein structure features in both carinata meal and canola meal were altered as incubation time increased (P canola meal, suggesting some relationship in structural make-up exhibited between them within protein region during 48 h rumen fermentation. Further studies are still needed to investigate detailed information on structural changes in protein of various feedstuffs in order to fully and deeply understand protein degradation during rumen fermentation on both metabolic basis and molecular biological basis.

  13. A Cadmium Anionic 1-D Coordination Polymer {[Cd(H2O6][Cd2(atr2(μ2-btc2(H2O4] 2H2O}n within a 3-D Supramolecular Charge-Assisted Hydrogen-Bonded and π-Stacking Network

    Directory of Open Access Journals (Sweden)

    Anas Tahli

    2016-03-01

    Full Text Available The hydrothermal reaction of 4,4′-bis(1,2,4-triazol-4-yl (btr and benzene-1,3,5-tricarboxylic acid (H3btc with Cd(OAc2·2H2O at 125 °C in situ forms 4-amino-1,2,4-triazole (atr from btr, which crystallizes to a mixed-ligand, poly-anionic chain of [Cd2(atr2(µ2-btc2(H2O4]2–. Together with a hexaaquacadmium(II cation and water molecules the anionic coordination-polymeric forms a 3-D supramolecular network of hexaaquacadmium(II-catena-[bis(4-amino-1,2,4-triazoletetraaquabis(benzene-1,3,5-tricarboxylatodicadmate(II] dihydrate, 1-D-{[Cd(H2O6][Cd2(atr2(µ2-btc2(H2O4] 2H2O}n which is based on hydrogen bonds (in part charge-assisted and π–π interactions.

  14. Corrosion inhibitor and method of use

    Energy Technology Data Exchange (ETDEWEB)

    Williams, D.A.; Holifield, P.K.; Looney, J.R.; McDougall, L.A.

    1991-03-26

    This paper discusses a corrosion inhibitor formulation capable of dispersion in aqueous well treating acids. It comprises from 1 to 25 wt % of a metal salt wherein the metal thereof is selected from the group consisting of Cu{sup +}, Sn, Zn, and a Group IIA metal having an atomic number from 12 to 56, a Group IVA metal having an atomic number of 22 or 40, a Group IIIB metal having an atomic number from 13 to 49, a Group VIA metal having an atomic number from 24 to 74, and a Group VB metal having an atomic number from 33 to 83; and mixtures thereof; from 3 to 50 wt% of a quaternary ammonium compound capable of forming a complex with the metal salt; sufficient amount of a highly polar aprotic solvent to dissolve the metal salt and the quaternary ammonium compounds, the concentration of the polar aprotic solvent being between 20 to 90 wt %; and from 1 to 15% of an organic amine dispersant for dispersing the complex of the quaternary ammonium compound and the metal salt in the sell treating acid, the wt % being based on the formulation. This patent also describes a method of acidizing a subterranean formation by injecting a well treating acid solution down pipe into the well. It comprises preparing the corrosion inhibitor formulation of claim 1; dispersing the formulation in the well treating acid solution to provide the solution with at least 0.08 wt % of the metal salt based on the combined weight of the well treating acid and formulation, and injecting the well treating acid solution containing the corrosion inhibitor formulation through the pipe into the formation.

  15. Kynurenine Aminotransferase Isozyme Inhibitors: A Review

    Directory of Open Access Journals (Sweden)

    Alireza Nematollahi

    2016-06-01

    Full Text Available Kynurenine aminotransferase isozymes (KATs 1–4 are members of the pyridoxal-5’-phosphate (PLP-dependent enzyme family, which catalyse the permanent conversion of l-kynurenine (l-KYN to kynurenic acid (KYNA, a known neuroactive agent. As KATs are found in the mammalian brain and have key roles in the kynurenine pathway, involved in different categories of central nervous system (CNS diseases, the KATs are prominent targets in the quest to treat neurodegenerative and cognitive impairment disorders. Recent studies suggest that inhibiting these enzymes would produce effects beneficial to patients with these conditions, as abnormally high levels of KYNA are observed. KAT-1 and KAT-3 share the highest sequence similarity of the isozymes in this family, and their active site pockets are also similar. Importantly, KAT-2 has the major role of kynurenic acid production (70% in the human brain, and it is considered therefore that suitable inhibition of this isozyme would be most effective in managing major aspects of CNS diseases. Human KAT-2 inhibitors have been developed, but the most potent of them, chosen for further investigations, did not proceed in clinical studies due to the cross toxicity caused by their irreversible interaction with PLP, the required cofactor of the KAT isozymes, and any other PLP-dependent enzymes. As a consequence of the possibility of extensive undesirable adverse effects, it is also important to pursue KAT inhibitors that reversibly inhibit KATs and to include a strategy that seeks compounds likely to achieve substantial interaction with regions of the active site other than the PLP. The main purpose of this treatise is to review the recent developments with the inhibitors of KAT isozymes. This treatise also includes analyses of their crystallographic structures in complex with this enzyme family, which provides further insight for researchers in this and related studies.

  16. The Epidemiology of FVIII Inhibitors in Indian Haemophilia A Patients.

    Science.gov (United States)

    Pinto, Patricia; Shelar, Tejashree; Nawadkar, Vidhya; Mirgal, Darshana; Mukaddam, Alfiya; Nair, Preethi; Kasatkar, Priyanka; Gaikwad, Tejasvita; Ali, Shahnaz; Jadli, Anshul; Patil, Rucha; Parihar, Anita; Shanbhag, Sharda; Kulkarni, Bipin; Ghosh, Kanjaksha; Shetty, Shrimati

    2014-12-01

    A serious complication of replacement therapy in patients with bleeding disorders is the development of 'inhibitors', particularly FVIII inhibitors in haemophilia A patients. This leads to an increase in the management cost, morbidity and mortality, especially post-operatively. The mechanism of FVIII inhibitor development is quite complex and it is difficult to predict inhibitor development, but a prompt and accurate diagnosis is critical as early therapy can save lives. The aim of this study was to screen patients with bleeding disorders in India for inhibitors, and to analyse and compare the prevalence of inhibitors in different regions in India. Patient details were recorded and blood samples were collected in sodium citrate vacutainers from 1,505 patients with bleeding disorders, in different cities in India. Coagulation and inhibitor screening assays were performed, followed by the Bethesda assay in inhibitor positive samples to quantify the FVIII inhibitor titre. Out of the 1,505 samples analysed, 1,285 were Haemophilia A patients, out of which 78 (6.07 %) were positive for 'FVIII Inhibitors'. The highest incidence of FVIII Inhibitors was seen in South India (13.04 %). The highest incidence of 20.99 % was observed in Chennai, followed by Hyderabad (13.33 %), Jammu (9.90 %) and Guwahati (8.51 %), respectively, with respect to the samples analysed. The other regions showed an inhibitor incidence <8 %. The incidence of inhibitors in haemophilia A patients is different in different regions of India; this may be due to the intensity of treatment, type of product or the genetic characteristics of these patients.

  17. Understanding the mechanisms of aromatase inhibitor resistance.

    Science.gov (United States)

    Miller, William R; Larionov, Alexey A

    2012-01-19

    Aromatase inhibitors (AIs) have a central role in the treatment of breast cancer; however, resistance is a major obstacle to optimal management. Evidence from endocrine, molecular and pathological measurements in clinical material taken before and after therapy with AIs and data from clinical trials in which AIs have been given as treatment either alone or in combination with other targeted agents suggest diverse causes for resistance. These include inherent tumour insensitivity to oestrogen, ineffective inhibition of aromatase, sources of oestrogenic hormones independent of aromatase, activation of signalling by non-endocrine pathways, enhanced cell survival and selection of hormone-insensitive cellular clones during treatment.

  18. Checkpoint inhibitors: a cutting edge in oncology.

    Science.gov (United States)

    Jago, C

    2017-07-01

    The checkpoint inhibitor field, and indeed the whole of immuno-oncology, is fast-paced and fascinating, with huge clinical and commercial potential. The challenge in the coming years will be to define the best type and combination of immunotherapy, and the best target population to receive it. Keytruda's ground-breaking approval for a biomarker-based rather than location-based indication is a solid step in this direction, and is likely to be followed by other such approvals. As the field develops, it is to be hoped that immuno-oncology therapeutics will continue to deliver the significant improvements in patient outcome that have been seen so far.

  19. A New Urease Inhibitor from Viola betonicifolia

    Directory of Open Access Journals (Sweden)

    Naveed Muhammad

    2014-10-01

    Full Text Available Urease has attracted much attention, as it is directly involved in the formation of infection stones and contributes to the pathogenesis of urolithiasis, pyelonephritis, ammonia and hepatic encephalopathy, hepatic coma and urinary catheter encrustation. Moreover, urease is the major cause of pathologies induced by H. pylori, such as gastritis and peptic ulcer. In the present work, the new natural compound, 3-methoxydalbergione, was isolated from Viola betonicifolia. A mechanistic study of this compound as a natural urease inhibitor was performed by using enzyme kinetics and docking studies. 3-Methoxydalbergione could be considered as a lead molecule for drugs useful in the urease associated diseases.

  20. Protease inhibitors targeting coronavirus and filovirus entry.

    Science.gov (United States)

    Zhou, Yanchen; Vedantham, Punitha; Lu, Kai; Agudelo, Juliet; Carrion, Ricardo; Nunneley, Jerritt W; Barnard, Dale; Pöhlmann, Stefan; McKerrow, James H; Renslo, Adam R; Simmons, Graham

    2015-04-01

    In order to gain entry into cells, diverse viruses, including Ebola virus, SARS-coronavirus and the emerging MERS-coronavirus, depend on activation of their envelope glycoproteins by host cell proteases. The respective enzymes are thus excellent targets for antiviral intervention. In cell culture, activation of Ebola virus, as well as SARS- and MERS-coronavirus can be accomplished by the endosomal cysteine proteases, cathepsin L (CTSL) and cathepsin B (CTSB). In addition, SARS- and MERS-coronavirus can use serine proteases localized at the cell surface, for their activation. However, it is currently unclear which protease(s) facilitate viral spread in the infected host. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl]amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. K11777 is already in advanced stages of development for a number of parasitic diseases, such as Chagas disease, and has proven to be safe and effective in a range of animal models. K11777 inhibition of SARS-CoV and Ebola virus entry was observed in the sub-nanomolar range. In order to assess whether cysteine or serine proteases promote viral spread in the host, we compared the antiviral activity of an optimized K11777-derivative with that of camostat, an inhibitor of TMPRSS2 and related serine proteases. Employing a pathogenic animal model of SARS-CoV infection, we demonstrated that viral spread and pathogenesis of SARS-CoV is driven by serine rather than cysteine proteases and can be effectively prevented by camostat. Camostat has been clinically used to treat chronic pancreatitis, and thus represents an exciting potential therapeutic for respiratory coronavirus infections. Our results indicate that camostat, or similar serine protease inhibitors, might be an effective option for treatment of SARS and