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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

    International Nuclear Information System (INIS)

    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. Corrosion inhibitor film formation studied by ATR-FTIR

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, S.; Jovancicevic, V. [Baker Petrolite, Sugar Land, TX (United States)

    1999-11-01

    The development of an inhibitor film is essential for the effective performance of a corrosion inhibitor. The use of attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) allows the development of inhibitor films on iron oxides to be monitored. For two distinct corrosion inhibitor chemistries, oleic imidazoline and phosphate ester, the film formation and corrosion processes are monitored on Fe{sub 3}O{sub 4} in a powdered form (a model surface). Additional data following on the physical and chemical properties are obtained using XPS and SEM techniques, which allows for a more complete characterization of the model inhibitor/oxide system. By the proper choice of system and measurement techniques, the complex phenomenon of corrosion inhibition may be analyzed directly.

  3. VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation

    International Nuclear Information System (INIS)

    High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. ATR inhibitor would be an effective tumor radiosensitizer with carbon ion irradiation. The online version of this article (doi:10.1186/s13014-015-0464-y) contains supplementary material, which is available to authorized users

  4. Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821: Phosphoproteomic Analysis

    Directory of Open Access Journals (Sweden)

    Barbora Šalovská

    2014-07-01

    Full Text Available DNA damaging agents such as ionizing radiation or chemotherapy are frequently used in oncology. DNA damage response (DDR—triggered by radiation-induced double strand breaks—is orchestrated mainly by three Phosphatidylinositol 3-kinase-related kinases (PIKKs: Ataxia teleangiectasia mutated (ATM, DNA-dependent protein kinase (DNA-PK and ATM and Rad3-related kinase (ATR. Their activation promotes cell-cycle arrest and facilitates DNA damage repair, resulting in radioresistance. Recently developed specific ATR inhibitor, VE-821 (3-amino-6-(4-(methylsulfonylphenyl-N-phenylpyrazine-2-carboxamide, has been reported to have a significant radio- and chemo-sensitizing effect delimited to cancer cells (largely p53-deficient without affecting normal cells. In this study, we employed SILAC-based quantitative phosphoproteomics to describe the mechanism of the radiosensitizing effect of VE-821 in human promyelocytic leukemic cells HL-60 (p53-negative. Hydrophilic interaction liquid chromatography (HILIC-prefractionation with TiO2-enrichment and nano-liquid chromatography—tandem mass spectrometry (LC-MS/MS analysis revealed 9834 phosphorylation sites. Proteins with differentially up-/down-regulated phosphorylation were mostly localized in the nucleus and were involved in cellular processes such as DDR, all phases of the cell cycle, and cell division. Moreover, sequence motif analysis revealed significant changes in the activities of kinases involved in these processes. Taken together, our data indicates that ATR kinase has multiple roles in response to DNA damage throughout the cell cycle and that its inhibitor VE-821 is a potent radiosensitizing agent for p53-negative HL-60 cells.

  5. Synergistic potentiation of (-)-lomaiviticin A cytotoxicity by the ATR inhibitor VE-821.

    Science.gov (United States)

    Colis, Laureen C; Herzon, Seth B

    2016-07-01

    (-)-Lomaiviticin A (1) is a cytotoxic bacterial metabolite that induces double-strand breaks in DNA. Here we show that the cytotoxicity of (-)-lomaiviticin A (1) is synergistically potentiated in the presence of VE-821 (7), an inhibitor of ataxia telangiectasia and Rad3-related protein (ATR). While 0.5nM 1 or 10μM 7 alone are non-lethal to K562 cells, co-incubation of the two leads to high levels of cell kill (81% and 94% after 24 and 48h, respectively). Mechanistic data indicate that cells treated with 1 and 7 suffer extensive DNA double-strand breaks and apoptosis. These data suggest combinations of 1 and 7 may be a valuable chemotherapeutic strategy. PMID:27177826

  6. Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970

    OpenAIRE

    Hall, Amy B.; Newsome, Dave; Wang, Yuxin; Boucher, Diane M.; Eustace, Brenda; Gu, Yong; Hare, Brian; Mac A. Johnson; Milton, Sean; Murphy, Cheryl E.; Takemoto, Darin; Tolman, Crystal; Wood, Mark; Charlton, Peter; Charrier, Jean-Damien

    2014-01-01

    Platinum-based DNA-damaging chemotherapy is standard-of-care for most patients with lung cancer but outcomes remain poor. This has been attributed, in part, to the highly effective repair network known as the DNA-damage response (DDR). ATR kinase is a critical regulator of this pathway, and its inhibition has been shown to sensitize some cancer, but not normal, cells in vitro to DNA damaging agents. However, there are limited in vivo proof-of-concept data for ATR inhibition. To address this w...

  7. Molecular Pathways: Targeting ATR in Cancer Therapy.

    Science.gov (United States)

    Karnitz, Larry M; Zou, Lee

    2015-11-01

    The human ATR gene encodes a kinase that is activated by DNA damage and replication stress as a central transducer of a checkpoint signaling pathway. Once activated, ATR phosphorylates multiple substrates, including the kinase Chk1, to regulate cell-cycle progression, replication fork stability, and DNA repair. These events promote cell survival during replication stress and in cells with DNA damage. Accordingly, there has been the tantalizing possibility that ATR inhibitors would be therapeutically useful, especially if they were more effective in tumor versus normal cells. Indeed, multiple studies have demonstrated that alterations that promote tumorigenesis, such as defects in the ATM-p53 pathway, constitutive oncogene activation, and acquisition of the alternative lengthening of telomeres pathway, render tumor cells sensitive to ATR inhibitor monotherapy and/or increase the synergy between ATR inhibitors and genotoxic chemotherapies. Now, nearly two decades after the discovery of ATR, two highly selective and potent ATR inhibitors, AZD6738 and VX-970, are in early-phase clinical trials either as monotherapies or paired with a variety of genotoxic chemotherapies. These trials will generate important insights into the effects of ATR inhibition in humans and the potential role of inhibiting this kinase in the treatment of human malignancies. PMID:26362996

  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 neutron spectral characterization

    International Nuclear Information System (INIS)

    The Advanced Test Reactor (ATR) at INEL provides intense neutron fields for irradiation-effects testing of reactor material samples, for production of radionuclides used in industrial and medical applications, and for scientific research. Characterization of the neutron environments in the irradiation locations of the ATR has been done by means of neutronics calculations and by means of neutron dosimetry based on the use of neutron activation monitors that are placed in the various irradiation locations. The primary purpose of this report is to present the results of an extensive characterization of several ATR irradiation locations based on neutron dosimetry measurements and on least-squares-adjustment analyses that utilize both neutron dosimetry measurements and neutronics calculations. This report builds upon the previous publications, especially the reference 4 paper. Section 2 provides a brief description of the ATR and it tabulates neutron spectral information for typical irradiation locations, as derived from the more historical neutron dosimetry measurements. Relevant details that pertain to the multigroup neutron spectral characterization are covered in section 3. This discussion includes a presentation on the dosimeter irradiation and analyses and a development of the least-squares adjustment methodology, along with a summary of the results of these analyses. Spectrum-averaged cross sections for neutron monitoring and for displacement-damage prediction in Fe, Cr, and Ni are given in section 4. In addition, section4 includes estimates of damage generation rates for these materials in selected ATR irradiation locations. In section 5, the authors present a brief discussion of the most significant conclusions of this work and comment on its relevance to the present ATR core configuration. Finally, detailed numerical and graphical results for the spectrum-characterization analyses in each irradiation location are provided in the Appendix

  10. The influence of ATM, ATR, DNA-PK inhibitors on the cytotoxic and genotoxic effects of dibenzo[def,p]chrysene on human hepatocellular cancer cell line HepG2.

    Science.gov (United States)

    Spryszyńska, Sylwia; Smok-Pieniążek, Anna; Ferlińska, Magdalena; Roszak, Joanna; Nocuń, Marek; Stępnik, Maciej

    2015-09-01

    The effect of inhibitors of phosphatidylinositol-3-kinase related kinases (PIKK): ataxia-telangiectasia mutated (ATM), ATM- and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK) on the response of HepG2 human liver cancer cells to dibenzo[def,p]chrysene (DBC) was investigated. High cytotoxicity of DBC (IC50=0.1μM) was observed after 72h incubation. PIKK inhibitors: KU55933 (5μM), NU7026 (10μM) or caffeine (1 and 2mM) when used alone did not significantly influence the cytotoxicity. However, two combinations: KU55933/NU7026 and caffeine/NU7026 significantly increased HepG2 viability (by 25%) after treatment with DBC at 0.5μM. The cytoprotective effect was confirmed by cell cycle and apoptosis/necrosis analysis. DNA damage level after exposure to DBC assessed by comet assay (single strand breaks) showed a long persistence and significant decrease after incubation of the cells in the presence the inhibitors (the combination of KU55933+NU7026 showed the strongest effect). Weak induction of reactive oxygen species (ROS) by DBC (0.5μM) was observed. Although, KU55933 and NU7026 when used alone did not increase ROS levels in the cells, their combination induced the ROS increase and moderately enhanced ROS generation by DBC. We propose a mechanism how cells with damaged DNA after exposure to DBC and under the condition of PIKK inhibition, may be at higher risk of undergoing malignant transformation. PMID:26338538

  11. Surface reengineering of RPA70N enables cocrystallization with an inhibitor of the replication protein A interaction motif of ATR interacting protein.

    Science.gov (United States)

    Feldkamp, Michael D; Frank, Andreas O; Kennedy, J Phillip; Patrone, James D; Vangamudi, Bhavatarini; Waterson, Alex G; Fesik, Stephen W; Chazin, Walter J

    2013-09-17

    Replication protein A (RPA) is the primary single-stranded DNA (ssDNA) binding protein in eukaryotes. The N-terminal domain of the RPA70 subunit (RPA70N) interacts via a basic cleft with a wide range of DNA processing proteins, including several that regulate DNA damage response and repair. Small molecule inhibitors that disrupt these protein-protein interactions are therefore of interest as chemical probes of these critical DNA processing pathways and as inhibitors to counter the upregulation of DNA damage response and repair associated with treatment of cancer patients with radiation or DNA-damaging agents. Determination of three-dimensional structures of protein-ligand complexes is an important step for elaboration of small molecule inhibitors. However, although crystal structures of free RPA70N and an RPA70N-peptide fusion construct have been reported, RPA70N-inhibitor complexes have been recalcitrant to crystallization. Analysis of the P61 lattice of RPA70N crystals led us to hypothesize that the ligand-binding surface was occluded. Surface reengineering to alter key crystal lattice contacts led to the design of RPA70N E7R, E100R, and E7R/E100R mutants. These mutants crystallized in a P212121 lattice that clearly had significant solvent channels open to the critical basic cleft. Analysis of X-ray crystal structures, target peptide binding affinities, and (15)N-(1)H heteronuclear single-quantum coherence nuclear magnetic resonance spectra showed that the mutations do not result in perturbations of the RPA70N ligand-binding surface. The success of the design was demonstrated by determining the structure of RPA70N E7R soaked with a ligand discovered in a previously reported molecular fragment screen. A fluorescence anisotropy competition binding assay revealed this compound can inhibit the interaction of RPA70N with the peptide binding motif from the DNA damage response protein ATRIP. The implications of the results are discussed in the context of ongoing efforts

  12. PUREX new substation ATR

    International Nuclear Information System (INIS)

    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

  13. ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency

    OpenAIRE

    Mohni, Kareem N.; Kavanaugh, Gina M.; Cortez, David

    2014-01-01

    The DNA damage response kinase ATR and its effector kinase CHEK1 are required for cancer cells to survive oncogene-induced replication stress. ATR inhibitors exhibit synthetic lethal interactions with deficiencies in the DNA damage response enzymes ATM and XRCC1 and with overexpression of the cell cycle kinase Cyclin E. Here we report a systematic screen to identify synthetic lethal interactions with ATR-pathway targeted drugs, rationalized by their predicted therapeutic utility in the oncolo...

  14. HEATR project: ATR algorithm parallelization

    Science.gov (United States)

    Deardorf, Catherine E.

    1998-09-01

    High Performance Computing (HPC) Embedded Application for Target Recognition (HEATR) is a project funded by the High Performance Computing Modernization Office through the Common HPC Software Support Initiative (CHSSI). The goal of CHSSI is to produce portable, parallel, multi-purpose, freely distributable, support software to exploit emerging parallel computing technologies and enable application of scalable HPC's for various critical DoD applications. Specifically, the CHSSI goal for HEATR is to provide portable, parallel versions of several existing ATR detection and classification algorithms to the ATR-user community to achieve near real-time capability. The HEATR project will create parallel versions of existing automatic target recognition (ATR) detection and classification algorithms and generate reusable code that will support porting and software development process for ATR HPC software. The HEATR Team has selected detection/classification algorithms from both the model- based and training-based (template-based) arena in order to consider the parallelization requirements for detection/classification algorithms across ATR technology. This would allow the Team to assess the impact that parallelization would have on detection/classification performance across ATR technology. A field demo is included in this project. Finally, any parallel tools produced to support the project will be refined and returned to the ATR user community along with the parallel ATR algorithms. This paper will review: (1) HPCMP structure as it relates to HEATR, (2) Overall structure of the HEATR project, (3) Preliminary results for the first algorithm Alpha Test, (4) CHSSI requirements for HEATR, and (5) Project management issues and lessons learned.

  15. 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.

  16. Inhibitors

    Science.gov (United States)

    ... wrong place in the body. Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from ... body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor ...

  17. ATR promotes cilia signalling: links to developmental impacts

    OpenAIRE

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

    2016-01-01

    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 ci...

  18. Involvement of ATM/ATR-p38 MAPK cascade in MNNG induced G1-S arrest

    Institute of Scientific and Technical Information of China (English)

    Ke-Qing Zhu; Suo-Jiang Zhang

    2003-01-01

    AIM: To understand the effect of low concentration of Nmethyl-N′-nitro-nitrosoguanidine (MNNG), which is a widely distributed environmental mutagen and carcinogen especially for human gastric cancer, on DNA damage and to study its possible pathway in regulating cell cycle arrest.METHODS: The DNA damage effect was measured by Comet assay. A specific phospho-(Ser/Thr) ATM/ATR substrate antibody was used to detect the damage sensor by Western blot. p38 kinase activity was measured by direct kinase assay,and immunoprecipitation for the possible connection between ATM/ATR and p38 MAPK. Flow cytometry analysis and p38MAPK specific inhibitor SB203580 were combined to detect the possible cell cycle arrest by p38 MAPK.RESULTS: With the same low concentration MNNG exposure (0.2μM 2.5 h), Comet assays indicated that strand breaks accumulated, Western blot and kinase assay showed ATM/ATR and p38 kinase activated, immunoprecipitation showed phospho-ATM/ATR substrate antibody combined with both p38 MAPK antibody and phospho-p38 MAPK antibody, p38MAPK pathway was involved in the G1-S arrest.CONCLUSION: Activation of ATM/ATR by MNNG induced DNA damage leads to activation of p38 MAPK, which involves in the G1 checkpoint in mammalian cells.

  19. Vanadium irradiation at ATR - neutronics aspects

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, I.C.; Smith, D.L. [Argonne National Laboratory, Chicago, IL (United States)

    1995-04-01

    Calculations were performed to estimate damage and transmutation rates in vanadium irradiated in the ATR (Advanced Test Reactor) located in Idaho. The main focuses of the study are to evaluate the transmutation of vanadium to chromium and to explore ways to design the irradiation experiment to avoid excessive transmutation. It was found that the A-hole of ATR produces damage rate of {approximately} 0.2%/dpa of vanadium to chromium. A thermal neutron filter can be incorporated into the design to reduce the vanadium-to-chromium transmutation rate to low levels. A filter 1-2 mm thick of gadolinium or hafnium can be used.

  20. Overview of the ATR power supplies

    International Nuclear Information System (INIS)

    The AGS to RHIC transfer line (ATR) transports a variety of beams from the Alternating Gradient Synchrotron (AGS) which gets its input from the Booster Synchrotron. In turn, the Booster receives input beams from either a Tandem Van de Graaff (heavy ions) or a Linac (protons). The AGS extracts beam bunches, up to a rate of 30 Hertz, to the ATR which feeds the Relativistic Heavy Ion Collider (RHIC) starting with the sextant test in January of 1997. The ATR is made up of the upgraded U line and the new W, X, and Y lines. A test in 1995 transported beam to the end of the W line. During normal operation, a pulsed switching magnet at the end of the W line will bend the beam into the X line or the Y line so that the two storage rings in RHIC are filled with counter rotating beams. The ATR line is comprised of 80 power supplies (PS's), 17 of which are upgraded AGS PS's. The remaining 63 PS's were newly purchased. These PS's range from bipolar 600 watt linear type trim magnet PS's to 1 Megawatt, thyristor, dipole PS's. Results of the commissioning runs will be presented, as well as descriptions of regulation, filtering, and analog and digital controls

  1. MIR-ATR sensor for process monitoring

    International Nuclear Information System (INIS)

    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. (paper)

  2. Ataxia telangiectasia mutated and Rad3 related (ATR protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Rebeka Sultana

    Full Text Available INTRODUCTION: Ataxia telangiectasia mutated and Rad3 Related (ATR protein kinase is a key sensor of single-stranded DNA associated with stalled replication forks and repair intermediates generated during DNA repair. XRCC1 is a critical enzyme in single strand break repair and base excision repair. XRCC1-LIG3 complex is also an important contributor to the ligation step of the nucleotide excision repair response. METHODS: In the current study, we investigated synthetic lethality in XRCC1 deficient and XRCC1 proficient Chinese Hamster ovary (CHO and human ovarian cancer cells using ATR inhibitors (NU6027. In addition, we also investigated the ability of ATR inhibitors to potentiate cisplatin cytotoxicity in XRCC1 deficient and XRCC1 proficient CHO and human cancer cells. Clonogenic assays, alkaline COMET assays, γH2AX immunocytochemistry, FACS for cell cycle as well as FITC-annexin V flow cytometric analysis were performed. RESULTS: ATR inhibition is synthetically lethal in XRCC1 deficient cells as evidenced by increased cytotoxicity, accumulation of double strand DNA breaks, G2/M cell cycle arrest and increased apoptosis. Compared to cisplatin alone, combination of cisplatin and ATR inhibitor results in enhanced cytotoxicity in XRCC1 deficient cells compared to XRCC1 proficient cells. CONCLUSIONS: Our data provides evidence that ATR inhibition is suitable for synthetic lethality application and cisplatin chemopotentiation in XRCC1 deficient ovarian cancer cells.

  3. The Design Method for the ATR High Burnup MOX Fuel

    International Nuclear Information System (INIS)

    The Power Reactor and Nuclear Fuel Development Corporation (PNC) has developed the advanced thermal reactor (ATR). PNC is demonstrating MOX fuel utilization in a prototype of ATR, Fugen (165 MWe), in which 638 MOX fuel assemblies have been loaded without a failure since 1979. PNC is developing the high burn-up MOX fuel for the ATR to contribute to MOX fuels for thermal reactors. The statistical design evaluation method that included the MOX fuel rod performance evaluation code 'FEMAXI-ATR' was developed for the ATR high bum-up MOX fuel rod; it was verified that the integrity of the fuel could be maintained over the whole irradiation period

  4. 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 inATR(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 ofsouthpaw, 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. PMID:26908596

  5. ATM and ATR:Sensing DNA damage

    Institute of Scientific and Technical Information of China (English)

    Jun Yang; Zheng-Ping Xu; Yun Huang; Hope E. Hamrick; Penelope J. Duerksen-Hughes; Ying-Nian Yu

    2004-01-01

    Cellular response to genotoxic stress is a very complex process, and it usually starts with the "sensing" or "detection" of the DNA damage, followed by a series of events that include signal transduction and activation of transcription factors. The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair, cell cycle arrest, and cell death. There have been extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process, including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood,human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.

  6. Towards universal enrichment nanocoating for IR-ATR waveguides.

    Science.gov (United States)

    Giammarco, James; Zdyrko, Bogdan; Petit, Laeticia; Musgraves, J David; Hu, Juejun; Agarwal, Anu; Kimerling, Lionel; Richardson, Kathleen; Luzinov, Igor

    2011-08-28

    Polymer multilayered nanocoating capable of concentrating various chemical substances at IR-ATR waveguide surfaces is described. The coating affinity to an analyte played a pivotal role in sensitivity enhancement of the IR-ATR measurements, since the unmodified waveguide did not show any analyte detection. PMID:21734984

  7. Registration of heavy metal ions and pesticides with ATR planar waveguide enzyme sensors

    Science.gov (United States)

    Nabok, Alexei; Haron, Saharudin; Ray, Asim

    2004-11-01

    The proposed novel type of enzyme optical sensors is based on a combination of SiO2/Si3N4/SiO2 planar waveguide ATR (attenuated total reflection) transducer, fabricated by standard silicon planar technology, with the composite polyelectrolyte self-assembled coating containing both organic chromophores and enzyme molecules. Such devices were deployed to monitor typical industrial and agricultural water pollutants, such as heavy metal ions and pesticides, acting as inhibitors of enzyme reactions. The sensitivity of registration of these pollutants in the range of 1 ppb was achieved. The use of different enzymes in the sensitive membrane provides a background for pattern recognition of the above pollutants.

  8. 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.

  9. 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

    ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR signaling pathway and contributes to full-scale activation...... 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...

  10. Safety significance of ATR passive safety response attributes

    International Nuclear Information System (INIS)

    The Advanced Test Reactor (ATR) at the Idaho National Engineering Laboratory was designed with some passive safety response attributes which contribute to the safety of the facility. The three passive safety attributes being evaluated in the paper are: 1) In-core and in-vessel natural convection cooling, 2) a passive heat sink capability of the ATR primary coolant system (PCS) for the transfer of decay power from the uninsulated piping to the confinement, and 3) gravity feed of emergency coolant makeup. The safety significance of the ATR passive safety response attributes is that the reactor can passively respond to most transients, given a reactor scram, to provide adequate decay power removal and a significant time for operator action should the normal active heat removal systems and their backup systems both fail. The ATR Interim Level 1 Probabilistic Risk Assessment (PRA) models and results were used to evaluate the significance to ATR fuel damage frequency (or probability) of the above three passive response attributes. The results of the evaluation indicate that the first attribute is a major safety characteristic of the ATR. The second attribute has a noticeable but only minor safety significance. The third attribute has no significant influence on the ATR firewater injection system (emergency coolant system)

  11. ATR-mediated regulation of nuclear and cellular plasticity.

    Science.gov (United States)

    Kidiyoor, Gururaj Rao; Kumar, Amit; Foiani, Marco

    2016-08-01

    ATR (Ataxia Telangiectasia and Rad3-related) is a member of the Phosphatidylinositol 3-kinase-related kinases (PIKKs) family, amongst six other vertebrate proteins known so far. ATR is indispensable for cell survival and its essential role is in sensing DNA damage and initiating appropriate repair responses. In this review we highlight emerging and recent observations connecting ATR to alternative roles in controlling the nuclear envelope, nucleolus, centrosome and other organelles in response to both internal and external stress conditions. We propose that ATR functions control cell plasticity by sensing structural deformations of different cellular components, including DNA and initiating appropriate repair responses, most of which are yet to be understood completely. PMID:27283761

  12. 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

  13. Validation of helios for ATR core follow analysis

    International Nuclear Information System (INIS)

    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. (author)

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

    OpenAIRE

    Lucian Cuibus; Rubén Maggio; Vlad Mureșan; Zorița Diaconeasa; Oana Lelia Pop; Carmen Socaciu

    2015-01-01

    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...

  15. 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.

  16. Validation of HELIOS for ATR Core Follow Analyses

    International Nuclear Information System (INIS)

    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.

  17. ATR National Scientific User Facility 2009 Annual Report

    International Nuclear Information System (INIS)

    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 and 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.

  18. Assessment of COTS IR image simulation tools for ATR development

    Science.gov (United States)

    Seidel, Heiko; Stahl, Christoph; Bjerkeli, Frode; Skaaren-Fystro, Paal

    2005-05-01

    Following the tendency of increased use of imaging sensors in military aircraft, future fighter pilots will need onboard artificial intelligence e.g. ATR for aiding them in image interpretation and target designation. The European Aeronautic Defence and Space Company (EADS) in Germany has developed an advanced method for automatic target recognition (ATR) which is based on adaptive neural networks. This ATR method can assist the crew of military aircraft like the Eurofighter in sensor image monitoring and thereby reduce the workload in the cockpit and increase the mission efficiency. The EADS ATR approach can be adapted for imagery of visual, infrared and SAR sensors because of the training-based classifiers of the ATR method. For the optimal adaptation of these classifiers they have to be trained with appropriate and sufficient image data. The training images must show the target objects from different aspect angles, ranges, environmental conditions, etc. Incomplete training sets lead to a degradation of classifier performance. Additionally, ground truth information i.e. scenario conditions like class type and position of targets is necessary for the optimal adaptation of the ATR method. In Summer 2003, EADS started a cooperation with Kongsberg Defence & Aerospace (KDA) from Norway. The EADS/KDA approach is to provide additional image data sets for training-based ATR through IR image simulation. The joint study aims to investigate the benefits of enhancing incomplete training sets for classifier adaptation by simulated synthetic imagery. EADS/KDA identified the requirements of a commercial-off-the-shelf IR simulation tool capable of delivering appropriate synthetic imagery for ATR development. A market study of available IR simulation tools and suppliers was performed. After that the most promising tool was benchmarked according to several criteria e.g. thermal emission model, sensor model, targets model, non-radiometric image features etc., resulting in a

  19. FLUX SENSOR EVALUATIONS AT THE ATR CRITICAL FACILITY

    International Nuclear Information System (INIS)

    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 protocols

  20. "ATR activation in response to ionizing radiation: still ATM territory"

    Directory of Open Access Journals (Sweden)

    Cuadrado Myriam

    2006-05-01

    Full Text Available Abstract Unrepaired DNA double-strand breaks (DSBs are a major cause for genomic instability. Therefore, upon detection of a DSB a rapid response must be assembled to coordinate the proper repair/signaling of the lesion or the elimination of cells with unsustainable amounts of DNA damage. Three members of the PIKK family of protein kinases -ATM, ATR and DNA-PKcs- take the lead and initiate the signaling cascade emanating from DSB sites. Whereas DNA-PKcs activity seems to be restricted to the phosphorylation of targets involved in DNA repair, ATM and ATR phosphorylate a broad spectrum of cell cycle regulators and DNA repair proteins. In the canonical model, ATM and ATR are activated by two different types of lesions and signal through two independent and alternate pathways. Specifically, ATR is activated by various forms of DNA damage, including DSBs, arising at stalled replication forks ("replication stress", and ATM is responsible for the signaling of DSBs that are not associated with the replication machinery throughout the cell cycle. Recent evidence suggests that this model might be oversimplified and that coordinated crosstalk between ATM and ATR activation routes goes on at the core of the DNA damage response.

  1. 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 surfac...... as cap securing means (322), as the cap (300B) is secured onto the ATR-IR plate (200) by a pressure clamp (108) and an arm (110) holding the pressure clamp (108) pressing on the bridge (322)....

  2. 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.

  3. 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.

  4. Design and implementation of an embedded software system for ATR

    Science.gov (United States)

    Wang, Yuehuan; Li, Shiyong

    2011-11-01

    This paper has designed and realized a coarse-grained, unbalanced, modularized parallel embedded software system for ATR. According to the characteristics of ATR algorithms, some control modules such as system monitoring, task assignment and hierarchical algorithm modules are realized in our system. There are different design principles for different modules. The task assignment module combines different modules into clusters based on mutually exclusive modules, and assigns them to different processors. The principle of combination is the minimum variance of load on different processors. The system satisfies the requirement of real-time performance due to this reasonable strategy for task assignment, with the flexibility and scalability significantly improved.

  5. ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity in Arabidopsis

    OpenAIRE

    Boltz, Kara A.; Leehy, Katherine; Song, Xiangyu; Nelson, Andrew D.; Shippen, Dorothy E.

    2012-01-01

    The CTC1/STN1/TEN1 (CST) complex is an essential constituent of plant and vertebrate telomeres. Here we show that CST and ATR (ataxia telangiectasia mutated [ATM] and Rad3-related) act synergistically to maintain telomere length and genome stability in Arabidopsis. Inactivation of ATR, but not ATM, temporarily rescued severe morphological phenotypes associated with ctc1 or stn1. Unexpectedly, telomere shortening accelerated in plants lacking CST and ATR. In first-generation (G1) ctc1 atr muta...

  6. FTIR-ATR imaging of coated oil capsules

    International Nuclear Information System (INIS)

    Complete text of publication follows. Coated oil capsules are used to deliver new functional food ingredients. In this study spherical capsules were investigated containing a core with fish oil coated with a transparent gelatine layer. The remaining actives are within a hard coating, which is applied on the gelatine capsules. For the microstructural characterization of the coating the following techniques were used: Fourier Transform Infrared (FTIR) microscopy using an Attenuated Total Reflection (ATR) crystal, Light Microscopy (LM), X-ray microtomography (μCT) and Scanning Electron Microscopy (SEM). For FTIR-ATR imaging the oil capsules were embedded in epoxy resin. The embedded sample was trimmed in a microtome using a glass knife for the initial rough trimming. For the final fracture a diamond knife was used to obtain the best possible surface. A Ge-crystal was brought in contact with the surface of interest. LM images were obtained using the visible light camera of the FTIR system. A principal component analysis was performed on the FTIR-ATR imaging showing the spatial distribution of some of the compounds. This study demonstrated that imaging techniques can be used to analyse the microstructure of coated oil capsules. Correlative microscopy of techniques like FTIR-ATR imaging, LM, XRT and SEM-EDX results in useful information about the spatial distribution of the chemical compounds and layer thickness of solid food samples.

  7. 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...

  8. 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.

  9. Integrate knowledge acquisition with target recognition through closed-loop ATR

    Science.gov (United States)

    Yu, Ssu-Hsin; McLaughlin, Pat; Zatezalo, Aleksandar; Hsiao, Kai-yuh; Boskovic, Jovan

    2015-05-01

    Automatic Target Recognition (ATR) algorithm performance is highly dependent on the sensing conditions under which the input data is collected. Open-loop fly-bys often produce poor results due to less than ideal measurement conditions. In addition, ATR algorithms must be extremely complicated to handle the diverse range of inputs with a resulting reduction in overall performance and increase in complexity. Our approach, closed-loop ATR (CL-ATR), focuses on improving the quality of information input to the ATR algorithms by optimizing motion, sensor settings and team (vehicle-vehicle-human) collaboration to dramatically improve classification accuracy. By managing the data collection guided by predicted ATR performance gain, we increase the information content of the data and thus dramatically improve ATR performance with existing ATR algorithms. CL-ATR has two major functions; first, an ATR utility function, which represents the performance sensitivity of ATR produced classification labels as a function of parameters that correlate to vehicle/sensor states. This utility function is developed off-line and is often available from the original ATR study as a confusion matrix, or it can be derived through simulation without direct access to the inner working of the ATR algorithm. The utility function is inserted into our CLATR framework to autonomously control the vehicle/sensor. Second, an on-board planner maps the utility function into vehicle position and sensor collection plans. Because we only require the utility function on-board, we can activate any ATR algorithm onto a unmanned aerial vehicle (UAV) platform no matter how complex. This pairing of ATR performance profiles with vehicle/sensor controls creates a unique and powerful active perception behavior.

  10. Comparison of HEU and LEU Fuel Neutron Spectrum for ATR Fuel Element and ATR Flux-Trap Positions

    International Nuclear Information System (INIS)

    The Advanced Test Reactor (ATR) is a high power and high neutron flux research reactor operating in the United States. Powered with highly enriched uranium (HEU), the ATR has a maximum thermal power rating of 250 MWth. Because of the high total core power and high neutron flux, the ATR is an ideal candidate for assessing the feasibility of converting an HEU driven reactor to a low-enriched core. An optimized low-enriched uranium (LEU) (U-10Mo) core conversion case, which can meet the project requirements, has been selected. However, LEU contains a significant quantity of high density U-238 (80.3 wt.%), which will harden the neutron spectrum in the core region. Based on the reference ATR HEU and the optimized LEU full core plate-by-plate (PBP) models, the present work investigates and compares the neutron spectra differences in the fuel element (FE), Northeast flux trap (NEFT), Southeast flux trap (SEFT), and East flux trap (EFT) positions. A detailed PBP MCNP ATR core model was developed and validated for fuel cycle burnup comparison analysis. The current ATR core with HEU U 235 enrichment of 93.0wt.% was used as the reference model. Each HEU fuel element contains 19 fuel plates with a fuel meat thickness of 0.508 mm (20 mil). In this work, an optimized LEU (U-10Mo) core conversion case with a nominal fuel meat thickness of 0.330 mm (13 mil) and the U-235 enrichment of 19.7 wt.% was used to calculate the impact of the neutron spectrum in FE and FT positions. MCNP-calculated results show that the neutron spectrum in the LEU FE is slightly harder than in the HEU FE, as expected. However, when neutrons transport through water coolant and beryllium (Be), the neutrons are thermalized to an equilibrium neutron spectrum as a function of water volume fraction in the investigated FT positions. As a result, the neutron spectrum differences of the HEU and LEU in the NEFT, SEFT, and EFT are negligible. To demonstrate that the LEU core fuel cycle performance can meet the

  11. FTIR-ATR imaging of TAED-detergent granules

    International Nuclear Information System (INIS)

    Complete text of publication follows. The microstructure of detergents products for textile cleaning determines to a large extent their physical properties of these products. Release of a certain compound at a given time can improve the washing effect. Tetraacetylethylenediamine (TAED) is an important ingredient of washing powder/tablets. Its function is to enhance the bleaching effect to remove stains on clothing at lower temperatures. TAED granules are post-dosed to the formulation and consist of 4 compounds e.g.; TAED, sodium sulphate, a polymer and clay. To elucidate the microstructure of the detergents granules Fourier Transform Infrared (FTIR) microscopy using an Attenuated Total Reflection (ATR) crystal and Light Microscopy (LM) were used for characterization. FTIR-ATR-imaging was performed to elucidate the location of the different compounds. A Ge-crystal was brought in contact with the surface of interest. A principal component analysis was performed on the FTIR-ATR image, thus revealing the spatial distribution of the compounds (Figure 1) within the detergent granule. The full spectra obtained in a pixel can be used for identification. Figure 1 shows the distribution of the different compounds present in the TAED granule. The structure of the granule on the right is very porous. It shows large TAED particles partially encapsulated by sulphate and surrounded by the embedding material. The clay and copolymer compounds are mainly located around inner TAED particles. Combing techniques like FTIR-ATR imaging and LM results in useful information about the spatial distribution of chemical compounds within TAED granules. The FTIR spectra are used for positively identifying the chemical compounds.

  12. 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.   

  13. Neutronics analysis of the DHCE experiment in ATR-ITV

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, I.C.; Smith, D.L.; Tsai, H. [Argonne National Lab., IL (United States)

    1997-08-01

    The preliminary analysis of the DHCE experiments in the ITV and ATR was performed and its was concluded that such a vehicle is suitable for this kind of experiment. It is recommended to place an extra filter material in the thermocouple sleeve (such as B-10), to improve the helium to dpa ratio profile during irradiation. Also, it was concluded that a preliminary estimation of period of time for replacement of the external filter would be around 5 dps`s.

  14. 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.

  15. Neutronics analysis of the DHCE experiment in ATR-ITV

    International Nuclear Information System (INIS)

    The preliminary analysis of the DHCE experiments in the ITV and ATR was performed and its was concluded that such a vehicle is suitable for this kind of experiment. It is recommended to place an extra filter material in the thermocouple sleeve (such as B-10), to improve the helium to dpa ratio profile during irradiation. Also, it was concluded that a preliminary estimation of period of time for replacement of the external filter would be around 5 dps's

  16. 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.

  17. The ABC transporter MgAtr4 is a virulence factor of Mycosphaerella graminicola that affects colonization of substomatal cavities in wheat leaves

    NARCIS (Netherlands)

    Stergiopoulos, I.; Zwiers, L.H.; Waard, de M.A.

    2003-01-01

    The role in virulence of the ATP-binding cassette (ABC) transporters MgAtr1, MgAtr2, MgAtr3, MgAtr4, and MgAtr5 from Mycosphaerella graminicola was analyzed by gene disruption or replacement on seedlings of the susceptible wheat cultivar Obelisk. Disruption strains of MgAtr1 and MgAtr2 and replaceme

  18. Analysis of the ATR fuel element swaging process

    International Nuclear Information System (INIS)

    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 ampersand 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

  19. Evaluating E-business in IT company : ATR Soft Oy

    OpenAIRE

    Franc, Eric

    2014-01-01

    The internet is now at an age where company can’t ignore having their products and services advertised on this channel. Internet is becoming a new way to gain and attract customers. The objective of this study is to evaluate if implementation of E-business could be viable for an IT software company. This study was commissioned by ATR Soft Oy and it begins with an overview of the company business model and product line. The theory section examines frameworks regarding E-business transforma...

  20. Cell cycle-dependent DNA damage signaling induced by ICRF-193 involves ATM, ATR, CHK2, and BRCA1

    International Nuclear Information System (INIS)

    Topoisomerase II is essential for cell proliferation and survival and has been a target of various anticancer drugs. ICRF-193 has long been used as a catalytic inhibitor to study the function of topoisomerase II. Here, we show that ICRF-193 treatment induces DNA damage signaling. Treatment with ICRF-193 induced G2 arrest and DNA damage signaling involving γ-H2AX foci formation and CHK2 phosphorylation. DNA damage by ICRF-193 was further demonstrated by formation of the nuclear foci of 53BP1, NBS1, BRCA1, MDC1, and FANCD2 and increased comet tail moment. The DNA damage signaling induced by ICRF-193 was mediated by ATM and ATR and was restricted to cells in specific cell cycle stages such as S, G2, and mitosis including late and early G1 phases. Downstream signaling of ATM and ATR involved the phosphorylation of CHK2 and BRCA1. Altogether, our results demonstrate that ICRF-193 induces DNA damage signaling in a cell cycle-dependent manner and suggest that topoisomerase II might be essential for the progression of the cell cycle at several stages including DNA decondensation

  1. ATR-FTIR Studies on the Packing Film%一种包装膜的ATR-FTIR的剖析

    Institute of Scientific and Technical Information of China (English)

    孙瑞卿; 张汉辉; 杨融生

    2001-01-01

    FTIR and ATR-FTIR of the packing film have been studied.The dimension of thickness is about 0.034 m/m,the right and wrong sides of this packing film is composed of polypropylene and polyethylene glycol terephthalate, respectively.%在FTIR中,使用透射谱及水平ATR对进口的一种包装膜进行分析,该膜的厚度大约为0.034 m/m,膜的两面分别由等规聚丙烯和聚对苯二甲酸乙二醇酯组成。

  2. ATR-FTIR Spectroscopy in the Undergraduate Chemistry Laboratory: Part I--Fundamentals and Examples

    Science.gov (United States)

    Schuttlefield, Jennifer D.; 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. Several examples of the use of FTIR-ATR spectroscopy in different undergraduate chemistry laboratory courses are presented here. These…

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

    DEFF Research Database (Denmark)

    2014-01-01

    ,300H,300J) to be attached to an ATR plate (200) to form a sample cavity (302) enclosing the sample (204). The cap (300G,300H,300J) comprises openings for allowing gas to enter and exit the sample cavity (304,306,308), cap sealing means (310) for providing a tight sealing between the ATR plate (200...

  4. Another Travesty of Representation: Phonological Representation and Phonetic Interpretation of ATR Harmony in Kalenjin.

    Science.gov (United States)

    Local, John; Lodge, Ken

    1996-01-01

    The Kalenjin group of languages, spoken mainly in western Kenya, displays a harmony system involving the phonological feature Advanced Tongue Root ([ATR]). The study reported here addresses issues of the phonological representation of the [ATR] in Kalenjin and its phonetic interpretation. Specifically, it is shown that (1) the harmony system…

  5. 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...

  6. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage

    DEFF Research Database (Denmark)

    Syljuåsen, Randi G; Sørensen, Claus Storgaard; Hansen, Lasse Tengbjerg;

    2005-01-01

    -nuclear phosphorylation of histone H2AX, p53, Smc1, replication protein A, and Chk1 itself in human S-phase cells. These phosphorylations were inhibited by ATR siRNA and caffeine, but they occurred independently of ATM. Chk1 inhibition also caused an increased initiation of DNA replication, which was accompanied by...... increased amounts of nonextractable RPA protein, formation of single-stranded DNA, and induction of DNA strand breaks. Moreover, these responses were prevented by siRNA-mediated downregulation of Cdk2 or the replication initiation protein Cdc45, or by addition of the CDK inhibitor roscovitine. We propose...... that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage. These results may help explain why Chk1 is an essential kinase and should be taken into account when drugs to inhibit this kinase are considered for use in...

  7. ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress

    International Nuclear Information System (INIS)

    Induction of apoptosis is pivotal for eliminating cells with damaged DNA or deregulated proliferation. We show that tumor suppressor ARF and ATM/ATR kinase pathways cooperate in the induction of apoptosis in response to elevated expression of c-myc, β-catenin or human papilloma virus E7 oncogenes. Overexpression of oncogenes leads to the formation of phosphorylated H2AX foci, induction of Rad51 protein levels and ATM/ATR-dependent phosphorylation of p53. Inhibition of ATM/ATR kinases abolishes both induction of Rad51 and phosphorylation of p53, and remarkably reduces the level of apoptosis induced by co-expression of oncogenes and ARF. However, the induction of apoptosis is downregulated in p53-/- cells and does not depend on activities of ATM/ATR kinases, indicating that efficient induction of apoptosis by oncogene activation depends on coordinated action of ARF and ATM/ATR pathways in the regulation of p53

  8. Thermal Analysis of Irradiation Experiments in the ATR

    Energy Technology Data Exchange (ETDEWEB)

    Paul Murray

    2012-09-01

    Reactor material testing in the INL's Advanced Test Reactor (ATR) involves modeling and simulation of each experiment to accurately determine the irradiation temperature. This paper describes thermal analysis of capsule experiments using gas gap temperature control and provides data on recent material tests that validate the modeling results. Static capsule experiments and lead-out capsule experiments are discussed. The source of temperature variation in capsule experiments and ways to mitigate these variations are also explained. Two examples of instrumented lead-out capsule experiments, TMIST-1 and UCSB-2, are presented. A comparison of measured and calculated temperatures is used to validate the thermal models and to ascertain the accuracy of the calculated temperature.

  9. Characterization and sintering of ATR aluminia from niobium

    International Nuclear Information System (INIS)

    The characterization of resultante slag from Aluminothermic Reduction (ATR) process to obtain metallic niobium is presented. The slag was characterized for concentration and phases of aluminia by X-ray diffractometry. The results show that 70% of the slag is constituted by α aluminia. The lixiviation and calcination of the slag increased the α aluminia concentration to 95%, the slag was used for producing samples to be burning in three furnaces: electrical resistance furnace in the air, and two furnaces in the vacuum. The burned samples were characterized by microscopy, ultrasonic analysis, density measurements and X-ray diffractometry. The sintering in the vacuum is possible because the samples burned in vacuum presented major density. The formation of NbO2 and mullite was observed, by X-ray diffractometry. The data from optical microscopy, density measurements and X-ray diffractometry show high porosity. (M.C.K.)

  10. Deep convolutional neural networks for ATR from SAR imagery

    Science.gov (United States)

    Morgan, David A. E.

    2015-05-01

    Deep architectures for classification and representation learning have recently attracted significant attention within academia and industry, with many impressive results across a diverse collection of problem sets. In this work we consider the specific application of Automatic Target Recognition (ATR) using Synthetic Aperture Radar (SAR) data from the MSTAR public release data set. The classification performance achieved using a Deep Convolutional Neural Network (CNN) on this data set was found to be competitive with existing methods considered to be state-of-the-art. Unlike most existing algorithms, this approach can learn discriminative feature sets directly from training data instead of requiring pre-specification or pre-selection by a human designer. We show how this property can be exploited to efficiently adapt an existing classifier to recognise a previously unseen target and discuss potential practical applications.

  11. Alternative Lengthening of Telomeres Renders Cancer Cells Hypersensitive to ATR Inhibitors

    OpenAIRE

    Flynn, Rachel Litman; Cox, Kelli E.; Jeitany, Maya; Wakimoto, Hiroaki; Bryll, Alysia R.; Ganem, Neil J.; Bersani, Francesca; Pineda, Jose R.; Suvà, Mario L.; Benes, Cyril H.; Haber, Daniel A.; Boussin, Francois D.; Zou, Lee

    2015-01-01

    Cancer cells rely on telomerase or the alternative lengthening of telomeres (ALT) pathway to overcome replicative mortality. ALT is mediated by recombination and is prevalent in a subset of human cancers, yet whether it can be exploited therapeutically remains unknown. Loss of the chromatin remodeling protein ATRX associates with ALT in cancers. Here, we show that ATRX loss compromises cell-cycle regulation of the telomeric non-coding RNA TERRA and leads to persistent association of replicati...

  12. 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.

  13. RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells.

    Science.gov (United States)

    Ragland, Ryan L; Patel, Sima; Rivard, Rebecca S; Smith, Kevin; Peters, Ashley A; Bielinsky, Anja-Katrin; Brown, Eric J

    2013-10-15

    The ATR-CHK1 axis stabilizes stalled replication forks and prevents their collapse into DNA double-strand breaks (DSBs). Here, we show that fork collapse in Atr-deleted cells is mediated through the combined effects the sumo targeted E3-ubiquitin ligase RNF4 and activation of the AURKA-PLK1 pathway. As indicated previously, Atr-deleted cells exhibited a decreased ability to restart DNA replication following fork stalling in comparison with control cells. However, suppression of RNF4, AURKA, or PLK1 returned the reinitiation of replication in Atr-deleted cells to near wild-type levels. In RNF4-depleted cells, this rescue directly correlated with the persistence of sumoylation of chromatin-bound factors. Notably, RNF4 repression substantially suppressed the accumulation of DSBs in ATR-deficient cells, and this decrease in breaks was enhanced by concomitant inhibition of PLK1. DSBs resulting from ATR inhibition were also observed to be dependent on the endonuclease scaffold protein SLX4, suggesting that RNF4 and PLK1 either help activate the SLX4 complex or make DNA replication fork structures accessible for subsequent SLX4-dependent cleavage. Thus, replication fork collapse following ATR inhibition is a multistep process that disrupts replisome function and permits cleavage of the replication fork. PMID:24142876

  14. 皮革产品的ATR-FTIR快速鉴定%High-Speed Examination of Leather Products by ATR-FTIR

    Institute of Scientific and Technical Information of China (English)

    张红雨; 徐琳; 王乃岩

    2004-01-01

    分析和比较真皮和人造革的ATR-FTIR红外谱图表明,两者的特征峰峰位并不重叠或干扰,其结构可以区分.用ATR-FTIR鉴定皮革产品具有准确、灵敏、快速、简便、对产品无损伤、无需预处理、易实现现场自动化等优点.

  15. 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.

  16. Interaction between PARP-1 and ATR in mouse fibroblasts is blocked by PARP inhibition

    OpenAIRE

    Kedar, Padmini S.; Stefanick, Donna F.; Horton, Julie K.; Wilson, Samuel H.

    2008-01-01

    Inhibition of PARP activity results in extreme sensitization to MMS-induced cell killing in cultured mouse fibroblasts. In these MMS-treated cells, PARP inhibition is accompanied by an accumulation of S-phase cells that requires signaling by the checkpoint kinase ATR (Horton et al. (2005) J. Biol. Chem., 280, 15773-15785). Here, we examined mouse fibroblast extracts for formation of a complex that may reflect association between the damage responsive proteins PARP-1 and ATR. Co-immunoprecipit...

  17. Modulation of Ionizing Radiation-Induced G2 Arrest by Cyclooxygenase-2 and its Inhibitor Celecoxib

    International Nuclear Information System (INIS)

    Purpose: Prolongation or attenuation of ionizing radiation (IR)-induced G2-M arrest in cyclooxygenase-2 (COX-2) overexpressing or celecoxib-treated cells, respectively, has been previously observed. To better understand the molecular mechanisms involved, we investigated the molecules involved in G2 checkpoint pathways after treatment with IR ± celecoxib. Methods and Materials: Various molecules in the G2 checkpoint pathways were investigated in HCT-116-Mock and -COX-2 cells. Western blot, reverse transcriptase polymerase chain reaction, confocal microscopy, and fluorescence activated cell sorter (FACS) analyses were performed to investigate whether expression and activity of the ataxia telangiectasia and rad3-related (ATR) could be modulated by COX-2 and its selective inhibitors. Results: COX-2 overexpression increased expression and activity of ATR after IR exposure. Celecoxib downregulated ATR in all tested cell lines independent of COX-2 expression, but downregulation was greater in COX-2 overexpressing cells after cells were irradiated. Celecoxib pretreatment before radiation caused strongly inhibited G2 arrest. Conclusions: COX-2 appears to prolong IR-induced G2 arrest by upregulating ATR. Celecoxib downregulated ATR preferentially in irradiated COX-2 overexpressing cells. Celecoxib may radiosensitize cancer cells by inhibiting G2 arrest through ATR downregulation.

  18. TopBP1和ATR-ATRIP在细胞周期中的作用及联系%Role and Relationship of TopBP1 and ATR-ATRIP in the Cell Life Cycle

    Institute of Scientific and Technical Information of China (English)

    黄神安; 熊高飞; 张吉翔

    2006-01-01

    TopBP1(topoisomerase Ⅱ beta-binding protein 1)和ATR(ataxia-telangiectasia mutated-and rad3-related)-ATRIP(ATR-interacting protein)通过调节一些因子在DNA损伤检控点(DNA damage checkpoint)中起着关键的作用,其中TopBP1可以激活ATR-ATRIP的复合体.文章着重阐述了TopBP1和ATR-ATRIP如何调控细胞周期并发挥其维护基因组完整性的作用.

  19. Feature-based ATR performance method for FLIR

    Science.gov (United States)

    Doria, David M.

    2004-09-01

    A performance model for FLIR automatic target recognition is discussed. Key aspects of this model are that (a) relationships between sensor optical resolution, sampling, noise and estimated P(ID) are implicitly defined, (b) premised on the use of the particular features that are used, the analysis of the matching structure leads to an explicit "shape similarity" measure between targets, (c) the notion of "shape" includes both internal signature attributes and external contour information; (d) the values of this shape measure can be measured for both true and false target models using combined CAD rendering, sensor models, and features, (e) in addition to the P(ID), the system also is able to predict the probability of declaration P(Declare|Target) for a given true target, (f) the system is able to predict the probability of false declaration for a given confuser or confuser to target similarity specification, (g) M (with M greater than or equal to 2) class problems are able to be handled, and (h) the diagonals along confusion matrices can be estimated directly using this approach. The model relies on analysis of performance of a particular type of shape-based features, with the goal of developing explicit relationships from low level features through high level model matching. Based on the predicted densities of the ensemble of features, the system approximates an expression for the likelihood of the observed features under noisy conditions with a given sensor, conditioned on the target type, aspect, and range. Using some engineering approximations that relate to the distance transform-type method of matching that is analyzed, a tractable form of a non-unique correspondence based approximate likelihood expression is obtained, which can be used to estimate bounds on the performance of similar sensor/ATR systems that rely on these features. Such an approach could also be applied to other phenomenologies, such as synthetic aperture radar, using an appropriate low

  20. ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair.

    Science.gov (United States)

    Brown, Adam D; Sager, Brian W; Gorthi, Aparna; Tonapi, Sonal S; Brown, Eric J; Bishop, Alexander J R

    2014-01-01

    DNA replication fork stalling or collapse that arises from endogenous damage poses a serious threat to genome stability, but cells invoke an intricate signaling cascade referred to as the DNA damage response (DDR) to prevent such damage. The gene product ataxia telangiectasia and Rad3-related (ATR) responds primarily to replication stress by regulating cell cycle checkpoint control, yet it's role in DNA repair, particularly homologous recombination (HR), remains unclear. This is of particular interest since HR is one way in which replication restart can occur in the presence of a stalled or collapsed fork. Hypomorphic mutations in human ATR cause the rare autosomal-recessive disease Seckel syndrome, and complete loss of Atr in mice leads to embryonic lethality. We recently adapted the in vivo murine pink-eyed unstable (pun) assay for measuring HR frequency to be able to investigate the role of essential genes on HR using a conditional Cre/loxP system. Our system allows for the unique opportunity to test the effect of ATR loss on HR in somatic cells under physiological conditions. Using this system, we provide evidence that retinal pigment epithelium (RPE) cells lacking ATR have decreased density with abnormal morphology, a decreased frequency of HR and an increased level of chromosomal damage. PMID:24675793

  1. 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.

  2. Evaluation of shooting distance by AFM and FTIR/ATR analysis of GSR.

    Science.gov (United States)

    Mou, Yongyan; Lakadwar, Jyoti; Rabalais, J Wayne

    2008-11-01

    The techniques of atomic force microscopy (AFM) and Fourier transform infrared attenuated total reflectance (FTIR/ATR) spectroscopy are applied to the analysis of gun-shot residue (GSR) to test their ability to determine shooting distance and discrimination of the powder manufacturers. AFM is a nondestructive technique that is capable of characterizing the shapes and size distributions of GSR particles with resolution down to less than a nanometer. This may be useful for estimation of the shooting distance. Our AFM images of GSR show that the size distribution of the particles is inversely proportional to the shooting distance. Discrimination of powder manufacturers is tested by FTIR/ATR investigation of GSR. Identifying the specific compounds in the GSR by FTIR/ATR was not possible because it is a mixture of the debris of several compounds that compose the residue. However, it is shown that the GSR from different cartridges has characteristic FTIR/ATR bands that may be useful in differentiating the powder manufacturers. It appears promising that the development of AFM and FTIR/ATR databases for various powder manufacturers may be useful in analysis and identification of GSR. PMID:18761553

  3. 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. PMID:25172681

  4. Modeling the attenuated total reflectance infrared (ATR-FTIR) spectrum of apatite

    Science.gov (United States)

    Aufort, Julie; Ségalen, Loïc; Gervais, Christel; Brouder, Christian; Balan, Etienne

    2016-06-01

    Attenuated total reflectance (ATR) infrared spectra were measured on a synthetic and a natural fluorapatite sample. A modeling approach based on the computation of the Fresnel reflection coefficient between the ATR crystal and the powder sample was used to analyze the line shape of the spectra. The dielectric properties of the samples were related to those of pure fluorapatite using an effective medium approach, based on Maxwell-Garnett and Bruggeman models. The Bruggeman effective medium model leads to a very good agreement with the experimental data recorded on the synthetic fluorapatite sample. The poorer agreement observed on the natural sample suggests a more significant heterogeneity of the sample at a characteristic length scale larger than the mid-infrared characteristic wavelength, i.e., about 10 micrometers. The results demonstrate the prominent role of macroscopic electrostatic effects over fine details of the microscopic structure in determining the line shape of strong ATR bands.

  5. 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

  6. 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.

  7. 粉煤灰激活中ATR/FTIR、FTIR和NMR的分析与比较

    Institute of Scientific and Technical Information of China (English)

    易志慧; 蒋海青; 王晓钧; 于士刚

    2007-01-01

    采用ATR/FTIR对南京热电厂Ⅰ级粉煤灰及经过NaOH激发后的样品进行了分析,并且同FTIR和NMR的分析结果进行比较。研究结果表明:以表征表面特征的ATR/FTIR方法可以清晰地表征粉煤灰表面出现的变化,且随着碱浓度的提高变化明显,而以表征宏观几率特征的FTIR和NMR则没有反映出粉煤灰表面出现的变化。ATR/FTIR在粉煤灰的表面研究中具有独到效果。

  8. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) imaging of tissues and live cells.

    Science.gov (United States)

    Andrew Chan, K L; Kazarian, Sergei G

    2016-03-29

    FTIR spectroscopic imaging is a label-free, non-destructive and chemically specific technique that can be utilised to study a wide range of biomedical applications such as imaging of biopsy tissues, fixed cells and live cells, including cancer cells. In particular, the use of FTIR imaging in attenuated total reflection (ATR) mode has attracted much attention because of the small, but well controlled, depth of penetration and corresponding path length of infrared light into the sample. This has enabled the study of samples containing large amounts of water, as well as achieving an increased spatial resolution provided by the high refractive index of the micro-ATR element. This review is focused on discussing the recent developments in FTIR spectroscopic imaging, particularly in ATR sampling mode, and its applications in the biomedical science field as well as discussing the future opportunities possible as the imaging technology continues to advance. PMID:26488803

  9. Esophago-gastric motility and nutritional management in a child with ATR-X syndrome.

    Science.gov (United States)

    Watanabe, Toshihiko; Arai, Katsuhiro; Takahashi, Masataka; Ohno, Michinobu; Sato, Kaori; Fuchimoto, Yasushi; Wada, Takahiko; Ida, Shinobu; Kawahara, Hisayoshi; Kanamori, Yutaka

    2014-08-01

    X-linked alpha thalassemia mental retardation (ATR-X) syndrome is an X-linked recessive disorder that often involves gastrointestinal symptoms. Aspiration pneumonia related to gastroesophageal reflux has been reported as the major cause of death, but gastrointestinal function has not been well investigated. The present report describes a child with ATR-X syndrome who suffered from periodical episodes of refractory vomiting. We investigated the function of upper alimentary tract and found that esophago-gastric dysmotility and severe gastric volvulus were the major causes of gastrointestinal symptoms. This child was surgically treated with anterior gastropexy and jejunal alimentation through gastrostomy, and the symptoms were relieved with good weight gain. This report may provide insight into the gastrointestinal function and nutritional management in children with ATR-X syndrome. PMID:25252072

  10. 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.

  11. ATR and transmission analysis of pigments by means of far infrared spectroscopy.

    Science.gov (United States)

    Kendix, Elsebeth L; Prati, Silvia; Joseph, Edith; Sciutto, Giorgia; Mazzeo, Rocco

    2009-06-01

    In the field of FTIR spectroscopy, the far infrared (FIR) spectral region has been so far less investigated than the mid-infrared (MIR), even though it presents great advantages in the characterization of those inorganic compounds, which are inactive in the MIR, such as some art pigments, corrosion products, etc. Furthermore, FIR spectroscopy is complementary to Raman spectroscopy if the fluorescence effects caused by the latter analytical technique are considered. In this paper, ATR in the FIR region is proposed as an alternative method to transmission for the analyses of pigments. This methodology was selected in order to reduce the sample amount needed for analysis, which is a must when examining cultural heritage materials. A selection of pigments have been analyzed in both ATR and transmission mode, and the resulting spectra were compared with each other. To better perform this comparison, an evaluation of the possible effect induced by the thermal treatment needed for the preparation of the polyethylene pellets on the transmission spectra of the samples has been carried out. Therefore, pigments have been analyzed in ATR mode before and after heating them at the same temperature employed for the polyethylene pellet preparation. The results showed that while the heating treatment causes only small changes in the intensity of some bands, the ATR spectra were characterized by differences in both intensity and band shifts towards lower frequencies if compared with those recorded in transmission mode. All pigments' transmission and ATR spectra are presented and discussed, and the ATR method was validated on a real case study. PMID:19266186

  12. Mutation analysis of the ATR gene in breast and ovarian cancer families

    International Nuclear Information System (INIS)

    Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for only 20–30% of the familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. The ATR (ataxia-telangiectasia- and Rad3-related) kinase is essential for the maintenance of genomic integrity. It functions both in parallel and cooperatively with ATM, but whereas ATM is primarily activated by DNA double-strand breaks induced by ionizing radiation, ATR has been shown to respond to a much broader range of DNA damage. Upon activation, ATR phosphorylates several important tumor suppressors, including p53, BRCA1 and CHK1. Based on its central function in the DNA damage response, ATR is a plausible candidate gene for susceptibility to cancer. We screened the entire coding region of the ATR gene for mutations in affected index cases from 126 Finnish families with breast and/or ovarian cancer, 75 of which were classified as high-risk and 51 as moderate-risk families, by using conformation sensitive gel electrophoresis and direct sequencing. A large number of novel sequence variants were identified, four of which – Glu254Gly, Ser1142Gly, IVS24-48G>A and IVS26+15C>T – were absent from the tested control individuals (n = 300). However, the segregation of these mutations with the cancer phenotype could not be confirmed, partly because of the lack of suitable DNA samples. The present study does not support a major role for ATR mutations in hereditary susceptibility to breast and ovarian cancer

  13. Associations of ATR and CHEK1 single nucleotide polymorphisms with breast cancer.

    Directory of Open Access Journals (Sweden)

    Wei-Yu Lin

    Full Text Available DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS. The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6 x 10(-5 and rs2155388 in CHEK1 (p=3.1 x 10(-6, but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12% and breast cancer risk, with a summary odds ratio (confidence interval of 0.90 (0.83-0.98 [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes.

  14. 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…

  15. S-phase-dependent p50/NF-кB1 phosphorylation in response to ATR and replication stress acts to maintain genomic stability

    OpenAIRE

    Crawley, Clayton D.; Kang, Shijun; Bernal, Giovanna M; Wahlstrom, Joshua S.; Voce, David J; Cahill, Kirk E.; Garofalo, Andrea; Raleigh, David R.; Weichselbaum, Ralph R.; Yamini, Bakhtiar

    2015-01-01

    The apical damage kinase, ATR, is activated by replication stress (RS) both in response to DNA damage and during normal S-phase. Loss of function studies indicates that ATR acts to stabilize replication forks, block cell cycle progression and promote replication restart. Although checkpoint failure and replication fork collapse can result in cell death, no direct cytotoxic pathway downstream of ATR has previously been described. Here, we show that ATR directly reduces survival by inducing pho...

  16. Multivariate analysis of ATR-FTIR spectra for assessment of oil shale organic geochemical properties

    Science.gov (United States)

    Washburn, Kathryn E.; Birdwell, Justin E.

    2013-01-01

    In this study, attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FTIR) was coupled with partial least squares regression (PLSR) analysis to relate spectral data to parameters from total organic carbon (TOC) analysis and programmed pyrolysis to assess the feasibility of developing predictive models to estimate important organic geochemical parameters. The advantage of ATR-FTIR over traditional analytical methods is that source rocks can be analyzed in the laboratory or field in seconds, facilitating more rapid and thorough screening than would be possible using other tools. ATR-FTIR spectra, TOC concentrations and Rock–Eval parameters were measured for a set of oil shales from deposits around the world and several pyrolyzed oil shale samples. PLSR models were developed to predict the measured geochemical parameters from infrared spectra. Application of the resulting models to a set of test spectra excluded from the training set generated accurate predictions of TOC and most Rock–Eval parameters. The critical region of the infrared spectrum for assessing S1, S2, Hydrogen Index and TOC consisted of aliphatic organic moieties (2800–3000 cm−1) and the models generated a better correlation with measured values of TOC and S2 than did integrated aliphatic peak areas. The results suggest that combining ATR-FTIR with PLSR is a reliable approach for estimating useful geochemical parameters of oil shales that is faster and requires less sample preparation than current screening methods.

  17. FTIR-ATR Monitoring and SEC/RI/MALLS characterization of ATRP synthesized hyperbranched polyacrylates

    OpenAIRE

    Gonçalves, Miguel; Costa, Mário Rui; Dias, Rolando

    2009-01-01

    This work reports the synthesis at 1 L scale of hyperbranched polyacrylates based upon acrylate/diacrylate monomers such as n-butyl acrylate (nBA)/1,6-hexanediol diacrylate (HDDA) and using atom transfer radical polymerization (ATRP). A FTIR-ATR immersion probe was used to monitor the polymerization reaction. FCT

  18. PKA-mediated phosphorylation of ATR promotes recruitment of XPA to UV-induced DNA damage.

    Science.gov (United States)

    Jarrett, Stuart G; Wolf Horrell, Erin M; Christian, Perry A; Vanover, Jillian C; Boulanger, Mary C; Zou, Yue; D'Orazio, John A

    2014-06-19

    The melanocortin 1 receptor (MC1R), which signals through cAMP, is a melanocytic transmembrane receptor involved in pigmentation, adaptive tanning, and melanoma resistance. We report MC1R-mediated or pharmacologically-induced cAMP signaling promotes nucleotide excision repair (NER) in a cAMP-dependent protein kinase A (PKA)-dependent manner. PKA directly phosphorylates ataxia telangiectasia and Rad3-related protein (ATR) at Ser435, which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA) to sites of nuclear UV photodamage, accelerating clearance of UV-induced photolesions and reducing mutagenesis. Loss of Ser435 within ATR prevents PKA-mediated ATR phosphorylation, disrupts ATR-XPA binding, delays recruitment of XPA to UV-damaged DNA, and elevates UV-induced mutagenesis. This study mechanistically links cAMP-PKA signaling to NER and illustrates potential benefits of cAMP pharmacological rescue to reduce UV mutagenesis in MC1R-defective, melanoma-susceptible individuals. PMID:24950377

  19. 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.

  20. Solid Acid-Catalyzed Cellulose Hydrolysis Monitored by In Situ ATR-IR Spectroscopy

    NARCIS (Netherlands)

    Zakzeski, J.; Grisel, R.J.H.; Smit, A.T.; Weckhuysen, B.M.

    2012-01-01

    The solid acid-catalyzed hydrolysis of cellulose was studied under elevated temperatures and autogenous pressures using in situ ATR-IR spectroscopy. Standards of cellulose and pure reaction products, which include glucose, fructose, hydroxymethylfurfural (HMF), levulinic acid (LA), formic acid, and

  1. MATERNAL ATRAZINE (ATR) ALTERS HYPOTHALAMIC DOPAMINE (HYP-DA) AND SERUM PROLACTIN (SPRL) IN MALE PUPS

    Science.gov (United States)

    Maternal Atrazine (ATR) alters hypothalamic dopamine (HYP-DA) and serum prolactin (sPRL) in male pups. 1Christopher Langdale, 2Tammy Stoker and 2Ralph Cooper. 1 Dept. of Cell Biology, North Carolina State University College of Veterinary Medicine, Raleigh, NC. 2 Endocrinology ...

  2. Nanocrystalline diamond sensor targeted for selective CRP detection: an ATR-FTIR spectroscopy study.

    Science.gov (United States)

    Andersson, Per Ola; Viberg, Pernilla; Forsberg, Pontus; Nikolajeff, Fredrik; Österlund, Lars; Karlsson, Mikael

    2016-05-01

    Protein immobilization on functionalized fluorine-terminated nanocrystalline (NCD) films was studied by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy using an immobilization protocol developed to specifically bind C-reactive protein (CRP). Using an ATR-FTIR spectroscopy method employing a force-controlled anvil-type configuration, three critical steps of the ex situ CRP immobilization were analyzed. First, the NCD surface was passivated by deposition of a copolymer layer consisting of polyethylene oxide and polypropylene oxide. Second, a synthetic modified polypeptide binder with high affinity to CRP was covalently attached to the polymeric film. Third, CRP dissolved in aqueous buffer in concentrations of 10-20 μg/mL was added on the functionalized NCD surface. Both the amide I and II bands, due to the polypeptide binder and CRP, were clearly observed in ATR-FTIR spectra. CRP amide I bands were extracted from difference spectra and yielded bands that agreed well with the reported amide I band of free (non-bonded) CRP in solution. Thus, our results show that CRP retains its secondary structure when it is attached to the polypeptide binders. Compared to previous IR studies of CRP in solution, about 200 times lower concentration was applied in the present study. Graphical Abstract Direct non-destructive ATR-FTIR analysis of C-reactive protein (CRP) selectively bound to functionalized nanocrystalline diamond (NCD) sensor surface. PMID:27007740

  3. ATR Mediates a Checkpoint at the Nuclear Envelope in Response to Mechanical Stress

    Czech Academy of Sciences Publication Activity Database

    Kumar, A.; Mazzanti, M.; Mistrik, M.; Košař, Martin; Beznoussenko, G.V.; Mironov, A. A.; Garrè, M.; Parazolli, D.; Shivashankar, G. V.; Scita, G.; Bartek, Jiří; Foiani, M.

    2014-01-01

    Roč. 158, č. 3 (2014), s. 633-646. ISSN 0092-8674 Grant ostatní: Marie Curie Intra-European(IT) 274093 Institutional support: RVO:68378050 Keywords : ATR * Mechanical Stress * cell cycle Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 32.242, year: 2014

  4. 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.

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

    International Nuclear Information System (INIS)

    Research highlights: → 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. → However, it is not clear exactly how PP5 participates in this process. → 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.

  6. 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

  7. Coupling of phonon-polariton modes at dielectric-dielectric interfaces by the ATR technique

    Science.gov (United States)

    Cocoletzi, G. H.; Olvera Hernández, J.; Martínez Montes, G.

    1989-08-01

    We report the calculated ATR dispersion relation of the interface phonon-polariton modes in the prism-dielectric-dielectric configuration. Comparison of electromagnetic dispersion relations (EMDR) with the ATR dispersion relations are presented for three different interfaces: I) GaAs/GaP, II) CdF2/CaF2 and III) CaF2/GaP in two propagation windows, using the Otto and Kretschmann geometries for p-polarized light. We have studied the three cases using angle and frequency scans for each window and geometry. The results indicate that it is possible to excite and detect phonon-polariton modes at the dielectric-dielectric interface.

  8. Phylogeny of cultivated and wild wheat species using ATR-FTIR spectroscopy

    Science.gov (United States)

    Demir, Pinar; Onde, Sertac; Severcan, Feride

    2015-01-01

    Within the last decade, an increasing amount of genetic data has been used to clarify the problems inherent in wheat taxonomy. The techniques for obtaining and analyzing these data are not only cumbersome, but also expensive and technically demanding. In the present study, we introduce infrared spectroscopy as a method for a sensitive, rapid and low cost phylogenetic analysis tool for wheat seed samples. For this purpose, 12 Triticum and Aegilops species were studied by Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy. Hierarchical cluster analysis and principal component analysis clearly revealed that the lignin band (1525-1505 cm-1) discriminated the species at the genus level. However, the species were clustered according to their genome commonalities when the whole spectra were used (4000-650 cm-1). The successful differentiation of Triticum and its closely related genus Aegilops clearly demonstrated the power of ATR-FTIR spectroscopy as a suitable tool for phylogenetic research.

  9. ATR-A1 irradiation experiment on vanadium alloys and low activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Tasi, H.; Strain, R.V.; Gomes, I.; Hins, A.G.; Smith, D.L.

    1996-04-01

    To study the mechanical properties of vanadium alloys under neutron irradiation at low temperatures, an experiment was designed and constructed for irradiation in the Advanced Test Reactor (ATR). The experiment contained Charpy, tensile, compact tension, TEM, and creep specimens of vanadium alloys. It also contained limited low-activation ferritic steel specimens as part of the collaborative agreement with Monbusho of Japan. The design irradiation temperatures for the vanadium alloy specimens in the experiment are {approx}200 and 300{degrees}C, achieved with passive gap-gap sizing and fill gas blending. To mitigate vanadium-to-chromium transmutation from the thermal neutron flux, the test specimens are contained inside gadolinium flux filters. All specimens are lithium-bonded. The irradiation started in Cycle 108A (December 3, 1995) and is expected to have a duration of three ATR cycles and a peak influence of 4.4 dpa.

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

    OpenAIRE

    Svečnjak Lidija; Baranović Goran; Vinceković Marko; Prđun Saša; Bubalo Dragan; Tlak Gajger Ivana

    2015-01-01

    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 obtain...

  11. 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. PMID:25476739

  12. High resolution ATR FTIR spectroscopy of hydrogenated diamond nanoparticles using diamond-coated prism

    Czech Academy of Sciences Publication Activity Database

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

    Tokyo : Prime International Co, 2011. s. 128. [International Conference on New Diamond and Nano carbons 2011 (NDNC 2011). 16.05.2011.-20.05.2011, Kunibiki Messe, Matsue] R&D Projects: GA MŠk LC510 Grant ostatní: AVČR(CZ) M100100902 Institutional research plan: CEZ:AV0Z10100521 Keywords : nanodiamond * ATR FTIR * hydrogenation Subject RIV: BM - Solid Matter Physics ; Magnetism

  13. FTIR-ATR spectroscopy – a new approach in root discrimination of crop and weed species

    OpenAIRE

    Meinen, Catharina; Rauber, Rolf

    2012-01-01

    Crop and weed species often compete for the same resources. To analyse below-ground competitive processes, crop and weed roots have to be distinguished from one another. Up to now, a reliable and easy method for plant root discrimination does not exist. In a recent study, Fourier transform infrared (FTIR) spectroscopy with an attenuated total reflection (ATR) device was successfully applied in root discrimination of distantly related plant species (pea/oat). In this experiment, we wanted to t...

  14. The Conference Proceedings of the 2003 Air Transport Research Society (ATRS) World Conference, Volume 3

    Science.gov (United States)

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

    2003-01-01

    Volume 3 of the 2003 Air Transport Reserch Society (ATRS) World Conference includes papers on topics relevant to airline operations worldwide. Specific topics include: European Union and civil aviation regimens;simulating decision making in airline operations, passenger points of view on convenient airports; route monopolies and nonlinear pricing; cooperation among airports in Europe; fleet modernizaiton in Brazil;the effects of deregulation on the growth of air transportation in Europe and the United States.

  15. Testing of the atr system of Leica TCRA 1103 plus total station

    OpenAIRE

    Šketa, Matic

    2014-01-01

    The aim of this paper is to test the automatic target recognition system of Leica TCRA1103 plus total station. A total station enables the automatic target recognition. The introductory part of my research is based on the development and automation of electronic total stations. Furthermore, the research is dedicated to the automatic target identifying system of Leica ATR. The aim of the practical part of this research is to test the accuracy of Leica TCRA1103 plus total station at horizont...

  16. Enhanced ATR algorithm for high resolution multi-band sonar imagery

    Science.gov (United States)

    Aridgides, Tom; Fernández, Manuel

    2008-04-01

    An improved automatic target recognition (ATR) processing string has been developed. The overall processing string consists of pre-processing, subimage adaptive clutter filtering (SACF), normalization, detection, data regularization, feature extraction, optimal subset feature selection, feature orthogonalization and classification processing blocks. A new improvement was made to the processing string, data regularization, which entails computing the input data mean, clipping the data to a multiple of its mean and scaling it, prior to feature extraction. The classified objects of 3 distinct 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, which resulted in a 3:1 reduction in false alarms. Two significant fusion algorithm improvements were made. First, a nonlinear 2nd order (Volterra) feature LLRT fusion algorithm was developed. Second, a repeated application of a subset Volterra feature selection / feature orthogonalization / LLRT fusion block was utilized. It was shown that cascaded Volterra feature LLRT fusion of the ATR processing strings outperforms baseline summing and single-stage Volterra 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.

  17. 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.

  18. ATR-IR Investigation of Solvent Interactions with Surface-Bound Polymers

    Science.gov (United States)

    2016-01-01

    Solvent interactions with bulk and surface-bound polymer brushes are crucial for functionalities such as controlled friction and thermoresponsive adhesion. To study such interactions, the temperature-induced solvent-quality changes and the effect of surface tethering on the mechanical and tribological properties of poly(dodecyl methacrylate) (P12MA) brushes have been investigated by means of attenuated total reflection infrared spectroscopy (ATR-IR), as well as atomic force microscopy (AFM) and lateral force microscopy (LFM). These results have been compared with temperature-dependent UV–visible spectrophotometry (UV–vis) data for the corresponding bulk polymer solutions. The ATR-IR results clearly show that increasing temperature enhances ethanol uptake in P12MA, which results in film swelling. This is accompanied by a marked increase in both adhesion and friction. We have also shown that a combination of solvents, such as toluene and ethanol, can lead to a temperature-dependent solvent partitioning within the polymer brush. To our knowledge this is the first time preferential solvent uptake in a grafted-from brush has been monitored via in situ ATR-IR. Moreover, we have observed remarkably different behavior for polymer chains in solution compared to the behavior of similar chains bound to a surface. The presented findings on the temperature-dependent solvent interactions of surface-grafted P12MA reveal previously unknown solvation phenomena and open up a range of possible applications in the area of stimuli-responsive materials. PMID:27397856

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

    International Nuclear Information System (INIS)

    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−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.

  20. 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 (4000-400cm(-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. PMID:27006210

  1. 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.

  2. Corrosion inhibitors

    International Nuclear Information System (INIS)

    In this paper, we briefly describe the characteristics, cost and electrochemical nature of the corrosion phenomena as well as some of the technologies that are currently employed to minimize its effect. The main subject of the paper however, deals with the description, classification and mechanism of protection of the so-called corrosion inhibitors. Examples of the use of these substances in different aggressive environments are also presented as means to show that these compounds, or their combination, can in fact be used as excellent and relatively cheap technologies to control the corrosion of some metals. In the last part of the paper, the most commonly used techniques to evaluate the efficiency and performance of corrosion inhibitors are presented as well as some criteria to make a careful and proper selection of a corrosion inhibitor technology in a given situation. (Author) 151 refs

  3. Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60)

    Czech Academy of Sciences Publication Activity Database

    Vávrová, J.; Zárybnická, L.; Lukášová, Emilie; Řezáčová, M.; Novotná, E.; Šinkorová, Z.; Tichý, Adam; Pejchal, J.; Ďurišová, K.

    2013-01-01

    Roč. 52, č. 4 (2013), s. 471-479. ISSN 0301-634X Institutional support: RVO:68081707 Keywords : DOUBLE-STRAND BREAKS * GAMMA-RADIATION * CANCER-CELLS Subject RIV: BO - Biophysics Impact factor: 1.582, year: 2013

  4. 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.

  5. Cleaning-in-place of immunoaffinity resins monitored by in situ ATR-FTIR spectroscopy.

    Science.gov (United States)

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

    2015-09-01

    In the next 10 years, the pharmaceutical industry anticipates that revenue from biotherapeutics will overtake those generated from small drug molecules. Despite effectively treating a range of chronic and life-threatening diseases, the high cost of biotherapeutics limits their use. For biotherapeutic monoclonal antibodies (mAbs), an important production cost is the affinity resin used for protein capture. Cleaning-in-place (CIP) protocols aim to optimise the lifespan of the resin by slowing binding capacity decay. Binding assays can determine resin capacity from the mobile phase, but do not reveal the underlying causes of Protein A ligand degradation. The focus needs to be on the stationary phase to examine the effect of CIP on the resin. To directly determine both the local Protein A ligand concentration and conformation on two Protein A resins, we developed a method based on attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy. ATR-FTIR spectroscopic imaging revealed that applying a carefully controlled load to agarose beads produces an even and reproducible contact with the internal reflection element. This allowed detection and quantification of the binding capacity of the stationary phase. ATR-FTIR spectroscopy also showed that Protein A proteolysis does not seem to occur under typical CIP conditions (below 1 M NaOH). However, our data revealed that concentrations of NaOH above 0.1 M cause significant changes in Protein A conformation. The addition of >0.4 M trehalose during CIP significantly reduced NaOH-induced ligand unfolding observed for one of the two Protein A resins tested. Such insights could help to optimise CIP protocols in order to extend resin lifetime and reduce mAb production costs. PMID:26159572

  6. Hydraulic Shuttle Irradiation System (HSIS) Recently Installed in the Advanced Test Reactor (ATR)

    International Nuclear Information System (INIS)

    Most test reactors are equipped with shuttle facilities (sometimes called rabbit tubes) whereby small capsules can be inserted into the reactor and retrieved during power operations. With the installation of Hydraulic Shuttle Irradiation System (HSIS) this capability has been restored to the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL). The general design and operating principles of this system were patterned after the hydraulic rabbit at Oak Ridge National Laboratory's (ORNL) High Flux Isotope Reactor (HFIR), which has operated successfully for many years. Using primary coolant as the motive medium the HSIS system is designed to simultaneously transport fourteen shuttle capsules, each 16 mm OD x 57 mm long, to and from the B-7 position of the reactor. The B-7 position is one of the higher flux positions in the reactor with typical thermal and fast (>1 Mev) fluxes of 2.8E+14 n/cm2/sec and 1.9E+14 n/cm2/sec respectively. The available space inside each shuttle is approximately 14 mm diameter x 50 mm long. The shuttle containers are made from titanium which was selected for its low neutron activation properties and durability. Shuttles can be irradiated for time periods ranging from a few minutes to several months. The Send and Receive Station (SRS) for the HSIS is located 2.5 m deep in the ATR canal which allows irradiated shuttles to be easily moved from the SRS to a wet loaded cask, or transport pig. The HSIS system first irradiated (empty) shuttles in September 2009 and has since completed a Readiness Assessment in November 2009. The HSIS is a key component of the ATR National Scientific User Facility (NSUF) operated by Battelle Energy Alliance, LLC and is available to a wide variety of university researchers for nuclear fuels and materials experiments as well as medical isotope research and production.

  7. 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

  8. 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

  9. Structure-Activity Relations In Enzymes: An Application Of IR-ATR Modulation Spectroscopy

    Science.gov (United States)

    Fringeli, Urs P.; Ahlstrom, Peter; Vincenz, Claudius; Fringeli, Marianna

    1985-12-01

    Relations between structure and specific activity in immobilized acetylcholinesterase (ACNE) have been studied by means of pH- and Ca++-modulation technique combined with attenuated total reflection (ATR) infrared (IR) spectroscopy and enzyme activity measurement. Periodic modulation of pH and Ca++-concentration enabled a periodic on-off switching of about 40% of the total enzyme activity. It was found that about 0.5 to 1% of the amino acids were involved in this process. These 15 to 30 amino acids assumed antiparallel pleated sheet structure in the inhibited state and random and/or helical structure in the activated state.

  10. FTIR-ATR monitoring and SEC/RI/MALLS characterization of ATRP synthesized hyperbranched polyacrylates

    OpenAIRE

    Gonçalves, Miguel; Pinto, Virgínia; Dias, Rolando; Costa, Mário Rui

    2010-01-01

    This work reports the synthesis at 1 L scale of hyperbranched polyacrylates based upon acrylate/diacrylate monomers such as n-butyl acrylate (nBA)/1,6-hexanediol diacrylate (HDDA) and using atom transfer radical polymerization (ATRP). A FTIR-ATR immersion probe was used to monitor the polymerization reaction. The dynamics of the build-up of polymer structure was studied by off-line analysis of samples at different reaction times by size exclusion chromatography (SEC) with detection of refract...

  11. Investigation on the adsorption characteristics of sodium benzoate and taurine on gold nanoparticle film by ATR-FTIR spectroscopy

    Science.gov (United States)

    Kumar, Naveen; Thomas, S.; Tokas, R. B.; Kshirsagar, R. J.

    2014-01-01

    Fourier transform infrared (FTIR) spectroscopic studies of sodium benzoate and taurine adsorbed on gold nanoparticle (AuNp) film on silanised glass slides have been studied by attenuated total reflection technique (ATR). The surface morphology of the AuNp films has been measured by Atomic Force Microscopy. The ATR spectra of sodium benzoate and taurine deposited on AuNp film are compared with ATR spectra of their powdered bulk samples. A new red-shifted band appeared along with the symmetric and asymmetric stretches of carboxylate group of sodium benzoate leading to a broadening of the above peaks. Similar behavior is also seen in the case of symmetric and asymmetric stretches of sulphonate group of taurine. The results indicate presence of both chemisorbed and physisorbed layers of both sodium benzoate and taurine on the AuNp film with bottom layer chemically bound to AuNp through carboxylate and sulphonate groups respectively.

  12. Measured thermal and fast neutron fluence rates ATR Cycle 101-B, October 11, 1993--November 27, 1993

    International Nuclear Information System (INIS)

    This report contains the thermal (2200 m/s) and fast (E>lMeV) neutron fluence rate data for ATR Cycle 101-B 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 fluence rate values corresponding to the particular elevations (relative to the 80 ft. core elevation) where the measurements were taken. The data in this report consists of (1) a table of the ATR power history and distribution, (2) a hard copy listing of all thermal and fast neutron fluence rates, (3) plots of both the thermal and fast neutron fluence rates, and (4) a magnetic record (3.5 inch diskette) containing a listing of only the fast neutron fluence rates, their assigned elevations proper header identification of all monitor positions contained herein

  13. 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.)

  14. 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.

  15. 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.

  16. ATR-FTIR microscopy in mapping mode for the study of verdigris and its secondary products

    Science.gov (United States)

    Prati, S.; Bonacini, I.; Sciutto, G.; Genty-Vincent, A.; Cotte, M.; Eveno, M.; Menu, M.; Mazzeo, R.

    2016-01-01

    To study degradation processes occurring on painting materials, the use of high-resolution micro-analytical techniques is highly requested since it provides a detailed identification and localisation of both the original and deteriorated ingredients. Among the various pigments recently studied, the characterisation of verdigris has received a major interest. This pigment has not a unique chemical formula, but its composition depends on the recipe employed for its manufacturing. Moreover, verdigris paints are not stable and are subject to a colour change from blue-green to green, which occurs in the first few months after the application. In this paper, we focused our attention on the use of ATR-FTIR mapping as a useful method to identify verdigris secondary products and pathways. Several mock-ups and real samples have been analysed, and the correlation among the detected compounds and their spatial location, obtained by the application of ATR-FTIR microscopy in mapping mode, allowed formulating some hypotheses on the degradation pattern of verdigris, which may feed the discussion on the transformation and stability of this pigment. From an analytical point of view, we showed how FTIR mapping approaches may be extremely useful both for the identification of compounds in complex matrix in which single spectra may limit the exhaustive characterisations due to bands overlapping and for the study of degradation pathways by taking into consideration the relative distribution of degradation products.

  17. 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. PMID:23871060

  18. DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage

    Institute of Scientific and Technical Information of China (English)

    Laura Zannini; Giacomo Buscemi; Ja-Eun Kim; Enrico Fontanella; Domenico Delia

    2012-01-01

    Human DBC1 (deleted in breast cancer-1; KIAA1967) is a nuclear protein that,in response to DNA damage,competitively inhibits the NAD+-dependent deacetylase SIRT1,a regulator of p53 apoptotic functions in response to genotoxic stress.DBC1 depletion in human cells increases SIRT1 activity,resulting in the deacetylation of p53 and protection from apoptosis.However,the mechanisms regulating this process have not yet been determined.Here,we report that,in human cell lines,DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related)kinases.Phosphorylated DBC1 bound to and inhibited SIRT1,resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death.Indeed,DBC1-mediated genotoxicity,which was shown in knockdown experiments to be dependent on SIRT1 and p53 expression,was defective in cells expressing the phospho-mutant DBC1T454A.This study describes the first post-translational modification of DBC1 and provides new mechanistic insight linking ATM/ATR to the DBC1-SIRT1-p53 apoptotic axis triggered by DNA damage.

  19. Characterization of Printing Inks Using DART-Q-TOF-MS and Attenuated Total Reflectance (ATR) FTIR.

    Science.gov (United States)

    Williamson, Rhett; Raeva, Anna; Almirall, Jose R

    2016-05-01

    The rise in improved and widely accessible printing technology has resulted in an interest to develop rapid and minimally destructive chemical analytical techniques that can characterize printing inks for forensic document analysis. Chemical characterization of printing inks allows for both discrimination of inks originating from different sources and the association of inks originating from the same source. Direct analysis in real-time mass spectrometry (DART-MS) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were used in tandem to analyze four different classes of printing inks: inkjets, toners, offset, and intaglio. A total of 319 samples or ~ 80 samples from each class were analyzed directly on a paper substrate using the two methods. DART-MS was found to characterize the semi-volatile polymeric vehicle components, while ATR-FTIR provided chemical information associated with the bulk components of these inks. Complimentary data results in improved discrimination when both techniques are used in succession resulting in >96% discrimination for all toners, 95% for all inkjets, >92% for all offset, and >54% for all intaglio inks. PMID:27122410

  20. 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.

  1. Diesel fuel processor for PEM fuel cells: Two possible alternatives (ATR versus SR)

    Science.gov (United States)

    Cutillo, A.; Specchia, S.; Antonini, M.; Saracco, G.; Specchia, V.

    There are large efforts in exploring the on-board reforming technologies, which would avoid the actual lack of hydrogen infrastructure and related safety issues. From this view point, the present work deals with the comparison between two different 10 kW e fuel processors (FP) systems for the production of hydrogen-rich fuel gas starting from diesel oil, based respectively on autothermal (ATR) and steam-reforming (SR) process and related CO clean-up technologies; the obtained hydrogen rich gas is fed to the PEMFC stack of an auxiliary power unit (APU). Based on a series of simulations with Matlab/Simulink, the two systems were compared in terms of FP and APU efficiency, hydrogen concentration fed to the FC, water balance and process scheme complexity. Notwithstanding a slightly higher process scheme complexity and a slightly more difficult water recovery, the FP based on the SR scheme, as compared to the ATR one, shows higher efficiency and larger hydrogen concentration for the stream fed to the PEMFC anode, which represent key issues for auxiliary power generation based on FCs as compared, e.g. to alternators.

  2. Gastritis crónica atrófica: mecanismos patogénicos por hipersensibilidad celular

    OpenAIRE

    Rosemary Recavarren Asencios; Sixto Recavarren Arce

    2002-01-01

    La Gastritis Crónica Atrófica, de alta incidencia en la infección por Helicobacter pylori, no ha tenido hasta hoy mecanismos patogénicos establecidos. La Gastritis por Helicobacter pylori, claramente relacionada a la Gastritis Crónica Activa Superficial, no ha encontrado mecanismos que la conecten con la Gastritis Crónica Atrófica. Hasta hace poco, eran consideradas por algunos autores como lesiones independientes. En el presente trabajo, se estudiaron 42 biopsias gástricas antrales o corpora...

  3. NON-DESTRUCTIVE TESTS OF LOCK TONGUES USED IN ATR-72 AIRCRAFT LANDING GEAR BASED ON MAGNETIC METHOD

    Directory of Open Access Journals (Sweden)

    Mirosław Malec

    2013-12-01

    Full Text Available The purpose of this work is to highlight the opportunities of using and analyzing process progression of Non-destructive Testing in aeronautical industries and technologies. This paper concentrates on magnetic-fluorescent method, which is used to showcase the practical test of lock tongue installed in ATR-72 aircraft landing gear.

  4. NON-DESTRUCTIVE TESTS OF LOCK TONGUES USED IN ATR-72 AIRCRAFT LANDING GEAR BASED ON MAGNETIC METHOD

    OpenAIRE

    Mirosław Malec; Tomasz Cieplak; Sławomir Walczuk

    2013-01-01

    The purpose of this work is to highlight the opportunities of using and analyzing process progression of Non-destructive Testing in aeronautical industries and technologies. This paper concentrates on magnetic-fluorescent method, which is used to showcase the practical test of lock tongue installed in ATR-72 aircraft landing gear.

  5. Quantitative in-situ ATR-FTIR studies on the selective interaction of polyelectrolyte multilayers with protein mixtures

    Czech Academy of Sciences Publication Activity Database

    Müller, M.; Bohatá, Karolína; Ouyang, W.; Kessler, B.; Pientka, Zbyněk; Brynda, Eduard

    Graz : Austrian Centre for Electron MIcroscopy and Nanoanalysis, 2007. S.26. [European Symposium on Polymer Spectroscopy /17./. 09.9.2007-12.09.2007, Seggauberg Leibnitz] Institutional research plan: CEZ:AV0Z40500505 Keywords : polyelectrolyte multilayers * ATR-FTIR studies Subject RIV: CD - Macromolecular Chemistry

  6. Adsorption of poly(ethylene oxide)-block-polylactide copolymers on polylactide as studied by ATR-FTIR spectroscopy

    Czech Academy of Sciences Publication Activity Database

    Popelka, Štěpán; Machová, Luďka; Rypáček, František

    2007-01-01

    Roč. 308, č. 2 (2007), s. 291-299. ISSN 0021-9797 R&D Projects: GA AV ČR IAA4050202 Institutional research pla n: CEZ:AV0Z40500505 Keywords : ATR-FTIR spectroscopy * copolymer adsorption * poly(ethylene oxide) Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.309, year: 2007

  7. 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.

  8. Application of ATR-FTIR spectroscopy in quantitative analysis of deuterium in basic solutions

    International Nuclear Information System (INIS)

    A method to measure the deuterium concentration in basic solutions, using Attenuated Total Reflection Fourier Transformed Infrared Spectroscopy (ATR-FTIR) is described. Deuterium quantification is based on the O-D bond stretching peak. A calibration curve is drawn, representing the peak intensity versus the deuterium percentage in a neutral solution. No calibration curve can be obtained with basic solutions, because of the strong absorbance due to hydroxide ions. Thus, an acidification is necessary prior to the analysis of a basic solution. The deuterium content of this acid solution is then measured. As we know the dilution caused by the acid addition, we can calculate the deuterium content of the initial basic solution. The relative uncertainty of this method is + or - 2%. (authors)

  9. Unidirectional Excitation of Graphene Plasmon in Attenuated Total Reflection (ATR) Configuration

    Science.gov (United States)

    Dai, Wei; Wu, Yue-Chao; Liu, Fang-Li

    2016-04-01

    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.

  10. Study of consumer fireworks post-blast residues by ATR-FTIR.

    Science.gov (United States)

    Martín-Alberca, Carlos; Zapata, Félix; Carrascosa, Héctor; Ortega-Ojeda, Fernando E; García-Ruiz, Carmen

    2016-03-01

    Specific analytical procedures are requested for the forensic analysis of pre- and post-blast consumer firework samples, which present significant challenges. Up to date, vibrational spectroscopic techniques such as Fourier transform infrared spectroscopy (FTIR) have not been tested for the analysis of post-blast residues in spite of their interesting strengths for the forensic field. Therefore, this work proposes a simple and fast procedure for the sampling and analysis of consumer firework post-blast residues by a portable FTIR instrument with an Attenuated Total Reflection (ATR) accessory. In addition, the post-blast residues spectra of several consumer fireworks were studied in order to achieve the identification of their original chemical compositions. Hence, this work analysed 22 standard reagents usually employed to make consumer fireworks, or because they are related to their combustion products. Then, 5 different consumer fireworks were exploded, and their residues were sampled with dry cotton swabs and directly analysed by ATR-FTIR. In addition, their pre-blast fuses and charges were also analysed in order to stablish a proper comparison. As a result, the identification of the original chemical compositions of the post-blast samples was obtained. Some of the compounds found were potassium chlorate, barium nitrate, potassium nitrate, potassium perchlorate or charcoal. An additional study involving chemometric tools found that the results might greatly depend on the swab head type used for the sampling, and its sampling efficiency. The proposed procedure could be used as a complementary technique for the analysis of consumer fireworks post-blast residues. PMID:26717839

  11. 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

  12. Rapid determination of free fatty acids in poultry feed lipid extracts by SB-ATR FTIR spectroscopy.

    Science.gov (United States)

    Sherazi, S T H; Mahesar, S A; Bhanger, M I; van de Voort, F R; Sedman, J

    2007-06-27

    A simple, rapid, and reproducible method has been developed for the quantitative determination of free fatty acid (FFA) content in lipids extracted from poultry feeds by Fourier transform infrared (FTIR) spectroscopy with the use of a single-bounce attenuated total reflectance (SB-ATR) accessory. An FTIR calibration curve was prepared by gravimetrically adding oleic acid (15-37%) to pure refined, bleached, and deodorized (RBD) canola oil and measuring the area of the COOH absorption band at 1710 cm-1. The oil from each of 12 poultry feed formulations was extracted using conventional Soxhlet extraction, and after evaporation of the solvent, the FFA content was determined by the conventional AOCS titrimetric procedure and by the SB-ATR/FTIR method. The SB-ATR/FTIR FFA predictions were related to those determined by the AOCS titrimetric method by linear regression, producing an R value of 0.999 and a SD of +/-0.28% FFA. Time-course spectra collected as lipids extracted into hexane indicated that a 15 min extraction was adequate to obtain a representative sample for FFA determination, with further extraction resulting in little, if any, change in the proportion of FFA in the lipid extract. Only a small volume of the hexane extract ( approximately 20 mL) yielded sufficient material for the SB-ATR/FTIR analysis. Thus, by shortening the extraction time and taking a small sample so as to reduce solvent removal time, the SB-ATR/FTIR procedure provides a very simple and rapid means of determining the FFA content of poultry feed lipids. PMID:17530766

  13. A testbed for architecture and fidelity trade studies in the Bayesian decision-level fusion of ATR products

    Science.gov (United States)

    Erickson, Kyle J.; Ross, Timothy D.

    2007-04-01

    Decision-level fusion is an appealing extension to automatic/assisted target recognition (ATR) as it is a low-bandwidth technique bolstered by a strong theoretical foundation that requires no modification of the source algorithms. Despite the relative simplicity of decision-level fusion, there are many options for fusion application and fusion algorithm specifications. This paper describes a tool that allows trade studies and optimizations across these many options, by feeding an actual fusion algorithm via models of the system environment. Models and fusion algorithms can be specified and then exercised many times, with accumulated results used to compute performance metrics such as probability of correct identification. Performance differences between the best of the contributing sources and the fused result constitute examples of "gain." The tool, constructed as part of the Fusion for Identifying Targets Experiment (FITE) within the Air Force Research Laboratory (AFRL) Sensors Directorate ATR Thrust, finds its main use in examining the relationships among conditions affecting the target, prior information, fusion algorithm complexity, and fusion gain. ATR as an unsolved problem provides the main challenges to fusion in its high cost and relative scarcity of training data, its variability in application, the inability to produce truly random samples, and its sensitivity to context. This paper summarizes the mathematics underlying decision-level fusion in the ATR domain and describes a MATLAB-based architecture for exploring the trade space thus defined. Specific dimensions within this trade space are delineated, providing the raw material necessary to define experiments suitable for multi-look and multi-sensor ATR systems.

  14. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    Science.gov (United States)

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated drugs, such as camptothecin, imazalil, itraconazole, hygromycin, and 4-nitroquinoline oxide. We also verified the relative transcript levels of the Atr genes in the A. nidulans imazalil-resistant mutants. These genes displayed a very complex pattern in different ima genetic backgrounds. The imaB mutant has higher basal transcript levels of AtrB and -D than those of the wild-type strain. The levels of these two genes are comparable when the imaB mutant is grown in the presence and absence of imazalil. The imaC, -D, and -H mutants have higher basal levels of AtrA than that of the wild type. The same behavior is observed for the relative transcript levels of AtrB in the imaG mutant background. PMID:11872487

  15. 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. PMID:26168232

  16. 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

  17. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    OpenAIRE

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated dr...

  18. 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

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

    International Nuclear Information System (INIS)

    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, hence promoting FCCI

  20. 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

  1. Two-dimensional ATR-FTIR Spectroscopic Study on the Water Diffusion Behavior in Polyimide/Silica Nanocomposite

    Science.gov (United States)

    Shen, Yi; Wang, Hai-tao; Zhong, Wei; Wu, Pei-yi

    2006-12-01

    To consider the reliability and performance of electronic devices based on polyimide derivatives, dynamic water sorption and diffusion behavior in a polyimide derivative: poly(4'4-oxydiphenylene pyromellitimide) (PMDA-ODA)/silica nanocomposite was investigated by two-dimensional ATR-FTIR spectroscopy, by which three states of water molecules owning different H-bonding strength were distinguished. The amounts and strength of H-bonding also played a significant role in determining the diffusion rate of the different states of water molecules. The type of aggregated water molecules which also formed H-bonding with silicic acid (residues) or polyimide system was the last one diffusing to the polymer side in contact with the ATR crystal element because the polymeric matrix blocked their diffusion to a great extent. The diffusion coefficient was also estimated to gain the information of the dynamic diffusion behavior.

  2. The air membrane-ATR integrated gas turbine power cycle: A method for producing electricity with low CO2 emissions

    International Nuclear Information System (INIS)

    The air membrane-auto thermal reforming (AM-ATR) gas turbine cycle combines features of the R-ATR power cycle, introduced at the University of Florence, with ceramic, air separation membranes to achieve a novel combined cycle process with fuel decarbonisation and near-zero CO2 emissions. Within this process, the natural gas fuel is converted to H2 and CO through the auto thermal reforming process (ATR), i.e. combined partial oxidation and steam methane reforming, within the air separation membrane reactor. In a subsequent process unit, the H2 content of the reformed fuel is enriched by the well known CO-CO2 shift reaction. This fuel is then sent to an amine based carbon dioxide removal unit and, finally, to two combustors: the first one is located upstream of the membrane reformer (in order to achieve the required working temperature) and the second one is downstream of the membrane to reach the desired turbine inlet temperature (TIT). The main advantage of the proposed concept over other decarbonisation processes is the coupling of the membrane and the ATR reactor. This coupling greatly reduces the mass flow of syngas with respect to the air blown ATR contained in the previously proposed R-ATR, thus lowering the size of the syngas treatment section. Furthermore, as the oxygen production is integrated at high temperatures in the power cycle, the efficiency penalty of producing oxygen is much smaller than for the traditional cryogenic oxygen separation. The main advantages over other integrated GT-membrane concepts are the lower membrane operating temperature, lower levels of required air separation at high partial pressure driving forces (leading to lower membrane surface areas) and the possibility to achieve a higher TIT with top firing without increasing CO2 emissions. When compared to power plants with tail end CO2 separation, the CO2 removal process treats a gas at pressure and with a significantly higher CO2 concentration than that of gas turbine exhausts

  3. Electrooxidation of ethanol on Pt and PtRu surfaces investigated by ATR surface-enhanced infrared absorption spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcio F.; Camara, Giuseppe A., E-mail: giuseppe.silva@ufms.br [Departamento de Quimica, Universidade Federal do Mato Grosso do Sul, Campo Grande-MS (Brazil); Batista, Bruno C.; Boscheto, Emerson [Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Sao Carlos-SP, (Brazil); Varela, Hamilton, E-mail: varela@iqsc.usp.br [Ertl Center for Electrochemistry and Catalysis, Gwangju Institute of Science and Technology (GIST), Gwangju (Korea, Republic of)

    2012-05-15

    Herein, it was investigated for the first time the electro-oxidation of ethanol on Pt and PtRu electrodeposits in acidic media by using in situ surface enhanced infrared absorption spectroscopy with attenuated total reflection (ATR-SEIRAS). The experimental setup circumvents the weak absorbance signals related to adsorbed species, usually observed for rough, electrodeposited surfaces, and allows a full description of the CO coverage with the potential for both catalysts. The dynamics of adsorption-oxidation of CO was accessed by ATR-SEIRAS experiments (involving four ethanol concentrations) and correlated with expressions derived from a simple kinetic model. Kinetic analysis suggests that the growing of the CO adsorbed layer is nor influenced by the presence of Ru neither by the concentration of ethanol. The results suggest that the C-C scission is not related to the presence of Ru and probably happens at Pt sites. (author)

  4. ATR-FT-IR spectroscopy in the region of 500-230 cm -1 for identification of inorganic red pigments

    Science.gov (United States)

    Vahur, Signe; Knuutinen, Ulla; Leito, Ivo

    2009-08-01

    It is demonstrated that micro-ATR-FT-IR in the low wave number range (500-230 cm -1) can be well used for identification of pigments in paint samples thereby markedly extending the possibilities of pigment identification by ATR-IR spectroscopy into the realm of pigments having no absorptions in the mid-IR region. Reference spectra of pigments can be conveniently obtained by mixing them with linseed oil in approximately 1:1 mass ratio. Vermilion (or cinnabar), read lead, different red iron oxide pigments and cadmium red can be identified. 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).

  5. RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling

    OpenAIRE

    Lindsey-Boltz, Laura A.; Kemp, Michael G.; Capp, Christopher; Sancar, Aziz

    2015-01-01

    The ATR-Chk1 signaling pathway mediates cellular responses to DNA damage and replication stress and is composed of a number of core factors that are conserved throughout eukaryotic organisms. However, humans and other higher eukaryotic species possess additional factors that are implicated in the regulation of this signaling network but that have not been extensively studied. Here we show that RHINO (for Rad9, Rad1, Hus1 interacting nuclear orphan) forms complexes with both the 9-1-1 checkpoi...

  6. Determination of drug content in semisolid formulations by non-invasive spectroscopic methods: FTIR - ATR, - PAS, - Raman and PDS

    Energy Technology Data Exchange (ETDEWEB)

    Gotter, B; Hein, J; Neubert, R H H [Institute of Pharmacy, Martin-Luther-University, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale (Germany); Faubel, W; Heissler, St, E-mail: bernhard.gotter@pharmazie.uni-halle.d [Institute of Functional Interfaces, Karlsruhe Institute of Technology, Herrmann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

    2010-03-01

    This study elucidates the potential use of photothermal deflection spectroscopy (PDS), FTIR photoacoustic (FTIR-PAS), FT Raman, and FTIR-attenuated total reflection (FTIR-ATR) spectroscopy as analytical tools for investigating the drug content in semisolid formulations. Regarding the analytical parameters, this study demonstrates the photothermal beam deflection to be definitely comparable to well established spectroscopic methods for this purpose. The correlation coefficients range from 0.990 to 0.999. Likewise, repeatability and limit of detection are comparable.

  7. 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.

  8. 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.)

  9. Advanced Test Reactor National Scientific User Facility (ATR NSUF) Monthly Report October 2014

    Energy Technology Data Exchange (ETDEWEB)

    Dan Ogden

    2014-10-01

    Advanced Test Reactor National Scientific User Facility (ATR NSUF) Monthly Report October 2014 Highlights • Rory Kennedy, Dan Ogden and Brenden Heidrich traveled to Germantown October 6-7, for a review of the Infrastructure Management mission with Shane Johnson, Mike Worley, Bradley Williams and Alison Hahn from NE-4 and Mary McCune from NE-3. Heidrich briefed the group on the project progress from July to October 2014 as well as the planned path forward for FY15. • Jim Cole gave two invited university seminars at Ohio State University and University of Florida, providing an overview of NSUF including available capabilities and the process for accessing facilities through the peer reviewed proposal process. • Jim Cole and Rory Kennedy co-chaired the NuMat meeting with Todd Allen. The meeting, sponsored by Elsevier publishing, was held in Clearwater, Florida, and is considered one of the premier nuclear fuels and materials conferences. Over 340 delegates attended with 160 oral and over 200 posters presented over 4 days. • Thirty-one pre-applications were submitted for NSUF access through the NE-4 Combined Innovative Nuclear Research Funding Opportunity Announcement. • Fourteen proposals were received for the NSUF Rapid Turnaround Experiment Summer 2014 call. Proposal evaluations are underway. • John Jackson and Rory Kennedy attended the Nuclear Fuels Industry Research meeting. Jackson presented an overview of ongoing NSUF industry research.

  10. The degradation potential of PET bottles in the marine environment: An ATR-FTIR based approach

    Science.gov (United States)

    Ioakeimidis, C.; Fotopoulou, K. N.; Karapanagioti, H. K.; Geraga, M.; Zeri, C.; Papathanassiou, E.; Galgani, F.; Papatheodorou, G.

    2016-03-01

    The dominance and persistence of plastic debris in the marine environment are well documented. No information exists in respect to their lifespan in the marine environment. Nevertheless, the degradation potential of plastic litter items remains a critical issue for marine litter research. In the present study, polyethylene terephthalate bottles (PETs) collected from the submarine environment were characterized using ATR-FTIR in respect to their degradation potential attributed to environmental conditions. A temporal indication was used as indicative to the years of presence of the PETs in the environment as debris. PETs seem to remain robust for approximately fifteen years. Afterwards, a significant decrease of the native functional groups was recorded; some even disappear; or new-not typical for PETs-are created. At a later stage, using the PET time series collected from the Saronikos Gulf (Aegean Sea–E. Mediterranean), it was possible to date bottles that were collected from the bottom of the Ionian Sea (W. Greece). It is the first time that such a study has been conducted with samples that were actually degraded in the marine environment.

  11. Radiation damage studies of membrane model systems by means of ATR-IR spectroscopy

    International Nuclear Information System (INIS)

    An investigation was made of the destruction of thin oriental layer systems by means of IR spectroscopy in an ATR (Attenuated Total Reflection) mode. 8 tripalmitin layers were deposited with transfer ratios between 0.95-1, 1 on always 2 Ge internal reflection plates, previously coated with a Cd-arachidate monolayer. Both Ge-plates were then mounted on a holder fitting like a photographic plate into a special device normally used for step-wedge exposures in the e.m. image plane. Through a fitting mask one of the plates was exposed on each side to 100 keV electrons. The IR spectrum of reference plate (not irradiated) showed no defects at all. In comparison a plate irradiated with effectively 5 x 10-4 Cb/cm2 at a measured current density of 1,24.10-8 A/cm2 shows serious defects in the tripalmitin layers, although this dose is far below what is considered necessary for a single heavy atom detection. (author)

  12. Development of ATR type steam separator performance analysis code and its validation, (1)

    International Nuclear Information System (INIS)

    The purpose of the study is to develop a method for predicting steam carryunder which is one of the important characteristics of a steam separator. Bubbles returning to the liquid surface and trapped by the re-circulating flow are calculated by tracking the behavior of bubbles moving in liquid bulk where velocity and temperature distributions have been calculated before-hand in conjunction with the Monte-Carlo method. Regarding the statistics of bubbles, a survey of references and visual tests have been conducted. To validate this method, several tests to measure bubble behavior under air/water conditions at atmospheric pressure and high temperature and pressure ranging 3 ∼ 7 MPa have been conducted with a full-scale steam separator. As a result, the developed method predicted with good precision the carryunder ratio obtained by the full-scale tests under the condition that carried-under void fraction was less than 20 %, but underestimated carryunder ratio in the ATR 'Fugen' reactor in which steam drum water level was shallow and average void fraction in water bulk was high. This method has a characteristic that carryunder ratio is underestimated in the case that void fraction is more than 20 %. (author)

  13. 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.

  14. ATR-SEIRAS study of CO adsorption and oxidation on Rh modified Au(111-25 nm) film electrodes in 0.1 M H2SO4

    OpenAIRE

    Xu, Qinqin; Berná Galiano, Antonio; Pobelov, Ilya V.; Rodes García, Antonio; Feliu, Juan M.; Wandlowski, Thomas; Kuzume, Akiyoshi

    2015-01-01

    Rh modified Au(111-25 nm) electrodes, prepared by electron beam evaporation and galvanostatic deposition, were employed to study adsorption and electro-oxidation of CO on Rh in 0.1 M sulfuric acid solution by in situ attenuated total reflection surface enhanced infrared absorption spectroscopy (ATR-SEIRAS). The results of ATR-SEIRAS experiments were compared with those obtained by infrared reflection absorption spectroscopy on three low-index Rh single crystal surfaces. The Rh film deposited ...

  15. Image-based ATR utilizing adaptive clutter filter detection, LLRT classification, and Volterra fusion with application to side-looking sonar

    Science.gov (United States)

    Aridgides, Tom; Fernández, Manuel

    2010-04-01

    An improved automatic target recognition (ATR) processing string has been developed. The overall processing string consists of pre-processing, subimage adaptive clutter filtering, detection, feature extraction, optimal subset feature selection, feature orthogonalization and classification processing blocks. The objects that are classified by three 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. These three ATR processing strings were individually developed and tuned by researchers from different companies. The utility of the overall processing strings and their fusion was demonstrated with an extensive side-looking sonar dataset. In this paper we describe a new processing improvement: six additional classification features are extracted, using primarily target shadow information and a feature extraction window whose length is now made variable as a function of range. This new ATR processing improvement resulted in a 3:1 reduction in false alarms. Two advanced fusion algorithms are subsequently applied: First, a nonlinear Volterra expansion (2nd order) feature-LLRT fusion algorithm is employed. Second, a repeated application of a subset Volterra feature selection / feature orthogonalization / LLRT fusion block is utilized. It is shown that cascaded Volterra feature- LLRT fusion of the ATR processing strings outperforms baseline "summing" and single-stage Volterra feature-LLRT fusion 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.

  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. Proton pump inhibitors

    Science.gov (United States)

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

  18. 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.

  19. ATR-FTIR characterization of transport properties of benzoic acid ion-pairs in silicone membranes.

    Science.gov (United States)

    Tantishaiyakul, Vimon; Phadoongsombut, Narubodee; Wongpuwarak, Wibul; Thungtiwachgul, Jatupit; Faroongsarng, Damrongsak; Wiwattanawongsa, Kamonthip; Rojanasakul, Yon

    2004-09-28

    A novel technique based on Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy was used to study the transport of benzoic acid ion-pairs/salts in silicone membranes. The benzoic acid ion-pairs were prepared using various counter-ions with different degrees of lipophilicity, e.g. triethylamine (TA), diethylamine (DE), tert-butylamine (t-BA), 2-amino-2-methyl-propanol (AMP), and 2-amino-2-methyl-propanediol (AMPD). Silicone membrane, treated or untreated with propylene glycol (PG), was placed on the surface of a ZnSe crystal and the transport solution was applied to the upper surface of the membrane. A mathematical model, based on Fick's second law describing the build up of permeant concentration at the membrane/crystal interface with time was applied to determine diffusion coefficients. Absorption due to the acid (1700 cm(-1)) or benzoate anion (1555 cm(-1)) was observed at different regions without the interference from PG or silicone membrane. Benzoate anion, a charged species, was observed to permeate the membrane. The permeation of benzoate anion from sodium benzoate and polar ion-pairs of AMP and AMPD was very low in contrast to their high-saturated concentrations in PG as compared to the t-BA ion-pair. This indicated that benzoate anion preferentially permeates the membrane as an ion-pair rather than a single anion; otherwise its permeation should correspond to its concentration in PG instead of the lipophilicity of the ion-pairs. Additionally, the diffusion coefficient values of benzoic acid and benzoate anions through the treated and untreated membranes were not statistically different. PMID:15363507

  20. ATR-FTIR investigations of secondary structure of lyophilized proteins in water and deuterated water

    International Nuclear Information System (INIS)

    The conformational and structural changes due to lyophilization of bovine hemoglobin, casein and trypsin of neutral pH value have been studied by FT-IR spectrometry using an Attenuated Total Reflectance (ATR) accessory (Bruker EQUINOX 55 spectrometer). Lyophilization induced significant structural alterations in proteins, characterized by a decrease in the α-helix and a significant increase in the β-sheet content. The proteins were lyophilized from twice-distilled water solution and deuterated water solution. The secondary structure was quantitatively determined using the second derivative of the protein spectra and curve fitting procedures to resolve the overlapping components under the amide I contour. The band of amide I, is due to the in-plane C=O stretching vibration, weakly coupled with C-N stretching and in-plane N-H bending. Each type of secondary structure (i.e. α-helix, β-sheet, β-turn and disordered) gives rise to different C-O stretching frequencies, hence, results in characteristic band positions which are designated by wavenumber (cm-1). In the Fourier domain derivative, the second-derivative analysis of infrared spectra allows direct quantitative analysis of the secondary structural components of proteins. Thus, the areas corresponding to the different types of secondary structure are quantitatively and qualitatively evaluated by integration and curve fitting. The second derivatives of all spectra were calculated using the spectrometer software OPUS. Before starting the fitting procedure, the obtained depths of the minima in the second derivative spectrum and, subsequently, the calculated maximum intensities were corrected for the interference of all neighboring peaks. The curve fitting is performed by stepwise iterative adjustment towards a minimum root-mean-square error of the different parameters determining the shape and position of the absorption peaks. (author)

  1. Coolant void reactivity behaviour in pressure tube type plutonium fuel lattices of ATR

    International Nuclear Information System (INIS)

    It is essential to the reactor physical field in respect of the thermal neutron reactor specially utilizing plutonium to consistently clarify the effect of the resonance in the around 0.3eV for plutonium239 and the effect of the various fuel compositions and fuel material concentrations on the void reactivity in the ATR lattice. For this purpose, using the improved WIMS code to be able to calculate the detailed thermal neutron spectrum containing the resonance in 0.3eV for plutonium239 and various components due to the reactivity relevant to the void reactivity, the void reactivity in the HWR lattice has been analyzed in detail. For the purpose of improving the accuracy of the calculated void reactivity, the nuclear data for the WIMS code has been replaced with the JENDL-3.1 library. As the results of the analysis, for the identical macro thermal neutron absorption cross section for fuel, the void reactivity is reduced to the negative side more for the MOX with high content of plutonium239 in plutonium than in uranium. The reduction of the void reactivity to the negative side by plutonium239 is due to the presence of the resonance in 0.3eV for plutonium239. That is because the higher the content of plutonium239 is, the less the recovery effect for neutron density within the resonance energy in 0.3eV is with increase in coolant void fraction, so that the decreased resonance nuclear fission rate for plutonium239 contributes to the negative side for the void reactivity. This effect is more remarkable for the larger pitch lattice with softer thermal neutron spectrum. (author)

  2. UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner.

    Directory of Open Access Journals (Sweden)

    Zhengke Li

    Full Text Available Xeroderma pigmentosum Group A (XPA is a crucial factor in mammalian nucleotide excision repair (NER and nuclear import of XPA from the cytoplasm for NER is regulated in cellular DNA damage responses in S-phase. In this study, experiments were carried out to determine the transport mechanisms that are responsible for the UV (ultraviolet-induced nuclear import of XPA. We found that, in addition to the nuclear localization signal (NLS of XPA, importin-α4 or/and importin-α7 are required for the XPA nuclear import. Further investigation indicated that, importin-α4 and importin-α7 directly interacted with XPA in cells. Interestingly, the binding of importin-α4 to XPA was dependent on UV-irradiation, while the binding of importin-α7 was not, suggesting a role for importin-α7 in nuclear translocation of XPA in the absence of DNA damage, perhaps with specificity to certain non-S-phases of the cell-cycle. Consistent with the previous report of a dependence of UV-induced XPA nuclear import on ataxia telangiectasia and Rad3-related protein (ATR in S-phase, knockdown of ATR reduced the amount of XPA interacting with importin-α4. In contrast, the GTPase XPA binding protein 1 (XAB1, previously proposed to be required for XPA nuclear import, showed no effect on the nuclear import of XPA in our siRNA knockdown analysis. In conclusion, our results suggest that upon DNA damage transport adaptor importin-α4 imports XPA into the nucleus in an ATR-dependent manner, while XAB1 has no role in this process. In addition, these findings reveal a potential new therapeutic target for the sensitization of cancer cells to chemotherapy.

  3. In situ-ATR-FTIR analysis on the uptake and release of streptomycin from polyelectrolyte complex layers

    Science.gov (United States)

    Torger, B.; Müller, M.

    2013-03-01

    In-situ ATR-FTIR spectroscopy and line shape analysis of the diagnostic spectral region was used to quantify the bound amount and release of the antibiotic streptomycin (STRP) at polyelectrolyte (PEL) multilayers (PEM) of poly(ethyleneimine) (PEI) and poly(acrylic acid) (PAA) or PEI and sodium alginate (ALG). Unlike common concepts based on the drug enrichment of the release medium, this analytical concept allowed to measure quantitatively the drug depletion in the delivery matrix. The measured kinetic in situ ATR-FTIR data were analysed by a modified Korsmeyer-Peppas equation based on two characteristic release parameters k and n. As main experimental parameters the number of PEL layers (adsorption steps) z and the STRP/PEL ratio were varied. For z = 8 the STRP/PEL ratio showed the most significant influence on release kinetics, whereby for STRP/PEL = 1:25 slowest (n = 0.77) and lowest (k = 21.4%) and for STRP/PEL = 1:5 most rapid (n = 0.30) and highest (k = 58.6%) drug releases were found. PEM-PEI/ALG-8 (STRP/PEL = 1:5) revealed slower release rates (n = 0.58) and lower released STRP amounts (k = 17.1%) compared to PEI/PAA. UV-VIS data on time dependent STRP enrichment of the release medium showed a similar trend compared to respective ATR-FTIR data on STRP depletion in PEM. Released amounts of around 1-2 mg from the herein introduced PEM films could be determined. The introduced analytical concept will be used as screening tool for other drugs, drug eluting films and bone substituting materials.

  4. Gastritis crónica atrófica: mecanismos patogénicos por hipersensibilidad celular

    Directory of Open Access Journals (Sweden)

    Rosemary Recavarren Asencios

    2002-07-01

    Full Text Available La Gastritis Crónica Atrófica, de alta incidencia en la infección por Helicobacter pylori, no ha tenido hasta hoy mecanismos patogénicos establecidos. La Gastritis por Helicobacter pylori, claramente relacionada a la Gastritis Crónica Activa Superficial, no ha encontrado mecanismos que la conecten con la Gastritis Crónica Atrófica. Hasta hace poco, eran consideradas por algunos autores como lesiones independientes. En el presente trabajo, se estudiaron 42 biopsias gástricas antrales o corporales, con Gastritis Crónica Atrófica en diferentes estadíos. Las lesiones histológicas que comprenden a esta última, van desde la "infiltración linfoide profunda" en las glándulas gástricas propias, hasta el reemplazo de las mismas por tejido fibroinflamatorio. Por métodos inmunohistoquímicos, hemos podido comprobar que las células linfoides que infiltran el estrato glandular propio del estómago están conformadas por linfocitos T CD8+ (citotóxicos y por células linfocíticas B secretoras de anticuerpos. Planteamos en el presente trabajo que, los linfocitos T citotóxicos agredirían a las glándulas propias antrales y corporales destruyéndolas y produciendo de esta forma su reemplazo por tejido fibroinflamatorio. Similares acciones se producirían por linfocitos B, pero a través de la secreción de anticuerpos locales contra células epiteliales glandulares gástricas.

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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 studies. In addition, our study led to the characterization of a

  6. 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

  7. 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.

  8. SB-ATR FTIR Spectroscopic Monitoring of Free Fatty Acids in Commercially Available Nigella sativa (Kalonji) Oil

    OpenAIRE

    2014-01-01

    Free fatty acids (FFA) in Nigella sativa (N. sativa) commercial and seed oil were determined using single-bounce attenuated total reflectance (SB-ATR) Fourier transform infrared (FTIR) spectroscopy. Gravimetrical mixing was done by adding 0.1–40% oleic acids in neutralized N. sativa oil containing 0.1% FFA. FTIR spectroscopy technique and partial least square (PLS) calibration were used to detect the absorption region of carbonyl (C=O) which is in the range of 1690–1727 cm−1. The results of P...

  9. Implantes angulados en la rehabilitación parcial de sectores posteriores en maxilares atróficos

    OpenAIRE

    Casar Espinosa, Juan Carlos

    2015-01-01

    Introducción: Tras la pérdida dental se producen una serie de cambios anatómicos que dificultan rehabilitación de los sectores posteriores en maxilares atróficos. Actualmente tenemos diferentes alternativas quirúrgicas para solventar estos problemas, como pueden ser las técnicas de elevación de seno maxilar, tanto con técnicas convencionales como con el empleo de osteotomos o las técnicas M.I.A.M.B.E. Otras alternativas pueden ser el empleo de injertos óseos, las rehabilitaciones con cant...

  10. The Mismatch-Binding Factor MutSβ Can Mediate ATR Activation in Response to DNA Double-Strand Breaks

    Czech Academy of Sciences Publication Activity Database

    Burdová, Kamila; Mihaljevic, B.; Sturzenegger, A.; Chappidi, N.; Janščák, Pavel

    2015-01-01

    Roč. 59, č. 4 (2015), s. 603-614. ISSN 1097-2765 R&D Projects: GA ČR GAP305/10/0281; GA ČR(CZ) GA14-05743S Grant ostatní: Oncosuisse(CH) KLS-02344-02-2009; Swiss National Science Foundation(CH) 31003A_146206; Novartis Foundation for Medical and Biological Research(CH) 11A16 Institutional support: RVO:68378050 Keywords : Ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase * DNA-damage response * DNA Double-Strand Breaks Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 14.018, year: 2014

  11. ATR-analysaattori raaka-aineen laadunvarmistuksessa : Kasviöljyseoksen peroksidiluvun määrittäminen

    OpenAIRE

    Oinonen, Iida

    2016-01-01

    Tämän opinnäytetyön toimeksiantajana toimi Valio Oy Turengin tehtaan laadunvalvontalaboratorio. Opinnäytetyön tarkoituksena oli selvittää Thermo ScientificTM Nicolet iSTM 50 -analysaattorin ATR-mittausmoduulin käyttömahdollisuuksia raaka-aineen laadunvarmistuksessa. Tavoite oli kehittää laitteelle menetelmä, jonka avulla lastenruokien raaka-aineiden laatua voidaan tehtaalla jatkossa entistä sujuvammin valvoa. Tutkittaviksi raaka-aineiksi haluttiin lastenruoissa käytettävät jauheet, vitam...

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

    International Nuclear Information System (INIS)

    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. 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]).

  14. 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.

  15. Department of Energy's Advanced Test Reactor (ATR), July 14--18, 1980: An independent on-site safety review

    International Nuclear Information System (INIS)

    The intent of this review was not to conduct a detailed in-depth audit, but rather to make a broad management assessment of ATR operations. The results of the review should only be considered as having identified trends or indications. The Team's observations and recommendations for the most part are based upon standards used for licensed reactor facility practices. These standards form the basis for many of the comments in this report. The Team believes that a uniform minimum standard of performance should be achieved in the operation of DOE reactors. In order to assure that this is accomplished, clear standards are necessary. Consistent with the past AEC and ERDA policy, the Team has used the standards of the commercial nuclear power industry. It is recognized that this approach is conservative, in that the ATR reactor has a significantly greater degree of inherent safety (lower pressure, temperature, power, etc.) than a licensed reactor. Although the Review Team found no indications or evidence that the plant is being operated in an unsafe manner, various areas were identified where improvements are either needed or should be considered to increase the safety of reactor operations

  16. ATR-FTIR spectroscopic studies on density changes of fused silica induced by localized CO2 laser treatment

    Institute of Scientific and Technical Information of China (English)

    张传超; 郑万国; 袁晓东; 张丽娟; 廖威; 晏中华; 陈静; 蒋一岚; 王海军; 栾晓雨; 叶亚云

    2015-01-01

    Surface density changes of the central region of the sites treated by using the CO2 laser-based non-evaporative dam-age mitigation for fused silica are investigated by the attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The ATR-FTIR peak shifts of the treated sites of fused silica are monitored to determine the changes of the corresponding density. For the quenching treated sites, the surface density is increased by (0.24±0.01)%compared with the initial density, but the laser annealing by the exposure of a power ramp down after damage mitigation effectively suppresses the structural changes of treated sites, which could reduce the increase of the corresponding density to (0.08±0.01)%. The results provide the sufficient evidence that the laser annealing by a power ramp down after damage mitigation has a positive effect on the control of the structural change induced by CO2 laser-based damage mitigation.

  17. In Situ ATR FTIR Spectroscopic Study of the Formation and Hydration of a Fucoidan/Chitosan Polyelectrolyte Multilayer.

    Science.gov (United States)

    Ho, Tracey T M; Bremmell, Kristen E; Krasowska, Marta; MacWilliams, Stephanie V; Richard, Céline J E; Stringer, Damien N; Beattie, David A

    2015-10-20

    The formation of fucoidan/chitosan-based polyelectrolyte multilayers (PEMs) has been studied with in situ Fourier transform infrared (FTIR) spectroscopy. Attenuated total reflectance (ATR) FTIR spectroscopy has been used to follow the sequential build-up of the multilayer, with peaks characteristic of each polymer being seen to increase in intensity with each respective adsorption stage. In addition, spectral processing has allowed for the extraction of spectra from individual adsorbed layers, which have been used to provide unambiguous determination of the adsorbed mass of the PEM at each stage of formation. The PEM was seen to undergo a transition in growth regimes during build-up: from supra-linear to linear. In addition, the wettability of the PEM has been probed at each stage of the build-up, using the captive bubble contact angle technique. The contact angles were uniformly low, but showed variation in value depending on the nature of the outer polymer layer, and this variation correlated with the overall percentage hydration of the PEM (determined from FTIR and quartz crystal microbalance data). The nature of the hydration water within the polyelectrolyte multilayer has also been studied with FTIR spectroscopy, specifically in situ synchrotron ATR FTIR microscopy of the multilayer confined between two solid surfaces. The acquired spectra have enabled the hydrogen bonding environment of the PEM hydration water to be determined. The PEM hydration water is seen to have an environment in which it is subject to fewer hydrogen bonding interactions than in bulk electrolyte solution. PMID:26421938

  18. Review of reactor physics activities relevant to FBR and ATR programmes in PNC, Japan, June 1977 to October 1978

    International Nuclear Information System (INIS)

    Reactor physics works in Power Reactor and Nuclear Fuel Development Corporation (PNC) are carried out in support of the FBR and ATR development programmes. The works are in progress with high efficiency, in cooperation of other related organizations in Japan and also overseas. The experimental fast reactor ''Joyo'' reached its full power of 50 MWt, being operated now to obtain technical data and experiences. The prototype fast breeder reactor ''Monju'' is nearing completion of its final design, and the surveys on its proposed site have been finished. The advanced thermal reactor ''Fugen'', a heavy water-moderated and boiling light water-cooled, reactor reached the criticality, and the power generation was successfully achieved. The data to be obtained are used for the development of a large demonstration reactor. After describing on these types of reactors briefly, the works on reactor physics are described as follows: for fast reactors, mockup experiment and analysis, evaluation of actinide nuclear data, development of core analytical method, and research on shielding; and for ATR, research with a deuterium critical assembly. (Mori, K.)

  19. 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.

  20. Low toxicity corrosion inhibitors

    International Nuclear Information System (INIS)

    This paper discusses the design and testing of low toxicity corrosion inhibitors. New chemistries have been investigated with respect to corrosion protection and impact on the marine environment. The resulting chemicals, while they are effective corrosion inhibitors, present significant improvements in terms of environmental properties over current products. The discussion includes results of the corrosion inhibition, toxicity, biodegradability and partitioning studies

  1. 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.; Baiker, A.

    2010-01-01

    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...... 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...

  2. 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.

  3. Quickly Identifying Different Species of Lavender Essential Oils by ATR-FTIR Coupled to PCA and DPLS%ATR-FTIR结合PCA及DPLS快速识别不同品种薰衣草精油

    Institute of Scientific and Technical Information of China (English)

    童红; 唐军; 张正方

    2014-01-01

    筛选有代表性的4个不同品种的96个薰衣草精油样品为试验对象,应用衰减全反射傅里叶变换红外光谱(ATR-FTIR)获得光谱数据,在主成分分析的基础上采用偏最小二乘辨别法(DPLS)建立薰衣草精油品种识别的模型。结果表明:主成分分析基本能实现品种区分,DPLS 法以68个样本作为校正集,交叉验证均方根标准差(RMSEE)为0.1590,以未知的28个样本进行预测,预测均方根标准差(RMSEP)为0.1860,品种识别率为100%,DPLS 法建立的模型对薰衣草精油品种有很好的识别和分类能力。将红外光谱与化学计量学方法结合,可为薰衣草精油品种的优良宏观质控提供一个快速、直观、可行的方法。%Use Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) to obtain spectral data for classification according to lavender oil cultivars,as a tool to guarantee varie-tal authenticity.96 samples belong to four most representative lavender cultivars.On the basis of PCA,its performance is also compared with that obtained using DPLS model.The results show that PCA can basically discriminate lavender oil cultivar.68 samples are as a calibration set in DPLS method,the RMSEE is 0.1590,28 unknown samples are as predictive samples,the RMSEP is 0. 1860;the correct identification rate of species is 100%.Based on these two data sets only,it seems that the DPLS method is the best of those considered here.The result indicates that a model which provides a quick,intuitive and feasible method has been built to discriminate lavender oils by using ATR-FTIR method combined with chemometrics techniques.

  4. 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

    -FTIR and XPS studies of the fulgimide samples revealed closely covered amide-terminated SAMs. Reversible photoswitching of the headgroup was read out by applying XPS, ATR-FTIR, and difference absorption spectra in the mid-IR. In XPS, we observed a reversible breathing of the amide/imide C1s and N1s signals...

  5. 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. A...

  6. 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…

  7. Xenopus Cds1 Is Regulated by DNA-Dependent Protein Kinase and ATR during the Cell Cycle Checkpoint Response to Double-Stranded DNA Ends

    Science.gov (United States)

    McSherry, Troy D.; Mueller, Paul R.

    2004-01-01

    The checkpoint kinase Cds1 (Chk2) plays a key role in cell cycle checkpoint responses with functions in cell cycle arrest, DNA repair, and induction of apoptosis. Proper regulation of Cds1 is essential for appropriate cellular responses to checkpoint-inducing insults. While the kinase ATM has been shown to be important in the regulation of human Cds1 (hCds1), here we report that the kinases ATR and DNA-dependent protein kinase (DNA-PK) play more significant roles in the regulation of Xenopus Cds1 (XCds1). Under normal cell cycle conditions, nonactivated XCds1 constitutively associates with a Xenopus ATR complex. The association of XCds1 with this complex does not require a functional forkhead activation domain but does require a putative SH3 binding region that is found in XCds1. In response to double-stranded DNA ends, the amino terminus of XCds1 is rapidly phosphorylated in a sequential pattern. First DNA-PK phosphorylates serine 39, a site not previously recognized as important in Cds1 regulation. Xenopus ATM, ATR, and/or DNA-PK then phosphorylate three consensus serine/glutamine sites. Together, these phosphorylations have the dual function of inducing dissociation from the ATR complex and independently promoting the full activation of XCds1. Thus, the checkpoint-mediated activation of XCds1 requires phosphorylation by multiple phosphoinositide 3-kinase-related kinases, protein-protein dissociation, and autophosphorylation. PMID:15509799

  8. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kevin G. Field; Richard Howard; Michael Teague

    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.

  10. 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.

  11. A hybrid original approach for prediction of the aerodynamic coefficients of an ATR-42 scaled wing model

    Directory of Open Access Journals (Sweden)

    Abdallah Ben Mosbah

    2016-02-01

    Full Text Available A new approach for the prediction of lift, drag, and moment coefficients is presented. This approach is based on the support vector machines (SVMs methodology and an optimization meta-heuristic algorithm called extended great deluge (EGD. The novelty of this approach is the hybridization between the SVM and the EGD algorithm. The EGD is used to optimize the SVM parameters. The training and validation of this new identification approach is realized using the aerodynamic coefficients of an ATR-42 wing model. The aerodynamic coefficients data are obtained with the XFoil software and experimental tests using the Price–Païdoussis wind tunnel. The predicted results with our approach are compared with those from the XFoil software and experimental results for different flight cases of angles of attack and Mach numbers. The main purpose of this methodology is to rapidly predict aircraft aerodynamic coefficients.

  12. Formulation and drug-content assay of microencapsulated antisense oligonucleotide to NF-κB using ATR-FTIR

    International Nuclear Information System (INIS)

    Antisense oligonucleotide to NF-κB sequence: 5′-GGA AAC ACA TCC TCC ATG-3′, was microencapsulated in an albumin matrix by the method of spray dryingTM. Spectral analysis was performed on varying drug loading formulations of both drugs by mid-IR attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An out of plane O–H bending vibration at 948 cm−1, unique to both the native and microencapsulated drugs was identified. The calculated peak areas corresponded to the drug loadings in the microsphere formulations. A standard curve could then be used to determine the drug content of an unknown microsphere formulation. Accuracy and precision were determined to be comparable to other analytical techniques such as HPLC. (paper)

  13. 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.

  14. Formulation and drug-content assay of microencapsulated antisense oligonucleotide to NF-κB using ATR-FTIR

    Science.gov (United States)

    Siwale, Rodney; Meadows, Fred; Mody, Vicky V.; Shah, Samit

    2013-09-01

    Antisense oligonucleotide to NF-κB sequence: 5‧-GGA AAC ACA TCC TCC ATG-3‧, was microencapsulated in an albumin matrix by the method of spray dryingTM. Spectral analysis was performed on varying drug loading formulations of both drugs by mid-IR attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An out of plane O-H bending vibration at 948 cm-1, unique to both the native and microencapsulated drugs was identified. The calculated peak areas corresponded to the drug loadings in the microsphere formulations. A standard curve could then be used to determine the drug content of an unknown microsphere formulation. Accuracy and precision were determined to be comparable to other analytical techniques such as HPLC.

  15. 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.

  16. Changes in the infrared attenuated total reflectance (ATR spectra of lignins from alfalfa stem with growth and development

    Directory of Open Access Journals (Sweden)

    JORDAN P. MARKOVIĆ

    2009-08-01

    Full Text Available Lignin is a poorly characterized polymer and its exact properties vary depending on both the species of the plant and its location within the plant. Three classes of lignins taken from alfalfa stem were examined. The investigation was concentrated on the determination of chemical changes in the lignins during growth and development by the attenuated total reflectance (ATR infrared (IR spectrometric technique. The spectrum of permanganate lignin was comparable to that of acid detergent lignin. The main differences were in the different relative absorbance of the peaks. The predominant component of acid detergent lignin and permanganate lignin was guaiacyl-type lignin. The predominant component of Klason lignin was syringyl-type lignin. A comparison between the signals from lignin in different development stages revealed the appearance of new peaks, which are indications of new bonds and changes in the structure of the lignins.

  17. Association atrésie de l'oesophage type 3 - microcéphalie: Un syndrome de Feingold incomplet?

    OpenAIRE

    Shongo, Mick Yapongombo; Lubala, Toni Kasole; Mbuyi, Sébastien Musanzayi; Makinko, Paul Ilunga; Ngwej, Dieudonné Tshikwej; Kabange, Felix Numbi

    2012-01-01

    L'atrésie de l'oesophage est une des malformations digestive les plus fréquentes en néonatologie. Il existe 5 types anatomiques, selon la présence et le siège de la fistule oeso-trachéale. Le diagnostic anténatal est difficile. A la naissance, le diagnostic est suspecté en salle de travail, devant l’échec du passage systématique d'une sonde digestive jusque dans l'estomac. Des trouble de la déglutition, une hyper sialorrhée, une détresse respiratoire sont ensuite retrouvés. Une fistule oeso-t...

  18. 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.

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

    2013-05-01

    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 to study the aerosol physical, chemical, hygroscopic and optical properties, as well as cloud microphysics. 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, allowing for a qualitative evaluation of emission influence on the respective air parcel. This study shows that the extensive aerosol parameters (aerosol mass and number concentrations) show vertical decreasing gradients and in some air masses maximum mass concentrations (mainly organics) in an intermediate layer (1-3 km). The observed mass concentrations (in the boundary layer (BL): between 10 and 30 μg m-3; lower free troposphere (LFT): 0.8 and 14 μg m-3) are high especially in comparison with the 2015 European norms for PM2.5 (25 μg m-3) and with previous airborne studies performed over England (Morgan et al., 2009; McMeeking et al., 2012). Particle number size distributions show a larger fraction of particles in the accumulation size range in the LFT compared to BL. The chemical composition of submicron aerosol particles is dominated by organics in the BL, while ammonium sulphate dominates the submicron aerosols in the LFT, especially in the aerosol particles originated from north-eastern Europe (~ 80%), also experiencing nucleation events along the transport. As a consequence, first the particle CCN acting ability, shown by the CCN/CN ratio, and second the average values of the scattering cross sections of optically active particles (i.e. scattering coefficient divided by the optical active particle concentration) are increased in the LFT compared to BL.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Binh T; Einerson, Jeffrey J

    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. The AGR-2 data streams addressed in this report include thermocouple (TC) temperatures, sweep gas data (flow rates including new FPM downstream flows, pressure, and moisture content), and FPMS data (release rates and release-to-birth rate ratios [R/Bs]) for each of the four U.S. capsules in the AGR-2 experiment (Capsules 2, 3, 5, and 6). The final data qualification status for these data streams is determined by a Data Review Committee comprised of AGR technical leads, Very High Temperature Reactor (VHTR) Program Quality Assurance (QA), and NDMAS analysts. The Data Review Committee, which convened just

  1. Low-temperature, low-cost growth of robust ATR GeO2 hollow fibers based on copper capillary tubes for transmission of CO2 laser light

    Science.gov (United States)

    Jing, Chengbin; Bai, Wei; Hu, Zhigao; Yang, Pingxiong; Liu, Aiyun; Lin, Fangtin; Shi, Yiwei; Chu, Junhao

    2014-02-01

    Attenuated total reflectance (ATR) infrared hollow waveguide attracts particular interest since it has both advantages of a hollow fiber and a light guiding mechanism similar to that of solid-core fibers. Presently, ATR hollow waveguides are mainly structured with single-crystal sapphire or glassy materials. These waveguides are somewhat brittle. More robust ATR hollow fibers are required in many military and domestic applications. In this work, ATR GeO2 hollow waveguides were prepared based on a copper capillary tube for transmitting CO2 laser light. The inner wall of the copper structural tube was polished using a high-pressure pulsed nanofluid technique. A hexagonal crystalline GeO2 reflective layer with sufficient thickness (>4 μm) was grown on the inner tube wall via a simple liquid phase deposition process at room temperature. The GeO2 coated copper hollow fiber exhibits a low-loss band within 10-11.5 μm. It can still be bent since the hollow-core size (1.4 mm) and the wall thickness (50 μm) are not too large. The transmissions of CO2 laser light are 91% and 43% under a straight condition and a 90° bend with a 30-cm radius condition, respectively. The waveguide displays high heat-resisting properties due to high thermal conductivity of the copper substrate tube and a high melting point (1115°C) of the GeO2 reflective layer. This work opens a door for low-temperature, low-cost growth of long ATR GeO2 infrared hollow fibers based on various substrate tubes, even including plastic capillary tubes.

  2. Small-molecule caspase inhibitors

    International Nuclear Information System (INIS)

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  3. Small-molecule caspase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Zhenodarova, S M [Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation)

    2010-02-28

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  4. Small-molecule caspase inhibitors

    Science.gov (United States)

    Zhenodarova, S. M.

    2010-02-01

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  5. Cholinesterase inhibitors from botanicals

    Directory of Open Access Journals (Sweden)

    Faiyaz Ahmed

    2013-01-01

    Full Text Available Alzheimer′s disease (AD is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh, appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through www.Chemspider.com are also presented and the scope for future research is discussed.

  6. Phosphodiesterase-5 inhibitors.

    Science.gov (United States)

    Cockrill, Barbara A; Waxman, Aaron B

    2013-01-01

    Nitric oxide (NO) signaling plays a key role in modulating vascular tone and remodeling in the pulmonary circulation. The guanylate cyclase/cyclic guanylate monophosphate-signaling pathway primarily mediates nitric oxide signaling. This pathway is critical in normal regulation of the pulmonary vasculature, and is an important target for therapy in patients with pulmonary hypertension. In the pulmonary vasculature, degradation of cGMP is primarily regulated by PDE-5, and inhibition of this enzyme has important effects on pulmonary vasculature smooth muscle tone. Large randomized placebo-controlled trials of PDE-5 inhibitors demonstrated improved exercise capacity, hemodynamics and quality of life in adult patients with PAH. This chapter will discuss the mechanisms of NO signaling in the vasculature, characteristics of the PDE5-inhibitors approved for treatment of PH, and review available data on the use of phosphodiesterase inhibitors in PH. PMID:24092343

  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. 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

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

    Directory of Open Access Journals (Sweden)

    S. Crumeyrolle

    2012-04-01

    Full Text Available 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

  10. Protein protease inhibitors in insects and comparison with mammalian inhibitors.

    Science.gov (United States)

    Eguchi, M

    1993-01-01

    1. Studies on insect protein protease inhibitors are summarized. Biochemical, genetic and physiological investigations of the silkworm are performed. 2. In addition, the properties and characteristics of fungal protease inhibitors from the silkworm (Bombyx mori) are described and their importance as defensive functions is emphasized. 3. This review also concerns comparative and evolutionary studies of protease inhibitors from various sources. 4. The biological significance of inhibitors is discussed in view of the extensive experimental results. PMID:8365101

  11. Corrosion inhibitor compositions

    International Nuclear Information System (INIS)

    A corrosion inhibitor compositon for hydrocarbon fuels consisting essentially of, by weight, (A) about 75% to 95% of at least one polymerized unsaturated aliphatic monocarboxylic acid, said unsaturated acid having 16 to 18 carbons per molecule, and (B) about 5% to 25% of at least one monoalkenylsuccinic acid in which the alkenyl group as 8 to 18 carbons

  12. Thymidine Phosphorylase Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Nencka, Radim

    Karachi : Bentham Science Publishers, 2011 - (Atta-ur-Rahman, F.; Choudhary, M.), s. 116-147 ISBN 978-1-60805-162-5 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Institutional research plan: CEZ:AV0Z40550506 Keywords : thymidine phosphorylase inhibitors * angiogenesis * cancer chemotherapy Subject RIV: CC - Organic Chemistry

  13. Sunflower trypsin inhibitor-1.

    Science.gov (United States)

    Korsinczky, Michael L J; Schirra, Horst Joachim; Craik, David J

    2004-10-01

    SFTI-1 is a bicyclic 14 amino acid peptide that was originally isolated from the seeds of the sunflower Helianthus annuus. It is a potent inhibitor of trypsin, with a sub-nanomolar K(i) value and is homologous to the active site region of the well-known family of serine protease inhibitors known as the Bowman-Birk trypsin inhibitors. It has a cyclic backbone that is cross-braced by a single disulfide bridge and a network of hydrogen bonds that result in a well-defined structure. SFTI-1 is amenable to chemical synthesis, allowing for the creation of synthetic variants. Alterations to the structure such as linearising the backbone or removing the disulfide bridge do not reduce the potency of SFTI-1 significantly, and minimising the peptide to as few as nine residues results in only a small decrease in reactivity. The creation of linear variants of SFTI-1 also provides a tool for investigating putative linear precursor peptides. The mechanism of biosynthesis of SFTI-1 is not yet known but it seems likely that it is a gene-coded product that has arisen from a precursor protein that may be evolutionarily related to classic Bowman-Birk inhibitors. PMID:15544530

  14. Inhibitors of histone demethylases

    DEFF Research Database (Denmark)

    Lohse, Brian; Kristensen, Jesper L; Kristensen, Line H; Agger, Karl; Helin, Kristian; Gajhede, Michael; Clausen, Rasmus P

    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...

  15. Caracterització fenotípica i assaig terapèutic en models murins transgènics d'atròfia muscular espinal

    OpenAIRE

    Dachs i Cabanas, Elisabet

    2012-01-01

    L’atròfia muscular espinal (AME) és una malaltia d’origen genètic que afecta, majoritàriament a la població infantil. La malaltia cursa amb una mort de les motoneurones  i atròfia muscular. El gen implicat és el survival motor neuron (SMN) que està delecionat en un 95% dels casos. El nostre estudi està dividit en dues parts: 1- l’aprofundiment de les alteracions musculars en dos models animals murins transgènics que pateixen les formes més greus d’AME (Tipus 1-2) i 2- estudi dels possibles e...

  16. In situ ATR-FTIR study of H2O and D2O adsorption on TiO2 under UV irradiation.

    Science.gov (United States)

    Belhadj, Hamza; Hakki, Amer; Robertson, Peter K J; Bahnemann, Detlef W

    2015-09-21

    The adsorption of water and deuterium oxide on TiO2 surfaces was investigated in the dark as well as under UV(A) irradiation using in situ ATR-FTIR spectroscopy under oxygen and oxygen free conditions. Adsorption of H2O-D2O mixtures revealed an isotopic exchange reaction occurring onto the surface of TiO2 in the dark. Under UV(A) irradiation, the amount of both OH and OD groups was found to be increased by the presence of molecular oxygen. Furthermore, the photocatalytic formation of hydroperoxide under oxygenated condition has been recorded utilizing Attenuated Total Reflection Fourier Transformed Infrared (ATR-FTIR) spectroscopy which appeared as new band at 3483 cm(-1). Different possible mechanisms are discussed in terms of the source of hydroxyl groups formed and/or hydration water on the TiO2 surface for the photocatalytic reaction and photoinduced hydrophilicity. PMID:26266701

  17. DETERMINATION OF THE QUANTITY OF I-135 RELEASED FROM THE AGR-1 TEST FUELS AT THE END OF ATR OPERATING CYCLE 138B

    Energy Technology Data Exchange (ETDEWEB)

    J. K. Hartwell; D. M. Scates; J. B. Walter; M. W. Drigert

    2007-05-01

    The AGR-1 experiment is a multiple fueled-capsule irradiation experiment being conducted in the Advanced Test Reactor (ATR) in support of the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. The experiment began irradiation in the ATR with a cycle that reached full power on December 26, 2006 and ended with shutdown of the reactor for a brief outage on February 10, 2007 at 0900. The AGR-1 experiment will continue cyclical irradiation for about 2.5 years. In order to allow estimation of the amount of radioiodine released during the first cycle, purge gas flow to all capsules continued for about 4 days after reactor shutdown. The FPMS data acquired during part of that shutdown flow period has been analyzed to elucidate the level of 135I released during the operating cycle.

  18. ATR-FTIR spectroscopy detects alterations induced by organotin(IV) carboxylates in MCF-7 cells at sub-cytotoxic/-genotoxic concentrations

    CERN Document Server

    Ahmad, Muhammad S; Hussain, Mukhtiar; Hanif, Muhammad; Ali, Saqib; Walsh, Michael J; Martin, Francis L; 10.1186/1757-5036-1-3

    2009-01-01

    The environmental impact of metal complexes such as organotin(IV) compounds is of increasing concern. Genotoxic effects of organotin(IV) compounds (0.01 microg/ml, 0.1 microg/ml or 1.0 microg/ml) were measured using the alkaline single-cell gel electrophoresis (comet) assay to measure DNA single-strand breaks (SSBs) and the cytokinesis-block micronucleus (CBMN) assay to determine micronucleus formation. Biochemical-cell signatures were also ascertained using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. In the comet assay, organotin(IV) carboxylates induced significantly-elevated levels of DNA SSBs. Elevated micronucleus-forming activities were also observed. Following interrogation using ATR-FTIR spectroscopy, infrared spectra in the biomolecular range (900 cm-1 - 1800 cm-1) derived from orga...

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

    OpenAIRE

    Armando Guerrero Peña; Francisco Anguebes Franseschi; Mepivoseth Castelán Estrada; Victorino Morales Ramos; Reyes García Zarracino; José C. Zavala Loría; Atl V. Córdova Quiroz

    2014-01-01

    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 id...

  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

    OpenAIRE

    Giampaolo Piga; David Gonçalves; T. J. U. Thompson; Antonio Brunetti; Assumpció Malgosa; Stefano Enzo

    2016-01-01

    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 (...

  1. Adsorption of poly(ethylene oxide)-block-poly(D,L-lactide) copolymers on polyactide surface studied by ATR-FTIR spectroscopy

    Czech Academy of Sciences Publication Activity Database

    Popelka, Štěpán; Machová, Luďka; Rypáček, František

    Prague: Czech Society for New Materials and Technologies, 2005. Poster Session II. [European Congress on Advanced Materials and Processes. 5.9.2005-8.9.2005, Prague] R&D Projects: GA AV ČR IAA4050202 Keywords : ATR FTIR * polylactide * surface Subject RIV: CD - Macromolecular Chemistry http://webdb.dgm.de/dgm_lit/prg/FMPro?-db=w_program&-recID=12953608&- format =prog_kurzfassung.htm&-lay=Standard&-find

  2. A DNA Damage Response Screen Identifies RHINO: a 9-1-1 and TopBP1 interacting protein required for ATR signaling

    OpenAIRE

    Cotta-Ramusino, Cecilia; 3, E. Robert McDonald; Hurov, Kristen; Sowa, Mathew E.; Harper, J. Wade; Elledge, Stephen J.

    2011-01-01

    The DNA damage response (DDR) is a protein kinase cascade that orchestrates DNA repair processes via transcriptional and post-translational mechanisms. Cell cycle arrest is a hallmark of the DDR. We performed a damage-induced cell cycle arrest screen and uncovered a critical role for Fanconi anemia (FA) and homologous recombination (HR) proteins in ATR signaling. HR was required to maintain prolonged cell cycle arrest and to prevent massive genomic instability. Over 100 high scoring DDR candi...

  3. Kinetic investigations on UV-induced photopolymerization reactions by real-time FTIR-ATR spectroscopy: the efficiency of photoinitiators at 313 and 222 nm

    International Nuclear Information System (INIS)

    Real-time FTIR-ATR spectroscopy was used to study the kinetics of photopolymerization reactions induced by monochromatic UV light. Various photoinitiators with a broad range of extinction coefficients were tested for their efficiency to start the curing reaction of a diacrylate on irradiation at 313 or 222 nm. The effect of the absorption and initiation properties of the photoinitiators on the polymerization rate was analyzed. At 222 nm, the acrylate was found to polymerize even without photoinitiator

  4. Quantification of pure refined olive oil adulterant in extra virgin olive oil using diamond cell atr-ftir spectroscopy

    International Nuclear Information System (INIS)

    The present study depicts spectroscopic method development to deliver a rapid, simple and reproducible quantification of pure refined olive oil (PROO) adulterant in extra virgin olive oil (EVOO) using partial least square (PLS) regression (statistical parameter). Single bounce attenuated total reflectance (SB-ATR) Fourier transform infrared (FTIR) was choice in the developed method. Blended standards of PROO and EVOO were obtained by their weight by weight percentage and the values were used to construct calibration curves for quantification. The optimum regression values (i.e. >0.99) were achieved using the combined frequencies of 3105-2761, 1838-1687, and 1482-440 cm-1 with regression coefficients (R2) 0.99718 and achieved residual mean square error of calibration (RMSEC) 1.40% w/w. To determine the suitability of developed method principal component spectra (PCS) diagnostic was also used. The results of the present study prove that the developed methods reported in preceding studies can be good option for more rapid and accurate determination of PROO adulteration in EVOO. (author)

  5. Improving batch cooling seeded crystallization of an organic weed-killer using on-line ATR FTIR measurement of supersaturation

    Science.gov (United States)

    Lewiner, F.; Févotte, G.; Klein, J. P.; Puel, F.

    2001-06-01

    In previous papers, a method for the calibration of ATR FTIR measurement of dissolved solid concentration during cooling crystallizations was presented, and efficient basic procedures for the determination of solubility and metastability curves were described. The present paper reports new experimental results. The crystallization of an organic product is studied thanks to on-line FTIR measurements of supersaturation and off-line crystal size distribution (CSD) determinations. The obtained information is shown to potentially allow a deeper examination of major industrial issues such as the reduction of batch-to-batch variations and the improvement of the CSD of the final particles. A particular attention is focused on the determination of appropriate seeding parameters such as the cooling rate of seeded slurries, the temperature of introduction and the amount of seed. The results obtained demonstrate that, although any modelling approach is outside the scope of this paper, the analysis of the measured supersaturation profiles allows some interpretation of mechanisms governing the final CSD, and consequently, the proposal of improved operating parameters.

  6. 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.

  7. Adsorption of Lysine on Na-Montmorillonite and Competition with Ca(2+): A Combined XRD and ATR-FTIR Study.

    Science.gov (United States)

    Yang, Yanli; Wang, Shengrui; Liu, Jingyang; Xu, Yisheng; Zhou, Xiaoyun

    2016-05-17

    Lysine adsorption at clay/aqueous interfaces plays an important role in the mobility, bioavailability, and degradation of amino acids in the environment. Knowledge of these interfacial interactions facilitates our full understanding of the fate and transport of amino acids. Here, X-ray diffraction (XRD) and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) measurements were used to explore the dynamic process of lysine adsorption on montmorillonite and the competition with Ca(2+) at the molecular level. Density functional theory (DFT) calculations were employed to determine the peak assignments of dissolved lysine in the solution phase. Three surface complexes, including dicationic, cationic, and zwitterionic structures, were observed to attach to the clay edge sites and penetrate the interlayer space. The increased surface coverage and Ca(2+) competition did not affect the interfacial lysine structures at a certain pH, whereas an elevated lysine concentration contributed to zwitterionic-type coordination at pH 10. Moreover, clay dissolution at pH 4 could be inhibited at a higher surface coverage with 5 and 10 mM lysine, whereas the inhibition effect was inconspicuous or undetected at pH 7 and 10. The presence of Ca(2+) not only could remove a part of the adsorbed lysine but also could facilitate the readsorption of dissolved Si(4+) and Al(3+) and surface protonation. Our results provide new insights into the process of lysine adsorption and its effects on montmorillonite surface sites. PMID:27118104

  8. Characterization of nasal paraffinoma following septorhinoplasty by attenuated total reflection--fourier transform infrared spectroscopy (ATR-FTIR).

    Science.gov (United States)

    Gil-Carcedo, Luis M; Martín-Gil, Jesús; Gil-Carcedo, Elisa S; Vallejo, Luis A; Martín-Gil, Francisco J

    2006-06-01

    Vaseline and paraffin have been injected into various parts of the body. Vaselinoma and paraffinoma are well-described complications, despite which nasal packing with Vaseline gauze is still common in the management of epistaxis, after rhinoplasty, endonasal surgery, to control bleeding and prevent synechiae or restenosis. Our aim is to highlight this complication, propose a safe method for its diagnosis and establish guidelines for its prevention. We report two cases of paraffinoma occurring after rhinoplasty and discuss prevention of this rare but serious complication, and suggest an alternative dressing. Attenuated total reflection (ATR) FI7R spectra have proven to be a definitive characterising tool for surgical extracts, guaranteeing detection of mineral products that histology does not offer. For these lesions we propose the name "petroleum oilomas" which we feel to be more appropriate than the more commonly used paraffinomas. Relevance of the work: a description of an innovative and safe method of diagnosis, and proposal of a procedure for postrhinoplasty packing (without mineral oils) to avoid this complication. PMID:16792177

  9. 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.

  10. Evaluating drug delivery with salt formation: Drug disproportionation studied in situ by ATR-FTIR imaging and Raman mapping.

    Science.gov (United States)

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

    2015-01-01

    Two different vibrational spectroscopic approaches, ATR-FTIR spectroscopic imaging and Raman mapping, were used to investigate the components within a tablet containing an ionised drug during dissolution experiments. Delivering certain drugs in their salt form is a method that can be used to improve the bioavailability and dissolution of the poorly aqueous soluble materials. However, these ionised species have a propensity to covert back to their thermodynamically favourable free acid or base forms. Dissolution experiments of the ionised drug in different aqueous media resulted in conversion to the more poorly soluble free acid form, which is detrimental for controlled drug release. This study investigates the chemical changes occurring to formulations containing a development ionised drug (37% by weight), in different aqueous pH environments. Firstly, dissolution in a neutral medium was studied, showing that there was clear release of ionised monosodium form of the drug from the tablet as it swelled in the aqueous medium. There was no presence of any drug in the monohydrate free acid form detected in these experiments. Dissolution in an acidic (0.1M HCl) solution showed disproportionation forming the free acid form. Disproportionation occurred rapidly upon contact with the acidic solution, initially resulting in a shell of the monohydrate free acid form around the tablet edges. This slowed ingress of the solution into the tablet before full conversion of the ionised form to the free acid form was characterised in the spectroscopic data. PMID:25910459

  11. 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.

  12. Mismatch repair-dependent G2 checkpoint induced by low doses of SN1 type methylating agents requires the ATR kinase.

    Science.gov (United States)

    Stojic, Lovorka; Mojas, Nina; Cejka, Petr; Di Pietro, Massimiliano; Ferrari, Stefano; Marra, Giancarlo; Jiricny, Josef

    2004-06-01

    S(N)1-type alkylating agents represent an important class of chemotherapeutics, but the molecular mechanisms underlying their cytotoxicity are unknown. Thus, although these substances modify predominantly purine nitrogen atoms, their toxicity appears to result from the processing of O(6)-methylguanine ((6Me)G)-containing mispairs by the mismatch repair (MMR) system, because cells with defective MMR are highly resistant to killing by these agents. In an attempt to understand the role of the MMR system in the molecular transactions underlying the toxicity of alkylating agents, we studied the response of human MMR-proficient and MMR-deficient cells to low concentrations of the prototypic methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We now show that MNNG treatment induced a cell cycle arrest that was absolutely dependent on functional MMR. Unusually, the cells arrested only in the second G(2) phase after treatment. Downstream targets of both ATM (Ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases were modified, but only the ablation of ATR, or the inhibition of CHK1, attenuated the arrest. The checkpoint activation was accompanied by the formation of nuclear foci containing the signaling and repair proteins ATR, the S(*)/T(*)Q substrate, gamma-H2AX, and replication protein A (RPA). The persistence of these foci implied that they may represent sites of irreparable damage. PMID:15175264

  13. [JAK2 inhibitors].

    Science.gov (United States)

    Hernández Boluda, Juan Carlos; Gómez, Montse; Pérez, Ariadna

    2016-07-15

    Pharmacological inhibition of the kinase activity of JAK proteins can interfere with the signaling of immunomodulatory cytokines and block the constitutive activation of the JAK-STAT pathway that characterizes certain malignancies, including chronic myeloproliferative neoplasms. JAK inhibitors may, therefore, be useful to treat malignancies as well as inflammatory or immune disorders. Currently, the most significant advances have been made in the treatment of myelofibrosis, where these drugs may lead to a remarkable improvement in the control of hyperproliferative manifestations. However, available data suggest that this treatment is not curative of myelofibrosis. In general, JAK2 inhibition induces cytopaenias, with this being considered a class side-effect. By contrast, the extrahaematologic toxicity profile varies significantly among the different JAK inhibitors. At present, there are several clinical trials evaluating the combination of ruxolitinib with other drugs, in order to improve its therapeutic activity as well as reducing haematologic toxicity. PMID:27033437

  14. Benzoylurea Chitin Synthesis Inhibitors.

    Science.gov (United States)

    Sun, Ranfeng; Liu, Chunjuan; Zhang, Hao; Wang, Qingmin

    2015-08-12

    Benzoylurea chitin synthesis inhibitors are widely used in integrated pest management (IPM) and insecticide resistance management (IRM) programs due to their low toxicity to mammals and predatory insects. In the past decades, a large number of benzoylurea derivatives have been synthesized, and 15 benzoylurea chitin synthesis inhibitors have been commercialized. This review focuses on the history of commercial benzolyphenylureas (BPUs), synthetic methods, structure-activity relationships (SAR), action mechanism research, environmental behaviors, and ecotoxicology. Furthermore, their disadvantages of high risk to aquatic invertebrates and crustaceans are pointed out. Finally, we propose that the para-substituents at anilide of benzoylphenylureas should be the functional groups, and bipartite model BPU analogues are discussed in an attempt to provide new insight for future development of BPUs. PMID:26168369

  15. Alpha glucosidase inhibitors.

    Science.gov (United States)

    Kalra, Sanjay

    2014-04-01

    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. Working to delay carbohydrate absorption in the gastrointestinal tract, they control postprandial hyperglycaemia and provide unquestioned cardiovascular benefit. Specially suited for a traditional Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds' of diabetology. The use of these oral antidiabetic drugs (OADs) that target pathophysiology in the early stages of type 2 diabetes, notably to reduce postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with time. This review describes the history of their development, mechanism of action, basic and clinical pharmacology, and suggests practical, evidence-based guidance for their optimal use. PMID:24864650

  16. Update on Aromatase Inhibitors

    Directory of Open Access Journals (Sweden)

    Seifert-Klauss V

    2015-01-01

    Full Text Available Aromatase inhibitors (AI block the last phase of estrogen production in many types of tissues which express the enzym aromatase, among them muscle, liver, adrenal, brain and fat. The enzyme catalyzes the last step of the biosynthesis of the estrogens, i. e. the aromatisation of testosterone to estradiol and of androstendion to estrone. Aromatase is localized in the membrane of the endoplasmatic reticulum and is also produced in the placenta and the gonads. Mutations in the gene CYP19A1, which codes for aromatase, can lead either to lack or excess of aromatase. Gene polymorphisms also influence the amount of bioavailable estrogen and bone density.br Indications: AI are approved for the treatment of postmenopausal women with hormone receptor positive breast cancer, both in the adjuvant setting as well as after recurrence and in progressive disease. In premenopausal and in perimenopausal women AI cause an increased sensitivity of the ovaries to follicle stimulating hormone (FSH and can thereby lead to a boosted estrogen answer – this effect is particularly pronounced in early perimenopausal women – so that these situations demand a combination with GnRH-analogue if AI treatment is to be initiated. Alternatively, tamoxifene may be used in premenopausal patients, with or without GnRH analogues. Treatment of premenopausal patients with hormone receptor positive breast cancer with aromatase inhibiting therapy alone constitutes an absolute contraindication. Aromatase inhibitors do not lead to estrogen receptor downregulation or block the receptor such as tamoxifene. An exceptional application is the application in reproductive medicine in women who do not have hormone receptor positive breast cancer: because of the higher sensitivity induced by AI-co-therapy, FSH-doses and -costs for assisted reproduction are reduced, and ovarian hyperstimulation syndrome (OHSS may be avoided. For premenopausal diseases which are said to be positively affected by

  17. Study in vitro of Er,Cr:YSGG laser effects in bone tissue by ATR-FTIR spectroscopy

    International Nuclear Information System (INIS)

    Laser proves to be, more and more, an effective tool for helping health professionals, being intensively used in ophthalmological and odontological procedures. In particular, high-density, infrared emitting lasers have great potential in cutting mineralized biological hard tissues, given their high absorption by hydroxyapatite and water, these tissues' main components. In comparison to mechanical instruments, laser presents a series of advantages, namely, smaller damage to the remaining tissue and promotion of homeostatic effect, apart from making it possible to execute procedures in areas with difficult access. However, for an efficient and safe use of this technique, it is necessary to know the effects of the laser irradiation on the tissue. The Fourier transform infrared (FTIR) technique is heavily used in the study of organic materials, because apart from making it possible to identify the materials' components, it also allows to prepare a semi quantitative analysis. This work aims to establish the ATR-FTIR technique in the characterization of natural and irradiated osseous tissue, and to verify the possible chemical and structural changes caused by irradiation. Firstly, the best conditions for the obtainment of bone sample spectra were determined. Then, bone samples, irradiated with the Er,Cr:YSGG (2,78 μm) infrared emitting laser (adjusted with different energy densities) were analyzed alongside with natural bone samples. It has been verified that the technique is effective in the bone tissue characterization, and that it is possible to observe the chemical changes caused by the temperature rise due to laser irradiation. It has been observed a gradual organic material loss as the energy density goes up. These results are the first steps in testing the Er,Cr:YSGG laser efficacy as a cutting tool, a pivotal aspect of its consolidation in clinical procedures. (author)

  18. ATR-FTIR and UV-Vis Spectroscopic Studies of Aqueous U(IV)-oxalate Complexes under Mild Acidic Conditions

    International Nuclear Information System (INIS)

    The redox transformation process between U(VI) and U(IV) likely involves the participation of soluble or dissolved U(IV) species, such as U(IV)-hydroxo compounds and organic/inorganic ligand complexes. However, their role in the redox process has not been well documented, partly due to the ready oxidation of soluble U(IV) species, and partly due to the assumption that soluble or dissolved forms of U(IV) account for only a minor fraction of uranium in groundwater systems. In this study, a bidentate chelate ligand, oxalate (Ox) was selected to examine the complexation behaviors of U(IV) and ultimately its impact on the U(IV) solubility in mildly acidic solutions. Although some early studies reported that oxalate and pyrophosphate, i. e., multivalent anions, can form soluble U(IV) complexes, the related thermodynamic data and evidences for chemical speciation are very scarce. In our previous work, the U(IV)-Ox 1:1 complex was identified by monitoring the gradual transition of the characteristic absorption spectrum of U(OH)3+ to that of UOx2+ upon the addition of oxalate at pH 1.6.2.0. This work aims to further provide spectroscopic evidence for the formation of multi-ligand complexes, i. e., U(Ox)n4-2n (n ≥ 2) at pH 2-5 using attenuated total reflectance (ATR)- FTIR spectroscopy and UV-Vis absorption spectroscopy. The solid phase of U(IV)-Ox complex system was also characterized through an XRD analysis. Analysis of the FTIR spectra is found to be useful to determine the complexation stoichiometry and to obtain the structural information of the complexes. The outcome of the spectroscopic analysis for the multi-ligand complexation equilibria will be discussed in detail

  19. XPS, SIMS and FTIR-ATR characterization of boronized graphite from the thermonuclear plasma device RFX-mod

    Science.gov (United States)

    Ghezzi, F.; Laguardia, L.; Caniello, R.; Canton, A.; Dal Bello, S.; Rais, B.; Anderle, M.

    2015-11-01

    In this paper the characterization of a thin (tens of nanometers) boron layer on fine grain polycrystalline graphite substrate is presented. The boron film is used as conditioning technique for the full graphite wall of the Reversed Field eXperiment-modified (RFX-mod) experiment, a device for the magnetic confinement of plasmas of thermonuclear interest. Aim of the present analysis is to enlighten the chemical structure of the film, the trapping mechanism that makes it a getter for oxygen and hydrogen and the reason of its loss of effectiveness after exposure to about 100 s of hydrogen plasma. X-ray Photoelectron Spectroscopy (XPS), Secondary Ions Mass Spectrometry (SIMS) and Fourier Transform Infra Red spectroscopy in combination with the Attenuated Total Reflectance (FTIR-ATR) were used to obtain the structure and the chemical composition of graphitic samples as coated or coated and subsequently exposed to hydrogen plasma after boron deposition. The boron layers on the only coated samples were found to be amorphous hydrogenated boron carbide plus a variety of bonds like B-B, B-H, B-O, B-OH, C-C, C-H, C-O, C-OH. Both the thickness and the homogeneity of the layers were found to depend on the distance of the sample from the anode during the deposition. The samples contained oxygen along the layer thickness, at level of 5%, bound to boron. The gettering action of the boron is therefore already active during the deposition itself. The exposure to plasma caused erosion of the boron film and higher content of H and O bound to boron throughout the whole thickness. The interaction of the B layer with plasma is therefore a bulk phenomenon.

  20. Inhibitors of lysosomal cysteine proteases

    OpenAIRE

    Lyanna O. L.; Chorna V. I.

    2011-01-01

    The review is devoted to the inhibitors of cysteine proteinases which are believed to be very important in many biochemical processes of living organisms. They participate in the development and progression of numerous diseases that involve abnormal protein turnover. One of the main regulators of these proteinases is their specific inhibitors: cystatins. The aim of this review was to present current knowledge about endogenous inhibitors of lysosomal cysteine proteases and their synthetic anal...

  1. Inhibitors of lysosomal cysteine proteases

    Directory of Open Access Journals (Sweden)

    Lyanna O. L.

    2011-04-01

    Full Text Available The review is devoted to the inhibitors of cysteine proteinases which are believed to be very important in many biochemical processes of living organisms. They participate in the development and progression of numerous diseases that involve abnormal protein turnover. One of the main regulators of these proteinases is their specific inhibitors: cystatins. The aim of this review was to present current knowledge about endogenous inhibitors of lysosomal cysteine proteases and their synthetic analogs.

  2. Molecular similarity of MDR inhibitors

    OpenAIRE

    Simon Gibbons; Mire Zloh

    2004-01-01

    Abstract: The molecular similarity of multidrug resistance (MDR) inhibitors was evaluated using the point centred atom charge approach in an attempt to find some common features of structurally unrelated inhibitors. A series of inhibitors of bacterial MDR were studied and there is a high similarity between these in terms of their shape, presence and orientation of aromatic ring moieties. A comparison of the lipophilic properties of these molecules has also been conducted suggesting that this ...

  3. ACE INHIBITORS: A COMPREHENSIVE REVIEW

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar Arora* and Ashish Chauhan

    2013-02-01

    Full Text Available Hypertension is a chronic increase in blood pressure, characterized as primary and secondary hypertension. The disorder is associated with various risk factors like obesity, diabetes, age, lack of exercise etc. Hypertension is being treated since ancient times by Ayurvedic, Chinese and Unani medicine. Now various allopathic drugs are available which include diuretics, calcium channel blockers, α-blockers, β-blockers, vasodilators, central sympatholytics and ACE-inhibitors. Non-pharmacological treatments include weight reduction, dietary sodium reduction, increased potassium intake and reduction in alcohol consumption. ACE-inhibitors are widely used in the treatment of hypertension by inhibiting the angiotensin converting enzyme responsible for the conversion of angiotensin I to angiotensin II (responsible for vasoconstriction. Various structure activity relationship studies led to the synthesis of ACE-inhibitors, some are under clinical development. This comprehensive review gives various guidelines on classification of hypertension, hypertension therapy including ancient, pharmacological, non-pharmacological therapies, pharmacoeconomics, historical perspectives of ACE, renin, renin angiotensin system (circulating vs local RAS, mechanism of ACE inhibitors, and development of ACE inhibitors. Review also emphasizes on the recent advancements on ACE inhibitors including drugs in clinical trials, computational studies on ACE-inhibitors, peptidomimetics, dual, natural, multi-functional ACE inhibitors, and conformational requirements for ACE-inhibitors.

  4. Synthesis of Lysine Methyltransferase Inhibitors

    Science.gov (United States)

    Ye, Tao; Hui, Chunngai

    2015-07-01

    Lysine methyltransferase which catalyze methylation of histone and nonhistone proteins, play a crucial role in diverse biological processes and has emerged as a promising target for the development of various human diseases, including cancer, inflammation, and psychiatric disorders. However, inhibiting Lysine methyltransferases selectively has presented many challenges to medicinal chemists. During the past decade, lysine methyltransferase inhibitors covering many different structural classes have been designed and developed. In this review, we describe the development of selective, small-molecule inhibitors of lysine methyltransferases with an emphasis on their discovery and chemical synthesis. We highlight the current state of lysine methyltransferase inhibitors and discuss future directions and opportunities for lysine methyltransferase inhibitor discovery.

  5. Radiation Induced Aging Effects in Polymeric Cable Insulators at CERN. Compilation of the DSC and ATR-FTIR data on irradiated CERN cables.

    CERN Document Server

    Sorin, I

    2009-01-01

    This second part of the Report on Radiation Induced Aging Effects in Polymeric Cable Insulators at CERN [1] summarizes in a tabulated form all the experimental DSC results obtained in this work, concerning the life-time evaluation of the selected CERN cables irradiated in different conditions. Several examples of DSC curves and ATR-FTIR spectra were included to support the future polymeric materials analysis. Information on the experimental conditions, the instruments, the basic concept of life-time evaluation using the DSC data, as well as the examples of data processing and interpretation are presented and discussed in reference [1].

  6. Xenopus Cds1 Is Regulated by DNA-Dependent Protein Kinase and ATR during the Cell Cycle Checkpoint Response to Double-Stranded DNA Ends

    OpenAIRE

    McSherry, Troy D.; Mueller, Paul R.

    2004-01-01

    The checkpoint kinase Cds1 (Chk2) plays a key role in cell cycle checkpoint responses with functions in cell cycle arrest, DNA repair, and induction of apoptosis. Proper regulation of Cds1 is essential for appropriate cellular responses to checkpoint-inducing insults. While the kinase ATM has been shown to be important in the regulation of human Cds1 (hCds1), here we report that the kinases ATR and DNA-dependent protein kinase (DNA-PK) play more significant roles in the regulation of Xenopus ...

  7. Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori

    OpenAIRE

    Luis Eduardo Bravo; Juan Carlos Bravo; José Luis Realpe

    2008-01-01

    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. ...

  8. 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

    2016-08-01

    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

  9. Histone deacetylase inhibitors enhance expression of NKG2D ligands in Ewing sarcoma and sensitize for natural killer cell-mediated cytolysis

    Directory of Open Access Journals (Sweden)

    Berghuis Dagmar

    2012-02-01

    Full Text Available Abstract Background Ewing sarcoma patients have a poor prognosis despite multimodal therapy. Integration of combination immunotherapeutic strategies into first-/second-line regimens represents promising treatment options, particularly for patients with intrinsic or acquired resistance to conventional therapies. We evaluated the susceptibility of Ewing sarcoma to natural killer cell-based combination immunotherapy, by assessing the capacity of histone deacetylase inhibitors to improve immune recognition and sensitize for natural killer cell cytotoxicity. Methods Using flow cytometry, ELISA and immunohistochemistry, expression of natural killer cell receptor ligands was assessed in chemotherapy-sensitive/-resistant Ewing sarcoma cell lines, plasma and tumours. Natural killer cell cytotoxicity was evaluated in Chromium release assays. Using ATM/ATR inhibitor caffeine, the contribution of the DNA damage response pathway to histone deacetylase inhibitor-induced ligand expression was assessed. Results Despite comparable expression of natural killer cell receptor ligands, chemotherapy-resistant Ewing sarcoma exhibited reduced susceptibility to resting natural killer cells. Interleukin-15-activation of natural killer cells overcame this reduced sensitivity. Histone deacetylase inhibitor-pretreatment induced NKG2D-ligand expression in an ATM/ATR-dependent manner and sensitized for NKG2D-dependent cytotoxicity (2/4 cell lines. NKG2D-ligands were expressed in vivo, regardless of chemotherapy-response and disease stage. Soluble NKG2D-ligand plasma concentrations did not differ between patients and controls. Conclusion Our data provide a rationale for combination immunotherapy involving immune effector and target cell manipulation in first-/second-line treatment regimens for Ewing sarcoma.

  10. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    OpenAIRE

    Čolović, Mirjana B; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are appl...

  11. Synergistic enhancement of NK cell-mediated cytotoxicity by combination of histone deacetylase inhibitor and ionizing radiation

    International Nuclear Information System (INIS)

    The overexpression of histone deacetylase (HDAC) and a subsequent decrease in the acetylation levels of nuclear histones are frequently observed in cancer cells. Generally it was accepted that the deacetylation of histones suppressed expression of the attached genes. Therefore, it has been suggested that HDAC might contribute to the survival of cancer cells by altering the NKG2D ligands transcripts. By the way, the translational regulation of NKG2D ligands remaines unclear in cancer cells. It appears the modulation of this unclear mechanism could enhance NKG2D ligand expressions and the susceptibility of cancer cells to NK cells. Previously, it was reported that irradiation can increase the surface expressions of NKG2D ligands on several cancer cell types without increasing the levels of NKG2D ligand transcripts via ataxia telangiectasia mutated and ataxia telangiectasia and Rad3 related (ATM-ATR) pathway, and suggested that radiation therapy might be used to increase the translation of NKG2D ligands. Two NSCLC cell lines, that is, A549 and NCI-H23 cells, were used to investigate the combined effects of ionizing radiation and HDAC inhibitors on the expressions of five NKG2D ligands. The mRNA expressions of the NKG2D ligands were quantitated by multiplex reverse transcription-PCR. Surface protein expressions were measured by flow cytometry, and the susceptibilities of cancer cells to NK cells were assayed by time-resolved fluorometry using the DELFIA® EuTDA cytotoxicity kit and by flow cytometry. The expressions of NKG2D ligands were found to be regulated at the transcription and translation levels. Ionizing radiation and HDAC inhibitors in combination synergistically increased the expressions of NKG2D ligands. Furthermore, treatment with ATM-ATR inhibitors efficiently blocked the increased translations of NKG2D ligands induced by ionizing radiation but did not block the increased ligand translations induced by HDAC inhibitors. The study confirms that increased NKG

  12. Fluorescence, CD, attenuated total reflectance (ATR) FTIR, and sup 13 C NMR characterization of the structure and dynamics of synthetic melittin and melittin analogues in lipid environments

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, A.J.; Prendergast, F.G. (Mayo Foundation, Rochester, MN (United States)); Kemple, M.D. (Indiana Univ.-Purdue Univ., Indianapolis (United States)); Brauner, J.W.; Mendelsohn, R. (Rutgers, The State Univ. of New Jersey, Newark (United States))

    1992-02-11

    The structure and dynamics of synthetic melittin (MLT) and MLT analogues bound to monomyristoylphosphatidylcholine micelles, dimyristoylphosphatidylcholine vesicles, and diacylphosphatidylcholine films have been investigated by fluorescence, CD, attenuated total reflectance (ATR) FTIR, and {sup 13}C NMR spectroscopy. All of these methods provide information about peptide secondary structure and/or about the environment of the single tryptophan side chain in these lipid environments. ATR-FTIR data provide additional information about the orientation of helical peptide segments with respect to the bilayer plane. Steady-state fluorescence anisotropy, fluorescence lifetime, and {sup 13}C NMR relaxation data are used in concert to provide quantitative information about the dynamics of a single {sup 13}C{alpha}-labeled glycine incorporated into each of the MLT peptides at position 12. The cumulative structural and dynamic data are consistent with a model wherein the N-terminal {alpha}-helical segment of these peptides is oriented perpendicular to the bilayer plane. Correlation times for the lysolipid-peptide complexes provide evidence for binding of a single peptide monomer per micelle. A model for the membranolytic action of MLT and MLT-like peptides is proposed.

  13. 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.

  14. 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.

  15. ATR-SEIRAS study of CO adsorption and oxidation on Rh modified Au(111-25 nm) film electrodes in 0.1 M H2SO4

    International Nuclear Information System (INIS)

    Rh modified Au(111-25 nm) electrodes, prepared by electron beam evaporation and galvanostatic deposition, were employed to study adsorption and electro-oxidation of CO on Rh in 0.1 M sulfuric acid solution by in situ attenuated total reflection surface enhanced infrared absorption spectroscopy (ATR-SEIRAS). The results of ATR-SEIRAS experiments were compared with those obtained by infrared reflection absorption spectroscopy on three low-index Rh single crystal surfaces. The Rh film deposited on Au(111-25 nm) electrode consists of 3D clusters forming a highly stepped [n(111) × (111)]-like surface with narrow (111) terraces. When CO was dosed at the hydrogen adsorption potential region, CO adsorbed in both atop (COL) and bridge (COB) configurations, as well as coadsorbed water species, were detected on the Rh film electrode. A partial interconversion of spectroscopic bands due to the CO displacement from bridge to atop sites was found during the anodic potential scan, revealing that there is a potential-dependent preference of CO adsorption sites on Rh surfaces. Our data indicate that CO oxidation on Rh electrode surface in acidic media involves coadsorbed water and follows the nucleation and growth model of a Langmuir-Hinshelwood type reaction

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

    International Nuclear Information System (INIS)

    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-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 mgPu/ghematite, 1.34 x 10-6 MPu/m2) 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.

  17. ATR-FTIR Based Pre and Post Formulation Compatibility Studies for the Design of Niosomal Drug Delivery System Containing Nonionic Amphiphiles and Chondroprotective Drug

    International Nuclear Information System (INIS)

    Pharmaceutical compatibility studies are considered as the most important and first screening stage during development of pharmaceutical drug product. Attenuated total reflectance/fourier transform infrared (ATR-FTIR) is one of the techniques currently available to pharmaceutical scientists for investigating the compatibilities between active drug and inactive pharmaceutical ingredients. The present study was designed to assess the interaction among different niosomes forming components i.e nonionic amphiphiles and chondroprotective/antiinflamatory drug Diacerein by ATR-FTIR method. Physical mixtures and niosomes were prepared by physical mixing and thin film hydration method, respectively. The individual niosomal components, physical mixtures as well as niosomal formulations were analyzed. The spectra of Diacerein showed characteristic peaks at 3300 cm/sup -1/(-COOH) and 760 cm/sup -1/(msubstituted benzene), Span 60 at 2916 cm/sup -1/(-OH), Span 80 at 1740 cm/sup -1/(5- membered ring), Span 85 at 1643 cm/sup -1/(ketone with 5-membered ring), Tween 20 at 1734 cm/sup 1/ (5-membered ring) and Tween 80 at 3488 cm/sup -1/(-OH). The characteristic peaks of Diacerein were present in niosomal formulations with slight shift at 3355-3379 cm/sup -1/(-COOH) and 760-770 cm/sup -1/(m-substituted benzene). This work suggested no significant interaction in characteristic peaks of Diacerein after combining with nonionic surfactants as physical mixtures and niosomal formulations which proposed potential for niosomes to encapsulate diacerein in their micro vicinity. (author)

  18. 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.

  19. ATR-FTIR and XPS study on the structure of complexes formed upon the adsorption of simple organic acids on aluminum hydroxide

    Institute of Scientific and Technical Information of China (English)

    GUAN Xiao-hong; CHEN Guang-hao; SHANG Chii

    2007-01-01

    Information on the binding of organic ligands to metal (hydr)oxide surfaces is useful for understanding the adsorption behaviour of natural organic matter (NOM) on metal (hydr)oxide. In this study, benzoate and salicylate were employed as the model organic ligands and aluminum hydroxide as the metal hydroxide. The attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra revealed that the ligands benzoate and salicylate do coordinate directly with the surface of hydrous aluminum hydroxide, thereby forming inner-sphere surface complexes. It is concluded that when the initial pH is acidic or neutral, monodentate and bridging complexes are to be formed between benzoate and aluminum hydroxide while bridging complexes predominate when the initial pH is alkalic. Monodentate and bridging complexes can be formed at pH 5 while precipitate and bridging complexes are formed at pH 7 when salicylate anions are adsorbed on aluminum hydroxide. The X-ray photoelectron (XP) spectra demonstrated the variation of C 1s binding energy in the salicyate and phenolic groups before and after adsorption. It implied that the benzoate ligands are adsorbed through the complexation between carboxylate moieties and the aluminum hydroxide surface, while both carboxylate group and phenolic group are involved in the complexation reaction when salicylate is adsorbed onto aluminum hydroxide. The information offered by the XPS confirmed the findings obtained with ATR-FTIR.

  20. A novel technique for the rapid determination of tributyl phosphate degradation from alkaline hydrolysis in aqueous and organic phases using FTIR-ATR and verification of this technique by gas chromatography

    International Nuclear Information System (INIS)

    This paper details a semi-quantitative method for determining tributyl phosphate (TBP) degradation from alkaline hydrolysis using FTIR-ATR accompanied by GC verification and it provides a method to extract TBP from aqueous media associated with its use in nuclear reprocessing. The amount of TBP determined by GC decreases from 95 to 36 % after approximately 4 1/2 h in the reaction. TBP present in the organic phase predicted by the FTIR-ATR technique shows that TBP decreases from 97 to 42 %. Up to 15 % of TBP and 40 % of DBP were extracted from the precipitate based on the extraction recoveries determined. (author)

  1. [Pharmacology of bone resorption inhibitor].

    Science.gov (United States)

    Menuki, Kunitaka; Sakai, Akinori

    2015-10-01

    Currently, bone resorption inhibitor is mainly used for osteoporosis. A number of these agents have been developed. These pharmacological action are various. Bisphosphonate inhibit functions of the osteoclasts by inducing apoptosis. On the one hand, RANK-ligand inhibitor and selective estrogen receptor modulator inhibit formation of osteoclasts. It is important to understand these pharmacological action for the selection of the appropriate medicine. PMID:26529923

  2. 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.

  3. Non-apoptotic programmed cell death with paraptotic-like features in bleomycin-treated plant cells is suppressed by inhibition of ATM/ATR pathways or NtE2F overexpression

    Czech Academy of Sciences Publication Activity Database

    Smetana, O.; Široký, Jiří; Houlné, G.; Opatrný, Z.; Chabouté, M.-E.

    2012-01-01

    Roč. 63, č. 7 (2012), s. 2631-2644. ISSN 0022-0957 Institutional research plan: CEZ:AV0Z50040702 Keywords : ATM /ATR pathways * cell cycle * double-strand break response Subject RIV: BO - Biophysics Impact factor: 5.242, year: 2012

  4. Identification of natural dyes on laboratory-dyed wool and ancient wool, silk, and cotton fibers using attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy and Fourier transform Raman spectroscopy.

    Science.gov (United States)

    Bruni, Silvia; De Luca, Eleonora; Guglielmi, Vittoria; Pozzi, Federica

    2011-09-01

    Attenuated total reflection (ATR) infrared and Fourier transform (FT) Raman spectra were obtained from wool threads dyed in the laboratory with natural dyes used in antiquity, following a procedure similar to ancient methods for dyeing wool. The ATR spectra were primarily dominated by the signals of the wool, making it difficult to identify the dye on the fibers only by visual inspection of the infrared spectrum. However, the Raman spectra showed more significant characteristics attributable to the dyes as previously studied in the literature on modern synthetic dyes. A library-search method was thus applied to the second derivatives of both the ATR and Raman spectra to verify the possibility of identifying the dye. Two libraries were constructed, one consisting of the ATR spectra of undyed wool (raw, washed, and mordanted) and the transmission spectra of pure dyes and the other consisting of the Raman spectra of undyed wool and of pure dyes. Correlation and first-derivative correlation search algorithms were used. The results presented here suggest that the two types of spectroscopy are complementary in this kind of work, allowing the almost complete identification of historic dyes on wool. In fact, through the combined use of the two searches, most dyes were identified with a good index of similarity and within the first five hits. Only for annatto was identification totally impossible using either technique. Subsequently the same method was applied to wool, silk, and cotton threads taken from ancient Caucasian and Chinese textiles. PMID:21929856

  5. Application of Attenuated Total Reflectance-Fourier Transformed Infrared (ATR-FTIR) Spectroscopy To Determine the Chlorogenic Acid Isomer Profile and Antioxidant Capacity of Coffee Beans.

    Science.gov (United States)

    Liang, Ningjian; Lu, Xiaonan; Hu, Yaxi; Kitts, David D

    2016-01-27

    The chlorogenic acid isomer profile and antioxidant activity of both green and roasted coffee beans are reported herein using ATR-FTIR spectroscopy combined with chemometric analyses. High-performance liquid chromatography (HPLC) quantified different chlorogenic acid isomer contents for reference, whereas ORAC, ABTS, and DPPH were used to determine the antioxidant activity of the same coffee bean extracts. FTIR spectral data and reference data of 42 coffee bean samples were processed to build optimized PLSR models, and 18 samples were used for external validation of constructed PLSR models. In total, six PLSR models were constructed for six chlorogenic acid isomers to predict content, with three PLSR models constructed to forecast the free radical scavenging activities, obtained using different chemical assays. In conclusion, FTIR spectroscopy, coupled with PLSR, serves as a reliable, nondestructive, and rapid analytical method to quantify chlorogenic acids and to assess different free radical-scavenging capacities in coffee beans. PMID:26725502

  6. 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

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

    International Nuclear Information System (INIS)

    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

  8. Selective Alcohol Oxidation by a Copper TEMPO Catalyst: Mechanistic Insights by Simultaneously Coupled Operando EPR/UV-Vis/ATR-IR Spectroscopy.

    Science.gov (United States)

    Rabeah, Jabor; Bentrup, Ursula; Stößer, Reinhard; Brückner, Angelika

    2015-09-28

    The first coupled operando EPR/UV-Vis/ATR-IR spectroscopy setup for mechanistic studies of gas-liquid phase reactions is presented and exemplarily applied to the well-known copper/TEMPO-catalyzed (TEMPO=(2,2,6,6-tetramethylpiperidin-1-yl)oxyl) oxidation of benzyl alcohol. In contrast to previous proposals, no direct redox reaction between TEMPO and Cu(I) /Cu(II) has been detected. Instead, the role of TEMPO is postulated to be the stabilization of a (bpy)(NMI)Cu(II) -O2 (⋅-) -TEMPO (bpy=2,2'-bipyridine, NMI=N-methylimidazole) intermediate formed by electron transfer from Cu(I) to molecular O2 . PMID:26174141

  9. 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.

  10. ATR-FTIR spectroscopy reveals polycyclic aromatic hydrocarbon contamination despite relatively pristine site characteristics: Results of a field study in the Niger Delta.

    Science.gov (United States)

    Obinaju, Blessing E; Martin, Francis L

    2016-01-01

    Fourier-transform infrared (FTIR) spectroscopy is an emerging technique to detect biochemical alterations in biological tissues, particularly changes due to sub-lethal exposures to environmental contaminants. We have previously shown the potential of attenuated total reflection FTIR (ATR-FTIR) spectroscopy to detect real-time exposure to contaminants in sentinel organisms as well as the potential to relate spectral alterations to the presence of specific environmental agents. In this study based in the Niger Delta (Nigeria), changes occurring in fish tissues as a result of polycyclic aromatic hydrocarbon (PAH) exposure at contaminated sites are compared to the infrared (IR) spectra of the tissues obtained from a relatively pristine site. Multivariate analysis revealed that PAH contamination could be occurring at the pristine site, based on the IR spectra and significant (P<0.0001) differences between sites. The study provides evidence of the IR spectroscopy techniques' sensitivity and supports their potential application in environmental biomonitoring. PMID:26826366

  11. El cuento de la verdad "El cuento de la verdad "El cuento de atrás" y "El lápiz del carpintero"

    OpenAIRE

    Bazán Rodríguez, Óscar

    2012-01-01

    Uno de los puntos claves que se ha venido trabajando en la literatura española contemporánea es el tratamiento de la memoria, y dentro de este tema, cómo se afronta un concepto tan inasible como el del “la verdad” desde un punto de vista narrativo. En este artículo nos aproximamos a la visión de “la verdad” a través de dos de las novelas más importantes que tocan la Guerra Civil española: “El cuarto de atrás”, de Carmen Martín Gaite; y “El lápiz del carpintero”, de Manuel Rivas...

  12. FTIR-ATR study of the influence of the pyrimidine analog of fluphenazine on the chain-melting phase transition of sphingomyelin membranes

    Science.gov (United States)

    Kuć, Marta; Cieślik-Boczula, Katarzyna; Świątek, Piotr; Jaszczyszyn, Agata; Gąsiorowski, Kazimierz; Malinka, Wiesław

    2015-09-01

    The membrane perturbing potency of the highly effective anti-multidrug resistance (MDR) pyrimidine analog of fluphenazine (FPh-prm), has been studied using attenuated total reflectance Fourier-transfer infrared spectroscopy (FTIR-ATR). The temperature- and FPh-prm-dose-dependent evolutions of the infrared spectra of FPh-prm/sphingomyelin (SM) mixtures were analyzed using principal component analysis (PCA). It has been postulated that the distinct anti-MDR activity of FPh-prm could be related to its ability to affect the modification of SM membranes. A reduction in the temperature of the chain-melting phase transition was observed in FPh-prm-mixed SM membranes together with the loosing of the phase transition cooperativity. Increasing the temperature led to the trans to gauche isomerization of FPh-prm-rich lipid membranes, which resulted in the gradual release of FPh-prm from the lipid membrane to the water phase.

  13. 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.

  14. Microbial inhibitors of cysteine proteases.

    Science.gov (United States)

    Kędzior, Mateusz; Seredyński, Rafał; Gutowicz, Jan

    2016-08-01

    Cysteine proteases are one of the major classes of proteolytic enzymes involved in a number of physiological and pathological processes in plants, animals and microorganisms. When their synthesis, activity and localization in mammalian cells are altered, they may contribute to the development of many diseases, including rheumatoid arthritis, osteoporosis and cancer. Therefore, cysteine proteases have become promising drug targets for the medical treatment of these disorders. Inhibitors of cysteine proteases are also produced by almost every group of living organisms, being responsible for the control of intracellular proteolytic activity. Microorganisms synthesize cysteine protease inhibitors not only to regulate the activity of endogenous, often virulent enzymes, but also to hinder the host's proteolytic defense system and evade its immune responses against infections. Present work describes known to date microbial inhibitors of cysteine proteases in terms of their structure, enzyme binding mechanism, specificity and pathophysiological roles. The overview of both proteinaceous and small-molecule inhibitors produced by all groups of microorganisms (bacteria, archaea, fungi, protists) and viruses is provided. Subsequently, possible applications of microbial inhibitors in science, medicine and biotechnology are also highlighted. PMID:27048482

  15. Electrochemical studies of corrosion inhibitors

    Science.gov (United States)

    Danford, M. D.

    1990-01-01

    The effect of single salts, as well as multicomponent mixtures, on corrosion inhibition was studied for type 1010 steel; for 5052, 1100, and 2219-T87 aluminum alloys; and for copper. Molybdate-containing inhibitors exhibit an immediate, positive effect for steel corrosion, but an incubation period may be required for aluminum before the effect of a given inhibitor can be determined. The absence of oxygen was found to provide a positive effect (smaller corrosion rate) for steel and copper, but a negative effect for aluminum. This is attributed to the two possible mechanisms by which aluminum can oxidize. Corrosion inhibition is generally similar for oxygen-rich and oxygen-free environments. The results show that the electrochemical method is an effective means of screening inhibitors for the corrosion of single metals, with caution to be exercised in the case of aluminum.

  16. Corrosion inhibitors from expired drugs.

    Science.gov (United States)

    Vaszilcsin, Nicolae; Ordodi, Valentin; Borza, Alexandra

    2012-07-15

    This paper presents a method of expired or unused drugs valorization as corrosion inhibitors for metals in various media. Cyclic voltammograms were drawn on platinum in order to assess the stability of pharmaceutically active substances from drugs at the metal-corrosive environment interface. Tafel slope method was used to determine corrosion rates of steel in the absence and presence of inhibitors. Expired Carbamazepine and Paracetamol tablets were used to obtain corrosion inhibitors. For the former, the corrosion inhibition of carbon steel in 0.1 mol L(-1) sulfuric acid solution was about 90%, whereas for the latter, the corrosion inhibition efficiency of the same material in the 0.25 mol L(-1) acetic acid-0.25 mol L(-1) sodium acetate buffer solution was about 85%. PMID:22561212

  17. Positron emitter labeled enzyme inhibitors

    International Nuclear Information System (INIS)

    This invention involves a new strategy for imagining 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 inactivators 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

  18. Less-toxic corrosion inhibitors

    Science.gov (United States)

    Humphries, T. S.

    1981-01-01

    Combinations of borates, nitrates, phosphates, silicates, and sodium MBT protect aluminum from corrosion in fresh water. Most effective combinations contained sodium phosphate and were alkaline. These inhibitors replace toxic chromates which are subject to governmental restrictions, but must be used in larger quantities. Experimental exposure times varied from 1 to 14 months depending upon nature of submersion solution.

  19. 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...

  20. PDE-5 inhibitors: clinical points.

    Science.gov (United States)

    Doumas, Michael; Lazaridis, Antonios; Katsiki, Niki; Athyros, Vasilios

    2015-01-01

    Erectile dysfunction is usually of vascular origin and is frequently encountered in men with cardiovascular disease. The introduction of phosphodiesterase-5 inhibitors has revolutionized the management of patients with erectile dysfunction. Currently available phosphodiesterase-5 inhibitors have distinct pharmacokinetic and pharmacodynamic properties, thus permitting for tailoring sexual therapy according to patient characteristics and needs. Phosphodiesterase-5 inhibitors possess vasorelaxing properties and exert systemic hemodynamic effects, which need to be taken into account when other cardiovascular drugs are co-administered. Special caution is needed with alpha-blockers, while the co-administration with nitrates is contra-indicated due to the risk of life-threatening hypotension. This review presents the advent of sexual therapy, describes the mechanism of action and the specific characteristics of commercially available phosphodiesterase-5 inhibitors, summarizes the efficacy and safety of these drugs with special emphasis on the cardiovascular system, and discusses the clinical criteria used for the selection of each drug for the individual patient. PMID:25392015

  1. Retroviral proteinases and their inhibitors

    Czech Academy of Sciences Publication Activity Database

    Sedláček, Juraj

    2000-01-01

    Roč. 3, 3,4 (2000), s. 23-24. [Proteolytic enzymes and their inhibitors in physiology and pathogenesis.. 14.09.2000, Plzen] Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology

  2. Corrosion Inhibitors for Reinforced Concrete

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    Steel corrosion in reinforced concrete structures has been a major problem across the U.S. Steel-reinforced concrete structures are continually subject to attack by corrosion brought on by naturally occurring environmental conditions. FerroGard, a corrosion inhibitor, developed by Sika Corporation, penetrates hardened concrete to dramatically reduce corrosion by 65% and extend the structure's service life.

  3. Biocatalysts with enhanced inhibitor tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shihui; Linger, Jeffrey; Franden, Mary Ann; Pienkos, Philip T.; Zhang, Min

    2015-12-08

    Disclosed herein are biocatalysts for the production of biofuels, including microorganisms that contain genetic modifications conferring tolerance to growth and fermentation inhibitors found in many cellulosic feedstocks. Methods of converting cellulose-containing materials to fuels and chemicals, as well as methods of fermenting sugars to fuels and chemicals, using these biocatalysts are also disclosed.

  4. 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 Study

  5. Lipoxygenase inhibitor peptides and their use

    OpenAIRE

    Schurink, M.; Boeriu, C.G.; Berkel, van, A.M.; Wichers, H.J.

    2006-01-01

    The present invention is in the field of enzyme inhibition. In particular it relates to peptide inhibitors for lipoxygenases. The lipoxygenase peptide inhibitors of have the potential to be used as therapeutic drugs as well as food preservatives.

  6. Observation of chemical modification of Asian Dust particles during long-range transport by the combined use of quantitative ED-EPMA and ATR-FT-IR imaging

    Directory of Open Access Journals (Sweden)

    Young-Chul Song

    2012-10-01

    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 FT-IR (ATR-FT-IR imaging has great potential for a detailed characterization of individual aerosol particles. In this study, individual Asian Dust particles collected during an Asian Dust storm event on 11 November 2011 in Korea were characterized by the combined use of low-Z particle EPMA and ATR-FT-IR imaging. The combined use of the two single-particle analytical techniques on the same individual particles showed that Asian Dust particles had experienced extensive chemical modification during long-range transport. 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 field observations of CaCl2 particles converted from CaCO3 for the Asian Dust sample collected in the planetary boundary layer. Thirty three particles contained NaNO3, which are the reaction products of sea-salt and NOx/HNO3, whereas no genuine sea-salt particles were encountered, indicating that sea-salt particles

  7. 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)

  8. Mangrove dolabrane-type of diterpenes tagalsins suppresses tumor growth via ROS-mediated apoptosis and ATM/ATR-Chk1/Chk2-regulated cell cycle arrest.

    Science.gov (United States)

    Neumann, Jennifer; Yang, Yi; Köhler, Rebecca; Giaisi, Marco; Witzens-Harig, Mathias; Liu, Dong; Krammer, Peter H; Lin, Wenhan; Li-Weber, Min

    2015-12-01

    Natural compounds are an important source for drug development. With an increasing cancer rate worldwide there is an urgent quest for new anti-cancer drugs. In this study, we show that a group of dolabrane-type of diterpenes, collectively named tagalsins, isolated from the Chinese mangrove genus Ceriops has potent cytotoxicity on a panel of hematologic cancer cells. Investigation of the molecular mechanisms by which tagalsins kill malignant cells revealed that it induces a ROS-mediated damage of DNA. This event leads to apoptosis induction and blockage of cell cycle progression at S-G2 phase via activation of the ATM/ATR-Chk1/Chk2 check point pathway. We further show that tagalsins suppress growth of human T-cell leukemia xenografts in vivo. Tagalsins show only minor toxicity on healthy cells and are well tolerated by mice. Our study shows a therapeutic potential of tagalsins for the treatment of hematologic malignancies and a new source of anticancer drugs. PMID:26061604

  9. 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.)

  10. The effect of calcium ions and sodium silicate on the adsorption of a model anionic flotation collector on magnetite studied by ATR-FTIR spectroscopy.

    Science.gov (United States)

    Potapova, E; Grahn, M; Holmgren, A; Hedlund, J

    2010-05-01

    Previous studies have shown that agglomeration of the magnetite concentrate after reverse flotation of apatite is negatively affected by the collector species adsorbed on the surface of magnetite. In this work, the effect of ionic strength, calcium ions and sodium silicate on the unwanted adsorption of a model anionic flotation collector on synthetic magnetite was studied in situ using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The amount of collector adsorbed was found to increase with increasing ionic strength at pH 8.5 providing evidence to the contribution of electrostatic forces to the adsorption of the collector. Adding sodium silicate to the system resulted in a threefold decrease in the amount of collector adsorbed compared to when no sodium silicate was added, confirming the depressing activity of sodium silicate on magnetite. Calcium ions were shown to increase the adsorption of both the collector and sodium silicate on magnetite. The depressing effect of sodium silicate on collector adsorption was completely suppressed in the presence of calcium ions under the conditions studied. Furthermore, the amount of collector adsorbed on magnetite from the silicate-collector solution increased 14 times upon addition of calcium ions suggesting that calcium ions in the process water may increase undesired adsorption of the collector on the iron oxide. PMID:20153478

  11. Surficial Siloxane-to-Silanol Interconversion during Room-Temperature Hydration/Dehydration of Amorphous Silica Films Observed by ATR-IR and TIR-Raman Spectroscopy.

    Science.gov (United States)

    Warring, Suzanne L; Beattie, David A; McQuillan, A James

    2016-02-16

    Silica has been frequently studied using infrared and Raman spectroscopy due to its importance in many practical contexts where its surface chemistry plays a vital role. The majority of these studies have utilized chemical-vapor-deposited films in vacuo after high-temperature calcination. However, room-temperature hydration and dehydration of thin silica particle films has not been well characterized in spite of the importance of such films as substrates for polymer and surfactant adsorption. The present study has utilized ATR-IR spectroscopy and thin silica particle films exposed to varying humidity to clearly show reversible conversion between surface siloxanes and hydrogen-bonded silanols without the need for semiempirical peak deconvolution. The IR spectra from corresponding hydration experiments on deuterated silica films has confirmed the vibrational mode assignments. The variation of humidity over silica films formed from silica suspensions of differing pH gave IR spectra consistent with the change in the relative populations of siloxide to silanol surface groups. In addition, total internal reflection Raman spectroscopy has been used to provide further evidence of room-temperature dehydroxylation, with spectral evidence for the presence of three-membered siloxane rings when films are dehydrated under argon. The confirmation of room-temperature siloxane-to-silanol interconversion is expected to benefit understanding in many silica surface chemical contexts. PMID:26804934

  12. 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.

  13. In situ ATR-IR spectroscopy study of adsorbed protein: Visible light denaturation of bovine serum albumin on TiO2

    Science.gov (United States)

    Bouhekka, A.; Bürgi, T.

    2012-11-01

    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 TiO2 films. The experiments were performed in water at concentrations of 10-6 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-1 to 1648 cm-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 α-helix decreases during visible light illumination whereas the percentage of random coil increases.

  14. Noninvasive detection by ATR and NIR-DR methods for skin-care ionic materials transported into the skin by iontophoresis

    Science.gov (United States)

    Ueda, Toyotoshi; Watanabe, Yukio; Akao, Ken-ichi; Suzuki, Harue

    2003-12-01

    Two analytical methods without damage to the skin were proposed in order to detect and measure the quantity of the medication transported into the skin by the iontophoresis. The infrared attenuated total reflection (ATR) method was proven to be able to evaluate the content of such a substance as sodium all- trans-retinoate or magnesium ℓ-ascorbyl-2-phosphate in the top (horny) layer of epidermis (about 1 μm under the skin surface), using characteristic bands to the above ion. Another method of near-infrared diffusive-reflection (NIR-DR) technique was shown probably to detect it in the dermis (1 mm under the surface), based on the shift of frequency and the change in intensity for the vibrational combination band of water molecules hydrating the ion. The quantity of the above material decreased monotonically in the horny layer for several hours after the treatment, while in the dermis it increased at first and then decreased via the maximum value.

  15. Kinase Inhibitors from Marine Sponges

    Directory of Open Access Journals (Sweden)

    Ana Zivanovic

    2011-10-01

    Full Text Available Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included.

  16. Thrombin Inhibitors from Different Animals

    OpenAIRE

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

    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 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 dev...

  17. Natural Products as Aromatase Inhibitors

    OpenAIRE

    Balunas, Marcy J.; Su, Bin; Brueggemeier, Robert W.; Kinghorn, A. Douglas

    2008-01-01

    With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating also the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purpos...

  18. ACE INHIBITORS: A COMPREHENSIVE REVIEW

    OpenAIRE

    Pradeep Kumar Arora* and Ashish Chauhan

    2013-01-01

    Hypertension is a chronic increase in blood pressure, characterized as primary and secondary hypertension. The disorder is associated with various risk factors like obesity, diabetes, age, lack of exercise etc. Hypertension is being treated since ancient times by Ayurvedic, Chinese and Unani medicine. Now various allopathic drugs are available which include diuretics, calcium channel blockers, α-blockers, β-blockers, vasodilators, central sympatholytics and ACE-inhibitors. Non-pharmacological...

  19. Carbonic anhydrase inhibitors drug design.

    Science.gov (United States)

    McKenna, Robert; Supuran, Claudiu T

    2014-01-01

    Inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) has pharmacologic applications in the field of antiglaucoma, anticonvulsant, antiobesity, and anticancer agents but is also emerging for designing anti-infectives (antifungal and antibacterial agents) with a novel mechanism of action. As a consequence, the drug design of CA inhibitors (CAIs) is a very dynamic field. Sulfonamides and their isosteres (sulfamates/sulfamides) constitute the main class of CAIs which bind to the metal ion in the enzyme active site. Recently the dithiocarbamates, possessing a similar mechanism of action, were reported as a new class of inhibitors. Other families of CAIs possess a distinct mechanism of action: phenols, polyamines, some carboxylates, and sulfocoumarins anchor to the zinc-coordinated water molecule. Coumarins and five/six-membered lactones are prodrug inhibitors, binding in hydrolyzed form at the entrance of the active site cavity. Novel drug design strategies have been reported principally based on the tail approach for obtaining all these types of CAIs, which exploit more external binding regions within the enzyme active site (in addition to coordination to the metal ion), leading thus to isoform-selective compounds. Sugar-based tails as well as click chemistry were the most fruitful developments of the tail approach. Promising compounds that inhibit CAs from bacterial and fungal pathogens, of the dithiocarbamate, phenol and carboxylate types have also been reported. PMID:24146385

  20. Bromodomains and their pharmacological inhibitors.

    Science.gov (United States)

    Gallenkamp, Daniel; Gelato, Kathy A; Haendler, Bernard; Weinmann, Hilmar

    2014-03-01

    Over 60 bromodomains belonging to proteins with very different functions have been identified in humans. Several of them interact with acetylated lysine residues, leading to the recruitment and stabilization of protein complexes. The bromodomain and extra-terminal domain (BET) proteins contain tandem bromodomains which bind to acetylated histones and are thereby implicated in a number of DNA-centered processes, including the regulation of gene expression. The recent identification of inhibitors of BET and non-BET bromodomains is one of the few examples in which effective blockade of a protein-protein interaction can be achieved with a small molecule. This has led to major strides in the understanding of the function of bromodomain-containing proteins and their involvement in diseases such as cancer and inflammation. Indeed, BET bromodomain inhibitors are now being clinically evaluated for the treatment of hematological tumors and have also been tested in clinical trials for the relatively rare BRD-NUT midline carcinoma. This review gives an overview of the newest developments in the field, with a focus on the biology of selected bromodomain proteins on the one hand, and on reported pharmacological inhibitors on the other, including recent examples from the patent literature. PMID:24497428

  1. 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.

  2. The burden of inhibitors in haemophilia patients.

    Science.gov (United States)

    Walsh, Christopher E; Jiménez-Yuste, Víctor; Auerswald, Guenter; Grancha, Salvador

    2016-08-31

    The burden of disease in haemophilia patients has wide ranging implications for the family and to society. There is evidence that having a current inhibitor increases the risk of morbidity and mortality. Morbidity is increased by the inability to treat adequately and its consequent disabilities, which then equates to a poor quality of life compared with non-inhibitor patients. The societal cost of care, or `burden of inhibitors', increases with the ongoing presence of an inhibitor. Therefore, it is clear that successful eradication of inhibitors by immune tolerance induction (ITI) is the single most important milestone one can achieve in an inhibitor patient. The type of factor VIII (FVIII) product used in ITI regimens varies worldwide. Despite ongoing debate, there is in vitro and retrospective clinical evidence to support the use of plasma-derived VWF-containing FVIII concentrates in ITI regimens in order to achieve early and high inhibitor eradication success rates. PMID:27528280

  3. Xylanase inhibitors bind to nonstarch polysaccharides.

    Science.gov (United States)

    Fierens, Ellen; Gebruers, Kurt; Courtin, Christophe M; Delcour, Jan A

    2008-01-23

    This study is an in-depth investigation of the interaction between polysaccharides and the proteinaceous xylanase inhibitors, Triticum aestivum xylanase inhibitor (TAXI), xylanase inhibitor protein (XIP), and thaumatin-like xylanase inhibitor (TLXI). The binding affinities of all three known types of xylanase inhibitors from wheat are studied by measuring the residual xylanase inhibition activity after incubation of the inhibitors in the presence of different polysaccharides, such as beta-glucans and (arabino)xylans. The binding affinities of all three xylanase inhibitors for (arabino)xylans increased with a decreasing arabinose/xylose ratio (A/X ratio). This phenomenon was observed both with water-extractable and water-unextractable (arabino)xylans. The inhibitors also interacted with different soluble and insoluble beta-glucans. None of the inhibitors tested had the ability to hydrolyze the polysaccharides investigated. The present findings contribute to the unraveling of the function of xylanase inhibitors in nature and to the prediction of the effect of added xylanases in cereal-based biotechnological processes, such as bread making and gluten-starch separation. PMID:18092758

  4. 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

  5. Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luis Eduardo Bravo

    2008-03-01

    Full Text Available 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

  6. In situ ATR-IR spectroscopy study of adsorbed protein: Visible light denaturation of bovine serum albumin on TiO2

    International Nuclear Information System (INIS)

    Highlights: ► We study the behavior of BSA protein adsorbed on TiO2 using in situ IR spectroscopy. ► We examine the secondary structure changes during light exposure. ► Visible light illumination creates random coil in the secondary structure of BSA. ► The denaturation of BSA adsorbed on TiO2 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 TiO2 films. The experiments were performed in water at concentrations of 10−6 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−1 to 1648 cm−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 α-helix decreases during visible light illumination whereas the percentage of random coil increases.

  7. Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity

    OpenAIRE

    Miroslav Pohanka

    2014-01-01

    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. Thi...

  8. 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...

  9. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors

    OpenAIRE

    Tan, Li; Wang, Jun; Tanizaki, Junko; Huang, Zhifeng; Aref, Amir R.; Rusan, Maria; Zhu, Su-Jie; Zhang, Yiyun; Ercan, Dalia; Liao, Rachel G.; Capelletti, Marzia; Zhou, Wenjun; Hur, Wooyoung; Kim, NamDoo; Sim, Taebo

    2014-01-01

    Inhibitors of the FGF receptors (FGFRs) are currently under clinical investigation for the treatment of various cancers. All currently approved kinase inhibitors eventually are rendered useless by the emergence of drug-resistant tumors. We used structure-based drug design to develop the first, to our knowledge, selective, next-generation covalent FGFR inhibitors that can overcome the most common form of kinase inhibitor resistance, the mutation of the so-called “gatekeeper” residue located in...

  10. 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

  11. The direct thrombin inhibitor hirudin.

    Science.gov (United States)

    Greinacher, Andreas; Warkentin, Theodore E

    2008-05-01

    This review discusses the pharmacology and clinical applications of hirudin, a bivalent direct thrombin inhibitor (DTI). Besides the current major indication for hirudin--anticoagulation of patients with heparin-induced thrombocytopenia (HIT)--the experience with hirudin in other indications, especially acute coronary syndromes, are briefly presented. Hirudins have been formally studied prior to their regulatory approval; however, important information on their side effects and relevant preventative measures only became available later. Therefore, current recommendations and dosing schedules for hirudin differ considerably from the information given in the package inserts. Drawbacks of hirudin and important precautions for avoiding potential adverse effects are discussed in detail in the third part of this review. PMID:18449411

  12. Angiotensin converting enzyme inhibitor induced hyperkalaemic paralysis

    OpenAIRE

    Dutta., D; Fischler, M; McClung, A

    2001-01-01

    Secondary hyperkalaemic paralysis is a rare condition often mimicking the Guillain-Barré syndrome. There have been a few case reports of hyperkalaemia caused by renal failure, trauma, and drugs where the presentation has been with muscle weakness. A case of hyperkalaemic paralysis caused by an angiotensin converting enzyme inhibitor is reported.


Keywords: hyperkalaemia; paralysis; ACE inhibitors

  13. Screening for potential inhibitors of influenza neuraminidase

    Institute of Scientific and Technical Information of China (English)

    Ai-linLIU; Guan-huaDU

    2004-01-01

    AIM: Applying the assay method of neuraminidase(NA) activity established for high throughput screening to find novel inhibitors of influenza virus NA. METHODS: Firstly, a virtual screening strategy was applied to our compound database to select drug-like compounds, and then a high throughput screening model of NA inhibitor was applied to test these compounds. RESULTS:

  14. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

    Directory of Open Access Journals (Sweden)

    Ververis K

    2013-02-01

    Full Text Available Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Histone deacetylase (HDAC inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza and depsipeptide (romidepsin, Istodax. More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the

  15. 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...

  16. [Recent development of selective cyclooxygenase-2 inhibitors].

    Science.gov (United States)

    Kawai, Shinichi

    2002-12-01

    Nonsteroidal anti-inflammatory drugs(NSAIDs) are clinically effective against the inflammatory symptoms of rheumatoid arthritis. Recent attention has been focused on selective cyclooxygenase(COX)-2 inhibitors, a type of NSAID that inhibits a subtype of COX. Because of the different actions of COX-1 and COX-2, selective COX-2 inhibitors were expected to reduce adverse reactions such as gastrointestinal disorders. Various clinical studies have confirmed that the efficacy of COX-2 inhibitors for RA is similar to that of conventional NSAIDs, but they cause fewer severe gastrointestinal disorders. The incidence of complications related to renal dysfunction, such as edema and hypertension, is not different. Patients using selective COX-2 inhibitors have recently been reported to show an increase in thrombotic complications such as myocardial infarction. Therefore, more data on adverse events should be collected in the future from large-scale clinical studies to further clarify the actual value of selective COX-2 inhibitors. PMID:12510364

  17. 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...... specific inhibitor of uPA. With the aim of creating better inhibitors based on the upain-2 scaffold, the following three strategies were explored: First, it was attempted to predefine the structure of upain-2 in solution by incorporating turn-inducing sequences and peptidomimetics. Additionally...... 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...

  18. 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 products for dairy and beef cattle.

  19. 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...

  20. Análisis comparativo para la búsqueda de un patrón en la realización de un doble mortal atrás con pirueta de salida en anillas

    OpenAIRE

    Miralles, K.; García, M.; Navarro, E

    2003-01-01

    El presente estudio ha sido realizado gracias a la colaboración del INEF de Madrid con el Equipo Nacional de Gimnasia Artística. Empleando fotogrametría tridimensional se ha comparado la técnica de ejecución de un doble mortal atrás con pirueta de salida en anillas de 3 gimnastas. El patrón de eficacia que vamos a utilizar la nota que el entrenador, haciendo las veces de juez, va a determinar, así catalogamos en un primer momento las ejecuciones analizadas. Como premisas supone...

  1. 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.

  2. Ablation of burned skin with ultra-short pulses laser to promote healing: evaluation by optical coherence tomography, histology, μATR-FTIR and Nonlinear Microscopy

    International Nuclear Information System (INIS)

    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 (λ = 785 nm, 90 fs, 2 kHz and 10 μJ/ 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 (μ-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 of

  3. 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

    2008-01-01

    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. Ataxia-te

  4. 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...

  5. VEGF Inhibitors for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Prakash S. Sukhramani

    2010-01-01

    Full Text Available Despite significant advances in systemic therapies, radiation oncology, and surgical techniques, many patients with cancer are still incurable. A novel therapeutic approach has been to target the vascular endothelial growth factors (VEGFs which are often mutated and/or over-expressed in many tumors. The ligands and receptors of VEGF family are well established as key regulators of angiogenesis and vasculogenesis processes. VEGF is a homodimeric, basic, 45 kDa glycoprotein specific for vascular endothelial cells. Specifically, VEGF participates in regulation of the female reproductive cycle, wound healing, inflammation, vascular permeability, vascular tone, hematopoiesis and also contributes to pathological angiogenesis disorders such as cancer, rheumatoid arthritis, diabetic retinopathy and the neovascular form of macular degeneration. Thus, the role of VEGF has been extensively studied in the pathogenesis and angiogenesis of human cancers. Clinical trials have anti-VEGF therapies are effective in reducing tumor size, metastasis and blood vessel formation. Clinically, this may result in increased progression free survival, overall patient survival rate and will expand the potential for combinatorial therapies. The aim of present review is on the cellular responses of VEGF inhibitors and their implications for cancer therapy.

  6. 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.

  7. Molecular Docking of Aromatase Inhibitors

    Directory of Open Access Journals (Sweden)

    Virapong Prachayasittikul

    2011-04-01

    Full Text Available Aromatase is an enzyme that plays a critical role in the development of estrogen receptor positive breast cancer. As aromatase catalyzes the aromatization of androstenedione to estrone, a naturally occurring estrogen, it is a promising drug target for therapeutic management. The undesirable effects found in aromatase inhibitors (AIs that are in clinical use necessitate the discovery of novel AIs with higher selectivity, less toxicity and improving potency. In this study, we elucidate the binding mode of all three generations of AI drugs to the crystal structure of aromatase by means of molecular docking. It was demonstrated that the docking protocol could reliably reproduce the interaction of aromatase with its substrate with an RMSD of 1.350 Å. The docking study revealed that polar (D309, T310, S478 and M374, aromatic (F134, F221 and W224 and non-polar (A306, A307, V370, L372 and L477 residues were important for interacting with the AIs. The insights gained from the study herein have great potential for the design of novel AIs.

  8. 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.

  9. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    Small-molecule kinase inhibitors are invaluable targeted therapeutics for the treatment of various human diseases, especially cancers. While the majority of approved and developed preclinical small-molecule inhibitors are characterized as type I or type II inhibitors that target the ATP......-binding pocket of kinases, the remarkable sequential and structural similarity among ATP pockets renders the selective inhibition of kinases a daunting challenge. Therefore, targeting allosteric pockets of kinases outside the highly conversed ATP pocket has been proposed as a promising alternative to overcome...

  10. 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.

  11. Use of total internal reflection Raman (TIR) and attenuated total reflection infrared (ATR-IR) spectroscopy to analyze component separation in thin offset ink films after setting on coated paper surfaces.

    Science.gov (United States)

    Kivioja, Antti; Hartus, Timo; Vuorinen, Tapani; Gane, Patrick; Jääskeläinen, Anna-Stiina

    2013-06-01

    The interactive behavior of ink constituents with porous substrates during and after the offset print process has an important effect on the quality of printed products. To help elucidate the distribution of ink components between the retained ink layer and the substrate, a variety of spectroscopic and microscopic analysis techniques have been developed. This paper describes for the first time the use of total internal reflection (TIR) Raman spectroscopy to analyze the penetration behavior of separated offset ink components (linseed oil, solid color pigment) in coated papers providing chemically intrinsic information rapidly, nondestructively, and with minimal sample preparation. In addition, the already widely applied technique of attenuated total reflection infrared spectroscopy (ATR-IR) was evaluated in parallel and compared. The results of the ATR-IR Raman clearly revealed an improvement in uppermost depth resolution compared with values previously published from other nondestructive techniques, and the method is shown to be capable of providing new knowledge of the setting of thin (0.25-2 μm) offset ink films, allowing the spreading and the penetration behavior on physically different paper coating surfaces to be studied. PMID:23735252

  12. 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 of......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...... intermediates. For Pt/Al2O3, lowering the pH induced the increasing surface coverage of key reaction intermediates like NOsteps1620cm−1 and “HNO”(ads)1540cm−1, as well as increased hydrogenation rates, explaining the higher TOF at lower pH as reported in the literature. For Pd/Al2O3, the effect of pH on...

  13. Inhibitors of alanine racemase enzyme: a review.

    Science.gov (United States)

    Azam, Mohammed Afzal; Jayaram, Unni

    2016-08-01

    Alanine racemase is a fold type III PLP-dependent amino acid racemase enzyme catalysing the conversion of l-alanine to d-alanine utilised by bacterial cell wall for peptidoglycan synthesis. As there are no known homologs in humans, it is considered as an excellent antibacterial drug target. The standard inhibitors of this enzyme include O-carbamyl-d-serine, d-cycloserine, chlorovinyl glycine, alaphosphin, etc. d-Cycloserine is indicated for pulmonary and extra pulmonary tuberculosis but therapeutic use of drug is limited due to its severe toxic effects. Toxic effects due to off-target affinities of cycloserine and other substrate analogs have prompted new research efforts to identify alanine racemase inhibitors that are not substrate analogs. In this review, an updated status of known inhibitors of alanine racemase enzyme has been provided which will serve as a rich source of structural information and will be helpful in generating selective and potent inhibitor of alanine racemase. PMID:26024289

  14. Strategies for discontinuation of proton pump inhibitors

    DEFF Research Database (Denmark)

    Haastrup, Peter; Paulsen, Maja S; Begtrup, Luise M;

    2014-01-01

    PURPOSE: Proton pump inhibitors (PPIs) are considered to be overprescribed. Consensus on how to attempt discontinuation is, however, lacking. We therefore conducted a systematic review of clinical studies on discontinuation of PPIs. METHODS: Systematic review based on clinical studies investigating...

  15. Cyanobacterial secondary metabolites as acetylcholinesterase inhibitors

    Czech Academy of Sciences Publication Activity Database

    Zelík, Petr; Masojídek, Jiří; Štys, Dalibor; Kopecký, Jiří

    Kunming : Verlag, 2006, s. 52-53. [International Conference on Applied Phycology /10./. Kunming (CN), 24.07.2005-28.07.2005] Institutional research plan: CEZ:AV0Z50200510 Keywords : cyanobacteria * acetylcholinesterase inhibitors Subject RIV: EE - Microbiology, Virology

  16. Progress and prospects on DENV protease inhibitors.

    Science.gov (United States)

    Timiri, Ajay Kumar; Sinha, Barij Nayan; Jayaprakash, Venkatesan

    2016-07-19

    New treatments are desperately required to combat increasing rate of dengue fever cases reported in tropical and sub-tropical parts of the world. Among the ten proteins (structural and non-structural) encoded by dengue viral genome, NS2B-NS3 protease is an ideal target for drug discovery. It is responsible for the processing of poly protein that is required for genome replication of the virus. Moreover, inhibitors designed against proteases were found successful in Human Immuno-deficiency Virus (HIV) and Hepatitis C Virus (HCV). Complete molecular mechanism and a survey of inhibitors reported against dengue protease will be helpful in designing effective and potent inhibitors. This review provides an insight on molecular mechanism of dengue virus protease and covers up-to-date information on different inhibitors reported against dengue proteases with medicinal chemistry perspective. PMID:27092412

  17. Effects of multiphase flow on corrosion inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y.; Jepson, W.P. [Ohio Univ., Athens, OH (United States); Chen, H.J. [Chevron Petroleum Technology Co., La Habra, CA (United States)

    1999-11-01

    This paper investigates the inhibition performance of a typical imidazoline based inhibitor under multiphase flow. Electrochemical impedance spectroscopy (EIS) measurements were carried out in a 101.6 mm I.D., 15 m long acrylic flow loop using ASTM substitute saltwater and carbon dioxide gas. This flow loop system can generate slug flow, fill pipe flow and other multiphase flow patterns. Effects of different flow conditions on inhibition performance of this typical inhibitor were examined. The system was maintained at a pressure of 0.136 MPa and a temperature of 40 C. EIS measurements for this inhibitor in a Rotating Cylinder Electrode (RCE) system were also conducted. Different equivalent circuit models were used to fit the experiment data for both the RCE and flow loop systems. The high shear stress and turbulence due to the mixing vortex and the bubble impact in multiphase flow can enhance the corrosion or reduce the inhibition performance of inhibitors.

  18. 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.

  19. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity.

    Science.gov (United States)

    Pohanka, Miroslav

    2014-01-01

    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. PMID:24893223

  20. Pharmacophore Identification of Hydroxamate HDAC 1 Inhibitors

    Institute of Scientific and Technical Information of China (English)

    YU,Liqin; LIU,Fei; CHEN,Yadong; YOU,Qidong

    2009-01-01

    A three-dimensional pharmacophore model was established based on 24 hydroxamate histone deacetylase(HDAC)inhibitors by HypoGen algorithm embedded in Catalyst software.The best pharmacophore hypothesis(Hypol),consisting of four chemical features(one hydrogen-bond acceptor,one aromatic ring and two hydrophobicgroups).has a correlation coefficient of 0.946.The Hypol Was also validated by a test set consisting of 20 othercompounds.Compared with the prior studies towards HDAC inhibitors the detailed chemical features of the"CAP"region in the reported HDAC inhibitors were for the first time depicted,which would be helpful in the further de-signing of novel HDAC inhibitors.

  1. 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.

  2. Lipoxygenase inhibitors derived from marine macroalgae.

    Science.gov (United States)

    Kurihara, Hideyuki; Kagawa, Yoshio; Konno, Remi; Kim, Sang Moo; Takahashi, Koretaro

    2014-03-01

    The solvent extracts from the algae Sargassum thunbergii (Sargassaceae) and Odonthalia corymbifera (Rhodomelaceae) were subjected to soybean lipoxygenase inhibitory screening. Two hydrophobic inhibitors were obtained from the extracts of S. thunbergii through inhibitory assay-guided fractionation. The inhibitors were identified as known exo-methylenic alkapolyenes (6Z,9Z,12Z,15Z)-1,6,9,12,15-henicosapentaene (1) and (6Z,9Z,12Z,15Z,18Z)-1,6,9,12,15,18-henicosahexaene (2). The alkapolyenes 1 and 2 showed higher inhibitory activity than the known inhibitor nordihydroguaiaretic acid (NDGA). Pheophytin a (3) was obtained from the extract of O. corymbifera. The inhibitor 3 also showed higher inhibitory activity than NDGA. This is the first report on lipoxygenase inhibition of exo-methylenic alkapolyenes and a chlorophyll a-related substance. PMID:24495846

  3. The Broad Stroke of Hsp90 Inhibitors: Painting over the RAF Inhibitor Paradox.

    Science.gov (United States)

    Vido, Michael J; Aplin, Andrew E

    2015-10-01

    The novel Hsp90 inhibitor XL888 is undergoing clinical investigation for use in conjunction with the rapidly accelerated fibrosarcoma (RAF) kinase inhibitor vemurafenib to treat unresectable melanoma. The addition of XL888 to current regimens may serve an additional purpose by blocking the RAF inhibitor paradox. Such activity could reduce adverse events in patients and provide a biomarker for the successful inhibition of Hsp90 target proteins. PMID:26358385

  4. 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...... plasminogen activators (apparent recovery > 200%). Sodium lauryl sulfate eliminates the major fibrinolytic enzyme inhibitors, but increases the activity of plasmin (apparent recovery > 200%) and plasminogen activator, urokinase type (apparent recovery 130%). Methylamine affects only plasmin inhibition. We...

  5. JAK2 inhibitors: are they the solution?

    OpenAIRE

    Santos, Fabio P S; Verstovsek, Srdan

    2011-01-01

    The discovery of the JAK2V617F mutation in patients with Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) started the era of targeted therapy for these diseases. Until now, patients had few treatment options available, usually restricted to hydroxyurea, interferon preparations, and chemotherapy in more aggressive cases. JAK2 inhibitors have been developed over the past 5 years, and the results of the first clinical trials with JAK2 inhibitors for patients with myelofibros...

  6. Current use of phosphodiesterase inhibitors in urology

    OpenAIRE

    Hakky, Tariq Said; Jain, Lakshay

    2015-01-01

    The causes of male erectile dysfunction (ED) are quite variable and are now commonly divided into etiologies such as ischemia, smooth muscle damage, or altered blood flow. Although varying rates of ED have been reported in literature, the number of men with ED is projected to increase worldwide by 2025 to approximately 322 million. Since the introduction of phosphodiesterase 5 (PDE5) inhibitors, there has been a paradigm shift in the treatment of ED because PDE5 inhibitors address a broad spe...

  7. 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. PMID:27537073

  8. Acquired Factor V Inhibitor: A Case Report

    OpenAIRE

    Gaćina, Petar; Kušec, Rajko; Čaržavec, Dubravka; Raić, Biserka; Stančić, Vladimir

    2006-01-01

    A 19-year-old asymptomatic man who was admitted to our hospital for investigation of prolonged screening coagulation assays, prothrombin time and activated partial thromboplastin time is presented. Further evaluation revealed factor V deficiency and the presence of specific factor V inhibitors. The appearance of these inhibitors may be associated with administration of some antibiotics, topical bovine thrombin preparations containing bovine factor V during surgical or dental procedures, after...

  9. Novel hemagglutinin-based influenza virus inhibitors

    OpenAIRE

    Shen, Xintian; Zhang, Xuanxuan; Liu, Shuwen

    2013-01-01

    Influenza virus has caused seasonal epidemics and worldwide pandemics, which caused tremendous loss of human lives and socioeconomics. Nowadays, only two classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase inhibitors respectively, are used for prophylaxis and treatment of influenza virus infection. Unfortunately, influenza virus strains resistant to one or all of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in influenza virus envelope, plays a c...

  10. Proton pump inhibitors decrease melanogenesis in melanocytes

    OpenAIRE

    Baek, Seung-Hwa; Lee, Sang-Han

    2015-01-01

    Proton pump inhibitors (PPIs) are widely used as inhibitors of gastric juice secretion for treatment of gastroesophageal reflux disease. However, there are no previous studies of the effects on melanogenesis resulting from PPI treatments. Therefore, the aim of the present study was to investigate the effects of PPIs on melanogenesis in melan-a cells derived from immortalized mouse melanocytes. Tyrosinase activity and copper-chelating activity were measured spectrophotometrically. In addition,...

  11. Endogenous angiogenesis inhibitors and their therapeutic implications.

    Science.gov (United States)

    Cao, Y

    2001-04-01

    A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to act specifically on the proliferating endothelial cell compartment of the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but may also provide an important therapeutic strategy for the treatment of cancer and other angiogenesis dependent diseases, including diabetic retinopathy and chronic inflammations. Systemic administration of these angiogenesis inhibitors in animals significantly suppresses the growth of a variety of tumors and their metastases. However, their production as functional recombinant proteins has been proven to be difficult. In addition, high dosages of these inhibitors are required to suppress tumor growth in animal studies. Other disadvantages of the antiangiogenic protein therapy include repeated injections, prolonged treatment, transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative strategies need to be developed in order to improve the clinical settings of antiangiogenic therapy. Developments of these strategies are ongoing and they include identification of more potent inhibitors, antiangiogenic gene therapy, improvement of protein/compound half-lives in the circulation, increase of their concentrations at the disease location, and combinatorial therapies with approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the above-mentioned disadvantages, a few inhibitors have entered into the early stages of clinical trials and

  12. Therapeutic Potential of Monoacylglycerol Lipase Inhibitors

    OpenAIRE

    Mulvihill, Melinda M.; Nomura, Daniel K.

    2012-01-01

    Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown benefitial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects tha...

  13. Interaction of U(VI) with Äspö diorite: A batch and in situ ATR FT-IR sorption study

    International Nuclear Information System (INIS)

    atmosphere. The U species in aqueous solution as well as sorbed on diorite were studied by in situ time-resolved attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy. A predominant sorbing species containing a UO2(CO3)34− moiety was identified. The extent of U sorption onto diorite was found to depend more on the low sorption affinity of the Ca2UO2(CO3)3(aq) complex than on reduction processes of uranium

  14. Natural inhibitors of tumor-associated proteases

    International Nuclear Information System (INIS)

    The turnover and remodelling of extracellular matrix (ECM) is an essential part of many normal biological processes including development, morphogenesis, and wound healing. ECM turnover also occurs in severe pathological situations like artherosclerosis, fibrosis, tumor invasion and metastasis. The major proteases involved in this turnover are serine proteases (especially the urokinase-type plasminogen activator/plasmin system), matrix metalloproteases (a family of about 20 zinc-dependent endopeptidases including collagenases, gelatinases, stromelysins, and membrane-type metalloproteases), and cysteine proteases. In vivo, the activity of these proteases is tightly regulated in the extracellular space by zymogen activation and/or controlled inhibition. In the present review, we give an overview on the structure and biochemical properties of important tumor-associated protease inhibitors such as plasminogen activator inhibitor type 1 and type 2 (PAI-1, PAI-2), tissue inhibitors of metalloproteinases (TIMP-1, -2, -3, and -4), and the cysteine protease inhibitor cystatin C. Interestingly, some of these inhibitors of tumor-associated proteases display multiple functions which rather promote than inhibit tumor progression, when the presence of inhibitors in the tumor tissue is not balanced. (author)

  15. Development of Radiosensitizer using farnesyltransferase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jong Seok; Choe, Yong Kyung; Han, Mi Young; Kim, Kwang Dong [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea)

    1999-03-01

    We selected some compounds that were reported to have an activity of farneyltransferase inhibitor and tested the hypothesis that they might be used to radiosensitize cells transformed by ras oncogenes. The inhibition of ras processing using some, but not all, inhibitors resulted in higher levels of cell death after {gamma}-irradiation and increased radiosensitivity in H-ras-transformed NIH3T3 cells and MCF-10A human tumor cells. They did not induce additional cell death in control cells that doe not have ras mutation. Furthermore, the treatment of inhibitors alone induced a weak G0/G1 block, whereas inhibitors in combination with {gamma}-irradiation induced an additional enrichment in the G2/M phase of the cell cycle that typically represents irradiation-induced growth arrest. At present, the underling mechanism by which the farnesylltransferase inhibitors exert radiosensitizing effect is not known. In summary, our results suggest and lead to the possibility that some of farnesylation inhibitors may prove clinically useful not only as antitumor agents, but also radiosensitizers of tumors whose growth is dependent on ras function. (author). 15 refs., 10 figs., 4 tabs.

  16. Aromatase inhibitors in the treatment of endometriosis.

    Science.gov (United States)

    Słopień, Radosław; Męczekalski, Błażej

    2016-03-01

    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. PMID:27095958

  17. Aromatase inhibitors in the treatment of endometriosis

    Science.gov (United States)

    Męczekalski, Błażej

    2016-01-01

    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. PMID:27095958

  18. 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.

  19. Proteasome inhibitor treatment in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Fawzia Bardag-Gorce

    2011-01-01

    Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements (glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC) were upregulated when rats fed alcohol were treated with a low dose of PS-341 (Bortezomib, Velcade(r)). This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease

  20. SGLT2 Inhibitors and the Diabetic Kidney.

    Science.gov (United States)

    Fioretto, Paola; Zambon, Alberto; Rossato, Marco; Busetto, Luca; Vettor, Roberto

    2016-08-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether

  1. Versatile templates for the development of novel kinase inhibitors: Discovery of novel CDK inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Dwyer, Michael P.; Paruch, Kamil; Alvarez, Carmen; Doll, Ronald J.; Keertikar, Kerry; Duca, Jose; Fischmann, Thierry O.; Hruza, Alan; Madison, Vincent; Lees, Emma; Parry, David; Seghezzi, Wolfgang; Sgambellone, Nicole; Shanahan, Frances; Wiswell, Derek; Guzi, Timothy J. (SPRI)

    2008-06-30

    A series of four bicyclic cores were prepared and evaluated as cyclin-dependent kinase-2 (CDK2) inhibitors. From the in-vitro and cell-based analysis, the pyrazolo[1,5-a]pyrimidine core (represented by 9) emerged as the superior core for further elaboration in the identification of novel CDK2 inhibitors.

  2. Selective cell adhesion inhibitors: Barbituric acid based alpha4beta7--MAdCAM inhibitors.

    Science.gov (United States)

    Harriman, Geraldine C; Brewer, Matthias; Bennett, Robert; Kuhn, Cyrille; Bazin, Marc; Larosa, Greg; Skerker, Paul; Cochran, Nancy; Gallant, Debra; Baxter, Deborah; Picarella, Dominic; Jaffee, Bruce; Luly, Jay R; Briskin, Michael J

    2008-04-01

    A novel series of barbituric acid derivatives were identified as selective inhibitors of alpha4beta7 MAdCAM (mucosal addressin cell adhesion molecule-1) interactions via a high throughput screening exercise. These inhibitors were optimized to submicromolar potencies in whole cell adhesion assays, retaining their selectivity over alpha4beta1 VCAM. PMID:18331794

  3. 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...

  4. 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.

  5. Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR FT-IR) Mapping Coupled with Multivariate Curve Resolution (MCR) for Studying the Miscibility of Chlorobutyl Rubber/Polyamide-12 Blends.

    Science.gov (United States)

    Tang, Yongjiao; Jing, Nan; Zhang, Pudun

    2015-11-01

    A series of chlorobutyl rubber/polyamide-12 (CIIR/PA-12) blends compatibilized by different amounts of maleic anhydride (MAH) grafted polypropylene (PP-g-MAH) were investigated by attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) mapping. Multivariate curve resolution (MCR) was used to process the FT-IR images. Both the spectra of pure components in the blends and their concentration distributions in a micro-region were acquired. Our results demonstrated that the blend with 15 parts per hundred rubber PP-g-MAH showed the best miscibility. An amide interphase and an imide interphase were inferred by analyzing the spectra of MCR component 3 of the blends with and without PP-g-MAH, respectively. Correspondingly, two different compatibilizing mechanisms were proposed for these blends. PMID:26647055

  6. Paraffin wax deposits and chemical inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Mendell, J.L.

    1970-01-01

    Solutions to this problem becomes necessary with the advent of extremely deep production, offshore production, and the probability of ocean-floor completions. The reasons for paraffin-wax accumulations are many and difficult to pinpoint. Inhibition of these paraffin deposits appears to be the best solution. Paraffin solvents and inhibitors are as follows: solvents, wetting agents, dispersants, and crystal modifiers. Solvents are effective, but can harm a refinery catalyst and create health hazards. Wetting agents and dispersants comprise the majority of chemicals used as paraffin wax inhibitors. Crystal modifiers are relatively new and may provide the most efficient means of reducing deposition. Evaluations of chemical paraffin inhibitors are outlined. Field test results which consider the various chemicals tested may give satisfactory results in determining which particular chemical can solve the problem of the particular situation. (38 refs.)

  7. Cough Syncope due to ACE Inhibitor

    Directory of Open Access Journals (Sweden)

    Filiz Koc

    2015-09-01

    Full Text Available Syncope is defined as a transient loss of consciousness due to sudden temporary decline in cerebral perfusion. Cough syncope is classically seen in middle aged obese men with obstructive pulmonary disease. In patients that use Angiotensin converting enzyme (ACE inhibitors, a dry persistent cough can emerge due to the side effects of this medication. Seventy years old male patient that use ACE inhibitor for hypertension accepted to the clinic with the complaint of syncope. A bout of coughing has developed during electroencephalography recording and 10 seconds in duration of subcortical like epileptiform discharges were viewed. The ACE inhibitor the patient was receiving was replaced with calcium channel blocker and no complaint was observed during the follow up period. [Cukurova Med J 2015; 40(3.000: 619-622

  8. Topoisomerase I inhibitors: camptothecins and beyond.

    Science.gov (United States)

    Pommier, Yves

    2006-10-01

    Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme. It is the only known target of the alkaloid camptothecin, from which the potent anticancer agents irinotecan and topotecan are derived. As camptothecins bind at the interface of the TOP1-DNA complex, they represent a paradigm for interfacial inhibitors that reversibly trap macromolecular complexes. Several camptothecin and non-camptothecin derivatives are being developed to further increase anti-tumour activity and reduce side effects. The mechanisms and molecular determinants of tumour response to TOP1 inhibitors are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage. PMID:16990856

  9. Synthesis of amino heterocycle aspartyl protease inhibitors.

    Science.gov (United States)

    Chambers, Rachel K; Khan, Tanweer A; Olsen, David B; Sleebs, Brad E

    2016-06-14

    Aspartyl proteases are important pharmacological targets. Historically aspartyl proteases have been commonly targeted with transition state derived peptidomimetics. The strategy to develop aspartyl protease inhibitors has undertaken a dramatic paradigm shift in the last 10 years. The pharmaceutical industry in 2005 disclosed several scaffolds or "head groups" that prompted the field to move beyond peptidomimetic derived inhibitors. Since the discovery of the first amino heterocycle aspartyl protease inhibitor, the amino hydantoin, industry and academia have positioned themselves for a foothold on the new molecular space, designing a variety of related "head groups". Both the design and synthetic efforts involved in constructing these scaffolds are varied and complex. Here we highlight the synthetic strategies used to access these amino heterocycle scaffolds. PMID:27143279

  10. Functional non-nucleoside adenylyl cyclase inhibitors.

    Science.gov (United States)

    Lelle, Marco; Hameed, Abdul; Ackermann, Lisa-Maria; Kaloyanova, Stefka; Wagner, Manfred; Berisha, Filip; Nikolaev, Viacheslav O; Peneva, Kalina

    2015-05-01

    In this study, we describe the synthesis of novel functional non-nucleoside adenylyl cyclase inhibitors, which can be easily modified with thiol containing biomolecules such as tumour targeting structures. The linkage between inhibitor and biomolecule contains cleavable bonds to enable efficient intracellular delivery in the reductive milieu of the cytosol as well as in the acidic environment within endosomes and lysosomes. The suitability of this synthetic approach was shown by the successful bioconjugation of a poor cell-permeable inhibitor with a cell-penetrating peptide. Additionally, we have demonstrated the excellent inhibitory effect of the compounds presented here in a live-cell Förster resonance energy transfer-based assay in human embryonic kidney cells. PMID:25319071

  11. Drug screening for influenza neuraminidase inhibitors

    Institute of Scientific and Technical Information of China (English)

    LIU; Ailin; CAO; Hongpeng; DU; Guanhua

    2005-01-01

    Neuraminidase (NA) is one of the most important targets to screen the drugs of anti-influenza virus A and B. After virtual screening approaches were applied to a compound database which possesses more than 10000 compound structures, 160 compounds were selected for bioactivity assay, then a High Throughput Screening (HTS) model established for influenza virus NA inhibitors was applied to detect these compounds. Finally, three compounds among them displayed higher inhibitory activities, the range of their IC50 was from 0.1 μmol/L to 3μmol/L. Their structural scaffolds are novel and different from those of NA inhibitors approved for influenza treatment, and will be useful for the design and research of new NA inhibitors. The resuit indicated that the combination of virtual screening with HTS was very significant to drug screening and drug discovery.

  12. Preliminary studies on vigna unguiculata trypsin inhibitor

    International Nuclear Information System (INIS)

    Investigation on the presence of trypsin inhibitor in vigna unguiculata at three stages of ripeness, i.e. as young beans obtained from first harvest usually consumed as vegetable, seed from beans picked two weeks after the first harvest and seed from beans picked four weeks after the first harvest, has been carried out. The conclusion drawn from this experiment showed the existence of trypsin inhibitor at those stages of ripeness. It is found that the older the stage of ripeness the greater the specific activity of trypsin inhibitor. Evidently the heated extract loss its antitryptic activity progressively with increasing heatings periods. Extract heated on a water bath at a constant temperature of 78 deg C during 20, 40 and 60 minutes, loss its antitryptic activity of about 53, 78 and 96% respectively. (author)

  13. Use of acetylcholinesterase inhibitors in Alzheimer's disease.

    Science.gov (United States)

    Moghul, S; Wilkinson, D

    2001-09-01

    Alzheimer's disease is a growing problem in an aging Western world, estimated to have cost the US economy USD 1.75 trillion. Until recently, the management of Alzheimer's disease largely comprised support for the family, nursing care and the use of unlicensed medication to control behavioral disturbances. The three new acetylcholinesterase inhibitors licensed to treat Alzheimer's disease (donepezil, rivastigmine and galantamine) have provided clinicians with a major impetus to their desire to diagnose and treat this lethal disease. Their effects on cognition are proven. More recent work on the effects of acetylcholinesterase inhibitors on behavioral symptoms, activities of daily living and caregiver burden have also been encouraging. Emerging work indicates their likely efficacy in other dementias (e.g., vascular dementia, dementia with Lewy bodies). This review summarizes the evidence concerning the impact of acetylcholinesterase inhibitors in dementia both currently and over the next 5 years. PMID:19811047

  14. Endogenous Matrix-Derived Inhibitors of Angiogenesis

    Directory of Open Access Journals (Sweden)

    Hans Petter Eikesdal

    2010-09-01

    Full Text Available Endogenous inhibitors of angiogenesis are proteins or fragments of proteins that are formed in the body, which can inhibit the angiogenic process. These molecules can be found both in the circulation and sequestered in the extracellular matrix (ECM surrounding cells. Many matrix-derived inhibitors of angiogenesis, such as endostatin, tumstatin, canstatin and arresten, are bioactive fragments of larger ECM molecules. These substances become released upon proteolysis of the ECM and the vascular basement membrane (VBM by enzymes of the tumor microenvironment. Although the role of matrix-derived angiogenesis inhibitors is well studied in animal models of cancer, their role in human cancers is less established. In this review we discuss the current knowledge about these molecules and their potential use as cancer therapeutics and biomarkers.

  15. 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

  16. Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF-κB-Regulated Anti-Apoptosis and p53/PCNA- and ATM/ATR-Chk1/2-Controlled DNA-Damage Response Pathways.

    Science.gov (United States)

    Zhao, Tuo; Tang, Xin; Umeshappa, Channakeshava Sokke; Ma, Hong; Gao, Haijun; Deng, Yulin; Freywald, Andrew; Xiang, Jim

    2016-09-01

    Microgravity has been known to induce cell death. However, its underlying mechanism is less studied. In this study, BL6-10 melanoma cells were cultured in flasks under simulated microgravity (SMG). We examined cell apoptosis, and assessed expression of genes associated with apoptosis and genes regulating apoptosis in cells under SMG. We demonstrate that SMG induces cell morphological changes and microtubule alterations by confocal microscopy, and enhances apoptosis by flow cytometry, which was associated with up- and down-regulation of pro-apoptotic and anti-apoptotic genes, respectively. Moreover, up- and down-regulation of pro-apoptotic (Caspases 3, 7, 8) and anti-apoptotic (Bcl2 and Bnip3) molecules was confirmed by Western blotting analysis. Western blot analysis also indicates that SMG causes inhibition of an apoptosis suppressor, pNF-κB-p65, which is complemented by the predominant localization of NF-κB-p65 in the cytoplasm. SMG also reduces expression of molecules regulating the NF-κB pathway including Uev1A, TICAM, TRAF2, and TRAF6. Interestingly, 10 DNA repair genes are down-regulated in cells exposed to SMG, among which down-regulation of Parp, Ercc8, Rad23, Rad51, and Ku70 was confirmed by Western blotting analysis. In addition, we demonstrate a significant inhibition of molecules involved in the DNA-damage response, such as p53, PCNA, ATM/ATR, and Chk1/2. Taken together, our work reveals that SMG promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF/NF-κB-regulated apoptosis and the p53/PCNA- and ATM/ATR-Chk1/2-controlled DNA-damage response pathways. Thus, our investigation provides novel information, which may help us to determine the cause of negative alterations in human physiology occurring at spaceflight environment. J. Cell. Biochem. 117: 2138-2148, 2016. © 2016 Wiley Periodicals, Inc. PMID:26887372

  17. 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.

  18. Green inhibitors. Rare Earth based systems

    International Nuclear Information System (INIS)

    Lanthanum, Cerium and Samarium chlorides have been investigated as uniform and pitting corrosion inhibitors of AISI 434 and AISI 304 stainless steels and AA 5083 Al-Mg alloy in 3.5% Na Cl aerated aqueous solutions. Their inhibitor power was evaluated by using electrochemical techniques such as Linear and Cyclic Polarisation. In each case, the highest protection degree was found in the solution dropped with 500 ppm of CeCl3. Similar results were obtained for additions of 500 ppm of LaCl3. Scanning Electron Microscopy and Energy Dispersive Spectroscopy allowed us to confirm the cathodic nature of the inhibition process. (Author) 27 refs

  19. 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.

  20. Small Universal Petri Nets with Inhibitor Arcs

    OpenAIRE

    Ivanov, Sergiu; Pelz, Elisabeth; Verlan, Sergey

    2013-01-01

    We investigate the problem of construction of small-size universal Petri nets with inhibitor arcs. We consider four descriptional complexity parameters: the number of places, transitions, inhibitor arcs, and the maximal degree of a transition, each of which we try to minimize. We give six constructions having the following values of parameters (listed in the above order): $(30,34,13,3)$, $(14, 31, 51, 8)$, $(11, 31, 79, 11)$, $(21,25,13,5)$, $(67, 64, 8, 3)$, $(58, 55, 8, 5)$ that improve the...

  1. 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 BACKGROUND: 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. METHODOLOGY AND PRINCIPAL FINDINGS: 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

  2. Pharmacogenomics of tamoxifen and aromatase inhibitors.

    Science.gov (United States)

    Ingle, James N

    2008-02-01

    In selection of therapy for women with breast cancer, the focus has been almost exclusively on the characteristics of the tumor, eg, estrogen receptor (ER) and HER-2. Until recently, essentially no attention has been paid to the host and her genetic makeup as it relates to the metabolism of different drugs. The first real clinical application of pharmacogenetics in breast cancer management relates to tamoxifen's biotransformation to active anticancer metabolites. New information has arisen on the metabolism of tamoxifen to the active metabolite, 4 hydroxy-N-desmethyl-tamoxifen (endoxifen). Endoxifen is a metabolite with antitumor activity and affinity for the ER that is similar to 4-hydroxy-tamoxifen, but 1 that is normally present in substantially higher concentrations. CYP2D6 plays a central role in the metabolism to endoxifen and 1 published study shows that genotypic differences in CYP2D6 and use of CYP2D6 inhibitors has an impact on outcomes of women treated with tamoxifen. The aromatase inhibitors represent a major class of drugs in the armamentarium against breast cancer. The aromatase gene has been resequenced and functional genomics have been performed on the identified nonsynonymous coding single nucleotide polymorphisms showing significant decreases in levels of activity. These findings are consistent with a hypothesis that genetic variation in the CYP19 gene might be important in the activity of aromatase inhibitors. Currently, the emphasis is on examining multiple genes (thus pharmacogenomics) in pharmacodynamic and pharmacokinetic pathways in women receiving aromatase inhibitors for breast cancer. PMID:18072234

  3. Quinazolines as cyclin dependent kinase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sielecki, Thais M.; Johnson, Tricia L.; Liu, Jie; Muckelbauer, Jodi K.; Grafstrom, Robert H.; Cox, Sarah; Boylan, John; Burton, Catherine R.; Chen, Haiying; Smallwood, Angela; Chang, Chong-Hwan; Boisclair, Michael; Benfield, Pamela A.; Trainor, George L.; Seitza, Steven P. (Dupont)

    2010-03-08

    Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.

  4. Proton pump inhibitors for irritable infants

    OpenAIRE

    Smith, Christine H.; Israel, David M.; Schreiber, Richard; Goldman, Ran D.

    2013-01-01

    Question Crying is common in infants; however, caring for infants with inconsolable crying, previously also known as colic or reflux, is often extremely distressing for parents. Is there a benefit to using gastric acid suppression (eg, proton pump inhibitors [PPIs]) in these infants?

  5. Polyphenolic Compounds as Pancreatic Lipase Inhibitors.

    Science.gov (United States)

    Buchholz, Tina; Melzig, Matthias F

    2015-07-01

    Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion. PMID:26132857

  6. Carborane-based carbonic anhydrase inhibitors

    Czech Academy of Sciences Publication Activity Database

    Brynda, Jiří; Mader, Pavel; Šícha, Václav; Fábry, Milan; Poncová, Kristýna; Bakardjiev, Mario; Grüner, Bohumír; Cígler, Petr; Řezáčová, Pavlína

    2013-01-01

    Roč. 52, č. 51 (2013), s. 13760-13763. ISSN 1433-7851 R&D Projects: GA TA ČR(CZ) TE01020028; GA AV ČR IAAX00320901 Institutional support: RVO:68378050 ; RVO:61388963 ; RVO:61388980 Keywords : carbonic anhydrases * carboranes * drug discovery * inhibitors * structure elucidation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.336, year: 2013

  7. 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.

  8. A chemotactic inhibitor in synovial fluid.

    Science.gov (United States)

    Matzner, Y; Partridge, R E; Babior, B M

    1983-01-01

    Synovial fluid was found to contain an inhibitor of neutrophil chemotaxis. The activity of this inhibitor was masked in native synovial fluid, but could be detected in fluid in which complement had been deactivated by mild heating. The inhibitor was most effective against the chemotactic activity of zymosan-activated serum (C5ades arg). It had little effect when N-formyl-methionyl-leucyl-phenylalanine served as chemoattractant. Inhibition was not the result of a direct effect on the neutrophils, since incubation of cells with synovial fluid did not alter their chemotactic response. The inhibitory activity was destroyed by boiling the synovial fluid or treating it with trypsin, suggesting that it is a protein (or proteins); it was not affected by hyaluronidase treatment. Gel filtration revealed that the inhibitor was present in native as well as decomplemented synovial fluid, and that its molecular weight was in the vicinity of 25,000. It is proposed that this inhibitory activity plays a role in the regulation of the inflammatory response in joints. PMID:6840801

  9. Randomized controlled trials of COX-2 inhibitors

    DEFF Research Database (Denmark)

    Stefansdottir, Gudrun; De Bruin, Marie L; Knol, Mirjam J;

    2011-01-01

    BACKGROUND: Naproxen, ibuprofen and diclofenac are frequently used as comparators in randomized controlled trials (RCTs) on the safety and efficacy of cyclooxygenase (COX)-2 inhibitors. Different comparator doses may influence the results of RCTs. It has been hypothesized that RCTs of COX-2...

  10. Proton pump inhibitors affect the gut microbiome

    NARCIS (Netherlands)

    Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Tigchelaar, Ettje F; 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

    2015-01-01

    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. Phenyltriazolinones as potent factor Xa inhibitors.

    Science.gov (United States)

    Quan, Mimi L; Pinto, Donald J P; Rossi, Karen A; Sheriff, Steven; Alexander, Richard S; Amparo, Eugene; Kish, Kevin; Knabb, Robert M; Luettgen, Joseph M; Morin, Paul; Smallwood, Angela; Woerner, Francis J; Wexler, Ruth R

    2010-02-15

    We have discovered that phenyltriazolinone is a novel and potent P1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S1 binding pocket which is larger in size to accommodate the phenyltriazolinone P1 substrate. PMID:20100660

  12. 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 dru

  13. Pharmacological caspase inhibitors: Research towards therapeutic perspectives

    Czech Academy of Sciences Publication Activity Database

    Kudělová, J.; Fleischmannová, Jana; Adamová, Eva; Matalová, Eva

    2015-01-01

    Roč. 66, č. 4 (2015), s. 473-482. ISSN 0867-5910 R&D Projects: GA ČR GB14-37368G Institutional support: RVO:67985904 Keywords : caspase * caspase inhibitor * apoptosis Subject RIV: EA - Cell Biology Impact factor: 2.386, year: 2014

  14. Novel in vitro inhibitory functions of potato tuber proteinaceous inhibitors.

    Science.gov (United States)

    Fischer, Matthias; Kuckenberg, Markus; Kastilan, Robin; Muth, Jost; Gebhardt, Christiane

    2015-02-01

    Plant protease inhibitors are a structurally highly diverse and ubiquitous class of small proteins, which play various roles in plant development and defense against pests and pathogens. Particular isoforms inhibit in vitro proteases and other enzymes that are not their natural substrates, for example proteases that have roles in human diseases. Mature potato tubers are a rich source of several protease inhibitor families. Different cultivars have different inhibitor profiles. With the objective to explore the functional diversity of the natural diversity of potato protease inhibitors, we randomly selected and sequenced 9,600 cDNA clones originated from mature tubers of ten potato cultivars. Among these, 120 unique inhibitor cDNA clones were identified by homology searches. Eighty-eight inhibitors represented novel sequence variants of known plant protease inhibitor families. Most frequent were Kunitz-type inhibitors (KTI), potato protease inhibitors I and II (PIN), pectin methylesterase inhibitors, metallocarboxypeptidase inhibitors and defensins. Twenty-three inhibitors were functionally characterized after heterologous expression in the yeast Pichia pastoris. The purified recombinant proteins were tested for inhibitory activity on trypsin, eleven pharmacological relevant proteases and the non-proteolytic enzyme 5-lipoxygenase. Members of the KTI and PIN families inhibited pig pancreas elastase, β-Secretase, Cathepsin K, HIV-1 protease and potato 5-lipoxygenase. Our results demonstrate in vitro inhibitory diversity of small potato tuber proteins commonly known as protease inhibitors, which might have biotechnological or medical applications. PMID:25260821

  15. DNA Methyltransferases Inhibitors from Natural Sources.

    Science.gov (United States)

    Zwergel, Clemens; Valente, Sergio; Mai, Antonello

    2016-01-01

    DNA methyltransferases (DNMTs) catalyze the methylation at cytosine-C5 mainly in a CpG dinucleotide context. Although DNA methylation is essential for fundamental processes like embryonic development or differentiation, aberrant expression and/or activities of DNMTs are involved in several pathologies, from neurodegeneration to cancer. DNMTs inhibition can arrest tumor growth, cells invasiveness and induce differentiation, whereas their increased expression is shown in numerous cancer types. Moreover, hypermethylated promoters of tumor suppressor genes lead to their silencing. Hence, the use of specific inhibitors of DNMT might reactivate those genes and stop or even reverse the aberrant cell processes. To date, the only approved DNMTs inhibitors for therapy belong to the nucleoside-based family of drugs, but they display relevant side effects as well as high chemical instability. Thus, there is a keen interest actually exists to develop novel, potent and safe inhibitors possessing a nonnucleoside structure. Increasing literature evidence is highlighting that natural sources could help the researchers to achieve this goal. Indeed, several polyphenols, flavonoids, antraquinones, and others are described able to inhibit DNMTs activity and/or expression, thus decreasing the methylation/silencing of different genes involved in tumorigenesis. These events can lead to re-expression of such genes and to cell death in diverse cancer cell lines. Epigallocatechin-3-gallate (1) and laccaic acid A (11) resulted the most effective DNMT1 inhibitors with submicromolar IC50 values, acting as competitive inhibitors. Compound 1 and 11 both displayed gene demethylation and re-activation in several cancers. However, all of the natural compounds described in this review showed important results, from gene reactivation to cell growth inhibition. Moreover, some of them displayed interesting activity even in rodent cancer models and very recently entered clinical trials. PMID:26303417

  16. Cost of care of haemophilia with inhibitors.

    Science.gov (United States)

    Di Minno, M N D; Di Minno, G; Di Capua, M; Cerbone, A M; Coppola, A

    2010-01-01

    In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding-related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short-term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost-utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health-related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors. PMID:19845772

  17. From the selective serotonin transporter inhibitor citalopram to the selective norepinephrine transporter inhibitor talopram

    DEFF Research Database (Denmark)

    Eildal, Jonas Nii Nortey; Andersen, Jacob; Kristensen, Anders Skov;

    2008-01-01

    Citalopram and talopram are structurally closely related, but they have very distinct pharmacological profiles as selective inhibitors of the serotonin and norepinephrine transporters, respectively. A systematic structure-activity relationship study was performed, in which each of the four...

  18. 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...

  19. 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

    2013-09-01

    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

  20. Protein inhibitor of neuronal nitric oxide synthase interacts with protein kinase A inhibitors.

    Science.gov (United States)

    Yu, Jianqiang; Yu, Long; Chen, Zheng; Zheng, Lihua; Chen, Xiaosong; Wang, Xiang; Ren, Daming; Zhao, Shouyuan

    2002-03-28

    Protein kinase A (PKA) and neuronal nitric oxide synthase (nNOS) are important signaling molecules. It is well known that PKA can specifically phosphorylate nNOS. But the underlying molecular mechanism is still obscure. Our data indicate that the protein inhibitor of nNOS (PIN) binds to protein kinase A inhibitors (PKIs), which suggests that PKIs, together with PIN, might mediate the phosphorylation of nNOS by PKA. PMID:11978406

  1. Characterizing resistance of Erysiphe necator to fungicides belonging to the quinone outside inhibitors and demethylation inhibitors

    OpenAIRE

    Rallos, Lynn Esther Espada

    2013-01-01

    Practical resistance of Erysiphe necator to quinone outside inhibitors (QoIs) is now widespread, and resistance to demethylation inhibitors (DMIs) has also developed.  The goal of this research was to characterize fungicide resistance by elucidating resistance mechanisms and determining its stability.  QoI resistance persisted for several years in a field population after QoI application ended.  Resistant isolates were highly competitive in mixed populations in competition assays under labora...

  2. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors

    Science.gov (United States)

    Tan, Li; Wang, Jun; Tanizaki, Junko; Huang, Zhifeng; Aref, Amir R.; Rusan, Maria; Zhu, Su-Jie; Zhang, Yiyun; Ercan, Dalia; Liao, Rachel G.; Capelletti, Marzia; Zhou, Wenjun; Hur, Wooyoung; Kim, NamDoo; Sim, Taebo; Gaudet, Suzanne; Barbie, David A.; Yeh, Jing-Ruey Joanna; Yun, Cai-Hong; Hammerman, Peter S.; Mohammadi, Moosa; Jänne, Pasi A.; Gray, Nathanael S.

    2014-01-01

    The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that resistance to FGFR inhibitors can be acquired through mutations in the FGFR gatekeeper residue, as clinically observed for FGFR4 in embryonal rhabdomyosarcoma and neuroendocrine breast carcinomas. Here we report on the use of a structure-based drug design to develop two selective, next-generation covalent FGFR inhibitors, the FGFR irreversible inhibitors 2 (FIIN-2) and 3 (FIIN-3). To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. We report the cocrystal structure of FGFR4 with FIIN-2, which unexpectedly exhibits a “DFG-out” covalent binding mode. The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance and provide the first example, to our knowledge, of a kinase inhibitor that covalently targets cysteines located in different positions within the ATP-binding pocket. PMID:25349422

  3. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors.

    Science.gov (United States)

    Tan, Li; Wang, Jun; Tanizaki, Junko; Huang, Zhifeng; Aref, Amir R; Rusan, Maria; Zhu, Su-Jie; Zhang, Yiyun; Ercan, Dalia; Liao, Rachel G; Capelletti, Marzia; Zhou, Wenjun; Hur, Wooyoung; Kim, NamDoo; Sim, Taebo; Gaudet, Suzanne; Barbie, David A; Yeh, Jing-Ruey Joanna; Yun, Cai-Hong; Hammerman, Peter S; Mohammadi, Moosa; Jänne, Pasi A; Gray, Nathanael S

    2014-11-11

    The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that resistance to FGFR inhibitors can be acquired through mutations in the FGFR gatekeeper residue, as clinically observed for FGFR4 in embryonal rhabdomyosarcoma and neuroendocrine breast carcinomas. Here we report on the use of a structure-based drug design to develop two selective, next-generation covalent FGFR inhibitors, the FGFR irreversible inhibitors 2 (FIIN-2) and 3 (FIIN-3). To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. We report the cocrystal structure of FGFR4 with FIIN-2, which unexpectedly exhibits a "DFG-out" covalent binding mode. The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance and provide the first example, to our knowledge, of a kinase inhibitor that covalently targets cysteines located in different positions within the ATP-binding pocket. PMID:25349422

  4. New inhibitor reduces corrosion in crude tower overhead

    Energy Technology Data Exchange (ETDEWEB)

    Tang, S.; Jiang, Z.; Mao, Q. (Wuhan Petrochemical Works (China))

    1994-09-19

    A Chinese refinery found its own imidazoline-type corrosion inhibitor to exhibit superior properties in laboratory and commercial testing. Tests in a crude-tower overhead system showed inhibition efficiency to be 96%. The paper discusses corrosion inhibitors used in the past, the composition of the new inhibitor, corrosion tests, commercial trials, and economics.

  5. Deletion Mutations Keep Kinase Inhibitors in the Loop.

    Science.gov (United States)

    Freed, Daniel M; Park, Jin H; Radhakrishnan, Ravi; Lemmon, Mark A

    2016-04-11

    Effective clinical application of conformationally selective kinase inhibitors requires tailoring drug choice to the tumor's activating mutation(s). In this issue of Cancer Cell, Foster et al. (2016) describe how activating deletions in BRAF, EGFR, and HER2 cause primary resistance to common inhibitors, suggesting strategies for improved inhibitor selection. PMID:27070691

  6. Isolation of pancreatic trypsin inhibitor from bovine pituitary glands.

    OpenAIRE

    Li, C. H.; Chung, D.

    1983-01-01

    A trypsin inhibitor has been isolated from bovine pituitary extracts. From its amino acid composition, NH2-terminal residue, mobility in paper electrophoresis, and behavior in high-performance liquid chromatography and from the tryptic pattern of the performic acid-oxidized material, it appears that the inhibitor is identical to the Kunitz and Northrop pancreatic trypsin inhibitor.

  7. Inhibitor analysis for a solar heating and cooling system

    Science.gov (United States)

    Tabony, J. H.

    1977-01-01

    A study of potential corrosion inhibitors for the NASA solar heating and cooling system which uses aluminum solar panels is provided. Research consisted of testing using a dynamic corrosion system, along with an economic analysis of proposed corrosion inhibitors. Very good progress was made in finding a suitable inhibitor for the system.

  8. 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.

  9. Template-Based de Novo Design for Type II Kinase Inhibitors and Its Extended Application to Acetylcholinesterase Inhibitors

    OpenAIRE

    Bo-Han Su; Yi-Syuan Huang; Chia-Yun Chang; Yi-Shu Tu; Yufeng J Tseng

    2013-01-01

    There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo desig...

  10. Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation

    OpenAIRE

    Prickaerts, L.; SIK, A.; Staay, van der, F.J.; Vente, de, W.; Blokland, A.

    2005-01-01

    Rationale Phosphodiesterase enzyme type 5 (PDE5) inhibitors and acetylcholinesterase (AChE) inhibitors have cognition-enhancing properties. However, it is not known whether these drug classes affect the same memory processes. Objective We investigated the memory-enhancing effects of the PDE5 inhibitor sildenafil and AChE inhibitors metrifonate and donepezil in the object recognition task to find out whether acquisition or consolidation processes were affected by these drugs. Methods The objec...

  11. Secreted and transmembrane wnt inhibitors and activators.

    Science.gov (United States)

    Cruciat, Cristina-Maria; Niehrs, Christof

    2013-03-01

    Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand-receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step. With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling. Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease. PMID:23085770

  12. 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

  13. Inhibitor prevents corrosion, scale in Chinese waterflood

    Energy Technology Data Exchange (ETDEWEB)

    Yong, W.; Jianhua, W. (Shengli Design Inst., Dongying (China))

    1994-03-14

    An imidazoline derivative-based series inhibitor has prevented both corrosion and scale formation in produced-water treatment and water-injection equipment in China National Petroleum Co.'s (CNPC) Shengli oil field. Development of the inhibitor started in 1986, and after successful field trials the chemical is now being extensively applied. To increase oil recovery, water injection is widely used in China's onshore oil fields. Oil production in the Shengli oil field, for example, requires injection of about 4 bbl of water/1 bbl of oil produced. The large volumes of produced formation water contain many substances that can cause serious corrosion and scale. Also, the makeup water from other sources, subsurface or surface, complicates water handling. The paper discusses the following: corrosion and scale, oxygen, carbon dioxide, H[sub 2]S and sulfur reducing bacteria, temperature, inhibition, field tests, applications, and economics.

  14. 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.

  15. New potential AChE inhibitor candidates.

    Science.gov (United States)

    de Paula, A A N; Martins, J B L; dos Santos, M L; Nascente, L de C; Romeiro, L A S; Areas, T F M A; Vieira, K S T; Gambôa, N F; Castro, N G; Gargano, R

    2009-09-01

    We have theoretically studied new potential candidates of acetylcholinesterase (AChE) inhibitors designed from cardanol, a non-isoprenoid phenolic lipid of cashew Anacardium occidentale nut-shell liquid. The electronic structure calculations of fifteen molecule derivatives from cardanol were performed using B3LYP level with 6-31G, 6-31G(d), and 6-311+G(2d,p) basis functions. For this study we used the following groups: methyl, acetyl, N,N-dimethylcarbamoyl, N,N-dimethylamine, N,N-diethylamine, piperidine, pyrrolidine, and N,N-methylbenzylamine. Among the proposed compounds we identified that the structures with substitution by N,N-dimethycarbamoyl, N,N-dimethylamine, and pyrrolidine groups were better correlated to rivastigmine, and represent possible AChE inhibitors against Alzheimer disease. PMID:19446931

  16. Protein synthesis inhibitor from potato tuber

    International Nuclear Information System (INIS)

    A protein fraction capable of inhibit in vitro protein synthesis was found in potato tubers in fresh and wounded tissue. Inhibitor activity from fresh tissue decays with wounding. Inhibition activity was detected absorbed to ribsomal fraction and cytosol of potato tuber tissue by a partially reconstituted in vitro system from potato tuber and wheat germ. Adsorbed ribosomal fraction was more suitable of purification. This fraction was washed from ribosomes with 0.3M KCl, concentrated with ammonium sulfate precipitation and purified through sephadex G100 and sephadex G-75 columns chromatography. After 61 fold purification adsorbed protein fraction can inhibit germination of maize, wheat and sesame seeds, as well as 3H-leucine incorporation into protein by imbibed maize embryos. Inhibition activity was lost by temperature, alkali and protease-K hydrolysis. Preliminar analysis could not show presence of reductor sugars. Physiological role of this inhibitor in relation to rest and active tissue remains to be studied

  17. Naphthyridines as novel BET family bromodomain inhibitors.

    Science.gov (United States)

    Mirguet, Olivier; Lamotte, Yann; Chung, Chun-Wa; Bamborough, Paul; Delannée, Delphine; Bouillot, Anne; Gellibert, Françoise; Krysa, Gael; Lewis, Antonia; Witherington, Jason; Huet, Pascal; Dudit, Yann; Trottet, Lionel; Nicodeme, Edwige

    2014-03-01

    Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure and facilitates the localisation of transcriptional complexes to specific genes, thereby regulating epigenetically controlled processes including gene transcription and mRNA elongation. Inhibitors of the bromodomain and extra-terminal (BET) proteins BRD2-4 and T, which prevent bromodomain binding to acetyl-modified histone tails, have shown therapeutic promise in several diseases. We report here the discovery of 1,5-naphthyridine derivatives as potent inhibitors of the BET bromodomain family with good cell activity and oral pharmacokinetic parameters. X-ray crystal structures of naphthyridine isomers have been solved and quantum mechanical calculations have been used to explain the higher affinity of the 1,5-isomer over the others. The best compounds were progressed in a mouse model of inflammation and exhibited dose-dependent anti-inflammatory pharmacology. PMID:24000170

  18. Synthesis of macrocyclic trypanosomal cysteine protease inhibitors

    OpenAIRE

    Chen, Yen Ting; Lira, Ricardo; Hansell, Elizabeth; McKerrow, James H.; Roush, William R.

    2008-01-01

    The importance of cysteine proteases in parasites, compounded with the lack of redundancy compared to their mammalian hosts makes proteases attractive targets for the development of new therapeutic agents. The binding mode of K11002 to cruzain, the major cysteine protease of Trypanosoma cruzi was used in the design of conformationally constrained inhibitors. Vinyl sulfone-containing macrocycles were synthesized via olefin ring-closing metathesis and evaluated against cruzain and the closely r...

  19. Octahedral ruthenium complexes as protein kinase inhibitors

    OpenAIRE

    Li FENG

    2010-01-01

    Die vorliegende Arbeit beschäftigt sich mit einer Strategie zur Darstellung von selektiven Proteinkinaseinhibitoren unter Verwendung starrer, oktaedrischer Rutheniumkomplexe als Strukturmerkmal. Nanomolare Inhibitoren für die Proteinkinasen PAK1, MLCK und DAPK1, sowie ein picomolarer Inhibitor für die Proteinkinase Pim1 wurden entwickelt. Diese Inhibitoren weisen eine außerordentlich hohe Selektivität gegenüber den anderen ...

  20. Corrosion Inhibitors as Penetrant Dyes for Radiography

    Science.gov (United States)

    Novak, Howard L.; Hall, Phillip B.

    2003-01-01

    Liquid/vapor-phase corrosion inhibitors (LVCIs) have been found to be additionally useful as penetrant dyes for neutron radiography (and perhaps also x-radiography). Enhancement of radiographic contrasts by use of LVCIs can reveal cracks, corrosion, and other defects that may be undetectable by ultrasonic inspection, that are hidden from direct optical inspection, and/or that are difficult or impossible to detect in radiographs made without dyes.

  1. Aromatase inhibitors and anti-synthetase syndrome.

    Science.gov (United States)

    Mascella, Fabio; Gianni, Lorenzo; Affatato, Alessandra; Fantini, Manuela

    2016-09-01

    Adjuvant therapy in postmenopausal women with endocrine-responsive breast cancer (BC) is actually centered on the use of anti-aromatase inhibitors (AI). Several reports, however, are emerging in literature associating the use of this drugs to rheumatic disorders. This case report describes the first case of anti-synthetase syndrome diagnosis after treatment with anti-estrogen agents in a patient with pre-existing rheumatoid arthritis. PMID:27225465

  2. Prostaglandin Inhibitors: Rational Therapy for Dysmenorrhea

    OpenAIRE

    Sorbie, Janet

    1982-01-01

    Dysmenorrhea affects at least 50% of women at some time in their lives. Painful contractions of the uterine muscle (similar to labor pains) are triggered by increased endometrial synthesis of prostaglandins, which appear in elevated amounts in the plasma and menstrual fluid of women with dysmenorrhea. Non-steroidal anti-inflammatory drugs, which have been used for years in arthritis, are effective prostaglandin inhibitors. Taken by mouth at the onset of menstruation, they can relieve dysmenor...

  3. Hyperkalaemia induced by carbonic anhydrase inhibitor.

    OpenAIRE

    Wakabayashi, Y.

    1991-01-01

    An 81-year-old man developed hyperkalaemic and hyperchloraemic metabolic acidosis following treatment with a carbonic anhydrase inhibitor for his glaucoma. He had mild renal failure and selective aldosterone deficiency was confirmed. In this case the treatment did not lead to hypokalaemia because of the limited potassium secretory capacity in the renal tubules from selective aldosterone deficiency; rather, it may have led to hyperkalaemia because metabolic acidosis induced by the carbonic anh...

  4. SGLT-2 inhibitors: the glucosuric antidiabetics

    OpenAIRE

    Rekha Thaddanee; Ajeet Kumar Khilnani; Gurudas Khilnani

    2013-01-01

    Despite availability of a number of oral antidiabetics, a sizeable population of diabetics remains uncontrolled. Thus there is growing need of new group of drugs for diabetic control. Understanding renal conservation of glucose by efficient reabsorption through sodium glucose cotransporter-2 (SGLT-2) has paved way for development of an entirely new group of drugs, the SGLT-2 inhibitors. These glucosuric antidiabetic agents have shown promise in early clinical studies. Canagliflozin is recentl...

  5. Luminometric method for screening retroviral protease inhibitors

    Czech Academy of Sciences Publication Activity Database

    Horáková, D.; Rumlová, Michaela; Pichová, Iva; Ruml, Tomáš

    2005-01-01

    Roč. 345, č. 1 (2005), s. 96-101. ISSN 0003-2697 R&D Projects: GA AV ČR(CZ) IAA4055304; GA MŠk(CZ) 1M0508; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z40550506 Keywords : retroviral protease * inhibitors * luminescent assay Subject RIV: CE - Biochemistry Impact factor: 2.670, year: 2005

  6. Corrosion protection with eco-friendly inhibitors

    International Nuclear Information System (INIS)

    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. (review)

  7. Aurora kinase inhibitors: Progress towards the clinic

    Czech Academy of Sciences Publication Activity Database

    Kollareddy, M.; Zheleva, D.; Dzubak, P.; Brahmkshatriya, Pathik; Lepšík, Martin; Hajduch, M.

    2012-01-01

    Roč. 30, č. 6 (2012), s. 2411-2432. ISSN 0167-6997 Grant ostatní: GA ČR(CZ) GA301/08/1649; GA ČR(CZ) GD303/09/H048 Institutional research plan: CEZ:AV0Z40550506 Keywords : Aurora kinases * cancer * inhibitors Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.498, year: 2012

  8. Pointing the finger at proton pump inhibitors

    Directory of Open Access Journals (Sweden)

    Emma L Walton

    2014-08-01

    Full Text Available This issue of the Biomedical Journal welcomes articles from a wide range of disciplines. We take a look at the optimization of surgical techniques in rabbits and visit some of the medical wonders of stem cell technology. In particular, we highlight Sasmita Biswal's discussion of an emerging link between the use of proton pump inhibitors and hospital-acquired Clostridium difficile infections, in addition to intriguing data showing that environmental enrichment protects hippocampal neurons from damage in stressed, diabetic rats.

  9. 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: 2.858, year: 2014

  10. 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.

  11. Topical calcineurin inhibitors in systemic lupus erythematosus

    OpenAIRE

    Lampropoulos, Christos

    2010-01-01

    Christos E Lampropoulos, David P D’CruzLupus Research Unit, Rayne Institute, St. Thomas’ Hospital, London, UKAbstract: Cutaneous lupus erythematosus (CLE) encompasses a variety of lesions that may be refractory to systemic or topical agents. Discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE) are the most common lesions in clinical practice. The topical calcineurin inhibitors, tacrolimus and pimecrolimus, have been used to treat resistant cu...

  12. 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: 3.321, year: 2014 http://www.sciencedirect.com/science/article/pii/S0042682215003864

  13. Alternative therapies for the management of inhibitors.

    Science.gov (United States)

    Shima, M; Lillicrap, D; Kruse-Jarres, R

    2016-07-01

    The development of inhibitors to factor VIII (FVIII) or factor IX (FIX) remains a major treatment complication encountered in the treatment of haemophilia. Not all patients with even the same severity and genotype develop inhibitors suggesting an underlying mechanism of tolerance against FVIII- or FIX-related immunity. One mechanism may be central tolerance observed in patients in whom the FVIII mutation enables some production of the protein. The other is a peripheral tolerance mechanism which may be evident in patients with null mutation. Recently, recombinant porcine FVIII (rpFVIII, Obixur, OBI-1, BAX801) has been developed for the haemostatic treatment of both congenital haemophilia with inhibitor (CHAWI) and acquired haemophilia A (AHA). In 28 subjects with AHA with life-/limb-threatening bleeding, rpFVIII reduced or stopped bleeding in all patients within 24 h. The cross-reactivity of anti-human FVIII antibodies to rpFVIII remains around 30-50%. Recently, new therapeutics based on the quite novel concepts have been developed and clinical studies are ongoing. These are humanized asymmetric antibody mimicking FVIIIa function by maintaining a suitable interaction between FIXa and FX (Emicizumab, ACE910), and small interfering RNAs (siRNA, ALN-AT3) suppress liver production of AT through post-transcriptional gene silencing and a humanized anti-TFPI monoclonal antibody (Concizumab). Their main advantages are longer half-life, subcutaneous applicability and efficacy irrespective of the presence of inhibitors which will make it easier to initiate more effective treatment especially early childhood. PMID:27405674

  14. Inhibitors of the AAA+ Chaperone p97

    Directory of Open Access Journals (Sweden)

    Eli Chapman

    2015-02-01

    Full Text Available It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA more than 10 years ago to treat refractory myeloma and later extended to lymphoma. Its use has increased the survival rate of myeloma patients by as much as three years. This success was followed with the recent accelerated approval of the natural product derived proteasome inhibitor carfilzomib (Kyprolis®, which is used to treat patients with bortezomib-resistant multiple myeloma. The success of these two drugs has validated protein quality control as a viable target to fight select cancers, but begs the question why are proteasome inhibitors limited to lymphoma and myeloma? More recently, these limitations have encouraged the search for additional targets within the protein quality control system that might offer heightened cancer cell specificity, enhanced clinical utility, a lower rate of resistance, reduced toxicity, and mitigated side effects. One promising target is p97, an ATPase associated with various cellular activities (AAA+ chaperone. p97 figures prominently in protein quality control as well as serving a variety of other cellular functions associated with cancer. More than a decade ago, it was determined that up-regulation of p97 in many forms of cancer correlates with a poor clinical outcome. Since these initial discoveries, a mechanistic explanation for this observation has been partially illuminated, but details are lacking. Understandably, given this clinical correlation, myriad roles within the cell, and its importance in protein quality control, p97 has emerged as a potential therapeutic target. This review provides an overview of efforts towards the discovery of small molecule inhibitors of p97, offering a synopsis of efforts that parallel the excellent reviews that currently exist on p97 structure, function, and

  15. Rust Inhibitor And Fungicide For Cooling Systems

    Science.gov (United States)

    Adams, James F.; Greer, D. Clay

    1988-01-01

    Mixture of benzotriazole, benzoic acid, and fungicide prevents growth of rust and fungus. Water-based cooling mixture made from readily available materials prevents formation of metallic oxides and growth of fungi in metallic pipes. Coolant remains clear and does not develop thick sludge tending to collect in low points in cooling systems with many commercial rust inhibitors. Coolant compatible with iron, copper, aluminum, and stainless steel. Cannot be used with cadmium or cadmium-plated pipes.

  16. Probing translation using small molecule inhibitors

    OpenAIRE

    Blanchard, Scott C; Cooperman, Barry S.; Wilson, Daniel N

    2010-01-01

    The translational apparatus of the bacterial cell remains one of the principal targets of antibiotics for the clinical treatment of infection worldwide. Since the introduction of specific translation inhibitors into clinical practise in the late 1940’s, intense efforts have been made to understand their precise mechanisms of action. Such research has often revealed significant and sometimes unexpected insights into many fundamental aspects of the translation mechanism. Central to progress in ...

  17. 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.

  18. Janus kinase inhibitors for rheumatoid arthritis.

    Science.gov (United States)

    Yamaoka, Kunihiro

    2016-06-01

    Treatment of autoimmune diseases, such as rheumatoid arthritis (RA), has advanced substantially over the past decade with the development of biologics targeting inflammatory cytokines. Recent progress in treating RA has been achieved with janus kinase (JAK) inhibitors (Jakinibs), an orally available disease-modifying anti-rheumatic drug targeting the intracellular kinase JAK and with similar efficacy to biologics. The first Jakinib approved for RA was tofacitinib, which exerted superiority to methotrexate and non-inferiority to tumor necrosis factor (TNF) inhibitors. In recent years, the Jakinib baricitinib has demonstrated superiority to both methotrexate and a TNF inhibitor, adalimumab. Given these promising findings, Jakinibs are expected to represent the next generation compounds for treating RA, and a number of Jakinibs are currently in clinical trials. Jakinibs can differ substantially in their selectivity against JAKs; tofacitinib and baricitinib target multiple JAKs, whereas the most recently developed Jakinibs target only a single JAK. The influence of Jakinib selectivity on efficacy and side effects is of great interest, requiring further careful observation. PMID:26994322

  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. The hunt for HIV-1 integrase inhibitors.

    Science.gov (United States)

    Lataillade, Max; Kozal, Michael J

    2006-07-01

    Currently, there are three distinct mechanistic classes of antiretrovirals: inhibitors of the HIV- 1 reverse transcriptase and protease enzymes and inhibitors of HIV entry, including receptor and coreceptor binding and cell fusion. A new drug class that inhibits the HIV-1 integrase enzyme (IN) is in development and may soon be available in the clinic. IN is an attractive drug target because it is essential for a stable and productive HIV-1 infection and there is no mammalian homologue of IN. Inhibitors of integrase enzyme (INI) block the integration of viral double-stranded DNA into the host cell's chromosomal DNA. HIV-1 integration has many potential steps that can be inhibited and several new compounds that target specific integration steps have been identified by drug developers. Recently, two INIs, GS-9137 and MK-0518, demonstrated promising early clinical trial results and have been advanced into later stage trials. In this review, we describe how IN facilitates HIV-1 integration, the needed enzyme cofactors, and the resultant byproducts created during integration. Furthermore, we review the different INIs under development, their mechanism of actions, site of IN inhibition, potency, resistance patterns, and discuss the early clinical trial results. PMID:16839248

  1. Cinnoline derivatives as human neutrophil elastase inhibitors.

    Science.gov (United States)

    Giovannoni, Maria Paola; Schepetkin, Igor A; Crocetti, Letizia; Ciciani, Giovanna; Cilibrizzi, Agostino; Guerrini, Gabriella; Khlebnikov, Andrei I; Quinn, Mark T; Vergelli, Claudia

    2016-08-01

    Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195. PMID:26194018

  2. 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.

  3. CYP17 inhibitors for prostate cancer therapy.

    Science.gov (United States)

    Vasaitis, Tadas S; Bruno, Robert D; Njar, Vincent C O

    2011-05-01

    Prostate cancer (PC) is now the second most prevalent cause of death in men in the USA and Europe. At present, the major treatment options include surgical or medical castration. These strategies cause ablation of the production of testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes. However, because these procedures do not affect adrenal, prostate and other tissues' androgen production, they are often combined with androgen receptor antagonists to block their action. Indeed, recent studies have unequivocally established that in castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Clearly, inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17α-hydroxy/17,20-lyase (hereafter referred to as CYP17) could prevent androgen production from all sources. Thus, total ablation of androgen production by potent CYP17 inhibitors may provide effective treatment of prostate cancer patients. This review highlights the role of androgen biosynthesis in the progression of prostate cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical development. Article from the special issue on Targeted Inhibitors. PMID:21092758

  4. SGLT-2 inhibitors: the glucosuric antidiabetics

    Directory of Open Access Journals (Sweden)

    Rekha Thaddanee

    2013-08-01

    Full Text Available Despite availability of a number of oral antidiabetics, a sizeable population of diabetics remains uncontrolled. Thus there is growing need of new group of drugs for diabetic control. Understanding renal conservation of glucose by efficient reabsorption through sodium glucose cotransporter-2 (SGLT-2 has paved way for development of an entirely new group of drugs, the SGLT-2 inhibitors. These glucosuric antidiabetic agents have shown promise in early clinical studies. Canagliflozin is recently approved for use in diabetes alone or along with other antidiabetics. Other highly selective inhibitors undergoing various stages of clinical developments are dapagliflozin, sergliflozin, remogliflozin, ipragliflozin, empagliflozin, luseogliflozin, tofogliflozin and desoxyrhaponticin. KGA-2727 (pyrazole-O-glucoside is the first selective SGLT-1 inhibitor undergoing intense preclinical testing. There are safety issues associated with this group like urogenital infections (fungal, weight loss, initial osmotic diuresis and increased incidence of cardiovascular events. The long term safety remains to be established. Despite these limitations, SGLT-2 inhibition offers a unique target for achieving adequate control of diabetes in adults. [Int J Basic Clin Pharmacol 2013; 2(4.000: 347-352

  5. Sulfated chitooligosaccharides as prolyl endopeptidase inhibitor.

    Science.gov (United States)

    Je, Jae-Young; Kim, Eun-Kyung; Ahn, Chang-Bum; Moon, Sang-Ho; Jeon, Byong-Tae; Kim, Bokyung; Park, Tae-Kyu; Park, Pyo-Jam

    2007-12-01

    Prolyl endopeptidase (PEP, EC 3.4.21.26) is a proline-specific endopeptidase with a serine-type mechanism, which digests small peptide-like hormones, neuroactive peptides, and various cellular factors. PEP has been involved in neurodegenerative disorders, therefore, the discovery of PEP inhibitors can revert memory loss caused by amnesic compounds. In this study, we prepared hetero-chitooligosaccharides (COSs) with different molecular sizes using ultrafiltration (UF) membrane reactor system from hetero-chitosan with different degrees of deacetylation (DD; 90%, 75% and 50% deacetylation), and synthesized sulfated COSs (SCOSs). PEP inhibitory activities of SCOSs were evaluated and the results showed that 50% deacetylated SCOSs (50-SCOSs) exhibited higher inhibitory activities than those of 90% and 75% deacetylated SCOSs (90-SCOSs and 75-SCOSs). Among the 50-SCOSs (50-SCOS I, 5000-10,000Da; 50-SCOS II, 1000-5000Da; 50-SCOS III, below 1000Da), 50-SCOS II possessed the highest inhibitory activity and IC(50) value was 0.38mg/ml. Kinetics studies with 50-SCOS II indicated a competitive enzyme inhibition with a K(i) value of 0.78mg/ml. It was concluded that the 50-SCOS II may be useful for PEP inhibitor and for developing a new type PEP inhibitor from carbohydrate based materials. PMID:17714777

  6. Radiolabeled enzyme inhibitors as pancreatic scanning agents

    International Nuclear Information System (INIS)

    Radiolabeled inhibitors of the pancreatic protease enzymes trypsin and chymotrypsin: I-125-soybean inhibitor (SBI), I-125-human antitrypsin (HAT), and 3H-diisopropylfluorophosphate (DFP) were studied in rats for their uptake in the pancreas. The protease enzyme inhibitor, SBI, was found to retain its enzymatic activity after radio-iodine labeling by iodine-monochloride method. Assay of tissues radioactivity at 5, 15, 30, 60 min and 24 hr after iv injection in rats showed pancreas:liver (P:L) ratios of < 1.4 and pancreas:blood (P:B) ratios of < 1 at all time intervals for each compound. However, ip injection of I-125 SBI showed preferential uptake in pancreas, P:L mean ratios [anti x (range)] of 6.0 (5.5 to 6.3) and P:B mean ratios of [anti x (range)] 2.60 (1.8 to 3.4), up to 60 minutes. These ratios resemble those of Se-75-selenomethionine except that kidney values are higher. Our data suggest that radiolabeled proteins can also show similar good early pancreatic uptake when given ip by escaping immediate liver metabolism. Proteins can readily be tagged with desirable gamma-emitting radionuclides (viz. I-131, I-123, Tc-99m) compared to amino acids and may potentially be suitable for imaging the pancreas. It may be important to study both iv and ip routes of administration in evaluating the specificity/affinity of potential pancreatic radiopharmaceuticals

  7. Topical calcineurin inhibitors in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Christos E Lampropoulos

    2010-04-01

    Full Text Available Christos E Lampropoulos, David P D’CruzLupus Research Unit, Rayne Institute, St. Thomas’ Hospital, London, UKAbstract: Cutaneous lupus erythematosus (CLE encompasses a variety of lesions that may be refractory to systemic or topical agents. Discoid lupus erythematosus (DLE and subacute cutaneous lupus erythematosus (SCLE are the most common lesions in clinical practice. The topical calcineurin inhibitors, tacrolimus and pimecrolimus, have been used to treat resistant cutaneous lupus since 2002 and inhibit the proliferation and activation of T-cells and suppress immune-mediated cutaneous inflammation. This article reviews the mechanism of action, efficacy, adverse effects, and the recent concern about their possible carcinogenic effect. Although the total number of patients is small and there is only one relevant randomized controlled study, the data are encouraging. Many patients, previously resistant to systemic agents or topical steroids, improved after four weeks of treatment. DLE and SCLE lesions were less responsive, reflecting the chronicity of the lesions, although more than 50% of patients still showed improvement. Topical calcineurin inhibitors may be a safe and effective alternative to topical steroids for CLE although the only approved indication is for atopic dermatitis.Keywords: tacrolimus, pimecrolimus, cutaneous lupus erythematosus, topical calcineurin inhibitors

  8. Immune Checkpoint Inhibitors in Older Adults.

    Science.gov (United States)

    Elias, Rawad; Morales, Joshua; Rehman, Yasser; Khurshid, Humera

    2016-08-01

    Cancer is primarily a disease of older adults. The treatment of advanced stage tumors usually involves the use of systemic agents that may be associated with significant risk of toxicity, especially in older patients. Immune checkpoint inhibitors are newcomers to the oncology world with improved efficacy and better safety profiles when compared to traditional cytotoxic drugs. This makes them an attractive treatment option. While there are no elderly specific trials, this review attempts to look at the current available data from a geriatric oncology perspective. We reviewed data from phase III studies that led to newly approved indications of checkpoint inhibitors in non-small cell lung cancer, melanoma, and renal cell cancer. Data were reviewed with respect to response, survival, and toxicity according to three groups: 75 years. Current literature does not allow one to draw definitive conclusions regarding the role of immune checkpoint inhibitors in older adults. However, they may offer a potentially less toxic but equally efficacious treatment option for the senior adult oncology patient. PMID:27287329

  9. 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

  10. 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+.

  11. 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.

  12. 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

  13. Purification and characterization of elastase-specific inhibitor. Sequence homology with mucus proteinase inhibitor.

    Science.gov (United States)

    Sallenave, J M; Ryle, A P

    1991-01-01

    Elastase-specific inhibitor (ESI) was purified from sputum of patients with chronic bronchitis and compared with mucus proteinase inhibitor (MPI, BrI) isolated, without the use of affinity chromatography on an enzyme, from non-purulent sputum of a patient with bronchial carcinoma. The N-terminal sequence of 27 residues of the latter was determined and showed serine as the only N-terminus. The partial N-terminal amino-acid sequence of ESI shows some homology with MPI, especially around the reactive site of MPI for human neutrophil elastase. This region could therefore be the reactive site of ESI. The thermodynamic and kinetic constants of the reactions of ESI with human neutrophil elastase and with porcine pancreatic elastase show that ESI is a fast-acting inhibitor. PMID:2039600

  14. Effects of arsenic trioxide on ATM/ATR gene expression and cell apoptosis in K562 cells%As2O3对K562 ATM/ATR基因表达和细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    叶敏军; 任行洲

    2008-01-01

    目的 探讨不同浓度As2O3对K562细胞ATM(Ataxia Telangiectasia Mutated)/ATR(ATM-Rad3-Related)基因表达的影响及相应的细胞周期变化和细胞凋亡机制.方法 以不同剂量的As2O3作用于K562细胞株,RT-PCR半定量检测ATM/ATR基因表达,流式细胞术检测P53、Annexin V和细胞周期.结果 随药物浓度升高,ATM基因表达量增强而ATR基因表达量降低,P53水平升高,细胞凋亡显著,亚二倍体和G1期细胞数增多,S期和G2/M期细胞减少.不加入药物的K562细胞ATM和ATR几乎不表达.结论 ATM和ATR基因表达变化呈As203浓度依赖的形式,且与P53水平、细胞周期和细胞凋亡率的改变相关.

  15. Metabolic Abnormalities Associated with the Use of Protease Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    Madhu N. Rao

    2006-01-01

    Full Text Available The use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection and AIDS has been associated with multiple abnormalities in glucose and lipid metabolism. Specifically, these abnormalities include insulin resistance, increased triglycerides and increased LDL cholesterol levels. The metabolic disturbances are due to a combination of factors, including the direct effect of medications, restoration to health and HIV disease, as well as individual genetic predisposition. Of the available anti-retroviral medications, indinavir has been associated with causing the most insulin resistance and ritonavir with causing the most hypertriglyceridemia.

  16. Sifuvirtide, a potent HIV fusion inhibitor peptide

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rui-Rui; Yang, Liu-Meng; Wang, Yun-Hua [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China); Pang, Wei [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China); Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Tam, Siu-Cheung [Department of Physiology, Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China); Tien, Po [Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Zheng, Yong-Tang, E-mail: zhengyt@mail.kiz.ac.cn [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)

    2009-05-08

    Enfuvirtide (ENF) is currently the only FDA approved HIV fusion inhibitor in clinical use. Searching for more drugs in this category with higher efficacy and lower toxicity seems to be a logical next step. In line with this objective, a synthetic peptide with 36 amino acid residues, called Sifuvirtide (SFT), was designed based on the crystal structure of gp41. In this study, we show that SFT is a potent anti-HIV agent with relatively low cytotoxicity. SFT was found to inhibit replication of all tested HIV strains. The effective concentrations that inhibited 50% viral replication (EC{sub 50}), as determined in all tested strains, were either comparable or lower than benchmark values derived from well-known anti-HIV drugs like ENF or AZT, while the cytotoxic concentrations causing 50% cell death (CC{sub 50}) were relatively high, rendering it an ideal anti-HIV agent. A GST-pull down assay was performed to confirm that SFT is a fusion inhibitor. Furthermore, the activity of SFT on other targets in the HIV life cycle was also investigated, and all assays showed negative results. To further understand the mechanism of action of HIV peptide inhibitors, resistant variants of HIV-1{sub IIIB} were derived by serial virus passage in the presence of increasing doses of SFT or ENF. The results showed that there was cross-resistance between SFT and ENF. In conclusion, SFT is an ideal anti-HIV agent with high potency and low cytotoxicity, but may exhibit a certain extent of cross-resistance with ENF.

  17. Sifuvirtide, a potent HIV fusion inhibitor peptide

    International Nuclear Information System (INIS)

    Enfuvirtide (ENF) is currently the only FDA approved HIV fusion inhibitor in clinical use. Searching for more drugs in this category with higher efficacy and lower toxicity seems to be a logical next step. In line with this objective, a synthetic peptide with 36 amino acid residues, called Sifuvirtide (SFT), was designed based on the crystal structure of gp41. In this study, we show that SFT is a potent anti-HIV agent with relatively low cytotoxicity. SFT was found to inhibit replication of all tested HIV strains. The effective concentrations that inhibited 50% viral replication (EC50), as determined in all tested strains, were either comparable or lower than benchmark values derived from well-known anti-HIV drugs like ENF or AZT, while the cytotoxic concentrations causing 50% cell death (CC50) were relatively high, rendering it an ideal anti-HIV agent. A GST-pull down assay was performed to confirm that SFT is a fusion inhibitor. Furthermore, the activity of SFT on other targets in the HIV life cycle was also investigated, and all assays showed negative results. To further understand the mechanism of action of HIV peptide inhibitors, resistant variants of HIV-1IIIB were derived by serial virus passage in the presence of increasing doses of SFT or ENF. The results showed that there was cross-resistance between SFT and ENF. In conclusion, SFT is an ideal anti-HIV agent with high potency and low cytotoxicity, but may exhibit a certain extent of cross-resistance with ENF.

  18. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang;

    2014-01-01

    pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending on......, in spite of a less favorable binding entropy and loss of a polar interaction. We conclude that increased flexibility of the peptide allows more favorable exosite interactions, which, in combination with the use of novel Arg analogues as P1 residues, can be used to manipulate the affinity and...

  19. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco; Giannuzzo, Andrea; Sørensen, Christiane Elisabeth; Novak, Ivana

    2015-01-01

    +/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... localizations in duct cell monolayers (Capan-1) and human pancreas, and notably the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs inhibited recovery of intracellular pH from acidosis. Furthermore, in rats treated with PPIs, pancreatic secretion was inhibited but concentrations of...

  20. 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.

  1. 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

  2. Structural selectivity of human SGLT inhibitors

    OpenAIRE

    Hummel, Charles S.; Lu, Chuan; Liu, Jie; Ghezzi, Chiari; Hirayama, Bruce A.; Loo, Donald D. F.; Kepe, Vladimir; Jorge R. Barrio; Wright, Ernest M.

    2011-01-01

    Human Na+-d-glucose cotransporter (hSGLT) inhibitors constitute the newest class of diabetes drugs, blocking up to 50% of renal glucose reabsorption in vivo. These drugs have potential for widespread use in the diabetes epidemic, but how they work at a molecular level is poorly understood. Here, we use electrophysiological methods to assess how they block Na+-d-glucose cotransporter SGLT1 and SGLT2 expressed in human embryonic kidney 293T (HEK-293T) cells and compared them to the classic SGLT...

  3. Recent chymase inhibitors and their effects in in vivo models.

    Science.gov (United States)

    Muto, Tsuyoshi; Fukami, Harukazu

    2002-12-01

    Recent efforts to discover novel chymase inhibitors have produced orally bioavailable compounds. Studies using such inhibitors have shed light on the pathophysiological roles of chymase, eg, a chymase inhibitor has prevented atherosclerosis, restenosis and myocardial infarction in respective animal models. In these cardiovascular diseases, angiotensin I is likely involved as a substrate for chymase. The studies using chymase inhibitors have also shown the potential role of chymase in other diseases, including atopic dermatitis, tissue fibrosis and rheumatoid arthritis; a chymase inhibitor also reduced ischemic reperfusion injury in the small intestine. These results suggest the existence of physiological substrates for chymase other than angiotensin I. Chymase inhibitors are promising for the treatment of cardiovascular as well as inflammatory diseases. PMID:12800055

  4. Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Kazi Abdus Salam

    2013-01-01

    Full Text Available Currently, hepatitis C virus (HCV infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin. The new therapy has significantly improved sustained virologic response (SVR; however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors.

  5. The Place of protease inhibitors in antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    S.B. Tenore

    2009-10-01

    Full Text Available With the introduction of highly active antiretroviral therapy, a number of drugs have been developed. The best choice concerning which antiretroviral analogs to start is always under discussion, especially in the choice between non-nucleoside reverse transcriptase inhibitors-based therapies and ritonavir-boosted protease inhibitors. Both are proven to control viral replication and lead to immunological gain. The choice between a non-nucleoside analog reverse transcriptase inhibitor and a protease inhibitor as a third antiretroviral drug in the therapy should consider factors related to the individual, as well as the inclusion of the best therapy in the patient's daily activities and potential adherence. The protease inhibitor-based therapies showed similar efficacy among the various inhibitors with characteristics concerning the adverse events from each medicine. For the treatment of protease-resistant patients, darunavir and tipranavir showed good efficacy with higher genetic barrier to resistance.

  6. Internet Selling Expansion Inhibitors: A Mixed Method Approach

    Directory of Open Access Journals (Sweden)

    Shahriar Azizi

    2013-01-01

    Full Text Available This research based on providing five questions has tried to identify and prioritize the main and sub inhibitors of internet selling boosting in Iran. A mixed method research (QUAN has been used in this research. In the qualitative phase, individual in-depth interviews have been done with seven e-shop managers. In this phase, 45 detailed inhibitors have been detected. These 45 inhibitors have been categorized in nine sub categories and four main categories. In the quantitative phase a 51-items questionnaires has been designed including six demographical and 45 specialized questions. Findings of the quantitative phase reveal that the main obstacles include legal, cultural, infrastructural and managerial inhibitors. In addition, sub category inhibitors include legal, governmental, telecommunication, society, human resource, transportation, financial and customer related.     Keywords: e-selling, Iran, Inhibitors, Mixed method.

  7. Towards a green hydrate inhibitor: imaging antifreeze proteins on clathrates.

    Directory of Open Access Journals (Sweden)

    Raimond Gordienko

    Full Text Available The formation of hydrate plugs in oil and gas pipelines is a serious industrial problem and recently there has been an increased interest in the use of alternative hydrate inhibitors as substitutes for thermodynamic inhibitors like methanol. We show here that antifreeze proteins (AFPs possess the ability to modify structure II (sII tetrahydrofuran (THF hydrate crystal morphologies by adhering to the hydrate surface and inhibiting growth in a similar fashion to the kinetic inhibitor poly-N-vinylpyrrolidone (PVP. The effects of AFPs on the formation and growth rate of high-pressure sII gas mix hydrate demonstrated that AFPs are superior hydrate inhibitors compared to PVP. These results indicate that AFPs may be suitable for the study of new inhibitor systems and represent an important step towards the development of biologically-based hydrate inhibitors.

  8. Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma.

    Science.gov (United States)

    Liu, Rui-Ming; Eldridge, Stephanie; Watanabe, Nobuo; Deshane, Jessy; Kuo, Hui-Chien; Jiang, Chunsun; Wang, Yong; Liu, Gang; Schwiebert, Lisa; Miyata, Toshio; Thannickal, Victor J

    2016-02-15

    Asthma is one of the most common respiratory diseases. Although progress has been made in our understanding of airway pathology and many drugs are available to relieve asthma symptoms, there is no cure for chronic asthma. Plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of tissue-type and urokinase-type plasminogen activators, has pleiotropic functions besides suppression of fibrinolysis. In this study, we show that administration of TM5275, an orally effective small-molecule PAI-1 inhibitor, 25 days after ovalbumin (OVA) sensitization-challenge, significantly ameliorated airway hyperresponsiveness in an OVA-induced chronic asthma model. Furthermore, we show that TM5275 administration significantly attenuated OVA-induced infiltration of inflammatory cells (neutrophils, eosinophils, and monocytes), the increase in the levels of OVA-specific IgE and Th2 cytokines (IL-4 and IL-5), the production of mucin in the airways, and airway subepithelial fibrosis. Together, the results suggest that the PAI-1 inhibitor TM5275 may have therapeutic potential for asthma through suppressing eosinophilic allergic response and ameliorating airway remodeling. PMID:26702150

  9. ACE-inhibitor induced angio-oedema treated with complement C1-inhibitor concentrate

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; Bygum, Anette

    2013-01-01

    ACE-inhibitor is an antihypertensive drug which is increasingly used to treat a wide range of medical conditions. A known adverse reaction is angio-oedema of the head and neck, which can become fatal when the upper airway is involved, causing asphyxia. We present a Caucasian man, who developed...

  10. Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils.

    Science.gov (United States)

    Sallenave, J M; Si Tahar, M; Cox, G; Chignard, M; Gauldie, J

    1997-06-01

    Secretory leukocyte proteinase inhibitor (SLPI) is the main neutrophil elastase (HLE) inhibitor found in the upper airways during pulmonary inflammation. It has been shown to be synthesized and secreted in vitro by epithelial cells and has been localized in tracheal glands and bronchiolar epithelial cells by immunocytochemistry. In this study, using immunodetection and immunopurification techniques with specific anti-SLPI immunoglobulin G (IgG), we show that SLPI is present as a native 14-kDa molecule in neutrophil cytosol. In addition, we demonstrate that SLPI is the major inhibitor of HLE present in neutrophil cytosol because pre-incubation with specific anti-SLPI IgG was able to inhibit completely the anti-HLE activity of the cytosol. SLPI can be secreted (probably in an inactive form) by neutrophils and its secretion is enhanced when the cells are stimulated with phorbol myristate acetate (PMA). Elafin, an elastase-specific inhibitor, is also present in minute amounts in neutrophil cytosol and its secretion can be up-regulated. The presence of SLPI in the cytosol of neutrophils may serve as a protective screen against proteinases spilling from azurophilic granules. An alternative or supplementary role may be the maintenance of a differentiated phenotype. PMID:9201260

  11. PARP Inhibitors for the Treatment and Prevention of Breast Cancer

    OpenAIRE

    Vinayak, Shaveta; Ford, James M.

    2010-01-01

    Poly (ADP-ribose) polymerase (PARP) inhibitors, a novel class of drugs that target tumors with DNA repair defects, have received tremendous enthusiasm. Early preclinical studies identified BRCA1 and BRCA2 tumors to be highly sensitive to PARP inhibitors as a result of homologous recombination defect. Based on this premise, PARP inhibitors have been tested in early phase clinical trials as a single agent in BRCA1 or BRCA2 mutation carriers and in combination with chemotherapy in triple-negativ...

  12. Natural compounds as corrosion inhibitors for highly cycled systems

    Energy Technology Data Exchange (ETDEWEB)

    Quraishi, M.A.; Farooqi, I.H.; Saini, P.A. [Corrosion Research Lab., Aligarh (India)

    1999-11-01

    Strict environmental legislations have led to the development of green inhibitors in recent years. In continuation of the authors` research work on development of green inhibitors, they have investigated the aqueous extracts of three plants namely: Azadirachta indica, Punica Granatum and Momordica charantia as corrosion inhibitors for mild steel in 3% NaCl using weight loss and electrochemical methods. All the investigated compounds exhibited excellent corrosion inhibition properties comparable to that of HEDP. Azadirachta showed better scale inhibition effect than HEDP.

  13. Cytochrome p450 inhibitory properties of common efflux transporter inhibitors.

    Science.gov (United States)

    Englund, Gunilla; Lundquist, Patrik; Skogastierna, Cristine; Johansson, Jenny; Hoogstraate, Janet; Afzelius, Lovisa; Andersson, Tommy B; Projean, Denis

    2014-03-01

    Drug transporter inhibitors are important tools to elucidate the contribution of transporters to drug disposition both in vitro and in vivo. These inhibitors are often unselective and affect several transporters as well as drug metabolizing enzymes, which can make experimental results difficult to interpret with confidence. We therefore tested 14 commonly used P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug-resistance associated protein (MRP) inhibitors as inhibitors of cytochrome P450 (P450) enzyme activities using recombinant enzymes. A subset of P-gp and/or CYP3A inhibitors were selected (cyclosporin A, elacridar, ketoconazole, quinidine, reserpine, and tacrolimus) for a comparison of P450 inhibition in human microsomes and hepatocytes. Most P-gp inhibitors showed CYP3A4 inhibition, with potencies often in a similar range as their P-gp inhibition, as well as less potent CYP2C19 inhibition. Other P450 enzymes were not strongly inhibited except a few cases of CYP2D6 inhibition. MRP and BCRP inhibitors showed limited P450 inhibition. Some inhibitors showed less P450 inhibition in human hepatocytes than human liver microsomes, for example, elacridar, probably due to differences in binding, permeability limitations, or active, P-gp mediated efflux of the inhibitor from the hepatocytes. Quinidine was a potent P450 inhibitor in hepatocytes but only showed weak inhibition in microsomes. Quinidine shows an extensive cellular uptake, which may potentiate intracellular P450 inhibition. Elacridar, described as a potent and selective P-gp inhibitor, displayed modest P450 inhibition in this study and is thus a useful model inhibitor to define the role of P-gp in drug disposition without interference with other processes. PMID:24396142

  14. α-Glucosidase inhibitors and their use in clinical practice

    OpenAIRE

    Derosa, Giuseppe; Maffioli, Pamela

    2012-01-01

    Post-prandial hyperglycemia still remains a problem in the management of type 2 diabetes mellitus. Of all available anti-diabetic drugs, α-glucosidase inhibitors seem to be the most effective in reducing post-prandial hyperglycemia. We conducted a review analyzing the clinical efficacy and safety of α-glucosidase inhibitors, both alone and in combination with other anti-diabetic drugs, with respect to glycemic control, inflammation and atherosclerosis. α-Glucosidase inhibitors proved to be ef...

  15. Novel in vitro inhibitory functions of potato tuber proteinaceous inhibitors

    OpenAIRE

    Fischer, M.; Kuckenberg, M.; Kastilan, R.; Muth, J; Gebhardt, C.

    2014-01-01

    Plant protease inhibitors are a structurally highly diverse and ubiquitous class of small proteins, which play various roles in plant development and defense against pests and pathogens. Particular isoforms inhibit in vitro proteases and other enzymes that are not their natural substrates, for example proteases that have roles in human diseases. Mature potato tubers are a rich source of several protease inhibitor families. Different cultivars have different inhibitor profiles. With the object...

  16. SCREENING OF HMG CO A REDUCTASE INHIBITOR PRODUCING MARINE ACTINOMYCETES

    OpenAIRE

    SRINU, PHANI BHUSHAN,MOGES, SRILAKSHMI, SANKAR, PRABHAKAR,LAKSHMINARAYANA

    2013-01-01

    The objective of the present study was screening of 3-hydroxy-3- methyl glutaryl Co A (HMG CoA) reductase inhibitor producing marine actinomycetes. A total of 65 morphologically different actinomycetes were screened for HMG CoA reductase inhibitor production in a two stage submerged fermentation and evaluated for HMG CoA reductase inhibitor activity by agar diffusion and thin layer chromatography technique using lovostatin as a control. Among 65 marine Actinomycete strains, only one strain pr...

  17. Green Plant Extract as a passivationpromoting Inhibitor for Reinforced Concrete

    OpenAIRE

    Abdulrahman A. S.; Mohammad Ismail

    2011-01-01

    The present corrosion inhibitors in market for the protection of steel reinforcement in concrete exposed to chloride attack are toxic to the environment and compromises sustainability drives. There is the needs to develop inhibitor that are eco-friendly and sustainable. In this work the ability of hydrophobic green plant extracts inhibitor (Bambusa arundinacea) to repassivates the chloride induced corrosion of steel was studied. Its efficacy and effectiveness was also compared with calcium ni...

  18. Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

    OpenAIRE

    Monteiro, L; Bonnemaison, D; Vekris, A. (A.); Petry, K G; Bonnet, J; Vidal, R.; Cabrita, J; Mégraud, F.

    1997-01-01

    A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet.

  19. Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

    Science.gov (United States)

    Monteiro, L; Bonnemaison, D; Vekris, A; Petry, K G; Bonnet, J; Vidal, R; Cabrita, J; Mégraud, F

    1997-04-01

    A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet. PMID:9157172

  20. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor

    OpenAIRE

    WU, JINGJING; Zhang, Mingzhi; Liu, Delong

    2016-01-01

    More and more targeted agents become available for B cell malignancies with increasing precision and potency. The first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. More selective BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being explored. Acalabrutinib (ACP-196) is a novel irreversible second-generation BTK inhibitor that was ...