Function of the ATR N-terminal domain revealed by an ATM/ATR chimera

International Nuclear Information System (INIS)

Chen Xinping; Zhao Runxiang; Glick, Gloria G.; Cortez, David

2007-01-01

The ATM and ATR kinases function at the apex of checkpoint signaling pathways. These kinases share significant sequence similarity, phosphorylate many of the same substrates, and have overlapping roles in initiating cell cycle checkpoints. However, they sense DNA damage through distinct mechanisms. ATR primarily senses single stranded DNA (ssDNA) through its interaction with ATRIP, and ATM senses double strand breaks through its interaction with Nbs1. We determined that the N-terminus of ATR contains a domain that binds ATRIP. Attaching this domain to ATM allowed the fusion protein (ATM*) to bind ATRIP and associate with RPA-coated ssDNA. ATM* also gained the ability to localize efficiently to stalled replication forks as well as double strand breaks. Despite having normal kinase activity when tested in vitro and being phosphorylated on S1981 in vivo, ATM* is defective in checkpoint signaling and does not complement cellular deficiencies in either ATM or ATR. These data indicate that the N-terminus of ATR is sufficient to bind ATRIP and to promote localization to sites of replication stress

ATR neutron spectral characterization

Energy Technology Data Exchange (ETDEWEB)

Rogers, J.W.; Anderl, R.A.

1995-11-01

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.

47 CFR 74.733 - UHF translator signal boosters.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false UHF translator signal boosters. 74.733 Section... Translator, and TV Booster Stations § 74.733 UHF translator signal boosters. (a) The licensee of a UHF television broadcast translator station may be authorized to operate one or more signal boosters for the...

48 CFR 733.103-73 - Protests excluded from consideration.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Protests excluded from consideration. 733.103-73 Section 733.103-73 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL... excluded from consideration. (a) Contract administration. Disputes between a contractor and USAID are...

44 CFR 73.3 - Denial of flood insurance coverage.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Denial of flood insurance coverage. 73.3 Section 73.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... sufficient to confirm its identity and location; (2) A clear and unequivocal declaration that the property is...

Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication

Directory of Open Access Journals (Sweden)

Antonio Postigo

2017-05-01

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

Safety significance of ATR passive safety response attributes

International Nuclear Information System (INIS)

Atkinson, S.A.

1990-01-01

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)

ATR-dependent bystander effects in non-targeted cells

International Nuclear Information System (INIS)

Burdak-Rothkamm, S.

2007-01-01

Complete text of publication follows. Radiation induced non-targeted bystander effects have been reported for a range of endpoints including the induction of γH2AX foci which serve as a marker for DNA double strand breaks. We have recently reported the induction of γH2AX foci in non-targeted bystander cells up to 48 hours after irradiation and the involvement of reactive oxygen species (ROS) and TGF-beta 1 in the induction of γH2AX foci (Oncogene (2007) 26:993-1002). Here, we wanted to determine the role of the PI3-like kinases ATM, ATR and DNA-PK in DNA damage signalling in bystander cells. Conditioned medium from T98G cells irradiated with 2 Gy of X-rays was transferred onto non-irradiated cells that were subsequently analysed for the induction of γH2AX, ATR and 53BP1 foci as well as clonogenic survival. Irradiated T98G glioma cells generated signals that induced γH2AX and 53BP1 foci in cells treated with the conditioned medium from irradiated cells. These foci co-localised with ATR foci. Inhibition of ATM and DNA-PK could not suppress the induction of bystander γH2AX foci whereas the mutation of ATR in Seckel cells abrogated bystander foci induction. A restriction of bystander foci to the S-phase of the cell cycle both in T98G cells and in ATR- proficient fibroblasts was observed. These results identify ATR as a central player within the bystander signalling cascade leading to γH2AX and 53BP1 foci formation, and suggest a mechanism of DNA damage induction in non-targeted cells. Further investigations have shown decreased clonogenic cell survival in bystander T98G and ATR wild-type fibroblasts. ATR mutated Seckel cells and also ATM-/- fibroblasts were resistant to this effect suggesting a role for both ATR and ATM in the bystander signalling cascade with regard to cell survival. Taken together, these observations support a hypothesis of DNA damage-induced accumulation of stalled replication forks in bystander cells which are subsequently processed by

Focusing and matching properties of the ATR transfer line

International Nuclear Information System (INIS)

Tsoupas, N.; Fischer, W.; Kewisch, J.; MacKay, W.W.; Peggs, S.; Pilat, F.; Tepikian, S.; Wei, J.

1997-01-01

The AGS to RHIC (AtR) beam transfer line has been constructed and will be used to transfer beam bunches from the AGS machine into the RHIC machine which is presently under construction at BNL. The original design of the AtR line has been modified. This article will present the optics of the various sections of the existing AtR beam line, as well as the matching capabilities of the AtR line to the RHIC machine

ATR Spent Fuel Options Study

International Nuclear Information System (INIS)

Connolly, Michael James; Bean, Thomas E.; Brower, Jeffrey O.; Luke, Dale E.; Patterson, M. W.; Robb, Alan K.; Sindelar, Robert; Smith, Rebecca E.; Tonc, Vincent F.; Tripp, Julia L.; Winston, Philip L.

2017-01-01

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

ATR Spent Fuel Options Study

Energy Technology Data Exchange (ETDEWEB)

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

2017-01-01

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

FLUX SENSOR EVALUATIONS AT THE ATR CRITICAL FACILITY

International Nuclear Information System (INIS)

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

2010-01-01

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

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

Science.gov (United States)

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

2016-05-03

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

On techniques of ATR lattice computation

International Nuclear Information System (INIS)

1997-08-01

Lattice computation is to compute the average nuclear constants of unit fuel lattice which are required for computing core nuclear characteristics such as core power distribution and reactivity characteristics. The main nuclear constants are infinite multiplying rate, neutron movement area, cross section for diffusion computation, local power distribution and isotope composition. As for the lattice computation code, WIMS-ATR is used, which is based on the WIMS-D code developed in U.K., and for the purpose of heightening the accuracy of analysis, which was improved by adding heavy water scattering cross section considering the temperature dependence by Honeck model. For the computation of the neutron absorption by control rods, LOIEL BLUE code is used. The extrapolation distance of neutron flux on control rod surfaces is computed by using THERMOS and DTF codes, and the lattice constants of adjoining lattices are computed by using the WIMS-ATR code. As for the WIMS-ATR code, the computation flow and nuclear data library, and as for the LOIEL BLUE code, the computation flow are explained. The local power distribution in fuel assemblies determined by the WIMS-ATR code was verified with the measured data, and the results are reported. (K.I.)

ATR Commissioning Software Task Force Report

Energy Technology Data Exchange (ETDEWEB)

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

1994-12-16

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

ATR confinement leakage determination

International Nuclear Information System (INIS)

Kuan, P.; Buescher, B.J.

1998-01-01

The air leakage rate from the Advanced Test Reactor (ATR) confinement is an important parameter in estimating hypothesized accidental releases of radiation to the environment. The leakage rate must be determined periodically to assure that the confinement has not degraded with time and such determination is one of the technical safety requirements of ATR operation. This paper reviews the methods of confinement leakage determination and presents an analysis of leakage determination under windy conditions, which can complicate the interpretation of the determined leakage rates. The paper also presents results of analyses of building air exchange under windy conditions. High wind can enhance air exchange and this could increase the release rates of radioisotopes following an accident

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...

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

Directory of Open Access Journals (Sweden)

Suchitra Natarajan

2013-03-01

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

A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation.

Science.gov (United States)

Kabeche, Lilian; Nguyen, Hai Dang; Buisson, Rémi; Zou, Lee

2018-01-05

The ataxia telangiectasia mutated and Rad3-related (ATR) kinase is crucial for DNA damage and replication stress responses. Here, we describe an unexpected role of ATR in mitosis. Acute inhibition or degradation of ATR in mitosis induces whole-chromosome missegregation. The effect of ATR ablation is not due to altered cyclin-dependent kinase 1 (CDK1) activity, DNA damage responses, or unscheduled DNA synthesis but to loss of an ATR function at centromeres. In mitosis, ATR localizes to centromeres through Aurora A-regulated association with centromere protein F (CENP-F), allowing ATR to engage replication protein A (RPA)-coated centromeric R loops. As ATR is activated at centromeres, it stimulates Aurora B through Chk1, preventing formation of lagging chromosomes. Thus, a mitosis-specific and R loop-driven ATR pathway acts at centromeres to promote faithful chromosome segregation, revealing functions of R loops and ATR in suppressing chromosome instability. Copyright © 2018, American Association for the Advancement of Science.

Safety significance of ATR [Advanced Test Reactor] passive safety response attributes

International Nuclear Information System (INIS)

Atkinson, S.A.

1989-01-01

The Advanced Test Reactor (ATR) at the Idaho National Engineering Laboratory was designed with some passive safety response attributes which contribute to the safety posture 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 for 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) model ands 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 Level 1 PRA because of the diversity and redundancy of the ATR firewater injection system (emergency coolant system). 8 refs., 4 figs., 1 tab

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

DEFF Research Database (Denmark)

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

2016-01-01

Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway...... in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults. Mechanistically...

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

Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila.

Science.gov (United States)

Park, Joung-Sun; Na, Hyun-Jin; Pyo, Jung-Hoon; Jeon, Ho-Jun; Kim, Young-Shin; Yoo, Mi-Ae

2015-05-01

The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut. We explored the role of ATM and ATR, utilizing immunostaining with an anti-pS/TQ antibody as an indicator of ATM/ATR activation, γ-irradiation as a DNA damage inducer, and the UAS/GAL4 system for cell type-specific knockdown of ATM, ATR, or both during adulthood. The results showed that the pS/TQ signals got stronger with age and after oxidative stress. The pS/TQ signals were found to be more dependent on ATR rather than on ATM in ISCs/enteroblasts (EBs). Furthermore, an ISC/EB-specific knockdown of ATR, ATM, or both decreased the number of ISCs and oxidative stress-induced ISC proliferation. The phenotypic changes that were caused by the ATR knockdown were more pronounced than those caused by the ATM knockdown; however, our data indicate that ATR and ATM are both needed for ISC maintenance and proliferation; ATR seems to play a bigger role than does ATM.

Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling.

Science.gov (United States)

Choi, Jun-Hyuk; Lindsey-Boltz, Laura A; Kemp, Michael; Mason, Aaron C; Wold, Marc S; Sancar, Aziz

2010-08-03

ATR kinase is a critical upstream regulator of the checkpoint response to various forms of DNA damage. Previous studies have shown that ATR is recruited via its binding partner ATR-interacting protein (ATRIP) to replication protein A (RPA)-covered single-stranded DNA (RPA-ssDNA) generated at sites of DNA damage where ATR is then activated by TopBP1 to phosphorylate downstream targets including the Chk1 signal transducing kinase. However, this critical feature of the human ATR-initiated DNA damage checkpoint signaling has not been demonstrated in a defined system. Here we describe an in vitro checkpoint system in which RPA-ssDNA and TopBP1 are essential for phosphorylation of Chk1 by the purified ATR-ATRIP complex. Checkpoint defective RPA mutants fail to activate ATR kinase in this system, supporting the conclusion that this system is a faithful representation of the in vivo reaction. Interestingly, we find that an alternative form of RPA (aRPA), which does not support DNA replication, can substitute for the checkpoint function of RPA in vitro, thus revealing a potential role for aRPA in the activation of ATR kinase. We also find that TopBP1 is recruited to RPA-ssDNA in a manner dependent on ATRIP and that the N terminus of TopBP1 is required for efficient recruitment and activation of ATR kinase.

MIR-ATR sensor for process monitoring

International Nuclear Information System (INIS)

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

2015-01-01

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

36 CFR 7.33 - Voyageurs National Park.

Science.gov (United States)

2010-07-01

... REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.33 Voyageurs National Park. (a) Fishing. Unless otherwise... intersection with the Black Bay to Moose Bay portage, across Locator, War Club, Quill, Loiten, and Shoepack... management, weather, and park management objectives. (4) Maps showing the designated routes are available at...

Advance of core design method for ATR

International Nuclear Information System (INIS)

Maeda, Seiichirou; Ihara, Toshiteru; Iijima, Takashi; Seino, Hideaki; Kobayashi, Tetsurou; Takeuchi, Michio; Sugawara, Satoru; Matsumoto, Mitsuo.

1995-01-01

Core characteristics of ATR demonstration plant has been revised such as increasing the fuel burnup and the channel power, which is achieved by changing the number of fuel rod per fuel assembly from 28 to 36. The research and development concerning the core design method for ATR have been continued. The calculational errors of core analysis code have been evaluated using the operational data of FUGEN and the full scale simulated test results in DCA (Deuterium Critical Assembly) and HTL (Heat Transfer Loop) at O-arai engineering center. It is confirmed that the calculational error of power distribution is smaller than the design value of ATR demonstration plant. Critical heat flux correlation curve for 36 fuel rod cluster has been developed and the probability evaluation method based on its curve, which is more rational to evaluate the fuel dryout, has been adopted. (author)

Grayscale optical correlator for real-time onboard ATR

Science.gov (United States)

Chao, Tien-Hsin; Zhou, Hanying; Reyes, George F.

2001-03-01

Jet Propulsion Laboratory has been developing grayscale optical correlator (GOC) for a variety of automatic target recognition (ATR) applications. As reported in previous papers, a 128 X 128 camcorder-sized GOC has been demonstrated for real-time field ATR demos. In this paper, we will report the recent development of a prototype 512 X 512 GOC utilizing a new miniature ferroelectric liquid crystal spatial light modulator with a 7-micrometers pixel pitch. Experimental demonstration of ATR applications using this new GOC will be presented. The potential of developing a matchbox-sized GOC will also be discussed. A new application of synthesizing new complex-valued correlation filters using this real-axis 512 X 512 SLM will also be included.

Acrosin inhibitor detecting along the boar epididymis

Czech Academy of Sciences Publication Activity Database

Maňásková-Postlerová, Pavla; Cozlová, Nina; Dorosh, Andriy; Šulc, Miroslav; Guyonet, B.; Jonáková, Věra

2016-01-01

Roč. 82, Jan 2016 (2016), s. 733-739 ISSN 0141-8130 R&D Projects: GA ČR(CZ) GAP503/12/1834; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GA14-05547S Institutional support: RVO:86652036 ; RVO:61388971 Keywords : Acrosin inhibitor * Boar epididymis * Spermatozoa Subject RIV: CE - Biochemistry Impact factor: 3.671, year: 2016

Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection

DEFF Research Database (Denmark)

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

2009-01-01

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

An ATR architecture for algorithm development and testing

Science.gov (United States)

Breivik, Gøril M.; Løkken, Kristin H.; Brattli, Alvin; Palm, Hans C.; Haavardsholm, Trym

2013-05-01

A research platform with four cameras in the infrared and visible spectral domains is under development at the Norwegian Defence Research Establishment (FFI). The platform will be mounted on a high-speed jet aircraft and will primarily be used for image acquisition and for development and test of automatic target recognition (ATR) algorithms. The sensors on board produce large amounts of data, the algorithms can be computationally intensive and the data processing is complex. This puts great demands on the system architecture; it has to run in real-time and at the same time be suitable for algorithm development. In this paper we present an architecture for ATR systems that is designed to be exible, generic and efficient. The architecture is module based so that certain parts, e.g. specific ATR algorithms, can be exchanged without affecting the rest of the system. The modules are generic and can be used in various ATR system configurations. A software framework in C++ that handles large data ows in non-linear pipelines is used for implementation. The framework exploits several levels of parallelism and lets the hardware processing capacity be fully utilised. The ATR system is under development and has reached a first level that can be used for segmentation algorithm development and testing. The implemented system consists of several modules, and although their content is still limited, the segmentation module includes two different segmentation algorithms that can be easily exchanged. We demonstrate the system by applying the two segmentation algorithms to infrared images from sea trial recordings.

ATR, Radiation Transport Models in Atmosphere at Various Altitudes

International Nuclear Information System (INIS)

1981-01-01

1 - Description of problem or function: ATR is a user-oriented code for calculating quickly and simply radiation environment problems at all altitudes in the atmosphere. The code is based on parametric models of a comprehensive data base of air transport results which were generated using discrete ordinates transport techniques for infinite homogeneous air. The effects of air-ground interface and non-uniform air density are treated as perturbation corrections on homogeneous air results. ATR includes parametric models for neutrons and secondary gamma rays as a function of space, energy and source- target angle out to angles of 550 g/cm 2 of air. ATR contains parameterizations of infinite medium air transport of neutrons and secondary gamma rays and correction factors for the air-ground interface and high altitude exponential air. It responds to a series of user-oriented commands which specify the source, geometry and print options to output a variety of useful air transport information, including energy-angle dependent fluence, dose, current, and isodose ranges. 2 - Method of solution: The version 3 differs from earlier versions in that version 3 contains the parameterization of the new neutron and secondary gamma rays data base that was calculated using the latest DNA approved cross sections for air. Other improvements to the ATR code include: parameterization and inclusion into ATR of new air- over-ground correction factors, low energy x-rays calculations, new fission source, and new convenience options. 3 - Restrictions on the complexity of the problem: ATR takes approximately 36,000 decimal words of storage. This can be lessened by overlaying different parts of the code

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

International Nuclear Information System (INIS)

Müller, M.; Torger, B.; Bittrich, E.; Kaul, E.; Ionov, L.; Uhlmann, P.; Stamm, M.

2014-01-01

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

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.

ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

DEFF Research Database (Denmark)

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

2013-01-01

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

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.

ATR Technical Specification Upgrade Program

International Nuclear Information System (INIS)

McCracken, R.T.; Durney, J.L.; Freund, G.A.

1990-01-01

The Advanced Test Reactor (ATR) is a 250 MW, uranium-aluminum fueled test reactor which began full power operation in 1969. The initial operation was controlled by an Operating Limits document based on the original Safety Analysis Report. Additional safety bases were later developed to support Technical Specifications which were approved and implemented in 1977. The Technical Specifications which were initially developed with content and format specified in ANSI/ANS--15.1, ''The Development of Technical Specifications for Research Reactors.'' The safety basis documentation and the Technical Specifications have been updated as required to maintain them current with the ATR facility configuration. All revisions have been made with a content, format and style consistent with the original. A major, two-phase program to upgrade the content, format and style is in progress. This paper describes the first phase of this program

Web-Enabled ATR/Fusion Development System

National Research Council Canada - National Science Library

Ruda, Harald

2001-01-01

.... We have designed a Web-Enabled ATR/Fusion Development System (WEADS) that will allow distributed development and execution of AIR and fusion algorithms using currently available infrastructures...

ATR National Scientific User Facility 2009 Annual Report

International Nuclear Information System (INIS)

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

2010-01-01

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 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.

ATR kinase regulates its attenuation via PPM1D phosphatase ...

Indian Academy of Sciences (India)

In eukaryotes, in response to replication stress, DNA damage response kinase, ATR is activated, whose signalling abrogationleads to cell lethality due to aberrant fork remodelling and excessive origin firing. Here we report that inhibition ofATR kinase activity specifically during replication stress recovery results in persistent ...

48 CFR 733.103-71 - Filing of protest.

Science.gov (United States)

2010-10-01

... GENERAL CONTRACTING REQUIREMENTS PROTESTS, DISPUTES, AND APPEALS Protests 733.103-71 Filing of protest. (a) Protests must be in writing and addressed to the Contracting Officer for consideration by the M/OAA... permitted or required by law or regulation. [61 FR 39094, July 26, 1996; 61 FR 51235, Oct. 1, 1996, as...

The COST733 circulation type classification software: an example for surface ozone concentrations in Central Europe

Science.gov (United States)

Demuzere, Matthias; Kassomenos, P.; Philipp, A.

2011-08-01

In the framework of the COST733 Action "Harmonisation and Applications of Weather Types Classifications for European Regions" a new circulation type classification software (hereafter, referred to as cost733class software) is developed. The cost733class software contains a variety of (European) classification methods and is flexible towards choice of domain of interest, input variables, time step, number of circulation types, sequencing and (weighted) target variables. This work introduces the capabilities of the cost733class software in which the resulting circulation types (CTs) from various circulation type classifications (CTCs) are applied on observed summer surface ozone concentrations in Central Europe. Firstly, the main characteristics of the CTCs in terms of circulation pattern frequencies are addressed using the baseline COST733 catalogue (cat 2.0), at present the latest product of the new cost733class software. In a second step, the probabilistic Brier skill score is used to quantify the explanatory power of all classifications in terms of the maximum 8 hourly mean ozone concentrations exceeding the 120-μg/m3 threshold; this was based on ozone concentrations from 130 Central European measurement stations. Averaged evaluation results over all stations indicate generally higher performance of CTCs with a higher number of types. Within the subset of methodologies with a similar number of types, the results suggest that the use of CTCs based on optimisation algorithms are performing slightly better than those which are based on other algorithms (predefined thresholds, principal component analysis and leader algorithms). The results are further elaborated by exploring additional capabilities of the cost733class software. Sensitivity experiments are performed using different domain sizes, input variables, seasonally based classifications and multiple-day sequencing. As an illustration, CTCs which are also conditioned towards temperature with various weights

Status report of the ATR SPING-3A and detailed calibration guideline

International Nuclear Information System (INIS)

Koeppen, L.D.; Rogers, J.W.

1985-12-01

The Radiation Measurements Laboratory (RML) onducted testing and an evaluation of the ATR SPING-3 after installation of the new ''A'' series software (firmware) and retrofit kit. The purpose of this report is to provide the ATR SPING-3A users with a document describing the present status of the unit, how the system was tested, a suggested calibration guideline, how the system should be operated for the ATR application, and why it should be used in this manner

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

Science.gov (United States)

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

2017-02-01

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

Homeostatic regulation of meiotic DSB formation by ATM/ATR

International Nuclear Information System (INIS)

Cooper, Tim J.; Wardell, Kayleigh; Garcia, Valerie; Neale, Matthew J.

2014-01-01

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

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.

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

International Nuclear Information System (INIS)

Pauklin, Siim; Kristjuhan, Arnold; Maimets, Toivo; Jaks, Viljar

2005-01-01

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

Protein phosphatase 5 is necessary for ATR-mediated DNA repair

International Nuclear Information System (INIS)

Kang, Yoonsung; Cheong, Hyang-Min; Lee, Jung-Hee; Song, Peter I.; Lee, Kwang-Ho; Kim, Sang-Yong; Jun, Jae Yeoul; You, Ho Jin

2011-01-01

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.

ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.

Science.gov (United States)

Cheng, Aifang; Zhao, Teng; Tse, Kai-Hei; Chow, Hei-Man; Cui, Yong; Jiang, Liwen; Du, Shengwang; Loy, Michael M T; Herrup, Karl

2018-01-09

ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. In keeping with this, both proteins bind to AP-2 complex components as well as to clathrin, suggesting roles in endocytosis and vesicle recycling. The two proteins play complementary roles in the DDR; ATM is engaged in the repair of double-strand breaks, while ATR deals mainly with single-strand damage. Unexpectedly, this complementarity extends to these proteins' synaptic function as well. Superresolution microscopy and coimmunoprecipitation reveal that ATM associates exclusively with excitatory (VGLUT1 + ) vesicles, while ATR associates only with inhibitory (VGAT + ) vesicles. The levels of ATM and ATR respond to each other; when ATM is deficient, ATR levels rise, and vice versa. Finally, blocking NMDA, but not GABA, receptors causes ATM levels to rise while ATR levels respond to GABA, but not NMDA, receptor blockade. Taken together, our data suggest that ATM and ATR are part of the cellular "infrastructure" that maintains the excitatory/inhibitory balance of the nervous system. This idea has important implications for the human diseases resulting from their genetic deficiency.

Initial characterization of the ATR [Advanced Test Reactor] Large Gamma Facility

International Nuclear Information System (INIS)

Schnitzler, B.G.; Rogers, J.W.

1986-05-01

Radiation fields in the ATR Large Gamma Facility test volume are characterized. The preliminary characterization efforts described in this report include total dose rate measurements in the facility, development of a simple methodology for calculating radiation fields from the ATR fuel element power histories, and a comparison of the measured and calculated values

PUREX new substation ATR

International Nuclear Information System (INIS)

Nelson, D.E.

1997-01-01

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

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.

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

Science.gov (United States)

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

2017-01-25

The DNA damage response (DDR) orchestrates a network of cellular processes that integrates cell-cycle control and DNA repair or apoptosis, which serves to maintain genome stability. DNA-PKcs (the catalytic subunit of the DNA-dependent kinase, encoded by PRKDC), ATM (ataxia telangiectasia, mutated), and ATR (ATM and Rad3-related) are related PI3K-like protein kinases and central regulators of the DDR. Defects in these kinases have been linked to neurodegenerative or neurodevelopmental syndromes. In all cases, the key neuroprotective function of these kinases is uncertain. It also remains unclear how interactions between the three DNA damage-responsive kinases coordinate genome stability, particularly in a physiological context. Here, we used a genetic approach to identify the neural function of DNA-PKcs and the interplay between ATM and ATR during neurogenesis. We found that DNA-PKcs loss in the mouse sensitized neuronal progenitors to apoptosis after ionizing radiation because of excessive DNA damage. DNA-PKcs was also required to prevent endogenous DNA damage accumulation throughout the adult brain. In contrast, ATR coordinated the DDR during neurogenesis to direct apoptosis in cycling neural progenitors, whereas ATM regulated apoptosis in both proliferative and noncycling cells. We also found that ATR controls a DNA damage-induced G 2 /M checkpoint in cortical progenitors, independent of ATM and DNA-PKcs. These nonoverlapping roles were further confirmed via sustained murine embryonic or cortical development after all three kinases were simultaneously inactivated. Thus, our results illustrate how DNA-PKcs, ATM, and ATR have unique and essential roles during the DDR, collectively ensuring comprehensive genome maintenance in the nervous system. The DNA damage response (DDR) is essential for prevention of a broad spectrum of different human neurologic diseases. However, a detailed understanding of the DDR at a physiological level is lacking. In contrast to many in

Advanced Test Reactor (ATR) Facility 10CFR830 Safety Basis Related to Facility Experiments

International Nuclear Information System (INIS)

Tomberlin, T.A.

2002-01-01

The Idaho National Engineering and Environmental Laboratory (INEEL) Advanced Test Reactor (ATR), a DOE Category A reactor, was designed to provide an irradiation test environment for conducting a variety of experiments. The ATR Safety Analysis Report, determined by DOE to meet the requirements of 10 CFR 830, Subpart B, provides versatility in types of experiments that may be conducted. This paper addresses two general types of experiments in the ATR facility and how safety analyses for experiments are related to the ATR safety basis. One type of experiment is more routine and generally represents greater risks; therefore this type of experiment is addressed with more detail in the safety basis. This allows individual safety analyses for these experiments to be more routine and repetitive. The second type of experiment is less defined and is permitted under more general controls. Therefore, individual safety analyses for the second type of experiment tend to be more unique from experiment to experiment. Experiments are also discussed relative to ''major modifications'' and DOE-STD-1027-92. Application of the USQ process to ATR experiments is also discussed

L'Atrésie colique:À propos de deux cas

African Journals Online (AJOL)

... dans un tableau d'occlusion néonatale haute. L'atrésie colique était de découverte fortuite en per-opératoire, associée à une atrésie grêlique. Le patient a bénéficié d'une double stomie, mais les suites opératoires ont été marquées par le décès dans un tableau de choc septique. A la lumière des ces deux observations ...

A Shld1-controlled POT1a provides support for repression of ATR signaling at telomeres through RPA exclusion.

Science.gov (United States)

Gong, Yi; de Lange, Titia

2010-11-12

We previously proposed that POT1 prevents ATR signaling at telomeres by excluding RPA from the single-stranded TTAGGG repeats. Here, we use a Shld1-stabilized degron-POT1a fusion (DD-POT1a) to study the telomeric ATR kinase response. In the absence of Shld1, DD-POT1a degradation resulted in rapid and reversible activation of the ATR pathway in G1 and S/G2. ATR signaling was abrogated by shRNAs to ATR and TopBP1, but shRNAs to the ATM kinase or DNA-PKcs did not affect the telomere damage response. Importantly, ATR signaling in G1 and S/G2 was reduced by shRNAs to RPA. In S/G2, RPA was readily detectable at dysfunctional telomeres, and both POT1a and POT1b were required to exclude RPA and prevent ATR activation. In G1, the accumulation of RPA at dysfunctional telomeres was strikingly less, and POT1a was sufficient to repress ATR signaling. These results support an RPA exclusion model for the repression of ATR signaling at telomeres. Copyright © 2010 Elsevier Inc. All rights reserved.

Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells.

Science.gov (United States)

García, Víctor; Lara-Chica, Maribel; Cantarero, Irene; Sterner, Olov; Calzado, Marco A; Muñoz, Eduardo

2016-01-26

Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer.

Generation and assessment of turntable SAR data for the support of ATR development

Science.gov (United States)

Cohen, Marvin N.; Showman, Gregory A.; Sangston, K. James; Sylvester, Vincent B.; Gostin, Lamar; Scheer, C. Ruby

1998-10-01

Inverse synthetic aperture radar (ISAR) imaging on a turntable-tower test range permits convenient generation of high resolution two-dimensional images of radar targets under controlled conditions for testing SAR image processing and for supporting automatic target recognition (ATR) algorithm development. However, turntable ISAR images are often obtained under near-field geometries and hence may suffer geometric distortions not present in airborne SAR images. In this paper, turntable data collected at Georgia Tech's Electromagnetic Test Facility are used to begin to assess the utility of two- dimensional ISAR imaging algorithms in forming images to support ATR development. The imaging algorithms considered include a simple 2D discrete Fourier transform (DFT), a 2-D DFT with geometric correction based on image domain resampling, and a computationally-intensive geometric matched filter solution. Images formed with the various algorithms are used to develop ATR templates, which are then compared with an eye toward utilization in an ATR algorithm.

Characterization and sintering of niobium-ATR alumina

International Nuclear Information System (INIS)

Sibuya, N.H.; Iwasaki, H.; Suzuki, C.K.; Pinatti, D.G.

1987-01-01

In the niobium aluminothermy a slag is produced, composed mostly of alumina and other compounds such as niobium oxide and silica. The phase composition of this ATR alumina was characterized by X-ray powder diffractometry, and afterwards this alumina was subjected to leaching processes. It was noticed that the original content of 70% α-alumina in slag rose to 95% after the calcination. ATR alumina (leached and calcined, and without any treatment) was used to make pressed bodies which were fired in air at 1200 to 1400 0 C for 1 to 10,5 hours; and in vacuum at 1550 to 1800$0C for 2 hours. Characterization was done by density measurements, X-ray diffractometry and ultrasonic analysis. Ultrasonic analysis of some vacuum fired bodies showed londitudinal velocities close to the value found in literature. Correlation of several techniques measurements disclosed the niobium oxide interference in sintering. (Author) [pt

Oxidative stress provokes distinct transcriptional responses in the stress-tolerant atr7 and stress-sensitive loh2 Arabidopsis thaliana mutants as revealed by multi-parallel quantitative real-time PCR analysis of ROS marker and antioxidant genes

NARCIS (Netherlands)

Mehterov, Nikolay; Balazadeh, Salma; Hille, Jacques; Toneva, Valentina; Mueller-Roeber, Bernd; Gechev, Tsanko

2012-01-01

The Arabidopsis thaliana atr7 mutant is tolerant to oxidative stress induced by paraquat (PQ) or the catalase inhibitor aminotriazole (AT), while its original background loh2 and wild-type plants are sensitive. Both, AT and PQ which stimulate the intracellular formation of H2O2 or superoxide anions,

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

Directory of Open Access Journals (Sweden)

Ana Belén Herrero

2017-05-01

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

Roles of ATR1 paralogs YMR279c and YOR378w in boron stress tolerance

International Nuclear Information System (INIS)

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

2011-01-01

Highlights: → ATR1 paralog YMR279c plays role in boron detoxification. → YMR279c overexpression lowers cytoplasmic boron levels. → ATR1 paralog YOR378w has no roles in boron stress response. -- Abstract: Boron is a necessary nutrient for plants and animals, however excess of it causes toxicity. Previously, Atr1 and Arabidopsis Bor1 homolog were identified as the boron efflux pump in yeast, which lower the cytosolic boron concentration and help cells to survive in the presence of toxic amount of boron. In this study, we analyzed ATR1 paralogs, YMR279c and YOR378w, to understand whether they participate in boron stress tolerance in yeast. Even though these genes share homology with ATR1, neither their deletion rendered cells boron sensitive nor their expression was significantly upregulated by boron treatment. However, expression of YMR279, but not YOR378w, from the constitutive GAPDH promoter on a high copy plasmid provided remarkable boron resistance by decreasing intracellular boron levels. Thus our results suggest the presence of a third boron exporter, YMR279c, which functions similar to ATR1 and provides boron resistance in yeast.

Pressure-modulation dynamic attenuated-total-reflectance (ATR) FT-IR spectroscopy

Science.gov (United States)

Marcott, C.; Story, G. M.; Noda, I.; Bibby, A.; Manning, C. J.

1998-06-01

A single-reflectance attenuated-total-reflectance (ATR) accessory with a diamond internal-reflection element was modified by the addition of a piezoelectric transducer. Initial dynamic pressure-modulation experiments have been performed in the sample compartment of a step-scanning FT-IR spectrometer. A sinusoidal pressure modulation applied to samples of isotactic polypropylene and linear low density polyethylene resulted in dynamic responses which appear to be similar to those observed in previous dynamic 2D IR experiments. Preliminary pressure-modulation dynamic ATR results are also reported for a styrene-butadiene-styrene triblock copolymer. The new method has the advantages that a much wider variety of sample types and geometries can be studied and less sample preparation is required. Dynamic 2D IR experiments carried out by ATR no longer require thin films of large area and sufficient strength to withstand the dynamic strain applied by a rheometer. The ability to obtain dynamic IR spectroscopic information from a wider variety of sample types and thicknesses would greatly expand the amount of useful information that could be extracted from normally complicated, highly overlapped IR spectra.

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

Science.gov (United States)

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

2017-10-01

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

Mox fuel utilization in ATR

OpenAIRE

下村 和生; 川太 徳夫

1987-01-01

ATR, a heavy-water moderated boiling-light-water cooled reactor developed in Japan, is a unique reactor with out-standing flexibility regarding nuclear fuel utilization, because it has superior properties concerning the utilization of plutonium, recovered uranium and depleted uranium. The development of this type of reactor is expected to contribute both to the stable supply of energy and to the establishment of plutonium utilization in Japan. Much effort has been and will be made on the deve...

RPA70 depletion induces hSSB1/2-INTS3 complex to initiate ATR signaling

OpenAIRE

Kar, Ananya; Kaur, Manpreet; Ghosh, Tanushree; Khan, Md. Muntaz; Sharma, Aparna; Shekhar, Ritu; Varshney, Akhil; Saxena, Sandeep

2015-01-01

The primary eukaryotic single-stranded DNA-binding protein, Replication protein A (RPA), binds to single-stranded DNA at the sites of DNA damage and recruits the apical checkpoint kinase, ATR via its partner protein, ATRIP. It has been demonstrated that absence of RPA incapacitates the ATR-mediated checkpoint response. We report that in the absence of RPA, human single-stranded DNA-binding protein 1 (hSSB1) and its partner protein INTS3 form sub-nuclear foci, associate with the ATR-ATRIP comp...

ATM/ATR-mediated phosphorylation of PALB2 promotes RAD51 function

DEFF Research Database (Denmark)

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

2016-01-01

DNA damage activates the ATM and ATR kinases that coordinate checkpoint and DNA repair pathways. An essential step in homology-directed repair (HDR) of DNA breaks is the formation of RAD51 nucleofilaments mediated by PALB2-BRCA2; however, roles of ATM and ATR in this critical step of HDR are poor...... function, as the PALB2-dependent checkpoint response is normal in cells expressing the phospho-deficient PALB2 mutant. Collectively, our findings highlight a critical importance of PALB2 phosphorylation as a novel regulatory step in genome maintenance after genotoxic stress....

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

Human papillomavirus detection using PCR and ATR-FTIR for cervical cancer screening

Science.gov (United States)

Rymsza, Taciana; Ribeiro, Eliane Aline; de Carvalho, Luis Felipe das Chagas e. Silva; Bhattacharjee, Tanmoy; de Azevedo Canevari, Renata

2018-05-01

The human papillomavirus (HPV) genital infection is considered one of the most common sexually transmitted diseases worldwide, and has been associated with cervical cancer. The objective of this study was to investigate the efficacy of the diagnostic methods: polymerase chain reaction (PCR) and Fourier transform infrared (FTIR) equipped with an ATR (Attenuated Total Reflectance) unit (Pike Tech) spectroscopy, to diagnose HPV infection in women undergoing gynecological examination. Seventeen patients (41.46%) of the 41 patients analyzed were diagnosed with exophytic/condyloma acuminate lesions by clinical analysis, 29 patients (70.7%) (G1 group) of the 41 patients, showed positive result for HPV cell injury by oncotic colpocitology and 12 patients (29.3%) (G2 group), presented negative result for cellular lesion and absence of clinical HPV lesion. Four samples were obtained per patient, which were submitted oncotic colpocitology analysis (Papanicolau staining, two samples), PCR (one sample) and ATR-FTIR analysis (one sample). L1 gene was amplified by PCR technique with specific GP5+/GP6+ and MY09/MY11 primers. PCR results were uniformly positive for presence of HPV in all analyzed samples. Multivariate analysis of ATR-FTIR spectra suggests no significant biochemical changes between groups and no clustering formed, concurring with results of PCR. This study suggests that PCR and ATR-FTIR are highly sensitive technique for HPV detection.

RPA-Binding Protein ETAA1 Is an ATR Activator Involved in DNA Replication Stress Response.

Science.gov (United States)

Lee, Yuan-Cho; Zhou, Qing; Chen, Junjie; Yuan, Jingsong

2016-12-19

ETAA1 (Ewing tumor-associated antigen 1), also known as ETAA16, was identified as a tumor-specific antigen in the Ewing family of tumors. However, the biological function of this protein remains unknown. Here, we report the identification of ETAA1 as a DNA replication stress response protein. ETAA1 specifically interacts with RPA (Replication protein A) via two conserved RPA-binding domains and is therefore recruited to stalled replication forks. Interestingly, further analysis of ETAA1 function revealed that ETAA1 participates in the activation of ATR signaling pathway via a conserved ATR-activating domain (AAD) located near its N terminus. Importantly, we demonstrate that both RPA binding and ATR activation are required for ETAA1 function at stalled replication forks to maintain genome stability. Therefore, our data suggest that ETAA1 is a new ATR activator involved in replication checkpoint control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of the ATR fuel element swaging process

International Nuclear Information System (INIS)

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

1995-12-01

This report documents a detailed evaluation of the swaging process used to connect fuel plates to side plates in Advanced Test Reactor (ATR) fuel elements. The swaging is a mechanical process that begins with fitting a fuel plate into grooves in the side plates. Once a fuel plate is positioned, a lip on each of two side plate grooves is pressed into the fuel plate using swaging wheels to form the joints. Each connection must have a specified strength (measured in terms, of a pullout force capacity) to assure that these joints do not fail during reactor operation. The purpose of this study is to analyze the swaging process and associated procedural controls, and to provide recommendations to assure that the manufacturing process produces swaged connections that meet the minimum strength requirement. The current fuel element manufacturer, Babcock and Wilcox (B 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

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

27 CFR 73.3 - What terms must I know to understand this part?

Science.gov (United States)

2010-04-01

... TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) PROCEDURES AND PRACTICES ELECTRONIC SIGNATURES; ELECTRONIC SUBMISSION OF FORMS General Provisions Definitions § 73.3 What terms must I know to understand... and/or actions are both unique to that individual and measurable. Digital signature. An electronic...

What factors determine patients' preference for tumour necrosis factor inhibitors in ankylosing spondylitis?

Science.gov (United States)

Fajri, Dessy W; Brand, Caroline A; Dharmage, Shyamali C; Martin, Belinda J; Buchanan, Russell R C; Schachna, Lionel

2009-05-01

Tumour necrosis factor inhibitor (TNFi) therapy, either intravenous (IV) or subcutaneous (SQ), demonstrates similar efficacy in ankylosing spondylitis (AS). The objective of this study was to examine factors influencing patient preference of TNFi. Fifty-nine (79.7%) participants were male with mean age 43.9 years and disease duration of 22.0 years. Fifty-nine patients (79.7%) agreed with the statement 'My doctor gave me a choice and I made a decision based on my personal preference'. Patients commenced first on IV TNFi most commonly cited reduced frequency of injections (96.6%), administration by a trained professional (89.7%) and use of infusion time for leisure activities (86.2%). Patients commenced on SQ TNFi cited flexibility with timing of treatment (80%), shortened administration time (73.3%) and the convenience of home therapy (73.3%). Shared clinical decision-making between clinicians and patients may be desirable for AS patients commencing TNFi therapy.

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-05-25

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

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

International Nuclear Information System (INIS)

Wang, Hui-Feng; Yan, Yan-Gang; Huo, Sheng-Juan; Cai, Wen-Bin; Xu, Qun-Jie; Osawa, Masatoshi

2007-01-01

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

Volvulus and bowel obstruction in ATR-X syndrome-clinical report and review of literature.

Science.gov (United States)

Horesh, Nir; Pery, Ron; Amiel, Imri; Shwaartz, Chaya; Speter, Chen; Guranda, Larisa; Gutman, Mordechai; Hoffman, Aviad

2015-11-01

Alpha thalassemia-mental retardation, X-linked (ATR-X) syndrome is a rare genetic disorder with a variety of clinical manifestations. Gastrointestinal symptoms described in this syndrome include difficulties in feeding, regurgitation and vomiting which may lead to aspiration pneumonia, abdominal pain, distention, and constipation. We present a 19-year-old male diagnosed with ATR-X syndrome, who suffered from recurrent colonic volvulus that ultimately led to bowel necrosis with severe septic shock requiring emergent surgical intervention. During 1 year, the patient was readmitted four times due to poor oral intake, dehydration and abdominal distention. Investigation revealed partial small bowel volvulus which resolved with non-operative treatment. Small and large bowel volvulus are uncommon and life-threatening gastrointestinal manifestations of ATR-X patients, which may contribute to the common phenomenon of prolonged food refusal in these patients. © 2015 Wiley Periodicals, Inc.

In vitro analysis of the role of replication protein A (RPA) and RPA phosphorylation in ATR-mediated checkpoint signaling.

Science.gov (United States)

Lindsey-Boltz, Laura A; Reardon, Joyce T; Wold, Marc S; Sancar, Aziz

2012-10-19

Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair.

In Vitro Analysis of the Role of Replication Protein A (RPA) and RPA Phosphorylation in ATR-mediated Checkpoint Signaling*

Science.gov (United States)

Lindsey-Boltz, Laura A.; Reardon, Joyce T.; Wold, Marc S.; Sancar, Aziz

2012-01-01

Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair. PMID:22948311

5 CFR 733.103 - Permitted political activities-employees who reside in designated localities.

Science.gov (United States)

2010-01-01

... subdivision designated by OPM under § 733.107 may: (1) Run as independent candidates for election to partisan..., accept, or receive a political contribution as, or on behalf of, an independent candidate for partisan... volunteer services as an independent candidate, or on behalf of an independent candidate, for local partisan...

[Relationship between PMI and ATR-FTIR Spectral Changes in Swine Costal Cartilages and Ribs].

Science.gov (United States)

Yao, Yao; Wang, Qi; Jing, Xiao-li; Li, Bing; Zhang, Yin-ming; Wang, Zhi-jun; Li, Cheng-zhi; Lin, Han-cheng; Zhang, Ji; Huang, Ping; Wang, Zhen-yuan

2016-02-01

To analyze postmortem chemical changes in Landrace costal cartilages and ribs using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, and to provide a novel technique for estimation of postmortem interval (PMI). The swines were sacrificed by hemorrhage and their costal cartilages and ribs were kept in 20 degrees C. The chemical analysis of the costal cartilages and ribs were performed using ATR-FTIR every 72 h. The correlation between the certain spectral parameters and PMI was also analyzed. The time-dependent changes of costal cartilages were more significant than ribs. There were no obvious changes for the main absorbance bands position, and some absorbance band ratios showed time-dependent changes and significant correlations with the PMI. ATR-FTIR has the ability to analyze postmortem chemical changes of the swine costal cartilages and ribs, and it can be a new method to estimate PMI based on spectroscopy.

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

ATR kinase regulates its attenuation via PPM1D phosphatase ...

Indian Academy of Sciences (India)

Debadrita Bhattacharya

2018-02-07

Feb 7, 2018 ... generated in response to ultraviolet and ionizing radiation (Lu et al. 2005a, b; Cha ... nocopy' each other's effects by uncovering persistent ATR signalling that in ...... been shown to indirectly stabilize PPM1D by mediating the.

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

International Nuclear Information System (INIS)

Duckwitz, Noel

2011-01-01

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

Analysis of cosmetic residues on a single human hair by ATR FT-IR microspectroscopy.

Science.gov (United States)

Pienpinijtham, Prompong; Thammacharoen, Chuchaat; Naranitad, Suwimol; Ekgasit, Sanong

2018-05-15

In this work, ATR FT-IR spectra of single human hair and cosmetic residues on hair surface are successfully collected using a homemade dome-shaped Ge μIRE accessary installed on an infrared microscope. By collecting ATR spectra of hairs from the same person, the spectral patterns are identical and superimposed while different spectral features are observed from ATR spectra of hairs collected from different persons. The spectral differences depend on individual hair characteristics, chemical treatments, and cosmetics on hair surface. The "Contact-and-Collect" technique that transfers remarkable materials on the hair surface to the tip of the Ge μIRE enables an identification of cosmetics on a single hair. Moreover, the differences between un-split and split hairs are also studied in this report. These highly specific spectral features can be employed for unique identification or for differentiation of hairs based on the molecular structures of hairs and cosmetics on hairs. Copyright © 2018 Elsevier B.V. All rights reserved.

Analysis of cosmetic residues on a single human hair by ATR FT-IR microspectroscopy

Science.gov (United States)

Pienpinijtham, Prompong; Thammacharoen, Chuchaat; Naranitad, Suwimol; Ekgasit, Sanong

2018-05-01

In this work, ATR FT-IR spectra of single human hair and cosmetic residues on hair surface are successfully collected using a homemade dome-shaped Ge μIRE accessary installed on an infrared microscope. By collecting ATR spectra of hairs from the same person, the spectral patterns are identical and superimposed while different spectral features are observed from ATR spectra of hairs collected from different persons. The spectral differences depend on individual hair characteristics, chemical treatments, and cosmetics on hair surface. The "Contact-and-Collect" technique that transfers remarkable materials on the hair surface to the tip of the Ge μIRE enables an identification of cosmetics on a single hair. Moreover, the differences between un-split and split hairs are also studied in this report. These highly specific spectral features can be employed for unique identification or for differentiation of hairs based on the molecular structures of hairs and cosmetics on hairs.

Gauvain e il corpo smembrato: allegorie nell'«Atre périlleux»

Directory of Open Access Journals (Sweden)

Maurizio Virdis

2013-07-01

Full Text Available L’Atre Périlleux è un romanzo anonimo francese del XIII secolo e fa parte della corrente letteraria che rimettere in questione il romanzo cortese di tradizione chrestieniana. Piú che all’ideologia o alle istanze della classe cavalleresca e della nobiltà minore, il nostro romanzo risponde alle prospettive e alle necessità intellettuali della clergie, che si fa gioco dei valori cavallereschi tradizionali. L’Atre Périlleux è condotto, con toni di humour e una trama complessa, su binari metaletterari e allegorici (di cui il corpo smembrato di Gauvain è il simbolo piú eminente, e si pone come critica della decadenza della società cortese, animato però dal proposito del rinnovamento morale di essa.L’Atre Périlleux is an anonymous French romance of the thirteenth century and it is part of the literary movement that calls into question the tradition of courtly romance dating back to Chrétien de Troyes. More than to the ideology and instances of the class of minor nobility and chivalry, our romance responds to the clergie’s needs and intellectual perspectives, and it mocks the traditional values of chivalry. L’Atre Périlleux is conducted, with a hint of humour and a complicated plot, on metaliterary and allegorical tracks (and Gauvain’s dismembered body is the most prominent symbol of this allegorical tone, so that our romance stands as a critique of courtly society decadence, nevertheless animated by the purpose of its moral renewal.

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

Science.gov (United States)

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

2016-01-01

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

Application of PSA level 1 for the Fugen prototype ATR plant

International Nuclear Information System (INIS)

Ikeda, H.; Iguchi, Y.; Sotsu, M.; Seki, O.; Satou, S.

1997-01-01

This paper presents application of PSA Level-1 for Prototype Advanced Thermal Reactor Plant ''Fugen'' in consideration of the design characteristics of such reactor and verify the safety aspect of Fugen using thus established procedure, ATR resembles the boiling water reactor (BWR) in a number of points, but there are also some differences between the ATR and the BWR. Therefore. PSA procedure have been established by taking such difference into consideration and by referring to experience of PSA in USA and Japan. Moreover, the core damage frequency was calculated on Fugen by using thus established procedure. As a result, it was verified that results including the maximum value of the uncertainty estimation were found to be quite satisfactory against the target value of reactor damage frequency defined by the International Atomic Energy Agency (IAEA). (author)

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.

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.

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.

In situ detection of cancerous kidney tissue by means of fiber ATR-FTIR spectroscopy

Science.gov (United States)

Sablinskas, Valdas; Velicka, Martynas; Pucetaite, Milda; Urboniene, Vidita; Ceponkus, Justinas; Bandzeviciute, Rimante; Jankevicius, Feliksas; Sakharova, Tatiana; Bibikova, Olga; Steiner, Gerald

2018-02-01

The crucial goal of kidney-sparing surgical resection of a malignant tumor is complete removal of the cancerous tissue. The exact border between the cancerous and normal tissues is not always possible to identify by naked eye, therefore, a supplementary intraoperative diagnosis is needed. Unfortunately, intraoperative pathology methods used nowadays are time consuming and of inadequate quality rendering not definitive diagnosis. It has recently been shown that ATR-FTIR spectroscopy can be used for fast discrimination between cancerous and normal kidney tissues by analyzing the collected spectra of the tissue touch imprint smears. Most prominent differences are obtained in the wavenumber region from 950 cm-1 to 1250 cm-1, where the spectral bands due to the molecular vibrations of glycogen arise in the spectra of cancerous tissue smears. Such method of detection of cancerous tissue is limited by requirement to transfer the suspected tissue from the body to the FTIR instrument and stamp it on an ATR crystal of the spectrometer. We propose a spectroscopic tool which exploits the same principle of detection of cancerous cells as mentioned above, but does not require the tissue to be transferred from the body to the spectrometer. The portable spectrometer used in this design is equipped with fiber ATR probe and a sensitive liquid nitrogen cooled MCT detector. The design of the fiber probe allows the ATR tip to be changed easily in order to use only new sterilized tips for each measurement point of the tissue. It also enables sampling multiple areas of the suspected tissue with high lateral resolution which, in turn, increases accuracy with which the marginal regions between normal and cancerous tissues can be identified. Due to the loss of optical signal in the fiber probe the spectra have lower signal-to-noise ratio than in the case of standard ATR sampling setup. However, software for the spectral analysis used with the fiber probe design is still able to distinguish

Achieving safety/risk goals for less ATR backup power upgrades

International Nuclear Information System (INIS)

Atkinson, S.A.

1995-01-01

The Advanced Test Reactor probabilistic risk assessment for internal fire and flood events defined a relatively high risk for a total loss of electric power possibly leading to core damage. Backup power sources were disabled due to fire and flooding in the diesel generator area with propagation of the flooding to a common switchgear room. The ATR risk assessment was employed to define options for relocation of backup power system components to achieve needed risk reduction while minimizing costs. The risk evaluations were performed using sensitivity studies and importance measures. The risk-based evaluations of relocation options for backup power systems saved over $3 million from what might have been otherwise considered open-quotes necessaryclose quotes for safety/risk improvement. The ATR experience shows that the advantages of a good risk assessment are to define risk significance, risk specifics, and risk solutions which enable risk goals to be achieved at the lowest cost

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-04-01

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

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

Science.gov (United States)

Remes, Z.; Kozak, H.; Rezek, B.; Ukraintsev, E.; Babchenko, O.; Kromka, A.; Girard, H. A.; Arnault, J.-C.; Bergonzo, P.

2013-04-01

Linear antenna microwave chemical vapor deposition process was used to homogeneously coat a 7 cm long silicon prism by 85 nm thin nanocrystalline diamond (NCD) layer. To show the advantages of the NCD-coated prism for attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) of nanoparticles, we apply diamond nanoparticles (DNPs) of 5 nm nominal size with various surface modifications by a drop-casting of their methanol dispersions. ATR-FTIR spectra of as-received, air-annealed, plasma-oxidized, and plasma-hydrogenated DNPs were measured in the 4000-1500 cm-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.

30 CFR 75.209 - Automated Temporary Roof Support (ATRS) systems.

Science.gov (United States)

2010-07-01

... of temporary support shall be used, as specified in the roof control plan, when— (1) Mining... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Automated Temporary Roof Support (ATRS) systems... COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Roof Support § 75.209...

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

A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors

Science.gov (United States)

2017-02-01

affecting the function of Fanconi Anemia (FA) genes ( FANCA /B/C/D2/E/F/G/I/J/L/M, PALB2) or DNA damage response genes involved in HR 5 (ATM, ATR...Award Number: W81XWH-10-1-0585 TITLE: A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors...To) 15 July 2010 – 2 Nov.2016 4. TITLE AND SUBTITLE A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP

Signaling through cGMP-dependent protein kinase I in the amygdala is critical for auditory-cued fear memory and long-term potentiation.

Science.gov (United States)

Paul, Cindy; Schöberl, Florian; Weinmeister, Pascal; Micale, Vincenzo; Wotjak, Carsten T; Hofmann, Franz; Kleppisch, Thomas

2008-12-24

Long-term potentiation (LTP) of inputs relaying sensory information from cortical and thalamic neurons to principal neurons in the lateral amygdala (LA) is thought to serve as a cellular mechanism for associative fear learning. Nitric oxide (NO), a messenger molecule widely implicated in synaptic plasticity and behavior, has been shown to enhance LTP in the LA as well as consolidation of associative fear memory. Additional evidence suggests that NO-induced enhancement of LTP and amygdala-dependent learning requires signaling through soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (cGK). Mammals possess two genes for cGK: the prkg1 gene gives rise to the cGK type I isoforms, cGKIalpha and cGKIbeta, and the prkg2 gene encodes the cGK type II. Reportedly, both cGKI and cGKII are expressed in the amygdala, and cGKII is involved in controlling anxiety-like behavior. Because selective pharmacological tools for individual cGK isoforms are lacking, we used different knock-out mouse models to examine the function of cGKI and cGKII for LTP in the LA and pavlovian fear conditioning. We found robust expression of the cGKI specifically in the LA with cGKIbeta as the prevailing isoform. We further show a marked reduction of LTP at both thalamic and cortical inputs to the LA and a selective impairment of auditory-cued fear memory in cGKI-deficient mutants. In contrast, cGKII null mutants lack these phenotypes. Our data suggest a function of cGKI, likely the beta isoform, in the LA, supporting synaptic plasticity and consolidation of fear memory.

Open source tools for ATR development and performance evaluation

Science.gov (United States)

Baumann, James M.; Dilsavor, Ronald L.; Stubbles, James; Mossing, John C.

2002-07-01

Early in almost every engineering project, a decision must be made about tools; should I buy off-the-shelf tools or should I develop my own. Either choice can involve significant cost and risk. Off-the-shelf tools may be readily available, but they can be expensive to purchase and to maintain licenses, and may not be flexible enough to satisfy all project requirements. On the other hand, developing new tools permits great flexibility, but it can be time- (and budget-) consuming, and the end product still may not work as intended. Open source software has the advantages of both approaches without many of the pitfalls. This paper examines the concept of open source software, including its history, unique culture, and informal yet closely followed conventions. These characteristics influence the quality and quantity of software available, and ultimately its suitability for serious ATR development work. We give an example where Python, an open source scripting language, and OpenEV, a viewing and analysis tool for geospatial data, have been incorporated into ATR performance evaluation projects. While this case highlights the successful use of open source tools, we also offer important insight into risks associated with this approach.

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

Science.gov (United States)

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

2017-09-01

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

Oxidative stress provokes distinct transcriptional responses in the stress-tolerant atr7 and stress-sensitive loh2 Arabidopsis thaliana mutants as revealed by multi-parallel quantitative real-time PCR analysis of ROS marker and antioxidant genes.

Science.gov (United States)

Mehterov, Nikolay; Balazadeh, Salma; Hille, Jacques; Toneva, Valentina; Mueller-Roeber, Bernd; Gechev, Tsanko

2012-10-01

The Arabidopsis thaliana atr7 mutant is tolerant to oxidative stress induced by paraquat (PQ) or the catalase inhibitor aminotriazole (AT), while its original background loh2 and wild-type plants are sensitive. Both, AT and PQ, which stimulate the intracellular formation of H₂O₂ or superoxide anions, respectively, trigger cell death in loh2 but do not lead to visible damage in atr7. To study gene expression during oxidative stress and ROS-induced programmed cell death, two platforms for multi-parallel quantitative real-time PCR (qRT-PCR) analysis of 217 antioxidant and 180 ROS marker genes were employed. The qRT-PCR analyses revealed AT- and PQ-induced expression of many ROS-responsive genes mainly in loh2, confirming that an oxidative burst plays a role in the activation of the cell death in this mutant. Some of the genes were specifically regulated by either AT or PQ, serving as markers for particular types of ROS. Genes significantly induced by both AT and PQ in loh2 included transcription factors (ANAC042/JUB1, ANAC102, DREB19, HSFA2, RRTF1, ZAT10, ZAT12, ethylene-responsive factors), signaling compounds, ferritins, alternative oxidases, and antioxidant enzymes. Many of these genes were upregulated in atr7 compared to loh2 under non-stress conditions at the first time point, indicating that higher basal levels of ROS and higher antioxidant capacity in atr7 are responsible for the enhanced tolerance to oxidative stress and suggesting a possible tolerance against multiple stresses of this mutant. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Inherited germline ATRX mutation in two brothers with ATR-X syndrome and osteosarcoma.

Science.gov (United States)

Ji, Jianling; Quindipan, Catherine; Parham, David; Shen, Lishuang; Ruble, David; Bootwalla, Moiz; Maglinte, Dennis T; Gai, Xiaowu; Saitta, Sulagna C; Biegel, Jaclyn A; Mascarenhas, Leo

2017-05-01

We report a family in which two brothers had an undiagnosed genetic disorder comprised of dysmorphic features, microcephaly, severe intellectual disability (non-verbal), mild anemia, and cryptorchidism. Both developed osteosarcoma. Trio exome sequencing (using blood samples from the younger brother and both parents) was performed and a nonsense NM_000489.4:c.7156C>T (p.Arg2386*) mutation in the ATRX gene was identified in the proband (hemizygous) and in the mother's peripheral blood DNA (heterozygous). The mother is healthy, does not exhibit any clinical manifestations of ATR-X syndrome and there was no family history of cancer. The same hemizygous pathogenic variant was confirmed in the affected older brother's skin tissue by subsequent Sanger sequencing. Chromosomal microarray studies of both brothers' osteosarcomas revealed complex copy number alterations consistent with the clinical diagnosis of osteosarcoma. Recently, somatic mutations in the ATRX gene have been observed as recurrent alterations in both osteosarcoma and brain tumors. However, it is unclear if there is any association between osteosarcoma and germline ATRX mutations, specifically in patients with constitutional ATR-X syndrome. This is the first report of osteosarcoma diagnosed in two males with ATR-X syndrome, suggesting a potential increased risk for cancer in patients with this disorder. © 2017 Wiley Periodicals, Inc.

AcEST: BP917517 [AcEST

Lifescience Database Archive (English)

Full Text Available TQQFPNQPASIQGNHHTM 1898 >tr|Q98SV6|Q98SV6_SCOCA Myostatin (Fragment) OS=Scomberom...ant alignments: (bits) Value tr|B8CGK5|B8CGK5_THAPS Predicted protein OS=Thalassiosira pseudo... 34 3.2 tr|Q98SV6|Q98SV6_SCOCA Myosta...tin (Fragment) OS=Scomberomorus cav... 33 5.4 tr|Q4UAA3|Q4UAA3_THEAN Putative uncha

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

International Nuclear Information System (INIS)

Murray, R.K.; Rogers, J.W.

1994-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-03-01

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

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

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

Science.gov (United States)

Pachaiappan, Rekha; Prakasarao, Aruna; Singaravelu, Ganesan

2017-02-01

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

Rabi like angular splitting in Surface Plasmon Polariton - Exciton interaction in ATR configuration

Science.gov (United States)

Hassan, Heba; Abdallah, T.; Negm, S.; Talaat, H.

2018-05-01

We have studied the coupling of propagating Surface Plasmon Polaritons (SPP) on silver films and excitons in CdS quantum dots (QDs). We employed the Kretschmann-Raether configuration of the attenuated total reflection (ATR) to propagate the SPP on silver film of thickness 47.5 nm at three different wavelengths. The CdS QD have been chemically synthesized with particular size such that its exciton of energy would resonate with SPP. High resolution transmission electron microscopy (HRTEM) and scan tunneling microscopy (STM) were used to measure the corresponding QDs size and confirm its shape. Further confirmation of the size has been performed by the effective mass approximation (EMA) model utilizing the band gap of the prepared QDs. The band gaps have been measured through UV-vis absorption spectra as well as scan tunneling spectroscopy (STS). The coupling has been observed as two branching dips in the ATR spectra indicating Rabi like splitting. To the best of our knowledge, this is the first time that Rabi interaction is directly observed in an ATR angular spectra. This observation is attributed to the use a high resolution angular scan (±0.005°), in addition to the Doppler width of the laser line as well as the energy distribution of the excitons. The effect of three different linker molecules (TOPO, HDA), (Pyridine) and (Tri-butylamine) as surface ligands, on SPP-Exciton interaction has been examined.

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.

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.

5 CFR 733.105 - Permitted political activities-employees who reside in designated localities and are employed in...

Science.gov (United States)

2010-01-01

... under § 733.107 may: (1) Run as independent candidates for election to partisan political office in... political contribution as, or on behalf of, an independent candidate for partisan political office in... uncompensated volunteer services as, or on behalf of, an independent candidate for partisan political office in...

5 CFR 733.102 - Exclusion of employees in the Criminal Division of the United States Department of Justice.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Exclusion of employees in the Criminal... OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) POLITICAL ACTIVITY-FEDERAL EMPLOYEES RESIDING IN DESIGNATED LOCALITIES § 733.102 Exclusion of employees in the Criminal...

Context and Quasi-Invariants in Automatic Target Recognition (ATR) with Synthetic Aperture Radar (SAR) Imagery

National Research Council Canada - National Science Library

Binford, Thomas

2000-01-01

.... Experiments based on conventional recognition techniques were conducted for comparisons. Study of persistent scattering confirms the feasibility of implementing a SAR ATR system using physical image features...

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

Science.gov (United States)

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

2017-09-01

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

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 - others: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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-02-15

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

DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair.

Science.gov (United States)

Serrano, M A; Li, Z; Dangeti, M; Musich, P R; Patrick, S; Roginskaya, M; Cartwright, B; Zou, Y

2013-05-09

Homologous recombination (HR) and nonhomologous end joining (NHEJ) are two distinct DNA double-stranded break (DSB) repair pathways. Here, we report that DNA-dependent protein kinase (DNA-PK), the core component of NHEJ, partnering with DNA-damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), regulates HR repair of DSBs. The regulation was accomplished through modulation of the p53 and replication protein A (RPA) interaction. We show that upon DNA damage, p53 and RPA were freed from a p53-RPA complex by simultaneous phosphorylations of RPA at the N-terminus of RPA32 subunit by DNA-PK and of p53 at Ser37 and Ser46 in a Chk1/Chk2-independent manner by ATR and ATM, respectively. Neither the phosphorylation of RPA nor of p53 alone could dissociate p53 and RPA. Furthermore, disruption of the release significantly compromised HR repair of DSBs. Our results reveal a mechanism for the crosstalk between HR repair and NHEJ through the co-regulation of p53-RPA interaction by DNA-PK, ATM and ATR.

ATR-FTIR for rapid detection and quantification of counterfeit medicines

OpenAIRE

Ogwu, John; Lawson, Graham; Tanna, Sangeeta

2015-01-01

From therapeutic to lifestyle medicines, the counterfeiting of medicines has been on the rise in recent times [1]. Estimates indicate that about 10% of medicines worldwide are counterfeits with much higher figures in developing countries [2]. Currently, the rapid screening of medicines is a challenge leaving many patients at risk [1]. This study considered the potential use of Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) for rapid quantitative analysis of ta...

Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage*

Science.gov (United States)

Acevedo, Julyana; Yan, Shan; Michael, W. Matthew

2016-01-01

A critical event for the ability of cells to tolerate DNA damage and replication stress is activation of the ATR kinase. ATR activation is dependent on the BRCT (BRCA1 C terminus) repeat-containing protein TopBP1. Previous work has shown that recruitment of TopBP1 to sites of DNA damage and stalled replication forks is necessary for downstream events in ATR activation; however, the mechanism for this recruitment was not known. Here, we use protein binding assays and functional studies in Xenopus egg extracts to show that TopBP1 makes a direct interaction, via its BRCT2 domain, with RPA-coated single-stranded DNA. We identify a point mutant that abrogates this interaction and show that this mutant fails to accumulate at sites of DNA damage and that the mutant cannot activate ATR. These data thus supply a mechanism for how the critical ATR activator, TopBP1, senses DNA damage and stalled replication forks to initiate assembly of checkpoint signaling complexes. PMID:27129245

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-07-01

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

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

Science.gov (United States)

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

2017-10-01

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

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

Science.gov (United States)

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

2016-06-01

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

PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

Science.gov (United States)

Maréchal, Alexandre; Li, Ju-Mei; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E; Jin, Jianping; Zou, Lee

2014-01-23

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. Copyright © 2014 Elsevier Inc. All rights reserved.

Fission yeast shelterin regulates DNA polymerases and Rad3(ATR kinase to limit telomere extension.

Directory of Open Access Journals (Sweden)

Ya-Ting Chang

2013-11-01

Full Text Available Studies in fission yeast have previously identified evolutionarily conserved shelterin and Stn1-Ten1 complexes, and established Rad3(ATR/Tel1(ATM-dependent phosphorylation of the shelterin subunit Ccq1 at Thr93 as the critical post-translational modification for telomerase recruitment to telomeres. Furthermore, shelterin subunits Poz1, Rap1 and Taz1 have been identified as negative regulators of Thr93 phosphorylation and telomerase recruitment. However, it remained unclear how telomere maintenance is dynamically regulated during the cell cycle. Thus, we investigated how loss of Poz1, Rap1 and Taz1 affects cell cycle regulation of Ccq1 Thr93 phosphorylation and telomere association of telomerase (Trt1(TERT, DNA polymerases, Replication Protein A (RPA complex, Rad3(ATR-Rad26(ATRIP checkpoint kinase complex, Tel1(ATM kinase, shelterin subunits (Tpz1, Ccq1 and Poz1 and Stn1. We further investigated how telomere shortening, caused by trt1Δ or catalytically dead Trt1-D743A, affects cell cycle-regulated telomere association of telomerase and DNA polymerases. These analyses established that fission yeast shelterin maintains telomere length homeostasis by coordinating the differential arrival of leading (Polε and lagging (Polα strand DNA polymerases at telomeres to modulate Rad3(ATR association, Ccq1 Thr93 phosphorylation and telomerase recruitment.

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

Directory of Open Access Journals (Sweden)

Adam Oleszko

2015-01-01

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

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

Science.gov (United States)

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

2018-01-01

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

Virtual screening and pharmacophore design for a novel theoretical inhibitor of macrophage stimulating factor as a metastatic agent.

Science.gov (United States)

Torktaz, Ibrahim; Mohamadhashem, Faezeh; Esmaeili, Abolghasem; Behjati, Mohaddeseh; Sharifzadeh, Sara

2013-01-01

Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP) is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD) software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.

Roles of nibrin and ATM/ATR kinases on the G2 checkpoint under endogenous or radio-induced DNA damage

Directory of Open Access Journals (Sweden)

Katherine Marcelain

2005-01-01

Full Text Available Checkpoint response to DNA damage involves the activation of DNA repair and G2 lengthening subpathways. The roles of nibrin (NBS1 and the ATM/ATR kinases in the G2 DNA damage checkpoint, evoked by endogenous and radio-induced DNA damage, were analyzed in control, A-T and NBS lymphoblast cell lines. Short-term responses to G2 treatments were evaluated by recording changes in the yield of chromosomal aberrations in the ensuing mitosis, due to G2 checkpoint adaptation, and also in the duration of G2 itself. The role of ATM/ATR in the G2 checkpoint pathway repairing chromosomal aberrations was unveiled by caffeine inhibition of both kinases in G2. In the control cell lines, nibrin and ATM cooperated to provide optimum G2 repair for endogenous DNA damage. In the A-T cells, ATR kinase substituted successfully for ATM, even though no G2 lengthening occurred. X-ray irradiation (0.4 Gy in G2 increased chromosomal aberrations and lengthened G2, in both mutant and control cells. However, the repair of radio-induced DNA damage took place only in the controls. It was associated with nibrin-ATM interaction, and ATR did not substitute for ATM. The absence of nibrin prevented the repair of both endogenous and radio-induced DNA damage in the NBS cells and partially affected the induction of G2 lengthening.

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

Monitoring of biofilm growth using ATR-leaky mode spectroscopy

International Nuclear Information System (INIS)

Leitz, M.; Franke, H.; Grattan, K.T.V.; Tamachkiarow, A.

2002-01-01

An approach to the in situ monitoring of biofilm formation using the technique of ATR-leaky mode spectroscopy is given as an example for the case of Cytophaga. The biofilm growth was studied on an aluminium layer and on a bilayer of the hydrogel agarose on aluminium. This metal was chosen because of its chemical stability in aqueous systems. The spectra obtained have been recorded using a flow cell to contain the suspension and nutrients over a period of several days. In the case considered using a prism surface coated with agarose, the experiments were performed by breeding in an incubator. (author)

Cadmium depletion impacts on hardening neutron spectrum for advanced fuel testing in ATR

International Nuclear Information System (INIS)

Chang, Gray S.

2011-01-01

For transmuting long-lived isotopes contained in spent nuclear fuel into shorter-lived fission products effectively is in a fast neutron spectrum reactor. In the absence of a fast spectrum test reactor in the United States of America (USA), initial irradiation testing of candidate fuels can be performed in a thermal test reactor that has been modified to produce a test region with a hardened neutron spectrum. A test region is achieved with a Cadmium (Cd) filter which can harden the neutron spectrum to a spectrum similar (although still somewhat softer) to that of the liquid metal fast breeder reactor (LMFBR). A fuel test loop with a Cd-filter has been installed within the East Flux Trap (EFT) of the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL). A detailed comparison analyses between the cadmium (Cd) filter hardened neutron spectrum in the ATR and the LMFBR fast neutron spectrum have been performed using MCWO. MCWO is a set of scripting tools that are used to couple the Monte Carlo transport code MCNP with the isotope depletion and buildup code ORIGEN-2.2. The MCWO-calculated results indicate that the Cd-filter can effectively flatten the Rim-Effect and reduce the linear heat rate (LHGR) to meet the advanced fuel testing project requirements at the beginning of irradiation (BOI). However, the filtering characteristics of Cd as a strong absorber quickly depletes over time, and the Cd-filter must be replaced for every two typical operating cycles within the EFT of the ATR. The designed Cd-filter can effectively depress the LHGR in experimental fuels and harden the neutron spectrum enough to adequately flatten the Rim-Effect in the test region. (author)

RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA.

Science.gov (United States)

Manfrini, Nicola; Trovesi, Camilla; Wery, Maxime; Martina, Marina; Cesena, Daniele; Descrimes, Marc; Morillon, Antonin; d'Adda di Fagagna, Fabrizio; Longhese, Maria Pia

2015-02-01

Eukaryotic cells respond to DNA double-strand breaks (DSBs) by activating a checkpoint that depends on the protein kinases Tel1/ATM and Mec1/ATR. Mec1/ATR is activated by RPA-coated single-stranded DNA (ssDNA), which arises upon nucleolytic degradation (resection) of the DSB. Emerging evidences indicate that RNA-processing factors play critical, yet poorly understood, roles in genomic stability. Here, we provide evidence that the Saccharomyces cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA. The lack of Xrn1 inhibits ssDNA generation at the DSB by preventing the loading of the MRX complex. By contrast, DSB resection is not affected in the absence of Rrp6 or Trf4, but their lack impairs the recruitment of RPA, and therefore of Mec1, to the DSB. Rrp6 and Trf4 inactivation affects neither Rad51/Rad52 association nor DSB repair by homologous recombination (HR), suggesting that full Mec1 activation requires higher amount of RPA-coated ssDNA than HR-mediated repair. Noteworthy, deep transcriptome analyses do not identify common misregulated gene expression that could explain the observed phenotypes. Our results provide a novel link between RNA processing and genome stability. © 2014 The Authors.

Applications of diamond crystal ATR FTIR spectroscopy to the characterization of ambers.

Science.gov (United States)

Guiliano, Michel; Asia, Laurence; Onoratini, Gérard; Mille, Gilbert

2007-08-01

Diamond crystal ATR FTIR spectroscopy is a rapid technique with virtually no sample preparation which requires small sample amounts and showed potential in the study of ambers. FTIR spectra of ambers present discriminating patterns and can be used to distinguish amber from immature resins as copal, to determine local or Baltic origin of archaeological ambers and to detect most of the falsifications encountered in the amber commercialisation.

Angiotensin converting enzyme inhibitors and Alzheimer disease in the presence of the apolipoprotein E4 allele.

Science.gov (United States)

Qiu, Wendy Wei Qiao; Lai, Angela; Mon, Timothy; Mwamburi, Mkaya; Taylor, Warren; Rosenzweig, James; Kowall, Neil; Stern, Robert; Zhu, Haihao; Steffens, David C

2014-02-01

The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACE inhibitors on AD. This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined. A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACE inhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACE inhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACE inhibitor (28% versus 10%, p = 0.03). ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education. The effects of ACE inhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACE inhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers. Copyright © 2014. Published by Elsevier Inc.

Structural Analysis of Spiropyran Polimers using ATR Spectroscopy

Energy Technology Data Exchange (ETDEWEB)

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

2006-01-01

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

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

International Nuclear Information System (INIS)

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.)

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

Czech Academy of Sciences Publication Activity Database

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

2017-01-01

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

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Stephanie Munk

2017-10-01

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

Radiation Measurements Laboratory (RML) calibration and assessment of the ATR SPING-3 stack effluent monitor

International Nuclear Information System (INIS)

Koeppen, L.D.; Rogers, J.W.; Simpson, O.D.

1983-12-01

An evaluation, calibration and assessment of the Eberline SPING-3 ATR stack effluent monitor was conducted. This unit which monitors particulate, iodine and noble gas effluents was producing abnormal results following the initial installation and operational testing. The purposes of this work were to find the causes of the abnormal results and correct them if possible; check the calibrations and adjust them if necessary; and to provide a better in-depth understanding of what the unit is monitoring and how well it performs under this application. Results have shown that there were some problems associated with the unit as initially installed and tested. These problems have been identified and suggested alternatives shown, the monitor was found to be applicable to some extent under the current conditions. The calibrations have been checked and adjustments made. More operation testing and evaluation is needed to assess how well this works under a variety of ATR operating conditions. 2 references, 10 figures, 3 tables

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

Science.gov (United States)

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

2018-01-01

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

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

International Nuclear Information System (INIS)

Walker, B. J.; Miller, D. T.

2017-01-01

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 160A which were measured by the Radiation Measurements Laboratory (RML).

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-06-06

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

Virtual Screening and Pharmacophore Design for a Novel Theoretical Inhibitor of Macrophage Stimulating Factor as a Metastatic Agent

Directory of Open Access Journals (Sweden)

Ibrahim Torktaz

2013-09-01

Full Text Available Introduction: Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Methods: Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. Results: The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Conclusion: Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.

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

Directory of Open Access Journals (Sweden)

JOSÉ CHÁVEZ-FERNÁNDEZ

2011-01-01

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

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

Czech Academy of Sciences Publication Activity Database

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

2013-01-01

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

Preliminary Assessment of ATR-C Capabilities to Provide Integral Benchmark Data for Key Structural/Matrix Materials that May be Used for Nuclear Data Testing and Analytical Methods Validation

Energy Technology Data Exchange (ETDEWEB)

John D. Bess

2009-07-01

The purpose of this document is to identify some suggested types of experiments that can be performed in the Advanced Test Reactor Critical (ATR-C) facility. A fundamental computational investigation is provided to demonstrate possible integration of experimental activities in the ATR-C with the development of benchmark experiments. Criticality benchmarks performed in the ATR-C could provide integral data for key matrix and structural materials used in nuclear systems. Results would then be utilized in the improvement of nuclear data libraries and as a means for analytical methods validation. It is proposed that experiments consisting of well-characterized quantities of materials be placed in the Northwest flux trap position of the ATR-C. The reactivity worth of the material could be determined and computationally analyzed through comprehensive benchmark activities including uncertainty analyses. Experiments were modeled in the available benchmark model of the ATR using MCNP5 with the ENDF/B-VII.0 cross section library. A single bar (9.5 cm long, 0.5 cm wide, and 121.92 cm high) of each material could provide sufficient reactivity difference in the core geometry for computational modeling and analysis. However, to provide increased opportunity for the validation of computational models, additional bars of material placed in the flux trap would increase the effective reactivity up to a limit of 1$ insertion. For simplicity in assembly manufacture, approximately four bars of material could provide a means for additional experimental benchmark configurations, except in the case of strong neutron absorbers and many materials providing positive reactivity. Future tasks include the cost analysis and development of the experimental assemblies, including means for the characterization of the neutron flux and spectral indices. Oscillation techniques may also serve to provide additional means for experimentation and validation of computational methods and acquisition of

Application of FTIR-ATR Spectroscopy for the quality control of wine spirits, brandies and grape marc spirits

OpenAIRE

Anjos, O.; Caldeira, I.

2013-01-01

This study attempted to apply a rapid method for the determination of methanol, acetaldehyde and ethyl acetate in wine spirits, brandies and grape marc spirits, using Fourier Transform Infrared – Attenuated Total Reflectance (ATR) Spectroscopy.

Atmospheric circulation influence on climatic trends in Europe: an analysis of circulation type classifications from the COST733 catalogue

Czech Academy of Sciences Publication Activity Database

Cahynová, Monika; Huth, R.

2016-01-01

Roč. 36, č. 7 (2016), s. 2743-2760 ISSN 0899-8418 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073 Institutional support: RVO:67179843 Keywords : atmospheric circulation * classification * circulation type * climatic trends * Europe * COST733 Subject RIV: EH - Ecology, Behaviour Impact factor: 3.760, year: 2016 http://onlinelibrary.wiley.com/doi/10.1002/joc.4003/abstract

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

Preliminary Assessment of ATR-C Capabilities to Provide Integral Benchmark Data for Key Structural/Matrix Materials that May be Used for Nuclear Data Testing and Analytical Methods Validation

Energy Technology Data Exchange (ETDEWEB)

John D. Bess

2009-03-01

The purpose of this research is to provide a fundamental computational investigation into the possible integration of experimental activities with the Advanced Test Reactor Critical (ATR-C) facility with the development of benchmark experiments. Criticality benchmarks performed in the ATR-C could provide integral data for key matrix and structural materials used in nuclear systems. Results would then be utilized in the improvement of nuclear data libraries and as a means for analytical methods validation. It is proposed that experiments consisting of well-characterized quantities of materials be placed in the Northwest flux trap position of the ATR-C. The reactivity worth of the material could be determined and computationally analyzed through comprehensive benchmark activities including uncertainty analyses. Experiments were modeled in the available benchmark model of the ATR using MCNP5 with the ENDF/B-VII.0 cross section library. A single bar (9.5 cm long, 0.5 cm wide, and 121.92 cm high) of each material could provide sufficient reactivity difference in the core geometry for computational modeling and analysis. However, to provide increased opportunity for the validation of computational models, additional bars of material placed in the flux trap would increase the effective reactivity up to a limit of 1$ insertion. For simplicity in assembly manufacture, approximately four bars of material could provide a means for additional experimental benchmark configurations, except in the case of strong neutron absorbers and many materials providing positive reactivity. Future tasks include the cost analysis and development of the experimental assemblies, including means for the characterization of the neutron flux and spectral indices. Oscillation techniques may also serve to provide additional means for experimentation and validation of computational methods and acquisition of integral data for improving neutron cross sections. Further assessment of oscillation

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

DEFF Research Database (Denmark)

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

2015-01-01

In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the...

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

Science.gov (United States)

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

2009-12-01

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

Prediction of the oversulphated chondroitin sulphate contamination of unfractionated heparin by ATR-IR spectrophotometry.

Science.gov (United States)

Norwig, J; Beyer, T; Brinz, D; Holzgrabe, U; Diller, M; Manns, D

2009-03-01

The detection of a contamination of heparin with oversulphated chondroitin sulphate (OSCS) was first analysed in an unfractionated heparin batch supplied to the US API-market in April 2006. OSCS is a semi-synthetic derivative of the natural occuring glycosaminoglycan chondroitin sulphate. Moreover some spectroscopic characteristics of the substance overlap with those of heparin, so that the infrared (IR) spectra are visually difficult to distinguish whereas (1)H-NMR (Nuclear Magnetic Resonance) spectroscopy or capillary electrophoresis (CE) provides identification by a simple visual inspection of either the spectrum or the electropherogram respectively. However, applying special tools of Multivariate Data Analysis (MVA) to the IR spectra an identification of the contaminated samples is possible. In detail a rapid Attenuation Total Reflectance-Infrared (ATR-IR) measurement was selected, which does not require any sample preparation. The result (contaminated or not contaminated) is predicted within a few minutes. A method transfer to mobile ATR-IR spectrometers seems to be possible. The analysis is based on the fact that the fingerprint of the OSCS IR spectrum (1st derivative) complies with a theoretically calculated principal component in the MVA.

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. © 2016 American Academy of Forensic Sciences.

Determination of alkaloids in capsules, milk and ethanolic extracts of poppy (Papaver somniferum L.) by ATR-FT-IR and FT-Raman spectroscopy.

Science.gov (United States)

Schulz, Hartwig; Baranska, Malgorzata; Quilitzsch, Rolf; Schütze, Wolfgang

2004-10-01

Fourier transform (FT) infrared spectroscopy using a diamond composite ATR crystal and NIR-FT-Raman spectroscopy techniques were applied for the simultaneous identification and quantification of the most important alkaloids in poppy capsules. Most of the characteristic Raman signals of the alkaloids can be identified in poppy milk isolated from unripe capsules. But also poppy extracts present specific bands relating clearly to the alkaloid fraction. Raman spectra obtained by excitation with a Nd:YAG laser at 1064 nm show no disturbing fluorescence effects; therefore the plant tissue can be recorded without any special preparation. The used diamond ATR technique allows to measure very small sample amounts (5-10 microL or 2-5 mg) without the necessity to perform time-consuming pre-treatments. When applying cluster analysis a reliable discrimination of "low-alkaloid" and "high-alkaloid" poppy single-plants can be easily achieved. The examples presented in this study provide clear evidence of the benefits of Raman and ATR-IR spectroscopy in efficient quality control, forensic analysis and high-throughput evaluation of poppy breeding material.

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)

Characterization and sintering of ATR aluminia from niobium

International Nuclear Information System (INIS)

Shibuya, N.H.

1987-01-01

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 NbO 2 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.) [pt

Measured thermal and fast neutron fluence rates ATR Cycle 99-A, November 23, 1992--January 23, 1993

International Nuclear Information System (INIS)

Murray, R.K.; Rogers, J.W.

1993-03-01

This report contains the thermal (2200 m/s) and fast (E>me) neutron fluence rate data for ATR Cycle 99-A which were measured by the Radiation Measurements Laboratory (RML) as requested by the Power ReactorPrograms (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 and proper header identification of all monitor positions contained herein. The fluence rates reported are for the average power levels given in the table of power history and distribution. All ''H'' holder monitor wires for this cycle are 54 inches long. All ''SR'' holder monitor wires for this cycle are 55 inches long. This length allows measurement of the full core region and makes the first count elevation 24.73 inches above core midplane. Due to the safety rod problems in the west lobe, ''BR'' holders were used in the W-1, 2, 3, and 4 positions. All ''BR'' holder monitor wires for this cycle are 56.25 inches long. The distance from the end of the wires to the first count position was 4.25 inches for all wires counted from this cycle

Atmospheric circulation influence on climatic trends in Europe: an analysis of circulation type classifications from the COST733 catalogue

Czech Academy of Sciences Publication Activity Database

Cahynová, Monika; Huth, Radan

2016-01-01

Roč. 36, č. 7 (2016), s. 2743-2760 ISSN 0899-8418 R&D Projects: GA ČR GAP209/10/2265; GA ČR(CZ) GPP209/12/P811 Institutional support: RVO:68378289 Keywords : atmospheric circulation * classification * circulation type * climatic trends * Europe * COST733 Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 3.760, year: 2016 http://onlinelibrary.wiley.com/doi/10.1002/joc.4003/abstract

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

NARCIS (Netherlands)

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

2016-01-01

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

Atròfia muscular espinal: mecanismes patogènics i estratègies terapèutiques en models murins de la malaltia

OpenAIRE

Cerveró Cebrià, Clàudia

2016-01-01

L’atròfia muscular espinal (AME) és una malaltia genètica que cursa amb mort de motoneurones espinals i atròfia muscular. S’ha caracteritzat un model murí d’AME, l’Smn2B/-, amb una clínica menys severa que la mostrada per altres models més extensament utilitzats. S’ha evidenciat una alteració multisistèmica acompanyant a la clàssicament coneguda del sistema neuromuscular. S’han estudiat les sinapsis colinèrgiques tipus C en l’AME i testat el paper del PRE-084 (agonista del receptor sigm...

ATR-IR spectroscopic cell for in situ studies at solid-liquid interface at elevated temperatures and pressures

NARCIS (Netherlands)

Koichumanova, Kamila; Visan, Aura; Geerdink, Bert; Lammertink, Rob G.H.; Mojet, Barbara; Seshan, Kulathuiyer; Lefferts, Leonardus

2017-01-01

An in situ ATR-IR spectroscopic cell suitable for studies at solid-liquid interface is described including the design and experimental details in continuous flow mode at elevated temperatures (230 °C) and pressures (30 bar). The design parameters considered include the cell geometry, the procedure

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

2016-01-01

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. PMID:27470880

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.

Modeling Microalgal Biosediment Formation Based on Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Monitoring.

Science.gov (United States)

Ogburn, Zachary L; Vogt, Frank

2018-03-01

With increasing amounts of anthropogenic pollutants being released into ecosystems, it becomes ever more important to understand their fate and interactions with living organisms. Microalgae play an important ecological role as they are ubiquitous in marine environments and sequester inorganic pollutants which they transform into organic biomass. Of particular interest in this study is their role as a sink for atmospheric CO 2 , a greenhouse gas, and nitrate, one cause of harmful algal blooms. Novel chemometric hard-modeling methodologies have been developed for interpreting phytoplankton's chemical and physiological adaptations to changes in their growing environment. These methodologies will facilitate investigations of environmental impacts of anthropogenic pollutants on chemical and physiological properties of marine microalgae (here: Nannochloropsis oculata). It has been demonstrated that attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can gain insights into both and this study only focuses on the latter. From time-series of spectra, the rate of microalgal biomass settling on top of a horizontal ATR element is derived which reflects several of phytoplankton's physiological parameters such as growth rate, cell concentrations, cell size, and buoyancy. In order to assess environmental impacts on such parameters, microalgae cultures were grown under 25 different chemical scenarios covering 200-600 ppm atmospheric CO 2 and 0.35-0.75 mM dissolved NO 3 - . After recording time-series of ATR FT-IR spectra, a multivariate curve resolution-alternating least squares (MCR-ALS) algorithm extracted spectroscopic and time profiles from each data set. From the time profiles, it was found that in the considered concentration ranges only NO 3 - has an impact on the cells' physiological properties. In particular, the cultures' growth rate has been influenced by the ambient chemical conditions. Thus, the presented spectroscopic�

Optical fingerprints of solid-liquid interfaces: a joint ATR-IR and first principles investigation

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Yang, L.; Niu, F.; Tecklenburg, S.; Pander, M.; Nayak, S.; Erbe, A.; Wippermann, S.; Gygi, F.; Galli, G.

Despite the importance of understanding the structural and bonding properties of solid-liquid interfaces for a wide range of (photo-)electrochemical applications, there are presently no experimental techniques available to directly probe the microscopic structure of solid-liquid interfaces. To develop robust strategies to interpret experiments and validate theory, we carried out attenuated total internal reflection (ATR-IR) spectroscopy measurements and ab initio molecular dynamics (AIMD) simulations of the vibrational properties of interfaces between liquid water and well-controlled prototypical semiconductor substrates. We show the Ge(100)/H2O interface to feature a reversible potential-dependent surface phase transition between Ge-H and Ge-OH termination. The Si(100)/H2O interface is proposed as a model system for corrosion and oxidation processes. We performed AIMD calculations under finite electric fields, revealing different pathways for initial oxidation. These pathways are predicted to exhibit unique spectral signatures. A significant increase in surface specificity can be achieved utilizing an angle-dependent ATR-IR experiment, which allows to detect such signatures at the interfacial layer and consequently changes in the hydrogen bond network. Funding from DOE-BES Grant No. DE-SS0008939 and the Deutsche Forschungsgemeinschaft (RESOLV, EXC 1069) are gratefully acknowledged.

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

Science.gov (United States)

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

2017-10-01

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

Encefalomenigocele atrésico parietal Parietal atresic encephalomeningocele

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Liliana Rivera Oliva

2011-09-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-11-01

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

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

DEFF Research Database (Denmark)

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

2018-01-01

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

Trial Watch: Targeting ATM–CHK2 and ATR–CHK1 pathways for anticancer therapy

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Manic, Gwenola; Obrist, Florine; Sistigu, Antonella; Vitale, Ilio

2015-01-01

The ataxia telangiectasia mutated serine/threonine kinase (ATM)/checkpoint kinase 2 (CHEK2, best known as CHK2) and the ATM and Rad3-related serine/threonine kinase (ATR)/CHEK1 (best known as CHK1) cascades are the 2 major signaling pathways driving the DNA damage response (DDR), a network of processes crucial for the preservation of genomic stability that act as a barrier against tumorigenesis and tumor progression. Mutations and/or deletions of ATM and/or CHK2 are frequently found in tumors and predispose to cancer development. In contrast, the ATR–CHK1 pathway is often upregulated in neoplasms and is believed to promote tumor growth, although some evidence indicates that ATR and CHK1 may also behave as haploinsufficient oncosuppressors, at least in a specific genetic background. Inactivation of the ATM–CHK2 and ATR–CHK1 pathways efficiently sensitizes malignant cells to radiotherapy and chemotherapy. Moreover, ATR and CHK1 inhibitors selectively kill tumor cells that present high levels of replication stress, have a deficiency in p53 (or other DDR players), or upregulate the ATR–CHK1 module. Despite promising preclinical results, the clinical activity of ATM, ATR, CHK1, and CHK2 inhibitors, alone or in combination with other therapeutics, has not yet been fully demonstrated. In this Trial Watch, we give an overview of the roles of the ATM-CHK2 and ATR-CHK1 pathways in cancer initiation and progression, and summarize the results of clinical studies aimed at assessing the safety and therapeutic profile of regimens based on inhibitors of ATR and CHK1, the only 2 classes of compounds that have so far entered clinics. PMID:27308506

Rapid quantification of TBP and TBP degradation product ratios by FTIR-ATR

International Nuclear Information System (INIS)

Gillens, A.R.; Powell, B.A.; Clemson University, Clemson, SC

2013-01-01

Tri-n-butyl phosphate (TBP) is the key complexant within the plutonium and uranium reduction extraction process used to extract uranium and plutonium from used nuclear fuel. During reprocessing TBP degrades to dibutyl phosphate (DBP), butyl acid phosphate (MBP), butanol, and phosphoric acid over time. A method for rapidly monitoring TBP degradation is needed for the support of nuclear forensics. Therefore, a Fourier transform infrared spectrometry-attenuated total reflectance (FTIR-ATR) technique was developed to determine approximate peak intensity ratios of TBP and its degradation products. The technique was developed by combining variable concentrations of TBP, DBP, and MBP to simulate TBP degradation. This method is achieved by analyzing selected peak positions and peak intensity ratios of TBP and DBP at different stages of degradation. The developed technique was tested on TBP samples degraded with nitric acid. In mock degradation samples, the 1,235 cm -1 peak position shifts to 1,220 cm -1 as the concentration of TBP decreases and DBP increases. Peak intensity ratios of TBP positions at 1,279 and 1,020 cm -1 relative to DBP positions at 909 and 1,003 cm -1 demonstrate an increasing trend as the concentration of DBP increases. The same peak intensity ratios were used to analyze DBP relative to MBP whereas a decreasing trend is seen with increasing DBP concentrations. The technique developed from this study may be used as a tool to determine TBP degradation in nuclear reprocessing via a rapid FTIR-ATR measurement without gas chromatography analysis. (author)

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

Science.gov (United States)

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

2016-10-01

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

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

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Gudi, Gennadi

2016-07-01

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

Glycation in human fingernail clippings using ATR-FTIR spectrometry, a new marker for the diagnosis and monitoring of diabetes mellitus.

Science.gov (United States)

Coopman, Renaat; Van de Vyver, Thijs; Kishabongo, Antoine Sadiki; Katchunga, Philippe; Van Aken, Elisabeth H; Cikomola, Justin; Monteyne, Tinne; Speeckaert, Marijn M; Delanghe, Joris R

2017-01-01

Although HbA1c is a good diagnostic tool for diabetes, the precarity of the health system and the costs limit the use of this biomarker in developing countries. Fingernail clippings contain ±85% of keratins, which are prone to glycation. Nail keratin glycation may reflect the average glycemia over the last months. We explored if attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) can be used as a non-invasive tool for assessing glycation in diabetes. Using ATR-FTIR spectroscopy, glycation and deglycation experiments with fructosamine 3-kinase allowed to identify the spectrum that corresponds with keratin glycation in fingernail clippings. Clippings of 105 healthy subjects and 127 diabetics were subjected to the standardized ATR-FTIR spectroscopy method. In vitro glycation resulted in an increased absorption at 1047cm -1 . Following enzymatic deglycation, this peak diminished significantly, proving that the AUC between 970 and 1140cm -1 corresponded with glycated proteins. Within-run CV of the assay was 3%. Storage of nail clippings at 37°C for 2weeks did not significantly change results. In diabetics, glycated nail protein concentrations (median: 1.51μmol/g protein, IQR: 1.37-1.85μmol/g protein) were significantly higher than in the controls (median: 1.19μmol/g protein, IQR: 1.09-1.26μmol/g protein) (p<0.0001). ROC analysis yielded an AUC of 0.92 at a cut-off point of 1.28μmol/g nail (specificity: 82%; sensitivity: 90%). No correlation was observed between the glycated nail protein concentrations and HbA1c. Protein glycation analysis in fingernails with ATR-FTIR spectroscopy could be an alternative affordable technique for diagnosing and monitoring diabetes. As the test does not consume reagents, and the preanalytical phase is extremely robust, the test could be particularly useful in developing countries. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Rapid, nondestructive estimation of surface polymer layer thickness using attenuated total reflection fourier transform infrared (ATR FT-IR) spectroscopy and synthetic spectra derived from optical principles.

Science.gov (United States)

Weinstock, B André; Guiney, Linda M; Loose, Christopher

2012-11-01

We have developed a rapid, nondestructive analytical method that estimates the thickness of a surface polymer layer with high precision but unknown accuracy using a single attenuated total reflection Fourier transform infrared (ATR FT-IR) measurement. Because the method is rapid, nondestructive, and requires no sample preparation, it is ideal as a process analytical technique. Prior to implementation, the ATR FT-IR spectrum of the substrate layer pure component and the ATR FT-IR and real refractive index spectra of the surface layer pure component must be known. From these three input spectra a synthetic mid-infrared spectral matrix of surface layers 0 nm to 10,000 nm thick on substrate is created de novo. A minimum statistical distance match between a process sample's ATR FT-IR spectrum and the synthetic spectral matrix provides the thickness of that sample. We show that this method can be used to successfully estimate the thickness of polysulfobetaine surface modification, a hydrated polymeric surface layer covalently bonded onto a polyetherurethane substrate. A database of 1850 sample spectra was examined. Spectrochemical matrix-effect unknowns, such as the nonuniform and molecularly novel polysulfobetaine-polyetherurethane interface, were found to be minimal. A partial least squares regression analysis of the database spectra versus their thicknesses as calculated by the method described yielded an estimate of precision of ±52 nm.

Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation

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Manuel J. Muñoz

2017-03-01

Full Text Available We have previously found that UV irradiation promotes RNA polymerase II (RNAPII hyperphosphorylation and subsequent changes in alternative splicing (AS. We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER, and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation.

Aplicación de las espectroscopias IR/ATR y Raman al estudio de la superficie de vidrios sometidos a molturación

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Pérez-Villar, S.

2008-04-01

Full Text Available The grinding process of vítreous silica and a conventional glass has been studied by means of Raman and IR/ATR spectroscopies. By using the obtained spectra, the positions and areas of the different bands have been calculated. The Raman spectra have been analysed using the Polymerisation Index (PI that indicates the depolymerization degree achieved on the particle surface after grinding. On the other hand, the IR/ATR spectra have been used to follow the positions of the symmetric and antisymmetric Si-O-Si bands. It has been observed that both techniques give similar results. These indicate that the depolymerisation degree increases with the grinding process. This depolymerisation is due to the broke of Si-O-Si bonds.

El proceso de molienda de sílice vítrea y un vidrio convencional se ha estudiado mediante espectroscopias IR/ATR y Raman. A partir de los espectros obtenidos para diferentes tamaños de partícula se calcularon tanto las posiciones como las áreas de las bandas que aparecían en cada espectro. Utilizando los espectros Raman se ha hecho uso del denominado Índice de Polimerización (IP el cual es indicativo del grado de despolimerización producido en la superficie de las partículas tras el proceso de molienda. Por otro lado, mediante los espectros IR/ATR y analizando las posiciones de las bandas de tensión simétrica y asimétrica de los enlaces Si-O-Si se ha podido seguir el citado proceso de molturación. Se ha observado, mediante ambas técnicas, como la superficie de las partículas se despolimeriza al disminuir el tamaño de partícula. Esta despolimerización es debida a la rotura de los enlaces Si-O-Si.

Parvovirus B19 NS1 protein induces cell cycle arrest at G2-phase by activating the ATR-CDC25C-CDK1 pathway.

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Peng Xu

2017-03-01

Full Text Available Human parvovirus B19 (B19V infection of primary human erythroid progenitor cells (EPCs arrests infected cells at both late S-phase and G2-phase, which contain 4N DNA. B19V infection induces a DNA damage response (DDR that facilitates viral DNA replication but is dispensable for cell cycle arrest at G2-phase; however, a putative C-terminal transactivation domain (TAD2 within NS1 is responsible for G2-phase arrest. To fully understand the mechanism underlying B19V NS1-induced G2-phase arrest, we established two doxycycline-inducible B19V-permissive UT7/Epo-S1 cell lines that express NS1 or NS1mTAD2, and examined the function of the TAD2 domain during G2-phase arrest. The results confirm that the NS1 TAD2 domain plays a pivotal role in NS1-induced G2-phase arrest. Mechanistically, NS1 transactivated cellular gene expression through the TAD2 domain, which was itself responsible for ATR (ataxia-telangiectasia mutated and Rad3-related activation. Activated ATR phosphorylated CDC25C at serine 216, which in turn inactivated the cyclin B/CDK1 complex without affecting nuclear import of the complex. Importantly, we found that the ATR-CHK1-CDC25C-CDK1 pathway was activated during B19V infection of EPCs, and that ATR activation played an important role in B19V infection-induced G2-phase arrest.

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

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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.

Arecoline-induced phosphorylated p53 and p21(WAF1) protein expression is dependent on ATM/ATR and phosphatidylinositol-3-kinase in clone-9 cells.

Science.gov (United States)

Chou, Wen-Wen; Guh, Jinn-Yuh; Tsai, Jung-Fa; Hwang, Chi-Ching; Chiou, Shean-Jaw; Chuang, Lea-Yea

2009-06-01

Betel-quid use is associated with liver cancer whereas its constituent arecoline is cytotoxic, genotoxic, and induces p53-dependent p21(WAF1) protein expression in Clone-9 cells (rat hepatocytes). The ataxia telangiectasia mutated (ATM)/rad3-related (ATR)-p53-p21(WAF1) and the phosphatidylinositol-3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathways are involved in the DNA damage response and the pathogenesis of cancers. Thus, we studied the role of ATM/ATR and PI3K in arecoline-induced p53 and p21(WAF1) protein expression in Clone-9 cells. We found that arecoline (0.5 mM) activated the ATM/ATR kinase at 30 min. The arecoline-activated ATM/ATR substrate contained p-p53Ser15. Moreover, arecoline only increased the levels of the p-p53Ser6, p-p53Ser15, and p-p53Ser392 phosphorylated p53 isoforms among the known isoforms. ATM shRNA attenuated arecoline-induced p-p53Ser15 and p21(WAF1) at 24 h. Arecoline (0.5 mM) increased phosphorylation levels of p-AktSer473 and p-mTORSer2448 at 30-60 min. Dominant-negative PI3K plasmids attenuated arecoline-induced p21(WAF1), but not p-p53Ser15, at 24 h. Rapamycin attenuated arecoline-induced phosphrylated p-p53Ser15, but not p21(WAF1), at 24 h. ATM shRNA, but not dominant-negative PI3K plasmids, attenuated arecoline-induced p21(WAF1) gene transcription. We conclude that arecoline activates the ATM/ATR-p53-p21(WAF1) and the PI3K/Akt-mTOR-p53 pathways in Clone-9 cells. Arecoline-induced phosphorylated p-p53Ser15 expression is dependent on ATM whereas arecoline-induced p21(WAF1) protein expression is dependent on ATM and PI3K. Moreover, p21(WAF1) gene is transcriptionally induced by arecoline-activated ATM. (c) 2009 Wiley-Liss, Inc.

Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.

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Pogrmic-Majkic, Kristina; Samardzija, Dragana; Fa, Svetlana; Hrubik, Jelena; Glisic, Branka; Kaisarevic, Sonja; Andric, Nebojsa

2014-11-01

Premature luteinization is a possible cause of infertility in women. It is currently unknown whether environmental chemicals can induce changes associated with premature luteinization. Using rat granulosa cells (GC) in vitro, we demonstrated that exposure to atrazine (ATR), a widely used herbicide, causes GC phenotype that resembles that of human premature luteinization. At the end of the 48-h stimulation with FSH, ATR-exposed GC showed (1) higher levels of progesterone, (2) overexpression of luteal markers (Star and Cyp11a1), and (3) an increase in progesterone:estradiol ratio above 1. Mechanistic experiments were conducted to understand the signaling events engaged by ATR that lead to this phenotype. Western blot analysis revealed prolonged phosphorylation of protein kinase B (AKT) and cAMP response element-binding protein (CREB) in ATR- and FSH-exposed GC. An increased level of ERK1/2-dependent transcriptional factor CCATT/enhancer-binding protein beta (CEBPB) was observed after 4 h of ATR exposure. Inhibitors of PI3K (wortmannin) and MEK (U0126) prevented ATR-induced rise in progesterone level and expression of luteal markers in FSH-stimulated GC. Atrazine intensified AKT and CEBPB signaling and caused Star overexpression in forskolin-stimulated GC but not in epidermal growth factor (EGF)-stimulated GC. In the presence of rolipram, a specific inhibitor of phosphodiesterase 4 (PDE4), ATR was not able to further elevate AKT phosphorylation, CEBPB protein level, and Star mRNA in FSH-stimulated GC, suggesting that ATR inhibits PDE4. Overall, this study showed that ATR acts as a FSH sensitizer leading to enhanced cAMP, AKT, and CEBPB signaling and progesterone biosynthesis, which promotes premature luteinization phenotype in GC. © 2014 by the Society for the Study of Reproduction, Inc.

An ATR-dependent function for the Ddx19 RNA helicase in nuclear R-loop metabolism.

Science.gov (United States)

Hodroj, Dana; Recolin, Bénédicte; Serhal, Kamar; Martinez, Susan; Tsanov, Nikolay; Abou Merhi, Raghida; Maiorano, Domenico

2017-05-02

Coordination between transcription and replication is crucial in the maintenance of genome integrity. Disturbance of these processes leads to accumulation of aberrant DNA:RNA hybrids (R-loops) that, if unresolved, generate DNA damage and genomic instability. Here we report a novel, unexpected role for the nucleopore-associated mRNA export factor Ddx19 in removing nuclear R-loops formed upon replication stress or DNA damage. We show, in live cells, that Ddx19 transiently relocalizes from the nucleopore to the nucleus upon DNA damage, in an ATR/Chk1-dependent manner, and that Ddx19 nuclear relocalization is required to clear R-loops. Ddx19 depletion induces R-loop accumulation, proliferation-dependent DNA damage and defects in replication fork progression. Further, we show that Ddx19 resolves R-loops in vitro via its helicase activity. Furthermore, mutation of a residue phosphorylated by Chk1 in Ddx19 disrupts its interaction with Nup214 and allows its nuclear relocalization. Finally, we show that Ddx19 operates in resolving R-loops independently of the RNA helicase senataxin. Altogether these observations put forward a novel, ATR-dependent function for Ddx19 in R-loop metabolism to preserve genome integrity in mammalian cells. © 2017 The Authors.

Measured thermal and fast neutron fluence rates, ATR Cycle 102-A, 11/28/93 thru 1/16/94

International Nuclear Information System (INIS)

Murray, R.K.; Rogers, J.W.

1994-02-01

This report contains the thermal (2,200 m/s) and fast (E > 1MeV) neutron fluence rate data for ATR Cycle 102-A 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 and proper header identification of all monitor positions contained herein. The fluence rates reported are for the average power levels given in the table of power history and distribution. All ''H'' holder monitoring wires for this cycle are 54 inches long. All ''SR'' holder monitor wires for this cycle are 55 inches long. This length allows measurement of the full core region and makes the first count elevation 24.73 inches above core midplane. Due to the safety rod problems in the west lobe, ''BR'' holders were used in the W-1, 2, 3, and 4 positions. All ''BR'' holder monitor wires for this cycle are 56.25 inches long. The distance from the end of the wires to the first count position was 4.25 inches for all wires counted from this cycle

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

Science.gov (United States)

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

2017-02-01

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

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

DEFF Research Database (Denmark)

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

2017-01-01

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

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.

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

Science.gov (United States)

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

2017-01-01

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

Trasmission and Reflection (ATR)Far-Infrared Spectroscopy Applied in the Analysis of Cultural Heritage Materials

OpenAIRE

Kendix, Elsebeth Langholz

2009-01-01

FIR spectroscopy is an alternative way of collecting spectra of many inorganic pigments and corrosion products found on art objects, which is not normally observed in the MIR region. Most FIR spectra are traditionally collected in transmission mode but as a real novelty it is now also possible to record FIR spectra in ATR (Attenuated Total Reflectance) mode. In FIR transmission we employ polyethylene (PE) for preparation of pellets by embedding the sample in PE. Unfortunately, ...

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

International Nuclear Information System (INIS)

Navarro, Jorge; Aryaeinejad, Rahmat; Nigg, David W.

2011-01-01

Effective and efficient Advanced Test Reactor (ATR) fuel management require state of the art core modeling tools. These new tools will need isotopic and burnup validation data before they are put into production. To create isotopic, burn up validation libraries and to determine the setup for permanent fuel scanner system a feasibility study was perform. The study consisted in measuring short and long cooling time fuel elements at the ATR canal. Three gamma spectroscopy detectors (HPGe, LaBr3, and HPXe) and two system configurations (above and under water) were used in the feasibility study. The first stage of the study was to investigate which detector and system configuration would be better suited for different scenarios. The second stage of the feasibility study was to create burnup and cooling time calibrations using experimental isotopic data collected and ORIGEN 2.2 burnup data. The results of the study establish that a better spectra resolution is achieve with an above the water configuration and that three detectors can be used in the permanent fuel scanner system for different situations. In addition it was conclude that a number of isotopic ratios and absolute measurements could be used to predict ATR fuel burnup and cooling times.

Quantitative analysis of glycated albumin in serum based on ATR-FTIR spectrum combined with SiPLS and SVM.

Science.gov (United States)

Li, Yuanpeng; Li, Fucui; Yang, Xinhao; Guo, Liu; Huang, Furong; Chen, Zhenqiang; Chen, Xingdan; Zheng, Shifu

2018-08-05

A rapid quantitative analysis model for determining the glycated albumin (GA) content based on Attenuated total reflectance (ATR)-Fourier transform infrared spectroscopy (FTIR) combining with linear SiPLS and nonlinear SVM has been developed. Firstly, the real GA content in human serum was determined by GA enzymatic method, meanwhile, the ATR-FTIR spectra of serum samples from the population of health examination were obtained. The spectral data of the whole spectra mid-infrared region (4000-600 cm -1 ) and GA's characteristic region (1800-800 cm -1 ) were used as the research object of quantitative analysis. Secondly, several preprocessing steps including first derivative, second derivative, variable standardization and spectral normalization, were performed. Lastly, quantitative analysis regression models were established by using SiPLS and SVM respectively. The SiPLS modeling results are as follows: root mean square error of cross validation (RMSECV T ) = 0.523 g/L, calibration coefficient (R C ) = 0.937, Root Mean Square Error of Prediction (RMSEP T ) = 0.787 g/L, and prediction coefficient (R P ) = 0.938. The SVM modeling results are as follows: RMSECV T  = 0.0048 g/L, R C  = 0.998, RMSEP T  = 0.442 g/L, and R p  = 0.916. The results indicated that the model performance was improved significantly after preprocessing and optimization of characteristic regions. While modeling performance of nonlinear SVM was considerably better than that of linear SiPLS. Hence, the quantitative analysis model for GA in human serum based on ATR-FTIR combined with SiPLS and SVM is effective. And it does not need sample preprocessing while being characterized by simple operations and high time efficiency, providing a rapid and accurate method for GA content determination. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of natural cellulase inhibitor mediated intensified biological pretreatment technology using Pleurotus florida for maximum recovery of cellulose from paddy straw under solid state condition.

Science.gov (United States)

Naresh Kumar, Manickam; Ravikumar, Rajarathinam; Thenmozhi, Senniyappan; Kirupa Sankar, Muthuvelu

2017-11-01

Inhibitor mediated intensified bio-pretreatment (IMBP) technology using natural cellulase inhibitor (NCI) for maximum cellulose recovery from paddy straw was studied. Pretreatment was carried out under solid state condition. Supplementation of 8% NCI in pretreatment medium improves cellulose recovery and delignification by 1.2 and 1.5-fold respectively, compared to conventional bio-pretreatment due to inhibition of 61% of cellulase activity in IMBP. Further increase in NCI concentration showed negative effect on Pleurotus florida growth and suppress the laccase productivity by 1.1-fold. Laccase activity in IMBP was found to be 2.0U/mL on 19 th day, which is higher than (1.5U/mL) conventional bio-pretreatment. Physico-chemical modifications in paddy straw before and after pretreatment were analysed by SEM, ATR-FTIR, XRD and TGA. According to these findings, the IMBP technology can be a viable eco-friendly technology for sustainable production of bioethanol with maximum cellulose recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

1981-02-01

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

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

Science.gov (United States)

Thomas L. Eberhardt

2009-01-01

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

DNA Damage Response Resulting from Replication Stress Induced by Synchronization of Cells by Inhibitors of DNA Replication: Analysis by Flow Cytometry.

Science.gov (United States)

Halicka, Dorota; Zhao, Hong; Li, Jiangwei; Garcia, Jorge; Podhorecka, Monika; Darzynkiewicz, Zbigniew

2017-01-01

Cell synchronization is often achieved by transient inhibition of DNA replication. When cultured in the presence of such inhibitors as hydroxyurea, aphidicolin or excess of thymidine the cells that become arrested at the entrance to S-phase upon release from the block initiate progression through S then G 2 and M. However, exposure to these inhibitors at concentrations commonly used to synchronize cells leads to activation of ATR and ATM protein kinases as well as phosphorylation of Ser139 of histone H2AX. This observation of DNA damage signaling implies that synchronization of cells by these inhibitors is inducing replication stress. Thus, a caution should be exercised while interpreting data obtained with use of cells synchronized this way since they do not represent unperturbed cell populations in a natural metabolic state. This chapter critically outlines virtues and vices of most cell synchronization methods. It also presents the protocol describing an assessment of phosphorylation of Ser139 on H2AX and activation of ATM in cells treated with aphidicolin, as a demonstrative of one of several DNA replication inhibitors that are being used for cell synchronization. Phosphorylation of Ser139H2AX and Ser1981ATM in individual cells is detected immunocytochemically with phospho-specific Abs and intensity of immunofluorescence is measured by flow cytometry. Concurrent measurement of cellular DNA content followed by multiparameter analysis allows one to correlate the extent of phosphorylation of these proteins in response to aphidicolin with the cell cycle phase.

Measured thermal and fast neutron fluence rates, ATR Cycle 100-BC, April 23, 1993--May 13, 1993

International Nuclear Information System (INIS)

Smith, L.D.; Murray, R.K.; Rogers, J.W.

1993-07-01

This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for ATR Cycle 100-BC 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 and proper header identification of all monitor positions contained herein. The fluence rates reported are for the average power levels given in the table of power history and distribution. All open-quotes Hclose quotes holder monitor wires for this cycle are 54 inches long. All open-quotes SRclose quotes holder monitor wires for this cycle are 55 inches long. This length allows measurement of the full core region and makes the first count elevation 24.73 inches above core midplane. Due to the safety rod problems in the west lobe, open-quotes BRclose quotes holders were used in the W-1, 2, 3, and 4 positions. All open-quotes BRclose quotes holder monitor wires for this cycle are 56.25 inches long. The distance from the end of the wires to the first count position was 4.25 inches for all wires counted from this cycle. The results from the measurements in the W-1, 2, 3, 4 monitor positions indicate that the safety rod followers were rotated to a different azimuthal orientation relative to the normal orientation. The results indicate that the rotation was counterclockwise from their normal orientation. This is the same condition observed starting with Cycle 99-B

Small Molecules Targeting Ataxia Telangiectasia and Rad3-Related (ATR) Kinase: An Emerging way to Enhance Existing Cancer Therapy

Czech Academy of Sciences Publication Activity Database

Andrs, M.; Korábečný, J.; Nepovimova, E.; Jun, D.; Hodný, Zdeněk; Kuca, K.

2016-01-01

Roč. 16, č. 3 (2016), s. 200-208 ISSN 1568-0096 Institutional support: RVO:68378050 Keywords : Ataxia telangiectasia and Rad3-related kinase (ATR) * cancer * chemosensitization * DNA damage response * phosphatidylinositol 3-kinase-related protein kinases (PIKK) * radiosensitization * synthetic lethality Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.992, year: 2016

Identification of herbarium whole-leaf samples of Epilobium species by ATR-IR spectroscopy.

Science.gov (United States)

Strgulc Krajsek, Simona; Buh, Primoz; Zega, Anamarija; Kreft, Samo

2008-02-01

A simple, high-accuracy FT-IR method based on attenuated total reflection (ATR) was developed for the rapid determination of leaf samples of Epilobium species. The method is superior to other analytical techniques, since there is no need of laborious sample preparation such as grinding or extraction and solvent removal. A total of 70 herbarium specimens, belonging to all 13 Epilobium and to 2 Chamerion species growing in Slovenia, were analyzed. With the 100 most-informative wavenumbers in the range 700-1800 cm(-1), we obtained over 90% accuracy of species identification, with discriminant multivariate statistical analysis on the measurements made on whole dried leaves.

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

Science.gov (United States)

Adams, Bret R; Golding, Sarah E; Rao, Raj R; Valerie, Kristoffer

2010-04-02

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

Investigation of ATR-FTIR spectroscopy as an alternative to the Water Leach Free Acidity test for cellulose acetate-based film

DEFF Research Database (Denmark)

Johansen, Karin Bonde; Shashoua, Yvonne

2005-01-01

Cellulose acetate film loses acetate groups on ageing which results in the formation of damaging acetic acid. Water-Leach Free Acidity Test (WLFAT) is the definitive technique to quantify acidity, but requires 1g film and 26 hours. ATR-FTIR spectroscopy is a non-destructive, rapid technique which...

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 N_3-10 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 (N_3-10 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 N_3-10 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.

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

International Nuclear Information System (INIS)

Portaccio, M.; Gravagnuolo, A.M.; Longobardi, S.; Giardina, P.; Rea, I.; De Stefano, L.; Cammarota, M.; Lepore, M.

2015-01-01

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

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.

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...

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

Science.gov (United States)

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

2007-07-01

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

Process computer system for the prototype ATR 'Fugen'

International Nuclear Information System (INIS)

Oteru, Shigeru

1979-01-01

In recent nuclear power plants, computers are regarded as one of component equipments, and data processing, plant monitoring and performance calculation tend to be carried out with one on-line computer. As plants become large and complex, and the operational conditions become strict, the system having the function of performance calculation and reflecting the results immediately to operation is introduced. In the process computer for the prototype ATR ''Fugen'', the function of prediction to simulate the state after operation before the operation accompanied by the change of reactivity in a core, such as the operation of control rods and the control of liquid poison during operation, was given in addition to the functions of data processing, plant monitoring and detailed performance calculation. Core periodic monitoring program, core operational aid program, core any time data collecting program, and core periodic data collecting program, and their application programs are explained. Core performance calculation is the calculation of thermal output distribution in the core and the various accompanying characteristics and the monitoring of thermal limiting values. The computer used is a Hitachi control computer HIDIC-500, and typewriters, a process colored display, an operating console and other peripheral equipments are connected to it. (Kako, I.)

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

DEFF Research Database (Denmark)

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

2011-01-01

Attenuated Total Reflectance (ATR) FT-IR spectroscopy gives in situ information on molecular concentration, organization and interactions in plant cell walls. We demonstrate its potential for further developments by a case study which combines ATR-FT-IR spectroscopy with a recently published DFT...... a decreasing degree of polymerization to be a plausible cause, although others may interfere. Keywords: Cellulose; Mannan; FT-IR; DFT; Molecular modelling; Palm kernel...

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

Directory of Open Access Journals (Sweden)

Bartošová Alica

2017-06-01

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

Convolutional neural network using generated data for SAR ATR with limited samples

Science.gov (United States)

Cong, Longjian; Gao, Lei; Zhang, Hui; Sun, Peng

2018-03-01

Being able to adapt all weather at all times, it has been a hot research topic that using Synthetic Aperture Radar(SAR) for remote sensing. Despite all the well-known advantages of SAR, it is hard to extract features because of its unique imaging methodology, and this challenge attracts the research interest of traditional Automatic Target Recognition(ATR) methods. With the development of deep learning technologies, convolutional neural networks(CNNs) give us another way out to detect and recognize targets, when a huge number of samples are available, but this premise is often not hold, when it comes to monitoring a specific type of ships. In this paper, we propose a method to enhance the performance of Faster R-CNN with limited samples to detect and recognize ships in SAR images.

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.

Asarone from Acori Tatarinowii Rhizoma Potentiates the Nerve Growth Factor-Induced Neuronal Differentiation in Cultured PC12 Cells: A Signaling Mediated by Protein Kinase A.

Directory of Open Access Journals (Sweden)

Kelly Y C Lam

Full Text Available Acori Tatarinowii Rhizoma (ATR, the rhizome of Acorus tatarinowii Schott, is being used clinically to treat neurological disorders. The volatile oil of ATR is being considered as an active ingredient. Here, α-asarone and β-asarone, accounting about 95% of ATR oil, were evaluated for its function in stimulating neurogenesis. In cultured PC12 cells, application of ATR volatile oil, α-asarone or β-asarone, stimulated the expression of neurofilaments, a bio-marker for neurite outgrowth, in a concentration-dependent manner. The co-treatment of ATR volatile oil, α-asarone or β-asarone, with low concentration of nerve growth factor (NGF potentiated the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitors, H89 and KT5720, in cultures blocked the ATR-induced neurofilament expression, as well as the phosphorylation of cAMP-responsive element binding protein (CREB. In the potentiation of NGF-induced signaling in cultured PC12 cells, α-asarone and β-asarone showed synergistic effects. These results proposed the neurite-promoting asarone, or ATR volatile oil, could be useful in finding potential drugs for treating various neurodegenerative diseases, in which neurotrophin deficiency is normally involved.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as an Analytical Method to Investigate the Secondary Structure of a Model Protein Embedded in Solid Lipid Matrices.

Science.gov (United States)

Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene; Medlicott, Natalie J

2018-02-01

Protein drugs may encounter conformational perturbations during the formulation processing of lipid-based solid dosage forms. In aqueous protein solutions, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can investigate these conformational changes following the subtraction of spectral interference of solvent with protein amide I bands. However, in solid dosage forms, the possible spectral contribution of lipid carriers to protein amide I band may be an obstacle to determine conformational alterations. The objective of this study was to develop an ATR FT-IR spectroscopic method for the analysis of protein secondary structure embedded in solid lipid matrices. Bovine serum albumin (BSA) was chosen as a model protein, while Precirol AT05 (glycerol palmitostearate, melting point 58 ℃) was employed as the model lipid matrix. Bovine serum albumin was incorporated into lipid using physical mixing, melting and mixing, or wet granulation mixing methods. Attenuated total reflection FT-IR spectroscopy and size exclusion chromatography (SEC) were performed for the analysis of BSA secondary structure and its dissolution in aqueous media, respectively. The results showed significant interference of Precirol ATO5 with BSA amide I band which was subtracted up to 90% w/w lipid content to analyze BSA secondary structure. In addition, ATR FT-IR spectroscopy also detected thermally denatured BSA solid alone and in the presence of lipid matrix indicating its suitability for the detection of denatured protein solids in lipid matrices. Despite being in the solid state, conformational changes occurred to BSA upon incorporation into solid lipid matrices. However, the extent of these conformational alterations was found to be dependent on the mixing method employed as indicated by area overlap calculations. For instance, the melting and mixing method imparted negligible effect on BSA secondary structure, whereas the wet granulation mixing method promoted

Uso de plasma rico en plaquetas autólogo en el tratamiento quirúrgico de pseudoartrosis atrófica de fémur y tibia

Directory of Open Access Journals (Sweden)

Julio C Vejarano-Solano

2013-04-01

Full Text Available Objetivo: Describir y evaluar los resultados del tratamiento quirúrgico de pseudoartrosis atrófica de fémur o tibia mediante el uso de plasma rico en plaquetas (PRP autólogo. Material y métodos: Estudio descriptivo longitudinal de 20 casos (19 pacientes de pseudoartrosis atrófica de fémur o tibia tratados quirúrgicamente con PRP autólogo en el Hospital Nacional Cayetano Heredia de Lima, desde enero del 2008 hasta enero del 2012. El PRP fue preparado en el banco de sangre del hospital a partir de una unidad de sangre autóloga. Se evaluó el tiempo de consolidación ósea mediante radiografías seriadas y se registraron las complicaciones. Resultados: Se incluyeron 12 varones y 7 mujeres, con edad promedio de 33,8 años (15 a 67 años. Se evidenció consolidación en el 95% de los pacientes, el tiempo promedio para la consolidación fue 25 semanas. Se observó un caso de persistencia de infección con cultivo positivo a E. coli y un caso de refractura. Conclusiones: El PRP autólogo tiene un efecto beneficioso en la reparación del tejido óseo en casos de pseudoartrosis atrófica.

Structural dependence of the efficiency of functionalization of silica-coated FeOx magnetic nanoparticles studied by ATR-IR

International Nuclear Information System (INIS)

Vargas, Angelo; Shnitko, Ivan; Teleki, Alexandra; Weyeneth, Stephen; Pratsinis, Sotiris E.; Baiker, Alfons

2011-01-01

The efficiency of propylamino functionalization of magnetic silica-coated FeO x nanoparticles prepared by different methods, including coprecipitation and flame aerosol synthesis, has been evaluated by attenuated total reflection infrared spectroscopy (ATR-IR) combined with a specific surface reaction, thus revealing the availability of the grafted functional groups. Large differences in the population of reactive groups were observed for the investigated materials, underlining the tight relation between the structure of nanoparticles and their suitability for organic functionalization. The materials possessed different core structure, surface area, and porosity, as evidenced by transmission electron microscopy and nitrogen adsorption-desorption isotherms. Grafting of aminopropyl groups using a standard procedure based on reaction with (3-aminopropyl)trimethoxysilane as source of the propylamino groups was performed, followed by classical dry analysis methods to determine the specific concentration of the organic functional groups (in mmol g -1 of material). ATR-IR spectroscopy in a specially constructed reactor cell was applied as wet methodology to determine the chemically available amount of such functional groups, showing that the materials possess largely different loading capacity, with a variability of up to 70% in the chemical availability of the organic functional group. The amount of (3-aminopropyl)trimethoxysilane used for functionalization was optimized, thus reaching a saturation limit characteristic of the material.

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]).

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

Directory of Open Access Journals (Sweden)

Bret R Adams

2010-04-01

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

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......, and minor oxidation of the lignin polymer compared to recent reference material. This is evidence for abiotic decay in the course of waterlogging....

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

International Nuclear Information System (INIS)

Gotter, B; Hein, J; Neubert, R H H; Faubel, W; Heissler, St

2010-01-01

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.

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

Science.gov (United States)

Coelho Neto, José

2015-07-01

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

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......We have prepared high-quality, densely packed, self-assembled monolayers (SAMs) of carboxy-terminated alkyl chains on Si(111). The samples were made by thermal grafting of methyl undec-10-enoate under an inert atmosphere and subsequent cleavage of the ester functionality to disclose the carboxylic...... zigzag-like substitution pattern for the ester- and carboxy-terminated monolayer. Hydrolysis of the remaining H-Si(111) bonds at the surface furnished HO-Si(111) groups according to XPS and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) studies. The amide-terminated alkyl...

Correlation Study of PVDF Membrane Morphology with Protein Adsorption: Quantitative Analysis by FTIR/ATR Technique

Science.gov (United States)

Ideris, N.; Ahmad, A. L.; Ooi, B. S.; Low, S. C.

2018-05-01

Microporous PVDF membranes were used as protein capture matrices in immunoassays. Because the most common labels in immunoassays were detected based on the colour change, an understanding of how protein concentration varies on different PVDF surfaces was needed. Herein, the correlation between the membrane pore size and protein adsorption was systematically investigated. Five different PVDF membrane morphologies were prepared and FTIR/ATR was employed to accurately quantify the surface protein concentration on membranes with small pore sizes. SigmaPlot® was used to find a suitable curve fit for protein adsorption and membrane pore size, with a high correlation coefficient, R2, of 0.9971.

Sensing molecular properties by ATR-SPP Raman spectroscopy on electrochemically structured sensor chips

International Nuclear Information System (INIS)

Zerulla, D.; Isfort, G.; Koelbach, M.; Otto, A.; Schierbaum, K.

2003-01-01

The use of electrochemically structured Al surfaces as sensor arrays for combinatorial chemistry and its detection via microscopic laser techniques from very small volumes has been explored. The methodology is based on three different techniques which will be discussed separately: firstly, attenuated total reflection (ATR) is used in connection with surface-plasmon-polariton (SPP) excitation. A thin Al layer, evaporated on sapphire or quartz and covered with a naturally grown oxide layer, provides an optimum enhancement and confinement of the electrical field close to the surface. This is revealed by calculations and experimental data. Secondly, a Raman microscope is applied, enabling chemical spot analysis in the visible and UV range with a lateral resolution close to the diffraction limit. Finally, its application to investigate electrochemically structured Al films is discussed

Effect of dissolved oxygen on two bacterial pathogens examined using ATR-FTIR spectroscopy, microelectrophoresis, and potentiometric titration.

Science.gov (United States)

Castro, Felipe D; Sedman, Jacqueline; Ismail, Ashraf A; Asadishad, Bahareh; Tufenkji, Nathalie

2010-06-01

The effects of dissolved oxygen tension during bacterial growth and acclimation on the cell surface properties and biochemical composition of the bacterial pathogens Escherichia coli O157:H7 and Yersinia enterocolitica are characterized. Three experimental techniques are used in an effort to understand the influence of bacterial growth and acclimation conditions on cell surface charge and the composition of the bacterial cell: (i) electrophoretic mobility measurements; (ii) potentiometric titration; and (iii) ATR-FTIR spectroscopy. Potentiometric titration data analyzed using chemical speciation software are related to measured electrophoretic mobilities at the pH of interest. Titration of bacterial cells is used to identify the major proton-active functional groups and the overall concentration of these cell surface ligands at the cell membrane. Analysis of titration data shows notable differences between strains and conditions, confirming the appropriateness of this tool for an overall charge characterization. ATR-FTIR spectroscopy of whole cells is used to further characterize the bacterial biochemical composition and macromolecular structures that might be involved in the development of the net surficial charge of the organisms examined. The evaluation of the integrated intensities of HPO(2)(-) and carbohydrate absorption bands in the IR spectra reveals clear differences between growth protocols. Taken together, the three techniques seem to indicate that the dissolved oxygen tension during cell growth or acclimation can noticeably influence the expression of cell surface molecules and the measurable cell surface charge, though in a strain-dependent fashion.

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

Directory of Open Access Journals (Sweden)

Bianca M Sirbu

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

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

Science.gov (United States)

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

2017-06-01

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

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 - others: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: 13.958, year: 2015

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…

cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland

Science.gov (United States)

De Jonge, Hugo R.; Tilly, Ben C.; Hogema, Boris M.; Pfau, Daniel J.; Kelley, Catherine A.; Kelley, Megan H.; Melita, August M.; Morris, Montana T.; Viola, Ryan M.

2013-01-01

The in vitro perfused rectal gland of the dogfish shark (Squalus acanthias) and filter-grown monolayers of primary cultures of shark rectal gland (SRG) epithelial cells were used to analyze the signal transduction pathway by which C-type natriuretic peptide (CNP) stimulates chloride secretion. CNP binds to natriuretic receptors in the basolateral membrane, elevates cellular cGMP, and opens cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in the apical membrane. CNP-provoked chloride secretion was completely inhibitable by the nonspecific protein kinase inhibitor staurosporine and the PKA inhibitor H89 but insensitive to H8, an inhibitor of type I and II isoforms of cGMP-dependent protein kinase (cGKI and cGKII). CNP-induced secretion could not be mimicked by nonhydrolyzable cGMP analogs added alone or in combination with the protein kinase C activator phorbolester, arguing against a role for cGK or for cGMP-induced PKC signaling. We failed to detect a dogfish ortholog of cGKII by molecular cloning and affinity chromatography. However, inhibitors of the cGMP-inhibitable isoform of phosphodiesterase (PDE3) including milrinone, amrinone, and cilostamide but not inhibitors of other PDE isoenzymes mimicked the effect of CNP on chloride secretion in perfused glands and monolayers. CNP raised cGMP and cAMP levels in the SRG epithelial cells. This rise in cAMP as well as the CNP and amrinone-provoked chloride secretion, but not the rise in cGMP, was almost completely blocked by the Gαi-coupled adenylyl cyclase inhibitor somatostatin, arguing against a role for cGMP cross-activation of PKA in CNP action. These data provide molecular, functional, and pharmacological evidence for a CNP/cGMP/PDE3/cAMP/PKA signaling cascade coupled to CFTR in the SRG. PMID:24259420

Structural dependence of the efficiency of functionalization of silica-coated FeO{sub x} magnetic nanoparticles studied by ATR-IR

Energy Technology Data Exchange (ETDEWEB)

Vargas, Angelo; Shnitko, Ivan [Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang Pauli Strasse 10, Hoenggerberg, HCI, 8093 Zurich (Switzerland); Teleki, Alexandra [Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich (Switzerland); Weyeneth, Stephen [Physik-Institut der Universitaet Zuerich, Winterthurerstrasse 190, 8057 Zuerich (Switzerland); Pratsinis, Sotiris E. [Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich (Switzerland); Baiker, Alfons, E-mail: baiker@chem.ethz.ch [Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang Pauli Strasse 10, Hoenggerberg, HCI, 8093 Zurich (Switzerland)

2011-01-15

The efficiency of propylamino functionalization of magnetic silica-coated FeO{sub x} nanoparticles prepared by different methods, including coprecipitation and flame aerosol synthesis, has been evaluated by attenuated total reflection infrared spectroscopy (ATR-IR) combined with a specific surface reaction, thus revealing the availability of the grafted functional groups. Large differences in the population of reactive groups were observed for the investigated materials, underlining the tight relation between the structure of nanoparticles and their suitability for organic functionalization. The materials possessed different core structure, surface area, and porosity, as evidenced by transmission electron microscopy and nitrogen adsorption-desorption isotherms. Grafting of aminopropyl groups using a standard procedure based on reaction with (3-aminopropyl)trimethoxysilane as source of the propylamino groups was performed, followed by classical dry analysis methods to determine the specific concentration of the organic functional groups (in mmol g{sup -1} of material). ATR-IR spectroscopy in a specially constructed reactor cell was applied as wet methodology to determine the chemically available amount of such functional groups, showing that the materials possess largely different loading capacity, with a variability of up to 70% in the chemical availability of the organic functional group. The amount of (3-aminopropyl)trimethoxysilane used for functionalization was optimized, thus reaching a saturation limit characteristic of the material.

ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage.

Science.gov (United States)

Perkhofer, Lukas; Schmitt, Anna; Romero Carrasco, Maria Carolina; Ihle, Michaela; Hampp, Stephanie; Ruess, Dietrich Alexander; Hessmann, Elisabeth; Russell, Ronan; Lechel, André; Azoitei, Ninel; Lin, Qiong; Liebau, Stefan; Hohwieler, Meike; Bohnenberger, Hanibal; Lesina, Marina; Algül, Hana; Gieldon, Laura; Schröck, Evelin; Gaedcke, Jochen; Wagner, Martin; Wiesmüller, Lisa; Sipos, Bence; Seufferlein, Thomas; Reinhardt, Hans Christian; Frappart, Pierre-Olivier; Kleger, Alexander

2017-10-15

Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576-90. ©2017 AACR . ©2017 American Association for Cancer Research.

ATR-FTIR Spectroscopic Evidence for Biomolecular Phosphorus and Carboxyl Groups Facilitating Bacterial Adhesion to Iron Oxides

Science.gov (United States)

Parikh, Sanjai J.; Mukome, Fungai N.D.; Zhang, Xiaoming

2014-01-01

Attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy has been used to probe the binding of bacteria to hematite (α-Fe2O3) and goethite (α-FeOOH). In situ ATR-FTIR experiments with bacteria (Pseudomonas putida, P. aeruginosa, Escherichia coli), mixed amino acids, polypeptide extracts, deoxyribonucleic acid (DNA), and a suite of model compounds were conducted. These compounds represent carboxyl, catecholate, amide, and phosphate groups present in siderophores, amino acids, polysaccharides, phospholipids, and DNA. Due in part to the ubiquitous presence of carboxyl groups in biomolecules, numerous IR peaks corresponding to outer-sphere or unbound (1400 cm−1) and inner-sphere (1310-1320 cm−1) coordinated carboxyl groups are noted following reaction of bacteria and biomolecules with α-Fe2O3 and α-FeOOH. However, the data also reveal that the presence of low-level amounts (i.e., 0.45-0.79%) of biomolecular phosphorous groups result in strong IR bands at ~1043 cm−1, corresponding to inner-sphere Fe-O-P bonds, underscoring the importance of bacteria associated P-containing groups in biomolecule and cell adhesion. Spectral comparisons also reveal slightly greater P-O-Fe contributions for bacteria (Pseudomonad, E. coli) deposited on α-FeOOH, as compared to α-Fe2O3. This data demonstrates that slight differences in bacterial adhesion to Fe oxides can be attributed to bacterial species and Fe-oxide minerals. However, more importantly, the strong binding affinity of phosphate in all bacteria samples to both Fe-oxides results in the formation of inner-sphere Fe-O-P bonds, signifying the critical role of biomolecular P in the initiation of bacterial adhesion. PMID:24859052

ATR-FTIR spectroscopy and quantitative multivariate analysis of paints and coating materials

Science.gov (United States)

Hayes, Philippa Alice; Vahur, Signe; Leito, Ivo

2014-12-01

The applicability of ATR-FTIR spectroscopy with partial least squares (PLS) data analysis was evaluated for quantifying the components of mixtures of paint binding media and pigments, and alkyd resins. PLS methods were created using a number of standard mixtures. Validation and measurement uncertainty estimation was carried out. Binary, ternary and quaternary mixtures of several common binding media and pigments were quantified, with standard measurement uncertainties in most cases below 3 g/100 g. Classes of components - aromatic anhydrides and alcohols - used in alkyd resin synthesis were also successfully quantified, with standard uncertainties in the range of 2-3 g/100 g. This is a more demanding application because in alkyd resins aromatic anhydrides and alcohols have reacted to form a polyester, and are not present in their original forms. Once a PLS method has been calibrated, analysis time and cost are significantly reduced from typical quantitative methods such as GC/MS. This is beneficial in the case of routine analysis where the components are known.

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

Science.gov (United States)

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

2017-08-15

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

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.

CAPABILITY ASSESSMENT OF MEASURING EQUIPMENT USING STATISTIC METHOD

Directory of Open Access Journals (Sweden)

Pavel POLÁK

2014-10-01

Full Text Available Capability assessment of the measurement device is one of the methods of process quality control. Only in case the measurement device is capable, the capability of the measurement and consequently production process can be assessed. This paper deals with assessment of the capability of the measuring device using indices Cg and Cgk.

Detection of creatinine enriched on a surface imprinted polystyrene film using FT-ATR-IR.

Science.gov (United States)

Sreenivasan, K

2006-01-01

The surface of polystyrene (PS) was chemically modified by coating a thin layer of polyaniline (PANI) by oxidizing aniline using ammonium persulfate. Affinity sites for creatinine, a clinically relevant molecule, were created in the coated layer by adding creatinine as print molecules during the oxidation. The imprinted layer adsorbed creatinine was compared to non-imprinted surface reflecting the creation of creatinine-specific sites on the surface. The equilibrium was attained rapidly, indicating that a material of this kind is suitable for sensing applications. The adsorbed creatinine on the surface was detected using the technique of Fourier transform attenuated total internal reflection infra red spectroscopy (FT-ATR-IR). The results show that molecularly imprinted surface can enrich molecules of interest and the enriched molecules can be detected using FT-IR.

Characterisation of 17th-18th centuries damask and gilt leathers by ATR-FTIR

Directory of Open Access Journals (Sweden)

Lina Falcão

2018-01-01

Full Text Available In this paper it is presented the characterisation of tannins used in the vegetable tanning of two types of European historic and decorative leathers from Portuguese collections, damask leathers and gilt leathers, dated from the 17th and 18th centuries. Extracts prepared from collected leather fibres were analysed by attenuated total reflectance – Fourier transform infrared (ATR-FTIR spectroscopy. Results were compared with data collected from different reference vegetable tanning materials which, according to historic and technical literature, were used in Europe during the Modern Age. This study allowed, in most cases, the characterisation of the tannins used to produce the studied decorative vegetable tanned leathers and, at the same time, the detection of chemical deterioration of leathers, particularly collagen hydrolysis, which was not visually perceived.

Chemical transitions of Areca semen during the thermal processing revealed by temperature-resolved ATR-FTIR spectroscopy and two-dimensional correlation analysis

Science.gov (United States)

Wang, Zhibiao; Wang, Xu; Pei, Wenxuan; Li, Sen; Sun, Suqin; Zhou, Qun; Chen, Jianbo

2018-03-01

Areca semen is a common herb used in traditional Chinese medicine, but alkaloids in this herb are categorized as Group I carcinogens by IARC. It has been proven that the stir-baking process can reduce alkaloids in Areca semen while keep the activity for promoting digestion. However, the changes of compositions other than alkaloids during the thermal processing are unclear. Understanding the thermal chemical transitions of Areca semen is necessary to explore the processing mechanisms and optimize the procedures. In this research, FTIR spectroscopy with a temperature-controlled ATR accessory is employed to study the heating process of Areca semen. Principal component analysis and two-dimensional correlation spectroscopy are used to interpret the spectra to reveal the chemical transitions of Areca semen in different temperature ranges. The loss of a few volatile compounds in the testa and sperm happens below 105 °C, while some esters in the sperm decreases above 105 °C. As the heating temperature is close to 210 °C, Areca semen begins to be scorched and the decomposition of many compounds can be observed. This research shows the potential of the temperature-resolved ATR-FTIR spectroscopy in exploring the chemical transitions of the thermal processing of herbal materials.

On three-dimensional nuclear thermo-hydraulic computation techniques for ATR

International Nuclear Information System (INIS)

1997-08-01

The three-dimensional computation code for nuclear thermo-hydraulic combination core LAYMON-2A is used for the calculation of the power distribution and the control rod reactivity value of the ATR. This code possesses various functions which are required for planning the core operation such as the search function for critical boric acid concentration, and can do various simulation calculations such as core burning calculation. Further, the three-dimensional analysis code for xenon dynamic characteristics in the core LAYMON-2C, in which the dynamic characteristic equation of xenon-samarium was incorporated into the LAYMON-2A code can take the change with time lapse of xenon-samarium concentration accompanying the change of power level and power distribution into account, and it is used for the analysis of the spatial vibration characteristics of power and the regional power control characteristics due to xenon in the core. As to the LAYMON-2A, the computation flow, power distribution and thermo-hydraulic computation models, and critical search function are explained. As to the LAYMON-2C, the computation flow is described. The comparison of the calculated values by using the LAYMON-2A code and the operation data of the Fugen is reported. (K.I.)

The Neurospora crassa UVS-3 epistasis group encodes homologues of the ATR/ATRIP checkpoint control system.

Science.gov (United States)

Kazama, Yusuke; Ishii, Chizu; Schroeder, Alice L; Shimada, Hisao; Wakabayashi, Michiyoshi; Inoue, Hirokazu

2008-02-01

The mutagen sensitive uvs-3 and mus-9 mutants of Neurospora show mutagen and hydroxyurea sensitivity, mutator effects and duplication instability typical of recombination repair and DNA damage checkpoint defective mutants. To determine the nature of these genes we used cosmids from a genomic library to clone the uvs-3 gene by complementation for MMS sensitivity. Mutation induction by transposon insertion and RIP defined the coding sequence. RFLP analysis confirmed that this sequence maps in the area of uvs-3 at the left telomere of LG IV. Analysis of the cDNA showed that the UVS-3 protein contains an ORF of 969 amino acids with one intron. It is homologous to UvsD of Aspergillus nidulans, a member of the ATRIP family of checkpoint proteins. It retains the N' terminal coiled-coil motif followed by four basic amino acids typical of these proteins and shows the highest homology in this region. The uvsD cDNA partially complements the defects of the uvs-3 mutation. The uvs-3 mutant shows a higher level of micronuclei in conidia and failure to halt germination and nuclear division in the presence of hydroxyurea than wild type, suggesting checkpoint defects. ATRIP proteins bind tightly to ATR PI-3 kinase (phosphatidylinositol 3-kinase) proteins. Therefore, we searched the Neurospora genome sequence for homologues of the Aspergillus nidulans ATR, UvsB. A uvsB homologous sequence was present in the right arm of chromosome I where the mus-9 gene maps. A cosmid containing this genomic DNA complemented the mus-9 mutation. The putative MUS-9 protein is 2484 amino acids long with eight introns. Homology is especially high in the C-terminal 350 amino acids that correspond to the PI-3 kinase domain. In wild type a low level of constitutive mRNA is present for both genes. It is transiently induced upon UV exposure.

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

Science.gov (United States)

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

2017-10-23

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

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

Influence of alkali metal cations/type of activator on the structure of alkali-activated fly ash - ATR-FTIR studies

Science.gov (United States)

Król, M.; Rożek, P.; Chlebda, D.; Mozgawa, W.

2018-06-01

Coal fly ash as a secondary aluminosiliceous raw material that is commonly used in the so-called geopolymerization process has been activated with different alkali hydroxides solutions: LiOH, NaOH and KOH. Changes in the aluminosilicate structure of the material during alkali-activation have been analyzed in detail on the basis of ATR/FT-IR spectra. These changes mainly affect both the integral intensity and FWHM of bands in the range of 1200-950 cm-1, however dehydration and carbonation process can be also analyzed based on obtaining results.

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)

Quantitative determination of polyphosphate in sediments using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy and partial least squares regression.

Science.gov (United States)

Khoshmanesh, Aazam; Cook, Perran L M; Wood, Bayden R

2012-08-21

Phosphorus (P) is a major cause of eutrophication and subsequent loss of water quality in freshwater ecosystems. A major part of the flux of P to eutrophic lake sediments is organically bound or of biogenic origin. Despite the broad relevance of polyphosphate (Poly-P) in bioremediation and P release processes in the environment, its quantification is not yet well developed for sediment samples. Current methods possess significant disadvantages because of the difficulties associated with using a single extractant to extract a specific P compound without altering others. A fast and reliable method to estimate the quantitative contribution of microorganisms to sediment P release processes is needed, especially when an excessive P accumulation in the form of polyphosphate (Poly-P) occurs. Development of novel approaches for application of emerging spectroscopic techniques to complex environmental matrices such as sediments significantly contributes to the speciation models of P mobilization, biogeochemical nutrient cycling and development of nutrient models. In this study, for the first time Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy in combination with partial least squares (PLS) was used to quantify Poly-P in sediments. To reduce the high absorption matrix components in sediments such as silica, a physical extraction method was developed to separate sediment biological materials from abiotic particles. The aim was to achieve optimal separation of the biological materials from sediment abiotic particles with minimum chemical change in the sample matrix prior to ATR-FTIR analysis. Using a calibration set of 60 samples for the PLS prediction models in the Poly-P concentration range of 0-1 mg g(-1) d.w. (dry weight of sediment) (R(2) = 0.984 and root mean square error of prediction RMSEP = 0.041 at Factor-1) Poly-P could be detected at less than 50 μg g(-l) d.w. Using this technique, there is no solvent extraction or chemical

Evaluation of Corrosion of the Dummy ''EE'' Plate 19 in YA Type ATR Fuel Element During Reactor PALM Cycles

International Nuclear Information System (INIS)

Brower, Jeffrey Owen; Glazoff, Michael Vasily; Eiden, Thomas John; Rezvoi, Aleksey Victor

2016-01-01

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

Altered chromatographic behaviour of mitochondrial ADP/ATP translocase induced by stabilization of the protein by binding of 6'-O-fluorescein-atractyloside.

Science.gov (United States)

Smith, Vernon R; Fearnley, Ian M; Walker, John E

2003-01-01

Atractyloside (ATR) is a high-affinity specific inhibitor of the mitochondrial ADP/ATP translocase (AAT). The binding of a fluorescent derivative, 6'- O -fluorescein-ATR (FATR), to mitochondria has been characterized. The binding constants obtained are in agreement with previously published values for ATR, demonstrating that FATR is a suitable probe of the AAT. AAT inhibited by FATR (FATR-AAT) was solubilized in dodecyl maltoside and purified by two separate ion-exchange chromatography steps at different pHs, which allowed FATR-AAT to be purified to homogeneity. The presence of the bound fluorescent probe enabled the inhibited AAT to be distinguished from the unliganded protein during chromatography, as they were markedly different in their chromatographic behaviour. The purified FATR-AAT was dimeric and in a single major conformation containing 1 mole FATR per mole of AAT dimer. In contrast, uninhibited AAT was monomeric and conformationally unstable. Use of the fluorescent ATR derivative in the development of the protocol enabled the stable dimeric AAT to be monitored directly and purified more effectively. The purification protocol was repeated using non-derivatized ATR, and highly pure AAT was obtained that was devoid of other members of the mitochondrial carrier family. PMID:14498831

Cooperative Enhancement of Radiosensitivity After Combined Treatment of 17-(Allylamino)-17-Demethoxygeldanamycin and Celecoxib in Human Lung and Colon Cancer Cell Lines

Science.gov (United States)

Kim, Young-Mee

2012-01-01

We investigated whether the combined treatment of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of heat-shock protein 90 (hsp90), and celecoxib, an inhibitor of cyclooxygenase-2, can cooperatively enhance the radiosensitivity of various human cancer cells. Combined treatment with 17-AAG and celecoxib, at clinically relevant concentrations, cooperatively induced radiosensitization in all tested cancer cells, but not in normal cells. Cooperative radiosensitization by the drug combination was also shown in a human tumor xenograft system. We found that ataxia-telangiectasia and rad3-related (ATR) and ataxia-telangiectasia mutated (ATM) are novel client proteins of hsp90. Combined treatment with 17-AAG and celecoxib cooperatively induced downregulation of ATR and ATM. In conclusion, combined treatment with 17-AAG and celecoxib at clinically relevant concentrations may significantly enhance the therapeutic efficacy of ionizing radiation. PMID:21830942

Inhibitors

Science.gov (United States)

... JM, and the Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor ... webinars on blood disorders Language: English (US) Español (Spanish) File Formats Help: How do I view different ...

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

International Nuclear Information System (INIS)

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

2013-01-01

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 drying TM . 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)

Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin.

Science.gov (United States)

Liu, Kang; Lin, Fang-Tsyr; Graves, Joshua D; Lee, Yu-Ju; Lin, Weei-Chin

2017-05-09

Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress. The effect on ATR response caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR-activating function during replication stress, TopBP1 interacts with Treslin in a Cdk-dependent manner to initiate DNA replication during normal growth. We find that mutp53 also interferes with TopBP1 replication function. Several contact, but not conformational, mutp53s enhance the interaction between TopBP1 and Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor. Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA replication: ( i ) Both contact and conformational mutp53s can bind TopBP1 and attenuate the checkpoint response to replication stress, and ( ii ) during normal growth, contact (but not conformational) mutp53s can override the Cdk2 requirement to promote replication by facilitating the TopBP1/Treslin interaction.

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

Science.gov (United States)

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

2017-11-01

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

In situ ATR FTIR studies of SO4 adsorption on goethite in the presence of copper ions.

Science.gov (United States)

Beattie, D A; Chapelet, J K; Gräfe, M; Skinner, W M; Smith, E

2008-12-15

Despite the existence of many single ion sorption studies on iron and aluminum oxides, fewer studies have been reported that describe cosorption reactions. In this work, we present an in situ ATR FTIR study of synergistic adsorption of sulfate (SO4) and copper (Cu) on goethite, which is representative of the minerals and ions present in mine wastes, acid sulfate soils, and other industrial and agricultural settings. Sulfate adsorption was studied as a function of varying pH, and as a function of increasing concentration in the absence and presence of Cu. The presence of Cu ions in solution had a complex effect on the ability of SO4 ions to be retained on the goethite surface with increasing pH, with complete desorption occurring near pH 7 and 9 in the absence and presence of Cu, respectively. In addition, Cu ions altered the balance of inner vs outer sphere adsorbed SO4. The solid phase partitioning of SO4 at pH 3 and pH 5 was elevated by the presence of Cu; in both cases Cu increased the affinity of SO4 for the goethite surface. Complementary ex situ sorption edge studies of Cu on goethite in the absence and presence of SO4 revealed that the Cu adsorption edge shifted to lower pH (6.3 --> 5.6) in the presence of SO4, consistent with a decrease of the electrostatic repulsion between the goethite surface and adsorbing Cu. Based on the ATR FTIR and bulk sorption data we surmise that the cosorption products of SO4 and Cu at the goethite-water interface were not in the nature of ternary complexes under the conditions studied here. This information is critical for the evaluation of the onset of surface precipitates of copper-hydroxy sulfates as a function of pH and solution concentration.

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.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as a Forensic Method to Determine the Composition of Inks Used to Print the United States One-cent Blue Benjamin Franklin Postage Stamps of the 19th Century.

Science.gov (United States)

Brittain, Harry G

2016-01-01

Through the combined use of infrared (IR) absorption spectroscopy and attenuated total reflectance (ATR) sampling, the composition of inks used to print the many different types of one-cent Benjamin Franklin stamps of the 19th century has been established. This information permits a historical evaluation of the formulations used at various times, and also facilitates the differentiation of the various stamps from each other. In two instances, the ink composition permits the unambiguous identification of stamps whose appearance is identical, and which (until now) have only been differentiated through estimates of the degree of hardness or softness of the stamp paper, or through the presence or absence of a watermark in the paper. In these instances, the use of ATR Fourier transform infrared spectroscopy (FT-IR) spectroscopy effectively renders irrelevant two 100-year-old practices of stamp identification. Furthermore, since the use of ATR sampling makes it possible to obtain the spectrum of a stamp still attached to its cover, it is no longer necessary to identify these blue Franklin stamps using their cancellation dates. © The Author(s) 2015.

Analysis code for pressure in reactor containment vessel of ATR. CONPOL

International Nuclear Information System (INIS)

1997-08-01

For the evaluation of the pressure and temperature in containment vessels in the events which are classified in the abnormal change of pressure, atmosphere and others in reactor containment vessels in accident among the safety evaluation events of the ATR, the analysis code for the pressure in reactor containment vessels CONPOL is used. In this report, the functions of the analysis code and the analysis model are shown. By using this analysis code, the rise of the pressure and temperature in a containment vessel is evaluated when loss of coolant accident occurs, and high temperature, high pressure coolant flows into it. This code possesses the functions of computing blow-down quantity and heat dissipation from reactor cooling facility, steam condensing heat transfer to containment vessel walls, and the cooling effect by containment vessel spray system. As for the analysis techniques, the models of reactor cooling system, containment vessel and steam discharge pool, and the computation models for the pressure and temperature in containment vessels, wall surface temperature, condensing heat transfer, spray condensation and blow-down are explained. The experimental analysis of the evaluation of the pressure and temperature in containment vessels at the time of loss of coolant accident is reported. (K.I.)

Nuclear magnetic resonance (1.40 T) and mid infrared (FTIR-ATR) associated with chemometrics as analytical methods for the analysis of methyl ester yield obtained by esterification reaction

Energy Technology Data Exchange (ETDEWEB)

Kollar, Sara R.M.; Suarez, Paulo A.Z., E-mail: psuarez@unb.br [Universidade de Brasilia (UnB), Brasília, DF (Brazil). Instituto de Química; Novotny, Etelvino H. [Embrapa Solos, Rio de Janeiro, RJ (Brazil); Nascimento, Claudia J. do [Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro, RJ, (Brazil). Instituto de Biociências

2017-07-01

In this work, we compared 1.40 T nuclear magnetic resonance (NMR) to 7.05 T (60 and 300 MHz for proton, respectively), and mid-infrared with attenuated total reflectance (FTIR-ATR), associated with chemometrics methods, for the quantification of the reaction yield during esterification of fatty acids with methanol. The results showed that the integrated intensities of the ester C=O stretching region, relative to the total C=O stretching region, is useful to quantify the fatty acid methyl ester (FAME) concentration. Comparing the results obtained by the different final models: NMR (1.40 T and 7.05 T), FTIR-ATR using multivariate partial last squares regression (PLS) with orthogonal signal correction (OSC), and univariate ordinary least squares (OLS), the NMR of 1.40 T (60 MHz for proton) showed more advantages when compared to a high field spectrometer, due to the non-use of cryogenic and solvents and less laborious work for obtaining results. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-08-01

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

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

International Nuclear Information System (INIS)

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.)

Computer analysis of ATR-FTIR spectra of paint samples for forensic purposes

Science.gov (United States)

Szafarska, Małgorzata; Woźniakiewicz, Michał; Pilch, Mariusz; Zięba-Palus, Janina; Kościelniak, Paweł

2009-04-01

A method of subtraction and normalization of IR spectra (MSN-IR) was developed and successfully applied to extract mathematically the pure paint spectrum from the spectrum of paint coat on different bases, both acquired by the Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) technique. The method consists of several stages encompassing several normalization and subtraction processes. The similarity of the spectrum obtained with the reference spectrum was estimated by means of the normalized Manhattan distance. The utility and performance of the method proposed were tested by examination of five different paints sprayed on plastic (polyester) foil and on fabric materials (cotton). It was found that the numerical algorithm applied is able - in contrast to other mathematical approaches conventionally used for the same aim - to reconstruct a pure paint IR spectrum effectively without a loss of chemical information provided. The approach allows the physical separation of a paint from a base to be avoided, hence a time and work-load of analysis to be considerably reduced. The results obtained prove that the method can be considered as a useful tool which can be applied to forensic purposes.

A Neural Network Controller New Methodology for the ATR-42 Morphing Wing Actuation

Directory of Open Access Journals (Sweden)

Abdallah Ben MOSBAH

2016-06-01

Full Text Available A morphing wing model is used to improve aircraft performance. To obtain the desired airfoils, electrical actuators are used, which are installed inside of the wing to morph its upper surface in order to obtain its desired shape. In order to achieve this objective, a robust position controller is needed. In this research, a design and test validation of a controller based on neural networks is presented. This controller was composed by a position controller and a current controller to manage the current consumed by the electrical actuators to obtain its desired displacement. The model was tested and validated using simulation and experimental tests. The results obtained with the proposed controller were compared to the results given by the PID controller. Wind tunnel tests were conducted in the Price-Païdoussis Wind Tunnel at the LARCASE laboratory in order to calculate the pressure coefficient distribution on an ATR-42 morphing wing model for different flow conditions. The pressure coefficients obtained experimentally were compared with their numerical values given by XFoil software.

Status Summary of FY16 Atom Probe Tomography Studies on UCSB ATR-2 Irradiated RPV Steels

Energy Technology Data Exchange (ETDEWEB)

Wells, Peter [Idaho National Lab. (INL), Idaho Falls, ID (United States); Odette, G. Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-05-01

The University of California Santa Barbara-2 RPV Steel Irradiation experiment was awarded in 2010 by the Nuclear Science User Facility (formerly ATR NSUF) through a competitive peer review proposal process. The experiment involved irradiation of nearly 1300 samples distributed over 13 capsules. The major objective of this experiment was to better understand embrittlement behavior of reactor pressure steels at doses beyond which available data exists yet may be achieved if reactor operating licenses are extended beyond 60 years. The experiment was instrumented during irradiation and active temperature control was used to maintain the temperature at the design temperature. Six samples were selected from a large matrix of materials to perform atom probe tomography (APT) to look at formation of high dose phases. The nature and formation behavior of these phases is discussed.

A Cadmium Anionic 1-D Coordination Polymer {[Cd(H2O6][Cd2(atr2(μ2-btc2(H2O4] 2H2O}n within a 3-D Supramolecular Charge-Assisted Hydrogen-Bonded and π-Stacking Network

Directory of Open Access Journals (Sweden)

Anas Tahli

2016-03-01

Full Text Available The hydrothermal reaction of 4,4′-bis(1,2,4-triazol-4-yl (btr and benzene-1,3,5-tricarboxylic acid (H3btc with Cd(OAc2·2H2O at 125 °C in situ forms 4-amino-1,2,4-triazole (atr from btr, which crystallizes to a mixed-ligand, poly-anionic chain of [Cd2(atr2(µ2-btc2(H2O4]2–. Together with a hexaaquacadmium(II cation and water molecules the anionic coordination-polymeric forms a 3-D supramolecular network of hexaaquacadmium(II-catena-[bis(4-amino-1,2,4-triazoletetraaquabis(benzene-1,3,5-tricarboxylatodicadmate(II] dihydrate, 1-D-{[Cd(H2O6][Cd2(atr2(µ2-btc2(H2O4] 2H2O}n which is based on hydrogen bonds (in part charge-assisted and π–π interactions.

Modulation of the DNA repair system and ATR-p53 mediated apoptosis is relevant for tributyltin-induced genotoxic effects in human hepatoma G2 cells.

Science.gov (United States)

Li, Bowen; Sun, Lingbin; Cai, Jiali; Wang, Chonggang; Wang, Mengmeng; Qiu, Huiling; Zuo, Zhenghong

2015-01-01

The toxic effects of tributyltin (TBT) have been extensively documented in several types of cells, but the molecular mechanisms related to the genotoxic effects of TBT have still not been fully elucidated. Our study showed that exposure of human hepatoma G2 cells to 1-4 μmol/L TBT for 3 hr caused severe DNA damage in a concentration-dependent manner. Moreover, the expression levels of key DNA damage sensor genes such as the replication factor C, proliferating cell nuclear antigen and poly (ADP-ribose) polymerase-1 were inhabited in a concentration-dependent manner. We further demonstrated that TBT induced cell apoptosis via the p53-mediated pathway, which was most likely activated by the ataxia telangiectasia mutated and rad-3 related (ATR) protein kinase. The results also showed that cytochrome c, caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 were involved in this process. Taken together, we demonstrated for the first time that the inhibition of the DNA repair system might be more responsible for TBT-induced genotoxic effects in cells. Then the generated DNA damage induced by TBT initiated ATR-p53-mediated apoptosis. Copyright © 2014. Published by Elsevier B.V.

Blood glucose measurement with multiple quantum cascade lasers using hollow-optical fiber-based ATR spectroscopy

Science.gov (United States)

Yoshioka, K.; Kino, S.; Matsuura, Y.

2018-02-01

For non-invasive blood glucose measurement, a measurement system based on mid-infrared ATR spectroscopy equipped with a combination of a QCL as a light source and a hollow-optical fiber as a beam delivery medium is developed. Firstly the measurement sensitivity of the system is evaluated by using glucose solutions and the result shows a significant correlation between optical absorbance and solution concentration. It is also confirmed that the system has a sensitivity that is enough for blood glucose measurement. Then optical absorption of human lips in the mid-infrared wavelength region is measured using a QCL with a wavenumber of 1080 cm-1 where human tissue exhibits strong absorption of glucose and its metabolites. As a result, the measured absorption follows the change of blood glucose well with a time delay of around 10 minutes and correlation factor between the absorbance and the blood glucose level is 0.42.

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

Directory of Open Access Journals (Sweden)

Jorge A. Orrego-Ruiz

2014-06-01

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

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

Science.gov (United States)

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

2018-05-01

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

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.

Fuzzy Gauge Capability (Cg and Cgk) through Buckley Approach

OpenAIRE

Seyed Habib A. Rahmati; Mohsen Sadegh Amalnick

2015-01-01

Different terms of the Statistical Process Control (SPC) has sketch in the fuzzy environment. However, Measurement System Analysis (MSA), as a main branch of the SPC, is rarely investigated in fuzzy area. This procedure assesses the suitability of the data to be used in later stages or decisions of the SPC. Therefore, this research focuses on some important measures of MSA and through a new method introduces the measures in fuzzy environment. In this method, which works b...

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.

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.

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

Science.gov (United States)

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

2018-01-01

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

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)

Xu, Qinqin; Berná, Antonio; Pobelov, Ilya V.; Rodes, 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 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 (CO L ) and bridge (CO B ) 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

Behavior of irradiated ATR/MOX fuel under reactivity initiated accident conditions (Joint research)

International Nuclear Information System (INIS)

Sasajima, Hideo; Fuketa, Toyoshi; Nakamura, Takehiko; Nakamura, Jinichi; Uetsuka, Hiroshi

2000-03-01

Pulse irradiation experiments with irradiated ATR/MOX fuel rods of 20 MWd/kgHM were conducted at the NSRR in JAERI to study the transient behavior of MOX fuel rod under reactivity initiated accident conditions. Four pulse irradiation experiments were performed with peak fuel enthalpy ranging from 335 J/g to 586 J/g, resulted in no failure of fuel rods. Deformation of the fuel rods due to PCMI occurred in the experiments with peak fuel enthalpy above 500 J/g. Significant fission gas release up to 20% was measured by rod puncture measurement. The generation of fine radial cracks in pellet periphery, micro-cracks and boundary separation over the entire region of pellet were observed. These microstructure changes might contribute to the swelling of fuel pellets during the pulse irradiation. This could cause the large radial deformation of fuel rod and high fission gas release when the pulse irradiation conducted at relatively high peak fuel enthalpy. In addition, fine grain structures around the plutonium spot and cauliflower structure in cavity of the plutonium spot were observed in the outer region of the fuel pellet. (author)

ATR-FTIR and Raman spectroscopic investigation of the electroporation-mediated transdermal delivery of a nanocarrier system containing an antitumour drug.

Science.gov (United States)

Balázs, Boglárka; Sipos, Péter; Danciu, Corina; Avram, Stefana; Soica, Codruta; Dehelean, Cristina; Varju, Gábor; Erős, Gábor; Budai-Szűcs, Mária; Berkó, Szilvia; Csányi, Erzsébet

2016-01-01

The aim of the present work was the optimization of the transdermal delivery of a lyotropic liquid crystal genistein-based formulation (LLC-GEN). LLC was chosen as medium in view of the poor solubility of GEN in water. Membrane diffusion and penetration studies were carried out with a Franz diffusion cell, through a synthetic membrane in vitro, a chick chorioallantoic membrane ex ovo, and ex vivo excised human epidermis. Thereafter, LLC-GEN was combined with electroporation (EP) to enhance the transdermal drug delivery. The synergistic effect of EP was verified by in vivo ATR-FTIR and ex vivo Raman spectroscopy on hairless mouse skin.

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

Science.gov (United States)

Sjogren, Caroline A; Larsen, Paul B

2017-09-01

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

Characterization of the cGMP-dependent protein kinase SmcGK1 of Schistosoma mansoni

Directory of Open Access Journals (Sweden)

Silke Leutner

2011-06-01

Full Text Available Schistosomes are trematode parasites and of worldwide medical importance for humans and animals. Growth and development of these parasites require a specific host environment, but also permanent communication processes between the two genders. Accumulating molecular evidence indicates that the responsible interactions are mediated by signal transduction processes. Conserved signaling molecules were identified, and first approaches made for their characterization. However, no representative of the conserved family of cGMP-dependent protein kinases (cGKs has been described in this parasite yet. Within the Schistosoma mansoni genome data-set we identified cGK homologs, of which one was investigated in more detail in this study. We present the cloning of SmcGK1, whose sequence shows homology to cGKs of higher eukaryotes. SmcGK1 was found to be gender-independently transcribed in adult schistosomes. The occurrence of SmcGK1 sense and antisense transcripts suggests that the expression of this gene is controlled at the post-transcriptional level. In situ hybridization experiments demonstrated a gonad-preferential expression profile in both genders indicating a role of SmcGK1, at least during sexual development of schistosomes. Using a cGK-specific inhibitor to treat adult schistosomes in vitro finally resulted in a multifaceted phenotype including slow motion, oocyte congestion, and reduced egg production.Esquistossomos são parasitas trematodos de importância médica em todo o mundo para o homem e os animais. O crescimento e o desenvolvimento destes parasitas requerem um ambiente específico do hospedeiro, mas também um processo de comunicação permanente entre parasitas dos dois sexos. Evidência molecular tem se acumulado e indica que as interações são mediadas por processos de transdução de sinal. Moléculas sinalizadoras conservadas foram identificadas, e as primeiras abordagens têm sido feitas para sua caracterização. Contudo, não foi

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

Discovery of natural mouse serum derived HIV-1 entry inhibitor(s).

Science.gov (United States)

Wei, M; Chen, Y; Xi, J; Ru, S; Ji, M; Zhang, D; Fang, Q; Tang, B

Among rationally designed human immunodeficiency virus 1 (HIV-1) inhibitors, diverse natural factors have showed as potent anti-HIV activity in human blood. We have discovered that the boiled supernatant of healthy mouse serum could suppress HIV-1 entry, and exhibited reduced inhibitory activity after trypsin digestion. Further analysis demonstrated that only the fraction containing 10-25 K proteins could inhibit HIV-1 mediated cell-cell fusion. These results suggest that the 10-25 K protein(s) is novel natural HIV-1 entry inhibitor(s). Our findings provide important information about novel natural HIV entry inhibitors in mouse serum.

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)

Khan, M.I.; Madni, A.; Ahmad, S.; Rehmanand, M.; Mahmood, M.A.; Khan, A.

2015-01-01

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)

A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K727, K733) with the oxime HI-6 and obidoxime in sarin-poisoned rats and mice.

Science.gov (United States)

Kassa, Jiri; Sepsova, Vendula; Matouskova, Lenka; Horova, Anna; Musilek, Kamil

2015-03-01

The ability of two novel bispyridinium oximes K727 and K733 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. To investigate the reactivating efficacy of the oximes, the rats were administered intramuscularly with atropine and oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of sarin at a dose of 24 µg/kg (LD50). The activity of acetylcholinesterase was measured at 60 min after sarin poisoning. The LD50 value of sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of sarin at five different doses. In vivo determined percentage of reactivation of sarin-inhibited rat blood, diaphragm and brain acetylcholinesterase showed that the potency of both novel oximes K727 and K733 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be the most efficient reactivator of sarin-inhibited acetylcholinesterase. While the oxime HI-6 was able to reduce the acute toxicity of sarin >3 times, both novel oximes and obidoxime decreased the acute toxicity of sarin HI-6 and, therefore, they are not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute sarin poisoning.

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

2013-05-01

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 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.

Enantioselective skin permeation of ibuprofen enantiomers: mechanistic insights from ATR-FTIR and CLSM studies based on synthetic enantiomers as naphthalimide fluorescent probes.

Science.gov (United States)

Che, Qi-en; Quan, Peng; Mu, Mao; Zhang, Xinfu; Zhao, Hanqing; Zhang, Yu; You, Song; Xiao, Yi; Fang, Liang

2014-10-01

The aim of this study was to investigate the mechanisms of different skin permeability of ibuprofen racemate and enantiomers. The percutaneous permeation of ibuprofen racemate and enantiomers through rabbit normal skin and damaged skin (without stratum corneum [SC]) was investigated in vitro using side-by-side diffusion cells. With the melting temperature-membrane transport model, the flux ratio of enantiomer/racemate was calculated from their thermodynamic properties obtained by differential scanning calorimetry. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) study was performed to evaluate the interaction between the enantiomers and the SC. New fluorescent probes were designed and utilized in confocal laser scanning microscopy (CLSM) study for visualization of the enantioselective permeation of the enantiomers through the intact rabbit skin. The flux of (S)-ibuprofen through normal skin was significantly higher than that of (RS)-ibuprofen and (R)-ibuprofen (p skin, there was no significant difference (p > 0.05). The predicted flux ratio of (S)-ibuprofen/(RS)-ibuprofen (2.50) was in close agreement with the experimentally determined ratio (2.48). These results were supported by ATR-FTIR and CLSM studies that indicated that a chiral environment of the skin led to the enantioselective permeation of enantiomers. The chiral nature of the SC and the different physicochemical properties of the enantiomers should be taken into account in the assessment of different skin permeability of the racemate and enantiomers. The synthetic fluorescent probes used in this study could visualize the enantioselective permeation of the chiral compounds across the skin.

Measurement of conjugated linoleic acid (CLA) in CLA-rich soy oil by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR).

Science.gov (United States)

Kadamne, Jeta V; Jain, Vishal P; Saleh, Mohammed; Proctor, Andrew

2009-11-25

Conjugated linoleic acid (CLA) isomers in oils are currently measured as fatty acid methyl esters by a gas chromatography-flame ionization detector (GC-FID) technique, which requires approximately 2 h to complete the analysis. Hence, we aim to develop a method to rapidly determine CLA isomers in CLA-rich soy oil. Soy oil with 0.38-25.11% total CLA was obtained by photo-isomerization of 96 soy oil samples for 24 h. A sample was withdrawn at 30 min intervals with repeated processing using a second batch of oil. Six replicates of GC-FID fatty acid analysis were conducted for each oil sample. The oil samples were scanned using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and the spectrum was collected. Calibration models were developed using partial least-squares (PLS-1) regression using Unscrambler software. Models were validated using a full cross-validation technique and tested using samples that were not included in the calibration sample set. Measured and predicted total CLA, trans,trans CLA isomers, total mono trans CLA isomers, trans-10,cis-12 CLA, trans-9,cis-11 CLA and cis-10,trans-12 CLA, and cis-9,trans-11 CLA had cross-validated coefficients of determinations (R2v) of 0.97, 0.98, 0.97, 0.98, 0.97, and 0.99 and corresponding root-mean-square error of validation (RMSEV) of 1.14, 0.69, 0.27, 0.07, 0.14, and 0.07% CLA, respectively. The ATR-FTIR technique is a rapid and less expensive method for determining CLA isomers in linoleic acid photo-isomerized soy oil than GC-FID.

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

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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.

El diálogo creativo en El cuarto de atrás : La búsqueda de una identidad en la memoria colectiva

OpenAIRE

Muñoz Åhlén, Anna-Maria

2017-01-01

Esta tesina tiene como objetivo analizar la relación entre C. y el interlocutor misterioso en El cuarto de atrás de Carmen Martín Gaite. Intentaremos averiguar qué recuerdos aparecen por medio del diálogo entre los interlocutores. Partiendo de allí, el trabajo enfocará qué recuerdos de infancia aparecen por medio del diálogo y de qué manera han influido en el personaje C. en el tiempo real de la creación de la novela. Como apoyo de interpretar la identidad del personaje nos apoyaremos princip...

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

DEFF Research Database (Denmark)

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

2010-01-01

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

Rapid and Simultaneous Prediction of Eight Diesel Quality Parameters through ATR-FTIR Analysis

Science.gov (United States)

Hatanaka, Rafael Rodrigues; Flumignan, Danilo Luiz; de Oliveira, José Eduardo

2018-01-01

Quality assessment of diesel fuel is highly necessary for society, but the costs and time spent are very high while using standard methods. Therefore, this study aimed to develop an analytical method capable of simultaneously determining eight diesel quality parameters (density; flash point; total sulfur content; distillation temperatures at 10% (T10), 50% (T50), and 85% (T85) recovery; cetane index; and biodiesel content) through attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and the multivariate regression method, partial least square (PLS). For this purpose, the quality parameters of 409 samples were determined using standard methods, and their spectra were acquired in ranges of 4000–650 cm−1. The use of the multivariate filters, generalized least squares weighting (GLSW) and orthogonal signal correction (OSC), was evaluated to improve the signal-to-noise ratio of the models. Likewise, four variable selection approaches were tested: manual exclusion, forward interval PLS (FiPLS), backward interval PLS (BiPLS), and genetic algorithm (GA). The multivariate filters and variables selection algorithms generated more fitted and accurate PLS models. According to the validation, the FTIR/PLS models presented accuracy comparable to the reference methods and, therefore, the proposed method can be applied in the diesel routine monitoring to significantly reduce costs and analysis time. PMID:29629209

Rapid and Simultaneous Prediction of Eight Diesel Quality Parameters through ATR-FTIR Analysis

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Maurilio Gustavo Nespeca

2018-01-01

Full Text Available Quality assessment of diesel fuel is highly necessary for society, but the costs and time spent are very high while using standard methods. Therefore, this study aimed to develop an analytical method capable of simultaneously determining eight diesel quality parameters (density; flash point; total sulfur content; distillation temperatures at 10% (T10, 50% (T50, and 85% (T85 recovery; cetane index; and biodiesel content through attenuated total reflection Fourier transform infrared (ATR-FTIR spectroscopy and the multivariate regression method, partial least square (PLS. For this purpose, the quality parameters of 409 samples were determined using standard methods, and their spectra were acquired in ranges of 4000–650 cm−1. The use of the multivariate filters, generalized least squares weighting (GLSW and orthogonal signal correction (OSC, was evaluated to improve the signal-to-noise ratio of the models. Likewise, four variable selection approaches were tested: manual exclusion, forward interval PLS (FiPLS, backward interval PLS (BiPLS, and genetic algorithm (GA. The multivariate filters and variables selection algorithms generated more fitted and accurate PLS models. According to the validation, the FTIR/PLS models presented accuracy comparable to the reference methods and, therefore, the proposed method can be applied in the diesel routine monitoring to significantly reduce costs and analysis time.

Rapid and Simultaneous Prediction of Eight Diesel Quality Parameters through ATR-FTIR Analysis.

Science.gov (United States)

Nespeca, Maurilio Gustavo; Hatanaka, Rafael Rodrigues; Flumignan, Danilo Luiz; de Oliveira, José Eduardo

2018-01-01

Quality assessment of diesel fuel is highly necessary for society, but the costs and time spent are very high while using standard methods. Therefore, this study aimed to develop an analytical method capable of simultaneously determining eight diesel quality parameters (density; flash point; total sulfur content; distillation temperatures at 10% (T10), 50% (T50), and 85% (T85) recovery; cetane index; and biodiesel content) through attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and the multivariate regression method, partial least square (PLS). For this purpose, the quality parameters of 409 samples were determined using standard methods, and their spectra were acquired in ranges of 4000-650 cm -1 . The use of the multivariate filters, generalized least squares weighting (GLSW) and orthogonal signal correction (OSC), was evaluated to improve the signal-to-noise ratio of the models. Likewise, four variable selection approaches were tested: manual exclusion, forward interval PLS (FiPLS), backward interval PLS (BiPLS), and genetic algorithm (GA). The multivariate filters and variables selection algorithms generated more fitted and accurate PLS models. According to the validation, the FTIR/PLS models presented accuracy comparable to the reference methods and, therefore, the proposed method can be applied in the diesel routine monitoring to significantly reduce costs and analysis time.

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.

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

Science.gov (United States)

Ciaffi, Laura; Koulla-Shiro, Sinata; Sawadogo, Adrien Bruno; Ndour, Cheik Tidiane; Eymard-Duvernay, Sabrina; Mbouyap, Pretty Rosereine; Ayangma, Liliane; Zoungrana, Jacques; Gueye, Ndeye Fatou Ngom; Diallo, Mohamadou; Izard, Suzanne; Bado, Guillaume; Kane, Coumba Toure; Aghokeng, Avelin Fobang; Peeters, Martine; Girard, Pierre Marie; Le Moing, Vincent; Reynes, Jacques; Delaporte, Eric

2017-09-01

(tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059. Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; ptreatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients. Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stress-triggered signaling affecting survival or suicide of Streptococcus pneumoniae.

Science.gov (United States)

Cortes, Paulo R; Piñas, Germán E; Cian, Melina B; Yandar, Nubia; Echenique, Jose

2015-01-01

Streptococcus pneumoniae is a major human pathogen that can survive to stress conditions, such as the acidic environment of inflammatory foci, and tolerates lethal pH through a mechanism known as the acid tolerance response. We previously described that S. pneumoniae activates acidic-stress induced lysis in response to acidified environments, favoring the release of cell wall compounds, DNA and virulence factors. Here, we demonstrate that F(0)F(1)-ATPase is involved in the response to acidic stress. Chemical inhibitors (DCCD, optochin) of this proton pump repressed the ATR induction, but caused an increased ASIL. Confirming these findings, mutants of the subunit c of this enzyme showed the same phenotypes as inhibitors. Importantly, we demonstrated that F(0)F(1)-ATPase and ATR are necessary for the intracellular survival of the pneumococcus in macrophages. Alternatively, a screening of two-component system (TCS) mutants showed that ATR and survival in pneumocytes were controlled in contrasting ways by ComDE and CiaRH, which had been involved in the ASIL mechanism. Briefly, CiaRH was essential for ATR (ComE represses activation) whereas ComE was necessary for ASIL (CiaRH protects against induction). They did not regulate F0F1-ATPase expression, but control LytA expression on the pneumococcal surface. These results suggest that both TCSs and F(0)F(1)-ATPase control a stress response and decide between a survival or a suicide mechanism by independent pathways, either in vitro or in pneumocyte cultures. This biological model contributes to the current knowledge about bacterial response under stress conditions in host tissues, where pathogens need to survive in order to establish infections. Copyright © 2014 Elsevier GmbH. All rights reserved.

[Research on Rapid Discrimination of Edible Oil by ATR Infrared Spectroscopy].

Science.gov (United States)

Ma, Xiao; Yuan, Hong-fu; Song, Chun-feng; Hu, Ai-qin; Li, Xiao-yu; Zhao, Zhong; Li, Xiu-qin; Guo Zhen; Zhu, Zhi-qiang

2015-07-01

A rapid discrimination method of edible oils, KL-BP model, was proposed by attenuated total reflectance infrared spectroscopy. The model extracts the characteristic of classification from source data by KL and reduces data dimension at the same time. Then the neural network model is constructed by the new data which as the input of the model. 84 edible oil samples which include sesame oil, corn oil, canola oil, blend oil, sunflower oil, peanut oil, olive oil, soybean oil and tea seed oil, were collected and their infrared spectra determined using an ATR FT-IR spectrometer. In order to compare the method performance, principal component analysis (PCA) direct-classification model, KL direct-classification model, PLS-DA model, PCA-BP model and KL-BP model are constructed in this paper. The results show that the recognition rates of PCA, PCA-BP, KL, PLS-DA and KL-BP are 59.1%, 68.2%, 77.3%, 77.3% and 90.9% for discriminating the 9 kinds of edible oils, respectively. KL extracts the eigenvector which make the distance between different class and distance of every class ratio is the largest. So the method can get much more classify information than PCA. BP neural network can effectively enhance the classification ability and accuracy. Taking full of the advantages of KL in extracting more category information in dimension reducing and the features of BP neural network in self-learning, adaptive, nonlinear, the KL-BP method has the best classification ability and recognition accuracy and great importance for rapidly recognizing edible oil in practice.

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......%) and 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...

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.

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.

Synergistic apoptosis induction in leukemic cells by the phosphatase inhibitor salubrinal and proteasome inhibitors.

Directory of Open Access Journals (Sweden)

Hannes C A Drexler

Full Text Available Cells adapt to endoplasmic reticulum (ER-stress by arresting global protein synthesis while simultaneously activating specific transcription factors and their downstream targets. These processes are mediated in part by the phosphorylation-dependent inactivation of the translation initiation factor eIF2alpha. Following restoration of homeostasis protein synthesis is resumed when the serine/threonine-protein phosphatase PP1 dephosphorylates and reactivates eIF2alpha. Proteasome inhibitors, used to treat multiple myeloma patients evoke ER-stress and apoptosis by blocking the ER-associated degradation of misfolded proteins (ERAD, however, the role of eIF2alpha phosphorylation in leukemic cells under conditions of proteasome inhibitor-mediated ER stress is currently unclear.Bcr-Abl-positive and negative leukemic cell lines were used to investigate the functional implications of PP1-related phosphatase activities on eIF2alpha phosphorylation in proteasome inhibitor-mediated ER stress and apoptosis. Rather unexpectedly, salubrinal, a recently identified PP1 inhibitor capable to protect against ER stress in various model systems, strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines. Salubrinal treatment did not affect the phosphorlyation status of eIF2alpha. Furthermore, the proapoptotic effect of salubrinal occurred independently from the chemical nature of the proteasome inhibitor, was recapitulated by a second unrelated phosphatase inhibitor and was unaffected by overexpression of a dominant negative eIF2alpha S51A variant that can not be phosphorylated. Salubrinal further aggravated ER-stress and proteotoxicity inflicted by the proteasome inhibitors on the leukemic cells since characteristic ER stress responses, such as ATF4 and CHOP synthesis, XBP1 splicing, activation of MAP kinases and eventually apoptosis were efficiently abrogated by the translational inhibitor cycloheximide.Although PP1

Preparation of Atomically Flat Si(111)-H Surfaces in Aqueous Ammonium Fluoride Solutions Investigated by Using Electrochemical, In Situ EC-STM and ATR-FTIR Spectroscopic Methods

International Nuclear Information System (INIS)

Bae, Sang Eun; Oh, Mi Kyung; Min, Nam Ki; Paek, Se Hwan; Hong, Suk In; Lee, Chi-Woo J.

2004-01-01

Electrochemical, in situ electrochemical scanning tunneling microscope (EC-STM), and attenuated total reflectance-FTIR (ATR-FTIR) spectroscopic methods were employed to investigate the preparation of atomically flat Si(111)-H surface in ammonium fluoride solutions. Electrochemical properties of atomically flat Si(111)-H surface were characterized by anodic oxidation and cathodic hydrogen evolution with the open circuit potential (OCP) of ca. .0.4 V in concentrated ammonium fluoride solutions. As soon as the natural oxide-covered Si(111) electrode was immersed in fluoride solutions, OCP quickly shifted to near .1 V, which was more negative than the flat band potential of silicon surface, indicating that the surface silicon oxide had to be dissolved into the solution. OCP changed to become less negative as the oxide layer was being removed from the silicon surface. In situ EC-STM data showed that the surface was changed from the initial oxide covered silicon to atomically rough hydrogen-terminated surface and then to atomically flat hydrogen terminated surface as the OCP moved toward less negative potentials. The atomically flat Si(111)-H structure was confirmed by in situ EC-STM and ATR-FTIR data. The dependence of atomically flat Si(111)-H terrace on mis-cut angle was investigated by STM, and the results agreed with those anticipated by calculation. Further, the stability of Si(111)-H was checked by STM in ambient laboratory conditions

ATR-Chk1-APC/C-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

DEFF Research Database (Denmark)

Yamada, M.; Watanabe, K.; Mistrik, M.

2013-01-01

replication. Stalled DNA replication evoked stabilization of the Cdc7-ASK (Dbf4) complex in a manner dependent on ATR-Chk1-mediated checkpoint signaling and its interplay with the anaphase-promoting complex/cyclosomeCdh1 (APC/C) ubiquitin ligase. Mechanistically, Chk1 kinase inactivates APC/C through...... degradation of Cdh1 upon replication block, thereby stabilizing APC/C substrates, including Cdc7-ASK (Dbf4). Furthermore, motif C of ASK (Dbf4) interacts with the N-terminal region of RAD18 ubiquitin ligase, and this interaction is required for chromatin binding of RAD18. Impaired interaction of ASK (Dbf4...

Synchrotron macro ATR-FTIR microspectroscopic analysis of silica nanoparticle-embedded polyester coated steel surfaces subjected to prolonged UV and humidity exposure.

Science.gov (United States)

Vongsvivut, Jitraporn; Truong, Vi Khanh; Al Kobaisi, Mohammad; Maclaughlin, Shane; Tobin, Mark J; Crawford, Russell J; Ivanova, Elena P

2017-01-01

Surface modification of polymers and paints is a popular and effective way to enhance the properties of these materials. This can be achieved by introducing a thin coating that preserves the bulk properties of the material, while protecting it from environmental exposure. Suitable materials for such coating technologies are inorganic oxides, such as alumina, titania and silica; however, the fate of these materials during long-term environmental exposure is an open question. In this study, polymer coatings that had been enhanced with the addition of silica nanoparticles (SiO2NPs) and subsequently subjected to environmental exposure, were characterized both before and after the exposure to determine any structural changes resulting from the exposure. High-resolution synchrotron macro ATR-FTIR microspectroscopy and surface topographic techniques, including optical profilometry and atomic force microscopy (AFM), were used to determine the long-term effect of the environment on these dual protection layers after 3 years of exposure to tropical and sub-tropical climates in Singapore and Queensland (Australia). Principal component analysis (PCA) based on the synchrotron macro ATR-FTIR spectral data revealed that, for the 9% (w/w) SiO2NP/polymer coating, a clear discrimination was observed between the control group (no environmental exposure) and those samples subjected to three years of environmental exposure in both Singapore and Queensland. The PCA loading plots indicated that, over the three year exposure period, a major change occurred in the triazine ring vibration in the melamine resins. This can be attributed to the triazine ring being very sensitive to hydrolysis under the high humidity conditions in tropical/sub-tropical environments. This work provides the first direct molecular evidence, acquired using a high-resolution mapping technique, of the climate-induced chemical evolution of a polyester coating. The observed changes in the surface topography of the

ATM protein is deficient in over 40% of lung adenocarcinomas.

Science.gov (United States)

Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

2016-09-06

Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption

Directory of Open Access Journals (Sweden)

Boutin Jean A

2010-10-01

Full Text Available Abstract Background Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts. Methods Human osteoclasts were generated from CD14+ monocytes. The effect of different kinase inhibitors on lysosomal acidification in human osteoclasts was investigated using acridine orange for different incubation times (45 minutes, 4 and 24 hours. The inhibitors were tested in an acid influx assay using microsomes isolated from human osteoclasts. Bone resorption by human osteoclasts on bone slices was measured by calcium release. Cell viability was measured using AlamarBlue. Results Of the 51 compounds investigated only few inhibitors were positive in both acidification and resorption assays. Rottlerin, GF109203X, Hypericin and Ro31-8220 inhibited acid influx in microsomes and bone resorption, while Sphingosine and Palmitoyl-DL-carnitine-Cl showed low levels of inhibition. Rottlerin inhibited lysosomal acidification in human osteoclasts potently. Conclusions In conclusion, a group of inhibitors all indicated to inhibit PKC reduced acidification in human osteoclasts, and thereby bone resorption, indicating that acid secretion by osteoclasts may be specifically regulated by PKC in osteoclasts.

Evaluation of Erosion of the Dummy ''EE'' Plate 19 in YA Type ATR Fuel Element During Reactor PALM Cycles

International Nuclear Information System (INIS)

Brower, Jeffrey O.; Glazoff, Michael V.; Eiden, Thomas J.; Rezvoi, Aleksey V.

2016-01-01

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

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)

Yu Peiqiang

2012-01-01

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

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.

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

Science.gov (United States)

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

2009-05-19

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

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.

Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.

Science.gov (United States)

Sun, Jiying; Shi, Lin; Kinomura, Aiko; Fukuto, Atsuhiko; Horikoshi, Yasunori; Oma, Yukako; Harata, Masahiko; Ikura, Masae; Ikura, Tsuyoshi; Kanaar, Roland; Tashiro, Satoshi

2018-05-08

Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities. © 2018, Sun et al.

Neutron monitoring measurements for the CIT [Compact Ignition Tokamak] materials irradiations in the ATR I1 position

International Nuclear Information System (INIS)

Rogers, J.W.; Anderl, R.A.

1989-12-01

Measurements were performed to help characterize the neutron environments in which the Compact Ignition Tokamak (CIT) materials were irradiated. These materials were irradiated in a lead shield plug assembly at the ATR I1 position. Neutron monitor materials were placed in the capsules in proximity with the CIT specimens. The neutron monitors sensed the neutrons through reactions that have different neutron energy region responses. By measuring the radioactivity of the neutron monitors it was possible to determine the neutron fluence rates (n/cm 2 /sec) and fluences (n/cm 2 ) at the locations of the monitors. It was also possible to determine the axial and radial gradients of the neutron environments near the specimens. This report presents the results obtained from these measurements for both the CIT number-sign 1 (ORNL 64-2) and CIT number-sign 2 (ORNL 64-1) capsules. In general, ASTM methods and procedures were used in all neutron monitoring associated activities. 7 refs., 9 figs., 10 tabs

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.

Interaction of ADP, atractyloside, and gummiferin on the ADP translocase of the inner mitochondrial membrane

Energy Technology Data Exchange (ETDEWEB)

Vignais, P V; Vignais, P M; Defaye, G; Lauquin, G; Doussiere, J; Chabert, J; Brandolin, G

1972-05-01

From international conference on mechanism in bioenergetica; Bari, Italy (1 May 1972). Two specific inhibitors of the adenine nucleotide translocation, gummiferin (GUM), identified to 4-carboxyatractyloside and atractyloside (ATR), were labeled with /sup 35/S and their binding properties to whole mitochondria and inner mitochondrial membrane vesicles used to monitor changes of membrane conformation induced by ADP. (auth)

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

Energy Technology Data Exchange (ETDEWEB)

Ogden, Dan [Idaho National Lab. (INL), Idaho Falls, ID (United States)

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.

Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study.

Science.gov (United States)

Sckolnick, Maria; Hui, Sek-Wen; Sen, Arindam

2008-02-28

Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.

ATR-IR spectroscopy for the detection of induced-phase transition in Langmuir-Blodgett monolayer film

International Nuclear Information System (INIS)

Widayati, Suci

1996-01-01

The rate at which a solid substrate is transferred through the Air/Water interface in the Langmuir-Blodgett process of preparing monomolecular films influences the final structure of the transferred film. This phenomenon has been observed from the attenuated total reflectance infra-red (ATR-IR) spectra of fatty acid monolayer transferred onto germanium substrate. This transfer-induced effect is most evidence when the monolayer is transferred from an expanded region of the surface-pressure-molecular area isotherm, but has limited influence on the hydrocarbon chain conformation of film molecules transferred in the condensed phases at high surface pressure. Such a conformational ordering may due to a kinetically limited phase transition taking place in the meniscus formed between the solid substrate and aqueous sub phase. In addition, these results suggest that the structure of the amphiphilic molecules may modulate the extent and nature of the dipping-speed-induced structural changes taking place in the monomolecular L-B film. In order to use monomolecular L-B films to accurately characterize the structure, orientation and phase properties of monolayers at the Air/Water interface, the L-B transfer must be performed at transfer speeds that minimize this structural phase transition

In situ observation on the dynamic process of evaporation and crystallization of sodium nitrate droplets on a ZnSe substrate by FTIR-ATR.

Science.gov (United States)

Zhang, Qing-Nuan; Zhang, Yun; Cai, Chen; Guo, Yu-Cong; Reid, Jonathan P; Zhang, Yun-Hong

2014-04-17

Sodium nitrate is a main component of aging sea salt aerosol, and its phase behavior has been studied repeatedly with wide ranges observed in the efflorescence relative humidity (RH) in particular. Studies of the efflorescence dynamics of NaNO3 droplets deposited on a ZnSe substrate are reported, using an in situ Fourier transform infrared attenuated total reflection (FTIR-ATR) technique. The time-dependence of the infrared spectra of NaNO3 aerosols accompanying step changes in RH have been measured with high signal-to-noise ratio. From the IR difference spectra recorded, changes of the time-dependent absorption peak area of the O-H stretching band (ν-OH, ∼3400 cm(-1)) and the nitrate out-of-plane bending band (ν2-NO3(-), ∼836 cm(-1)) are obtained. From these measurements, changes in the IR signatures can be attributed to crystalline and solution phase nitrate ions, allowing the volume fraction of the solution droplets that have crystallized to be determined. Then, using these clear signatures of the volume fraction of droplets that have yet to crystallize, the homogeneous and heterogeneous nucleation kinetics can be studied from conventional measurements using a steady decline in RH. The nucleation rate measurements confirm that the rate of crystallization in sodium nitrate droplets is considerably less than in ammonium sulfate droplets at any particular degree of solute supersaturation, explaining the wide range of efflorescence RHs observed for sodium nitrate in previous studies. We demonstrate that studying nucleation kinetics using the FTIR-ATR approach has many advantages over brightfield imaging studies on smaller numbers of larger droplets or measurements made on single levitated particles.

Allosteric small-molecule kinase inhibitors

DEFF Research Database (Denmark)

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

2015-01-01

current barriers of kinase inhibitors, including poor selectivity and emergence of drug resistance. In spite of the small number of identified allosteric inhibitors in comparison with that of inhibitors targeting the ATP pocket, encouraging results, such as the FDA-approval of the first small...

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

Energy Technology Data Exchange (ETDEWEB)

Brower, Jeffrey O. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor; Glazoff, Michael V. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor; Eiden, Thomas J. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor; Rezvoi, Aleksey V. [Idaho National Lab. (INL), Idaho Falls, ID (United States). Advanced Test Reactor

2016-08-01

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

Solid-state characterization of triamcinolone acetonide nanosuspensiones by X-ray spectroscopy, ATR Fourier transforms infrared spectroscopy and differential scanning calorimetry analysis

Directory of Open Access Journals (Sweden)

Eva García-Millán

2017-12-01

Full Text Available The data presented in this article describe the physical state of the triamcinolone acetonide (TA in nanosuspension stabilized with polyvinyl alcohol (PVA and poloxamer 407 (PL. The data were assessed by X-ray spectroscopy, ATR Fourier transforms infrared spectroscopy measurements (FTIR, and Differential scanning calorimetry (DSC analysis. PVA, PL and polymeric mixture (PVA and PL were compared with nanosuspension and the interactions between drug triamcinolone acetonide and polymers were studied. The data are related and are complementary to the research article entitle “Improved release of triamcinolone acetonide from medicated soft contact lenses loaded with drug nanosuspensions” (García-Millán et al., 2017 [1]. Keywords: Triamcinolona acetonide nanosuspensiones, X-ray spectroscopy, FTIR spectroscopy, DSC

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

Directory of Open Access Journals (Sweden)

María Tenorio-Gómez

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

SGLT2 inhibitors.

Science.gov (United States)

Dardi, I; Kouvatsos, T; Jabbour, S A

2016-02-01

Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Single-particle investigation of summertime and wintertime Antarctic sea spray aerosols using low-Z particle EPMA, Raman microspectrometry, and ATR-FTIR imaging techniques

Science.gov (United States)

Eom, Hyo-Jin; Gupta, Dhrubajyoti; Cho, Hye-Rin; Hwang, Hee Jin; Do Hur, Soon; Gim, Yeontae; Ro, Chul-Un

2016-11-01

Two aerosol samples collected at King Sejong Korean scientific research station, Antarctica, on 9 December 2011 in the austral summer (sample S1) and 23 July 2012 in the austral winter (sample S2), when the oceanic chlorophyll a levels on the collection days of the samples were quite different, by ˜ 19 times (2.46 vs. 0.13 µg L-1, respectively), were investigated on a single-particle basis using quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA), called low-Z particle EPMA, Raman microspectrometry (RMS), and attenuated total reflection Fourier transform infrared (ATR-FTIR) imaging techniques to obtain their characteristics based on the elemental chemical compositions, molecular species, and mixing state. X-ray analysis showed that the supermicron summertime and wintertime Antarctic aerosol samples have different elemental chemical compositions, even though all the individual particles analyzed were sea spray aerosols (SSAs); i.e., the contents of C, O, Ca, S, and Si were more elevated, whereas Cl was more depleted, for sample S1 than for sample S2. Based on qualitative analysis of the chemical species present in individual SSAs by the combined application of RMS and ATR-FTIR imaging, different organic species were observed in samples S1 and S2; i.e., Mg hydrate salts of alanine were predominant in samples S1 and S2, whereas Mg salts of fatty acids internally mixed with Mg hydrate salts of alanine were significant in sample S2. Although CaSO4 was observed significantly in both samples S1 and S2, other inorganic species, such as Na2SO4, NaNO3, Mg(NO3)2, SiO2, and CH3SO3Mg, were observed more significantly in sample S1, suggesting that those compounds may be related to the higher phytoplankton activity in summer.

Proposal of AAA-battery-size one-shot ATR Fourier spectroscopic imager for on-site analysis: Simultaneous measurement of multi-components with high accuracy

Science.gov (United States)

Hosono, Satsuki; Qi, Wei; Sato, Shun; Suzuki, Yo; Fujiwara, Masaru; Hiramatsu, Hiroyuki; Suzuki, Satoru; Abeygunawardhana, P. K. W.; Wada, Kenji; Nishiyama, Akira; Ishimaru, Ichiro

2015-03-01

For simultaneous measurement of multi-components on-site like factories, the ultra-compact (diameter: 9[mm], length: 45[mm], weight: 200[g]) one-shot ATR (Attenuated Total Reflection) Fourier spectroscopic imager was proposed. Because the proposed one-shot Fourier spectroscopic imaging is based on spatial-phase-shift interferometer, interferograms could be obtained with simple optical configurations. We introduced the transmission-type relativeinclined phase-shifter, that was constructed with a cuboid prism and a wedge prism, onto the optical Fourier transform plane of infinity corrected optical systems. And also, small light-sources and cameras in the mid-infrared light region, whose size are several millimeter on a side, are essential components for the ultra-compact spectroscopic configuration. We selected the Graphite light source (light source area: 1.7×1.7[mm], maker: Hawkeye technologies) whose radiation factor was high. Fortunately, in these days we could apply the cost-effective 2-dimensional light receiving device for smartphone (e.g. product name: LEPTON, maker: FLIR, price: around 400USD). In the case of alcoholic drinks factory, conventionally workers measure glucose and ethanol concentrations by bringing liquid solution back to laboratories every day. The high portable spectroscopy will make it possible to measure multi-components simultaneously on manufacturing scene. But we found experimentally that absorption spectrum of glucose and water and ethanol were overlapped each other in near infrared light region. But for mid-infrared light region, we could distinguish specific absorption peaks of glucose (@10.5[μm]) and ethanol (@11.5[μm]) independently from water absorption. We obtained standard curve between absorption (@9.6[μm]) and ethanol concentration with high correlation coefficient 0.98 successfully by ATR imaging-type 2-dimensional Fourier spectroscopy (wavelength resolution: 0.057[μm]) with the graphite light source (maker: Hawkeye

Fabrication, inspection, and test plan for the Advanced Test Reactor (ATR) Mixed-Oxide (MOX) fuel irradiation project

International Nuclear Information System (INIS)

Wachs, G.W.

1997-11-01

The Department of Energy (DOE) Fissile Materials Disposition Materials Disposition Program (FMDP) has announced that reactor irradiation of MOX fuel is one of the preferred alternatives for disposal of surplus weapons-usable plutonium (Pu). MOX fuel has been utilized domestically in test reactors and on an experimental basis in a number of Commercial Light Water Reactors (CLWRs). Most of this experience has been with Pu derived from spent low enriched uranium (LEU) fuel, known as reactor grade (RG) Pu. The MOX fuel test will be irradiated in the ATR to provide preliminary data to demonstrate that the unique properties of surplus weapons-derived or weapons-grade (WG) plutonium (Pu) do not compromise the applicability of this MOX experience base. In addition, the test will contribute experience with irradiation of gallium-containing fuel to the data base required for resolution of generic CLWR fuel design issues (ORNL/MD/LTR-76). This Fabrication, Inspection, and Test Plan (FITP) is a level 2 document as defined in the FMDP LWR MOX Fuel Irradiation Test Project Plan (ORNL/MD/LTR-78)

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.

Degradation patterns of natural and synthetic textiles on a soil surface during summer and winter seasons studied using ATR-FTIR spectroscopy

Science.gov (United States)

Ueland, Maiken; Howes, Johanna M.; Forbes, Shari L.; Stuart, Barbara H.

2017-10-01

Textiles are a valuable source of forensic evidence and the nature and condition of textiles collected from a crime scene can assist investigators in determining the nature of the death and aid in the identification of the victim. Until now, much of the knowledge of textile degradation in forensic contexts has been based on the visual inspection of material collected from soil environments. The purpose of the current study was to investigate the potential of a more quantitative approach to the understanding of forensic textile degradation through the application of infrared spectroscopy. Degradation patterns of natural and synthetic textile materials as they were subjected to a natural outdoor environment in Australia were investigated. Cotton, polyester and polyester - cotton blend textiles were placed on a soil surface during the summer and winter seasons and were analysed over periods 1 and 1.5 years, respectively, and examined using attenuated total reflectance (ATR) spectroscopy. Statistical analysis of the spectral data obtained for the cotton material correlated with visual degradation and a difference in the onset of degradation between the summer and winter season was revealed. The synthetic material did not show any signs of degradation either visually or statistically throughout the experimental period and highlighted the importance of material type in terms of preservation. The cotton section from the polyester - cotton blend samples was found to behave in a similar manner to that of the 100% cotton samples, however principal component analysis (PCA) demonstrated that the degradation patterns were less distinct in both the summer and winter trial for the blend samples. These findings indicated that the presence of the synthetic material may have inhibited the degradation of the natural material. The use of statistics to analyse the spectral data obtained for textiles of forensic interest provides a better foundation for the interpretation of the data

Synchrotron macro ATR-FTIR microspectroscopic analysis of silica nanoparticle-embedded polyester coated steel surfaces subjected to prolonged UV and humidity exposure.

Directory of Open Access Journals (Sweden)

Jitraporn Vongsvivut

Full Text Available Surface modification of polymers and paints is a popular and effective way to enhance the properties of these materials. This can be achieved by introducing a thin coating that preserves the bulk properties of the material, while protecting it from environmental exposure. Suitable materials for such coating technologies are inorganic oxides, such as alumina, titania and silica; however, the fate of these materials during long-term environmental exposure is an open question. In this study, polymer coatings that had been enhanced with the addition of silica nanoparticles (SiO2NPs and subsequently subjected to environmental exposure, were characterized both before and after the exposure to determine any structural changes resulting from the exposure. High-resolution synchrotron macro ATR-FTIR microspectroscopy and surface topographic techniques, including optical profilometry and atomic force microscopy (AFM, were used to determine the long-term effect of the environment on these dual protection layers after 3 years of exposure to tropical and sub-tropical climates in Singapore and Queensland (Australia. Principal component analysis (PCA based on the synchrotron macro ATR-FTIR spectral data revealed that, for the 9% (w/w SiO2NP/polymer coating, a clear discrimination was observed between the control group (no environmental exposure and those samples subjected to three years of environmental exposure in both Singapore and Queensland. The PCA loading plots indicated that, over the three year exposure period, a major change occurred in the triazine ring vibration in the melamine resins. This can be attributed to the triazine ring being very sensitive to hydrolysis under the high humidity conditions in tropical/sub-tropical environments. This work provides the first direct molecular evidence, acquired using a high-resolution mapping technique, of the climate-induced chemical evolution of a polyester coating. The observed changes in the surface

Proteinaceous alpha-araylase inhibitors

DEFF Research Database (Denmark)

Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.

2004-01-01

-amylase inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha...

Syk inhibitors.

Science.gov (United States)

Chihara, Kazuyasu; Kimura, Yukihiro; Honjo, Chisato; Takeuchi, Kenji; Sada, Kiyonao

2013-01-01

Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.

Thermal deterioration of virgin olive oil monitored by ATR-FTIR analysis of trans content.

Science.gov (United States)

Tena, Noelia; Aparicio, Ramón; García-González, Diego L

2009-11-11

The monitoring of frying oils by an effective and rapid method is one of the demands of food companies and small food retailers. In this work, a method based on ATR-FTIR has been developed for monitoring the oil degradation in frying procedures. The IR bands changing during frying in sunflower, soybean, and virgin olive oils have been examined in their linear relationship with the content of total polar compounds, which is a preferred parameter for frying control. The bands assigned to conjugated and isolated trans double bonds that are commonly used for the determination of trans content provided the best relationships. Then, the area covering 978-960 cm(-1) was chosen to build a model for predicting polar material content for the particular case of virgin olive oil. A virgin olive oil was heated up to 94 h, and samples collected every 2 h constituted the training set. These samples were analyzed to obtain their FTIR spectra and to determine the composition of fatty acids and the content of total polar compounds. The excellent results predicting the polar material content (adjusted R(2) 0.997) was successfully validated with an external set of samples. The analysis of the fatty acid composition confirmed the relationship between the trans content and the content of total polar compounds.

E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

Science.gov (United States)

Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

2009-05-01

E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

Resveratrol mediated cell death in cigarette smoke transformed breast epithelial cells is through induction of p21Waf1/Cip1 and inhibition of long patch base excision repair pathway

Energy Technology Data Exchange (ETDEWEB)

Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India); Choudhuri, Tathagata [Institute of Life Sciences, Nalco Square, Bhubaneswar, Orissa 751023 (India); Department of Biotechnology, Visva Bharati University, Santiniketan, West Bengal (India); Kundu, Chanakya Nath, E-mail: cnkundu@gmail.com [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India)

2014-03-15

Cigarette smoking is a key factor for the development and progression of different cancers including mammary tumor in women. Resveratrol (Res) is a promising natural chemotherapeutic agent that regulates many cellular targets including p21, a cip/kip family of cyclin kinase inhibitors involved in DNA damage-induced cell cycle arrest and blocking of DNA replication and repair. We have recently shown that cigarette smoke condensate (CSC) prepared from commercially available Indian cigarette can cause neoplastic transformation of normal breast epithelial MCF-10A cell. Here we studied the mechanism of Res mediated apoptosis in CSC transformed (MCF-10A-Tr) cells in vitro and in vivo. Res mediated apoptosis in MCF-10A-Tr cells was a p21 dependent event. It increased the p21 protein expression in MCF-10A-Tr cells and MCF-10A-Tr cells-mediated tumors in xenograft mice. Res treatment reduced the tumor size(s) and expression of anti-apoptotic proteins (e.g. PI3K, AKT, NFκB) in solid tumor. The expressions of cell cycle regulatory (Cyclins, CDC-2, CDC-6, etc.), BER associated (Pol-β, Pol-δ, Pol-ε, Pol-η, RPA, Fen-1, DNA-Ligase-I, etc.) proteins and LP-BER activity decreased in MCF-10A-Tr cells but remain significantly unaltered in isogenic p21 null MCF-10A-Tr cells after Res treatment. Interestingly, no significant changes were noted in SP-BER activity in both the cell lines after Res exposure. Finally, it was observed that increased p21 blocks the LP-BER in MCF-10A-Tr cells by increasing its interaction with PCNA via competing with Fen-1 after Res treatment. Thus, Res caused apoptosis in CSC-induced cancer cells by reduction of LP-BER activity and this phenomenon largely depends on p21. - Highlights: • Resveratrol (Res) caused reduction of MCF-10A-Tr cell growth by inducing apoptosis. • Res caused cell cycle arrest and DNA damage in p21 dependent manner. • Res mediated LP-BER reduction in MCF-10A-Tr cells was a p21 dependent phenomenon. • Res inhibits BER and PI

Resveratrol mediated cell death in cigarette smoke transformed breast epithelial cells is through induction of p21Waf1/Cip1 and inhibition of long patch base excision repair pathway

International Nuclear Information System (INIS)

Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit; Choudhuri, Tathagata; Kundu, Chanakya Nath

2014-01-01

Cigarette smoking is a key factor for the development and progression of different cancers including mammary tumor in women. Resveratrol (Res) is a promising natural chemotherapeutic agent that regulates many cellular targets including p21, a cip/kip family of cyclin kinase inhibitors involved in DNA damage-induced cell cycle arrest and blocking of DNA replication and repair. We have recently shown that cigarette smoke condensate (CSC) prepared from commercially available Indian cigarette can cause neoplastic transformation of normal breast epithelial MCF-10A cell. Here we studied the mechanism of Res mediated apoptosis in CSC transformed (MCF-10A-Tr) cells in vitro and in vivo. Res mediated apoptosis in MCF-10A-Tr cells was a p21 dependent event. It increased the p21 protein expression in MCF-10A-Tr cells and MCF-10A-Tr cells-mediated tumors in xenograft mice. Res treatment reduced the tumor size(s) and expression of anti-apoptotic proteins (e.g. PI3K, AKT, NFκB) in solid tumor. The expressions of cell cycle regulatory (Cyclins, CDC-2, CDC-6, etc.), BER associated (Pol-β, Pol-δ, Pol-ε, Pol-η, RPA, Fen-1, DNA-Ligase-I, etc.) proteins and LP-BER activity decreased in MCF-10A-Tr cells but remain significantly unaltered in isogenic p21 null MCF-10A-Tr cells after Res treatment. Interestingly, no significant changes were noted in SP-BER activity in both the cell lines after Res exposure. Finally, it was observed that increased p21 blocks the LP-BER in MCF-10A-Tr cells by increasing its interaction with PCNA via competing with Fen-1 after Res treatment. Thus, Res caused apoptosis in CSC-induced cancer cells by reduction of LP-BER activity and this phenomenon largely depends on p21. - Highlights: • Resveratrol (Res) caused reduction of MCF-10A-Tr cell growth by inducing apoptosis. • Res caused cell cycle arrest and DNA damage in p21 dependent manner. • Res mediated LP-BER reduction in MCF-10A-Tr cells was a p21 dependent phenomenon. • Res inhibits BER and PI

The effects of residual platelets in plasma on plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays.

Directory of Open Access Journals (Sweden)

Marlien Pieters

Full Text Available Due to controversial evidence in the literature pertaining to the activity of plasminogen activator inhibitor-1 in platelets, we examined the effects of residual platelets present in plasma (a potential pre-analytical variable on various plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays. Blood samples were collected from 151 individuals and centrifuged at 352 and 1500 g to obtain plasma with varying numbers of platelet. In a follow-up study, blood samples were collected from an additional 23 individuals, from whom platelet-poor (2000 g, platelet-containing (352 g and platelet-rich plasma (200 g were prepared and analysed as fresh-frozen and after five defrost-refreeze cycles (to determine the contribution of in vitro platelet degradation. Plasminogen activator inhibitor-1 activity, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasma clot lysis time, β-thromboglobulin and plasma platelet count were analysed. Platelet α-granule release (plasma β-thromboglobulin showed a significant association with plasminogen activator inhibitor-1 antigen levels but weak associations with plasminogen activator inhibitor-1 activity and a functional marker of fibrinolysis, clot lysis time. Upon dividing the study population into quartiles based on β-thromboglobulin levels, plasminogen activator inhibitor-1 antigen increased significantly across the quartiles while plasminogen activator inhibitor-1 activity and clot lysis time tended to increase in the 4th quartile only. In the follow-up study, plasma plasminogen activator inhibitor-1 antigen was also significantly influenced by platelet count in a concentration-dependent manner. Plasma plasminogen activator inhibitor-1 antigen levels increased further after complete platelet degradation. Residual platelets in plasma significantly influence plasma plasminogen activator inhibitor-1 antigen levels mainly

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.

Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer.

Science.gov (United States)

Eggemann, Holm; Altmann, Udo; Costa, Serban-Dan; Ignatov, Atanas

2018-02-01

Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC). We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy. The median follow-up was 106 months (range 3-151 months) and 42 months (range 2-115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated. MBC was characterized by older age, advanced tumor stage, and higher rate of lymph node metastases, in comparison with FBC. Matching analysis was performed using six prognostic criteria: patient age, tumor stage, tumor grade, lymph node status, human epidermal growth factor receptor (HER2) status, and administration of chemotherapy. The female and male patients were matched 2:1. In this analysis, 316 women and 158 men treated with TAM, and 60 women and 30 men treated with AI, were included. The overall survival (OS) was estimated by the Kaplan-Meier method and was compared between FBC and MBC. TAM-treated FBC and MBC patients had similar 5-year OS, 85.1 and 89.2%, respectively (p = 0.972). Notably, FBC patients treated with AI had significantly greater 5-year OS (85.0%) in comparison with AI-treated MBC patients (5-year OS of 73.3%; p = 0.028). The OS of TAM-treated patients with MBC was similar to the OS of TAM-treated FBC patients, whereas AI treatment is associated with poorer survival of MBC patients.

mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms.

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Costanza Bogani

Full Text Available BACKGROUND: Dysregulated signaling of the JAK/STAT pathway is a common feature of chronic myeloproliferative neoplasms (MPN, usually associated with JAK2V617F mutation. Recent clinical trials with JAK2 inhibitors showed significant improvements in splenomegaly and constitutional symptoms in patients with myelofibrosis but meaningful molecular responses were not documented. Accordingly, there remains a need for exploring new treatment strategies of MPN. A potential additional target for treatment is represented by the PI3K/AKT/mammalian target of rapamycin (mTOR pathway that has been found constitutively activated in MPN cells; proof-of-evidence of efficacy of the mTOR inhibitor RAD001 has been obtained recently in a Phase I/II trial in patients with myelofibrosis. The aim of the study was to characterize the effects in vitro of mTOR inhibitors, used alone and in combination with JAK2 inhibitors, against MPN cells. FINDINGS: Mouse and human JAK2V617F mutated cell lines and primary hematopoietic progenitors from MPN patients were challenged with an allosteric (RAD001 and an ATP-competitive (PP242 mTOR inhibitor and two JAK2 inhibitors (AZD1480 and ruxolitinib. mTOR inhibitors effectively reduced proliferation and colony formation of cell lines through a slowed cell division mediated by changes in cell cycle transition to the S-phase. mTOR inhibitors also impaired the proliferation and prevented colony formation from MPN hematopoietic progenitors at doses significantly lower than healthy controls. JAK2 inhibitors produced similar antiproliferative effects in MPN cell lines and primary cells but were more potent inducers of apoptosis, as also supported by differential effects on cyclinD1, PIM1 and BcLxL expression levels. Co-treatment of mTOR inhibitor with JAK2 inhibitor resulted in synergistic activity against the proliferation of JAK2V617F mutated cell lines and significantly reduced erythropoietin-independent colony growth in patients with

Imiquimod activates p53-dependent apoptosis in a human basal cell carcinoma cell line.

Science.gov (United States)

Huang, Shi-Wei; Chang, Shu-Hao; Mu, Szu-Wei; Jiang, Hsin-Yi; Wang, Sin-Ting; Kao, Jun-Kai; Huang, Jau-Ling; Wu, Chun-Ying; Chen, Yi-Ju; Shieh, Jeng-Jer

2016-03-01

The tumor suppressor p53 controls DNA repair, cell cycle, apoptosis, autophagy and numerous other cellular processes. Imiquimod (IMQ), a synthetic toll-like receptor (TLR) 7 ligand for the treatment of superficial basal cell carcinoma (BCC), eliminates cancer cells by activating cell-mediated immunity and directly inducing apoptosis and autophagy in cancer cells. To evaluate the role of p53 in IMQ-induced cell death in skin cancer cells. The expression, phosphorylation and subcellular localization of p53 were detected by real-time PCR, luciferase reporter assay, cycloheximide chase analysis, immunoblotting and immunocytochemistry. Using BCC/KMC1 cell line as a model, the upstream signaling of p53 activation was dissected by over-expression of TLR7/8, the addition of ROS scavenger, ATM/ATR inhibitors and pan-caspase inhibitor. The role of p53 in IMQ-induced apoptosis and autophagy was assessed by genetically silencing p53 and evaluated by a DNA content assay, immunoblotting, LC3 puncta detection and acridine orange staining. IMQ induced p53 mRNA expression and protein accumulation, increased Ser15 phosphorylation, promoted nuclear translocation and up-regulated its target genes in skin cancer cells in a TLR7/8-independent manner. In BCC/KMC1 cells, the induction of p53 by IMQ was achieved through increased ROS production to stimulate the ATM/ATR-Chk1/Chk2 axis but was not mediated by inducing DNA damage. The pharmacological inhibition of ATM/ATR significantly suppressed IMQ-induced p53 activation and apoptosis. Silencing of p53 significantly decreased the IMQ-induced caspase cascade activation and apoptosis but enhanced autophagy. Mutant p53 skin cancer cell lines were more resistant to IMQ-induced apoptosis than wildtype p53 skin cancer cell lines. IMQ induced ROS production to stimulate ATM/ATR pathways and contributed to p53-dependent apoptosis in a skin basal cell carcinoma cell line BCC/KMC1. Copyright © 2015 Japanese Society for Investigative Dermatology

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents.

Science.gov (United States)

Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

2013-01-01

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 advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while

Determination of main fruits in adulterated nectars by ATR-FTIR spectroscopy combined with multivariate calibration and variable selection methods.

Science.gov (United States)

Miaw, Carolina Sheng Whei; Assis, Camila; Silva, Alessandro Rangel Carolino Sales; Cunha, Maria Luísa; Sena, Marcelo Martins; de Souza, Scheilla Vitorino Carvalho

2018-07-15

Grape, orange, peach and passion fruit nectars were formulated and adulterated by dilution with syrup, apple and cashew juices at 10 levels for each adulterant. Attenuated total reflectance Fourier transform mid infrared (ATR-FTIR) spectra were obtained. Partial least squares (PLS) multivariate calibration models allied to different variable selection methods, such as interval partial least squares (iPLS), ordered predictors selection (OPS) and genetic algorithm (GA), were used to quantify the main fruits. PLS improved by iPLS-OPS variable selection showed the highest predictive capacity to quantify the main fruit contents. The selected variables in the final models varied from 72 to 100; the root mean square errors of prediction were estimated from 0.5 to 2.6%; the correlation coefficients of prediction ranged from 0.948 to 0.990; and, the mean relative errors of prediction varied from 3.0 to 6.7%. All of the developed models were validated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantized Algebras of Functions on Homogeneous Spaces with Poisson Stabilizers

Science.gov (United States)

Neshveyev, Sergey; Tuset, Lars

2012-05-01

Let G be a simply connected semisimple compact Lie group with standard Poisson structure, K a closed Poisson-Lie subgroup, 0 topology on the spectrum of C( G q / K q ). Next we show that the family of C*-algebras C( G q / K q ), 0 < q ≤ 1, has a canonical structure of a continuous field of C*-algebras and provides a strict deformation quantization of the Poisson algebra {{C}[G/K]} . Finally, extending a result of Nagy, we show that C( G q / K q ) is canonically KK-equivalent to C( G/ K).

New insights into the mechanism of interaction between CO2 and polymers from thermodynamic parameters obtained by in situ ATR-FTIR spectroscopy.

Science.gov (United States)

Gabrienko, Anton A; Ewing, Andrew V; Chibiryaev, Andrey M; Agafontsev, Alexander M; Dubkov, Konstantin A; Kazarian, Sergei G

2016-03-07

This work reports new physical insights of the thermodynamic parameters and mechanisms of possible interactions occurring in polymers subjected to high-pressure CO2. ATR-FTIR spectroscopy has been used in situ to determine the thermodynamic parameters of the intermolecular interactions between CO2 and different functional groups of the polymers capable of specific interactions with sorbed CO2 molecules. Based on the measured ATR-FTIR spectra of the polymer samples subjected to high-pressure CO2 (30 bar) at different temperatures (300-340 K), it was possible to characterize polymer-polymer and CO2-polymer interactions. Particularly, the enthalpy and entropy of the formation of the specific non-covalent complexes between CO2 and the hydroxy (-OH), carbonyl (C[double bond, length as m-dash]O) and hydroxyimino ([double bond, length as m-dash]N-OH) functional groups of the polymer samples have been measured. Furthermore, the obtained spectroscopic results have provided an opportunity for the structure of these complexes to be proposed. An interesting phenomenon regarding the behavior of CO2/polymer systems has also been observed. It has been found that only for the polyketone, the value of enthalpy was negative indicating an exothermic process during the formation of the CO2-polymer non-covalent complexes. Conversely, for the polyoxime and polyalcohol samples there is a positive enthalpy determined. This is a result of the initial polymer-polymer interactions requiring more energy to break than is released during the formation of the CO2-polymer complex. The effect of increasing temperature to facilitate the breaking of the polymer-polymer interactions has also been observed. Hence, a mechanism for the formation of CO2-polymer complexes was suggested based on these results, which occurs via a two-step process: (1) the breaking of the existing polymer-polymer interactions followed by (2) the formation of new CO2-polymer non-covalent interactions.

Identification of fermentation inhibitors in wood hydrolyzates and removal of inhibitors by ion exchange and liquid-liquid extraction

Science.gov (United States)

Luo, Caidian

1998-12-01

Common methods employed in the ethanol production from biomass consist of chemical or enzymatic degradation of biomass into sugars and then fermentation of sugars into ethanol or other chemicals. However, some degradation products severely inhibit the fermentation processes and substantially reduce the efficiency of ethanol production. How to remove inhibitors from the reaction product mixture and increase the production efficiency are critical in the commercialization of any processes of energy from biomass. The present study has investigated anion exchange and liquid-liquid extraction as potential methods for inhibitor removal. An analytical method has been developed to identify the fermentation inhibitors in a hydrolyzate. The majority of inhibitors present in hybrid poplar hydrolyzate have positively been identified. Ion exchange with weak basic Dowex-MWA-1 resin has been proved to be an effective mean to remove fermentation inhibitors from hybrid poplar hydrolyzate and significantly increase the fermentation productivity. Extraction with n-butanol might be a preferred way to remove inhibitors from wood hydrolyzates and improve the fermentability of sugars in the hydrolyzates. n-Butanol also removes some glucose, mannose and xylose from the hydrolyzate. Inhibitor identification reveals that lignin and sugar degradation compounds including both aromatic and aliphatic aldehydes and carboxylic acids formed in hydrolysis, plus fatty acids and other components from wood extractives are major fermentation inhibitors in Sacchromyces cerevisiae fermentation. There are 35 components identified as fermentation inhibitors. Among them, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid, syringic acid, syringaldehyde, and ferulic acid are among the most abundant aromatic inhibitors in hybrid poplar hydrolyzate. The conversion of aldehyde groups into carboxylic acid groups in the nitric acid catalyzed hydrolysis reduces the toxicity of the hydrolyzate. A wide spectrum of

Inga laurina trypsin inhibitor (ILTI) obstructs Spodoptera frugiperda trypsins expressed during adaptive mechanisms against plant protease inhibitors.

Science.gov (United States)

Machado, Suzy Wider; de Oliveira, Caio Fernando Ramalho; Zério, Neide Graciano; Parra, José Roberto Postali; Macedo, Maria Lígia Rodrigues

2017-08-01

Plant protease inhibitors (PIs) are elements of a common plant defense mechanism induced in response to herbivores. The fall armyworm, Spodoptera frugiperda, a highly polyphagous lepidopteran pest, responds to various PIs in its diet by expressing genes encoding trypsins. This raises the question of whether the PI-induced trypsins are also inhibited by other PIs, which we posed as the hypothesis that Inga laurina trypsin inhibitor (ILTI) inhibits PI-induced trypsins in S. frugiperda. In the process of testing our hypothesis, we compared its properties with those of selected PIs, soybean Kunitz trypsin inhibitor (SKTI), Inga vera trypsin inhibitor (IVTI), Adenanthera pavonina trypsin inhibitor (ApTI), and Entada acaciifolia trypsin inhibitor (EATI). We report that ILTI is more effective in inhibiting the induced S. frugiperda trypsins than SKTI and the other PIs, which supports our hypothesis. ILTI may be more appropriate than SKTI for studies regarding adaptive mechanisms to dietary PIs. © 2017 Wiley Periodicals, Inc.

Reduction rules for reset/inhibitor nets

NARCIS (Netherlands)

Verbeek, H.M.W.; Wynn, M.T.; Aalst, van der W.M.P.; Hofstede, ter A.H.M.

2010-01-01

Reset/inhibitor nets are Petri nets extended with reset arcs and inhibitor arcs. These extensions can be used to model cancellation and blocking. A reset arc allows a transition to remove all tokens from a certain place when the transition fires. An inhibitor arc can stop a transition from being

Plasmid-free CRISPR/Cas9 genome editing in Plasmodium falciparum confirms mutations conferring resistance to the dihydroisoquinolone clinical candidate SJ733.

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Emily D Crawford

Full Text Available Genetic manipulation of the deadly malaria parasite Plasmodium falciparum remains challenging, but the rise of CRISPR/Cas9-based genome editing tools is increasing the feasibility of altering this parasite's genome in order to study its biology. Of particular interest is the investigation of drug targets and drug resistance mechanisms, which have major implications for fighting malaria. We present a new method for introducing drug resistance mutations in P. falciparum without the use of plasmids or the need for cloning homologous recombination templates. We demonstrate this method by introducing edits into the sodium efflux channel PfATP4 by transfection of a purified CRISPR/Cas9-guide RNA ribonucleoprotein complex and a 200-nucleotide single-stranded oligodeoxynucleotide (ssODN repair template. Analysis of whole genome sequencing data with the variant-finding program MinorityReport confirmed that only the intended edits were made, and growth inhibition assays confirmed that these mutations confer resistance to the antimalarial SJ733. The method described here is ideally suited for the introduction of mutations that confer a fitness advantage under selection conditions, and the novel finding that an ssODN can function as a repair template in P. falciparum could greatly simplify future editing attempts regardless of the nuclease used or the delivery method.

New organic single crystal of (benzylthio)acetic acid: Synthesis, crystal structure, spectroscopic (ATR-FTIR, 1H and 13C NMR) and thermal characterization

Science.gov (United States)

Sienkiewicz-Gromiuk, Justyna; Tarasiuk, Bogdan; Mazur, Liliana

2016-04-01

(Benzylthio)acetic acid (Hbta) was synthesized with 78% yield from benzyl chloride and thiourea as substrates. Well-shaped crystals of Hbta were grown by slow solvent evaporation technique from pure methanol. The compound was investigated by single-crystal X-ray and powder diffraction techniques and was also characterized by other analytical methods, like ATR-FTIR, 1H and 13C NMR and TG/DSC. The acid molecule adopts bent conformation in the solid state. The crystal structure of Hbta is stabilized by numerous intermolecular interactions, including O-H···O, C-H···O, C-H···S and C-H···π contacts. Thermal decomposition of the obtained material takes place above 150 °C.

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

Science.gov (United States)

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

2018-01-01

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

Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

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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

Measurement and characterization of external oil in the fried waxy maize starch granules using ATR-FTIR and XRD.

Science.gov (United States)

Chen, Long; Tian, Yaoqi; Sun, Binghua; Cai, Canxin; Ma, Rongrong; Jin, Zhengyu

2018-03-01

Concerns regarding increased dietary oil uptake have prompted efforts to investigate the oil absorption and distribution in fried starchy foods. In the present study, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, together with a chloroform-methanol method, was used to analyze the external and internal oil contents in fried starchy samples. The micromorphology of fried starchy samples was further investigated using scanning electron microscope (SEM), polarized light microscope (PLM) and confocal laser scanning microscopy (CLSM). The results indicated that large amounts of oil were absorbed in or within waxy maize starch, but the majority of oil was located near the surface layer of the starch granules. After defatting, the internal oil was thoroughly removed, while a small amount of external oil remained. As evidenced by the changes of the crystalline characteristics with the help of X-ray diffraction (XRD), the interaction between starch and lipids on the surface was confirmed to form V-type complex compounds during frying at high moisture. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

Kandhro, A.A.; Saleem, R.; Laghari, A.H.; Sultana, R.

2014-01-01

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)

Histone Deacetylase Inhibitors as Anticancer Drugs.

Science.gov (United States)

Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

2017-07-01

Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

Histone Deacetylase Inhibitors as Anticancer Drugs

Directory of Open Access Journals (Sweden)

Tomas Eckschlager

2017-07-01

Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

Alternativas a la elevación de seno maxilar: rehabilitación del sector posterior del maxilar atrófico mediante implantes pterigoideos Alternatives to maxillary sinus lift: posterior area of the atrophic maxilla rehabilitation by means pterigoideal implants

Directory of Open Access Journals (Sweden)

X. Rodríguez-Ciurana

2008-12-01

Full Text Available El primer y segundo molar son los dientes que se pierden más a menudo debido a la enfermedad periodontal y al exceso de fuerzas oclusales. A pesar de la frecuencia del edentulismo parcial del sector posterior raramente se ubican los implantes más allá de los premolares debido al aumento del índice de fallos. El escaso volumen óseo y la pobre mineralización del sector posterior del maxilar comprometen la viabilidad de las rehabilitaciones con implantes a largo plazo. Además, la cresta ósea a nivel del seno maxilar, en el maxilar atrófico, no suele permitir el anclaje de implantes de 10 mm. Se han propuesto varias técnicas para rehabilitar el sector posterior del maxilar atrófico: implantes cortos, extensiones protésicas, injerto sinusal, implante cigomático. El implante pterigoideo es otro de los posibles tratamientos para rehabilitar el sector posterior del maxilar atrófico. Anclado en el hueso cortical de la apófisis del esfenoides el implante pterigoideo evita la necesidad de injertar o utilizar extensiones protésicas. El objetivo de este artículo es analizar las indicaciones, la técnica, complicaciones y supervivencia del implante pterigoideo en el sector posterior del maxilar atrófico.The first and second molar are the teeth most commonly lost in the maxilla, mainly due to periodontal disease and excessive occlusal force. 1 Although partial edentulism of the posterior maxilla is common, implants are seldom placed distal to the premolars because failure rates in the posterior maxilla have historically been high. Poor volume and low density of bone are the worst conditions for long-term anchorage in the maxilla. 7 Moreover, bone under the maxillary sinus, in the atrophic maxilla, is usually insufficient to enable placement of 10 mm implants. Several techniques have been proposed to restore the atrophic posterior maxilla: short implants, prosthetic cantilevers, sinus bone graft, zigomatic fixtures. Pterygoid implants are

Forensic Hair Differentiation Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy.

Science.gov (United States)

Manheim, Jeremy; Doty, Kyle C; McLaughlin, Gregory; Lednev, Igor K

2016-07-01

Hair and fibers are common forms of trace evidence found at crime scenes. The current methodology of microscopic examination of potential hair evidence is absent of statistical measures of performance, and examiner results for identification can be subjective. Here, attenuated total reflection (ATR) Fourier transform-infrared (FT-IR) spectroscopy was used to analyze synthetic fibers and natural hairs of human, cat, and dog origin. Chemometric analysis was used to differentiate hair spectra from the three different species, and to predict unknown hairs to their proper species class, with a high degree of certainty. A species-specific partial least squares discriminant analysis (PLSDA) model was constructed to discriminate human hair from cat and dog hairs. This model was successful in distinguishing between the three classes and, more importantly, all human samples were correctly predicted as human. An external validation resulted in zero false positive and false negative assignments for the human class. From a forensic perspective, this technique would be complementary to microscopic hair examination, and in no way replace it. As such, this methodology is able to provide a statistical measure of confidence to the identification of a sample of human, cat, and dog hair, which was called for in the 2009 National Academy of Sciences report. More importantly, this approach is non-destructive, rapid, can provide reliable results, and requires no sample preparation, making it of ample importance to the field of forensic science. © The Author(s) 2016.

[ACE inhibitors and the kidney].

Science.gov (United States)

Hörl, W H

1996-01-01

Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

Synergistic effect of iodide ion addition on the inhibition of mild steel corrosion in 1 M HCl by 3-amino-2-methylbenzylalcohol

Energy Technology Data Exchange (ETDEWEB)

Obot, I.B., E-mail: obot@kfupm.edu.sa; Madhankumar, A.

2016-07-01

The inhibition of mild steel corrosion in 1 M HCl aqueous solution by 3-amino-2-methylbenzylalcohol (AMBA) was investigated using weight loss, electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP) and cyclic voltammametry (CV) techniques. Attenuated total reflectance infrared spectroscopy (ATR-IR), contact angle (CA) and scanning electron microscopy (SEM) measurements were carried out to confirm the adsorption of AMBA on mild steel surface. Computer simulations using density functional theory (DFT) and Monte Carlo methodologies were further employed to provide insights into the mechanism of interaction between the inhibitor and the steel surface. All the results confirmed that AMBA is a good corrosion inhibitor for mild steel in 1 M HCl. The addition of NaI was found to increase the inhibition effect of AMBA on mild steel to a considerable extent. DFT results reveal that the N atom together with the π-systems in the aromatic ring were the active sites for the interaction of AMBA with steel surface. Furthermore, the negative value of the adsorption energy obtained from the Monte Carlo simulation indicates the stability of the adsorbed inhibitor film on the steel surface. - Graphical abstract: EIS spectra and adsorption configuration of AMBA on Fe (110). - Highlights: • 3-amino-2-methylbenzylalcohol inhibit mild steel corrosion in acid medium. • ATR-IR, contact angle, SEM, were used for steel surface characterization. • DFT and Monte Carlo simulations provide atomic and molecular level insights. • The theoretical data clearly support the experimental results obtained.

Natural inhibitors of tumor-associated proteases

International Nuclear Information System (INIS)

Magdolen, U.; Krol, J.; Sato, S.; Schmitt, M.; Magdolen, V.; Krueger, A.; Mueller, M.M.; Sperl, S.

2002-01-01

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)

Dynamic changes to survivin subcellular localization are initiated by DNA damage

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Maritess Gay Asumen

2010-07-01

Full Text Available Maritess Gay Asumen1, Tochukwu V Ifeacho2, Luke Cockerham3, Christina Pfandl4, Nathan R Wall31Touro University’s College of Osteopathic Medicine, Vallejo, CA, USA; 2University of Southern California, Los Angeles, CA, USA; 3Center for Health Disparities Research and Molecular Medicine, Loma Linda University, CA, USA; 4Green Mountain Antibodies, Burlington, VT, USAAbstract: Subcellular distribution of the apoptosis inhibitor survivin and its ability to relocalize as a result of cell cycle phase or therapeutic insult has led to the hypothesis that these subcellular pools may coincide with different survivin functions. The PIK kinases (ATM, ATR and DNA-PK phosphorylate a variety of effector substrates that propagate DNA damage signals, resulting in various biological outputs. Here we demonstrate that subcellular repartitioning of survivin in MCF-7 cells as a result of UV light-mediated DNA damage is dependent upon DNA damage-sensing proteins as treatment with the pan PIK kinase inhibitor wortmannin repartitioned survivin in the mitochondria and diminished it from the cytosol and nucleus. Mitochondrial redistribution of survivin, such as was recorded after wortmannin treatment, occurred in cells lacking any one of the three DNA damage sensing protein kinases: DNA-PK, ATM or ATR. However, failed survivin redistribution from the mitochondria in response to low-dose UV occurred only in the cells lacking ATM, implying that ATM may be the primary kinase involved in this process. Taken together, this data implicates survivian’s subcellular distribution is a dynamic physiological process that appears responsive to UV light- initiated DNA damage and that its distribution may be responsible for its multifunctionality.Keywords: survivin, PIK kinases, ATM, ATR, DNA-PK

AGR-2 Data Qualification Report for ATR Cycles 147A, 148A, 148B, and 149A

International Nuclear Information System (INIS)

Abbott, Michael L.; Daum, Keith A.

2011-01-01

This report presents the data qualification status of fuel irradiation data from the first four reactor cycles (147A, 148A, 148B, and 149A) of the on-going second Advanced Gas Reactor (AGR-2) experiment as recorded in the NGNP Data Management and Analysis System (NDMAS). This includes data received by NDMAS from the period June 22, 2010 through May 21, 2011. AGR-2 is the second in a series of eight planned irradiation experiments for the AGR Fuel Development and Qualification Program, which supports development of the very high temperature gas-cooled reactor (VHTR) under the Next Generation Nuclear Plant (NGNP) Project. Irradiation of the AGR-2 test train is being performed at the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL) and is planned for 600 effective full power days (approximately 2.75 calendar years) (PLN-3798). The experiment is intended to demonstrate the performance of UCO (uranium oxycarbide) and UO2 (uranium dioxide) fuel produced in a large coater. Data qualification status of the AGR-1 experiment was reported in INL/EXT-10-17943 (Abbott et al. 2010).

AGR-2 Data Qualification Report for ATR Cycles 147A, 148A, 148B, and 149A

Energy Technology Data Exchange (ETDEWEB)

Michael L. Abbott; Keith A. Daum

2011-08-01

This report presents the data qualification status of fuel irradiation data from the first four reactor cycles (147A, 148A, 148B, and 149A) of the on-going second Advanced Gas Reactor (AGR-2) experiment as recorded in the NGNP Data Management and Analysis System (NDMAS). This includes data received by NDMAS from the period June 22, 2010 through May 21, 2011. AGR-2 is the second in a series of eight planned irradiation experiments for the AGR Fuel Development and Qualification Program, which supports development of the very high temperature gas-cooled reactor (VHTR) under the Next Generation Nuclear Plant (NGNP) Project. Irradiation of the AGR-2 test train is being performed at the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL) and is planned for 600 effective full power days (approximately 2.75 calendar years) (PLN-3798). The experiment is intended to demonstrate the performance of UCO (uranium oxycarbide) and UO2 (uranium dioxide) fuel produced in a large coater. Data qualification status of the AGR-1 experiment was reported in INL/EXT-10-17943 (Abbott et al. 2010).

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

Science.gov (United States)

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

2012-04-01

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

Aromatase inhibitors in pediatrics.

Science.gov (United States)

Wit, Jan M; Hero, Matti; Nunez, Susan B

2011-10-25

Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole and anastrozole--currently approved as adjuvant therapy for breast cancer--have stimulated off-label use of aromatase inhibitors in pediatrics for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts; hyperandrogenism, for example, testotoxicosis (also known as familial male-limited precocious puberty) and congenital adrenal hyperplasia; pubertal gynecomastia; and short stature and/or pubertal delay in boys. Current data suggest that aromatase inhibitors are probably effective in the treatment of patients with aromatase excess syndrome or testotoxicosis, partially effective in Peutz-Jeghers and McCune-Albright syndrome, but probably ineffective in gynecomastia. Insufficient data are available in patients with congenital adrenal hyperplasia or functional ovarian cysts. Although aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral deformities, a decrease in serum HDL cholesterol levels and increase of erythrocytosis, are reasons for caution.

[The primary structure of the alpha-amylase inhibitor Hoe 467A from Streptomyces tendae 4158. A new class of inhibitors].

Science.gov (United States)

Aschauer, H; Vértesy, L; Nesemann, G; Braunitzer, G

1983-10-01

The native or modified alpha-amylase inhibitor Hoe 467A - isolated from the culture medium of Streptomyces tendae 4158 - and overlapping peptides were degraded by the automatic Edman technique. The oxidized or aminoethylated or oxidized and maleoylated inhibitor was digested with trypsin and the native inhibitor with pepsin. Further digestion with Staphylococcus aureus proteinase was also carried out. After peptic digestion two cystin peptides were isolated, which allowed the establishment of the disulfide bonds. The alpha-amylase inhibitor is a polypeptid consisting of 74 amino-acid residues with a molecular mass of 7958 Da. The inhibitor is composed of all naturally occurring amino acids except methionine and phenylalanine and shows no sequence homology to known inhibitors. The clinical and pharmacological importance in respect to the inhibitors ability for inactivation of human salivary and pancreatic alpha-amylase is discussed. Especially the proteinase resistance of the inhibitor enables a clinical application in human (e.g. Diabetes mellitus) per os.

Squash inhibitor family of serine proteinases

International Nuclear Information System (INIS)

Otlewski, J.; Krowarsch, D.

1996-01-01

Squash inhibitors of serine proteinases form an uniform family of small proteins. They are built of 27-33 amino-acid residues and cross-linked with three disulfide bridges. The reactive site peptide bond (P1-P1') is between residue 5 (Lys, Arg or Leu) and 6 (always Ile). High resolution X-ray structures are available for two squash inhibitors complexed with trypsin. NMR solution structures have also been determined for free inhibitors. The major structural motif is a distorted, triple-stranded antiparallel beta-sheet. A similar folding motif has been recently found in a number of proteins, including: conotoxins from fish-hunting snails, carboxypeptidase inhibitor from potato, kalata B1 polypeptide, and in some growth factors (e.g. nerve growth factor, transforming growth factor β2, platelet-derived growth factor). Squash inhibitors are highly stable and rigid proteins. They inhibit a number of serine proteinases: trypsin, plasmin, kallikrein, blood clotting factors: X a and XII a , cathepsin G. The inhibition spectrum can be much broadened if specific amino-acid substitutions are introduced, especially at residues which contact proteinase. Squash inhibitors inhibit proteinases via the standard mechanism. According to the mechanism, inhibitors are substrates which exhibit at neutral pH a high k cat /K m index for hydrolysis and resynthesis of the reactive site, and a low value of the hydrolysis constant. (author)

Metal corrosion inhibitors and ecology

International Nuclear Information System (INIS)

Krasts, H.; Svarce, J.; Berge, B.

1999-01-01

The use of metal corrosion inhibitors in water is one of the cheapest method to protect metals against corrosion. However, the used inhibitors can come to surface water in the course of time and can become as source of environmental pollution. It is important to co-ordinate amount of substances in the elaborated inhibitors not only with demands for metal protection, but also with demands for quality of surface water and drinking water according to normative statements: 3.5 mg/l (as PO 4 ) for hexametaphosphate, tripolyphosphate and phosphonate; 40 mg/l (as SiO 2 for silicate, up to 1 mg/l for CU 2+ ; up to 5 mg/l for Zn 2+ ; up to 1 mg/l for B; up to 0.5 mg/l for Mo 2+ . The examples of the elaborated inhibitors are given. Many organic substances can be used as corrosion inhibitors, but there is shortage of standard methods for their analysis in water in Latvia. Removing of salt's deposits from boilers needs elaboration of a separate normative statement for dispersing waste water which content chloride at high concentration and heavy metals. (authors)

Invertase proteinaceous inhibitor of Cyphomandra betacea Sendt fruits.

Science.gov (United States)

Ordóñez, R M; Isla, M I; Vattuone, M A; Sampietro, A R

2000-01-01

This work describes a new invertase proteinaceous inhibitor from Cyphomandra betacea Sendt. (tomate de arbol) fruits. The proteinaceous inhibitor was isolated and purified from a cell wall preparation. The pH stability, kinetics of the inhibition of the C. betacea invertase, inhibition of several higher plant invertases and lectin nature of the inhibitor were studied. The inhibitor structure involves a single polypeptide (Mr = 19000), as shown by gel filtration and SDS-PAGE determinations. N-terminal aminoacid sequence was determined. The properties and some structural features of the inhibitor are compared with the proteinaceous inhibitors from several plant species (Beta vulgaris L., Ipomoea batatas L. and Lycopersicon esculentum Mill.). All these inhibitors share lectinic properties, some common epitopes, some aminoacid sequences and a certain lack of specificity towards invertases of different species, genera and even plant family. In consequence, the inhibitors appear to belong to the same lectin family. It is now known that some lectins are part of the defence mechanism of higher plants against fungi and bacteria and this is a probable role of the proteinaceous inhibitors.

Cathepsin D inhibitors

Directory of Open Access Journals (Sweden)

M. Gacko

2007-11-01

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

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.

Single-particle investigation of summertime and wintertime Antarctic sea spray aerosols using low-Z particle EPMA, Raman microspectrometry, and ATR-FTIR imaging techniques

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H.-J. Eom

2016-11-01

Full Text Available Two aerosol samples collected at King Sejong Korean scientific research station, Antarctica, on 9 December 2011 in the austral summer (sample S1 and 23 July 2012 in the austral winter (sample S2, when the oceanic chlorophyll a levels on the collection days of the samples were quite different, by  ∼  19 times (2.46 vs. 0.13 µg L−1, respectively, were investigated on a single-particle basis using quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA, called low-Z particle EPMA, Raman microspectrometry (RMS, and attenuated total reflection Fourier transform infrared (ATR-FTIR imaging techniques to obtain their characteristics based on the elemental chemical compositions, molecular species, and mixing state. X-ray analysis showed that the supermicron summertime and wintertime Antarctic aerosol samples have different elemental chemical compositions, even though all the individual particles analyzed were sea spray aerosols (SSAs; i.e., the contents of C, O, Ca, S, and Si were more elevated, whereas Cl was more depleted, for sample S1 than for sample S2. Based on qualitative analysis of the chemical species present in individual SSAs by the combined application of RMS and ATR-FTIR imaging, different organic species were observed in samples S1 and S2; i.e., Mg hydrate salts of alanine were predominant in samples S1 and S2, whereas Mg salts of fatty acids internally mixed with Mg hydrate salts of alanine were significant in sample S2. Although CaSO4 was observed significantly in both samples S1 and S2, other inorganic species, such as Na2SO4, NaNO3, Mg(NO32, SiO2, and CH3SO3Mg, were observed more significantly in sample S1, suggesting that those compounds may be related to the higher phytoplankton activity in summer.

[Syk inhibitors].

Science.gov (United States)

Kimura, Yukihiro; Chihara, Kazuyasu; Takeuchi, Kenji; Sada, Kiyonao

2013-07-01

Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in the University of Fukui in 1991. Syk is known to be essential for the various physiological functions, especially in hematopoietic lineage cells. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Recently, novel Syk inhibitors were developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure, and function of Syk, and then describe the novel Syk inhibitors and their current status. Furthermore, we will introduce our findings of the adaptor protein 3BP2 (c-Abl SH3 domain-binding protein-2), as a novel target of Syk.

Organization of the gene coding for human protein C inhibitor (plasminogen activator inhibitor-3). Assignment of the gene to chromosome 14

NARCIS (Netherlands)

Meijers, J. C.; Chung, D. W.

1991-01-01

Protein C inhibitor (plasminogen activator inhibitor-3) is a plasma glycoprotein and a member of the serine proteinase inhibitor superfamily. In the present study, the human gene for protein C inhibitor was isolated and characterized from three independent phage that contained overlapping inserts

Inhibitor chymotrypsynowy nasion wiechliny łąkowej (Poa pratensis [Chymotrypsin inhibitor from Poa pratensis seeds

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I. Lorenc-Kubis

2015-01-01

Full Text Available A chymotrypsin inhibitor was isolated from Poa pratensis seeds. The inhibitor showed also antytriptic activity. It is a termostable protein, soluble in water, sodium chloride, but insoluble in 5% trichloracetic acid and 0.15 M sulphosalicylic acid.

A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes.

Science.gov (United States)

Cha, Seon-Ah; Park, Yong-Moon; Yun, Jae-Seung; Lim, Tae-Seok; Song, Ki-Ho; Yoo, Ki-Dong; Ahn, Yu-Bae; Ko, Seung-Hyun

2017-04-13

Previous studies suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different effects on the lipid profile in patients with type 2 diabetes. We investigated the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in patients with type 2 diabetes. From January 2013 to December 2015, a total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were consecutively enrolled. We compared the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile at baseline and after 24 weeks of treatment. To compare lipid parameters between the two groups, we used the analysis of covariance (ANCOVA). A total of 184 patients completed follow-up (mean age: 53.1 ± 6.9 years, mean duration of diabetes: 7.1 ± 5.7 years). From baseline to 24 weeks, HDL-cholesterol (HDL-C) levels were increased by 0.5 (95% CI, -0.9 to 2.0) mg/dl with a DPP-4 inhibitor and by 5.1 (95% CI, 3.0 to 7.1) mg/dl with an SGLT2 inhibitor (p = 0.001). LDL-cholesterol (LDL-C) levels were reduced by 8.4 (95% CI, -14.0 to -2.8) mg/dl with a DPP-4 inhibitor, but increased by 1.3 (95% CI, -5.1 to 7.6) mg/dl with an SGLT2 inhibitor (p = 0.046). There was no significant difference in the mean hemoglobin A1c (8.3 ± 1.1 vs. 8.0 ± 0.9%, p = 0.110) and in the change of total cholesterol (TC) (p = 0.836), triglyceride (TG) (p = 0.867), apolipoprotein A (p = 0.726), apolipoprotein B (p = 0.660), and lipoprotein (a) (p = 0.991) between the DPP-4 inhibitor and the SGLT2 inhibitor. The SGLT2 inhibitor was associated with a significant increase in HDL-C and LDL-C after 24 weeks of SGLT2 inhibitor treatment in patients with type 2 diabetes compared with those with DPP-4 inhibitor treatment in this study. This study was conducted by retrospective medical record review.

Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

Science.gov (United States)

Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

2011-02-10

Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.

Application of reflectance spectroscopies (FTIR-ATR & FT-NIR) coupled with multivariate methods for robust in vivo detection of begomovirus infection in papaya leaves

Science.gov (United States)

Haq, Quazi M. I.; Mabood, Fazal; Naureen, Zakira; Al-Harrasi, Ahmed; Gilani, Sayed A.; Hussain, Javid; Jabeen, Farah; Khan, Ajmal; Al-Sabari, Ruqaya S. M.; Al-khanbashi, Fatema H. S.; Al-Fahdi, Amira A. M.; Al-Zaabi, Ahoud K. A.; Al-Shuraiqi, Fatma A. M.; Al-Bahaisi, Iman M.

2018-06-01

Nucleic acid & serology based methods have revolutionized plant disease detection, however, they are not very reliable at asymptomatic stage, especially in case of pathogen with systemic infection, in addition, they need at least 1-2 days for sample harvesting, processing, and analysis. In this study, two reflectance spectroscopies i.e. Near Infrared reflectance spectroscopy (NIR) and Fourier-Transform-Infrared spectroscopy with Attenuated Total Reflection (FT-IR, ATR) coupled with multivariate exploratory methods like Principle Component Analysis (PCA) and Partial least square discriminant analysis (PLS-DA) have been deployed to detect begomovirus infection in papaya leaves. The application of those techniques demonstrates that they are very useful for robust in vivo detection of plant begomovirus infection. These methods are simple, sensitive, reproducible, precise, and do not require any lengthy samples preparation procedures.

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.

Biological abatement of cellulase inhibitors

Science.gov (United States)

Bio-abatement uses a fungus to metabolize and remove fermentation inhibitors. To determine whether bio-abatement could alleviate enzyme inhibitor effects observed in biomass liquors after pretreatment, corn stover at 10% (w/v) solids was pretreated with either dilute acid or liquid hot water. The ...

Use of selective-serotonin reuptake inhibitors and platelet aggregation inhibitors among individuals with co-occurring atherosclerotic cardiovascular disease and depression or anxiety

Directory of Open Access Journals (Sweden)

J Douglas Thornton

2016-12-01

Full Text Available Objective: Medications commonly used to treat heart disease, anxiety, and depression can interact resulting in an increased risk of bleeding, warranting a cautious approach in medical decision making. This retrospective, descriptive study examined the prevalence and the factors associated with the use of both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor among individuals with co-occurring atherosclerotic cardiovascular disease and anxiety or depression. Methods: Respondents aged 22 years and older, alive throughout the study period, and diagnosed with co-occurring atherosclerotic cardiovascular disease and anxiety or depression (n = 1507 in years 2007 through 2013 of the Medical Expenditures Panel Survey were included. The use of treatment was grouped as follows: selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Results: Overall, 16.5% used both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, 61.2% used selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and 22.3% used neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Respondents aged over 65 years (adjusted odds ratio = 1.93 (95% confidence interval = 1.08–3.45 and having a diagnosis of diabetes (adjusted odds ratio = 1.63 (95% confidence interval = 1.15–2.31 and hypertension (adjusted odds ratio = 1.84 (95% confidence interval = 1.04–3.27 were more likely to be prescribed the combination. Conclusion: The drug interaction was prevalent in patients who are already at higher risk of health disparities and worse outcomes thus requiring vigilant evaluation.

Emerging Corrosion Inhibitors for Interfacial Coating

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Mona Taghavikish

2017-12-01

Full Text Available Corrosion is a deterioration of a metal due to reaction with environment. The use of corrosion inhibitors is one of the most effective ways of protecting metal surfaces against corrosion. Their effectiveness is related to the chemical composition, their molecular structures and affinities for adsorption on the metal surface. This review focuses on the potential of ionic liquid, polyionic liquid (PIL and graphene as promising corrosion inhibitors in emerging coatings due to their remarkable properties and various embedment or fabrication strategies. The review begins with a precise description of the synthesis, characterization and structure-property-performance relationship of such inhibitors for anti-corrosion coatings. It establishes a platform for the formation of new generation of PIL based coatings and shows that PIL corrosion inhibitors with various heteroatoms in different form can be employed for corrosion protection with higher barrier properties and protection of metal surface. However, such study is still in its infancy and there is significant scope to further develop new structures of PIL based corrosion inhibitors and coatings and study their behaviour in protection of metals. Besides, it is identified that the combination of ionic liquid, PIL and graphene could possibly contribute to the development of the ultimate corrosion inhibitor based coating.

Structural Mechanism of the Pan-BCR-ABL Inhibitor Ponatinib (AP24534): Lessons for Overcoming Kinase Inhibitor Resistance

Energy Technology Data Exchange (ETDEWEB)

Zhou, Tianjun; Commodore, Lois; Huang, Wei-Sheng; Wang, Yihan; Thomas, Mathew; Keats, Jeff; Xu, Qihong; Rivera, Victor M.; Shakespeare, William C.; Clackson, Tim; Dalgarno, David C.; Zhu, Xiaotian (ARIAD)

2012-01-20

The BCR-ABL inhibitor imatinib has revolutionized the treatment of chronic myeloid leukemia. However, drug resistance caused by kinase domain mutations has necessitated the development of new mutation-resistant inhibitors, most recently against the T315I gatekeeper residue mutation. Ponatinib (AP24534) inhibits both native and mutant BCR-ABL, including T315I, acting as a pan-BCR-ABL inhibitor. Here, we undertook a combined crystallographic and structure-activity relationship analysis on ponatinib to understand this unique profile. While the ethynyl linker is a key inhibitor functionality that interacts with the gatekeeper, virtually all other components of ponatinib play an essential role in its T315I inhibitory activity. The extensive network of optimized molecular contacts found in the DFG-out binding mode leads to high potency and renders binding less susceptible to disruption by single point mutations. The inhibitory mechanism exemplified by ponatinib may have broad relevance to designing inhibitors against other kinases with mutated gatekeeper residues.

SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products

Science.gov (United States)

Sowd, Gregory A.; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L.; Fanning, Ellen

2014-01-01

Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PKcs kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PKcs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5′ to 3′ end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication. PMID:25474690

SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

Directory of Open Access Journals (Sweden)

Gregory A Sowd

2014-12-01

Full Text Available Simian virus 40 (SV40 and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs kinase activity, facilitates some aspects of double strand break (DSB repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR and do not colocalize with non-homologous end joining (NHEJ factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

Laura: Soybean variety lacking Kunitz trypsin inhibitor

Directory of Open Access Journals (Sweden)

Srebrić Mirjana

2010-01-01

Full Text Available Grain of conventional soybean varieties requires heat processing to break down trypsin inhibitor's activity before using as food or animal feed. At the same time, protein denaturation and other qualitative changes occur in soybean grain, especially if the temperature of heating is not controlled. Two types of trypsin inhibitor were found in soybean grain the Kunitz trypsin inhibitor and the Bowman-Birk inhibitor. Mature grain of soybean Laura is lacking Kunitz trypsin inhibitor. Grain yield of variety Laura is equal to high yielding varieties from the maturity group I, where it belongs. Lacking of Kunitz-trypsin inhibitor makes soybean grain suitable for direct feeding in adult non ruminant animals without previous thermal processing. Grain of variety Laura can be processed for a shorter period of time than conventional soybeans. This way we save energy, and preserve valuable nutritional composition of soybean grain, which is of interest in industrial processing.

Corrosion inhibitors. Manufacture and technology

International Nuclear Information System (INIS)

Ranney, M.W.

1976-01-01

Detailed information is presented relating to corrosion inhibitors. Areas covered include: cooling water, boilers and water supply plants; oil well and refinery operations; fuel and lubricant additives for automotive use; hydraulic fluids and machine tool lubes; grease compositions; metal surface treatments and coatings; and general processes for corrosion inhibitors

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...

SGLT2 Inhibitors May Predispose to Ketoacidosis.

Science.gov (United States)

Taylor, Simeon I; Blau, Jenny E; Rother, Kristina I

2015-08-01

Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that increase urinary excretion of glucose, thereby improving glycemic control and promoting weight loss. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs increase the risk of diabetic ketoacidosis. In May 2015, the Food and Drug Administration issued a warning that SGLT2 inhibitors may lead to ketoacidosis. Using PubMed and Google, we conducted Boolean searches including terms related to ketone bodies or ketoacidosis with terms for SGLT2 inhibitors or phlorizin. Priority was assigned to publications that shed light on molecular mechanisms whereby SGLT2 inhibitors could affect ketone body metabolism. SGLT2 inhibitors trigger multiple mechanisms that could predispose to diabetic ketoacidosis. When SGLT2 inhibitors are combined with insulin, it is often necessary to decrease the insulin dose to avoid hypoglycemia. The lower dose of insulin may be insufficient to suppress lipolysis and ketogenesis. Furthermore, SGLT2 is expressed in pancreatic α-cells, and SGLT2 inhibitors promote glucagon secretion. Finally, phlorizin, a nonselective inhibitor of SGLT family transporters decreases urinary excretion of ketone bodies. A decrease in the renal clearance of ketone bodies could also increase the plasma ketone body levels. Based on the physiology of SGLT2 and the pharmacology of SGLT2 inhibitors, there are several biologically plausible mechanisms whereby this class of drugs has the potential to increase the risk of developing diabetic ketoacidosis. Future research should be directed toward identifying which patients are at greatest risk for this side effect and also to optimizing pharmacotherapy to minimize the risk to patients.

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.

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.

Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

Directory of Open Access Journals (Sweden)

Shohei Sakuda

2014-03-01

Full Text Available Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control.

Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

Science.gov (United States)

Sakuda, Shohei; Prabowo, Diyan Febri; Takagi, Keiko; Shiomi, Kazuro; Mori, Mihoko; Ōmura, Satoshi; Nagasawa, Hiromichi

2014-01-01

Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A) inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III) and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control. PMID:24674936

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Science.gov (United States)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) Antidepressant SNRIs help relieve depression symptoms, such as irritability and sadness, ... effects they may cause. By Mayo Clinic Staff Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class ...

Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor.

Science.gov (United States)

Honma, Daisuke; Kanno, Osamu; Watanabe, Jun; Kinoshita, Junzo; Hirasawa, Makoto; Nosaka, Emi; Shiroishi, Machiko; Takizawa, Takeshi; Yasumatsu, Isao; Horiuchi, Takao; Nakao, Akira; Suzuki, Keisuke; Yamasaki, Tomonori; Nakajima, Katsuyoshi; Hayakawa, Miho; Yamazaki, Takanori; Yadav, Ajay Singh; Adachi, Nobuaki

2017-10-01

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B-cell lymphoma cells harboring gain-of-function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL-AF9, MLL-AF4, and AML1-ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Application of reflectance spectroscopies (FTIR-ATR & FT-NIR) coupled with multivariate methods for robust in vivo detection of begomovirus infection in papaya leaves.

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Haq, Quazi M I; Mabood, Fazal; Naureen, Zakira; Al-Harrasi, Ahmed; Gilani, Sayed A; Hussain, Javid; Jabeen, Farah; Khan, Ajmal; Al-Sabari, Ruqaya S M; Al-Khanbashi, Fatema H S; Al-Fahdi, Amira A M; Al-Zaabi, Ahoud K A; Al-Shuraiqi, Fatma A M; Al-Bahaisi, Iman M

2018-06-05

Nucleic acid & serology based methods have revolutionized plant disease detection, however, they are not very reliable at asymptomatic stage, especially in case of pathogen with systemic infection, in addition, they need at least 1-2days for sample harvesting, processing, and analysis. In this study, two reflectance spectroscopies i.e. Near Infrared reflectance spectroscopy (NIR) and Fourier-Transform-Infrared spectroscopy with Attenuated Total Reflection (FT-IR, ATR) coupled with multivariate exploratory methods like Principle Component Analysis (PCA) and Partial least square discriminant analysis (PLS-DA) have been deployed to detect begomovirus infection in papaya leaves. The application of those techniques demonstrates that they are very useful for robust in vivo detection of plant begomovirus infection. These methods are simple, sensitive, reproducible, precise, and do not require any lengthy samples preparation procedures. Copyright © 2018 Elsevier B.V. All rights reserved.

Structure-Based Search for New Inhibitors of Cholinesterases

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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.

Biological abatement of cellulase inhibitors.

Science.gov (United States)

Cao, Guangli; Ximenes, Eduardo; Nichols, Nancy N; Zhang, Leyu; Ladisch, Michael

2013-10-01

Removal of enzyme inhibitors released during lignocellulose pretreatment is essential for economically feasible biofuel production. We tested bio-abatement to mitigate enzyme inhibitor effects observed in corn stover liquors after pretreatment with either dilute acid or liquid hot water at 10% (w/v) solids. Bio-abatement of liquors was followed by enzymatic hydrolysis of cellulose. To distinguish between inhibitor effects on enzymes and recalcitrance of the substrate, pretreated corn stover solids were removed and replaced with 1% (w/v) Solka Floc. Cellulose conversion in the presence of bio-abated liquors from dilute acid pretreatment was 8.6% (0.1x enzyme) and 16% (1x enzyme) higher than control (non-abated) samples. In the presence of bio-abated liquor from liquid hot water pretreated corn stover, 10% (0.1x enzyme) and 13% (1x enzyme) higher cellulose conversion was obtained compared to control. Bio-abatement yielded improved enzyme hydrolysis in the same range as that obtained using a chemical (overliming) method for mitigating inhibitors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phosphodiesterase inhibitors in clinical urology.

Science.gov (United States)

Ückert, Stefan; Kuczyk, Markus A; Oelke, Matthias

2013-05-01

To date, benign diseases of the male and female lower urinary and genital tract, such as erectile dysfunction, bladder overactivity, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and symptoms of female sexual dysfunction (including arousal and orgasmic disorders), can be therapeutically approached by influencing the function of the smooth musculature of the respective tissues. The use of isoenzyme-selective phosphodiesterase (PDE) inhibitors is considered a great opportunity to treat various diseases of the human urogenital tract. PDE inhibitors, in particular the PDE5 (cyclic GMP PDE) inhibitors avanafil, lodenafil, sildenafil, tadalafil, udenafil and vardenafil, are regarded as efficacious, having a fast onset of drug action and an improved effect-to-adverse event ratio, combining a high response rate with the advantage of an on-demand intake. The purpose of this review is to summarize recent as well as potential future indications, namely, erectile dysfunction, Peyronie's disease, overactive bladder, urinary stone disease, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and premature ejaculation, for the use of PDE inhibitors in clinical urology.

F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort

Science.gov (United States)

Schwarz, John; Astermark, Jan; Menius, Erika D.; Carrington, Mary; Donfield, Sharyne M.; Gomperts, Edward D.; Nelson, George W.; Oldenburg, Johannes; Pavlova, Anna; Shapiro, Amy D.; Winkler, Cheryl A.; Berntorp, Erik

2012-01-01

Background Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in hemophilia A. It has been suggested that differences in the distribution of factor VIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Design and Methods Data from the HIGS Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1+H2) and inhibitor risk among individuals of genetically-determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and HLA were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Results H3 was associated with higher inhibitor risk among those genetically-identified (N=49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N=223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Conclusion H3 was not an independent predictor of inhibitor risk. Further, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. PMID:22958194

Monoamine depletion by reuptake inhibitors

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Hinz M

2011-10-01

Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc, Cape Coral, FL; 2Stein Orthopedic Associates, Plantation, FL; 3DBS Labs Inc, Duluth, MN, USABackground: Disagreement exists regarding the etiology of cessation of the observed clinical results with administration of reuptake inhibitors. Traditionally, when drug effects wane, it is known as tachyphylaxis. With reuptake inhibitors, the placebo effect is significantly greater than the drug effect in the treatment of depression and attention deficit hyperactivity disorder, leading some to assert that waning of drug effects is placebo relapse, not tachyphylaxis.Methods: Two groups were retrospectively evaluated. Group 1 was composed of subjects with depression and Group 2 was composed of bariatric subjects treated with reuptake inhibitors for appetite suppression.Results: In Group 1, 200 subjects with depression were treated with citalopram 20 mg per day. A total of 46.5% (n = 93 achieved relief of symptoms (Hamilton-D rating score ≤ 7, of whom 37 (39.8% of whom experienced recurrence of depression symptoms, at which point an amino acid precursor formula was started. Within 1–5 days, 97.3% (n = 36 experienced relief of depression symptoms. In Group 2, 220 subjects were treated with phentermine 30 mg in the morning and citalopram 20 mg at 4 pm. In this group, 90.0% (n = 198 achieved adequate appetite suppression. The appetite suppression ceased in all 198 subjects within 4–48 days. Administration of an amino acid precursor formula restored appetite suppression in 98.5% (n = 195 of subjects within 1–5 days.Conclusion: Reuptake inhibitors do not increase the total number of monoamine molecules in the central nervous system. Their mechanism of action facilitates redistribution of monoamines from one place to another. In the process, conditions are induced that facilitate depletion of monoamines. The "reuptake inhibitor monoamine depletion theory" of this paper

Theoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors: insight into structure-based inhibitor design.

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Shen, Mingyun; Zhou, Shunye; Li, Youyong; Li, Dan; Hou, Tingjun

2013-10-01

LIM kinases (LIMKs), downstream of Rho-associated protein kinases (ROCKs) and p21-activated protein kinases (PAKs), are shown to be promising targets for the treatment of cancers. In this study, the inhibition mechanism of 41 pyrrolopyrimidine derivatives as LIMK2 inhibitors was explored through a series of theoretical approaches. First, a model of LIMK2 was generated through molecular homology modeling, and the studied inhibitors were docked into the binding active site of LIMK2 by the docking protocol, taking into consideration the flexibility of the protein. The binding poses predicted by molecular docking for 17 selected inhibitors with different bioactivities complexed with LIMK2 underwent molecular dynamics (MD) simulations, and the binding free energies for the complexes were predicted by using the molecular mechanics/generalized born surface area (MM/GBSA) method. The predicted binding free energies correlated well with the experimental bioactivities (r(2) = 0.63 or 0.62). Next, the free energy decomposition analysis was utilized to highlight the following key structural features related to biological activity: (1) the important H-bond between Ile408 and pyrrolopyrimidine, (2) the H-bonds between the inhibitors and Asp469 and Gly471 which maintain the stability of the DFG-out conformation, and (3) the hydrophobic interactions between the inhibitors and several key residues (Leu337, Phe342, Ala345, Val358, Lys360, Leu389, Ile408, Leu458 and Leu472). Finally, a variety of LIMK2 inhibitors with a pyrrolopyrimidine scaffold were designed, some of which showed improved potency according to the predictions. Our studies suggest that the use of molecular docking with MD simulations and free energy calculations could be a powerful tool for understanding the binding mechanism of LIMK2 inhibitors and for the design of more potent LIMK2 inhibitors.

Aromatic inhibitors derived from ammonia-pretreated lignocellulose hinder bacterial ethanologenesis by activating regulatory circuits controlling inhibitor efflux and detoxification

Directory of Open Access Journals (Sweden)

David H. Keating

2014-08-01

Full Text Available Efficient microbial conversion of lignocellulosic hydrolysates to biofuels is a key barrier to the economically viable deployment of lignocellulosic biofuels. A chief contributor to this barrier is the impact on microbial processes and energy metabolism of lignocellulose-derived inhibitors, including phenolic carboxylates, phenolic amides (for ammonia-pretreated biomass, phenolic aldehydes, and furfurals. To understand the bacterial pathways induced by inhibitors present in ammonia-pretreated biomass hydrolysates, which are less well studied than acid-pretreated biomass hydrolysates, we developed and exploited synthetic mimics of ammonia-pretreated corn stover hydrolysate (ACSH. To determine regulatory responses to the inhibitors normally present in ACSH, we measured transcript and protein levels in an Escherichia coli ethanologen using RNA-seq and quantitative proteomics during fermentation to ethanol of synthetic hydrolysates containing or lacking the inhibitors. Our study identified four major regulators mediating these responses, the MarA/SoxS/Rob network, AaeR, FrmR, and YqhC. Induction of these regulons was correlated with a reduced rate of ethanol production, buildup of pyruvate, depletion of ATP and NAD(PH, and an inhibition of xylose conversion. The aromatic aldehyde inhibitor 5-hydroxymethylfurfural appeared to be reduced to its alcohol form by the ethanologen during fermentation, whereas phenolic acid and amide inhibitors were not metabolized. Together, our findings establish that the major regulatory responses to lignocellulose-derived inhibitors are mediated by transcriptional rather than translational regulators, suggest that energy consumed for inhibitor efflux and detoxification may limit biofuel production, and identify a network of regulators for future synthetic biology efforts.

Predicting DPP-IV inhibitors with machine learning approaches

Science.gov (United States)

Cai, Jie; Li, Chanjuan; Liu, Zhihong; Du, Jiewen; Ye, Jiming; Gu, Qiong; Xu, Jun

2017-04-01

Dipeptidyl peptidase IV (DPP-IV) is a promising Type 2 diabetes mellitus (T2DM) drug target. DPP-IV inhibitors prolong the action of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), improve glucose homeostasis without weight gain, edema, and hypoglycemia. However, the marketed DPP-IV inhibitors have adverse effects such as nasopharyngitis, headache, nausea, hypersensitivity, skin reactions and pancreatitis. Therefore, it is still expected for novel DPP-IV inhibitors with minimal adverse effects. The scaffolds of existing DPP-IV inhibitors are structurally diversified. This makes it difficult to build virtual screening models based upon the known DPP-IV inhibitor libraries using conventional QSAR approaches. In this paper, we report a new strategy to predict DPP-IV inhibitors with machine learning approaches involving naïve Bayesian (NB) and recursive partitioning (RP) methods. We built 247 machine learning models based on 1307 known DPP-IV inhibitors with optimized molecular properties and topological fingerprints as descriptors. The overall predictive accuracies of the optimized models were greater than 80%. An external test set, composed of 65 recently reported compounds, was employed to validate the optimized models. The results demonstrated that both NB and RP models have a good predictive ability based on different combinations of descriptors. Twenty "good" and twenty "bad" structural fragments for DPP-IV inhibitors can also be derived from these models for inspiring the new DPP-IV inhibitor scaffold design.

Aromatase inhibitors and breast cancer prevention.

Science.gov (United States)

Litton, Jennifer Keating; Arun, Banu K; Brown, Powel H; Hortobagyi, Gabriel N

2012-02-01

Endocrine therapy with selective estrogen receptor modulators (SERMs) has been the mainstay of breast cancer prevention trials to date. The aromatase inhibitors, which inhibit the final chemical conversion of androgens to estrogens, have shown increased disease-free survival benefit over tamoxifen in patients with primary hormone receptor-positive breast cancer, as well as reducing the risk of developing contralateral breast cancers. The aromatase inhibitors are being actively evaluated as prevention agents for women with a history of ductal carcinoma in situ as well as for women who are considered to be at high risk for developing primary invasive breast cancer. This review evaluates the available prevention data, as evidenced by the decrease in contralateral breast cancers, when aromatase inhibitors are used in the adjuvant setting, as well as the emerging data of the aromatase inhibitors specifically tested in the prevention setting for women at high risk. Exemestane is a viable option for breast cancer prevention. We continue to await further follow-up on exemestane as well as other aromatase inhibitors in the prevention setting for women at high risk of developing breast cancer or with a history of ductal carcinoma in situ.

DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

Science.gov (United States)

Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

2016-08-23

Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

Monoamine Oxidase B Inhibitors in Parkinson's Disease.

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Dezsi, Livia; Vecsei, Laszlo

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials. A literature search was conducted in PubMed for 'PD treatment', 'MAO-B inhibitors', 'selegiline', 'rasagiline', 'safinamide' and 'clinical trials' with 'MAO-B inhibitors' in 'Parkinson' disease'. MAO-B inhibitors have a favorable pharmacokinetic profile, improve the dopamine deficient state and may have neuroprotective properties. Safinamide exhibits an anti-glutamatergic effect as well. When applied as monotherapy, MAO-B inhibitors provide a modest, but significant improvement of motor function and delay the need for levodopa. Rasagiline and safinamide were proven safe and effective when added to a dopamine agonist in early PD. As add-on to levodopa, MAO-B inhibitors significantly reduced off-time and were comparable in efficacy to COMT inhibitors. Improvements were achieved as regards certain non-motor symptoms as well. Due to the efficacy shown in clinical trials and their favorable side-effect profile, MAO-B inhibitors are valuable drugs in the treatment of PD. They are recommended as monotherapy in the early stages of the disease and as add-on therapy to levodopa in advanced PD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

"In situ" observation of the role of chloride ion binding to monkey green sensitive visual pigment by ATR-FTIR spectroscopy.

Science.gov (United States)

Katayama, Kota; Furutani, Yuji; Iwaki, Masayo; Fukuda, Tetsuya; Imai, Hiroo; Kandori, Hideki

2018-01-31

Long-wavelength-sensitive (LWS) pigment possesses a chloride binding site in its protein moiety. The binding of chloride alters the absorption spectra of LWS; this is known as the chloride effect. Although the two amino acid substitutions of His197 and Lys200 influence the chloride effect, the molecular mechanism of chloride binding, which underlies the spectral tuning, has yet to be clarified. In this study, we applied ATR-FTIR spectroscopy to monkey green (MG) pigment to gain structural information of the chloride binding site. The results suggest that chloride binding stabilizes the β-sheet structure on the extracellular side loop with perturbation of the retinal polyene chain, promotes a hydrogen bonding exchange with the hydroxyl group of Tyr, and alters the protonation state of carboxylate. Combining with the results of the binding analyses of various anions (Br - , I - and NO 3 - ), our findings suggest that the anion binding pocket is organized for only Cl - (or Br - ) to stabilize conformation around the retinal chromophore, which is functionally relevant with absorbing long wavelength light.

Enzyme structure and interaction with inhibitors

International Nuclear Information System (INIS)

London, R.E.

1983-01-01

This article reviews some of the results of studies on the 13 C-labeled enzyme dihydrofolate reductase (DHFR). Nuclear magnetic resonance (NMR) techniques are used in combination with isotopic labeling to learn about the structure and dynamics of this enzyme. 13 C-labeling is used for the purpose of studying enzyme/substrate and enzyme/inhibitor interactions. A second set of studies with DHFR was designed to investigate the basis for the high affinity between the inhibitor methotrexate and DHFR. The label was placed on the inhibitor, rather than the enzyme

ELISA analysis of soybean trypsin inhibitors in processed foods.

Science.gov (United States)

Brandon, D L; Bates, A H; Friedman, M

1991-01-01

Soybean proteins are widely used in human foods in a variety of forms, including infant formulas, flour, protein concentrates, protein isolates, soy sauces, textured soy fibers, and tofu. The presence of inhibitors of digestive enzymes in soy proteins impairs the nutritional quality and possibly the safety of soybeans and other legumes. Processing, based on the use of heat or fractionation of protein isolates, does not completely inactivate or remove these inhibitors, so that residual amounts of inhibitors are consumed by animals and humans. New monoclonal antibody-based immunoassays can measure low levels of the soybean Kunitz trypsin inhibitor (KTI) and the Bowman-Birk trypsin and chymotrypsin inhibitor (BBI) and the Bowman-Birk foods. The enzyme-linked immunosorbent assay (ELISA) was used to measure the inhibitor content of soy concentrates, isolates, and flours, both heated and unheated; a commercial soy infant formula; KTI and BBI with rearranged disulfide bonds; browning products derived from heat-treatment of KTI with glucose and starch; and KTI exposed to high pH. The results indicate that even low inhibitor isolates contain significant amounts of specific inhibitors. Thus, infants on soy formula consume about 10 mg of KTI plus BBI per day. The immunoassays complement the established enzymatic assays of trypsin and chymotrypsin inhibitors, and have advantages in (a) measuring low levels of inhibitors in processed foods; and (b) differentiating between the Kunitz and Bowman-Birk inhibitors. The significance of our findings for food safety are discussed.

Classification of Cytochrome P450 1A2 Inhibitors and Non-Inhibitors by Machine Learning Techniques

DEFF Research Database (Denmark)

Vasanthanathan, Poongavanam; Taboureau, Olivier; Oostenbrink, Chris

2009-01-01

of CYP1A2 inhibitors and non-inhibitors. Training and test sets consisted of about 400 and 7000 compounds, respectively. Various machine learning techniques, like binary QSAR, support vector machine (SVM), random forest, kappa nearest neighbors (kNN), and decision tree methods were used to develop...

Retro-binding thrombin active site inhibitors: identification of an orally active inhibitor of thrombin catalytic activity.

Science.gov (United States)

Iwanowicz, Edwin J; Kimball, S David; Lin, James; Lau, Wan; Han, W-C; Wang, Tammy C; Roberts, Daniel G M; Schumacher, W A; Ogletree, Martin L; Seiler, Steven M

2002-11-04

A series of retro-binding inhibitors of human alpha-thrombin was prepared to elucidate structure-activity relationships (SAR) and optimize in vivo performance. Compounds 9 and 11, orally active inhibitors of thrombin catalytic activity, were identified to be efficacious in a thrombin-induced lethality model in mice.

Contemporary protease inhibitors and cardiovascular risk

DEFF Research Database (Denmark)

Lundgren, Jens; Mocroft, Amanda; Ryom, Lene

2018-01-01

PURPOSE OF REVIEW: To review the evidence linking use of HIV protease inhibitors with excess risk of cardiovascular disease (CVD) in HIV+ populations. RECENT FINDINGS: For the two contemporary most frequently used protease inhibitors, darunavir and atazanavir [both pharmacologically boosted...

Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection

DEFF Research Database (Denmark)

Borges, Álvaro H; Lundh, Andreas; Tendal, Britta

2016-01-01

BACKGROUND: Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. METHODS: ...

Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

Energy Technology Data Exchange (ETDEWEB)

Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

2012-03-01

Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): a drug use investigation.

Science.gov (United States)

Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

2014-11-01

Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Potential non-oncological applications of histone deacetylase inhibitors.

Science.gov (United States)

Ververis, Katherine; Karagiannis, Tom C

2011-01-01

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutic drugs. Their clinical utility in oncology stems from their intrinsic cytotoxic properties and combinatorial effects with other conventional cancer therapies. To date, the histone deacetylase inhibitors suberoylanilide hydroxamic acid (Vorinostat, Zolinza®) and depsipeptide (Romidepsin, Istodax®) have been approved by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Further, there are currently over 100 clinical trials involving the use of histone deacetylase inhibitors in a wide range of solid and hematological malignancies. The therapeutic potential of histone deacetylase inhibitors has also been investigated for numerous other diseases. For example, the cytotoxic properties of histone deacetylase inhibitors are currently being harnessed as a potential treatment for malaria, whereas the efficacy of these compounds for HIV relies on de-silencing latent virus. The anti-inflammatory properties of histone deacetylase inhibitors are the predominant mechanisms for other diseases, such as hepatitis, systemic lupus erythematosus and a wide range of neurodegenerative conditions. Additionally, histone deacetylase inhibitors have been shown to be efficacious in animal models of cardiac hypertrophy and asthma. Broad-spectrum histone deacetylase inhibitors are clinically available and have been used almost exclusively in preclinical systems to date. However, it is emerging that class- or isoform-specific compounds, which are becoming more readily available, may be more efficacious particularly for non-oncological applications. The aim of this review is to provide an overview of the effects and clinical potential of histone deacetylase inhibitors in various diseases. Apart from applications in oncology, the discussion is focused on the potential efficacy of histone deacetylase inhibitors for the treatment of neurodegenerative diseases, cardiac

Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

KAUST Repository

Ramadan, Ahmed M Ali

2011-06-26

The uidA gene, encoding for β-glucuronidase (GUS), is the most frequently used reporter gene in plants. As a reporter enzyme, GUS can be assayed both qualitatively and quantitatively. In wheat, there are numerous reports of failure in detecting GUS enzyme activity in tissues of transgenic plants, while other reports have suggested presence of β-glucuronidase inhibitor(s) in wheat tissues. In the present study, we show that the β-glucuronidase enzyme activity is not only tissue-specific but also genotype-dependent. Our data demonstrate that the glucuronic acid could be the candidate inhibitor for β-glucuronidase enzyme activity in wheat leaves and roots. It should be noted that the assays to detect β-glucuronidase enzyme activity in wheat should be interpreted carefully. Based on the data of our present study, we recommend studying the chemical pathways, the unintended effects and the possible loss-of-function of any candidate transgene prior to transformation experiments. © 2011 Springer Science+Business Media B.V.

Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

KAUST Repository

Ramadan, Ahmed M Ali; Eissa, Hala F.; El-Domyati, Fotouh M.; Saleh, Osama Mesilhy; Ibrahim, Nasser E.; Salama, M. I.; Mahfouz, Magdy M.; Bahieldin, Ahmed M.

2011-01-01

The uidA gene, encoding for β-glucuronidase (GUS), is the most frequently used reporter gene in plants. As a reporter enzyme, GUS can be assayed both qualitatively and quantitatively. In wheat, there are numerous reports of failure in detecting GUS enzyme activity in tissues of transgenic plants, while other reports have suggested presence of β-glucuronidase inhibitor(s) in wheat tissues. In the present study, we show that the β-glucuronidase enzyme activity is not only tissue-specific but also genotype-dependent. Our data demonstrate that the glucuronic acid could be the candidate inhibitor for β-glucuronidase enzyme activity in wheat leaves and roots. It should be noted that the assays to detect β-glucuronidase enzyme activity in wheat should be interpreted carefully. Based on the data of our present study, we recommend studying the chemical pathways, the unintended effects and the possible loss-of-function of any candidate transgene prior to transformation experiments. © 2011 Springer Science+Business Media B.V.

The "SWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both?

Science.gov (United States)

Nissan, Moriah H; Solit, David B

2011-12-01

Activating mutations in the BRAF gene are among the most prevalent kinase mutations in human cancer. BRAF mutations are most frequent in patients with melanoma where they occur in approximately 50% of patients with advanced disease. Remarkable clinical activity has recently been reported with highly selective RAF inhibitors in melanoma patients whose tumors harbor V600E BRAF mutations. The response rates of RAF inhibitors in patients with BRAF-mutant melanomas far exceed the activity level of any prior therapy studied in this disease. The results suggest that we have entered an era of personalized therapy for patients with metastatic melanoma in which treatment selection will be guided by BRAF mutational status. This review will discuss the strengths, weaknesses, opportunities and threats ("SWOT") of developing RAF and MEK selective inhibitors as anti-cancer therapies, recent insights into the mechanisms of intrinsic and acquired resistance to these agents, and current efforts to develop mechanism-based combination therapies.

Regulation of collagenase inhibitor production in chondrosarcoma chondrocytes

International Nuclear Information System (INIS)

Harper, J.; Harper, E.

1987-01-01

Swarm rat chondrosarcoma chondrocytes produce an inhibitor of collagenase. This inhibitor is similar to those isolated from normal cartilage tissues. These cells will synthesize proteins in the absence of serum. Since serum contains inhibitors of collagenase, it is necessary to culture cells without serum in order to obtain accurate measurements of enzyme and inhibitor levels. They examined the effect of insulin on inhibitor secretion by cultures of Swarm rat chondrosarcoma chondrocytes. They observed a 2.5 to 3.5 fold stimulation of inhibitory activity in the presence of as little as 10 ng/ml insulin as compared to controls in serum free Dulbecco's modified Eagle's medium supplemented with 4.5 g/l glucose. The units of inhibitor were determined over a 7 day culture period. Medium was harvested daily and assayed for collagenase activity and for inhibition of a known collagenase from rabbit skin or human skin, using the 14 C-glycine peptide release assay. The amount of inhibitor obtained from days 2 through 7 were: 1.4 unit (control), 3.8 units (10 ng/ml insulin), 5.2 units (1 μg/ml insulin). The addition of 1 mM dibutyryl cyclic AMP to these chondrocytes in the presence of 1 μg/ml insulin caused a decrease in the level of inhibitor, suggesting that a dephosphorylation event may be necessary for this stimulation by insulin to occur

SAJOG 733.indd

African Journals Online (AJOL)

Methods. Pregnant women (N=800) attending an antenatal clinic were recruited at their first visit. ... Department of Obstetrics and Gynaecology, Maulana Azad Medical College, Delhi University, India .... test is therefore a poor screening test for.

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.

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.

Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding.

Science.gov (United States)

Huang, Kai-Fa; Liaw, Su-Sen; Huang, Wei-Lin; Chia, Cho-Yun; Lo, Yan-Chung; Chen, Yi-Ling; Wang, Andrew H-J

2011-04-08

Aberrant pyroglutamate formation at the N terminus of certain peptides and proteins, catalyzed by glutaminyl cyclases (QCs), is linked to some pathological conditions, such as Alzheimer disease. Recently, a glutaminyl cyclase (QC) inhibitor, PBD150, was shown to be able to reduce the deposition of pyroglutamate-modified amyloid-β peptides in brain of transgenic mouse models of Alzheimer disease, leading to a significant improvement of learning and memory in those transgenic animals. Here, we report the 1.05-1.40 Å resolution structures, solved by the sulfur single-wavelength anomalous dispersion phasing method, of the Golgi-luminal catalytic domain of the recently identified Golgi-resident QC (gQC) and its complex with PBD150. We also describe the high-resolution structures of secretory QC (sQC)-PBD150 complex and two other gQC-inhibitor complexes. gQC structure has a scaffold similar to that of sQC but with a relatively wider and negatively charged active site, suggesting a distinct substrate specificity from sQC. Upon binding to PBD150, a large loop movement in gQC allows the inhibitor to be tightly held in its active site primarily by hydrophobic interactions. Further comparisons of the inhibitor-bound structures revealed distinct interactions of the inhibitors with gQC and sQC, which are consistent with the results from our inhibitor assays reported here. Because gQC and sQC may play different biological roles in vivo, the different inhibitor binding modes allow the design of specific inhibitors toward gQC and sQC.

Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro

NARCIS (Netherlands)

Walker, J.B.; Hughes, B.; James, I.; Haddock, P.; Kluft, C.; Bajzar, L.

2003-01-01

Two competitive inhibitors of TAFIa (activated thrombin-activable fibrinolysis inhibitor), 2-guanidinoethyl-mercaptosuccinic acid and potato tuber carboxypeptidase inhibitor, variably affect fibrinolysis of clotted human plasma. Depending on their concentration, the inhibitors shortened, prolonged,

Replacement inhibitors for tank farm cooling coil systems

International Nuclear Information System (INIS)

Hsu, T.C.

1995-01-01

Sodium chromate has been an effective corrosion inhibitor for the cooling coil systems in Savannah River Site (SRS) waste tanks for over 40 years. Due to their age and operating history, cooling coils occasionally fail allowing chromate water to leak into the environment. When the leaks spill 10 lbs. or more of sodium chromate over a 24-hr period, the leak incidents are classified as Unusual Occurrences (UO) per CERCLA (Comprehensive Environmental Response, Compensation and Liability Act). The cost of reporting and cleaning up chromate spills prompted High Level Waste Engineering (HLWE) to initiate a study to investigate alternative tank cooling water inhibitor systems and the associated cost of replacement. Several inhibitor systems were investigated as potential alternatives to sodium chromate. All would have a lesser regulatory impact, if a spill occurred. However, the conversion cost is estimated to be $8.5 million over a period of 8 to 12 months to convert all 5 cooling systems. Although each of the alternative inhibitors examined is effective in preventing corrosion, there is no inhibitor identified that is as effective as chromate. Assuming 3 major leaks a year (the average over the past several years), the cost of maintaining the existing inhibitor was estimated at $0.5 million per year. Since there is no economic or regulatory incentive to replace the sodium chromate with an alternate inhibitor, HLWE recommends that sodium chromate continue to be used as the inhibitor for the waste tank cooling systems

The safety of proton pump inhibitors in pregnancy

DEFF Research Database (Denmark)

Nielsen, Gunnar Lauge; Sørensen, Henrik Toft; Thulstrup, Ane Marie

1999-01-01

AIM: To assess the safety of proton pump inhibitors during pregnancy. METHODS: Fifty-one pregnant women exposed to proton pump inhibitors around the time of conception or during pregnancy were compared with 13 327 controls without exposure to any prescribed drug in a population-based study based...... birth weight or number of preterm deliveries in pregnancies exposed to proton pump inhibitors. However, further monitoring is warranted in order to establish or rule out a potential association between the use of proton pump inhibitors and increased risk of either cardiac malformations or preterm birth....

Epithelial tissue hyperplasia induced by the RAF inhibitor PF-04880594 is attenuated by a clinically well-tolerated dose of the MEK inhibitor PD-0325901.

Science.gov (United States)

Torti, Vince R; Wojciechowicz, Donald; Hu, Wenyue; John-Baptiste, Annette; Evering, Winston; Troche, Gabriel; Marroquin, Lisa D; Smeal, Tod; Yamazaki, Shinji; Palmer, Cynthia L; Burns-Naas, Leigh Ann; Bagrodia, Shubha

2012-10-01

Clinical trials of selective RAF inhibitors in patients with melanoma tumors harboring activated BRAFV600E have produced very promising results, and a RAF inhibitor has been approved for treatment of advanced melanoma. However, about a third of patients developed resectable skin tumors during the course of trials. This is likely related to observations that RAF inhibitors activate extracellular signal-regulated kinase (ERK) signaling, stimulate proliferation, and induce epithelial hyperplasia in preclinical models. Because these findings raise safety concerns about RAF inhibitor development, we further investigated the underlying mechanisms. We showed that the RAF inhibitor PF-04880594 induces ERK phosphorylation and RAF dimerization in those epithelial tissues that undergo hyperplasia. Hyperplasia and ERK hyperphosphorylation are prevented by treatment with the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD-0325901 at exposures that extrapolate to clinically well-tolerated doses. To facilitate mechanistic and toxicologic studies, we developed a three-dimensional cell culture model of epithelial layering that recapitulated the RAF inhibitor-induced hyperplasia and reversal by MEK inhibitor in vitro. We also showed that PF-04880594 stimulates production of the inflammatory cytokine interleukin 8 in HL-60 cells, suggesting a possible mechanism for the skin flushing observed in dogs. The complete inhibition of hyperplasia by MEK inhibitor in epithelial tissues does not seem to reduce RAF inhibitor efficacy and, in fact, allows doubling of the PF-04880594 dose without toxicity usually associated with such doses. These findings indicated that combination treatment with MEK inhibitors might greatly increase the safety and therapeutic index of RAF inhibitors for the treatment of melanoma and other cancers. ©2012 AACR.

Janus Associated Kinases Inhibitors in the Pharmacological Thera

Directory of Open Access Journals (Sweden)

Daniela Santos1

2017-01-01

Full Text Available Janus associated kinases inhibitors are a new strategy for the treatment of different clinical conditions like immunologic, inflammatory and oncology disorders. The aim of this study was to perform a review of all Janus associated kinases inhibitors available in national and international pharmaceutical market, their therapeutic indications and adverse effects, and the potential indications for investigation of those already available in the pharmaceutical market. It was also performed a review of the main new Janus associated kinases inhibitors that are still in clinical research. A literature review was conducted by consulting the summary of product characteristics of Janus associated kinases inhibitors available in the pharmaceutical market and a research in the bibliographic database PubMed using the terms «JAK inhibitors», «Janus associated kinases inhibitors» and «Janus kinases inhibitors». Ninety-five publications were included in the present review, published from January 2014 to January 2015. Drug databases of the European Medicines Agency and United States Food and Drug Administration were also consulted to search for Janus associated kinases inhibitors authorized in clinical practice. Currently, ruxolitinib and tofacitinib are available in the pharmaceutical market and oclatinib is approved as a veterinary medicinal product. Both drugs approved for human use have major adverse effects at hematological and immunological levels, which enhance the importance of the pharmacist’s role in the monitoring of patients involved in these treatments. However, several molecules are in pre-clinical and clinical studies trying to prove its potential in the treatment of several immunologic, inflammatory and oncology disorders. Thus, it is still necessary to deepen the knowledge in this area in order to overcome the risks of therapy with these agents. These risks weighed against the benefits of its clinical use have compromised the progress of

Positron emitter labeled enzyme inhibitors

International Nuclear Information System (INIS)

Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.; Langstrom, B.

1990-01-01

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

Inhibition of matrix metalloproteinase-2 by PARP inhibitors

International Nuclear Information System (INIS)

Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D.; Pacher, Pal; Schulz, Richard

2009-01-01

Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC 50 values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity.

Inhibition of matrix metalloproteinase-2 by PARP inhibitors

Energy Technology Data Exchange (ETDEWEB)

Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D. [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada); Pacher, Pal [National Institutes of Health, NIAAA, Laboratory of Physiologic Studies, Bethesda, MD (United States); Schulz, Richard, E-mail: richard.schulz@ualberta.ca [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada)

2009-10-02

Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC{sub 50} values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity.

The Wonders of Phosphodiesterase‑5 Inhibitors: A Majestic History

African Journals Online (AJOL)

A milestone in drug discovery was the selective inhibitors of. PDE‑5 that ... the pharmacotherapeutics of PDE‑5 inhibitors and the majestic history that led to their discovery. ..... including HIV protease inhibitors, ketoconazole, itraconazole,.

Inactivation of proteinaceous protease inhibitors of soybeans by isolated fungi

NARCIS (Netherlands)

Meijer, M.M.T.; Spekking, W.T.J.; Sijtsma, L.; Bont, de J.A.M.

1995-01-01

Proteinaceous protease inhibitors, Kunitz Soybean Trypsin Inhibitor (KSTI) and Bowman Birk Inhibitor (BBI), in legume seeds reduce the digestibility of proteins in feed of monogastric animals. Enzymatic inactivation of these inhibitors will increase the nutritional value of the feed. The aim of this

SGLT2 inhibitors: are they safe?

Science.gov (United States)

Filippas-Ntekouan, Sebastian; Filippatos, Theodosios D; Elisaf, Moses S

2018-01-01

Sodium-glucose linked transporter type 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with positive cardiovascular and kidney effects. The aim of this review is to present the safety issues associated with SGLT2 inhibitors. Urogenital infections are the most frequently encountered adverse events, although tend to be mild to moderate and are easily manageable with standard treatment. Although no increased acute kidney injury risk was evident in the major trials, the mechanism of action of these drugs requires caution when they are administered in patients with extracellular volume depletion or with drugs affecting renal hemodynamics. Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly. Regarding other adverse events, SGLT2 inhibitors do not increase the risk of hypoglycemia even when co-administered with insulin, but a decrease in the dose of sulphonylureas may be needed. The available data do not point to a causative role of SGLT2 inhibitors on malignancy risk, however, these drugs should be used with caution in patients with known hematuria or history of bladder cancer. SGLT2 inhibitors seem to be safe and effective in the treatment of diabetes but more studies are required to assess their long-term safety.

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.

Conservation of Moroccan manuscript papers aged 150, 200 and 800 years. Analysis by infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and scanning electron microscopy energy dispersive spectrometry (SEM-EDS).

Science.gov (United States)

Hajji, Latifa; Boukir, Abdellatif; Assouik, Jamal; Lakhiari, Hamid; Kerbal, Abdelali; Doumenq, Pierre; Mille, Gilbert; De Carvalho, Maria Luisa

2015-02-05

The preservation of manuscripts and archive materials is a serious problem for librarians and restorers. Paper manuscript is subjected to numerous degradation factors affecting their conservation state. This research represents an attempt to evaluate the conservation restoration process applied in Moroccan libraries, especially the alkaline treatment for strengthening weakened paper. In this study, we focused on six samples of degraded and restored paper taken from three different Moroccan manuscripts aged 150, 200 and 800 years. In addition, the Japanese paper used in restoration has been characterized. A modern paper was also analyzed as reference. A three-step analytical methodology based on infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectrometry (SEM-EDS) analysis was developed before and after restoration in order to determine the effect of the consolidation treatment on the paper structure. The results obtained by XRD and ATR-FTIR disclosed the presence of barium sulfate (BaSO4) in all restored paper manuscripts. The presence of calcium carbonate (CaCO3) in all considered samples was confirmed by FTIR spectroscopy. The application of de-acidification treatment causes significant changes connected with the increase of intensity mostly in the region 1426 cm(-1), assigned to the asymmetric and symmetric CO stretching mode of calcite, indicating the effectiveness of de-acidification procedure proved by the rise of the alkaline reserve content allowing the long term preservation of paper. Observations performed by SEM magnify the typical paper morphology and the structure of fibbers, highlighting the effect of the restoration process, manifested by the reduction of impurities. Copyright © 2014 Elsevier B.V. All rights reserved.

Experimental and theoretical studies of benzoxazines corrosion inhibitors

Directory of Open Access Journals (Sweden)

Abdulhadi Kadhim

Full Text Available 2-Methyl-4H-benzo[d][1,3]oxazin-4-one (BZ1 and 3-amino-2-methylquinazolin-4(3H-one (BZ2 were evaluated for their corrosion inhibition properties on mild steel (MS in hydrochloric acid solution by weight loss technique and scanning electron microscopy. Results show the inhibition efficiency values depend on the amount of nitrogen in the inhibitor, the inhibitor concentration and the inhibitor molecular weight with maximum inhibition efficiency of 89% and 65% for BZ2 and BZ1 at highest concentration of the compounds. Keywords: Methylquinazoline, Benzoxazines, Corrosion, Inhibitors

Acid corrosion inhibitor

Energy Technology Data Exchange (ETDEWEB)

Chen, N G

1964-04-28

An acid corrosion inhibitor is prepared by a 2-stage vacuum evaporation of effluents obtained from the ammonia columns of the coking oven plant. The effluent, leaving a scrubber in which the phenols are removed at a temperature of 98$C, passes through a quartz filter and flows into a heated chamber in which it is used for preheating a solution circulating through a vacuum unit, maintaining the temperature of the solution at 55$ to 60$C. The effluent enters a large tank in which it is boiled at 55$ to 60$C under 635 to 640 mm Hg pressure. Double evaporation of this solution yields a very effective acid corrosion inhibitor. Its corrosion-preventing effect is 97.9% compared with 90.1% for thiourea and 88.5% for urotropin under identical conditions.

Novel dual small-molecule HIV inhibitors: scaffolds and discovery strategies.

Science.gov (United States)

Song, Anran; Yu, Haiqing; Wang, Changyuan; Zhu, Xingqi; Liu, Kexin; Ma, Xiaodong

2015-01-01

Searching for safe and effective treatments for HIV infection is still a great challenge worldwide in spite of the 27 marketed anti-HIV drugs and the powerful highly active antiretroviral therapy (HAART). As a promising prospect for generation of new HIV therapy drugs, multiple ligands (MDLs) were greatly focused on recently due to their lower toxicity, simplified dosing and patient adherence than single-target drugs. Till now, by disrupting two active sites or steps of HIV replications, a number of HIV dual inhibitors, such as CD4-gssucap120 inhibitors, CXCR4-gp20 inhibitors, RT-CXCR4 inhibitors, RT-protease inhibitors, RT-integrase inhibitors, and RTassociated functions inhibitors have been identified. Generally, these dual inhibitors were discovered mainly through screening approaches and design strategies. Of these compounds, the molecules bearing small skeletons exhibited strong anti-HIV activity and aroused great attention recently. Reviewing the progress of the dual small-molecule HIV inhibitors from the point of view of their scaffolds and discovery strategies will provide valuable information for producing more effective anti-HIV drugs. In this regard, novel dual small-molecule HIV inhibitors were illustrated, and their discovery paradigms as the major contents were also summarized in this manuscript.

SGLT2 inhibitors: molecular design and potential differences in effect.

Science.gov (United States)

Isaji, Masayuki

2011-03-01

The physiological and pathological handling of glucose via sodium-glucose cotransporter-2 (SGLT2) in the kidneys has been evolving, and SGLT2 inhibitors have been focused upon as a novel drug for treating diabetes. SGLT2 inhibitors enhance renal glucose excretion by inhibiting renal glucose reabsorption. Consequently, SGLT2 inhibitors reduce plasma glucose insulin independently and improve insulin resistance in diabetes. To date, various SGLT2 inhibitors have been developed and evaluated in clinical studies. The potency and positioning of SGLT2 inhibitors as an antidiabetic drug are dependent on their characteristic profile, which induces selectivity, efficacy, pharmacokinetics, and safety. This profile decides which SGLT2 inhibitors can be expected for application of the theoretical concept of reducing renal glucose reabsorption for the treatment of diabetes. I review the structure and advancing profile of various SGLT2 inhibitors, comparing their similarities and differences, and discuss the expected SGLT2 inhibitors for an emerging category of antidiabetic drugs.

A review of Kuala Lumpur International Airport (KLIA) as a competitive South-East Asia hub

Science.gov (United States)

Bardai, A. M.; Er, A. Z.; Johari, M. K.; Noor, A. A. Mohd

2017-12-01

This paper is aimed to determine the strengths and weaknesses of Kuala Lumpur International Airport (KUL) against its competitors in Southeast Asia countries. Due to the geographical and market relevance issues, several airport hubs around KUL are chosen for comparison: Changi International Airport (SIN), Suvarnabhumi International Airport (BKK) and Soekarno-Hatta International Airport (CGK). Strengths, weaknesses, opportunities and threats (SWOT) analysis is used to evaluate the comparative situation between the airports in relation to changing industry and market environment. The study discovers some competitive edges for KUL. Nonetheless, the airport still has to be improved to face future challenges and it is under imminent threat of new aircraft technology.

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.

Microarray-based screening of heat shock protein inhibitors.

Science.gov (United States)

Schax, Emilia; Walter, Johanna-Gabriela; Märzhäuser, Helene; Stahl, Frank; Scheper, Thomas; Agard, David A; Eichner, Simone; Kirschning, Andreas; Zeilinger, Carsten

2014-06-20

Based on the importance of heat shock proteins (HSPs) in diseases such as cancer, Alzheimer's disease or malaria, inhibitors of these chaperons are needed. Today's state-of-the-art techniques to identify HSP inhibitors are performed in microplate format, requiring large amounts of proteins and potential inhibitors. In contrast, we have developed a miniaturized protein microarray-based assay to identify novel inhibitors, allowing analysis with 300 pmol of protein. The assay is based on competitive binding of fluorescence-labeled ATP and potential inhibitors to the ATP-binding site of HSP. Therefore, the developed microarray enables the parallel analysis of different ATP-binding proteins on a single microarray. We have demonstrated the possibility of multiplexing by immobilizing full-length human HSP90α and HtpG of Helicobacter pylori on microarrays. Fluorescence-labeled ATP was competed by novel geldanamycin/reblastatin derivatives with IC50 values in the range of 0.5 nM to 4 μM and Z(*)-factors between 0.60 and 0.96. Our results demonstrate the potential of a target-oriented multiplexed protein microarray to identify novel inhibitors for different members of the HSP90 family. Copyright © 2014 Elsevier B.V. All rights reserved.

Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase.

Science.gov (United States)

Rota, Paola; La Rocca, Paolo; Piccoli, Marco; Montefiori, Marco; Cirillo, Federica; Olsen, Lars; Orioli, Marica; Allevi, Pietro; Anastasia, Luigi

2018-02-06

Neuraminidase activity is essential for the infection and propagation of paramyxoviruses, including human parainfluenza viruses (hPIVs) and the Newcastle disease virus (NDV). Thus, many inhibitors have been developed based on the 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid inhibitor (DANA) backbone. Along this line, herein we report a series of neuraminidase inhibitors, having C4 (p-toluenesulfonamido and azido substituents) and C5 (N-perfluorinated chains) modifications to the DANA backbone, resulting in compounds with 5- to 15-fold greater potency than the currently most active compound, the N-trifluoroacetyl derivative of DANA (FANA), toward the NDV hemagglutinin-neuraminidase (NDV-HN). Remarkably, these inhibitors were found to be essentially inactive against the human sialidase NEU3, which is present on the outer layer of the cell membrane and is highly affected by the current NDV inhibitor FANA. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treatment with a JNK inhibitor increases, whereas treatment with a p38 inhibitor decreases, H2O2-induced calf pulmonary arterial endothelial cell death.

Science.gov (United States)

Park, Woo Hyun

2017-08-01

Oxidative stress induces apoptosis in endothelial cells (ECs). Reactive oxygen species (ROS) promote cell death by regulating the activity of various mitogen-activated protein kinases (MAPKs) in ECs. The present study investigated the effects of MAPK inhibitors on cell survival and glutathione (GSH) levels upon H 2 O 2 treatment in calf pulmonary artery ECs (CPAECs). H 2 O 2 treatment inhibited the growth and induced the death of CPAECs, as well as causing GSH depletion and the loss of mitochondrial membrane potential (MMP). While treatment with the MEK or JNK inhibitor impaired the growth of H 2 O 2 -treated CPAECs, treatment with the p38 inhibitor attenuated this inhibition of growth. Additionally, JNK inhibitor treatment increased the proportion of sub-G 1 phase cells in H 2 O 2 -treated CPAECs and further decreased the MMP. However, treatment with a p38 inhibitor reversed the effects of H 2 O 2 treatment on cell growth and the MMP. Similarly, JNK inhibitor treatment further increased, whereas p38 inhibitor treatment decreased, the proportion of GSH-depleted cells in H 2 O 2 -treated CPAECs. Each of the MAPK inhibitors affected cell survival, and ROS or GSH levels differently in H 2 O 2 -untreated, control CPAECs. The data suggest that the exposure of CPAECs to H 2 O 2 caused the cell growth inhibition and cell death through GSH depletion. Furthermore, JNK inhibitor treatment further enhanced, whereas p38 inhibitors attenuated, these effects. Thus, the results of the present study suggest a specific protective role for the p38 inhibitor, and not the JNK inhibitor, against H 2 O 2 -induced cell growth inhibition and cell death.

JAK inhibitors in autoinflammation.

Science.gov (United States)

Hoffman, Hal M; Broderick, Lori

2018-06-11

Interferonopathies are a subset of autoinflammatory disorders with a prominent type I IFN gene signature. Treatment of these patients has been challenging, given the lack of response to common autoinflammatory therapeutics including IL-1 and TNF blockade. JAK inhibitors (Jakinibs) are a family of small-molecule inhibitors that target the JAK/STAT signaling pathway and have shown clinical efficacy, with FDA and European Medicines Agency (EMA) approval for arthritic and myeloproliferative syndromes. Sanchez and colleagues repurposed baricitinib to establish a significant role for JAK inhibition as a novel therapy for patients with interferonopathies, demonstrating the power of translational rare disease research with lifesaving effects.

HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

DEFF Research Database (Denmark)

Vanangamudi, Murugesan; Poongavanam, Vasanthanathan; Namasivayam, Vigneshwaran

2017-01-01

BACKGROUND: Design of inhibitors for HIV-1 reverse transcriptase inhibition (HIV-1 RT) is one of the successful chemotherapies for the treatment of HIV infection. Among the inhibitors available for HIV-1 RT, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have shown to be very promising......: The conformation dependent-alignment based (CoMFA and CoMSIA) methods have been proven very successful ligand based strategy in the drug design. Here, CoMFA and CoMSIA studies reported for structurally distinct NNRTIs including thiazolobenzimidazole, dipyridodiazepinone, 1,1,3-trioxo [1,2,4]-thiadiazine...

Inhibitors of Fatty Acid Synthase for Prostate Cancer

Science.gov (United States)

2012-05-01

compounds. For example, numerous classes of acetyl- cholinesterase inhibitors have been developed, m any with fe mtomolar binding affinities (7). This...AD_________________ Award Number: W81XWH-09-1-0204 TITLE: Inhibitors of Fatty Acid Synthase for...CONTRACT NUMBER Inhibitors of Fatty Acid Synthase for Prostate Cancer 5b. GRANT NUMBER W81XWH-09-1-0204 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer

DEFF Research Database (Denmark)

Jacobsen, Kirstine; Bertran-Alamillo, Jordi; Molina, Miguel Angel

2017-01-01

Non-small-cell lung cancer patients with activating epidermal growth factor receptor (EGFR) mutations typically benefit from EGFR tyrosine kinase inhibitor treatment. However, virtually all patients succumb to acquired EGFR tyrosine kinase inhibitor resistance that occurs via diverse mechanisms....... The diversity and unpredictability of EGFR tyrosine kinase inhibitor resistance mechanisms presents a challenge for developing new treatments to overcome EGFR tyrosine kinase inhibitor resistance. Here, we show that Akt activation is a convergent feature of acquired EGFR tyrosine kinase inhibitor resistance......, across a spectrum of diverse, established upstream resistance mechanisms. Combined treatment with an EGFR tyrosine kinase inhibitor and Akt inhibitor causes apoptosis and synergistic growth inhibition in multiple EGFR tyrosine kinase inhibitor-resistant non-small-cell lung cancer models. Moreover...

Does plasminogen activator inhibitor-1 drive lymphangiogenesis?

DEFF Research Database (Denmark)

Bruyère, Françoise; Melen-Lamalle, Laurence; Blacher, Silvia

2010-01-01

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and...

Nontoxic corrosion inhibitors for N80 steel in hydrochloric acid

Directory of Open Access Journals (Sweden)

M. Yadav

2016-11-01

Full Text Available The purpose of this paper is to evaluate the protective ability of 1-(2-aminoethyl-2-oleylimidazoline (AEOI and 1-(2-oleylamidoethyl-2-oleylimidazoline (OAEOI as corrosion inhibitors for N80 steel in 15% hydrochloric acid, which may find application as eco-friendly corrosion inhibitors in acidizing processes in petroleum industry. Different concentrations of synthesized inhibitors AEOI and OAEOI were added to the test solution (15% HCl and the corrosion inhibition of N80 steel in hydrochloric acid medium containing inhibitors was tested by weight loss, potentiodynamic polarization and AC impedance measurements. Influence of temperature (298–323 K on the inhibition behavior was studied. Surface studies were performed by using FTIR spectra and SEM. Both the inhibitors, AEOI and OAEOI at 150 ppm concentration show maximum efficiency 90.26% and 96.23%, respectively at 298 K in 15% HCl solution. Both the inhibitors act as mixed corrosion inhibitors. The adsorption of the corrosion inhibitors at the surface of N80 steel is the root cause of corrosion inhibition.

Indanones as high-potency reversible inhibitors of monoamine oxidase.

Science.gov (United States)

Mostert, Samantha; Petzer, Anél; Petzer, Jacobus P

2015-05-01

Recent reports document that α-tetralone (3,4-dihydro-2H-naphthalen-1-one) is an appropriate scaffold for the design of high-potency monoamine oxidase (MAO) inhibitors. Based on the structural similarity between α-tetralone and 1-indanone, the present study involved synthesis of 34 1-indanone and related indane derivatives as potential inhibitors of recombinant human MAO-A and MAO-B. The results show that C6-substituted indanones are particularly potent and selective MAO-B inhibitors, with IC50 values ranging from 0.001 to 0.030 μM. C5-Substituted indanone and indane derivatives are comparatively weaker MAO-B inhibitors. Although the 1-indanone and indane derivatives are selective inhibitors of the MAO-B isoform, a number of homologues are also potent MAO-A inhibitors, with three homologues possessing IC50 values 1-indanone as a reversible MAO inhibitor with a competitive mode of inhibition. It may be concluded that 1-indanones are promising leads for the design of therapies for neurodegenerative and neuropsychiatric disorders such as Parkinson's disease and depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Insights into the molecular evolution of peptidase inhibitors in arthropods.

Science.gov (United States)

Alonso, Joaquin; Martinez, Manuel

2017-01-01

Peptidase inhibitors are key proteins involved in the control of peptidases. In arthropods, peptidase inhibitors modulate the activity of peptidases involved in endogenous physiological processes and peptidases of the organisms with which they interact. Exploring available arthropod genomic sequences is a powerful way to obtain the repertoire of peptidase inhibitors in every arthropod species and to understand the evolutionary mechanisms involved in the diversification of this kind of proteins. A genomic comparative analysis of peptidase inhibitors in species belonging to different arthropod taxonomic groups was performed. The results point out: i) species or clade-specific presence is shown for several families of peptidase inhibitors; ii) multidomain peptidase inhibitors are commonly found in many peptidase inhibitor families; iii) several families have a wide range of members in different arthropod species; iv) several peptidase inhibitor families show species-specific (or clade-specific) gene family expansions; v) functional divergence may be assumed for particular clades; vi) passive expansions may be used by natural selection to fix adaptations. In conclusion, conservation and divergence of duplicated genes and the potential recruitment as peptidase inhibitors of proteins from other families are the main mechanisms used by arthropods to fix diversity. This diversity would be associated to the control of target peptidases and, as consequence, to adapt to specific environments.

ROCK inhibitors in ocular disease

Directory of Open Access Journals (Sweden)

Eva Halasz

2016-12-01

Full Text Available Rho kinases (ROCKs have a crucial role in actin-cytoskeletal reorganization and thus are involved in broad aspects of cell motility, from smooth muscle contraction to neurite outgrowth. The first marketed ROCK inhibitor, called fasudil, has been used safely for treatment of cerebral vasospasm since 1995 in Japan. During the succeeding decades ROCK inhibitors have been applied in many pathological conditions from central nervous system disorders to cardiovascular disease as potential therapeutic agents or experimental tools to help understand the underlying (pathomechanisms. In 2014, a fasudil derivate named ripasudil was accepted for clinical use in glaucoma and ocular hypertension. Since ROCK kinases are widely expressed in ocular tissues, they have been implicated in the pathology of many ocular conditions such as corneal dysfunction, glaucoma, cataract, diabetic retinopathy, age-related macular degeneration, and retinal detachment. This paper aims to provide an overview of the most recent status/application of ROCK inhibitors in the field of eye disease.

SGLT-2 Inhibitors and Cardiovascular Risk

DEFF Research Database (Denmark)

Cavender, Matthew A; Norhammar, Anna; Birkeland, Kåre I

2018-01-01

BACKGROUND: Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. OBJECTIVES: This study sought...... to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. METHODS: The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes...... evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)....

Protein C Inhibitor-A Novel Antimicrobial Agent

NARCIS (Netherlands)

Malmström, E.; Mörgelin, M.; Malmsten, M.; Johansson, L.; Norrby-Teglund, A.; Shannon, O.; Schmidtchen, A.; Meijers, J.C.M.; Herwald, H.

2009-01-01

Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which

Electrochemical Behaviour of Environmentally Friendly Inhibitor of ...

African Journals Online (AJOL)

Electrochemical Behaviour of Environmentally Friendly Inhibitor of Aloe Secundiflora Extract in Corrosion Control of Carbon Steel in Soft Water Media. ... The investigation was performed at different inhibitor concentrations under static and dynamic conditions using a Rotating Disk Electrode (RDE). The impedance and ...

Kinetics study of heterogeneous reactions of ozone with erucic acid using an ATR-IR flow reactor.

Science.gov (United States)

Leng, Chunbo; Hiltner, Joseph; Pham, Hai; Kelley, Judas; Mach, Mindy; Zhang, Yunhong; Liu, Yong

2014-03-07

The ozone initiated heterogeneous oxidation of erucic acid (EA) thin film was investigated using a flow system combined with attenuated total reflection infrared spectroscopy (ATR-IR) over wide ranges of ozone concentrations (0.25-60 ppm), thin film thickness (0.1-1.0 μm), temperatures (263-298 K), and relative humidities (0-80% RH) for the first time. Pseudo-first-order rate constants, kapp, and overall reactive uptake coefficients, γ, were obtained through changes in the absorbance of C[double bond, length as m-dash]O stretching bands at 1695 cm(-1), which is assigned to the carbonyl group in carboxylic acid. Results showed that the reaction followed the Langmuir-Hinshelwood mechanism and kapp was largely dominated by surface reaction over bulk phase reaction. In addition, both the kapp and the γ values showed very strong temperature dependences (∼two orders of magnitude) over the temperature range; in contrast, they only slightly increased with increasing RH values from 0-80%. According to the kapp values as a function of temperature, the activation energy for the heterogeneous reaction was estimated to be 80.6 kJ mol(-1). Our results have suggested that heterogeneous reactions between ozone and unsaturated solid surfaces likely have a substantially greater temperature dependence than liquid ones. Moreover, the hygroscopic properties of EA thin films before and after exposure to ozone were also studied by measurement of water uptake. Based on the hygroscopicity data, the insignificant RH effect on reaction kinetics was probably due to the relatively weak water uptake by the unreacted and reacted EA thin films.

Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma.

Science.gov (United States)

Baranski, Zuzanna; Booij, Tijmen H; Cleton-Jansen, Anne-Marie; Price, Leo S; van de Water, Bob; Bovée, Judith V M G; Hogendoorn, Pancras C W; Danen, Erik H J

2015-07-01

Conventional high-grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis-free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti-apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G2 cell-cycle arrest; Chk1 protein levels were attenuated and ATR-Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven-depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven-controlled ATR-Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix-embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR-Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Identification of catechols as histone-lysine demethylase inhibitors

DEFF Research Database (Denmark)

Nielsen, Anders L; Kristensen, Line H; Stephansen, Karen B

2012-01-01

Identification of inhibitors of histone-lysine demethylase (HDM) enzymes is important because of their involvement in the development of cancer. An ELISA-based assay was developed for identification of inhibitors of the HDM KDM4C in a natural products library. Based on one of the hits with affinity...... in the low µM range (1, a catechol), a subset of structurally related compounds was selected and tested against a panel of HDMs. In this subset, two inhibitors (2 and 10) had comparable affinities towards KDM4C and KDM6A but no effect on PHF8. One inhibitor restored H3K9me3 levels in KDM4C transfected U2-OS...

Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

International Nuclear Information System (INIS)

Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E.

2007-01-01

Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time

Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

Directory of Open Access Journals (Sweden)

Santos Cavaiola T

2018-04-01

Full Text Available Tricia Santos Cavaiola, Jeremy Pettus Division of Endocrinology and Metabolism, University of California San Diego, San Diego, CA, USA Abstract: As the first cardiovascular (CV outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM, the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME® trial, which investigated the sodium glucose cotransporter 2 (SGLT2 inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL, which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. Keywords: canagliflozin, cardiovascular outcomes, dapagliflozin, empagliflozin, mechanisms, sodium glucose cotransporter 2 inhibitors

Synthesis and Application of Pyrrolidone-containing Shale Inhibitors

Science.gov (United States)

Liu, Yonggui; Hou, Jie; Zhang, Yang; Yan, Jing; Song, Tao; Xu, Yongjun

2018-03-01

New generation polyamine inhibitors are amino-terminated polyethers with excellent inhibiting capabilities; they play a key role in borehole stabilization and reservoir protection. However, polyamine inhibitors are limited by their poor thermal stability, which can be attributed to the presence of ether bonds in their molecular structures. We propose a three-step synthesis approach fora novel pyrrolidone-containing polyamine inhibitor (DYNP) by introducing N-vinyl-2-pyrrolidone (NVP) on divinyloxyethane. This polyamine inhibitor exhibits an optimized molecular structure and has enhanced heat resistance. Characterizations by infrared (IR) spectroscopy and evaluation tests demonstrate several advantages of DYNP inhibitors, including excellent inhibiting capability (superior to similar materials such as polyamines), improved heat resistance (reasonable stability at temperatures up to 240°C), and good compatibility with both fresh water and salt water drilling fluids. These can be attributed to the presence of considerable amounts of amino groups in the repeating unit of DYNP molecules. The DYNP inhibitor was applied in over 20 boreholes in tight oil blocks in Daqing Oilfield to relieve hydration of formations with high shale contents. For instance, drilling in the 2033.5m horizontal section of Dragon 2 borehole was smooth, with a borehole diameter expansion ratio below 10%.

Inhibitor specificity of recombinant and endogenous caspase-9.

Science.gov (United States)

Ryan, Ciara A; Stennicke, Henning R; Nava, Victor E; Burch, Jennifer B; Hardwick, J Marie; Salvesen, Guy S

2002-01-01

Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. To elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde ('Ac-DEVD-CHO'), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone ('Z-VAD-FMK') and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein ('XIAP') against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. These findings were also mirrored in cell expression studies. We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo, making the potency of inhibitors highly context-dependent. This is supported by survival data from a mouse model of apoptosis driven by Sindbis virus expressing either p35 or a catalytic mutant of caspase-9. These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro, yet fails to block caspase-9-mediated cell death. PMID:12067274

Classification of Breast Cancer Resistant Protein (BCRP) Inhibitors and Non-Inhibitors Using Machine Learning Approaches.

Science.gov (United States)

Belekar, Vilas; Lingineni, Karthik; Garg, Prabha

2015-01-01

The breast cancer resistant protein (BCRP) is an important transporter and its inhibitors play an important role in cancer treatment by improving the oral bioavailability as well as blood brain barrier (BBB) permeability of anticancer drugs. In this work, a computational model was developed to predict the compounds as BCRP inhibitors or non-inhibitors. Various machine learning approaches like, support vector machine (SVM), k-nearest neighbor (k-NN) and artificial neural network (ANN) were used to develop the models. The Matthews correlation coefficients (MCC) of developed models using ANN, k-NN and SVM are 0.67, 0.71 and 0.77, and prediction accuracies are 85.2%, 88.3% and 90.8% respectively. The developed models were tested with a test set of 99 compounds and further validated with external set of 98 compounds. Distribution plot analysis and various machine learning models were also developed based on druglikeness descriptors. Applicability domain is used to check the prediction reliability of the new molecules.

The effects of residual platelets in plasma on plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays

NARCIS (Netherlands)

M. Pieters (Marlien); S.A. Barnard (Sunelle A.); D.T. Loots (Du Toit); D.C. Rijken (Dingeman)

2017-01-01

textabstractDue to controversial evidence in the literature pertaining to the activity of plasminogen activator inhibitor-1 in platelets, we examined the effects of residual platelets present in plasma (a potential pre-analytical variable) on various plasminogen activator inhibitor-1 and plasminogen

Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

Science.gov (United States)

Thakur, Rupamoni; Mukherjee, Ashis K

2017-06-01

Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

New test for oil soluble/water dispersible gas pipeline inhibitors

Energy Technology Data Exchange (ETDEWEB)

Stegmann, D.W.; Asperger, R.G.

1987-01-01

The wheel test provides good mixing of the condensate and water phases, the coupons are exposed to both phases. Therefore, the wheel test cannot distinguish between inhibitors that need continuous mixing of the these phases to maintain a water dispersion of the inhibitor and inhibitors that will self disperse into the water. This concept becomes important for pipelines in stratified flow where the water can settle out. In these cases with low turbulence, the inhibitor must self disperse into the water to be effective. The paper describes a test method to measure the effectiveness of an inhibitor and its ability to self disperse. The effectiveness of several inhibitors as predicted by the new test method is discussed relative to data from the wheel test and breaker tests. Field performance of these inhibitors in a gas gathering line, with liquids in stratified flow, are cities and compared with the results of the various laboratory tests.

Aromatase inhibitors in men: effects and therapeutic options

Directory of Open Access Journals (Sweden)

de Jong Frank H

2011-06-01

Full Text Available Abstract Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended.

Urinary trypsin inhibitor - an experimental and clinical study

International Nuclear Information System (INIS)

Berling, B.M.

1991-01-01

The urinary trypsin inhibitor (UTI) is an acid stable proteinase inhibitor present in blood and urine. It was purified from urine using affinity chromatography, ion exchange chromatography and gel filtration. Two forms of UTI were present in urine, A and B. A radioimmunoassay for measurement of UTI in urine and plasma was performed. The normal level of UTI in plasma and serum was about 2 mg/l. The normal excretion in urine was about 8 mg per 24 hours. The plasma and urine levels of UTI were studied in patients with acute pancreatitis and in patients undergoing cholecystectomy. Uremic patients had a marked increase of UTI in plasma compatible with decreased glomerular filtration. In samples from healthy persons as well as from patients only inhibitor A was found. Inhibitor B has recently been renamed bikunin because of its two Kunitz-type inhibiting domains. Inhibitor A might be called tetrakunin. Radioactively labeled UTI (inhibitor A) was injected intravenously in three male volunteers. The plasma half-life of 125 I UTI was 2 hours. Free biologically active inhibitor was found in the urine during the first four hours after injection. The organ distribution of intravenously injected 125 I UTI was studied in rats. Fifteen minutes after injection the major part of the radioactivity was found in the kidneys, suggesting that the kidneys are the primary site of UTI metabolism. Using immunohistochemical techniques UTI was found in the proximal tubules of the normal human kidney further indicating the tubular reabsorption and methabolisms of UTI

Characterization of silver halide fiber optics and hollow silica waveguides for use in the construction of a mid-infrared attenuated total reflection fourier transform infrared (ATR FT-IR) spectroscopy probe.

Science.gov (United States)

Damin, Craig A; Sommer, André J

2013-11-01

Advances in fiber optic materials have allowed for the construction of fibers and waveguides capable of transmitting infrared radiation. An investigation of the transmission characteristics associated with two commonly used types of infrared-transmitting fibers/waveguides for prospective use in a fiber/waveguide-coupled attenuated total internal reflection (ATR) probe was performed. Characterization of silver halide polycrystalline fiber optics and hollow silica waveguides was done on the basis of the transmission of infrared light using a conventional fiber optic coupling accessory and an infrared microscope. Using the fiber optic coupling accessory, the average percent transmission for three silver halide fibers was 18.1 ± 6.1% relative to a benchtop reflection accessory. The average transmission for two hollow waveguides (HWGs) using the coupling accessory was 8.0 ± 0.3%. (Uncertainties in the relative percent transmission represent the standard deviations.) Reduced transmission observed for the HWGs was attributed to the high numerical aperture of the coupling accessory. Characterization of the fibers/waveguides using a zinc selenide lens objective on an infrared microscope indicated 24.1 ± 7.2% of the initial light input into the silver halide fibers was transmitted. Percent transmission obtained for the HWGs was 98.7 ± 0.1%. Increased transmission using the HWGs resulted from the absence or minimization of insertion and scattering losses due to the hollow air core and a better-matched numerical aperture. The effect of bending on the transmission characteristics of the fibers/waveguides was also investigated. Significant deviations in the transmission of infrared light by the solid-core silver halide fibers were observed for various bending angles. Percent transmission greater than 98% was consistently observed for the HWGs at the bending angles. The combined benefits of high percent transmission, reproducible instrument responses, and increased bending

Azidoblebbistatin, a photoreactive myosin inhibitor

Science.gov (United States)

Képiró, Miklós; Várkuti, Boglárka H.; Bodor, Andrea; Hegyi, György; Drahos, László; Kovács, Mihály; Málnási-Csizmadia, András

2012-01-01

Photoreactive compounds are important tools in life sciences that allow precisely timed covalent crosslinking of ligands and targets. Using a unique technique we have synthesized azidoblebbistatin, which is a derivative of blebbistatin, the most widely used myosin inhibitor. Without UV irradiation azidoblebbistatin exhibits identical inhibitory properties to those of blebbistatin. Using UV irradiation, azidoblebbistatin can be covalently crosslinked to myosin, which greatly enhances its in vitro and in vivo effectiveness. Photo-crosslinking also eliminates limitations associated with the relatively low myosin affinity and water solubility of blebbistatin. The wavelength used for photo-crosslinking is not toxic for cells and tissues, which confers a great advantage in in vivo tests. Because the crosslink results in an irreversible association of the inhibitor to myosin and the irradiation eliminates the residual activity of unbound inhibitor molecules, azidoblebbistatin has a great potential to become a highly effective tool in both structural studies of actomyosin contractility and the investigation of cellular and physiological functions of myosin II. We used azidoblebbistatin to identify previously unknown low-affinity targets of the inhibitor (EC50 ≥ 50 μM) in Dictyostelium discoideum, while the strongest interactant was found to be myosin II (EC50 = 5 μM). Our results demonstrate that azidoblebbistatin, and potentially other azidated drugs, can become highly useful tools for the identification of strong- and weak-binding cellular targets and the determination of the apparent binding affinities in in vivo conditions. PMID:22647605

Predicting the Performance of Organic Corrosion Inhibitors

Directory of Open Access Journals (Sweden)

David A. Winkler

2017-12-01

Full Text Available The withdrawal of effective but toxic corrosion inhibitors has provided an impetus for the discovery of new, benign organic compounds to fill that role. Concurrently, developments in the high-throughput synthesis of organic compounds, the establishment of large libraries of available chemicals, accelerated corrosion inhibition testing technologies, and the increased capability of machine learning methods have made discovery of new corrosion inhibitors much faster and cheaper than it used to be. We summarize these technical developments in the corrosion inhibition field and describe how data-driven machine learning methods can generate models linking molecular properties to corrosion inhibition that can be used to predict the performance of materials not yet synthesized or tested. We briefly summarize the literature on quantitative structure–property relationships models of small organic molecule corrosion inhibitors. The success of these models provides a paradigm for rapid discovery of novel, effective corrosion inhibitors for a range of metals and alloys in diverse environments.

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

Inhibitor development and mortality in non-severe hemophilia A.

Science.gov (United States)

Eckhardt, C L; Loomans, J I; van Velzen, A S; Peters, M; Mauser-Bunschoten, E P; Schwaab, R; Mazzucconi, M G; Tagliaferri, A; Siegmund, B; Reitter-Pfoertner, S E; van der Bom, J G; Fijnvandraat, K

2015-07-01

The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications. We assessed the association between the occurrence of inhibitors and mortality in patients with non-severe HA. In this retrospective cohort study, clinical data and vital status were collected for 2709 non-severe HA patients (107 with inhibitors) who were treated between 1980 and 2011 in 34 European and Australian centers. Mortality rates for patients with and without inhibitors were compared. During 64,200 patient-years of follow-up, 148 patients died (mortality rate, 2.30 per 1000 person-years; 95% confidence interval (CI), 1.96-2.70) at a median age of 64 years (interquartile range [IQR], 49-76). In 62 patients (42%) the cause of death was hemophilia related. Sixteen inhibitor patients died at a median age of 71 years (IQR, 60-81). In ten patients the inhibitor was present at time of death; seven of them died of severe bleeding complications. The all-cause mortality rate in inhibitor patients was > 5 times increased compared with that for those without inhibitors (age-adjusted mortality rate ratio, 5.6). Inhibitor development in non-severe hemophilia is associated with increased mortality. High rates of hemophilia-related mortality in this study indicate that non-severe hemophilia is not mild at all and stress the importance of close follow-up for these patients. © 2015 International Society on Thrombosis and Haemostasis.